Special Considerations in The Evaluation and Management of Breast Cancer in Men

Curr Probl Cancer 40 (2016) 163–171
Contents lists available at ScienceDirect
Curr Probl Cancer
journal homepage: www.elsevier.com/locate/cpcancer
Special considerations in the evaluation and

management of breast cancer in men1
Suleiman Alfred Massarweh, MDa,b,⁎, Gloria L. Choi, NPc
a r tic l e in f o a bs t r a c t
Breast cancer in men is relatively uncommon but its

Keywords: incidence has been rising. Traditionally, the management
Breast cancer in men of breast cancer in men is based on extrapolation from
Estrogen receptor clinical trials of breast cancer in women, due to the much
BRCA2 more extensive data available in women with this disease.
Androgen receptor There are, however, unique characteristics that distinguish
Tamoxifen breast cancer in men and these should be taken into
consideration when managing this patient population.
Breast cancer in men is more frequently estrogen receptor
(ER) and progesterone receptor (PgR) positive, and less
frequently HER2 amplified. Lobular carcinoma, which
accounts for 10–15% of breast cancers in women, is excep-
tionally rare in men. Genetic risk factors, particularly BRCA2
mutations, are increasingly recognized as a key risk factor for
breast cancer in men and genetic testing is now routinely
recommended for all men diagnosed with breast cancer.
Tamoxifen remains the gold standard endocrine therapy for
breast cancer in men, but other endocrine agents such as the
aromatase inhibitors (AI) and fulvestrant are increasingly
being used. While superior to tamoxifen in postmenopausal
women, the use of AIs for adjuvant therapy in men with
breast cancer may not be optimal since the physiology of
1
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit
sectors.
a
Division of Oncology, Stanford University School of Medicine
b
Stanford Cancer Institute, Stanford, CA, USA
c
Stanford Healthcare, Stanford, CA, USA
n
Corresponding author: Suleiman Alfred Massarweh, MD, Stanford Division of Oncology, CCSR 4115, 269 Campus Dr., Stanford,
CA 94305. Tel.: +650 724 8935, fax: +650 724 9230.
E-mail address: massarweh1@stanford.edu (S.A. Massarweh).
http://dx.doi.org/10.1016/j.currproblcancer.2016.09.003
0147-0272/& 2016 Elsevier Inc. All rights reserved.
Downloaded for andromeda masako (andromeda72@yahoo.com) at Universitas Sumatra Utara from ClinicalKey.com by Elsevier on
May 14, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
164 S.A. Massarweh, G.L. Choi / Curr Probl Cancer 40 (2016) 163–171
hormonal regulation in men resembles that of premeno-

