Elsevier

Clinical Breast Cancer

Volume 13, Issue 5, October 2013, Pages 309-314
Clinical Breast Cancer

Review
New Approaches in the Management of Male Breast Cancer

https://doi.org/10.1016/j.clbc.2013.04.003Get rights and content

Abstract

Male breast cancer (MBC) is a rare condition that accounts for 0.1% of all male cancers. Our current evidence base for treatment is derived from female breast cancer (FBC) patients. Risk factors for MBC include age, genetic predisposition, race, sex hormone exposure, and environmental factors. Most patients present later and with more advanced disease than comparable FBC patients. Tumors are likely to be estrogen receptor and progesterone receptor positive, with the most common histologic type being invasive ductal carcinoma. Triple assessment remains the criterion standard for diagnosis. Primary MBC is mostly managed initially by simple mastectomy, with the option of breast conserving surgery, which carries an increased risk of recurrence. Sentinel node biopsy is recommended as the initial procedure for staging the axilla. Reconstructive surgery focuses on achieving primary skin closure, and radiotherapy largely follows treatment protocols validated in FBC. We recommend chemotherapy for men with more advanced disease, in particular, those with estrogen receptor negative histology. MBC responds well to endocrine therapy, although it is associated with significant adverse effects. Third-generation aromatase inhibitors are promising but raise concerns due to their failure to prevent estrogen synthesis in the testes. Fulvestrant remains unproven as a therapy, and data on trastuzumab is equivocal with HER2 receptor expression and functionality unclear in MBC. In metastatic disease, drug-based hormonal manipulation remains a first-line therapy, followed by systemic chemotherapy for hormone-refractory disease. Prognosis for MBC has improved over the past 30 years, with survival affected by disease staging, histologic classification, and comorbidity.

Introduction

Male breast cancer (MBC) is a rare but important condition that accounts for 0.1% of all male cancers and carries a higher mortality than its more common female equivalent. Comprising 0.6%-1% of all breast cancers, and with a European prevalence of 1/100,000, MBC has a paucity of clinical and epidemiologic studies in the literature; knowledge of important variations in MBC compared with female breast cancer (FBC) is not, therefore, as well understood as it could be. Compared with FBC, MBC tumors tend to express estrogen receptor (ER) and progesterone receptor (PR) more often, have a differing distribution of cellular origin, are affected differently by various environmental risk factors, and have a lower overall survival rate.1, 2 The risk factors for MBC are summarized in Table 1. In addition, the presence of gynecomastia is not considered a risk factor.3 This article summarizes the key risk factors and clinical features of MBC before going on to consider, in detail, the latest evidence for effective management of the condition.

Section snippets

The Diagnostic Pathway

Patients most commonly present with a painless breast lump.4 Rarely, patients may present with axillary lymphadenopathy alone or with Paget disease of the breast.3, 5 Nipple involvement usually occurs earlier in the disease when compared with FBC; typical changes are ulceration, retraction, or discharge.4 As in FBC, triple assessment (clinical examination followed by imaging and biopsy) is the criterion standard when diagnosing MBC. Clinical examination is invaluable, although it must be noted

Surgical Management of the Breast

Most MBC patients are treated with simple mastectomy in contrast to the breast conserving surgery (BCS) techniques, eg, lumpectomy, now popular with FBC. BCS is considered less appropriate in MBC due mainly to the comparative scarcity of breast tissue and more advanced staging at diagnosis; MBC generally has larger tumors and higher rates of chest wall and retroareolar infiltration. Three studies that compared outcomes in patients undergoing BCS vs. mastectomy are summarized in Table 3. From

Surgical Management of the Axilla

Axillary surgery in breast cancer has become less aggressive in a bid to limit common complications such as arm paraesthesia, chronic pain, lymphedema, and impaired shoulder movement. After the success of sentinel node biopsy (SNB) in FBC, the technique was first described in a case of MBC in 1999.50 It has become increasingly popular with studies that yielded sentinel node identification rates of 96%-100%, in which dual techniques of blue dye and radioisotope localization are used.51, 52

Cytotoxic Chemotherapy

Chemotherapy in breast cancer may be cytotoxic or endocrine in its therapeutic target, with adverse effects and outcomes differing between the sexes. Cytotoxic chemotherapy for MBC, in both the adjuvant and neoadjuvant settings, remains a poorly studied field. There is a limited evidence base that suggests that adjuvant chemotherapy reduces rates of relapse in MBC, but currently such regimens are prescribed less frequently in male disease compared with similar FBC patients matched for age and

Endocrine Chemotherapy

Approximately 90% of MBC is ER+, which strongly supports the use of adjuvant hormonal therapy as a cornerstone of treatment just as it is in female disease. The criterion standard is tamoxifen, a selective ER modulator used in both male and female ER+ disease. Tamoxifen effectively reduces recurrence rates and improves survival. No clinical trials support the use of tamoxifen in MBC. Many retrospective studies, however, have found benefit in using the hormonal adjuvant. One study, of 39 MBC

Monoclonal Antibodies

Trastuzumab, a HER2 downregulator, has proved itself a successful member of the treatment arsenal in FBC. Its role in MBC is less clear, however, because the HER2 receptor appears to be overexpressed less frequently compared with FBC.69 By inferring from its success in women, and with one case report that describes its successful use in metastatic MBC, it seems reasonable to offer trastuzumab to men with HER2+ tumors.70

