Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results

Louise A. Brinton(National Institutes of Health), Michael B. Cook(National Institutes of Health), Valerie McCormack(Centre international de recherche sur le cancer), Kristina Johnson(University of Ottawa), Håkan Olsson(Lund University), John T. Casagrande(University of Southern California), Rosie Cooke, Roni T. Falk(National Institutes of Health), Susan M. Gapstur(American Cancer Society), Mia M. Gaudet(American Cancer Society), J. Michael Gaziano, Georgios Gkiokas(National and Kapodistrian University of Athens), Pascal Guénel(Université Paris-Sud), B. E. Henderson(University of Southern California), A. R. Hollenbeck(AARP), Ann W. Hsing(Cancer Prevention Institute of California), L. N. Kolonel(University of Hawaiʻi at Mānoa), Claudine Isaacs(Georgetown University), Jay H. Lubin(National Institutes of Health), Karin B. Michels(Harvard University Press), Eva Negri(Mario Negri Institute for Pharmacological Research), Dominick Parisi(FSG), Eleni Petridou(National and Kapodistrian University of Athens), M. C. Pike(University of Southern California), Elio Ríboli(Imperial College London), Howard D. Sesso, K. Snyder(FSG), Anthony J. Swerdlow, The European Rare Cancer Study Group(Mario Negri Institute for Pharmacological Research), D Trichopoulos(University of Oslo), Giske Ursin(Maastricht University), Piet A. van den Brandt(Kaiser Permanente), Stephen K. Van Den Eeden(Folkhälsans Forskningscentrum), Elisabete Weiderpass, Walter C. Willett(University of Southern Denmark), Marianne Ewertz(Fred Hutch Cancer Center), D. B. Thomas
JNCI Journal of the National Cancer Institute
February 19, 2014
10.1093/jnci/djt465
Cited by 162Open Access
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Abstract

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.

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