pausal rather than postmenopausal women. Emerging areas
of investigation include the role of genomic risk stratification
to gain further insight into the biology of breast cancer in
men, the study of the androgen receptor (AR) as a
therapeutic target, and the role of gonadal suppression in
the management of the disease. There is clearly a more
consorted effort to study breast cancer in men as a unique
disease in order to have a better understanding of its biology
and we are likely to witness further advances that will help
us better manage this unique disease situation.
& 2016 Elsevier Inc. All rights reserved.
Introduction and epidemiology
The American Cancer Society estimates that approximately 2600 men would be diagnosed
with breast cancer in the United States in 2016,1 which accounts for 1% of all breast cancer cases
(in both sexes), and no more than 0.03% of all new cancers in men.1 Approximately 440 men
would die from breast cancer in 2016, with a mortality rate of 17%, which is almost identical to
the risk of mortality from breast cancer in women, and this accounts for 0.13% of all cancer
deaths in men.1
Because of its rarity, much of how we treat breast cancer in men is based on the more
extensive data available on breast cancer in women. Data on breast cancer in men are
predominantly derived from retrospective single institution studies, and prospective random-
ized therapeutic trials are lacking. It is important to note that, despite its rarity, it is clear that the
incidence of breast cancer in men is rising1,2 in parallel to the increasing incidence of breast
cancer in women, but at a smaller rate,2 possibly related to the added contribution of
mammography screening in women.
Risk factors
Most men diagnosed with breast cancer have no identifiable risk factors, but there is
evidence that certain conditions of hormonal imbalance, either estrogen excess or androgen
deficiency, may play an etiologic role. Conditions of estrogen excess include chronic liver
disease,3,4 obesity,5,6 pharmacological estrogen therapy,7 and very rarely gonadal suppression in
prostate cancer.8 In obese men, levels of endogenous estrogens may be increased with more
conversion of androgens to estradiol and estrone in fat tissue,6 and exogenous estrogen
use has been reported in connection with breast cancer rarely reported in male-to-female
transsexuals.9
Conditions associated with lowered testosterone have been implicated in the etiology of
breast cancer in men, including testicular conditions such as orchitis, undescended testes,
orchiectomy, and Klinefelter syndrome.10,11 Occupational heat exposure, which may affect
testicular function, has also been associated with increased risk of breast cancer in men,
including in steel and blast furnace workers.12
Gynecomastia may be associated with breast cancer, and autopsy studies report that as many
as 50% of all men with breast cancer may have associated gynecomastia present.13 A recent US
Veterans population study confirmed the association of breast cancer in men with gynecomastia,
Klinefelter syndrome, obesity, and orchitis, which lends further support to the role of hormonal
factors in the etiology of breast cancer in men.14 Interestingly, that same study suggested that
cholelithiasis might be a risk factor for the development of breast cancer in black men.
S.A. Massarweh, G.L. Choi / Curr Probl Cancer 40 (2016) 163–171 165
More recent data from the Male Breast Cancer Pooling Project reported a significant
association of breast cancer in men with increased weight and body mass index, Klinefelter
syndrome, and diabetes, with a suggestion of an association with cryptorchidism and orchitis.15
Importantly, baseline circulating estradiol levels were higher in men with breast cancer
compared to controls from this study, supporting the role of endogenous estrogens as a risk
factor for breast cancer in men.16 Although alcohol and tobacco were previously postulated to be
associated with breast cancer in men, more recent studies suggest no conclusive association.17
Genetic factors
A possible familial connection to breast cancer in men has been recognized with the
increased disease risk in relatives of men with breast cancer, both women and men.18 BRCA2
mutations appear to be the strongest risk factor for breast cancer in men with a lifetime risk of
7%, which is approximately 80-100 times more than the general population.19 In 237 families
affected by breast cancer, 76% of the families with men and women with breast cancer had
BRCA2 mutations.20 Interestingly, BRCA1 mutations do not appear to be associated with an
increased risk of breast cancer in men21 with a lifetime risk of just over 1%.19 Other gene
