Breast Surgery A Companion to Specialist Surgical Practice

The role of adjuvant radiotherapy in the management of breast cancer
243
established than for IBC and use of adjuvant RT var-
ies across the UK with no clear standard of care.5
All these trials used a dose fractionation sched-
ule of 50 Gy in 25 fractions over 5  weeks. The
EORTC trial6 randomised 1010 women with clini-
cally or mammographically detected DCIS ≤5 cm
in size to wide local excision alone or wide lo-
cal excision plus whole breast irradiation (50 Gy
in 25 fractions over 5  weeks). The 10-year local
relapse-free rate was 85% with RT compared to
74% with surgery alone (hazard ratio (HR) 0.53,
P < 0.001). In situ local recurrence rates were 7%
and 13% respectively and invasive rates were also
7% and 13%. In the NSABP B-17 trial7 818 pa-
tients were randomised to +/− whole-breast radio-
therapy (WBRT) after lumpectomy. RT reduced
the local relapse rate from 16.8% to 7.7% (rela-
tive risk (RR) 0.38, 95% confidence interval (CI)
0.25–0.59; P < 0.00001). In a recent update of
the trial with 10-year follow-up, invasive recur-
rence within the ipsilateral breast was associated
with a slightly higher risk of death. In contrast,
recurrence of DCIS was not.8 The UK/ANZ trial9
recruited 1701 patients treated by BCS. Patients
were randomised into four treatment groups (BCS
alone, BCS + RT, BCS + tamoxifen and BCS + RT +
tamoxifen). Approximately 90% of patients were
≥50 years and screen detected. Median follow-up
was 53 months. Local recurrence rates were 22%,
8%, 18% and 6% respectively. Adjuvant RT was
associated with a significant reduction for both
DCIS and IBC ipsilateral recurrence (HR 0.38, P
< 0.0001). Radiotherapy reduced the risk of recur-
rence by 64% for DCIS (P = 0.0004) and by 55%
for invasive year cancer (P = 0.01). The Swedish
DCIS trial (SweDCIS)10 randomised 1067 pa-
tients after wide excision for DCIS to WBRT or
no WBRT. There was a risk reduction of 16% in
ipsilateral events (in situ or invasive carcinoma)
at 10 years from RT (95% CI 10.3–21.6%) and
a relative risk of 0.40 (95% CI, 0.30–0.54%).
The effect of RT in women was lower in women
younger than 50, but there was a substantial ben-
efit in women >60 years. Results of the four trials
were pooled in a Cochrane review11 and showed
that the risk of ipsilateral ­invasive recurrence was
halved by radiotherapy at 10 years (HR 0.50, 95%
CI 0.32–0.76) with about 50% of the ipsilateral
breast tumour recurrence (IBTR) being invasive
and 50% DCIS. In a subgroup analysis according
to age (50 years, presence or absence of com-
edo necrosis and tumour size >/<10 mm) all sub-
groups derived benefit from RT. Women >50 years
appeared to experience a greater reduction in re-
currence than compared to younger women (HR
0.35 (>50) vs. 0.67 (<50)). What limits interpreta-
tion, as others have pointed out,5 is that none of
the trials were designed prospectively for subgroup
analyses. In addition, there have been criticisms of
the quality of the DCIS trials, summarised in a re-
view,13 and problems with these trials include de-
ficiencies in radiological–pathological correlation,
measurement of tumour size,14 routine imaging of
pathology specimens, postoperative imaging, defi-
nition and classification of lesions,7 definition of
tumour-free margins,15 consistency in inclusion/
exclusion criteria, randomisation procedures and
insufficient statistical power to detect small differ-
ences in survival.12 Attempts have been made to de-
fine a subset of patients from whom postoperative
radiotherapy might be omitted. In the E5194 non-
randomised study of wide local excision alone in
711 patients with low- or intermediate-grade DCIS
≤ 2.5 cm or high-grade ≤1 cm with margins ≥3 mm
with median follow-up of 6.7 years, the 5-year ip-
silateral recurrence rate was 6.1%.16 A continued
increase in the rate of IBTR beyond 5 years is of
concern and long-term follow-up will be needed to
determine if omission of radiotherapy is safe.
The absolute benefits of radiotherapy on local con-
trol are greater in high-grade compared to low-grade
DCIS. The thresholds for recommending radiother-
apy vary widely internationally. In some centres ra-
diotherapy is confined to patients with high-grade
DCIS, whereas other women with all grades of
DCIS are treated following BCS on the basis17 that
there is no group that does not benefit. One of the
arguments for a more conservative approach to se-
lection is that these patients are subject to the same
risks of radiation-induced morbidity (including car-
diac damage, rib fractures and pneumonitis) as pa-
tients with invasive breast cancer. In some groups of
women with DCIS mortality rates are <1% and so
this encourages a more cautious approach in recom-
mending adjuvant breast irradiation. That said, the
There are four randomised trials that have
investigated the value of the addition of whole-
breast irradiation and/or tamoxifen to BCS.6–12
All show that postoperative radiotherapy reduces
the risk of in ipsilateral recurrence of DCIS and
development of invasive breast cancer.

Chapter 15
244
risks, for example, of ­cardiopulmonary morbidity
have been substantially reduced by the use of three-
dimensional CT planning.
In clinical practice, radiotherapy is used selectively
based on patient age, the size of the DCIS, grade
of DCIS, adequacy of excision, the patient's general
health and their wishes.
Is there a role for a boost
dose after whole-breast
irradiation for DCIS?
A multi-institution retrospective study compar-
ing wide local excision alone, wide local excision
and whole-breast radiotherapy among 373 pa-
tients ≤45 years showed a reduced risk of relapse at
10 years in patients treated with a boost dose (86%)
compared to no boost (72%).18 However, this study
was potentially subject to selection bias, with the
possibility that higher risk patients were more likely
to have received a boost.19 The role of the boost and
of hypofractionation is currently under investigation
in the international BIG 3-07 trial. Patients with non-
low-risk DCIS are randomised after whole-breast ir-
radiation to a boost of 16 Gy in eight fractions or no
boost. An external beam dose fractionation regimen
(the standard of 50 Gy in 25 fractions over 5 weeks)
or a hypofractionated regimen of 42.5 Gy in 16 daily
fractions are options that are included in the ran-
domisation or can be selected in the trial. The pri-
mary end-point is time to local recurrence.
Role of adjuvant radiotherapy
in invasive breast cancer
The Oxford overview
The overall impact of radiotherapy on local
­recurrence and survival is best appreciated from
the 5-yearly updates of the Oxford overview of
randomised trials of radiation after both breast-­
conserving surgery and mastectomy. The conclu-
sions have changed dramatically since the first
overview in 1978, which showed an adverse effect
of RT on survival after mastectomy,21 largely due to
the adverse effects of excessive cardiac irradiation
from now obsolete orthovoltage techniques.
However, in 2005, the first evidence emerged of
the beneficial effect of a reduction in local recur-
rence from RT on the overall survival23 of 42 000
women in 78 randomised trials.
This ratio was confirmed in a more recent meta-
analysis confined to over 10 000 women of trials of
breast-conserving surgery with or without adjuvant
whole breast irradiation.24 It should be noted that
the primary end-point in the latter overview has
been changed from previous radiotherapy over-
views to include any first recurrence, whether this
is locoregional or metastatic. The overall impact of
adjuvant radiotherapy is an impressive 50% reduc-
tion in the risk of any first recurrence. However,
the absolute benefits of radiotherapy are less in
older lower-risk patients (Fig.  15.1). The 10-year
risk of any recurrence was reduced by radiotherapy
by 15.7% (35% to 19.3%; 95% CI 13.7–17.7,
2P < 0.00001) and the 15-year mortality fell from
25.2% to 21.4% (an absolute reduction of 3.8%;
95% CI 1.6–6.0, 2P = 0.00005). In 7287 pN0 pa-
tients, the equivalent risk was reduced from 31% to
15.6%, which is a 15.4% absolute reduction (95%
At present it can be argued that since all
subgroups of patients with DCIS benefit from RT
after BCS, all should receive it.
Whether giving a boost dose to the site of
excision of DCIS after whole-breast irradiation confers
similar benefit to that seen in invasive breast cancer
is unclear. Retrospective pooled data18 suggest
there may be a benefit.
There is a limited evidence base for
hypofractionation in DCIS. In a retrospective study
from Toronto of patients with DCIS treated with
conventional (50 Gy in 25 fractions) or hypofractionated
(42.4 Gy in 16 fractions or 40 Gy/16 + 12.5 Gy boost)
WBRT after breast-conserving surgery for DCIS
(median follow-up 3.76 years), there was no difference
in local control or toxicity.20
In the 2000 overview of radiotherapy trials, a
2% benefit in 20-year survival was counterbalanced
by an excess of non-breast cancer mortality,
predominantly vascular, again a residual effect of
older trials.22 This provides a strong rationale for
radiotherapy techniques that reduce cardiac dose.
A key observation from the Oxford overview
of radiotherapy trials was that for every four local
recurrences prevented, one breast cancer death
was avoided, now known as the ‘4:1 ratio’.23

The role of adjuvant radiotherapy in the management of breast cancer
245
10-year risk (%)
0
100
75
50
25
>Lumpectomy, ER-positive no tamoxifen (85%)
or ER-poor (15%)
>Lumpectomy, ER-positive no tamoxifen (79%)
or ER-poor (21%)
10-year risk (%)
0
100
75
50
25
Lumpectomy, ER-poor
Lumpectomy, ER-poor
10-year risk (%)
0
100
75
50
25
Lumpectomy, ER-positive no tamoxifen
Lumpectomy, ER-positive no tamoxifen
Tumour size T1 (1–20mm)
Tumour size T2 (21–50mm)
10-year risk (%)
0
100
75
50
25
Low grade
<40 40- 50- 60- 70+
Intermediate grade
<40 40- 50- 60- 70+
High grade
<40 40- 50- 60- 70+
Lumpectomy, ER-positive with tamoxifen
Age (years)
Low grade
<40 40- 50- 60- 70+
Intermediate grade
<40 40- 50- 60- 70+
High grade
<40 40- 50- 60- 70+
Age (years)
Lumpectomy, ER-positive with tamoxifen
Figure 15.1  •  Absolute 10-year risks (%) of any (locoregional or distant) first recurrence with and without radiotherapy
(RT) following breast-conserving surgery (BCS) in pathologically node-negative women by patient and trial characteristics,
as estimated by regression modelling of data for 7287 women. Bars show 10-year risks in women allocated to BCS
only. Dark sections show 10-year risks in women allocated to BCS plus RT, light sections show absolute reduction with
RT. ER, oestrogen receptor. Reprinted from The Lancet. Early Breast Cancer Trialists' Collaborative (EBCTCG). Effect of
radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of
individual patient data for 10 801 women in 17 randomised trials. Lancet 2011; 378 (9804):1707–16. With permission
from Elsevier.

Chapter 15
246
CI 13.2–17.6, 2P < 0.00001) with a 3.3% absolute
reduction in mortality from 20.5% to 17.2%. In
pN1 (1050 patients) the 10-year reduction in risk
of recurrence was greater (21.2%; 95% CI 14.5–
27.9, 2P < 0.00001) from 63.7% to 42.5% with
an 8.5% reduction in 15-year breast cancer mor-
tality (95% CI 1.8–15.2, 2P = 0.01) from 51.3%
death to 42.8%. The risk of any first recurrence at
10 years was influenced by tumour size, age, grade,
use of tamoxifen, oestrogen receptor (ER) status and
extent of local breast surgery (Fig. 15.2). The pro-
portional reduction in first recurrence is similar ir-
respective of age. However, the absolute reduction in
risk is much less for women >70 years. Most recur-
rences (75%) were locoregional and were higher in
the no RT groups (25%) compared to 8% in the RT
arms. The dominant effect on locoregional recur-
rence from RT was in the first year but there was a
lesser but still substantial impact up to 9 years.
Is there a subgroup of patients
from whom postoperative
radiotherapy can be omitted?
This would be attractive, particularly in older pa-
tients who may find attendance for several weeks
of radiotherapy burdensome. The current consensus
is that no group has as yet been identified. Whole-
breast radiotherapy reduces the risk of IBTR in all
subgroups, although the absolute benefit in low
risk, small (<2 cm), well differentiated, hormone
receptor-positive, node-negative tumours is small.
Six hundred and thirty-six women, 70 years or older
with T1, N0, M0 breast tumours, were randomised
after breast-conserving surgery and tamoxifen to
whole-breast irradiation or no further treatment.
The difference in local recurrence was 3% at 5 years
(4% vs. 1%) in favour of adjuvant irradiation.25
Breast oedema, skin fibrosis and pain were all more
frequent in the irradiated group. In an accompanying
editorial27 the value of radiotherapy was questioned
given the small difference in local recurrence. However,
no axillary surgical staging procedure was included in
this study so it is possible that the some higher risk,
node-positive patients were enrolled. In addition, as
the authors acknowledge, the trial was underpowered.
It is well recognised that there is a persistent pattern
of local recurrence of up to 1% per year at least up to
10 years.28 This concern is validated by the update of
the CALGB trial showing that at a median follow-up
of 10.5 years, the difference in local recurrence has in-
creased to 7% (9% vs. 2%).26 Of the 43% of patients
who had died only 7% of deaths were due to breast
cancer, reflecting the competing risks of death from
non-breast cancer causes, predominantly vascular, in
older patients with breast cancer.
Absolute reduction (%) in 15-year risk
of breast cancer death (95% Cl)
-10
-5
0
5
10
15
20
0
5
10
15
20
25
30
Absolute reduction (%) in 10-year risk
of any first recurrence
No RT
pNO-lower
pNO-
intermediate
pN+
pNO-large
predicted
absolute
recurrence
reduction
Figure 15.2  •  Absolute reduction in 15-year risk of breast
cancer death with radiotherapy (RT) after breast-conserving
surgery versus absolute reduction in 10-year risk of any
(locoregional or distant) recurrence. Women with pNO
disease are subdivided by the predicted absolute reduction
in 10-year risk of any recurrence suggested by regression
modelling (pNO large ≥ 20%, pNO intermediate 10–19%,
pNO lower<10%). Vertical lines are 95% CIs. Sizes of dark
boxes are proportional to amount of information. Dashed
line: one death from breast cancer avoided for every four
recurrences avoided. pNO, pathologically node negative;
pN+, pathologically node positive. Reprinted from The
Lancet. Effect of radiotherapy after breast-conserving
surgery on 10-year recurrence and 15-year breast
cancer death: meta-analysis of individual patient data for
10 801 women in 17 randomised trials. Lancet 2011;
378(9804):1707–16. With permission from Elsevier.
It remains controversial as to whether there is
any subgroup of patients from whom postoperative
radiotherapy can be omitted.
The only randomised trial to address the issue
of the omission of postoperative radiotherapy in ‘low-
risk’ women after breast-conserving surgery is the
US Cancer and Leukemia Group B (CALGB) trial.25,26

The role of adjuvant radiotherapy in the management of breast cancer
247
Two additional trials shed light on the possibil-
ity of the omission of RT in some patients. The
Italian 55-75 trial29 randomised 749 women with T
(<2.5 cm) N0/1, M0 breast cancer to whole-breast
irradiation (50 Gy in 2-Gy fractions) after quadran-
tectomy and systemic therapy. For N0 patients, sen-
tinel lymph node biopsy (SLNB) was undertaken.
SLNB-positive patients were additionally treated by
axillary clearance. This trial is not directly compa-
rable to the CALGB trial since it was not exclusive
to older patients and higher risk patients with one to
three involved nodes were included as well as hor-
mone receptor-positive and -negative tumours. At
a median follow-up of 53 months, the cumulative
incidence of IBTR was 2.5% in the surgery-alone
arm and 0.7% in the surgery plus radiotherapy
arm. The smaller difference in IBTR (1.8%) in the
Italian 55-75 trial compared to the CALGB trial
largely reflects the greater volume of breast tissue
resected by quadrantectomy compared to lumpec-
tomy. The PRIME II trial,30 currently in the follow-
up phase, included over 1300 patients ≥65  years
with T<3 cm pathologically axillary node-negative
breast cancer after breast-conserving surgery (mini-
mum 1 mm clear margin) and adjuvant endocrine
therapy who were randomised to whole-breast ir-
radiation (40–50 Gy) or no whole-breast radiother-
apy. Other randomised trials of breast-conserving
surgery with or without postoperative radiotherapy
that have included but were not limited to older
patients do not provide an answer to the question
of the omission of postoperative radiotherapy after
breast-conserving surgery. In a Canadian trial,31 age
was an independent risk factor with a higher locore-
gional recurrence rate (LRR) in women over the
age of 50. However, a low-risk group with an LRR
<10% could not be identified. In the Milan III trial,
women over the age of 55 years had a lower risk
of recurrence (3.8% vs. 8.8% for the whole popu-
lation).32 In the Scottish conservation trial,33 there
was a trend to a lower recurrence rate with age, par-
ticularly between 60 and 70 years. No difference in
local recurrence was observed in the NSABP B-06
trial for women older or younger than 50 years.34
The upper age of the trial, however, is not stated.
It should be noted, however, that 5-year local re-
currence rates in more recently published studies of
breast conservation are falling to around 3%.36 In
part this is due to better imaging, screening, surgery
and systemic therapy, particularly the introduction
of aromatase inhibitors. So the absolute benefits
in local control from whole-breast irradiation for
older patients are likely to diminish. There is a need
to identify better markers of women who are genu-
inely at low risk of local recurrence to better define
clinical ‘low-risk’ categories and then provide level I
evidence to underpin this approach.
Breast boost after breast-
conserving surgery for invasive
breast cancer
There is level I evidence that a boost of irradia-
tion to the site of excision after breast-conserving
surgery improves local control in older as well as
young patients. The EORTC boost trial randomised
over 5000 T1/2, N0, NIM0 patients after breast-­
conserving surgery with clear margins and whole-
breast irradiation (50 Gy) to a boost of 16 Gy in
eight fractions or no boost. The original analysis37 at
5 years of follow-up showed that the benefit in local
control was only statistically significant in women
under the age of 50. However, at 10 years of follow-
up,38 all age groups were shown to benefit, although
the reduction in local recurrence (7.3% vs. 3.8%) was
only 3.5% in the over 60 years of age group.
Impact of adjuvant whole-
breast radiotherapy on quality
of life
It might be assumed that the quality of life of
older patients treated with postoperative radio-
therapy would be worse than for patients treated
by breast-conserving surgery and adjuvant endo-
crine therapy alone due to the burden of attending
for several weeks of radiotherapy. However, there
is good evidence that adjuvant radiotherapy is well
tolerated by the majority of older patients.39,40 The
only trial to address this issue is the PRIME I trial.
At present international consensus is that
postoperative radiotherapy after breast-conserving
surgery should be the standard of care for all fit
patients irrespective of age.35
On this basis37,38 all patients, including
patients over the age of 60, should be considered
for a breast boost and whole-breast irradiation.

