Abstract
Purpose
Male breast cancer is associated with female breast cancer in families but whether male breast cancer clusters with other discordant cancers has not been studied. As concordant male breast cancers are utterly rare, discordant associations of male breast cancer with other cancers may reveal genetic and possible environmental risk factors contributing to male breast cancer susceptibility.
Methods
We calculated relative risks (RRs) for male breast cancer in families with discordant cancers, and conversely, for discordant cancers in families of male breast cancer patients, based on 15.7 million individuals in the Swedish Family-Cancer Database.
Results
Among 1428 male breast cancer patients, 16.2% had a female relative diagnosed with breast cancer. Ovarian and female anal cancers showed the strongest associations with male breast cancer (p value < 0.0005). The other significant associations included colorectal, small intestinal, and thyroid cancers, cancer of unknown primary and non-Hodgkin lymphoma but these were each based on a single positive association with male breast cancer. The RRs for male breast cancer were increased in families in which multiple patients were diagnosed with diverse cancers, reaching an RR of 2.58 when three or more family members were affected.
Conclusions
The results suggest that male breast cancer shares susceptibility with a number of other cancers but confirmation is needed in other datasets.
Similar content being viewed by others
References
Rosenblatt KA, Thomas DB, McTiernan A, Austin MA, Stalsberg H, Stemhagen A, Thompson WD, Curnen MG, Satariano W, Austin DF et al (1991) Breast cancer in men: aspects of familial aggregation. J Natl Cancer Inst 83(12):849–854
Anderson D, Badzioch M (1991) Breast cancer risks in relatives of male breast cancer patients. J Natl Cancer Inst 84:1114–1117
Bevier M, Sundquist K, Hemminki K (2012) Risk of breast cancer in families of multiple affected women and men. Breast Cancer Res Treat 132(2):723–728. doi:10.1007/s10549-011-1915-2
Dong C, Hemminki K (2001) Second primary breast cancer in men. Breast Cancer Res Treat 66:171–172
Hemminki K, Granstrom C (2002) Re: risk of subsequent cancer following breast cancer in men. J Natl Cancer Inst 94:1892
Hemminki K, Scelo G, Boffetta P, Mellemkjaer L, Tracey E, Andersen A, Brewster DH, Pukkala E, McBride M, Kliewer EV, Chia KS, Pompe-Kirn V, Martos C, Jonasson JG, Li X, Brennan P (2005) Second primary malignancies in patients with male breast cancer. Br J Cancer 92:1288–1292
Liede A, Karlan BY, Narod SA (2004) Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol 22:735–742
Ottini L, Palli D, Rizzo S, Federico M, Bazan V, Russo A (2010) Male breast cancer. Crit Rev Oncol Hematol 73(2):141–155. doi:10.1016/j.critrevonc.2009.04.003
Silvestri V, Barrowdale D, Mulligan AM, Neuhausen SL, Fox S, Karlan BY, Mitchell G, James P, Thull DL, Zorn KK, Carter NJ, Nathanson KL, Domchek SM, Rebbeck TR, Ramus SJ, Nussbaum RL, Olopade OI, Rantala J, Yoon SY, Caligo MA, Spugnesi L, Bojesen A, Pedersen IS, Thomassen M, Jensen UB, Toland AE, Senter L, Andrulis IL, Glendon G, Hulick PJ, Imyanitov EN, Greene MH, Mai PL, Singer CF, Rappaport-Fuerhauser C, Kramer G, Vijai J, Offit K, Robson M, Lincoln A, Jacobs L, Machackova E, Foretova L, Navratilova M, Vasickova P, Couch FJ, Hallberg E, Ruddy KJ, Sharma P, Kim SW, Teixeira MR, Pinto P, Montagna M, Matricardi L, Arason A, Johannsson OT, Barkardottir RB, Jakubowska A, Lubinski J, Izquierdo A, Pujana MA, Balmana J, Diez O, Ivady G, Papp J, Olah E, Kwong A, Nevanlinna H, Aittomaki K, Perez Segura P, Caldes T, Van Maerken T, Poppe B, Claes KB, Isaacs C, Elan C, Lasset C, Stoppa-Lyonnet D, Barjhoux L, Belotti M, Meindl A, Gehrig A, Sutter C, Engel C, Niederacher D, Steinemann D, Hahnen E, Kast K, Arnold N, Varon-Mateeva R, Wand D, Godwin AK, Evans DG, Frost D, Perkins J, Adlard J, Izatt L, Platte R, Eeles R, Ellis S, Hamann U, Garber J, Fostira F, Fountzilas G, Pasini B, Giannini G, Rizzolo P, Russo A, Cortesi L, Papi L, Varesco L, Palli D, Zanna I, Savarese A, Radice P, Manoukian S, Peissel B, Barile M, Bonanni B, Viel A, Pensotti V, Tommasi S, Peterlongo P, Weitzel JN, Osorio A, Benitez J, McGuffog L, Healey S, Gerdes AM, Ejlertsen B, Hansen TV, Steele L, Ding YC, Tung N, Janavicius R, Goldgar DE, Buys SS, Daly MB, Bane A, Terry MB, John EM, Southey M, Easton DF, Chenevix-Trench G, Antoniou AC, Ottini L (2016) Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the consortium of investigators of modifiers of BRCA1/2. Breast Cancer Res 18(1):15. doi:10.1186/s13058-016-0671-y