mutations reported in association with breast cancer in men include PTEN and CHEK2, and more
recently PALB2 mutations, with a frequency of 1%-2% in men with breast cancer who are not
carriers of BRCA2 mutations.22
Based on these available data, the National Comprehensive Cancer Network’s practice
guidelines recommend genetic testing for all men with breast cancer and for individuals who
have a family history of breast cancer in a male relative. There is no screening recommendation
by the National Comprehensive Cancer Network for breast cancer in men who are mutation
carriers, in view of the lack of evidence to support screening in this population.23
Clinical presentation and diagnostic evaluation
A painless subareolar mass is the presenting symptom in 85% of men with breast cancer, with
a slightly higher risk for the left breast involvement.24 Other symptoms include nipple discharge,
ulceration or bleeding of the nipple or skin, pain or swelling in the breast, or symptoms related
to metastatic disease.25
Nipple involvement has been reported to be as high as 40%-50%, perhaps because of the small
volume of breast tissue in men and the central location of most tumors.26 Clinically involved
axillary nodes may occur in 40%-55% of patients,27 but a clinical presentation of palpable axillary
nodes with an occult breast tumor is quite an unusual occurrence.28
The main differential diagnosis in a man with a breast lump is between breast cancer and
gynecomastia, which is a much more common problem29 and typically presents as a soft, mobile
subareolar mass, that can be bilateral.30 Lipoma may be the most frequently encountered benign
tumor of the breast in men and is clinically soft, mobile, and painless.30 The distinction on
physical examination between a benign and malignant breast cancer may on occasion be less
clear, but a bloody nipple discharge strongly supports a diagnosis of cancer.31 Diagnostic
evaluation of breast masses in men follows the same guidelines as in women, including the need
for mammography and ultrasound. A core biopsy for the evaluation of suspected breast cancer
provides adequate histologic and biomarker evaluation.
Pathology
Infiltrating ductal carcinoma accounts for 85%-90% of breast cancers in men,32 and lobular
carcinoma occurs rarely, probably because of the lack of terminal lobules in men.24,33,34 Other
histologic subtypes such as papillary, medullary, tubular, and mucinous carcinomas, have been
reported,2,35 with papillary tumors being the second most histology at approximately 2.6% of
cases.2,30 One entity that deserves a special mention is granular cell tumor of the breast, which
may appear similar to breast cancer clinically and on imaging36 and may need to be excised in
order to see its distinctive histologic and immunohistochemical features. Excision alone is
adequate, and recognition of this tumor is important to avoid risk of unnecessary mastectomy
and lymph node surgery.
Immunohistochemistry
Breast cancer in men expresses estrogen receptor (ER) and progesterone receptor (PgR) more
commonly than in women. A study from the Surveillance, Epidemiology, and End Results database
reported a 90% frequency of ER positivity in 680 men with breast cancer and 81% rate of PgR
positivity.2 More recent studies show an even higher frequency of ER and PgR positivity in up to
96% of cases,37,38 potentially related to the changing cutoff for ER and PgR positivity in more
recent guidelines. Regardless, it is very clear that breast cancer in men is highly driven by ER
disease biology in the vast majority of patients, and ER, therefore, serves as an important
predictor for antiestrogen benefit in the treatment of this disease.
Interestingly, HER2 expression occurs in no more than 5%-15% of breast cancer in men,32,38-40
clearly less often present compared to breast cancer in women. It appears to be associated with
younger age at diagnosis in men,38 which is reminiscent of the younger median age at diagnosis
of ER-positive/HER2-positive breast cancer in women.41
Androgen receptor (AR) expression may be present in as many as 87% of breast cancer cases in
men,32 and this may have important therapeutic implications in the future study of this disease.
Genomics alterations
Mutations in PIK3CA and TP53 appear to be less frequent in men with breast cancer whereas
mutations in DNA repair genes may be more frequent.42 Interestingly, amplification of Cyclin D1
is seen in up to 12% of breast cancer cases in men, and is overexpressed by immunohistochem-
istry in 63%,43 which may further lend support to the central role of ER signaling in the biology of
breast cancer in men and may have therapeutic implications in future studies of endocrine