Chapter 15
248
It randomised 255 T1/2, N0, M0 patients treated by
breast-conserving surgery and endocrine therapy to
whole-breast radiotherapy (40–50 Gy) or no further
therapy. There was no overall difference in global
quality of life measured by the EORTC breast QoL
measures41 at 5 years.
Hypofractionated dose
fractionation regimens
Shorter radiation regimens than the internationally
recognised standard of whole-breast irradiation of
50 Gy in 25 fractions over 5 weeks would be par-
ticularly attractive to older patients to reduce the
burden of lengthy periods of outpatient attendance
and associated fatigue.
In the UK START A trial, two postoperative hypo-
fractionated dose fractionation regimens, 39 Gy in
13 fractions of 3.2 Gy and 41.6 Gy in 13 fractions
of 3 Gy, were compared with 50 Gy in 25 fractions
in 2236 women treated by mastectomy or breast-
conserving surgery. All regimens were given over
5 weeks. The 5-year LRR was 3.6%, 3.5% and 5.2%
for 50 Gy, 41.6 Gy and 39 Gy respectively.42 In the
START B trial, 40 Gy in 15 fractions over 3 weeks
was compared to 50 Gy in 25 fractions over 5 weeks
in 2215 women after primary surgery. The 5-year
locoregional recurrence rates were 2.2% and 3.3%
for 40-Gy and 50-Gy regimens respectively. Breast
cosmesis was superior in the 40-Gy arm. In both
trials the shorter regimens provided similar locore-
gional control to the standard 50 Gy. The National
Institute for Clinical Excellence (NICE) has adopted
a 40 Gy in 15 fractions dose fractionation regimen
as the new UK standard for adjuvant postoperative
radiotherapy.45 In the Canadian trial,44 1234 pa-
tients with T1/2 axillary node-negative breast can-
cer were randomised after breast-conserving surgery
with clear margins to a hypofractionated regimen
(42.5 Gy in 16 fractions over 3.5 weeks) of whole-
breast irradiation or to 50 Gy in 25 fractions over
5 weeks. No boost was given to the site of excision.
At 10 years the local recurrence rate was 6.7% in the
standard arm and 6.2% in the test arm. Breast cos-
mesis was similar in both arms of the trial. There has
been little consensus on the generalisability of the
findings of the START and Canadian hypofraction-
ation trials. The recent ASTRO Consensus statement
recommends that hypofractionated whole-breast ir-
radiation (HF-WBI) is confined to women 50 years
or older with T1/2 N0 disease not receiving chemo-
therapy or nodal irradiation.46 There is uncertainty
about the long-term effects of hypofractionated
radiotherapy on the heart. The ASTRO consensus
statement therefore advises that HF-WBI should
only be used where the heart is excluded from the
radiation fields. In contrast, 40 Gy in 15 fractions
has been endorsed by the guidelines of the National
Institute for Clinical Excellence for postconservation
and postmastectomy irradiation,45 a much broader
application of shortened fractionation.
The results of other hypofractionated dose frac-
tionation regimens have been reported in non-­
randomised studies. Kirova et al.,47 in a series of 317
patients aged 70 years or over treated with 32.5 Gy
in five fractions once weekly of 6.5 Gy, found similar
all-cause-free, local recurrence-free and metastasis-
free survival to conventionally fractionated radio-
therapy of 50 Gy in 25 daily fractions over 5 weeks.
Acute skin toxicity with the HF-WBI regimen was
acceptable and no different from the conventionally
fractionated patients of similar age. Cosmesis was
also similar. However, late complications measured
on the LENT-SOMA (late effects normal tissue –
subjective, objective management, analytic) showed
a higher incidence of grade 1–2 fibrosis (33%) with
HF-WBI compared with conventionally fractionated
therapy (15%). Similar rates of late effects were seen
using the same hypofractionated regimen.48
Partial breast irradiation
Partial breast irradiation (PBI) in which adjuvant
irradiation is delivered exclusively or in higher dos-
age to the primary site than the rest of the breast
This implies that, while quality of life is
in general a relevant issue in selecting patients
for treatment, it should not be a major factor in
determining whether or not older patients are
recommended to receive postoperative radiotherapy.41
While there is no randomised trial testing
hypofractionation in older patients, the results of
two UK trials42,43 and one Canadian trial44 are likely
to be practice changing for patients of all ages.
Both trials show that breast cancer is sensitive to
fraction size and that fewer larger fractions provide
equivalent local control with similar or reduced
breast toxicity.

The role of adjuvant radiotherapy in the management of breast cancer
249
is being investigated in a number of randomised
trials. The rationale for this approach is that lo-
cal recurrences occur predominantly at or close to
the site of excision.34,49 A number of techniques
are being studied in clinical trials, including exter-
nal beam import low,50 intraoperative kilovoltage
(TARGIT)51 (Fig. 15.3)/electron therapy (ELIOT)52
and intraoperative or postoperative brachyther-
apy.53 The rationale and indications for these tech-
niques have recently been reviewed.54 Of particular
interest to older patients are single fraction intraop-
erative techniques, which avoid the inconvenience
of attendance for several weeks of daily outpatient
radiotherapy. The only published randomised trial
of PBI is the TARGIT A trial,51 which randomised
predominantly low-risk postmenopausal patients
randomised to intraoperative radiotherapy (IORT)
with the Intrabeam device (Fig. 15.3) using 50 kV
X-rays (20 Gy to the surface of the applicator) or to
whole-breast irradiation. The local recurrence rate
was very low in both arms of the trial but the follow-
up was relatively short (4 years). The Kaplan–Meier
estimate of ipsilateral breast tumour recurrence at
4 years was 1.20% (95% CI 0.53–2.71) in the tar-
geted intraoperative radiotherapy group (Fig. 15.3)
and 0.95% (95% CI 0.39–2.31) in the external
beam radiotherapy group. The results, however,
are confounded by the option of investigators to
supplement IORT with external beam if the inves-
tigator considered that there were additional risk
factors for recurrence on the excision specimen.55,56
The main drawback of the technique is that irradia-
tion is delivered before the margins of excision are
assessed on the operative specimen. Intraoperative
electrons (3–12 MeV) using a mobile linear acceler-
ator delivering 21 Gy to the 90% isodose are being
studied by the Milan group, shielding the chest wall
with lead if required.52
Postoperative brachytherapy after lumpectomy us-
ing low-dose-rate implants over 4–5 days or high
dose rate typically twice daily for 5 days has yielded
low local recurrence rates.57,58 Largely in response
to the adoption of PBI outside of clinical trials pre-
dominantly in the USA and some parts of Europe,
consensus guidelines for the use of PBI have been
published by ASTRO and GEC, ESTRO.46,53 While
these guidelines may be a pragmatic approach to
PBI, they are not based on level I evidence.
Postmastectomy irradiation
It has long been established that postmastectomy
radiation therapy (PMRT) reduces the relative risk
of locoregional recurrence by about two-thirds in
a
b
Figure 15.3  •  Targeted intraoperative radiotherapy techniques with the Intrabeam system. (a) The applicator being
placed in the tumour bed. (b) The X-ray source is delivered to the tumour bed by use of a surgical support stand. The
sterile applicator is joined with a sterile drape that is used to cover the stand during treatment delivery. Reprinted from
The Lancet. Vaidya JS, Joseph DJ, Tobias JS et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy
for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 2010;
376(9735):91–102. With permission from Elsevier.
In the absence of level I evidence, it is important
that older patients are not recommended to have
PBI outside the confines of clinical trials. Patients
should be made aware, as the ASTRO guidelines
endorse,46 that whole-breast irradiation has a
much longer track record of safety and efficacy.
Until more level I evidence is published, PBI should
remain investigational.

Chapter 15
250
randomised trials.59–62 However, the impact on
overall survival has been controversial.22,63,64
An explanation for this survival benefit is that tumour
cells in local recurrence may have a greater proclivity
to metastasise than the original primary tumour.65
Support is lent to this idea by the fact that patients with
local recurrence have a higher breast cancer mortality
than patients with a new primary breast tumour.66,67
As Chung and Harris65 point out, there is a reduction
in local failure rate from chemotherapy alone (50% in
ER-positive disease at 5 years and one-third irrespec-
tive of ER status), although where the combination of
chemotherapy and radiation achieves more impact on
local control than either treatment alone.68,69
Role of postmastectomy
radiotherapy in intermediate
risk breast cancer
The role of PMRT in the intermediate-risk group
(i.e. women with a 10–19% 10-year risk of lo-
coregional recurrence) with one to three involved
axillary nodes or axillary node negative but with
other risk factors, e.g. grade 3 histology and/or lym-
phovascular invasion remains controversial with
proponents and sceptics of routine PMRT in this
setting.70,71 What is unclear is the generalisability
of the Danish and British Columbia trials to con-
temporary practice. The locoregional failure rate
in the Danish and Canadian trials was greater than
in many contemporary non-randomised American
series. This might in part be explained by subop-
timal axillary surgery with a median of only seven
nodes removed in the Danish trials and 11 in the
British Columbia trial. An additional criticism was
the intensity of chemotherapy.72 Furthermore, the
duration of cyclophosphamide, methotrexate and
5-fluorouracil (CMF) changed over the course
of the Danish premenopausal trial. Early in the
trial CMF was given for 12  months but this was
­subsequently shortened to 6  months. In addition
only 1 year of adjuvant tamoxifen was given in the
Danish 82b trial in contrast to the current standard
of 5 years. The risk of local relapse in intermediate-
risk patients was of the order of 5–15%73 and better
quality surgery and anthracycline-based adjuvant
chemotherapy will reduce this so that further reduc-
tions in risk by PMRT might be too low to justify
giving irradiation to all such women.
In response to concerns about the adequacy of
axillary surgery in the Danish trials, a subgroup
analysis of 1000 patients from the DBCG 82b and
82c trials was undertaken. It showed a survival ad-
vantage in women with one to three involved nodes
as well as those with four or more nodes. The au-
thors and others74 interpreted this analysis as im-
plying that all node-positive patients should receive
postmastectomy irradiation. Others have argued
that the somewhat historic Danish trial data are
not translatable to contemporary practice71 since
patients with similar levels of risk are now treated
with anthracycline-based chemotherapy rather than
the CMF-based regimens used in the Danish and
Canadian high-risk premenopausal studies.59,61
The role of PMRT in ‘intermediate-risk’ breast
cancer is currently being investigated in the MRC/
EORTC BIG 2- 04 SUPREMO trial.75 This includes
a biological substudy TRANS-SUPREMO designed
to analyse molecular markers associated with risk of
relapse. Biological factors may be important in se-
lecting patients for PMRT. Of note, an unplanned
subgroup analysis of more than 1000 patients in the
Danish 82b and 82c trials by ER, progesterone re-
ceptor and human epidermal growth factor receptor
(HER-2) status showed that the survival benefit of
PMRT was confined to hormone receptor-positive
patients and that hormone receptor-negative or triple
negative or HER-2-positive patients did not derive a
survival advantage.76 A possible explanation is that
these high-risk patients already have disseminated
disease on which PMRT is likely to have little impact.
Adjuvant radiotherapy in
older patients
Local control in breast cancer is as important for
older patients as it is for their younger counterparts,
whether after mastectomy or after breast-conserving
surgery. Radiotherapy, in conjunction with sur-
gery, continues to play a key role in ­achieving this.
The Oxford overview of randomised trials of ad-
juvant radiotherapy demonstrates that good local
A key watershed in the delivery of
locoregional radiotherapy of patients after
mastectomy was the publication in 1997 of the
Danish and Canadian randomised trials that
demonstrated a 10-year 9% survival benefit from the
addition of comprehensive locoregional radiotherapy
after mastectomy to systemic therapy in high-risk
premenopausal59,61 and postmenopausal women.60

The role of adjuvant radiotherapy in the management of breast cancer
251
control contributes to reducing breast cancer mor-
tality.77 There is, however, little level I evidence for
the role of adjuvant radiotherapy in breast cancer
in older patients largely due to the historical ex-
clusion of patients over the age of 70 from clini-
cal trials. Extrapolation of the results of trials of
adjuvant radiotherapy in younger patients to older
patients may not be appropriate given the different
biology of breast cancer in older patients and the
competing risks of non-breast cancer death in this
age group. In general older patients tend to have
more favourable biological prognostic factors than
younger patients with a higher proportion of hor-
mone receptor-positive tumours. This advantage is
counterbalanced by exclusion of older patients from
national breast screening programmes. As a result,
presentation with locally advanced disease with as-
sociated poor prognosis is still seen in older women.
For older patients with breast cancer, postoperative
whole-breast irradiation after breast-conserving sur-
gery remains the standard of care. Postmastectomy
radiotherapy is advised for ‘high-risk’ older pa-
tients. In ‘intermediate-risk’ breast cancer, its role is
controversial. Tolerance of radiotherapy in general
is good in older patients and does not impair quality
of life. Multimodality therapy should not be with-
held from older patients.
Axillary irradiation
With the rapid replacement of routine axillary
clearance by sentinel node biopsy as a less morbid
method of staging the axilla, the optimal manage-
ment of patients with micro- or macrometastases in
the axillary nodes and the role of axillary irradia-
tion is a focus of ongoing current debate. Central to
this discussion is the interpretation of the American
College of Surgeons Oncology Group Z0011 phase
III trial,78 which randomised patients with T1–T2
sentinel node biopsy-positive invasive breast can-
cer treated by breast-conserving surgery to no fur-
ther surgery or to axillary lymph node dissection
(ALND). Patients with micro- or macrometastases in
one or two sentinel nodes were included. The whole
breast was irradiated by tangential fields and sys-
temic therapy given as appropriate. This was a non-
inferiority trial with an intended target accrual of
1900 patients, although less than half were actually
accrued. At a median follow-up of 6.3 years there
was no difference found in 5-year rates of locore-
gional recurrence (1.6% for SLNB alone compared
to 3.1% in the ALND arm) or in overall survival
(92.5% vs. 91.8% respectively). The hazard ratio
for overall survival was 0.79 (90% CI 0.56–1.11)
When adjusted for age and systemic therapy, the HR
rose to 0.87 (90% CI 0.62–1.23). Both these figures
were interpreted by the authors as demonstrating
non-inferiority of the SLNB-alone arm and endors-
ing a policy of observation only in SLNB patients
without the need for axillary irradiation. However,
there are major issues with this trial. Firstly, the trial
was closed prematurely after the accrual of 900 pa-
tients, less than half of the planned target accrual
of 1900 patients. The trial was therefore potentially
underpowered to detect the primary end-point of
overall survival (500 deaths were needed to have
90% power to confirm non-­inferiority of SLNB
compared to axillary node dissection) although it
did reach its statistical end-point. Secondly, there
was no quality assurance of the radiotherapy of
the trial to confirm that there was no difference in
field placements between the two arms of the trial.
In the SLNB arm, radiation oncologists might have
been tempted to raise the upper border of tangential
fields in order to cover more of the axillary nodes.
This is currently being investigated. If there was
genuinely no difference then this would be reassuring
that there was no bias in RT technique. A number of
possible explanations for the low event rates in the
axilla have been postulated,79 including the low-risk
population studied, the impact of systemic therapy
and immune surveillance mechanisms suppressing
axillary disease. Certainly event rates in contem-
porary trials of therapy in early breast cancer have
been falling. However, the impact of immune sur-
veillance mechanisms in dealing with axillary dis-
ease is poorly understood and remains speculative.
To address concerns about leaving residual axillary
disease untreated after SLNB, a number of algo-
rithms have been developed to predict the probabil-
ity of non-sentinel lymph node involvement. These
algorithms have been tested retrospectively, gener-
ally in small cohorts of a few hundred patients with
positive sentinel nodes. In the recent study, for ex-
ample, on a cohort of 159 patients from China,80
the Cambridge and Mou models outperformed
the Mayo, Tenon, MD Anderson, Memorial Sloan
Kettering, Turkish, Llubjana, SNUH and Louisville
models. However, there remain limitations to these
models in predicting residual axillary disease. There
is at present limited data to inform best practice,
and such data may not be an argument to convince

