Radiation Therapy in Male Breast Cancer

Oncology & Hematology Review, 2014;10(1):61–5

Abstract:

Male breast cancer (MBC) is a relatively rare disease and because the dedicated literature on MBC is limited, management typically follows guidelines established for female breast cancer (FBC). Although radiation therapy (RT) constitutes a critical role in the treatment of MBC, several unique challenges influence its use. Most men with breast cancer present at an older age with more extensive and advanced stage disease than women. In contrast to the predominance of breast conservation therapy in women with breast cancer, the majority of men are treated with mastectomy, with or without post-mastectomy radiation. Although no prospective or randomized trials are available, retrospective data suggests that surgery followed by adjuvant RT significantly improves locoregional control (LRC) in men. This article reviews the utilisation, efficacy, and complications associated with adjuvant RT in MBC.
Keywords: Male breast cancer, radiotherapy, adjuvant, outcomes, locoregional control, survival
Disclosure: The authors have no conflicts of interest to declare.
Received: November 01, 2013 Accepted November 22, 2013 Citation Oncology & Hematology Review, 2014;10(1):61–5
Correspondence: Jordan M Cloyd, MD, Department of Surgery, Stanford University, 300 Pasteur Dr, MC5641, Stanford, CA, US. E: jcloyd@stanford.edu

An erratum to this article can be found below.

In the US, approximately 1 % of all breast cancer cases and less than 1 % of all male cancers are male breast cancer (MBC) cases. An estimated 2,240 cases of MBC will be diagnosed in the US in 2013 compared with 232,340 cases of female breast cancer (FBC).1 Due to its rarity, large prospective studies and randomised controlled trials focused on treatment options for MBC are not available. Management, therefore, has been largely dependent on results from large trials in women with breast cancer. Several unique challenges exist in men with breast cancer that influence the role of adjuvant radiotherapy (RT). Men are not screened for breast cancer and commonly present at an older age and higher stage than women, and are more likely to present with a palpable mass that is centrally located.2,3 Due to the location and the low volume of normal breast tissue in men, there is a high propensity for nipple, chest wall and nodal involvement3,4 resulting in more advanced stage at diagnosis and possibly greater need for post-mastectomy radiation (PMRT).2 Based on data from randomised clinical trials, adjuvant RT improves locoregional control (LRC) following lumpectomy and radiation in many circumstances.5–8 In this article, we review the literature associated with the role of adjuvant RT in MBC.

Role of Radiation Therapy in Locoregional Control
Post-mastectomy Radiotherapy
In the US, PMRT has traditionally been indicated in women with four or more positive lymph nodes, T3 tumours or stage III disease.9,10 Multiple randomised trials have demonstrated improvement in LRC and overall survival (OS) with the addition of PMRT (see Table 1). The Danish 82b trial demonstrated the use of PMRT, in conjunction with systemic chemotherapy, reduced local failure (LF) by 23 % and improved diseasefree survival (DFS) and OS by 14 % and 9 %, respectively.7 In the Danish 82c trial the use of PMRT, in addition to hormonal therapy, reduced LF by 27 % and improved OS by 9 %.8 The British Columbia trial similarly demonstrated a reduction in LF of 16 % with an OS improvement of 10 % with the addition of PMRT to adjuvant chemotherapy.11

For women with one to three positive nodes, the indications for PMRT are more controversial. A subgroup analysis of the Danish 82b and 82c trials included only patients with eight or more nodes removed, demonstrating that PMRT improved 15-year survival in all patients, and reduced LF rates in both groups of women with one to three positive nodes and four or more positive nodes.12 The presence of high-risk features including young age, nodal ratio (number of positive nodes compared with number of nodes examined), lymphovascular invasion, extracapsular extension, margin status and histological grade13 also influence physician recommendations for PMRT. The standard treatment for PMRT is currently 30 treatments to the chest wall, level I–III axillary nodes, supraclavicular nodes and, in certain cases, internal mammary nodes, delivered 5 days per week. Hypofractionated regimens, or shorter treatment courses with larger doses of RT per treatment, are not commonly offered post-mastectomy due to limited data.

Breast Conservation Therapy
Breast conservation therapy (BCT) is defined as partial mastectomy (e.g. lumpectomy, segmentectomy, quandrectomy) followed by RT with or without adjuvant hormonal or systemic chemotherapy. Since the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 trial demonstrated equivalent survival outcomes among women with breast cancer undergoing radical mastectomy, total mastectomy with PMRT or simple mastectomy with axillary node dissection (ALND), there has been a shift to less extensive surgery.6 NSABP B-06 compared modified radical mastectomy (MRM), lumpectomy and lumpectomy with adjuvant RT, demonstrating that the addition of RT to lumpectomy reduced ipsilateral recurrence from 39.2 % to 14.3 %.5 Similar results have been demonstrated for women with ductal carcinoma in situ (DCIS) in the European Organisation for Research and Treatment of Cancer (EORTC) 1085314 and United Kingdom Coordinating Committee On Cancer Research trials.15 The NSABP B-17 and B-24 randomised trials reinforced the results of B-06, with reduction in ipsilateral invasive and non-invasive recurrences with the addition of RT to lumpectomy.16–18 The accepted fractionation for adjuvant RT after lumpectomy usually involves 30–33 treatments, delivered 5 days per week. Hypofractionated whole-breast RT delivered in 16–20 treatments has proved its safety in randomised trials19–21 and is gaining acceptance in the US.

Axillary Radiation
Currently, the primary indication for adding dedicated axillary RT in FBC is four or more positive lymph nodes following ALND or inadequate ALND.22 The decision to add a field for supraclavicular nodal RT in patients with one to three positive nodes depends on other high-risk features (e.g. lymphovascular invasion, extracapsular extension, etc.) Regional nodal RT in women with more than four positive lymph nodes results in improved regional, axillary and supraclavicular LRC.23 The percentage of involved nodes is also predictive of axillary control rates, with improved rates when the percent of involved nodes is less than, or equal to, 50 %.24 This topic remains an area of investigational interest.

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Keywords: Male breast cancer, radiotherapy, adjuvant, outcomes, locoregional control, survival