therapy reminiscent of recent studies in women with ER-positive breast cancer.44
Treatment of breast cancer in men
Local management
Mastectomy has been the traditional surgical treatment for breast cancer in men and breast-
conserving surgery (BCS) has been used infrequently. Overall, less than 15% of men with breast
cancer undergo BCS even though as many as 56% of them have T1 lesions as reported in the
recent report of the International Male Breast Cancer Program32 and could, therefore, be
candidates for breast conservation.
Successful breast conservation with lumpectomy and radiation therapy has been reported in men
with small breast cancers,45 and a recent study of 6263 men with breast cancer from the Surveillance,
Epidemiology, and End Results database suggested that men with T1-T2 tumors and node-negative
disease had favorable outcomes with the use of breast conservation.46 If BCS is deemed to be
appropriate in a man with breast cancer, adjuvant breast radiation should be employed.
The use of sentinel node procedures has largely replaced more extensive axillary node
surgery in women with a negative axilla and can be used to study axillary node involvement in
men with breast cancer. Sentinel lymph node procedures in men with breast cancer can help
prevent the unnecessary removal of more lymph nodes and help with recovery from surgery.47
Adjuvant radiation therapy to the chest wall and axilla is not clearly defined in men with
breast cancer, but several retrospective studies have found that postmastectomy radiation
reduces the risk of local recurrence, although without an improvement in overall survival.48,49 It
is appropriate to use chest wall and regional nodal radiation in men with similar risk factors in
women after mastectomy, such as large primary tumors, chest wall invasion, positive margins, or
multiple positive lymph nodes.
Adjuvant systemic therapy
Endocrine therapy
Endocrine therapy is the mainstay adjuvant treatment for breast cancer in men, with 2
studies reporting an improved survival after adjuvant tamoxifen.50,51 The rate of adherence to
tamoxifen in men with breast cancer appears high,52 suggesting that it is well tolerated in this
patient population. Of important consideration, the standard duration of adjuvant tamoxifen in
women has typically been 5 years, but most studies in men were shorter, suggesting that
tamoxifen benefit may actually be underestimated in men. With recent studies reporting on the
benefit of extended tamoxifen beyond 5 years in women with breast cancer,53 it is not
unreasonable to consider extending adjuvant tamoxifen in men with breast cancer as well.
Aromatase inhibitors (AIs) have emerged in large adjuvant trials in postmenopausal women as a
superior treatment option for ER-positive breast cancer, with improved relapse-free survival
compared to tamoxifen.54-56 AIs work by blocking the peripheral conversion of androstendione to
17 β-estradiol, which leads to estrogen deprivation and inhibition of ER signaling as a
consequence.57 In a population-based study of men with breast cancer who were treated in
communities throughout the United States, tamoxifen decreased the risk of death from breast
cancer, but there was no decrease in mortality among men who received AI therapy.58 Interestingly,
a recent study of 257 men with breast cancer treated in the adjuvant setting, AI use was actually
associated with a higher mortality compared to tamoxifen (32% vs 18%), suggesting that AI therapy
may actually be an inferior treatment.59 Based on the available evidence, tamoxifen should remain
as the standard adjuvant therapy for men with breast cancer, and aromatase inhibitors should not
be used as adjuvant therapy in this population until more data become available on their use.60
It may not be entirely surprising that AIs might be inferior to tamoxifen in men, since
administration of AIs would initially lower estradiol levels but may lead to an increase in
luteinizing hormone (LH) and follicle stimulating hormone through the hypothalamic feedback
loop, and that in turn would increase circulating androgens; the precursors to estradiol.60-62
Furthermore, because of the high frequency of AR positivity in men with breast cancer, elevated
serum testosterone may by itself stimulate breast cancer growth through its action on AR.
Hormonal regulation and the use of AIs as single agents in men may, therefore, resemble the
physiology of estradiol regulation in premenopausal rather than postmenopausal women.
Consequently, if an AI is to be used in men with breast cancer, LH releasing hormone (LHRH)
agonists may be necessary to use in combination, not unlike premenopausal women with breast