Chapter 15
252
all surgeons that observation only is an option for
selected patients with involved nodes following
SLNB. An option to complete axillary dissection is
axillary irradiation, as it is proven therapy to con-
trol axillary disease, although there is limited level I
evidence. The Edinburgh randomised trial included
patients treated by BCS and mastectomy and com-
pared ALND to axillary RT in axillary lymph node
sample-positive patients.81 It showed no difference
in regional control at 5 years or in overall survival.
The trial provided excellent data on axillary mor-
bidity showing a low incidence of lymphoedema
in the axillary RT arm but some long-term limita-
tion of shoulder mobility. Higher levels of persistent
lymphoedema complicated ANLD. The ongoing
AMAROS trial82 is comparing ANLD and axillary
irradiation in patients with sentinel node metasta-
ses. Identifying more reliably the subset of patients
with sentinel node macrometastases who need
­axillary irradiation requires more level I evidence.
In the absence of such evidence, a pragmatic ap-
proach to selecting higher risk patients on the basis
of number of positive sentinel nodes, tumour size,
ER status and presence or absence of lymphovascu-
lar invasion proposed by Haffty et al.79 (Table 15.1)
is a reasonable pragmatic approach.
Minimising radiation-induced
cardiac morbidity
Older radiotherapy techniques that led to excess
­radiation-induced cardiac toxicity and mortal-
ity have been replaced by three-dimensional plan-
ning84 and breath holding techniques1 to minimise
cardiac irradiation in left-sided tumours. In suc-
cessive cohorts of patients treated in the USA, ra-
diation-induced cardiac mortality has fallen.85 This
almost certainly reflects the introduction of three-­
dimensional planning for breast cancer. Ischaemic
heart disease is commoner in older patients. While
the cardiac sequelae of adjuvant breast irradiation
may take 10 years to manifest themselves, this la-
tency may be within the life expectancy of older
patients with early breast cancer. At least the same
priority should be given to minimising cardiac ir-
radiation in older as in younger patients.
Clinical and
pathological
parameters
No. of
positive
sentinel
nodes
Total no.
of sentinel
nodes
sampled
Probability
of additional
nodes* (%)
Probability
of ad-
ditional
nodes† (%)
Probability
of four or
more nodes
involved‡ (%)
Field design
IDC, 1.0 cm, LVI
negative, ER positive
1 (IHC only)
3
3
8
<1
Tangents only
IDC, 1.8 cm, G3, LVI
negative, ER positive,
unifocal
1 (macro)
2
27
24
2
High tangents
IDC, 2.0 cm, ER
negative, LVI positive
2 (macro)
2
63
55
30
High tangents/
consider full
nodal irradiation
ILC, 4.0 cm, ER
positive, multifocal,
LVI negative
2 (macro)
2
77
64
40
High tangents/
consider full
nodal irradiation
IDC, 3.0 cm, ER
negative, LVI positive,
multifocal
3 (macro
with ENE)
3
78
95
80
Full nodal
irradiation
Table 15.1  •  Suggested approach for radiation field design in patients with positive sentinel node biopsy without
axillary lymph node dissection
Abbreviations: ENE, extranodal extension; ER, oestrogen receptor; G, grade; IDC, infiltrating ductal carcinoma; IHC,
immunohistochemistry; ILC, infiltrating lobular carcinoma; LVI, lymphovascular invasion; Macro, macroscopic.
*On the basis of the Memorial-Sloan Kettering Cancer Center nomogram.
†On the basis of the MD Anderson Center nomogram.
‡Katz et al.83
Modified from Haffty BG, Hunt KK, Harris JR et al. Positive sentinel nodes without axillary dissection: implications for the radiation
oncologist. J Clin Oncol 2011; 29:4479–81.

The role of adjuvant radiotherapy in the management of breast cancer
253
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• The role of postmastectomy irradiation in the one to three node-positive group is controversial.

Chapter 15
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258
16
Lesley Fallowfield
Valerie Jenkins
Psychosocial issues in breast cancer
Introduction
The diagnosis of breast cancer, for women at any
age and stage, brings with it a myriad of emotions,
provoked by the decisions needed and concerns
about the surgery, systemic treatments and likely
prognosis. Conveying options to anxious patients
is not easy. The increasingly complex nature of the
disease, in terms of its molecular profile and ap-
propriate novel targeted therapies, necessitates ever
more advanced communication skills if patients are
to make informed choices.
This chapter deals with many of the psychosocial is-
sues associated with treatments for breast cancer, but
is not exhaustive. It reflects some of the most topical
questions of the day, which include delay in presenta-
tion, quality of life associated with adjuvant and tar-
geted therapies, and dilemmas associated with ductal
carcinoma in situ. We also discuss the efficacy of inter-
ventions aimed at preventing or ameliorating some of
the problems associated with diagnosis and treatment.
Delay in presentation
Despite efforts to increase awareness, many women
in the UK present late with their breast cancer; this
delay can be due to patient or provider factors.
Patient delay refers to the interval between first
detection of symptoms and first medical consulta-
tion. The period that most authors accept as pro-
longed delay is 12 weeks or more,1 although others
regard patient delay as 4 weeks or more.2 Provider
or ­system delay is usually taken to be the interval
between first presentation to the GP and initial
treatment, and is not easy to define. Some of the
reasons for patient delay can be ignorance of the
symptoms, or fears about breast cancer and its as-
sociated treatments.
Unfortunately, delay of greater than 3 months is as-
sociated with worse outcomes. In the UK it has been
shown to contribute to the difference in survival be-
tween rich and poor3 and ethnic groups, especially
Black African women.4 Also, older women who have
lower levels of knowledge about the signs and symp-
toms of breast cancer are more likely than younger
women to present late. In a survey of 712 older (67–
73 years) British women, 50% believed their lifetime
risk of developing breast cancer was 1 in 100 and
75% were not aware that age was a risk factor.5 In
an attempt to improve breast awareness, Linsell et al.
conducted a randomised controlled trial (RCT) with
867 women attending for their final routine appoint-
ment on the UK NHS Breast Screening Programme.6
Women were randomised to receive a scripted 10-
minute interaction with a radiographer plus a book-
let that conveyed key breast awareness messages, the
booklet alone or usual care. The primary outcome
was the proportion of women achieving breast can-
cer awareness at 1  month. Results from this RCT
did show an increased awareness in the intervention
group compared with usual care at 1 month (32.8%
vs. 4.1%), and the booklet versus usual care
(12.7% vs. 4.1%), which was largely maintained
at 12  months. Whether knowledge translates into

Psychosocial issues in breast cancer
259
a change in behaviour is yet to be determined. A
systematic review of the efficacy of interventions to
promote cancer awareness and early presentation
reveals some evidence that interventions delivered
at an individual level can promote cancer awareness
in the short term, but insufficient evidence that these
promote early presentation with cancer symptoms.7
Individuals' behaviours are not governed by a single
set of attitudes and can change over time, therefore
predicting which factors determine change is in-
volved and complex.
Psychosocial issues with
breast cancer surgery
Decision-making
Although surgeons perform breast-conserving sur-
gery (BCS) wherever possible, this does not always
translate into measurable reductions in psychologi-
cal morbidity. Some have suggested that psycho-
logical morbidity could be prevented if only women
were allowed to choose their preferred surgical
treatments. Although the proponents of more con-
sumerist approaches strongly assert the putative
benefits of active participation in treatment deci-
sion-making, these benefits are not well supported
by firm data. In one study, the decision-making pref-
erences of 150 women with newly diagnosed breast
cancer were established and compared with those of
200 women with benign breast disease. The major-
ity of women with breast cancer preferred a more
passive role, whereas the majority of the benign dis-
ease group wished for a more collaborative role.8
Data from the USA examined decision-making in
1884 women with ductal carcinoma in situ (DCIS)
and invasive breast cancer. Results showed that al-
though only 11.5% had clinical contraindications
to BCS, 30% had mastectomy as their initial surgi-
cal treatment. The majority of the women (41%)
reported that they had been the primary decision-
maker, 37% felt that the decision was shared with
the surgeon and 22% felt that the decision had been
made by their surgeon.9 Intriguingly, the greater
the patient involvement in decision-making the
more likely that mastectomy was the preferred sur-
gery. After adjusting for clinical and demographic
­variables, significant correlations were found. Only
5.8% of women whose surgeon made the decision
had a mastectomy compared with 16.8% of the
women who shared decision-making and 27% of
those who made the decision themselves (P = 0.003).
The primary reason for a mastectomy prefer-
ence was fear about recurrence. Although 80% of
women expressed a high degree of confidence about
their decisions, fewer than 50% were able to answer
correctly a true/false question about the lack of a
survival difference between mastectomy and BCS.
Effects of type of surgery
Many have asserted that the type of surgery makes a
difference to patients' quality of life (QoL). However,
except for differences in perception of body image,
the literature comparing the other psychosocial se-
quelae of BCS with mastectomy is ambiguous and
shows a lack of substantial benefits.10–12 Few have
examined QoL prospectively beyond a 2-year period,
yet approximately 80% of women with breast cancer
survive ≥5 years.13 Engle et al.14 measured long-term
QoL in women (n = 990) treated with BCS or mas-
tectomy at regular intervals over 5 years. The cross-
sectional data showed that mastectomy patients had
significantly (P<0.01) lower satisfaction with body
image, role and sexual functioning scores, and their
lives were more disrupted than BCS patients. Another
study showed that at 5 years women who had BCS
had a significant increase in overall QoL compared
with those who had a mastectomy.15 Surprising dif-
ferences were found by Collins et al. examining QoL
in women (n = 549) who had BCS, mastectomy or
mastectomy plus reconstruction.16 The researchers
adjusted the analysis to take account of the severity
of surgical side-effects by type of operation. In the
model without surgical side-effect severity, women
who underwent mastectomy plus reconstruction re-
ported poorer body image than those who had BCS
at all time points except the last (T4: 2 years post op).
When they adjusted for surgical side-effect severity,
body image scores did not differ significantly from
patients with BCS. Also, women who had mastec-
tomy alone had a better body image at T2 (6 months)
than those who had reconstruction (P = 0.011). The
authors explained that dissatisfaction with body im-
age can be explained in part by patients' experience
of surgical side-effects, ­including wound infections.
However, the severity of the side-effects did not sub-
stantially weaken the effects of an elevated depressed
mood on patients' body image problems.

Chapter 16
260
Impact of axillary surgery on
quality of life
Sentinel lymph node biopsy (SLNB) is now estab-
lished as an accurate, minimally invasive means
of providing regional staging for primary breast
cancer, and the standard of care for patients with
clinically node-negative breast cancer.17 In the UK
ALMANAC (Axillary Lymphatic Mapping Against
Nodal Axillary Clearance) trial of 1031 patients,
data showed that women who received standard ax-
illary treatment recovered more slowly than those in
the SLNB group (P<0.01).18 The ALMANAC trial
showed that the benefits of sentinel node biopsy are
not only reduction of unnecessary resection of the
axilla, but also a marked reduction in unwanted
sequelae such as arm morbidity, thus permitting a
better quality of life, without sacrificing any stag-
ing accuracy. However, 25% of the SLNB group
required further axillary surgery or radiotherapy to
the axilla because of spread of disease. Additional
surgery is normally conducted 2  weeks later and
this two-stage procedure has advantages and disad-
vantages. The latter include the psychological and
physical stress associated with a second operation;
conversely, the delay could be viewed as a benefit
by some, giving time to adjust to the knowledge
that their breast cancer has spread. Recently some
units are able to offer intraoperative SLNB analy-
sis, which allows immediate progression to axillary
clearance in patients found to have positive nodes.
However, there is still debate amongst clinicians on
the accuracy of intraoperative analysis,19,20 but find-
ings from women who had and had not experienced
this diagnostic technique revealed a positive incli-
nation towards the one-step axillary surgery. The
advantages included: knowing the result straight
away, less anaesthesia, fewer days in hospital and
consequently more cost-effectiveness for the NHS.21
Ductal carcinoma in situ
Women given the diagnosis of ductal carcinoma in
situ (DCIS), be it low, moderate or high grade, can
be left wondering whether or not they have breast
cancer. Some describe it as ‘a very early form of
breast cancer’22 or pre-cancerous condition. Most
often it is found through mammographic screening
and the incidence is increasing. Although mortality
risk is low, treatments are similar to that demanded
of invasive breast cancer (surgery, radiotherapy, en-
docrine therapy) and women are left confused. The
psychological and QoL impacts of having a label of
DCIS and how it affected women's lives have been
subject to review.23 Studies show that although those
with low/intermediate-grade DCIS have an excellent
prognosis and normal life expectancy, many women
experience substantial psychological distress. Cross-
sectional studies have compared psychosocial out-
comes of women with DCIS with those with early
invasive breast cancer (EBC).24,25 Findings suggest
DCIS patients have better physical health, sex life
and social functioning than women with invasive
breast cancer. However, despite the relatively good
prognosis, DCIS patients held perceptions about the
risk of recurrence and dying comparable to women
with EBC. Other research showed that women had
inaccurate perceptions about their risk of invasive
disease and spread of DCIS to other parts of their
body that changed little across an 18-month period;
these perceptions were strongly related to distress.26
Lauszier et  al. reported similar levels of psycho-
logical distress in women with DCIS and those with
invasive disease who had a worse prognosis.27 So al-
though women with DCIS reported significantly bet-
ter physical health, it did not offset the psychological
distress felt of having a cancer diagnosis. This finding
is supported from results of a UK-based study with
50 women with DCIS, whose QoL, psychological
functioning and body image were measured at three
time points (baseline, 6 and 9 months). The results
provide a valuable insight of emotional distress dur-
ing the first year post-­diagnosis, with some women
experiencing significant levels of distress both in the
short and long term.28 Previous DCIS research has
proposed that some of the influencing factors for
this distress are confusion about the diagnosis and
prognosis, ­together with inaccurate risk perceptions.
There remains considerable controversy about
the natural history of low-grade DCIS and it is
now commonly diagnosed by routine breast can-
cer screening. The diagnosis and treatment of a
condition that may not cause problems during the
patient's lifetime is considered by some to be both
overdiagnosis and overtreatment.29 There are few
conclusive data demonstrating that low-grade DCIS
commonly develops into invasive cancer, prompt-
ing some to question the use of the word carcinoma
in the diagnosis. Conducting randomised trials to