Moran A, O’Hara C, Khan S, Shack L, Woodward E, Maher ER, Lalloo F, Evans DG (2012) Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations. Fam Cancer 11(2):235–242. doi:10.1007/s10689-011-9506-2
Maatta K, Rantapero T, Lindstrom A, Nykter M, Kankuri-Tammilehto M, Laasanen SL, Schleutker J (2016) Whole-exome sequencing of finnish hereditary breast cancer families. Eur J Hum Genet 25(1):85–93. doi:10.1038/ejhg.2016.141
Deb S, Lakhani SR, Ottini L, Fox SB (2016) The cancer genetics and pathology of male breast cancer. Histopathology 68(1):110–118. doi:10.1111/his.12862
Hemminki K, Ji J, Brandt A, Mousavi SM, Sundquist J (2010) The Swedish Family-Cancer Database 2009: prospects for histology-specific and immigrant studies. Int J Cancer 126:2259–2267. doi:10.1002/ijc.24795
Hemminki K, Sundquist J, Brandt A (2012) Do discordant cancers share familial susceptibility? Eur J Cancer 48:1200–1207. doi:10.1016/j.ejca.2011.09.017
zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2:342–350
Hussain SK, Sundquist J, Hemminki K (2008) Familial clustering of cancer at human papillomavirus-associated sites according to the Swedish Family-Cancer Database. Int J Cancer 122(8):1873–1878. doi:10.1002/ijc.23265
Pavlidis N, Pentheroudakis G (2012) Cancer of unknown primary site. Lancet 379:1428–1435. doi:10.1016/S0140-6736(11)61178-1
Hemminki K, Ji J, Sundquist J, Shu X (2011) Familial risks in cancer of unknown primary: tracking the primary sites. J Clin Oncol 29:435–440
Naslund-Koch C, Nordestgaard BG, Bojesen SE (2016) Increased risk for other cancers in addition to breast cancer for CHEK2*1100delC Heterozygotes estimated from the copenhagen general population study. J Clin Oncol 34(11):1208–1216. doi:10.1200/jco.2015.63.3594
Yu H, Frank C, Sundquist J, Hemminki A, Hemminki K (2017) Common cancers share familial susceptibility: implications for cancer genetics and counselling. J Med Genet. doi:10.1136/jmedgenet-2016-103932
Frank C, Sundquist J, Hemminki A, Hemminki K (2017) Familial associations between prostate cancer and other cancers. Eur Urol 71:162–165. doi:10.1016/j.eururo.2016.07.031
Frank C, Sundquist J, Hemminki A, Hemminki K (2017) Risk of other cancers in families with melanoma: novel familial links. Scientific reports 7:42601. doi:10.1038/srep42601
Frank C, Sundquist J, Yu H, Hemminki A, Hemminki K (2017) Concordant and discordant familial cancer: familial risks, proportions and population impact. Int J Cancer 140:1510–1516
Acknowledgements
A.H. is Jane and Aatos Erkko Professor of Oncology at the University of Helsinki. This work was funded by the German Cancer Aid, the EU Transcan funding by the German Federal Ministry of Education and Research, Jane and Aatos Erkko Foundation, University of Helsinki and Helsinki University Central Hospital, and the Swedish Research Council for Health, Working Life and Welfare (in Swedish: FORTE; Reg. No. 2013-1836), and FORTE (Reg. No. 2014-0804) and the Swedish Research Council (2012-2378 and 2014-10134) as well as ALF funding from Region Skåne.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
AH. is shareholder in Targovax ASA. A.H. is employee and shareholder in TILT Biotherapeutics Ltd. Other authors declared no conflict of interest.
Rights and permissions
About this article
Cite this article
Zheng, G., Yu, H., Hemminki, A. et al. Familial associations of male breast cancer with other cancers. Breast Cancer Res Treat 166, 897–902 (2017). https://doi.org/10.1007/s10549-017-4468-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-017-4468-1