cancer.63 A recent pooled analysis on the use of AI in metastatic breast cancer in men, with or
without an LHRH agonist, suggested that LHRH use increased response rates compared to AI
alone, but no correlation with improved progression-free survival was seen.61
Adjuvant chemotherapy
Recommendations for adjuvant chemotherapy in men with breast cancer have been largely
derived from studies in women, with limited reports suggesting improved outcomes with
adjuvant chemotherapy.26 Preferred adjuvant chemotherapy combinations include doxorubicin
or cyclophosphamide (AC) and weekly paclitaxel, docetaxel or cyclophosphamide (TC), similar to
breast cancer in women.64 As most men with early breast cancer have ER-positive breast cancer,
chemotherapy may not add significant benefit to adjuvant tamoxifen given for an appropriate
duration. The 21-gene recurrence score (Oncotype DX), which has been used in women to
estimate potential benefit from chemotherapy,65,66 may have potential for use in men with
breast cancer as well. Preliminary data show a similar distribution of low, intermediate, and
high-risk recurrence scores between men and women with breast cancer,67 and it is not
unreasonable to use recurrence score in treatment decisions for men with breast cancer as we
await more data on its use.
Triple negative and HER2-positive breast cancer in men, although extremely unlikely to be
seen in practice, should be treated following the same treatment guidelines that exist for women
with these types of breast cancer.
Treatment of metastatic breast cancer in men
Historically, gonadal ablation was the mainstay of treatment since the original reported
improvement of bone metastasis after orchiectomy in 1942.68 A review of gonadal ablative
therapies in 447 patients, response rates were 55% for orchiectomy, 80% for adrenalectomy, and
56% for hypophysectomy.69 Although largely of historical significance, the observations from
gonadal ablation strategies further support the idea that disease response in men with breast
cancer is similar to hormonal regulation in premenopausal women, and this is critical as we plan
future trials in men with breast cancer.
Tamoxifen has been used in the treatment of men with metastatic breast cancer, with 1 study
reporting a cumulative response rate of 48%.70
Data on the use of AI therapy in men with metastatic breast cancer are more limited,61,62,71
with a recent pooled analysis reporting improved disease response when an LHRH agonist was
used in combination.61
Fulvestrant, which degrades ER,72 was recently reported for the treatment of men with
metastatic ER-positive breast cancer,73,74 with a pooled analysis of 23 treated patients suggesting
a reasonable activity with few side effects.74 Of note, the dose of fulvestrant in all reported cases
of breast cancer in men was 250 mg monthly, and it is most appropriate to offer patients high-
dose fulvestrant if its use is considered.
Targeting the androgen receptor (AR), which is expressed in up to 87% of men with breast
cancer,32 may be a promising strategy for the treatment of men with metastatic breast cancer. A
recent pooled analysis of 60 men with metastatic breast cancer suggested that using an LHRH
agonist with either an AI or with cyproterone acetate, improves efficacy over monotherapy, with
a median progression-free survival of 11.6 months for combined hormonal blockade vs
6 months, and an overall survival of 29.7 vs 22 months.75 This suggests that AR blockade,
including in combination with an LHRH agonist, might be worthwhile pursuing in future studies.
Lastly, chemotherapy can be used for patients with metastatic disease that has become
refractory to hormonal agents. Generally, agents to consider for metastatic disease in men
include doxorubicin, paclitaxel, docetaxel, eribulin, capecitabine, and gemcitabine.64
Summary and future directions
Breast cancer in men presents us with a unique challenge and deserves special consideration
in its evaluation, management, and future study. It has a higher frequency of ER expression than
in women, and has a closer resemblance to the physiology of hormonal regulation in
premenopausal than postmenopausal women with breast cancer. Genetic testing is now
routinely recommended for all men with breast cancer, particularly for BRCA2 mutations, and
BCS with sentinel node biopsy is of increasing interest as an alternative approach in appropriate
patient candidates. Tamoxifen remains as the standard adjuvant endocrine therapy, and AI use is
best avoided in this setting until more data are available. AI therapy may be considered in
metastatic disease, however, but may be more effective if combined with gonadal suppression
