Male Breast Cancer: Clinicopathological, Immunohistochemical and Radiological Study
Bermal HASBAY1, Filiz AKA BOLAT1, Hüseyin Özgür AYTAÇ2, Murat KUŞ2, Ayşin POURBAGHER3
1Department of Pathology, Başkent University, Faculty of Medicine, ADANA, TURKEY
2Department of General Surgery, Başkent University, Faculty of Medicine, ADANA, TURKEY
2Department of Radiology, Başkent University, Faculty of Medicine, ADANA, TURKEY
Keywords: Male breast cancer, Diagnosis, Survival
To evaluate the pathological and radiological features, immunohistochemical profile and treatment methods of primary male breast
carcinoma cases diagnosed at our center.
Material and Method: The pathology archive between 2006 and 2019 was reviewed and the data of 27 male patients diagnosed as primary breast
cancer were retrospectively evaluated.
Results: The age of the patients ranged between 40-86 years. The left breast was involved in 17 patients. The mean tumor diameter was 2.35
± 1.09 cm. Of the 27 cases, 8 were dead and 19 were alive. The mean follow-up duration was 37.45 ± 24.84 months. The mean estimated life
expectancy was 65±14.7 months. The most common complaint was a swelling in the breast. The time interval between the onset of complaints
and admittance to hospital ranged from three months to two years. The most common histopathological diagnosis was invasive carcinoma - no
special type. The most common surgical procedure was mastectomy with lymph node dissection. Nine patients had metastatic lymph nodes. In
terms of the hormone profiles, 24 were Estrogen receptor positive, 21 were Progesterone receptor positive and six were Her2/neu positive. Three
patients had triple-negative tumors.
Conclusion: Male breast carcinoma is a rare disease but its frequency has been increasing recently. As breast cancer is more commonly attributed
to women, the diagnosis is usually delayed until later stages in males. Public awareness should therefore be increased and breast cancer should
be considered in the differential diagnosis especially in the presence of breast swelling and complaints related to the breast skin so that the
appropriate biopsy can be obtained without delay.
Male breast cancer (MBC) is a very rare disease accounting
for nearly 1% of all cancers in males (1-7). However, its
incidence has recently been increasing with approximately
2000 to 2500 new cases reported annually in the United
States (1, 3, 8-12). Although male breast cancer occurs in all
age groups, it is frequently observed between 60 and 70 years
of age on average (2, 3, 10,12-14). Genetic factors, BRCA2
mutations, family history, obesity, Klinefelters syndrome,
gynecomastia, liver disease, orchitis, undescended testicle,
alcohol use, exogenous estrogen and testosterone use, and
radiation are accused in the etiology (1, 8, 9, 15-17). Patients
mostly present with a painless mass, nipple discharge, skin
ulceration, or nipple retraction (2, 4). The most common
type is invasive carcinoma - no specific type (IC-NST) (2,
3, 9). Ultrasonography (USG) and Magnetic Resonance
Imaging (MRI) are used radiologically, and biopsy and/or
surgical excision is required for definitive diagnosis (2, 5).
The aim of this study was to evaluate the rare male breast
cancer in terms of clinical, pathological, radiological, and therapeutic methods and to discuss the results with the
We retrospectively evaluated the pathology archive of
our hospital between January 2006 and August 2019 and
included 27 cases diagnosed as primary breast cancers in
this study. Clinical follow-up of the cases was obtained
from the electronic data system and the record archive of
A 12-year electronic data search was performed using the
laboratory information system with the breast and male
keywords in the diagnostic line. Biopsies had been obtained
from a total of 87 patients, including 38 with tumors,
36 gynecomastia cases, and 7 lipomas, 2 hamartomas,
one granulomatous inflamation, one fibroadenoma +
gynecomastia, one cystic lymphangioma, and one ductal
ectasia. Eight of these 38 tumor cases were metastatic to the
breast and 30 were primary cases. One of the 30 primary
tumor cases was a liposarcoma of the breast and two were pure ductal carcinoma in situ (DCIS) without invasive
components. These three cases were excluded and a total
of 27 patients were included in the study (Table I). The
patients were evaluated retrospectively for age, tumor size,
tumor localization, histological grade; hormone profile with
estrogen receptor (ER), progesterone receptor (PR), Her2/
neu; the American Joint Committee on Cancer (AJCC)
Tumor, Node, Metastases (TNM) stage; progression,
recurrence, survival, radiological features, surgery, and
therapy modalities (adjuvant, neoadjuvant chemotherapy
and/or radiotherapy and hormonotherapy).
