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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 526-529
 

Male breast cancer: A single institute experience


1 Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
2 Department of Surgical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiation Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication10-Mar-2016

Correspondence Address:
V Raina
Department of Medical Oncology, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.178399

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 » Abstract 

BACKGROUND: Male breast cancer (MBC) is a rare disease and accounts for 1% of all breast cancers. There is limited data on MBC from India. The aim of our study was to assess clinico-pathological parameters and outcome in MBC patients. MATERIALS AND METHODS: This analysis was carried out in 76 patients of MBC who were registered at Institute Rotary Cancer Hospital of All India Institute Of Medical Sciences between 1996 and 2012. Patients' records were retrospective reviewed and data obtained from the computer database using International Classification of Diseases code (C-50). RESULTS: The median age was 59 years (range: 28-80). The median duration of symptoms was 11 months (range: 0.5-40). Breast lump was the most common presenting symptom (left > right side). American Joint Committee on Cancer (7th edition) stage distribution was Stage I-2.6%, Stage II-13.1%, Stage III-59.3% and Stage IV-25%. Modified radical mastectomy was the commonest surgical procedure. Moreover, 30% of tumors were high-grade and 70% had pathological node positive disease. Estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2)/neu positivity was 80% and 28%, respectively. Triple negative breast cancer constituted 19% of cases. With a median follow-up of 36 months, 3 years relapse free survival and overall survival was 60% and 80%. Advanced stage and visceral metastasis at baseline predicted poor outcome. CONCLUSION: MBC constituted 0.8% at our institute. Our study population had a longer time to presentation, advanced disease at presentation, more HER2/neu positivity and triple negativity higher than the available literature.


Keywords: India, male breast cancer, outcome


How to cite this article:
Gogia A, Raina V, Deo S, Shukla N K, Mohanti B K. Male breast cancer: A single institute experience. Indian J Cancer 2015;52:526-9

How to cite this URL:
Gogia A, Raina V, Deo S, Shukla N K, Mohanti B K. Male breast cancer: A single institute experience. Indian J Cancer [serial online] 2015 [cited 2018 May 27];52:526-9. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/526/178399





 » Introduction Top


Male breast cancer (MBC) is a rare disease, accounting 1% of all of breast cancers and 0.5% of all malignancies in men.[1] The incidence of MBC is higher in North America and Europe as compared with other Asian countries.[2] The age adjusted incidence rate for MBC in New Delhi, a urban cancer registry, is 0.3/100,000.[3] Some studies have shown that the incidence of MBC has increased since last two decades, but still it remains a rare condition.[4] Because of its low incidence the information on MBC has been collected from retrospective analysis from case series. Most of treatment guidelines for management of MBC have been obtained from results of female breast cancer studies. Pre-disposing factors for MBC include family history (in the first degree relative), hormones (high estrogen and prolactin levels), radiation exposure, diseases associated with hyperestrogenemia like cirrhosis of the liver and genetic syndromes, such as Klinefelter disease.[5] Nearly, 90% of MBCs express the estrogen receptor (ER) and 81% express the progesterone receptor (PR) and 2-15% tumor over express human epidermal growth factor receptor 2 human epidermal growth factor receptor 2 (HER2)/neu.[6],[7],[8] The prognostic and predictive role of HER2/neu for MBC is not well-defined. There is a paucity of data on MBC from India. Our objectives were to study the clinico-pathological characteristics and outcome of MBC patients at our center.