Psychosocial issues in breast cancer
261
­determine whether or not active surveillance or
giving endocrine therapy is as safe an option as
immediate surgery is important but fraught with
difficulty. Outcomes of both the safety and psy-
chosocial sequelae of hormone therapy (IBIS II) are
awaited. Clinical trials comparing surgery with ac-
tive monitoring or hormone therapy for low-grade
DCIS are urgently required.
Hormone therapy
RCTs have demonstrated the efficacy of selective
oestrogen receptor modulators (SERMs) such as
tamoxifen in preventing recurrence in oestrogen
receptor (ER)-positive early breast cancer, and
in other studies the superiority of the aromatase
inhibitors (AIs). Recommendations worldwide
mean that most women will have to endure at
least 5 years of therapy. Unfortunately there is still
uncertainty as to which women really benefit from
these drugs. ER positivity is not a sensitive enough
marker. A substantial number of women at low
risk of recurrence with small tumours, who have
had complete local excision and radiotherapy, de-
rive no extra benefit from this therapy but experi-
ence considerable iatrogenic harm. Many of these
side-effects go under-reported, unrecognised and
untreated.
Studies comparing clinician-reported (via case
report forms in trials) and patient-reported (via
validated questionnaires and interviews) quality of
life rather than life-threatening side effects show
little concordance.30–33 Apart from this inaccurate
reporting, severe and/or untreated side-effects can lead
to discontinuation of therapy or non-adherence in
between 25% and 55% of patients.34,35 Ameliorative
interventions are consequently an important and
neglected area of research. In the section below we
present an overview of some of the evidence for
various interventions aimed at the primary side-­
effects: vasomotor complaints, gynaecological/
sexual issues and musculoskeletal problems, espe-
cially arthralgia.
Vasomotor problems
Hot flushes and drenching night sweats are some of
the most commonly reported problems (30–45%)
associated with all hormone treatments.34,35 Not
only are they extremely unpleasant but they inter-
fere with sleep and impact on numerous other activ-
ities of daily living and quality of life. Mechanisms
are complex but are probably oestrogen withdrawal
rather than related to absolute levels of circulating
oestrogen. Hormone replacement therapy (HRT)
is of course a useful treatment for menopausal hot
flushes but HRT is not appropriate for breast can-
cer, as shown in the HABITS trial.36 Other amelio-
rative interventions are shown in Table 16.1.
The evidence for efficacy for most of the dietary
changes, herbal remedies and practical interventions
is very thin, and there have been reports that some of
the unregulated herbal supplements may be danger-
ous and potentiate the adverse events of orthodox
anticancer treatments. Other interventions are wor-
thy of more examination.
Acupuncture
A systematic review of acupuncture in breast can-
cer showed that of the three RCTs employing sham
acupuncture control arms, only one was favourable
in reducing hot flush frequency; however, a meta-
analysis has suggested a benefit overall (P = 0.05),
although there was marked heterogeneity in the
data.37 One study of acupuncture compared with
HRT favoured HRT, another two comparing acu-
puncture versus venlafaxine or relaxation therapy
found a small benefit for acupuncture but no dif-
ferences between groups. All these studies suffer
from small numbers. A more comprehensive study
enrolled women who had experienced more than
seven hot flushes per day for 7 consecutive days.38
Patients were randomised to acupuncture or con-
trol. Primary outcome was hot flush frequency with
Complementary therapies
Acupuncture, relaxation,
paced breathing, yoga, t'ai chi,
mindfulness, hypnosis
Dietary changes
Avoidance of alcohol, caffeine
and spicy foods
Supplements and herbal
remedies
Dong quai, primrose oil, red
clover, Black Cohosh, Mexican
yam
Practical advice
Dressing in layers, menopausal
pyjamas and chillows, air-
conditioning, fans and drinking
cold water
SSRIs and SNRIs
e.g. venlafaxine, paroxetine
Table 16.1  •  Ameliorative interventions for side-effects

Chapter 16
262
a wide variety of other secondary end-points. Both
frequency and intensity of hot flushes were signifi-
cantly reduced in the acupuncture arm (P<0.001).
There were also reductions in sleep disturbance
and other somatic symptoms as measured with the
Women's Health Questionnaire (WHQ).39
Relaxation, mindfulness, yoga, hypnosis
Stress and anxiety are common features associated
with the diagnosis and treatment of breast cancer
and appear to contribute to the frequency and in-
tensity of symptoms.40,41 It seems a reasonable hy-
pothesis therefore that any behavioural technique
that reduces stress may help vasomotor complaints.
As with acupuncture these studies often lack good
controls and include only small numbers but there
does appear to be some beneficial evidence in sup-
port of hypnosis,42 ­relaxation/paced breathing,43,44
yoga45 and group cognitive behavioural therapy.46
From a clinical point of view all these interventions
have the advantages of being inexpensive, very ac-
ceptable and attractive to women, and importantly
have no adverse events.
Selective serotonin reuptake inhibitors
(SSRIs) and selective norepinephrine
reuptake inhibitors (SNRIs)
Clinicians who are sceptical about the previously
mentioned interventions are often more comfort-
able recommending drug therapies such as the selec-
tive serotonin or norepinephrine uptake inhibitors.
Venlafaxine has been tested in numerous studies. An
important double-blind placebo-controlled RCT of
different doses revealed a significant reduction in
hot flush scores (P<0.001) but some side-effects,
including a dry mouth, appetite loss and constipa-
tion.47 A double-blind crossover study with parox-
etine showed a significant reduction in hot flushes
(P<0.001); furthermore, patients were less likely to
discontinue a 10-mg dose compared with 20 mg,
as the latter dose resulted in greater toxicity.48 In
a double-blind crossover RCT of fluoxetine there
was a 24% improvement in hot flush reduction fa-
vouring fluoxetine (P = 0.02).49 Likewise, another
randomised double-blind crossover study favoured
sertraline.50 This project also examined preference
and demonstrated that 48% of patients preferred
sertraline, 11% placebo and 41% had no prefer-
ence. Anxieties still exist about the potential effects
of CYP 2D6 inhibition for some patients taking
tamoxifen and SSRIs, although most recent research
has failed to offer compelling cause for concern. The
benefits of SSRIs and SNRIs in hot flush reduction are
clear, but the side-effects sometimes outweigh these
and may lead to discontinuation. Research on effi-
cacy and safety with newer antidepressants such as
mirtazapine or citalopram is ongoing, and also with
the anticonvulsant gabapentin, to see if they have
fewer side-effects. Gabapentin produces a 35–66%
reduction in hot flash score but patients prefer venla-
faxine 2:1 over gabapentin. Likewise, there are sev-
eral comparative trials being conducted of different
treatments using reductions of vasomotor problems
and patient preference as outcomes.51 Most recent
research has suggested that escitalopram (Cipralex)
conveys benefits without too many side-effects.52
Gynaecological/sexual problems
The AIs and SERMs create numerous gynaeco-
logical and sexual problems for patients. Discharge
(5–17%) is probably higher in tamoxifen than in
the AIs but vaginal dryness affects between approxi-
mately 16% and 40% of women taking anastro-
zole, exemestane or letrozole.33 As a consequence,
­previously sexually active women may experience
dyspareunia (15–18%) and a loss of libido (16–45%).
In extreme cases patients may develop very unpleas-
ant and painful vulvo-vaginal atrophy. The most
appropriate ameliorative intervention for dryness
and dyspareunia is regular use of moisturisers such
as Replens®. Lubricants alone are insufficient. For
vulvo-vaginal atrophy there are suggestions from
early phase trials that progesterone and testosterone
creams may help.53 For clinicians worried about
oestrogen in breast cancer, studies have shown that
Estring® has a low systemic uptake of oestrogen.54
Musculoskeletal problems
and arthralgia
Adjuvant trials of anastrozole,55 letrozole56 and ex-
emestane57 show reports of joint pains and stiffness
or arthralgia to be common (20–30%). A survey
of UK clinicians reported that AI-induced arthral-
gia is a distinct clinical problem, with limited data
on its aetiology and management.58 Arthralgic pain

Psychosocial issues in breast cancer
263
and stiffness can be an important reason for discon-
tinuation of AI therapy. Unfortunately, these do not
always respond to analgesia, they negatively im-
pact on QoL and can lead to non-adherence. The
mechanism remains uncertain and is certainly dif-
ferent from the normal aches and pains of ageing.
Oestrogen deprivation, together with the release
of pro-inflammatory cytokines (interleukin-1β, tu-
mour necrosis factor-α), is the most likely cause.59
Crew et  al. conducted a small crossover study
of full-body and auricular acupuncture, 30 min,
twice weekly for 6 weeks on 27 women who had
been taking an AI for at least 6 months and who
were experiencing arthralgia.60 Using numerous val-
idated patient-reported outcome measures (PROs),
the authors reported significant improvements
in worst pain (P = 0.01), pain severity (P = 0.02),
functional interference (P = 0.02), functional ability
(P = 0.02) and overall physical well-being (P = 0.04).
SSRIs and SNRIs
Duloxetine is an SNRI used for multiple chronic
pain. Henry et  al. reported a small pilot study for
postmenopausal women on AIs with new or worsen-
ing pain.61 Duloxetine 30 mg daily was administered
for 7 days, then increasing to 60 mg daily. The study
employed many patient-reported outcome (PRO)
measures, looking at quality-of-life symptoms, sleep
quality, menopause and hot flushes, but the pri-
mary end-point was a 30% decrease in pain. Results
showed that 21 of 29 evaluable patients reported
≥30% decreased pain. The authors also reported
other significant improvements including the amount
of interference caused by pain and improvement in
hot flushes, depression and sleep. Although 78% of
patients continued on treatment, it did cause fatigue,
xerostomia and headache. This was a very small study
but the drug seems worthy of examination in a larger
RCT. In an observational study vitamin D deficiency
was suggested as the cause of musculoskeletal pain62
and a double-blind placebo-controlled RCT of high-
dose vitamin D seemed to improve pain reports.63
Hormone therapy undoubtedly benefits many
women with breast cancer but quality-of-life-­
threatening toxicities may be much more of a prob-
lem than commonly acknowledged. We require
systematic assessment of the impact of treatment using
validated PROs so that evidence-based interventions
can be offered in a timely manner. It is also clear that
we need to conduct much more high-­quality research
into ameliorative interventions with sensible numbers
of patients and using robust outcome measures.
Exercise
In the past, cancer patients were usually advised to
rest and avoid physical effort. However, it is now
well established that excessive rest and lack of physi-
cal activity may result in severe deconditioning and
reduced physical functioning. Women undergoing
chemotherapy or radiation therapy as adjuvant
treatment for breast cancer commonly experience
debilitating side-effects including nausea,64 fatigue,65
weight gain66 and mood disturbances.67 These side-
effects can interfere with daily activities such as self-
care or return to work and exercise for patients with
cancer is strongly supported by national cancer char-
ities. A report by Macmillan suggested that patients
who are receiving cancer treatments engage in two
and a half hours of exercise a week.68 This advice
is in line with the Department of Health guidelines
that recommend two and a half hours of moderate
to vigourous intensity exercise for adults each week,
moderate exercise defined as swimming or a brisk
walk.69 Adherence to exercise programmes is, how-
ever, a problem and the mean dropout rate from su-
pervised exercise programmes has remained at 50%
over the decades.70 However, being diagnosed with
a serious illness can prompt an individual to change
their lifestyle and there are media reports of individ-
uals running half-marathons even whilst undergoing
treatments for breast cancer.71
Whilst these are uplifting accounts, running a
half-marathon will not appeal to the majority of
women undergoing treatments for breast cancer.
However, there are reports that less intensive ex-
ercise can be of benefit, both during and follow-
ing treatment. Courneya and colleagues have been
involved in this area of research for many  years,
examining via RCTs which exercise programmes
engage patients and also the barriers and predictors
of exercise behaviour. In one study they randomised
242 women initiating chemotherapy treatment to
resistance training, aerobic exercise or usual care
for the duration of their chemotherapy regimens
(mean of 17 weeks).72 Although neither aerobic nor
resistance exercise significantly improved QoL in
breast cancer patients receiving chemotherapy, the
programmes improved self-esteem, physical fitness,

Chapter 16
264
body composition and chemotherapy completion
rate without causing lymphoedema or significant
adverse events. At 6-month follow-up, the women
were sent a questionnaire that assessed QoL, self-
esteem, fatigue, anxiety, depression and exercise
behaviours.73 Eighty-three per cent (201/242)
­responded; compared to usual care, those who par-
ticipated in the resistance training maintained an
increase in self-esteem. There was a reduction in
anxiety in the aerobic group that had not been ob-
served during chemotherapy. The authors also mea-
sured which factors, personal and clinical, predicted
exercise training responses.74 They found patients
who had a preference for resistance training had
improved QoL when they were assigned to receive
it, compared with usual care (P = 0.008). Patients
who had no preference had improved QoL when
they were assigned to receive either programme
(P = 0.014). The barriers to supervised exercise
varied but over half were directly attributed to the
disease and side-effects of treatments.75 Exercise be-
haviour 6 months after the trial was predicted by a
wide range of demographic, medical, behavioural,
fitness, psychosocial and motivational variables,
which highlights the difficulties with promoting and
maintaining fitness.76 A Cochrane review of exer-
cise in women receiving adjuvant therapy for breast
cancer that included nine controlled trials involving
452 patients concluded that physical exercise can
improve physical function even during cancer treat-
ment. This review also considered that there was
still not enough evidence about the effect of exercise
on outcomes such as fatigue, mood disturbances,
immune function and weight gain.77
There are other forms of ‘exercise’ that may ap-
pear more attractive to patients with breast can-
cer, including yoga and Pilates. An evidence-based
review of yoga as a complementary therapy for
patients with cancer, including six RCTs, con-
cluded that yoga helped improve mood, QoL and
decrease anxiety.78 More research is warranted on
whether yoga can improve specific physical dam-
age, for example arm morbidity following axillary
surgery.
Conclusion
There are a large number of studies showing that
the adjuvant systemic therapies that form part of
the management pre- and post-breast cancer surgery
impact on the quality of patients' lives. In a recent
report of 653 women with breast cancer, substantial
numbers sought help with symptoms: hot flushes
(41%), night sweats (36%), loss of interest in sex
(30%), difficulty sleeping (25%), fatigue (22%) and
extreme vaginal dryness (19%).79 Chemotherapy-
induced ovarian failure was reported by 29% of the
breast cancer patients seen. A wide range of man-
agement approaches were offered, with 55% of the
women prescribed non-hormonal pharmacologi-
cal therapies for vasomotor symptoms, including
vitamin E 400 IU twice daily (21%), venlaflaxine
75 mg CR once daily (13%), clonidine 50 μg twice
daily (11%), or gabapentin 300 mg three times daily
(4%). As found in other studies, vasomotor symp-
toms, sexual dysfunction and sleep disturbance are
the most distressing menopausal symptoms requir-
ing attention. Menopausal symptom management
after breast cancer is complex and demands a multi-
disciplinary approach with interventions appropri-
ately tested and monitored.
Summary
The treatments available to women with breast can-
cer continue to improve, offering many the prospect
of cure or lengthier lives. Despite these advances
and improvements in the delivery of care and pro-
vision of support services, the diagnosis of breast
cancer still causes considerable distress. Women
cope in many different ways with the knowledge
that they have a potentially life-threatening disease
requiring unpleasant treatments. For some it is a
major emotional and social catastrophe, whereas
others approach it with a degree of equanimity
and/or stoicism. It is sometimes difficult to predict
how women will react, adapt and adjust to what
lies ahead. Greater awareness of some of the psy-
chosocial, sexual and cognitive dysfunction associ-
ated with different treatments should enable us to
design interventions to prevent or ameliorate their
problems. The importance of provision of good
clear information delivered in a supportive, honest
and empathic manner should not be overlooked.
The communication skills of a surgeon can exert a
surprisingly useful psychotherapeutic impact on a
woman and her ability to cope with the disease and
its treatment.

Psychosocial issues in breast cancer
265
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• Despite efforts to increase awareness, many women in the UK present late with their breast cancer;
there is some evidence that interventions delivered at an individual level can promote cancer awareness
in the short term, but insufficient evidence that these promote early presentation of cancer symptoms.
• There is considerable controversy as to whether or not screening results in overdiagnosis and
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ameliorative interventions.