using LHRH agonist.
The inability to conduct prospective clinical trials in men with breast cancer has been an
impediment to progress in this field, and much of the available treatment strategies continue to be
an extrapolation from data on breast cancer in women. It is becoming increasingly apparent,
however, that breast cancer in men represents a unique disease entity, and we need a more
consorted effort to study this patient population in well-designed, highly collaborative future trials.
References
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66:7–30.
2. Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN. Breast carcinoma in men: a population-based study.
Cancer 2004;101:51–57.
3. Anderson WF, Devesa SS. Breast carcinoma in men. Cancer 2005;103:432–433.
4. Sorensen HT, Friis S, Olsen JH, Thulstrup AM, Mellemkjaer L, Linet M, et al. Risk of breast cancer in men with liver
cirrhosis. Am J Gastroenterol 1998;93:231–233.
5. Ewertz M, Holmberg L, Tretli S, Pedersen BV, Kristensen A. Risk factors for male breast cancer—a case-control study
from Scandinavia. Acta Oncol 2001;40:467–471.
6. Hsing AW, McLaughlin JK, Cocco P, Co Chien HT, Fraumeni JF Jr. Risk factors for male breast cancer (United States).
Cancer Causes Control 1998;9:269–275.
7. McClure J, Higgins CC. Bilateral carcinoma of male breast after estrogen therapy. J Am Med Assoc 1951;146:7–9.
8. Thellenberg C, Malmer B, Tavelin B, Gronberg H. Second primary cancers in men with prostate cancer: an increased
risk of male breast cancer. J Urol 2003;169:1345–1348.
9. Symmers WS. Carcinoma of breast in trans-sexual individuals after surgical and hormonal interference with the
primary and secondary sex characteristics. Br Med J 1968;2:83–85.
10. Thomas DB, Jimenez LM, McTiernan A, Rosenblatt K, Stalsberg H, Stemhagen A, et al. Breast cancer in men: risk
factors with hormonal implications. Am J Epidemiol 1992;135:734–748.
11. Evans DB, Crichlow RW. Carcinoma of the male breast and Klinefelter’s syndrome: is there an association? CA Cancer
J Clin 1987;37:246–251.
12. Rosenbaum PF, Vena JE, Zielezny MA, Michalek AM. Occupational exposures associated with male breast cancer. Am J
Epidemiol 1994;139:30–36.
13. Andersen JA, Gram JB. Male breast at autopsy. Acta Pathol Microbiol Immunol Scand A 1982;90:191–197.
14. Brinton LA, Carreon JD, Gierach GL, McGlynn KA, Gridley G. Etiologic factors for male breast cancer in the U.S.
Veterans Affairs medical care system database. Breast Cancer Res Treat 2010;119:185–192.
15. Brinton LA, Cook MB, McCormack V, Johnson KC, Olsson H, Casagrande JT, et al. Anthropometric and hormonal risk
factors for male breast cancer: male breast cancer pooling project results. J Natl Cancer Inst 2014:106. djt465.
16. Brinton LA, Key TJ, Kolonel LN, Michels KB, Sesso HD, Ursin G, et al. Prediagnostic sex steroid hormones in relation to
male breast cancer risk. J Clin Oncol 2015;33:2041–2050.
17. Cook MB, Guenel P, Gapstur SM, van den Brandt PA, Michels KB, Casagrande JT, et al. Tobacco and alcohol in relation
to male breast cancer: an analysis of the male breast cancer pooling project consortium. Cancer Epidemiol Biomarkers
Prev 2015;24:520–531.
18. Olsson H, Andersson H, Johansson O, Moller TR, Kristoffersson U, Wenngren E. Population-based cohort
investigations of the risk for malignant tumors in first-degree relatives and wives of men with breast cancer.
Cancer 1993;71:1273–1278.
19. Johansen Taber KA, Morisy LR, Osbahr AJ 3rd, Dickinson BD. Male breast cancer: risk factors, diagnosis, and
management (Review). Oncol Rep 2010;24:1115–1120.
20. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of
the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet
1998;62:676–689.
21. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to
chromosome 17q21. Science 1990;250:1684–1689.
22. Ding YC, Steele L, Kuan CJ, Greilac S, Neuhausen SL. Mutations in BRCA2 and PALB2 in male breast cancer cases from
the United States. Breast Cancer Res Treat 2011;126:771–778.
23. NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High Risk Assessment: Breast and Ovarian Cancers.
http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf; 2015.
24. Giordano SH. A review of the diagnosis and management of male breast cancer. Oncologist 2005;10:471–479.
25. Erlichman C, Murphy KC, Elhakim T. Male breast cancer: a 13-year review of 89 patients. J Clin Oncol. 1984;2:
903–909.
26. Giordano SH, Buzdar AU, Hortobagyi GN. Breast cancer in men. Ann Intern Med 2002;137:678–687.
27. Guinee VF, Olsson H, Moller T, Shallenberger RC, van den Blink JW, Peter Z, et al. The prognosis of breast cancer in
males. A report of 335 cases. Cancer 1993;71:154–161.
