• Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (LAB, MBC, RTF, JHL); Section on Environment and Radiation, International Agency for Research on Cancer, Lyon, France (VM); Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada (KCJ); Department of Oncology, Lund University, Lund, Sweden (HO); Department of Preventive Medicine, University of Southern California, Los Angeles, CA (JTC, BEH, MCP, GU); Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, UK (RC, AJS); Epidemiology Research Program, American Cancer Society, Atlanta, GA (SMG, MMG); Department of Medicine (JMG), Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics, Gynecology and Reproductive Biology (KBM), and Divisions of Preventive Medicine and Aging (HDS), Brigham and Women's Hospital, Boston, MA; MAVERIC, VA Boston Healthcare System, Boston, MA (JMG); Department of Surgery, Aretaieion University Hospital, Athens, Greece (GG); Center for Research in Epidemiology and Population Health, INSERM Unit 1018, Paris-Sud University, Villejuif, France (PG); AARP Research, AARP, Washington, DC (AH); Cancer Prevention Institute of California, Freemont, CA (AWH); Division of Epidemiology, Department of Health Research and Policy, and Stanford Cancer Institute, Stanford School of Medicine, Stanford University, Palo Alto, CA (AWH); Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI (LNK); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC (CI); Department of Epidemiology (KBM) and Department of Nutrition (WCW), Harvard School of Public Health, Boston, MA (KBM); Istituto di Richerche Farmacologiche, Milan, Italy (EN, DT); IMS, Inc, Rockville, MD (DP, KS); Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Athens, Greece (ETP); School of Public Health, Imperial C

BACKGROUND: The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.

METHODS: In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design-specific (case-control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided.

RESULTS: Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86).

CONCLUSIONS: Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.