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268
17
Steven Thrush
J. Michael Dixon
Benign breast disease
Introduction
Over 90% of patients presenting to a breast clinic
have normal breasts or benign breast disease.1
An understanding of the aetiology, symptoms
and management will ensure correct treatment
and patient satisfaction. The expectation that the
breast surgeon's role is simply to diagnose or ex-
clude breast cancer has long disappeared. Benign
breast disease causes considerable morbidity and
anxiety, and with increasing patient awareness
and expectations, the number of such patients at-
tending clinics is increasing. Effective treatment
includes accurate diagnosis followed by adequate
explanation of the condition, provision of relevant
information related to the diagnosis and how it is
best managed. This is a rewarding part of a breast
specialist's workload.
Benign breast disease can be divided into congeni-
tal abnormalities, aberrations of normal breast de-
velopment and involution (ANDI) and conditions
secondary to some extrinsic precipitatory factors
(non-ANDI).
Congenital abnormalities
Although not diseases as such, developmental ab-
normalities of the breast can cause considerable
concern and are not uncommon reasons for referral
to a breast clinic.
Supernumerary nipples and
accessory breast tissue
Accessory breast tissue is usually found in the ax-
illa and supernumerary or accessory nipples are
usually seen below the breast and above the um-
bilicus. Accessory nipples vary and are usually just
rudimentary but can include glandular tissue (acces-
sory breast). Accessory nipples in the bra line can be
excised if they cause irritation.
Accessory breast tissue tends to become more
prominent or obvious during pregnancy (Fig. 17.1).
Reassurance and an explanation of the cause of the
‘lump’ are usually all that is required. Surgical exci-
sion should be reserved for those truly symptom-
atic, as they are difficult to excise cosmetically and
surgery is associated with significant morbidity.2
Liposuction during excision helps define the planes
between the accessory breast and the fascia of the
axilla. As with normal breast tissue, both benign
and malignant conditions can develop within acces-
sory breast tissue.3
Breast hypoplasia
This is failure of one or both (rarely) breasts to develop
fully and can be congenital or acquired. Genetic causes
include Poland's syndrome and ­ulnar–mammary
­syndrome. Poland's syndrome is a group of conditions

Benign breast disease
269
associated with the absence of hypoplasia of the pec-
toralis major muscle, the chest wall and varying de-
grees of syndactyly.4 It is rare and usually only partial
in nature. It is more common in men than in women.
Acquired abnormalities in breast development can be
caused by iatrogenic trauma or radiotherapy.
Treatment of hypoplasia and Poland's syndrome
depends on the degree of deformity. Mild asym-
metry is a common problem and usually only re-
assurance is needed. If the asymmetry is marked,
augmentation of the smaller breast with or with-
out tissue expansion and/or reduction or aug-
mentation of the opposite breast may be required
(Fig. 17.2). Tissue expansion is often required as
there are differing amounts of skin on the two
breasts. A pedicled or free myocutaneous flap,
with or without an implant, can be used to recon-
struct any muscle defect and produce symmetry in
cases of severe hypoplasia or aplasia. Fat transfer
(lipofilling) has also been described as a technique
to correct or aid correction of breast hypoplasia
either alone or combined with a breast implant.5,6
Hypoplasia can also be associated with tubular
or tuberous breasts. This deformity can affect one
or both breasts and the breast shape is caused by a
constricting ring at the base of the breast, limiting
vertical and horizontal growth. The surgical man-
agement of this group of conditions is challenging
and often unsatisfactory. Tissue expansion com-
bined with radial incisions on the deep aspect of
the breast to divide the constricting ring usually
improves contour. The large nipple–areola com-
plex may need to be reduced in size. Lipofilling is
being used increasingly in such patients.6
Macromastia is the excessive development of the
breasts. This tends to occur during puberty (juve-
nile hypertrophy) or with onset of lactation (gesta-
tional). Prepubertal breast enlargement may occur
very rarely in conjunction with a hormone-secreting
tumour. Juvenile hypertrophy results from exces-
sive proliferation of ducts and stromal tissue but
no lobule formation. Significant psychological and
physical problems can be caused by macromastia
and patients with significant breast enlargement
benefit from breast reduction. This procedure is not
Figure 17.1  •  Bilateral accessory breasts in axilla.
Figure 17.2  •  Hypoplasia pre- and post-surgery with expansion followed by implant.

Chapter 17
270
­without complications and should be performed by
an appropriately trained surgeon.7
Aberrations of normal breast
development and involution
Defining what represents breast disease and what is
normal is not a new problem. The ANDI classifica-
tion8 was developed to provide a framework to help
understanding of the pathogenesis and subsequent
management of benign breast disease. Most benign
diseases arise from normal physiological processes
and range from normality to mild abnormality (ab-
erration) to severe abnormality (disease). The breast
passes through phases related to the levels of circu-
lating hormones and their effects on the ducts, lob-
ule and stroma. The phases are breast development,
cyclical change and involution (Table 17.1).
Fibroadenomas
A fibroadenoma is classified as an aberration of
normal breast development and is made up of a
combination of connective tissue and proliferatory
epithelium (Fig. 17.3).9 It is not a neoplasm or be-
nign tumour as it does not arise from a single cell.
Fibroadenomas arise from the hormone-dependent
terminal duct lobular unit and are influenced by
hormones, e.g. increasing in size during pregnancy.
The stromal element of these tumours defines their
classification and behaviour. A ‘simple’ fibro-
adenoma contains stroma of low cellularity and
regular cytology. Phyllodes tumours may or may
not arise from fibroadenomas but contain stroma
with much more marked cellularity and atypia.
Although phyllodes tumours cannot always be dif-
ferentiated on core biopsy with 100% certainty
from fibroadenomas, it is usually possible to tell
whether phyllodes is likely and when the lesion is
a simple fibroadenoma. All discrete masses over
the age of 23 should have a core biopsy – multiple
passes with three samples of the lesion. Although
ultrasound can usually differentiate fibroadenomas
from cancers and guidelines indicate ultrasound is
safe under 25, experience from medicolegal prac-
tice indicates the cut-off should be younger at 24
or below.
Simple fibroadenomas
These are benign, extremely mobile, discrete, rub-
bery masses that present symptomatically in young
women or are an incidental finding during breast im-
aging. They are a ‘frequent’ condition and are seen
most commonly at the time of greatest lobular devel-
opment in the late teens and early twenties. They are
usually solitary findings but some women develop
multiple lesions in one or both breasts. The aetiology
is unknown but has been linked to the oral contracep-
tive and Epstein–Barr virus following immunosup-
pression. They are highly mobile due to encapsulation
and pliability of the breast tissue. This can make them
appear to be much more superficial on examination
than their true position, important to appreciate
when embarking on removal under local anaesthetic.
Age (years)
Normal process
Aberration
<25
Breast development


Stromal
Juvenile
hypertrophy

Lobular
Fibroadenoma
25–40
Cyclical activity
Cyclical mastalgia
Cyclical nodularity
(diffuse or focal)
35–55
Involution


Lobular
Macrocysts

Stromal
Sclerosing lesions

Ductal
Duct ectasia
Table 17.1  •  Aberrations of normal breast development
and involution
Fibroadenomas were observed for 2 years in
women under 40 years of age: the majority did not
change in size (55%), some got smaller or resolved
(37%) and only a small number increased in size
(8%), the majority of which were in women under
the age of 20.10
Figure 17.3  •  Fibroadenoma.

Benign breast disease
271
In older women (>23 years of age) it is clearly es-
sential to differentiate a fibroadenoma from breast
cancer by triple assessment including core biopsy.
Rapid growth of a fibroadenoma is rare but can
­occur in either adolescence (juvenile fibroadenoma)
or in the perimenopausal age group (Fig.  17.4).
Tumours over 5 cm are termed ‘giant fibroadenoma’
and are seen more commonly in African countries.11
On macroscopic appearance fibroadenomas are dis-
crete, bosselated, whitish tumours that appear to
bulge when cut through. Only rarely does cancer
develop within a fibroadenoma but when it does it
tends to be non-invasive and lobular in nature.12
Management
The management of fibroadenomas depends on the
patients' age and preference as well as the results
of triple assessment. Core biopsy (multiple cores) is
now preferred to cytology to confirm the ­diagnosis
of a fibroadenoma. In patients with lesions under
4 cm, where histology confirms the diagnosis, the
patient can then be reassured and discharged. In
women presenting with multiple clinical and ra-
diological fibroadenomata, core biopsy should be
undertaken of the largest lesions – either one from
both breasts or two from the same breast.
Excision is rarely indicated unless the fibroadenoma
is obviously symptomatic, it increases significantly in
size or causes significant distortion of the breast pro-
file. Lesions measuring over 4 cm in size are usually
removed, as should those with histological concern
about stromal activity. Large fibroadenomas can be ob-
served providing they have been adequately sampled.
Although it is important to take account of the wishes
of the patient when considering surgery, these are influ-
enced by the manner in which the facts are presented.
All patients should be given written information,
which is available online from Breast Cancer Care.
Excision should be performed through a cosmeti-
cally placed incision, which includes a submammary,
axillary and circumareolar incision. Another option
is to remove fibroadenomas with a ­mammotome.13
With larger lesions (>5 cm where histology has
shown no suggestion that it could be a phyllodes
tumour), it is safe to section the tumour in situ and
remove it through a small incision below the breast
to improve cosmetic outcome. Large lesions are best
be removed cosmetically through an inframammary
incision. Removal of excess skin is rarely required in
young women, particularly when removing a large
juvenile fibroadenoma (Fig. 17.4). In some very large
lesions later revisional surgery is required but it is
important to leave this for up to a  year after the
initial excision as skin retracts and the breast re-
shapes itself over this period. Recurrence of a fibro-
adenoma can occasionally occur but is rare and it
may be due to undiagnosed adjacent lesions rather
than incomplete excision.
Tubular and lactating adenomas
A fibroadenoma consists of fibroconnective stroma
containing glandular structures. The glandular el-
ement is lined by a single or multiple layers of epi-
thelial cells. When the entire lesion consists of glands
with very little intervening stroma, this is termed a
tubular adenoma. Lactating adenomas are similar
to tubular adenomas, but occur in the pregnant or
lactating breast and are often multiple. Tubular ad-
enomas in non-pregnant women are clinically simi-
lar to fibroadenomas and are managed identically.
Mammographically
punctuate
microcalcification
within the acini may be visible. Lactating adenomas
can be managed conservatively once a diagnosis has
been established through breastfeeding unless there is
clinical concern. They tend to regress following cessa-
tion of breastfeeding.
Hamartoma
Hamartomas are common benign breast lesions
and are composed of variable amounts of adipose,
glandular and fibrous tissues. They are usually
­asymptomatic but may be palpable and feel like
soft fibroadenomas. Most occur in women over 35.
Mammographically they usually have a classical
appearance (circumscribed area consisting of both
soft tissue and lipomatous elements, surrounded
by a thin radiolucent zone). They also differ sub-
tly on ultrasound and are often ­misdiagnosed as
Figure 17.4  •  Juvenile fibroadenoma right breast.

Chapter 17
272
fibroadenomas. Management is similar to that of
fibroadenomas. It is important when performing a
core biopsy of a possible hamartoma to inform the
pathologist that the lesion may be a hamartoma as
otherwise they are often reported as normal breast
tissue on core biopsy.
Phyllodes tumour and sarcoma
The aetiology of phyllodes (leaf-like) tumours is un-
known. They are less common than fibroadenomas
(ratio of presentation 1:4014) and constitute about
2.5% of all fibroepithelial tumours. The age of on-
set is 15–20 years later than fibroadenomas. They
can grow rapidly, sometimes producing marked dis-
tortion and cutaneous venous engorgement, which
occasionally can lead to ulceration. The majority
are benign in nature and feel like large fibroadeno-
mas, and are diagnosed only following core biopsy.
They are rarely fixed to skin or muscle. When cut
during removal they are more brownish in colour
than fibroadenomas and can have areas of necro-
sis within. Most diagnoses of phyllodes tumour are
made before operation, on core biopsy, and the aim
of surgery should be to remove the lesion with a
clear macroscopic margin.
Differentiating benign from malignant phyllodes
can be difficult and involves assessment of the size,
ratio of stroma and epithelium, the border of the le-
sion, stromal cellularity and the number of stromal
mitoses, and the presence or absence of necrosis.
Current classification identifies benign, borderline
and malignant phyllodes tumours.
Overall, phyllodes tumours recur locally in ap-
proximately 20% of patients. Most locally re-
current tumours are histologically similar to the
original lesions but occasionally benign phyllodes
recur as borderline lesions. Malignant phyllodes tu-
mours recur earlier on average than benign lesions.
For benign lesions, total excision with clear margins
(≥1 mm) is sufficient.15 For borderline and malig-
nant lesions a wider margin is recommended and
this may necessitate mastectomy with or without a
myocutaneous flap for skin cover or breast recon-
struction in large lesions. Regional lymph node
metastases are seen rarely in malignant phyllodes tu-
mours, with nodes being affected in approximately
5%. Metastatic spread, when it occurs, is similar in
pattern to that of sarcomas. Fewer than 5% of all
phyllodes tumours metastasise and approximately
25% of those classified as malignant metastasise,
depending on the exact criteria used for classifica-
tion. Treatment of metastatic disease is discourag-
ing, with no sustained remissions reported from
radiation, hormonal treatment or chemotherapy.
Nipple discharge
Nipple discharge accounts for 5% of referrals to a
breast clinic,16 with up to 20% of these caused by in
situ or malignant disease.17 The important features
to assess are whether the discharge is from a sin-
gle or multiple ducts, is coloured or bloodstained,
is induced or spontaneous, and is affecting one or
both breasts. The frequency, colour and consistency
of the discharge should be noted. Blood-coloured
discharge or discharge that contains significant
amounts of blood on testing has been reported by
some but not all authors to be more likely to arise
from a cancer than coloured discharge that contains
no blood on testing.18 The sensitivity and specificity
of blood in the discharge is, however, not high.
Persistent discharge (≥2 per  week) is also more
likely to be associated with a significant causative
lesion (such as a papilloma or cancer). The aim is to
differentiate between physiological causes and duc-
tal pathology (Fig. 17.5). Discharge can be elicited
by squeezing around the nipple in 20% of women19
and is often noted following mammography. If dis-
charge is associated with a lump, then management
is directed to the diagnosis of the lump.
Figure 17.5  •  Multiduct physiological discharge. Note
the range of colours characteristic of physiological
discharge.

Benign breast disease
273
Galactorrhoea should only be diagnosed if the dis-
charge is bilateral, copious, pale milky in colour and
from multiple ducts. Some women continue to pro-
duce milk for many months after they have stopped
breastfeeding but galactorrhoea usually develops
long after cessation of breastfeeding. Prolactin
levels should be checked and, if raised (>1000
mIU/L), the cause can be secondary to medication or
a pituitary tumour. If the serum prolactin is normal,
then reassurance and a full explanation of the aetiol-
ogy are often all that is required. If there are persis-
tent symptoms, the ducts underneath the nipple can
be ligated.
Coloured opalescent discharge, from multiple ducts,
is common. It is usually physiological discharge.
In older women thick yellow discharge can result
from duct ectasia. Serosanguineous and/or bloody
discharge from a single duct is more likely to be asso-
ciated with papillomas, epithelial hyperplasia, ductal
carcinoma in situ (DCIS) or an invasive carcinoma.
Investigation
Assessment includes a careful breast examination to
identify the presence or absence of a breast mass.
Firm pressure applied around the areola can help to
identify the site of any dilated duct (pressure over a
dilated duct will produce the discharge); this is help-
ful in defining where an incision should be made
for any subsequent surgery. The nipple is squeezed
with firm digital pressure and if fluid is expressed,
the site and character of the discharge are recorded.
Testing of the discharge for haemoglobin determines
whether blood is present but this is of limited value,
although bloodstained discharge is more likely to
be associated with malignancy. Fewer than 20%
of patients who have a bloodstained discharge or
who have a discharge containing moderate or large
amounts of blood have an underlying malignancy.
Age is said to be an important predictor of malig-
nancy; in one series, 3% of patients younger than
40, 10% of patients between ages 40 and 60, and
32% of patients older than 60 years who presented
with nipple discharge as their only symptom were
found to have cancers.20 The absence of blood in
nipple discharge is not an absolute indication that
the discharge is unrelated to an underlying malig-
nancy, as demonstrated in a series of 108 patients
where the sensitivity of haemoccult testing was only
50%. Nipple discharge cytology is of little use due
to its poor sensitivity.21,22
A number of techniques have evolved to deter-
mine the aetiology and avoid unnecessary surgery.
Ductoscopy, using a microendoscope passed into the
offending duct, allows direct visualisation. There are
encouraging reports of its use (see Chapter 3), espe-
cially in directing duct excision at surgery23 and de-
tecting deeper lesions that may be missed by blind
central excision.24 Ductal lavage is a technique in
which the duct is cannulated, irrigated with saline
and the subsequent discharge examined cytologically.
This technique increases cell yield by 100 times that
of simple discharge cytology.25 Ductography (imaging
of the ductal system) can identify intraductal lesions.
Although this investigation has only a 60% sensitivity
for malignancy, a filling defect or duct cut-off has a
high positive predictive value for the presence of either
a papilloma or a carcinoma.26,27 Ductography, how-
ever, is a painful procedure and is not widely practised.
At present, the major role of ductoscopy is as an
adjunct to surgery; by using simple transillumina-
tion of the skin overlying the lesion during ductos-
copy, limited duct excision is possible. The role of
ductal lavage has been questioned due to large vari-
ations in its sensitivity and specificity.28,29 During
ductoscopy, visualised lesions can be biopsied and
in one report 38 of 46 women with biopsy-proven
papillomas were observed for 2 years with no re-
ported missed cancers.24 The role of ductoscopy
in the assessment of nipple discharge is set to in-
crease as the quality of equipment improves and it
becomes more widely available. A benefit of both
ductography and ductoscopy is that they allow
identification of the site of any lesion in younger
women, allowing localisation and excision of the
causative lesion while retaining the ability to lactate
(Fig. 17.6). A mammogram should be performed as
part of the assessment of patients over 35 years of
age with a discharge. The sensitivity in this group
of patients is low, at 57%.21 Digital mammography
has been shown to have a greater pick-up rate than
film mammography in women under 50 or with
dense breasts.30 Ultrasound can sometimes identify
papillomas and malignant lesions in the ducts close
to the nipple.31 Papillomas visualised on ultrasound
can then be biopsied or removed using a vacuum-
assisted core biopsy device.32
If no abnormality is found on clinical or mam-
mographic examination, patients are managed
­according to whether the discharge is from a single
duct or multiple ducts (Fig. 17.6). Any patient with