28. Crichlow RW. Carcinoma of the male breast. Surg Gynecol Obstet 1972;134:1011–1019.
29. Braunstein GD. Gynecomastia. N Engl J Med 1993;328:490–495.
30. Chau A, Jafarian N, Rosa M. Male breast: clinical and imaging evaluations of benign and malignant entities with
histologic correlation. Am J Med 2016, http://dx.doi.org/10.1016/jamjmed2016.01.009. [Epub Feb 1, 2016].
31. Amoroso WL RGF, Treves N. Serous and serosanguinous discharge from the male nipple. Arch Surg 1956;73:319–329.
32. Cardoso F, Bartlett J, Slaets L, van Deurzen C, van Leewen-Stok E, Porter P, et al. Abstract S6-05: characterization of
male breast cancer: first results of the EORTC10085/TBCRC/BIG/NABCG International Male BC Program. Cancer Res
2015;75:S6-05-S6.
33. Sanchez AG, Villanueva AG, Redondo C. Lobular carcinoma of the breast in a patient with Klinefelter’s syndrome.
A case with bilateral, synchronous, histologically different breast tumors. Cancer 1986;57:1181–1183.
34. Nance KV, Reddick RL. In situ and infiltrating lobular carcinoma of the male breast. Hum Pathol 1989;20:1220–1222.
35. De Rosa G, Giordano G, Boscaino A, Terracciano L, Donofrio V, De Dominicis G. Intracystic papillary carcinoma of the
male breast. A case report (histochemical, immunohistochemical and ultrastructural study). Tumori 1992;78:37–42.
36. Taglietti L, Vettoretto N, Blanzuoli L, Giovanetti M. Granular cell tumor of the male breast. Updates Surg 2011;63:
139–142.
37. Masci G, Caruso M, Caruso F, Salvini P, Carnaghi C, Giordano L, et al. Clinicopathological and immunohistochemical
characteristics in male breast cancer: a retrospective case series. Oncologist 2015;20:586–592.
38. Chavez-Macgregor M, Clarke CA, Lichtensztajn D, Hortobagyi GN, Giordano SH. Male breast cancer according to
tumor subtype and race: a population-based study. Cancer 2013;119:1611–1617.
39. Rudlowski C, Friedrichs N, Faridi A, Fuzesi L, Moll R, Bastert G, et al. Her-2/neu gene amplification and protein
expression in primary male breast cancer. Breast Cancer Res Treat 2004;84:215–223.
40. Wang-Rodriguez J, Cross K, Gallagher S, Djahanban M, Armstrong JM, Wiedner N, et al. Male breast carcinoma:
correlation of ER, PR, Ki-67, Her2-Neu, and p53 with treatment and survival, a study of 65 cases. Mod Pathol 2002;15:
853–861.
41. Alqaisi A, Chen L, Romond E, Chambers M, Stevens M, Pasley G, et al. Impact of estrogen receptor (ER) and human
epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for
tumor biology and research. Breast Cancer Res Treat 2014;148:437–444.
42. Piscuoglio S, Ng CK, Murray MP, Guerini-Rocco E, Martelotto LG, Geyer FC, et al. The genomic landscape of male
breast cancers. Clin Cancer Res 2016, http://dx.doi.org/10.1158/1078-0432.CCR-15-2840. [published online first
March 9, 2016].
43. Barlund M, Kuukasjarvi T, Syrjakoski K, Auvinen A, Kallioniemi A. Frequent amplification and overexpression of
CCND1 in male breast cancer. Int J Cancer 2004;111:968–971.
44. Turner NC, Ro J, Andre F, Loi S, Verma S, Iwata H, et al. Palbociclib in hormone-receptor-positive advanced breast
cancer. N Engl J Med 2015;373:209–219.
45. Vetto J, Jun SY, Paduch D, Eppich H, Shih R. Stages at presentation, prognostic factors, and outcome of breast cancer
in males. Am J Surg 1999;177:379–383.
46. Zaenger D, Rabatic BM, Dasher B, Mourad WF. Is breast conserving therapy a safe modality for early-stage male
breast cancer? Clin Breast Cancer 2016;16:101–104 http://dx.doi.org/10.1016/j.clbc.2015.11.005. [Epub Nov 17].
47. Gennari R, Renne G, Travaini L, Bassi F, Zurrida S. Sentinel node biopsy in male breast cancer: future standard
treatment? Eur J Surg 2001;167:461–462.
48. Donegan WL, Redlich PN, Lang PJ, Gall MT. Carcinoma of the breast in males: a multiinstitutional survey. Cancer
1998;83:498–509.
49. Zabel A, Milker-Zabel S, Zuna I, Wannenmacher M, Debus J. External beam radiotherapy in the treatment of male
breast carcinoma: patterns of failure in a single institute experience. Tumori 2005;91:151–155.
50. Ribeiro G. Male breast carcinoma—a review of 301 cases from the Christie Hospital & Holt Radium Institute,
Manchester. Br J Cancer 1985;51:115–119.
51. Goss PE, Reid C, Pintilie M, Lim R, Miller N. Male breast carcinoma: a review of 229 patients who presented to the
Princess Margaret Hospital during 40 years: 1955–1996. Cancer 1999;85:629–639.
52. Bradley KL, Tyldesley S, Speers CH, Woods R, Villa D. Contemporary systemic therapy for male breast cancer. Clin
Breast Cancer 2014;14:31–39.
53. Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, et al. Long-term effects of continuing adjuvant tamoxifen to
10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised
trial. Lancet 2013;381:805–816.
54. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or
in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005;365:60–62.
55. Buzdar AU. Letrozole compared with tamoxifen as initial adjuvant therapy for breast cancer. J Clin Oncol 2007;25:
2147–2148.
56. van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, et al. Adjuvant tamoxifen and exemestane
in early breast cancer (TEAM): a randomised phase 3 trial. Lancet 2011;377:321–331.
57. Osborne CK. Aromatase inhibitors in relation to other forms of endocrine therapy for breast cancer. Endocr Relat
Cancer 1999;6:271–276.
58. Harlan LC, Zujewski JA, Goodman MT, Stevens JL. Breast cancer in men in the United States: a population-based
study of diagnosis, treatment, and survival. Cancer 2010;116:3558–3568.
59. Eggemann H, Ignatov A, Smith BJ, Altmann U, von Minckwitz G, Rohl FW, et al. Adjuvant therapy with tamoxifen
compared to aromatase inhibitors for 257 male breast cancer patients. Breast Cancer Res Treat 2013;137:465–470.
60. Korde LA, Zujewski JA, Kamin L, Giordano S, Domchek S, Anderson WF, et al. Multidisciplinary meeting on male
breast cancer: summary and research recommendations. J Clin Oncol 2010;28:2114–2122.
61. Zagouri F, Sergentanis TN, Azim HA Jr., Chrysikos D, Dimopoulos MA, Psaltopoulou T. Aromatase inhibitors in male
breast cancer: a pooled analysis. Breast Cancer Res Treat 2015;151:141–147.
62. Maugeri-Sacca M, Barba M, Vici P, Pizzuti L, Sergi D, De Maria R, et al. Aromatase inhibitors for metastatic male
breast cancer: molecular, endocrine, and clinical considerations. Breast Cancer Res Treat 2014;147:227–235.
63. Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, et al. Adjuvant exemestane with ovarian
suppression in premenopausal breast cancer. N Engl J Med 2014;371:107–118.
64. Barh D. Biomarkers, critical disease pathways, drug targets, and alternative medicine in male breast cancer. Curr
Drug Targets 2009;10:1–8.
65. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Prospective validation of a 21-gene
expression assay in breast cancer. N Engl J Med 2015;373:2005–2014.
66. Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, et al. Prognostic and predictive value of the
21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast
cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 2010;11:55–65.
67. Shak S, Palmer G, Baehner FL, Millward C, Watson D, Sledge GW. Molecular characterization of male breast cancer by
standardized quantitative RT-PCR analysis: first large genomic study of 347 male breast cancers compared to 82,434
female breast cancers. ASCO Meet Abstr 2009;27:549.
68. Farrow JH, Adair FE. Effect of orchidectomy on skeletal metastases from cancer of the male breast. Science 1942;95:
654.
69. Jaiyesimi IA, Buzdar AU, Sahin AA, Ross MA. Carcinoma of the male breast. Ann Intern Med 1992;117:771–777.
70. Patterson JS, Battersby LA, Bach BK. Use of tamoxifen in advanced male breast cancer. Cancer Treat Rep 1980;64:
801–804.
71. Giordano SH, Hortobagyi GN. Leuprolide acetate plus aromatase inhibition for male breast cancer. J Clin Oncol
2006;24:e42–e43.
72. Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, et al. Results of the CONFIRM phase III trial
comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive
advanced breast cancer. J Clin Oncol 2010;28:4594–4600.
73. Agrawal A, Cheung KL, Robertson JF. Fulvestrant in advanced male breast cancer. Breast Cancer Res Treat 2007;101:
123.
74. Zagouri F, Sergentanis TN, Chrysikos D, Dimopoulos MA, Psaltopoulou T. Fulvestrant and male breast cancer:
a pooled analysis. Breast Cancer Res Treat 2015;149:269–275.
75. Di Lauro L, Pizzuti L, Barba M, Sergi D, Sperduti I, Mottolese M, et al. Role of gonadotropin-releasing hormone
analogues in metastatic male breast cancer: results from a pooled analysis. J Hematol Oncol 2015;8:1–5.

Special Considerations in The Evaluation and Management of Breast Cancer in Men

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Special Considerations in The Evaluation and Management of Breast Cancer in Men

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Curr Probl Cancer 40 (2016) 163–171

Contents lists available at ScienceDirect

Curr Probl Cancer

journal homepage: www.elsevier.com/locate/cpcancer

Special considerations in the evaluation and

Breast cancer in men is relatively uncommon but its

hormonal regulation in men resembles that of premeno-

Introduction and epidemiology

Clinical presentation and diagnostic evaluation

Treatment of breast cancer in men

Adjuvant systemic therapy

Treatment of metastatic breast cancer in men

Summary and future directions

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