Immunohistochemical (IHC) assays were performed
using monoclonal antibodies against ER (Clone EP1, Code
M3643, Dako, Denmark), PR (Clone Y85, 60-0056-7,
Genemed, Germany), and Her 2/neu (Code A0485, Dako,
Denmark). ER and PR status was studied by obtaining
positive and negative control tissues and using ready-touse
solutions in the Leica bond max device. We followed
the ASCO and CAP recommendations for reporting the
IHC assay results for ER, PR and Her2/neu. All cases with
at least 1% positive cells were considered receptor positive
for ER and PR (18).
Her2/neu status can be determined by assessing protein
expression on the membrane of tumor cells using IHC or
by assessing the number of Her2/neu gene copies using in
situ hybridization (ISH). The results for Her2/neu testing
by IHC were reported according to the intensity and the percentage of positive staining in tumor cells (0, 1+, 2+,
3+). Scores of 0 and 1+ were considered negative for Her2
amplification. A score of 3+ was considered positive. A
score of 2 was considered equivocal and ISH was ordered
for confirmation (19).
Statistical analysis was performed using the SPSS statistical
package software (Version 17.0, SPSS Inc., Chicago, IL,
USA). All numerical data were expressed as median values
(minimum-maximum) or as proportions. The association
with overall survival was analyzed using the log-rank test
to examine their relationship when different variables were
applied. The survival curve was plotted using standard
Written consent was not obtained from the patients since
the study was designed retrospectively and needed no
The age of the patients ranged from 40 to 86 years (mean
age: 62.52 years, median age: 61 years). The left breast was
involved in 17 of 27 (63%) patients and the right breast in
10 of 27 (37%). The mean tumor diameter was 2.35 ± 1.09
cm (min. 0.6 cm, max. 4.5 cm). Of the 27 cases, 8 (29.6%)
were dead, 19 (70.4%) were alive. The mean follow up time
was 37.45 ± 24.84 months (4-80 months). The estimated
life expectancy of all patients was 65 ± 14.7 months. Most
of the patients presented with swelling of the breast, but to a lesser extent they suffered from areolar wounds, redness,
and bloody discharge.
The most common histopathological diagnosis was ICNST
(85.2%). There were two (7.4%) invasive lobular
carcinoma cases (ILC-Figure 1A), both with negative
epithelial-cadherin staining (Figure 1B); one case (3.7%) of
invasive micropapillary carcinoma with apocrine features
(IMPC-Figure 2), and one case of mixed carcinoma (ICNST
+ Cribriform). Three of the cases with IC-NST
contained neuroendocrine differentiation areas. According
to the Modified Bloom and Richardson score, 14 cases were
grade 3 (51.9%), 11 cases were grade 2 (40.7%), and two
cases were grade 1 (7.4%).
Click Here to Zoom
|Figure 1: A) Invasive lobular carcinoma. Discohesive cells
in desmoplastic stroma (H&E; x200). B) Loss of E-cadherin
expression is typical of lobular carcinoma cells (IHC; x100).
Click Here to Zoom
|Figure 2: Invasive micropapillary carcinoma with apocrine
features tumor cells with granular, eosinophilic cytoplasm and
enlarged nuclei with prominent nucleoli (H&E; x200).
When evaluated in terms of pT, 7 cases (25.9%) were
pT1, 11 cases (40.8%) were pT2, and 2 cases (7.4%) were
pT4. Two of the 7 (25.9%) cases with missing pT were
diagnosed with ready-to-use paraffin blocks and five with core biopsies and were no longer followed-up. Two
patients underwent excisional biopsy, 3 patients underwent
mastectomy, 11 patients underwent mastectomy with
lymph node dissection (LND), and 4 patients underwent
mastectomy with sentinel lymph node dissection (SLND).
Metastatic lymph nodes were observed in 9 out of 15 cases
with lymph node sampling, whereas lymph nodes were
reactive in 6 cases (summarized in Table II).