Chapter 17
274
­spontaneous single-duct discharge should undergo
surgery to determine the cause of the discharge if it is:
• bloodstained or contains moderate to large
amounts of blood on testing;
• persistent (at least twice per week);
• associated with a mass;
• a new serosanguineous discharge in a
postmenopausal woman.
Aetiology
Duct ectasia
This is benign dilatation and shortening of the ter-
minal ducts within 3 cm of the nipple. It is a com-
mon condition and increases in incidence with age.
It should not be confused with periductal mastitis,
which occurs in younger women and is secondary
to cigarette smoking. Duct ectasia can present as
nipple discharge, nipple retraction (giving a slit-
like appearance) or a palpable mass. It is usually
asymptomatic. The discharge is usually creamy and
cheesy in nature. Bilateral multiduct green discharge
is physiological and not related to duct ectasia.
Ductal papillomas
There are three main forms: a solitary-duct discrete
papilloma, multiple papillomas or juvenile papilloma-
tosis (Swiss cheese disease). Papillomas are character-
ised by formation of epithelial fronds that have both
the luminal epithelial and the outer myoepithelial
cell layers, supported by a fibrovascular stroma. The
epithelial component can be subject to a spectrum of
morphological changes ranging from metaplasia to
hyperplasia, atypical hyperplasia and in situ carci-
noma. A solitary intraductal papilloma, which occurs
in a large duct (within 5 cm of the nipple), is the com-
monest form and is the most common aetiology of
a bloody nipple discharge. They are most frequently
seen in the 30–50 age group and can be palpated in
one-third of patients. As papillomas have a thin stalk,
they have the potential to tort and necrose. Half of
women with papillomas have bloody discharge while
the other half have a serous discharge.33
Women with multiple intraductal papilloma syn-
drome have many peripheral duct papillomas. There
has to be a minimum of five clearly separate papil-
lomas within a localised segment of breast tissue,
usually in a peripheral location. These tend not to
present as nipple discharge but as a palpable lump
and ­usually occur at a younger age than single pap-
illomas. They are only associated with an increased
risk of malignancy if they contain areas of atypical hy-
perplasia. Repeated excision of papillomas in patients
with multiple intraductal papillomas can result in
significant breast asymmetry. One option in such pa-
tients is to excise such lesions with a vacuum-assisted
core biopsy device. This provides sufficient material
for the pathologist to assess that all excised lesions
are benign. Surgery to excise the affected duct system
with an oncoplastic procedure to reshape the breast
is preferential to mastectomy if biopsies show atypia.
Juvenile papillomatosis is a very rare condition
defined as severe ductal papillomatosis occurring in
young women <30 years old and usually presents as
a painless, mobile mass (similar to fibroadenoma).
Persistent spontaneous†
nipple discharge
Abnormal
Investigate as for
mass lesion or
mammographic
abnormality
*See indications section in total duct excision
†At least twice per week
Single-duct
discharge
Breast feeding
not an issue
Normal
Multiple-duct
discharge
Distressing
symptoms
Total duct
excision
Reassurance
Localised duct
excision
Consider ductoscopy
or ductogram
Microdochectomy
+/− total duct excision*
No distressing
symtoms
Investigations
• Clinical examination
• Mammography
Wishes to preserve
ability to breast feed
Figure 17.6  •  Investigation of nipple discharge.

Benign breast disease
275
Treatment is by complete excision. Patients with this
condition (and their close family) may be at some
increased risk of subsequent breast cancer, especially
if the lesion is bilateral and there is significant family
history. Close clinical surveillance is indicated.
Ductal carcinoma in situ
Bloody nipple discharge with or without the pres-
ence of Paget's disease constitutes one-third of all
symptomatic in situ patients.34 Only rarely does an
invasive cancer cause nipple discharge in the ab-
sence of a clinical mass. In most series, ductal car-
cinoma in situ (DCIS) is responsible for less than
20% of unilateral single-duct nipple discharge.19
The diagnosis is often made only following surgical
excision of the affected duct.
Bloody nipple discharge in pregnancy
Bilateral bloody nipple discharge detected either
visibly or on testing during pregnancy or lactation
is common. In 20% of women who develop nipple
discharge during pregnancy, blood is evident on
testing. The likely cause is hypervascularity of de-
veloping breast tissue; provided that the discharge
is multiductal and/or bilateral it is benign, resolves
spontaneously and requires no specific treatment.35
Nipple adenoma
Nipple adenomas present as a non-discrete, palpa-
ble growth of the papilla of the nipple (see Fig. 17.7).
There may be nipple discoloration and contour
change noted. Nipple adenomas tend to cause ero-
sion of the nipple tip and commonly present as a
bloody discharge from the surface of the nipple.
They are benign in nature and definitive treatment
is complete excision. It is caused by ductal hyper-
plasia of the lactiferous ducts and is seen most com-
monly in women of between 40 and 50 years of age.
Surgery
Microdochectomy
A single duct can be removed by microdochectomy.
This is performed through either a radial incision or
preferably a circumareolar incision. Expression of
the discharge should not be performed until the pa-
tient is in theatre and fully draped in order to provide
the best chance of identifying the offending duct. The
discharging duct is cannulated and either a lacrimal
probe placed or methylene blue injected and an inci-
sion made. The probe aids identification of the rel-
evant duct and dissection of this from surrounding
ducts/breast tissue. A length of at least 2–3 cm should
be removed. The excised duct should be opened to
Figure 17.7  •  Nipple adenomas.

Chapter 17
276
ensure a cause for the discharge is present and the
distal remnant inspected to ensure that the entire di-
lated duct has been excised. If the residual duct is
dilated, then it should be split, opened and inspected.
Microdochectomy should not damage surrounding
normal ducts and allows subsequent breastfeeding.
If performing a duct excision directed by ductoscopy,
then having identified an abnormality in the duct, the
light is used to direct the surgical excision. Once the
excision has been performed, the nipple should be
squeezed gently to ensure that the discharging duct
has been excised.
Total duct excision or division
In women of non-childbearing age, total duct exci-
sion is an option for a single-duct discharge. Current
evidence suggests that total duct excision is more
likely to result in a specific diagnosis and less likely
to miss underlying malignancy than microdochec-
tomy.36 Total duct excision can also be used for
­multiple-duct discharge if the discharge is copious
and affecting quality of life, and is often performed
for periductal mastitis. The operation involves divid-
ing all the ducts from the underside of the nipple
and removing surrounding breast tissue to a depth of
2 cm behind the nipple–areola complex.37 A circum-
areolar incision is used. Patients should be warned
that there is a small risk of nipple tip necrosis (<1%),
reduced sensation (40%) and nipple inversion asso-
ciated with this operation. Patients undergoing sur-
gery for periductal mastitis require total removal of
all ducts from behind the nipple; leaving even small
remnants of ducts predisposes to recurrence. Because
the lesions of periductal mastitis usually contain
organisms, patients should receive appropriate sys-
temic antibiotic treatment during the operation and
for 5 days after surgery. Options for antibiotic ther-
apy include amoxicillin–clavulanate or a combina-
tion of erythromycin and metronidazole.
For patients having cosmetic nipple eversion, the
procedure can be performed through a limited inci-
sion and the ducts divided, ensuring that the nipple
everts naturally without the need for sutures.
Mastalgia
Most women at some point during their lives will
suffer from breast pain. The aim for clinicians is to
differentiate between true mastalgia (pain originat-
ing within the breast) and referred pain. Women with
­referred pain describe the pain as unilateral, associ-
ated with activity and reproduced by pressure on the
chest wall. Non-steroidal anti-inflammatory drugs,
either taken orally or applied topically, can relieve
such symptoms. True mastalgia is associated with
swelling and nodularity of the breasts. It resolves
spontaneously in 20–40% of women but can recur.
Due to the hormonal aetiology, true breast pain
is often worse before and relieved after menstrua-
tion. Exacerbating factors include the perimeno-
pausal state (where hormone levels fluctuate) and
the use of exogenous hormones (hormone replace-
ment therapy or the oral contraceptive pill). The
cause of cyclical mastalgia is unknown but studies
have implicated excess production of prolactin,38
excess oestrogen,39 insufficient progesterone,40 or
increased receptor sensitivity in breast tissue caused
by a raised ratio of saturated fatty acids to essential
fatty acids.41
Assessment
A full history and examination should be performed.
The patient should be rolled and the underlying
chest wall – often the site of the pain – palpated. In
women over 40 years of age, mammography should
be performed to exclude an occult malignancy (ap-
proximately 5% of women with breast cancer com-
plain of pain,14 while 2.7% of women presenting
with pain as their main symptom are diagnosed
with breast cancer42). If a dominant lump or lumpi-
ness is palpable, then this will dictate further man-
agement. Most breast pain, and this includes many
women with cyclical breast pain, arises in the chest
wall. Analgesia, a firm bra worn 24 hours a day and
gentle stretching exercises such as swimming are ef-
fective treatments.
Treatment
Reassurance that the symptoms are not related to
an underlying malignancy is the most effective treat-
ment for mastalgia.43 Following this, the majority
will require no further treatment.
Evening primrose oil (EPO) is not effective, as
two double-blind, randomised, crossover trials
comparing EPO versus placebo showed no benefit
for EPO.44,45 The original work that advocated its
use has never been published other than in abstract
form.46 Other agents that have been shown to have
some benefit include phyto-oestrogens (e.g. soya
milk)47 and Agnus castus (a fruit extract).48

Benign breast disease
277
Reducing fat intake to less than 15% of dietary
calories has been shown to improve symptoms in
cyclical mastalgia.49 The patients who responded
showed changes in their serum lipid profiles but the
study was not blinded so placebo effects cannot be
excluded and the diet is not easy to adhere to in the
long term.
In severe pain, medication can be used but compli-
cations of these treatments need to be outlined to
the patient. Treatment should be either tamoxifen
10 mg daily or danazol. Tamoxifen 20 mg daily was
superior to placebo in a double-blind, randomised,
controlled trial and pain relief was maintained in
72% of women 1  year after use.50 Tamoxifen
restricted to the luteal phase of the menstrual cycle
abolished pain in 85% of women. Recurrent pain at
1  year was seen in 25% and the rate of adverse
effects was 21%.51 Tamoxifen 10 mg daily has fewer
side-effects and is as effective as 20 mg when com-
pared with danazol 200 mg daily.52
Tamoxifen is not licensed for use in mastalgia.
Toremifene, another selective oestrogen receptor
modulator, has also recently demonstrated its ef-
fectiveness in treating mastalgia. In a randomised,
­double-blind trial of 195 women with persistent
(lasting longer than 6 months) mastalgia, they as-
signed patients to toremifene 30 mg daily or a
matched placebo for three menstrual cycles. This
demonstrated a significant benefit for toremifene
but with no significant difference in adverse events
between the two groups.54
A phase II trial using afimoxifene (4-hydroxy-
tamoxifen) delivered locally to the breast as a trans-
dermal hydroalcoholic gel daily over four cycles
has shown statistically significant improvements
in signs and symptoms of cyclical mastalgia across
patient- and physician-rated scales, with excellent
tolerability and safety. There is strong evidence that
this tamoxifen metabolite is absorbed into the breast
tissue but does not have the systemic effects associ-
ated with tamoxifen.55 It is not used in the UK.
Bromocriptine should not be used, due to its high
rate of adverse effects (80%).56 Selective serotonin
reuptake inhibitors have been reported as being of
some benefit in mastalgia as part of premenstrual syn-
drome;57 they also have effects on fatty acid profiles.
Breast cysts
Palpable breast cysts are a common presentation to
a breast clinic and affect 7% of all women.14 Small
cysts have no significance except their potential to
grow. Larger cysts present typically in the fifth de-
cade and are usually multiple in nature. Cysts can
be divided into apocrine and non-apocrine, depend-
ing on the consistency of the fluid found within the
cyst. The only relevance of this classification is that
apocrine cysts have a higher tendency to recur.58
Imaging
Mammographically, breast cysts have characteristic
haloes but ultrasound is essential to the management
of cystic disease. Not only does ultrasound distinguish
between solid and cystic lesions, it also provides infor-
mation on the cyst wall and fluid consistency. It is also
an adjunct in ensuring accurate differentiation of sim-
ple from complex cysts, as well as allowing complete
aspiration. A simple cyst has a smooth outline with no
internal echoes and posterior enhancement. Complex
(or complicated or atypical) cysts are characterised
by internal echoes or thin septations, thickened and/
or irregular wall, and absent posterior enhancement.
Complex cysts are rarely malignant and require aspi-
ration or review with a follow-up scan several months
later. If the cyst wall shows any projections into the
centre of the cyst, this may indicate the presence of an
intracystic papilloma or carcinoma and core biopsy of
the projected area is indicated.
Management
Asymptomatic cysts should be left alone. Large,
symptomatic or painful cysts should be aspirated
to dryness. If the fluid is bloodstained it should be
sent for cytology; otherwise it should be discarded.
If a palpable mass is still present after aspiration,
further imaging and biopsy are indicated. If the cyst
recurs, then repeat aspiration can be performed.
There is a slightly increased relative risk of develop-
ing breast cancer in women with cysts but this is not
significant enough to warrant surveillance.
Tamoxifen is superior to danazol, with
fewer adverse effects: 53% of patients receiving
tamoxifen were pain free at 1 year compared with
37% of patients receiving danazol. Tamoxifen 10 mg
daily or danazol can be given only during the luteal
phase of the menstrual cycle and results in similar
improvements in symptoms, but with a marked
reduction in adverse effects.51,53

Chapter 17
278
Sclerotic/fibrotic lesions
Stromal involution can produce areas of fibro-
sis within the breast supporting tissues. Three
different groups of such lesions are described:
sclerosing adenosis, radial scars and complex
sclerosing ­lesions (CSLs). Sclerosing adenosis can
present with a palpable mass and breast pain.
Mammographically, it can be associated with
microcalcificaton. It differs histologically from
radial scars and CSLs in the degree of excessive
myoepithelial proliferation seen together with the
fibrosis. Radial scars and CSLs are considered to
be part of the same process but are differentiated
on size (radial scar, ≤1 cm; CSL, >1 cm). Radial
scars and CSLs are usually asymptomatic and dis-
covered as part of mammographic screening but
can rarely present as a palpable mass. Both lesions
may serve as a background for the development of
atypical epithelial proliferations, including atypi-
cal hyperplasia and carcinoma in situ. Even in the
absence of atypia there is some suggestion that the
presence of such lesions increases the individual's
risk of malignancy.59 All these lesions, though be-
nign in nature, are difficult to distinguish from
malignancy mammographically, macroscopically
and histologically. Percutaneous biopsy of these
lesions with a large-gauge vacuum-assisted core
needle is reliable, providing there is no associ-
ated atypia, at least 12 cores are performed and
there is concordance with radiological findings.60
Malignancy cannot be excluded reliably when
there is limited sampling, the presence of atypia
or discordance with the radiological appearance
of the lesion. Then open excision is recommended.
Pseudoangiomatous stromal
hyperplasia of the breast (PASH)
PASH is a benign myofibroblastic proliferation of
non-specialised mammary stroma. It is frequently
a microscopic incidental finding in breast biopsies
performed for benign or malignant disease. It has
been reported to form breast masses and some of
these have been reported to be sizeable. Whether
PASH is the cause of these masses or an epiphenom-
enon, for instance extensive PASH is seen commonly
within a juvenile fibroadenoma, is not clear. The
aetiology is not known and assuming that PASH
explains the cause of any localised mass is unwise.
The histological appearance has caused confusion
with mammary angiosarcoma, so immunohisto-
chemical vascular markers may be required to dis-
tinguish these two conditions.
Fibromatosis
Fibromatosis or desmoid tumour of the breast is
an extremely rare entity. Fibromatosis is an infil-
trative fibroblastic and myofibroblastic prolifera-
tion with significant risk for local recurrence, but
no metastatic potential. Fibromatosis is uncom-
mon in the mammary gland and accounts for less
than 0.2% of all primary breast lesions. It prob-
ably arises from the fascia of the underlying chest
wall muscles rather than on the breast tissue it-
self. It may be indistinguishable from malignancy
on ultrasound, mammography, physical examina-
tion and on gross evaluation. Fibromatosis is a
spectrum of conditions from extremely indolent
areas principally of fibrosis to a more prolifera-
tive infiltrative lesion. Establishing the diagnosis
can be difficult on core biopsy and larger vacuum-
assisted needle biopsies provide more tissue for
the pathologist to assess. Open biopsy may be
necessary if a diagnosis is not evident on needle
biopsy. Once it is established that the diagnosis is
fibromatosis (this may involve sending the biopsy
for an expert opinion), then the initial treatment
is observation only. If the lesion increases in size
and becomes symptomatic, particularly if it infil-
trates the chest wall and encases the intercostal
nerves, when it can cause marked discomfort and
pain, then surgical excision should be considered.
If the lesion recurs and becomes symptomatic or
the initial excision involves removal of portions
of the chest wall, then surgery should aim to re-
move all the disease with a 1-cm clear margin.
There is little evidence of a benefit of chemother-
apy or radiotherapy in recurrent or incompletely
excised disease. Tamoxifen has been reported
to be of benefit but these lesions are oestrogen
receptor (ER) alpha negative, although reports
suggest they are ER beta rich. Symptomatic re-
currence is an issue only for a small percentage
of patients with fibromatosis following excision
and is often evident because of nerve entrapment,
which results in local pain.