 » Materials and Methods Top


A total of 76 patients with diagnosis of invasive breast cancer were registered between January 1996 and December 2012 in the Department of Medical Oncology, Institute Rotary Cancer Hospital of All India Institute of Medical Sciences. Patients' details were collected from our computer database and patients' files from medical records section. The last follow-up of all patients was done on June 2013. Immunohistochemical testing to determine ER and PR and HER2/neu receptor status was performed using the standard procedures on 4 μm sections of paraffin embedded tissue specimens stained with the monoclonal antibodies (1:400; Thermo, USA), (1:400; Spring, USA) and (1:100; Thermo, USA) for ER, PR and HER2/neu respectively. Nuclear staining greater than 1% of tumor cell was considered as positive for ER and PR. Patients were considered HER2-positive if they had immunohistochemistry (IHC) 3++ or fluorescence in situ hybridization (FISH) was amplified (more than 6 copies of HER2/neu gene or HER2/neu: CEP17 ratio of more than two) by DAKO Hercep Test. Triple negative breast cancer was defined as negativity for ER, PR and HER2/neu (IHC score 0 or 1 + or FISH non-amplified). Overall survival (OS) was defined as the time period between diagnosis and death from any cause. Relapse free survival (RFS) (only for non-metastatic patients) was defined as the time period from diagnosis to the occurrence of relapse. Progression free survival (PFS) (only for metastatic patients) was defined as the time period from diagnosis to the occurrence of relapse or progression. Patients who did not experience any event/death or lost to follow-up were censored for survival analysis. Baseline categorical variables were analyzed using Chi-square test or Fisher's exact test. Non-categorical variables were analyzed using t-test or Mann-Whitney test. RFS, PFS and OS were determined by Kaplan Meier survival curves. Log rank test was used to compare survival. Univariate and multivariate analyses were performed to identify prognostic factors for survival. Cox proportional hazards model was used to calculate hazard ratio. Estimates were considered to be statistically significant for values of P < 0.05. Statistical Package for the Social Sciences (SPSS Inc., 233 South Wacker Drive, 11th Floor, Chicago, IL) version 10 software was used for statistical analysis.


 » Results Top


A total of 76 patients were diagnosed with breast cancer between January 1996 and December 2012. The common descriptive characteristics of patients are presented in [Table 1]. The median age at diagnosis was 59 years (range: 28-80 years). Seven patients had a family history of breast cancer. Most common symptoms were breast lump followed by pain, nipple retraction, ulcer and bleeding. Seventy patients had infiltrating ductal carcinoma rest were papillary and one case of lobular carcinoma. The median clinical tumor size was 4.2 cm. Complete hormone profile was evaluable in 53 patients. ER, PR and HER2/neu positivity rate was 78%, 75% and 28%, respectively. Triple negativity is found in 19% of cases. 19 patients (25%) had metastatic disease (Stage IV) at presentation, 2 patients had Stage I, 10 patients had Stage II and the remaining 45 patients (59%) had Stage III disease. Twenty patients were associated with different co-morbities such as coronary artery disease, diabetes mellitus, hypertension or a combination.
Table 1: Patient and disease characteristics

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MRM was the most common surgical procedure performed for MBC patients in our institute, which was performed in 60%, 30% underwent radical mastectomy and only one patient underwent simple mastectomy. Treatment details are given in [Table 2]. 37 patients received post-operation radiotherapy, 4 patients received neoadjuvant chemotherapy (NACT) and 37 patients received adjuvant chemotherapy. Adjuvant and palliative hormonal treatment (tamoxifen 20 mg once in a day) was given in 57 patients. Six received six courses of 5-fluorouracil, epirubicin, cyclophosphamide (FEC), 26 patients received sequential four cycle of FEC cycles followed by four cycles docetaxel and 5 patients received cyclophosphamide, metotrexate and 5-fluorouracil chemotherapy.
Table 2: Treatment characteristics