Click Here to Zoom
|Table II: Clinico-pathological characteristics of 27 patients with male breast cancer.
When examined radiologically, 20/27 of the cases had a
USG. Four patients had mammography. On USG, 19/20
cases had an irregularly confined lesion with a solid lobule
appearance that was suspicious in terms of malignancy.
In another case, the USG appearance was reported to
be compatible with bilateral lipoma but the biopsy was
reported as IMPC with apocrine features. Four of our
patients had breast carcinoma as well as a second primary
carcinoma consisting of one small cell lung carcinoma,
one lung adenocarcinoma, one prostate adenocarcinoma,
and one thyroid papillary carcinoma. Four of our cases
metastasized: two to the bone, one to the pleura, and the
other to the bone and liver. Pagets disease was present in
three cases (Figure 3). The hormone profile was positive
for ER in 24 (88.9%) and negative in three (11.1%). PR was
positive in 21 (77.8%) patients and negative in six (22.2%)
patients. Her2/neu was negative in 21 (77.8%) and positive
in six (22.2%) cases. There were 3 (11.1%) patients with
triple-negative breast cancer. DCIS accompanied the main
pathology in 10 (37%) of the patients. Two (7.4%) patients
had multifocal tumors, which were ILC and IMPC with
apocrine features. Of the 27 cases, 19 (70.4%) were being
followed-up and 8 (29.6%) were out of follow-up. Five cases
did not come back after core biopsy, and two cases had a ready-made paraffin block for diagnosis confirmation, and
one case was lost to follow-up after 20 months. Thus eight
cases could not be followed-up.
Click Here to Zoom
|Figure 3: Nipple epidermis containing Paget cells with palestained
cytoplasm and irregular nuclei (H&E; x200).
Six of the patients who died had IC-NST, one had IC-NST
with cribriform carcinoma, and the other had ILC.
The treatment protocols of 19 patients were chemotherapy
(CT) + radiotherapy (RT) in 15 and Tamoxifen (TMX)
and/or Trastuzumab (TTZ) were added to the treatment in
case of hormone receptor positivity. Two of the other four
patients were treated only with TMX, one with RT + TMX,
and one with CT + TMX + TTZ.
Although male breast cancer is very rare compared to
women, its incidence has been increasing in recent years.
Approximately 2000-2500 new cases are added each year
in the United States, while this rate is 1/100000 in India
(1, 7-9, 11, 20). We should therefore pay attention to the
clinical, genetic and epidemiological features of male
breast cancer. Although seen in all age groups, it is mostly
observed between the ages of 60 and 65 years (1, 3, 4). In
our series, the ages ranged from 40 to 86 years, with an
average age of 61 years.
The most common complaint is generally a palpable mass
in the breast. Although signs such as nipple discharge,
mass, contraction, scarring, and redness in the breast are
seen in many cases, they are generally ignored and delays
in diagnosis are therefore experienced as the hospital
admissions are late (13). In our series, the most common
complaint was swelling of the breast, followed by a nonhealing
wound on the nipple, bloody discharge, and redness.
There were delays that ranged from 3 months to 2 years
between the onset of the complaints and first symptom and
admission to the hospital. The reason for the delay may
be related to the fact that breast cancer is more commonly
associated with women in the community. The diagnosis
is made by the history, physical examination, radiological
methods, and histopathological examinations. We first
use USG radiologically at our institution in the event of a
suspected abnormality during a clinical examination. Due
to the rarity of male breast cancer, we attempt to avoid
likely unnecessary radiation. If sonographic findings are
suspicious, a biopsy is the next step. Male BC is diagnosed by mammography and/or USG and confirmed by a core
biopsy that is always performed following a suspicious
Male breast cancer is mostly seen in the left breast (2). It
was also more commonly observed in the left breast in our
series (17/27). Age, race, family history, obesity, genetic
factors (especially BRCA2 mutations), gynecomastia,
Klinefelter syndrome, Cowden syndrome, liver diseases
that cause an estrogen increase, cirrhosis, ionized radiation
and prolonged heat exposure (increases prolactin level) due
to environmental factors, alcohol, and excess consumption
of red meat are mostly accused in the etiology (1, 2, 7-9, 12,
13, 17). In our series, two patients had a history of radiation
(due to lung cancer), three patients had gynecomastia, one
patient had obesity, three patients had diabetes and CRF
(dialysis patient), and four patients had a history of breast
carcinoma in their sisters. One of our patients with a family
history also had an alcohol use disorder and diabetes, and
another had gynecomastia. Gynecomastia can be observed
in 6-38% of men with breast cancer (16). Three of our
patients (11.1%) had gynecomastia.
