Breast cancer survival in Nordic BRCA2 mutation carriers—unconventional association with oestrogen receptor status

• Published in: British Journal of Cancer
• Main Authors: Olafsdottir, Elinborg J., Borg, Ake, Jensen, Maj-Britt, Gerdes, Anne-Marie, Johansson, Anna L. V., Barkardottir, Rosa B., Johannsson, Oskar T., Ejlertsen, Bent, Sønderstrup, Ida Marie Heeholm, Hovig, Eivind, Lænkholm, Anne-Vibeke, Hansen, Thomas van Overeem, Olafsdottir, Gudridur H., Rossing, Maria, Jonasson, Jon G., Sigurdsson, Stefan, Loman, Niklas, Nilsson, Martin P., Narod, Steven A., Tryggvadottir, Laufey
• Other Authors: Nordic Cancer Union, Icelandic Cancer Society. SAN is supported by the Peter Gilgan Centre for Cancer in Women.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Springer Science and Business Media LLC 2020
• Subjects: Cancer Research; Oncology; Iceland
• Online Access: http://dx.doi.org/10.1038/s41416-020-01056-4; https://www.nature.com/articles/s41416-020-01056-4.pdf; https://www.nature.com/articles/s41416-020-01056-4

Abstract Background The natural history of breast cancer among BRCA2 carriers has not been clearly established. In a previous study from Iceland, positive ER status was a negative prognostic factor. We sought to identify factors that predicted survival after invasive breast cancer in an expanded cohort of BRCA2 carriers. Methods We studied 608 women with invasive breast cancer and a pathogenic BRCA2 mutation (variant) from four Nordic countries. Information on prognostic factors and treatment was retrieved from health records and by analysis of archived tissue specimens. Hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. Results About 77% of cancers were ER-positive, with the highest proportion (83%) in patients under 40 years. ER-positive breast cancers were more likely to be node-positive (59%) than ER-negative cancers (34%) ( P < 0.001). The survival analysis included 584 patients. Positive ER status was protective in the first 5 years from diagnosis (multivariate HR = 0.49; 95% CI 0.26–0.93, P = 0.03); thereafter, the effect was adverse (HR = 1.91; 95% CI 1.07–3.39, P = 0.03). The adverse effect of positive ER status was limited to women who did not undergo endocrine treatment (HR = 2.36; 95% CI 1.26–4.44, P = 0.01) and patients with intact ovaries (HR = 1.99; 95% CI 1.11–3.59, P = 0.02). Conclusions The adverse effect of a positive ER status in BRCA2 carriers with breast cancer may be contingent on exposure to ovarian hormones.