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At last follow-up, 27 patients had relapsed, bone was the most common systemic site followed by liver [Table 3]. The median time to relapse was 40 months. Nineteen patients had shown metastatic disease upfront. The most common site of upfront metastasis was bone followed by lung and liver [Table 4]. Most of them were treated with hormonal treatment and 3 patients received combination regimen docetaxel, epirubicin and cyclophosphamide. Median progression free period was 20 months for metastatic group. At the end of the study period, 36 patients died. OS rate at 3 years was 95%, 80%, 65% and 30% in Stage I, Stage II, Stage III and Stage IV respectively (log rank test, P < 0.001). Three years OS and RFS was 80% and 60% [Figure 1]. Clinical tumor size, tumor stage, pathological nodal and tumor stage, emerged as significant prognostic factors for RFS in univariate analysis. Only clinical tumor stage emerged as significant prognostic factors by multivariate analysis for RFS in non-metastatic cases. Clinical tumor size, tumor stage, pathological nodal and tumor stage, emerged as significant prognostic factors for OS in univariate analysis. However, only pathological nodal stage was the factors found to be significantly prognostic by multivariate analysis [Table 5].
Table 3: Site of first relapse

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Table 4: Upfront metastatic sites

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Figure 1: Kaplan Meir survival curve; (a) Relapse free survival (b) Progression free survival

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Table 5: Multivariate analysis for relapse free and overall survival

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 » Discussion Top


The incidence of MBC is 1% in Western countries, 0.5% in some part of Asian countries.[9] Review of surveillance, epidemiology and end result (SEER) data indicate a rise in the incidence of MBC, from 1.0/100,000 men in the late 1970s to 1.2/100,000 men from 2000 to 2004.[10] There is lack of data on breast cancer from India, however incidence is 0.8% at our institute. Our study showed that the median age of MBC diagnosis is 59 years (range: 28-80 years), which is 8 years earlier than other studies.[9],[11] Positive family history was found in 10% of cases. Inherited mutation in BRCA 1 and 2 increases the risk of MBC by 10-20% in previous study, but genetic testing was not performed in any of our patients. Analysis from the SEER cancer registry show that 93.7% of MBCs are ductal or unclassified carcinomas and only 1.5% are lobular.[12] Invasive ductal carcinoma was the most common histological subtype in our analysis and rest were papillary and one case of lobular carcinoma. Approximately, 90% of MBCs express the ER, 81% express the PR and 2-15% over express HER2/neu.[6],[7],[8] In our analysis, we found complete hormone profile in 53 patients with ER positivity rate of 78%, PR positivity rate of 75% and HER2 positivity rate of 28%. The interesting finding in our analysis is triple negativity of MBC, which accounts for 19%, as compared with 22% in female breast cancer at our institute. Out of seven triple negative patients, 3 patient present upfront metastatic disease, three locally advance breast cancer and one early breast cancer. Since 1970, radical mastectomies have been replaced with the MRM Thus, the MRM is the standard treatment for MBC at present.[13],[14],[15],[16] A total of 27 patients underwent surgery at our center; rest of them had surgical intervention at private sector and were referred to us for adjuvant treatment. MRM was the most common procedure at our institute. Breast conservation surgery was not done in any of our patient. Post-operative adjuvant treatment received in 70% of cases with standard doses and schedule. Four patients in our study received NACT and 37 patients received adjuvant chemotherapy. Disease specific survival and OS rates in MBC among 1,986 male patients in the SEER database are shown 90% and 70%, respectively at 5 years.[12] In univariate analyses of same analysis HR-negative status and high tumor grade were associated with poorer survival, but these factors do not appear to have independent prognostic value on multivariate analysis. In our analysis, three RFS and OS was 60% and 80% with a median follow-up of 36 months. The result of our analysis is not comparable with existing literature because of advanced presentation, different immunophenotypic profile, small sample size and short follow-up. Twenty patient in our study have different comorbidities in combination or alone such as coronary artery disease, diabetes and hypertension and 15 patients died of acute coronary syndrome. The presence of comorbidities limits the possibility of treatment. There were two Indian studies published by Shukla et al. and Chikaraddi et al.[17],[18] The salient features and comparison are described in [Table 6]. Limitation of this study included retrospective analysis, small sample size, referral bias and unavailability of complete hormonal profile in 25% of cases.
Table 6: Male breast cancer: Indian studies

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 » Conclusion Top


MBC constituted 0.8% at our institute. Our study population had a longer time to presentation, advanced disease at presentation, more HER2/neu positivity and triple negativity higher than the available literature. Multicentric prospective clinical trials would be necessary to know predictive and prognostic factor to improve the outcome in MBC.

