This study aimed to clarify the breast cancer prognosis in Japanese patients with BRCA1/2 pathogenic variant. We analyzed 2235 women with breast cancer who underwent BRCA1/2 genetic testing between 1996 and 2018 using data from the Japanese hereditary breast and ovarian cancer syndrome registry. The cumulative risk for contralateral and ipsilateral breast cancers and time to death since the first breast cancer were stratified based on the BRCA1/2 variant status. The median follow-up was 3.0 years (0.1–34.1 years) after the first breast cancer. The annual average risks of contralateral breast cancer in BRCA1 and BRCA2 and non-BRCA1/2 pathogenic variant carriers were 4.0%, 2.9%, and 1.9%, respectively (P = 0.001). The annual average risks of ipsilateral breast cancer in the three groups were 2.7%, 1.4%, and 1.1%, respectively (P = 0.06). BRCA1 pathogenic variant carriers had significantly higher risks of contralateral (hazard ratio 1.91, P < 0.001) and ipsilateral (hazard ratio 2.00, P = 0.02) breast cancers than non-BRCA1/2 pathogenic variant carriers. The time to death by the BRCA1/2 variant status was not significantly difference (P = 0.28). The prognosis of breast cancer patients who received standard treatment was comparable regardless of the BRCA1/2 variant status.
Subscribe to Journal
Get full journal access for 1 year
only $41.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Melchor L, Benitez J. The complex genetic landscape of familial breast cancer. Hum Genet. 2013;132:845–63.
Graeser MK, Engel C, Rhiem K, Gadzicki D, Bick U, Kast K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009;27:5887–92.
van Sprundel TC, Schmidt MK, Rookus MA, Brohet R, van Asperen CJ, Rutgers EJ, et al. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer. 2005;93:287–92.
Malone KE, Begg CB, Haile RW, Borg A, Concannon P, Tellhed L, et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol. 2010;28:2404–10.
Robson M, Gilewski T, Haas B, Levin D, Borgen P, Rajan P, et al. BRCA-associated breast cancer in young women. J Clin Oncol. 1998;16:1642–9.
Verhoog LC, Brekelmans CTM, Seynaeve C, van den Bosch LMC, Dahmen G, van Geel AN, et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet. 1998;351:316–21.
Bordeleau L, Panchal S, Goodwin P. Prognosis of BRCA-associated breast cancer: a summary of evidence. Breast Cancer Res Treat. 2010;119:13–24.
Schaapveld M, Visser O, Louwman WJ, Willemse PH, de Vries EG, van der Graaf WT, et al. The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands. Breast Cancer Res Treat. 2008;110:189–97.
Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C, vd Ouweland A, Menke-Pluymers MB, Bartels CC, et al. Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer. 2007;43:867–76.
Valachis A, Nearchou AD, Lind P. Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2014;144:443–55.
Metcalfe K, Lynch HT, Ghadirian P, Tung N, Kim-Sing C, Olopade OI, et al. Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2011;127:287–96.
Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, Solin LJ, et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006;24:2437–43.
Goodwin PJ, Phillips KA, West DW, Ennis M, Hopper JL, John EM, et al. Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International Prospective Breast Cancer Family Registry population-based cohort study. J Clin Oncol. 2012;30:19–26.
Arai M, Yokoyama S, Watanabe C, Yoshida R, Kita M, Okawa M, et al. Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan. J Hum Genet. 2018;63:447–57.
Brekelmans CT, Seynaeve C, Menke-Pluymers M, Bruggenwirth HT, Tilanus-Linthorst MM, Bartels CC, et al. Survival and prognostic factors in BRCA1-associated breast cancer. Ann Oncol. 2006;17:391–400.
Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, et al. Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med. 2007;357:115–23.
Honrado E, Benitez J, Palacios J. The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications. Mod Pathol. 2005;18:1305–20.
Rubinstein WS. Hereditary breast cancer: pathobiology, clinical translation, and potential for targeted cancer therapeutics. Fam Cancer. 2008;7:83–9.
Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, et al. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. Jama. 2015;313:1347–61.
The authors thank the secretariat of the Japanese HBOC Consortium for assembly of data and the registration committee for supporting us.
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Yoshimura, A., Yokoyama, S., Iwata, H. et al. Incidence of contralateral and ipsilateral breast cancers and prognosis in BRCA1/2 pathogenic variant carriers based on the Japanese HBOC Consortium registration. J Hum Genet (2020). https://doi.org/10.1038/s10038-020-00850-5