Although the mean tumor size reported in the literature is
2 to 3.5 cm, it can vary between 0.5 and 12.5 cm (2, 3, 13).
In our series, tumor size ranged from 0.6 to 4.5 cm, with an
average of 2.35 cm, in accordance with the literature.
Among male breast cancers, IC-NST (80-90%) is the most
common histopathological diagnosis followed by papillary
carcinomas. Less often, ILC, mucinous carcinoma and
apocrine carcinoma are detected (8, 14). In our series, 23
IC-NST, two ILC, one IMPC with apocrine features, and
one mixed carcinoma (IC-NST with cribriform carcinoma)
were observed, consistent with the literature. A total of
two ILC were identified in our study, both with negative
epithelial-cadherin staining. Pagets disease is a rare disease
and constitutes 1% of breast cancers. It is an eczematous
skin disease, usually associated with an underlying breast
cancer (6). Considering that male breast cancers constitute
1% of all breast cancers, the incidence of Pagets disease in
male breast cancer is very low. In our series, Pagets disease
was associated with breast cancer in three (11.1%) cases
(Figure 3). Therefore, Pagets disease should be considered
in the differential diagnosis of non-healing wounds of the
nipple, and biopsy should be performed to exclude an
In terms of grade, an MBC study found that 73% were
grade 3 while another retrospective study of 1180 MBC
from the SEER database demonstrated that 39% were grade
3 (20, 21). In our study, 14 cases were grade 3 (51.9%) and 11 cases were grade 2 (40.7%). In a few studies, the median
survival has been shown to be significantly poor in highgrade
(grade 3) tumors (14). However, no such significant
correlation was seen between tumor grade and outcome
(p= 0.65) in our study.
Axillary involvement is present in approximately 30-50%
of the cases at the time of diagnosis (2,14) and was present
in 9/27 (33%) of our cases. Most male breast cancers are
usually positive for ER (65-97%) and PR (60-85%) (2, 4,
13, 14, 22, 23). The Her2/neu positivity rate is 3-28%
(14, 22, 24). The rate of triple-negative breast carcinoma
varies between 3 and 19% (14, 24). In our series, ER was
positive in 24 (88.9%), PR was positive in 21 (77.8%),
and Her2 / neu was positive in 6 (22.2%) patients. FISH
was performed in patients with a Her2/neu score of 2
by immunohistochemistry to confirm the diagnosis.
Prostate, lung, skin, gastrointestinal system, and thyroid
cancers can be seen as a secondary malignancy in 5-33%
of male breast cancer patients (2, 3, 8, 23). In our series,
the secondary malignancies were two lung cancers, one
prostate cancer, and one thyroid cancer.
Since male breast cancer is rare, standard approaches have
historically relied on the results of trials in female breast
cancer (22). Treatment methods vary according to the
tumor stage and surgery, CT, RT, and hormone treatment
methods can be used in single or combined forms (3, 17).
Surgically, mastectomy rather than breast-conserving
surgery was performed in the vast majority of cases in the
literature (12, 17). Mastectomy was also the most common
procedure in our series.
Our study has the limitations of a retrospective study from
a single institution conducted over a long period. On the
other hand, we believe the fact that all of our patients
underwent a multidisciplinary diagnosis and follow-up
process contributed to data standardization.
Since the prognosis of male breast cancer is the same as that
of female breast cancer of the same stage, early diagnosis is
the most important factor for treatment success.
For this reason, breast cancer should be considered in the
differential diagnosis and an appropriate biopsy should
be performed in case of complaints about breast skin and
breast swelling in order to diagnose the condition at an
earlier stage. It is important to raise public awareness by
explaining that breast cancer is not unique to women, to
teach self breast examination to men, and even to start
breast screening programs similar to those for women for
CONFLICT of INTEREST
No conflict of interest was declared by the authors.
The authors declared that this study has received no
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