 
 » References Top

1.
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2.
Tajima N, Tsukuma H, Oshima A. Descriptive epidemiology of male breast cancer in Osaka, Japan. J Epidemiol 2001;11:1-7.  Back to cited text no. 2
    
3.
Manoharan N, Tyagi BB, Raina V. Cancer incidences in rural Delhi – 2004-05. Asian Pac J Cancer Prev 2010;11:73-7.  Back to cited text no. 3
    
4.
Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN. Breast carcinoma in men: A population-based study. Cancer 2004;101:51-7.  Back to cited text no. 4
    
5.
Sasco AJ, Lowenfels AB, Pasker-de Jong P. Review article: Epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors. Int J Cancer 1993;53:538-49.  Back to cited text no. 5
    
6.
Wick MR, Sayadi H, Ritter JH, Hill DA, Reddy VB, Gattuso P. Low-stage carcinoma of the male breast. A histologic, immunohistochemical, and flow cytometric comparison with localized female breast carcinoma. Am J Clin Pathol 1999;111:59-69.  Back to cited text no. 6
    
7.
Bloom KJ, Govil H, Gattuso P, Reddy V, Francescatti D. Status of HER-2 in male and female breast carcinoma. Am J Surg 2001;182:389-92.  Back to cited text no. 7
    
8.
Rudlowski C, Friedrichs N, Faridi A, Füzesi 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;84:215-23.  Back to cited text no. 8
    
9.
Cutuli B, Le-Nir CC, Serin D, Kirova Y, Gaci Z, Lemanski C, et al. Male breast cancer. Evolution of treatment and prognostic factors. Analysis of 489 cases. Crit Rev Oncol Hematol 2010;73:246-54.  Back to cited text no. 9
    
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Speirs V, Shaaban AM. The rising incidence of male breast cancer. Breast Cancer Res Treat 2009;115:429-30.  Back to cited text no. 10
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Hill TD, Khamis HJ, Tyczynski JE, Berkel HJ. Comparison of male and female breast cancer incidence trends, tumor characteristics, and survival. Ann Epidemiol 2005;15:773-80.  Back to cited text no. 11
    
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Giordano SH, Buzdar AU, Hortobagyi GN. Breast cancer in men. Ann Intern Med 2002;137:678-87.  Back to cited text no. 12
    
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Martin AM, Weber BL. Genetic and hormonal risk factors in breast cancer. J Natl Cancer Inst 2000;92:1126-35.  Back to cited text no. 13
    
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Ouriel K, Lotze MT, Hinshaw JR. Prognostic factors of carcinoma of the male breast. Surg Gynecol Obstet 1984;159:373-6.  Back to cited text no. 14
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Gough DB, Donohue JH, Evans MM, Pernicone PJ, Wold LE, Naessens JM, et al. A 50-year experience of male breast cancer: Is outcome changing? Surg Oncol 1993;2:325-33.  Back to cited text no. 15
    
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Cutuli B, Lacroze M, Dilhuydy JM, Velten M, De Lafontan B, Marchal C, et al. Male breast cancer: Results of the treatments and prognostic factors in 397 cases. Eur J Cancer 1995;31A:1960-4.  Back to cited text no. 16
    
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Shukla NK, Seenu V, Goel AK, Raina V, Rath GK, Singh R, et al. Male breast cancer: A retrospective study from a regional cancer center in northern India. J Surg Oncol 1996;61:143-8.  Back to cited text no. 17
    
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Chikaraddi SB, Krishnappa R, Deshmane V. Male breast cancer in Indian patients: Is it the same? Indian J Cancer 2012;49:272-6.  Back to cited text no. 18
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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