Benign breast disease
279
Non-ANDI conditions
Breast infections
Infection is a common problem affecting the
breast,61 and can be divided into lactational, non-
lactational and postsurgical. The skin overlying the
breast can also become infected either primarily or
secondarily because of infection developing in an
existing lesion such as an epidermoid cyst or as a
consequence of a generalised skin condition such as
hidradenitis suppurativa.
Lactational infections
Mastitis secondary to breastfeeding occurs in ap-
proximately 5% of puerperal women and is most
common during the first month or during weaning
as the baby's teeth develop. Staphylococcus aureus
is the usual organism and it enters the duct system
through the nipple. There is usually a history of
a cracked nipple and/or problems with milk flow.
Patients initially present with pain, localised ery-
thema and swelling. If this progresses, the inflam-
mation can affect large areas of the breast and the
patient can become toxic. Promoting milk flow
by continuing to breastfeed and the early use of
appropriate antibiotics markedly reduces the rate
of subsequent abscess formation. Infections devel-
oping within the first few weeks may result from
organisms transmitted in hospital and may be re-
sistant to commonly used antibiotics. Over half
of organisms that cause breast infection produce
penicillinase.62 Co-amoxiclav or flucloxacillin and
erythromycin are the antibiotics of preference.
Tetracycline, ciprofloxacin and chloramphenicol
should not be used to treat infection in breastfeed-
ing women because these drugs enter breast milk
and may harm the child.
Non-lactational infections
Non-lactational infections are grouped into periph-
eral or periareolar. Those infections in the periare-
olar area are seen in young women and are often
secondary to periductal mastitis (associated with
heavy cigarette smoking).63 Substances in cigarette
smoke may directly or indirectly damage the wall
of subareolar ducts. Accumulation of toxic metabo-
lites, such as lipid peroxidase, epoxides, nicotine
and cotinine in the breast ducts has been demon-
strated to occur in smokers within 15 minutes of a
woman starting to breastfeed.64 Smoking has also
been shown to inhibit growth of Gram-positive bac-
teria, leading to an overgrowth of Gram-negative
bacteria.65 This may affect the normal bacterial
flora and allow overgrowth of pathogenic aerobic
and anaerobic Gram-negative bacteria, and would
explain the presence of these organisms in the le-
sions of periductal mastitis. Microvascular changes
have also been recorded and it could be that ciga-
rettes cause some local ischaemia. The view is that
the combination of damage due to toxins, micro-
vascular damage by lipid peroxidases, and altered
bacterial flora produces the clinical manifestations
of periductal mastitis.
Patients present with periareolar inflammation often
associated with a mass or abscess. The organisms caus-
ing this infection are usually mixed and include anaer-
obes. Periareolar sepsis has a high rate of recurrence.
Peripheral non-lactational breast abscesses are three
times more common in premenopausal women than
in menopausal or postmenopausal women. The ae-
tiology of these infections is unclear but although it
was reported that these are commonly associated with
diabetes, rheumatoid arthritis, steroid treatment and
trauma, this is untrue.66 The usual organism respon-
sible is S. aureus. Very rarely, an infection is related to
underlying comedo necrosis in DCIS. For this reason
a mammogram should be performed in women over
35 years of age after resolution of the inflammation.
Postsurgical infection
Infections can present in the acute postsurgical period
or after the wound has healed. There was formerly
conflicting evidence of the benefit of prophylactic an-
tibiotics during clean breast surgery, although studies
have now shown a small but consistent benefit from a
single perioperative dose of a broad-spectrum antibi-
otic such as co-amoxiclav.67 The most common organ-
isms causing early infection include normal skin flora,
S. aureus or organisms derived from the terminal
ducts.68 Most surgeons give antibiotics routinely to
patients having implants inserted. Patients ­having
surgery for periductal mastitis are at increased risk of
postoperative infection and all these patients should
have intraoperative and postoperative ­antibiotics that
cover the range of organisms isolated from this condi-
tion. ‘Seromas’ are frequent and can ­become infected
following aspiration or as a result of ­reduced resis-
tance to infection during chemotherapy. Radiotherapy
interferes with both the blood and lymphatic flow
to the breast, and its effect is to ­increase rates of

Chapter 17
280
­infection in the treated area; when infection occurs,
prolonged and high-dose antibiotic therapy may be
required in such pateints. Redness and oedema of
the breast following breast-conserving surgery are
not uncommon (especially after radiotherapy). This
usually occurs between 3 and 12 months following
surgery. This is unresponsive to antibiotics and has an
incidence of 3–5% in patients following radiotherapy
for breast-conserving surgery.69 It appears to be re-
lated to obstructed lymphatic flow and responds to
manual lymphatic drainage.
If an implant becomes infected, intensive antibi-
otic therapy is occasionally effective but usually the
prosthesis has to be removed. Replacing an infected
implant following thorough lavage has been re-
ported to be effective but is rarely performed.70 It is
not uncommon for implants to become infected after
a minor surgical intervention (such as dental work)
or during chemotherapy given as adjuvant therapy
or as treatment for metastatic disease. Prophylactic
antibiotics should be considered for patients with
implants undergoing major dental work.
Treatment
The basis of treatment for all breast infections is
use of a broad-spectrum antibiotic and draining any
collections of pus.
This has allowed management of breast infection
to become outpatient based. Protocols validated
within the Edinburgh Breast Unit have demonstrated
that few if any breast abscesses require incision
and drainage under general anaesthesia.75 All ab-
scesses should be assessed by ultrasound and if
pus is present the surgeon or radiologist aspirates
this, usually under ultrasound guidance (Figs 17.8
and 17.9). Patients are reviewed every 2–3  days
and any further collections aspirated until no fur-
ther pus forms. Drainage of pus by making a small
stab incision in the skin under local anaesthesia
is performed in patients where the overlying skin
is thinned or necrotic (Fig. 17.10). The incision to
drain any breast abscess should be just large enough
to allow the pus to drain (1 cm or less), which mini-
mises later scarring. Ultrasound provides a simple
method for differentiating an abscess from celluli-
tis, allows assessment of any loculation, which is
rare, and permits complete aspiration of all pus.
Experience in the Edinburgh Breast Unit of using
ultrasound to assist aspiration of breast abscesses is
that it is quick and simple to learn and use. Local
anaesthetic (1% lignocaine with 1:200 000 adrena-
line) is injected into non-inflamed skin away from
the abscess and along the needle track and is then
irrigated into the abscess cavity. Aspiration is then
relatively painless and the local anaesthetic helps if
the pus is thick by diluting the pus to allow aspira-
tion. Periareolar non-lactational abscesses can be
treated and cured by repeated aspiration. Due to
the recurrent nature of periareolar infection, recur-
rent abscess formation is common and in such pa-
tients when all signs of acute infection have settled,
which takes at least 6 weeks, careful surgical exci-
sion of any residual abscess and affected ducts is
often required. A mammary duct fistula (a connec-
tion between the infected and damaged duct and
the skin, usually at the edge of the areola) ­develops
Due to the difficulty of predicting the presence
of pus within an inflamed breast, ultrasound with or
without aspiration should be performed.71 The need
for open drainage in breast abscesses has been
superseded by the use of aspiration.72–74
Figure 17.8  •  Aspiration of abscesses under ultrasound guidance. (a) Ultrasound view of a breast abscess. (b) The
needle can be seen entering the abscess on the right, allowing aspiration to be performed.
a
b

Benign breast disease
281
in up to one-third of patients after incision and
drainage of a periareolar abscess.76 Fistulas require
definitive surgical management. Options include
fistulotomy, cutting down on a probe into the fis-
tula and allowing healing by secondary intention,
which is painful after surgery and produces an
ugly scar, and fistula excision and primary closure.
Excising a fistula is easier through a radial scar, but
circumareolar ­incision produces the best cosmetic
outcome. Complete excision of the granulation tis-
sue lined tract (plus the affected ducts under the
nipple) and primary closure requires antibiotic
cover (Fig. 17.11). There is a high risk of recurrence
in the presence of postoperative wound infection.77
An important aspect of the management of puer-
peral breast infections is the continued expression of
Figure 17.9  •  (a) Lactating abscess: skin red but normal at presentation. (b) Lactating abscess following aspiration.
a
a
Figure 17.10  •  Abscess of the left breast with thinned overlying skin: (a) before incision; (b) after incision and drainage
through a small stab incision.
a
b

Chapter 17
282
milk, with the most efficient breast pump being the
baby's mouth. Emptying the breast increases the rate
of a good outcome in infective mastitis78 and although
bacteria and the antibiotic are present in the milk, this
does not appear to harm the child.79 It is rarely neces-
sary to suppress lactation but in severe unremitting or
repeated infections, the prolactin antagonist cabergo-
line is effective at stopping milk flow.
It is essential to remember that inflammatory car-
cinoma can be difficult to differentiate from breast
infection. If the inflammatory mass does not settle
on appropriate management, then core biopsy of
any abnormal area should be considered.
Other infections
Granulomatous mastitis
This is a rare condition, characterised by non-
caseating granulomas and microabcesses confined to a
breast lobule.80 Patients present with a firm irregular
mass (which is often indistinguishable from a carci-
noma) or multiple or recurrent abscesses (Fig. 17.12).
The mass can be extremely tender. Young parous
women are most frequently affected and there is
no association with smoking. The role of organ-
isms in the aetiology of this condition is unclear but
one study did isolate corynebacteria from nine of
12 women with granulomatous lobular ­mastitis.81
The most common species isolated was the newly de-
scribed Corynebacterium kroppenstedtii, ­followed by
Corynebacterium amycolatum and Corynebacterium
tuberculostearicum. These organisms are, however,
sensitive to penicillin and tetracycline, and treatment
with these antibiotics does not produce resolution
of granulomatous lobular mastitis so it is unlikely
that these organisms have a major role. In patients
diagnosed as having granulomatous lobular masti-
tis on core biopsy, excision of the mass should be
avoided, as it is often followed by persistent wound
discharge and failure of the wound to heal. Steroids
and other immunosuppressive agents have been used
with varying reports of their efficacy.82 There is no
convincing evidence that steroids alter the course
of this condition. They do improve symptoms dur-
ing administration of high doses but the condition
then worsens when the dose is reduced. Reports of
the benefit of injecting depot steroid are emerging.
We no longer use steroids in this condition. It re-
solves spontaneously over a period of 6–18 months.
Treatment is supportive and is aimed at treating as-
sociated infection and abscesses.
Hidradenitis suppurativa
Hidradenitis is a condition affecting the apocrine
glands of the skin, including the axillae, perineum and/
or breast areas. It is much commoner in smokers and
the organisms responsible are similar to those present
Figure 17.11  •  Diagrammatic illustration of the steps involved in excision of a mammary duct fistula performed through
a circumareolar incision with primary wound closure under antibiotic cover.

Benign breast disease
283
in periareolar sepsis. Treatment in the acute phase com-
prises management of any infection/abscesses by ap-
propriate antibiotics and aspiration or drainage of any
abscess. Excision of the affected area with skin graft-
ing has been reported to be effective in approximately
50% of patients and may be the only long-term option
for some patients. Smoking cessation is also beneficial.
Miscellaneous benign lesions
Montgomery's gland problems
Throughout the areola are blind-ending glands that
produce fluid to lubricate the areola during breast-
feeding. These glands can become blocked, form-
ing hard nodules on the periphery of the areola.
Occasionally these can become infected. Unless
symptomatic, the management of these prominent
Montgomery's glands is reassurance.
Fat necrosis
Following trauma to the breast, fat necrosis can
occur. Fat necrosis can produce either a mass that
can feel similar on palpation and appear similar on
imaging to a breast carcinoma or a cystic oily collec-
tion. Patients usually give a history of direct trauma
(or surgery) to the affected breast and examination
may reveal bruising. It is important to assess such
patients with imaging and not dismiss dimpling and
bruising as fat necrosis. Histologically, fat necrosis
is characterised by anucleate fat cells, surrounded
by histiocytic giant cells and foamy macrophages.
Severe fat necrosis can follow seat-belt damage and
such patients often have a significant defect in the
breast with significant distortion at the site where
the seat-belt has disrupted a significant area of
breast fat.
Lipomas
Due to the fatty nature of the breast it is not surpris-
ing that lipomas are common. They tend to present
in the fifth decade14 and have to be distinguished
from any sinister cause. Imaging shows a radiolu-
cent lobulated mass. Fine-needle aspiration is often
reported as inadequate (C1) due to fat only being
aspirated and is not recommended. A pseudolipoma
Figure 17.12  •  Granulomatous lobular mastitis in its various presentations with skin changes, a mass and abscesses.

Chapter 17
284
is a mass that clinically appears to be a simple li-
poma but is actually caused by a small cancer that
produces compressed fat lobules as the suspensory
ligaments of the breast shorten. Liposarcomas occur
only very rarely in the breast.83 Larger or symptom-
atic lipomas can be excised. Some of the larger lipo-
mas develop deep in the fascia overlying the chest
wall muscles.
Granular cell tumours
This is an uncommon, usually benign neoplasm that
originates from Schwann cells of peripheral nerves
in the breast. About 6% of all granular cell tumours
involve the breast. The mean age at diagnosis is
40  years. Clinically and on imaging they are dif-
ficult to differentiate from a breast carcinoma due
to their fibrous consistency, fixation to the pectoral
fascia and skin retraction. Granular cell tumours
are usually benign but there have been reports of
malignant cases. Treatment is by local excision, en-
suring a narrow clear margin to prevent recurrence.
Diabetic mastopathy
This is a form of sclerosis occurring in premeno-
pausal women, and occasionally men, with long-
standing type I diabetes, often associated with other
diabetic complications, particularly retinopathy.
It can result clinically in one or more hard masses
within the breast that have features making it in-
distinguishable clinically from malignancy, but on
histology the findings are of sclerosing lymphocytic
lobulitis or ‘diabetic mastopathy’. The disease prob-
ably represents an immune reaction to the abnormal
accumulation of altered extracellular matrix in the
breast, which is a manifestation of the effects of hy-
perglycaemia on connective tissue. It does not seem
to predispose to breast carcinoma or lymphoma and
in patients without diabetes it is not clear why some
get it and others do not.84
Haematomas
These most commonly follow trauma such as a road
traffic incident, but can occur after core biopsy, fine-
needle aspiration or open biopsy. In extremely un-
usual circumstances a breast carcinoma may present
with a spontaneous haematoma. Breast ­haematoma
can also occur spontaneously in patients on antico-
agulant therapy.
Para areola cysts
These cysts are rare and occur in pubertal and post-
pubertal teenagers (11–16 years), presenting as dis-
crete superficial cystic masses at the areola margin;
occasionally they become infected. They can be
interpreted as solid on ultrasonography because
of numerous internal echoes. Diagnosis and treat-
ment can be by aspiration, although if they cause
no symptoms and ultrasonography shows a cystic
lesion, no intervention is required as they disappear
with time.
Mondor's disease
Mondor's disease is spontaneous superficial throm-
bophlebitis of a breast vein. It is often initially painful
and often there may be a history of trauma or sur-
gery to the breast. Clinically, there may be a thick-
ened palpable cord with associated erythema. Its
aetiology in the absence of surgery, trauma or infec-
tion is unknown. It is a self-limiting condition that
normally resolves within a couple of weeks but can
be very painful. ­Non-steroidal anti-inflammatory
agents massaged over the area of tenderness im-
prove the pain. Mondor's disease most commonly
involves one or more of three venous channels:
the thoracoepigastric vein, the lateral thoracic
vein and the superior epigastric vein. The upper,
inner portion of the breast is never involved.
Gynaecomastia
True gynaecomastia is caused by hyperplasia of the
stromal and ductal tissue of the male breast. It is
responsible for considerable embarrassment and
worry and is the commonest condition affecting the
male breast (Fig. 17.13). Pseudogynaecomastia gives
a similar appearance but is due to excess adipose
tissue with no increase in stromal or ductal tissue.
Both types can present together.85 Gynaecomastia
associated with Klinefelter syndrome is associated
with actual lobule formation and a risk of breast
cancer approaching that of the female population.