Radiotherapy

Radiotherapy in MBC, as with chemotherapy, has a paucity of data with which to inform the design of effective treatment regimens. The treatment is used routinely in MBC, in contrast to more sparing use in female disease, because the smaller volume of male breast tissue makes achieving comfortable surgical margins a challenge.71 This is reflected in the highly variable rate of local recurrence in male disease.61, 72 Radiotherapy is associated with significant cardiovascular and pulmonary

Managing Metastatic Disease

Hormonal manipulation remains the first-line therapy for metastatic MBC with cytotoxic chemotherapy as second-line therapy. Hormonal therapy was originally performed surgically via orchidectomy, hypophysectomy, or adrenalectomy. Such approaches were effective in 55%-80% of cases but were traumatic and carried their own morbidity.74 Today, the only such surgery still routinely performed is therapeutic gonadal ablation in ER+ metastatic disease. Hormonal manipulation with tamoxifen is as

Prognosis

The age-adjusted incidence of MBC is increasing for reasons that remain unknown. In contrast to the bimodal age distribution in women, and probably due to the absence of any sudden hormonal changes such as those seen at menopause, the unimodal rate of incidence in men does not slow at age 50 years but continues to climb, as seen in Figure 1.10, 77 Mortality in MBC has continued to improve over the past 30 years despite its late presentation.9 Survival is influenced by the presence of

Conclusion

MBC, although rare, carries significant morbidity and mortality, and understanding it more fully remains a useful and urgent goal. Much of the evidence and rationale for treating the disease derives from our experience with FBC, an approach that has yielded significant improvements in outcomes. However, fundamental anatomic and physiological differences between men and women mean that specific male studies are welcome and needed, even though the scarcity of patients makes this difficult.

Disclosure

The authors have stated that they have no conflicts of interest.

References (79)

  • B. Cutuli et al.

    Ductal carcinoma in situ of the male breast. Analysis of 31 cases

    Eur J Cancer

    (1997)
  • M. Golshan et al.

    Breast conservation for male breast carcinoma

    Breast

    (2007)
  • A.D. Hill et al.

    Sentinel node biopsy in male breast cancer

    Eur J Surg Oncol

    (1999)
  • J.E. Rusby et al.

    Sentinel lymph node biopsy in men with breast cancer: a report of 31 consecutive procedures and review of the literature

    Clin Breast Cancer

    (2006)
  • J.C. Boughey et al.

    Comparative analysis of sentinel lymph node operation in male and female breast cancer patients

    J Am Coll Surg

    (2006)
  • B. Cutuli et al.

    Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centers' experience

    Int J Radiat Oncol Biol Phys

    (2002)
  • N. Pemmaraju et al.

    Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects

    Ann Oncol

    (2012)
  • A. Goldhirsch et al.

    Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer

    Ann Oncol

    (2009)
  • A. Chakravarthy et al.

    Post-mastectomy radiation in male breast cancer

    Radiother Oncol

    (2002)
  • Z.A. Nahleh

    Hormonal therapy for male breast cancer: a different approach for a different disease

    Cancer Treat Rev

    (2006)
  • W.F. Anderson et al.

    Is male breast cancer similar or different than female breast cancer?

    Breast Cancer Res Treat

    (2004)
  • A. Agrawal et al.

    Male breast cancer: a review of clinical management

    Breast Cancer Res Treat

    (2007)
  • G.-L. Gu et al.

    Axillary metastasis as the first manifestation of male breast cancer: a case report

    Cases J

    (2008)
  • L.A. Korde et al.

    Multidisciplinary meeting on male breast cancer: summary and research recommendations

    J Clin Oncol

    (2010)
  • S.H. Giordano et al.

    Breast carcinoma in men: a population-based study

    Cancer

    (2004)
  • V.W. Chen et al.

    Histological characteristics of breast carcinoma in blacks and whites

    Cancer Epidemiol Biomarkers Prev

    (1994)
  • C. Erlichman et al.

    Male breast cancer: a 13-year review of 89 patients

    J Clin Oncol

    (1984)
  • K.A. Johansen Taber et al.

    Male breast cancer: risk factors, diagnosis, and management [review]

    Oncol Rep

    (2010)
  • D. Palli et al.

    Association between the BRCA2 N372H variant and male breast cancer risk: a population-based case-control study in Tuscany, Central Italy

    BMC Cancer

    (2007)
  • A.M. Martin et al.

    Genetic and hormonal risk factors in breast cancer

    J Natl Cancer Inst

    (2000)
  • N. Orr et al.

    Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

    Nat Genet

    (2012)
  • J.A. McClure et al.

    Bilateral carcinoma of male breast after estrogen therapy

    J Am Med Assoc

    (1951)
  • W.S. Symmers

    Carcinoma of breast in trans-sexual individuals after surgical and hormonal interference with the primary and secondary sex characteristics

    Br Med J

    (1968)
  • R. Hultborn et al.

    Prevalence of Klinefelter's syndrome in male breast cancer patients

    Anticancer Res

    (1997)
  • A.J. Swerdlow et al.

    Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study

    J Natl Cancer Inst

    (2005)
  • W. Krause

    Male breast cancer—an andrological disease: risk factors and diagnosis

    Andrologia

    (2004)
  • D.B. Thomas et al.

    Breast cancer in men: risk factors with hormonal implications

    Am J Epidemiol

    (1992)
  • H.T. Sørensen et al.

    Risk of breast cancer in men with liver cirrhosis

    Am J Gastroenterol

    (1998)
  • P.H. Lahmann et al.

    Physical activity and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition

    Cancer Epidemiol Biomarkers Prev

    (2007)
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