Benign breast disease
285
Gynaecomastia can occur from any age and pres-
ents as a concentric painful swelling. It is a common
condition, occurring in at least 35% of men at some
time in their life. It is benign and usually reversible.
An important differential diagnosis is a primary
breast cancer but breast cancers present with eccen-
tric masses that are usually painless.
The aetiology of gynaecomastia is due to a relative
hyperoestrogenism.86 This is caused by decreased
androgen production, increased oestrogen produc-
tion or an increase in peripheral aromatisation. In
patients where no endocrine abnormality or drug
is found, the cause may be a reduction in andro-
gen receptors and/or a local increase in aromatase
activity.87 Causes can be divided into physiologi-
cal, pathological, drug induced (medicinal and rec-
reational) and idiopathic. Excess intake of beer or
lager can result in gynaecomastia as a consequence
of the phyto-oestrogens present in these drinks.
A combination of regular cannabis use and drinking
large volumes of lager is particularly potent at caus-
ing gynaecomastia.
1. Physiological, or primary, gynaecomastia shows
a trimodal pattern, with peaks in the neonatal
period, puberty and senescence. It is often self-
limiting but will occasionally require treatment.
2. Pathological causes are listed in Box 17.1.
3. Common drugs that produce gynaecomastia in-
clude: spironolactone (antiandrogen); histamine
H2 antagonists, antipsychotics and methyldopa
(gonadotrophin disturbance); digoxin, cannabis
and griseofulvin (oestrogen receptor competi-
tors); and anabolic steroids (Box 17.2). HIV
treatment with highly active anti-retrovirals is
also commonly associated.
The degree of gynaecomastia is classified using
appearance (Table  17.2). A thorough history will
usually elicit the underlying cause. Examination
of breast, axilla, testes and abdomen should be
performed.
Investigations of gynaecomastia are directed to ex-
cluding a primary breast carcinoma or a secondary
pathological cause. Biochemical assessment (liver
and renal function tests, γ-glutamyltransferase,
prolactin,
α-fetoprotein,
β-human
chorionic
gonadotrophin and total testosterone) is only re-
quired in rapidly growing gynaecomastia. Imaging
(with mammography and/or ultrasound) plus
­biopsy (fine-needle aspiration cytology and/or core
biopsy) can be performed if the cause of the gyn-
aecomastia is indeterminate, or if surgery is being
considered or cancer is suspected.
Treatment
Reassurance of the transient and benign nature
is often all that is required in the management of
potential gynaecomastia. More than 80% resolve
within 2  years without any treatment. In drug-
related gynaecomastia, withdrawal of the drug
or change to an alternative should be considered.
For pathological gynaecomastia, the underlying
cause needs to be addressed.
For those cases requiring treatment there are two
options: medical treatment and surgical excision.
Figure 17.13  •  Bilateral senescent gynaecomastia.
Decreased androgens
Reduced production
• Chromosomal abnormalities, e.g. Klinefelter's syndrome
• Bilateral cryptorchidism
• Hyperprolactinaemia
• Bilateral torsion
• Viral orchitis
• Renal failure
Androgen resistance
• Testicular feminisation
Increased oestrogens
Increased secretion
• Testicular tumours
• Carcinoma of the lung
Increased peripheral aromatisation
• Liver disease
• Adrenal disease
• Thyrotoxicosis
Box 17.1  •  Pathological causes of gynaecomastia

Chapter 17
286
Medical management benefits from a high success
rate and avoidance of an operation.
In the UK, danazol is the only drug licensed for
the treatment of gynaecomastia. A short 6-week
course is recommended, with 100 mg b.d. for the
first  week ­followed by 100 mg t.d.s. for the sec-
ond to sixth weeks, response being assessed at the
eighth week. Imaging and clinical photography can
be used to evaluate success of treatment. Repeat
courses may be required. Tamoxifen at a daily dose
of 10 mg produces excellent response rates and is
the drug we use in the limited number of patients
we treate with medication.
Due to the high risk of poor cosmesis associated
with gynaecomastia surgery and subsequent risk of
litigation, operation should only be considered after
medical failure or where the gynaecomastia is large
(class IIa/III). Marking the extent of the gynaeco-
mastia prior to surgery is essential. Patients with
limited gynaecomastia can have excision performed
through a periareolar incision to reduce scarring.
The use of lighted retractors and diathermy aids
surgery. A disc of breast tissue should be left be-
hind the nipple combined with an intact pectoral
fascia and overlying fat to prevent retraction and
fixation to the muscle (saucer deformity). Skin
flaps are kept thick to prevent deformity and skin
necrosis. Patients should be warned about nipple
necrosis, sensory changes and recurrence, as well
as cosmetic problems. In larger cases excess skin is
removed, requiring repositioning of the nipple and
even free nipple grafts.91 In young patients, excess
skin often corrects itself without need for excision.
The use of liposuction alone or combined with lim-
ited surgery or mammotomy improves cosmetic
outcomes. Ultrasound-assisted liposuction allows
Hormones
• Anabolic steroids (bodybuilders)
• Oestrogenic agonists
• Antiandrogens (treatment of prostate cancer),
e.g. cyproterone acetate, goserelin
Recreational drugs
• Alcohol
• Cannabis
• Heroin
Cardiovascular drugs
• Digoxin
• Spironolactone
• Captopril
• Enalapril
• Amiodarone
• Nefedipine
• Verapamil
Antiulcer drugs
• Cimetidine
• Ranitidine
• Omeprazole
Antibiotics
• Ketoconazole
• Metronidazole
• Minocycline
Psychoactive agents
• Tricylic antidepressants
• Diazepam
• Phenothiazines
Others
• Domperidone
• Metoclopramide
• Penicillamine
• Phenytoin
• Theophylline
Box 17.2  •  Drugs associated with gynaecomastia
The evidence for the three commonly prescribed
drugs (danazol,88 tamoxifen89 and clomifene90) is
based on small non-randomised trials and does not
include recurrence rates, optimum dose, length of
treatment or associated long-term risks. Tamoxifen
at a dose of 10 mg is the agent of choice.
Grade
Clinical appearance
I
Small but visible breast
development with little
redundant skin
IIa
Moderate breast
development with no
redundant skin
IIb
Moderate breast
development with redundant
skin
III
Marked breast development
with much redundant skin
Table 17.2  •  Classification of gynaecomastia
From Simon BE, Hoffman S, Kahn S. Classification and
surgical correction of gynecomastia. Plast Reconstr Surg 1973;
51:48–52.105 With permission from Lippincott, Williams & Wilkins.
© American Society of Plastic Surgeons.

Benign breast disease
287
treatment of more fibrous areas and increases the
number of patients suitable for this technique.92 An
approach to management including liposuction is
outlined in Fig. 17.14.93 In those for whom surgery
has produced an unsatisfactory cosmetic result, fur-
ther liposuction and lipofilling can be effective in
achieving a satisfactory final result.
Common complications of
cosmetic breast surgery
Cosmetic surgical procedures to the breast are in-
creasing in popularity. The frequency of patients
presenting with symptoms either as a consequence
of previous operations or with an unrelated prob-
lem in a patient who has undergone cosmetic sur-
gery means an understanding of such procedures
and their complications can allow rapid diagnosis
and that the treatment is appropriate. It is highly
recommended that if there are complications from
recent surgery the operating surgeon assesses their
own patient runs better. However, it is not uncom-
mon for these patients to be referred to a breast
clinic.
Assessment involves a detailed history of the origi-
nal procedure as well as standard triple assessment.
In the augmented patient it is useful to know the
type of implant used (particularly with the recent
knowledge that some implants have a high rate
of leakage and rupture) as well as the size, shape,
composition and its position (subpectoral or sub-
mammary). The time since surgery and any post-
operative surgical complications (e.g. haematoma)
should also be recorded. Examination will show
if any breast reductions or mastopexy (breast lift)
have been performed. In the patient who has under-
gone a reduction mammaplasty it is useful to know
the approximate volume reduction and whether
there were wound healing problems.
Imaging of breasts post-cosmetic surgery can pose
technical challenges. Scarring and calcification from
fat necrosis is commonly seen after breast reduction
and can make mammographic interpretation diffi-
cult. Assessment of the augmented breast should in-
clude mammography (using the Ekland technique)
and ultrasound. Magnetic resonance imaging (MRI)
is useful in assessing disease extent and is the tech-
nique of choice if implant rupture is suspected. Due
to the obvious risk of implant damage, any needle
biopsy of an augmented breast should be performed
under image guidance.
Breast augmentation
complications
Capsular contraction
Any foreign tissue placed within a body will pro-
duce a reaction or scar. The scarring around an
implant produces a capsule, which contracts over
time. Due to the relative inertness of silicone and
the textured surface of modern implants, capsular
contracture causing symptoms or significant distor-
tion is less common than it used to be. It can be
exacerbated by postoperative complications such
as haematoma or a subclinical infection. Capsular
contraction tends to produce pain, change in shape
Liposuction
Liposuction
Open excision
Open excision
Skin reduction
Redundant
skin
Residual
lump
Residual
lump
Consider skin
excision
Firm subcutaneous
nodule only
Moderate to large
breast
Small to moderate
breast
Figure 17.14  •  Algorithm for management of gynaecomastia.

Chapter 17
288
and hardness of the breast. A grading for capsular
contraction is shown in Box  17.3. Treatment de-
pends on severity of symptoms and patient wishes.
Removal plus capsulotomy or capsulectomy for
rupture is the standard treatment with or without
re-augmentation.
Rippling/palpable implant edge
Due to the pressure effect of the implant on the
breast tissue, some degree of glandular atrophy can
occur. This can make the underlying implant more
palpable, especially in the thin woman. Round, non-
cohesive implants, due to their softness and fluid
nature, can have a palpable ‘rippling’. This is com-
monly felt superiorly when placed submammary in
a slim patient or if there is marked ptosis. Rippling
and sometimes the implant edge can be felt on the
medial or lateral edges if there is a large implant or
paucity of glandular cover. Treatment is reassurance
and explanation, lipofilling the area above the rip-
pling or revisional surgery to place the implant in
the submuscular plane.
Implant rupture
Rupture is most commonly due to implant failure over
time but may be caused by trauma or iatrogenic injury.
Modern silicone breast implants tend to contain cohe-
sive gel, which tends not to have the same frequency of
rupture seen with liquid silicone implants.
Women with rupture present with pain, change
in breast shape or a lump. Once identified, treat-
ment is removal of implant plus capsule. Residual
silicone can leak into the breast and chest wall
and cause a reaction producing hard lumps
(silicone granulomas). Silicone can also migrate to
axillary nodes, which can become quite large. They
have a snowstorm appearance on ultrasound, which
is quite typical. Care should be taken in removing
such nodes. They are the sentinel nodes of the breast
and aggressive removal of nodes containing silicone
can cause both breast and arm oedema. Therefore,
these nodes should only be removed if there is defi-
nite evidence they are causing symptoms.
Breast reduction problems
Fat necrosis
Scarring and fat necrosis can result from devascu-
larisation of fatty breast tissue or following wound
healing problems. This may not be noticed until
some time has passed postsurgery. Triple assess-
ment will rule out any malignancy and allow for
reassurance. Large areas that are symptomatic can
be treated by a combination of liposuction and
lipofilling.
Inclusion cyst
An inclusion cyst occurs due to implantation of ke-
ratinising squamous epithelium within the dermis if
an area of incomplete de-epithelialised skin (usually
the pedicle for the nipple) has been buried during a
breast reduction operation. A discrete lump may be
palpable or an impalpable lesion may be discovered
on subsequent mammographic screening.
Assessment of patients with
benign breast disease
The current issues include:
• Is a one-stop clinic the best method of
diagnosing breast disease?
• Fine-needle aspiration cytology, core biopsy or
both?
• Should benign breast disease become the remit
of nurse specialists?
One-stop clinics
The aim of the one-stop clinic is to provide the pa-
tient with all the relevant investigations and to es-
tablish a diagnosis at the initial visit. This requires
Grade I (absent)
The breast is soft with no palpable capsule and looks
natural.
Grade II (minimal)
The breast is slightly firm, with a palpable capsule but looks
normal.
Grade III (moderate)
The breast is firm with an easily palpable capsule and looks
abnormal.
Grade IV (severe)
The breast is hard, cold, painful and distorted.
Box 17.3  •  Classification of capsular contraction

Benign breast disease
289
the availability of a breast radiologist to provide
immediate interpretation of the examination and
investigations. Even with all these available, a de-
finitive diagnosis is not always possible.94 There
are benefits in reducing anxiety in such a service
(especially in the majority with normal breasts or
benign disease) but this benefit is only in the short
term.95 Patients like these clinics and they reduce
the number of clinic visits and letters, improving
administration efficiency. Although there have been
concerns that immediate reporting may affect ac-
curacy and that there may be a possible detrimental
psychological aspect for those with cancer,96 these
are more than offset by the benefits. It is well rec-
ognised that at the time when a patient is given
bad news, little other information provided in the
consultation is remembered. By concentrating on
establishing and delivering a diagnosis at the first
visit, it is then possible to have a more useful and
constructive second visit to consider management
of any cancer detected.
Fine-needle aspiration cytology,
core biopsy or both?
Fine-needle aspiration cytology was the mainstay
of diagnosis of symptomatic breast lumps for more
than 30  years. Its introduction allowed preopera-
tive diagnosis and avoided a large number of open
excision biopsies. It has the benefit of being easy
to perform, but can cause patient discomfort and
has a high sensitivity and specificity (in experienced
hands97). The result can be interpreted quickly, al-
lowing rapid diagnosis. Its major disadvantage is
that it does not provide architectural information on
the area examined and therefore cannot differenti-
ate in situ and invasive disease. It has been reported
that it is possible to grade tumours on cytology98
and although it can provide oestrogen receptor sta-
tus,99 full profiling is not possible from cytology.
There is little if any benefit from combining fine-
needle aspiration (FNA) and core biopsy as FNA
disrupts the cancer, makes it more difficult to visu-
alise and this may adversely affect subsequent core
biopsy accuracy. The only continuing role of FNA
in patients with breast cancer is in assessment of
suspicious lymph nodes. If recurrence is suspected
core biopsy should be performed of the recurrence
because knowledge of the current ER and HER-2
status of the cancer is essential and these can differ
from the initial primary tumour.
There is increasing evidence that symptomatic
lumps should be biopsied under ultrasound guid-
ance.101 This ensures that the abnormality is visu-
alised with the biopsy needle within it, improving
sensitivity. Suitably trained surgeons or breast phy-
sicians, as well as radiologists, can undertake these
biopsies safely.102
Future management of
benign breast disease
The last few  years have seen the expansion of
breast physicians, nurse specialists and the for-
mation of nurse consultants. Their roles have ex-
panded to help with the increasing breast workload
and the lack of breast specialists. There is evidence
that such professionals can play an important
part in symptomatic clinics, perform follow-
up clinics and run symptom-specific clinics (e.g.
mastalgia clinics) as long as there is specialist
back-up.103,104 The future roles of these individu-
als are likely to expand. One note of caution: in
a clinic of 30 symptomatic patients run by three
or four individuals, there will be an average three
cancers – that is, one per individual in the clinic. If
a nurse specialist does one new patient clinic once
a week, they may only see 40–45 cases of breast
cancer per  year. Some breast abnormalities and
cancer types are rare. What is not clear is what is
adequate training for such individuals. If any indi-
vidual is to give a ‘consultant’ opinion in such clin-
ics, then ideally they should have seen hundreds
of breast cancers and the whole range of common
and rare presentations before they make final deci-
sions on whether patients can be discharged. This
is also true for trainees who cover for consultant
surgeons in such clinics. The breast surgeons of the
future may be less involved in diagnosis and more
active surgically.
Core biopsy has taken over as the preoperative
technique of choice for diagnosing palpable breast
lumps and areas of nodularity.100 The improved
sensitivity and specificity and greater information
available (architecture, oestrogen receptor and
human epidermal growth factor receptor 2 (HER-2)
status, grade, presence of vascular invasion or
calcification) with core biopsy is the reason for this
change.

Chapter 17
290
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