Clinical Study

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

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.

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Fig. 1
Fig. 2: Cumulative incidence of breast cancer death according to ER status, stratified on oophorectomy and endocrine therapy (deaths due to other causes treated as competing events).

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Acknowledgements

We thank the Nordic women who participated in the studies. All colleagues are thanked for their contribution of BRCA2 data.

Author information

Affiliations

Authors

Contributions

Conception, design and study supervision: L.T. Acquisition of data: L.T., A.B., A.-M.G., R.B.B., O.T.J., B.E., E.H., S.S., N.L. and M.P.N. Analysis of clinical data: A.B., I.M.H.S., A.-V.L., T.v.O.H., G.H.O., M.R. and J.G.J. Statistical analysis and critical review: E.J.O., M.-B.J. and A.L.V.J. Interpretation of the results and writing of the original draft: L.T. and S.A.N. All authors revised the paper and approved the final version.

Corresponding author

Correspondence to Laufey Tryggvadottir.

Ethics declarations

Ethics approval and consent to participate

The study was approved by The Danish Data Protection Agency (2009-41-3611) and the Danish Ethical Committee (registration number 33483), The National Bioethics Committee of Iceland (VSN-13-133-V5), The Norwegian Data Inspectorate (ref. 2001/2988-2) and Ethical Review Board (ref. S-02030) and (ref. 2015/2382) and The Regional Ethical Review Board in Lund. All Norwegian and Swedish patients consented to the study. The Danish Ethical Committee gave a waiver concerning consent to this study, and genetic testing is part of routine diagnostics in Denmark. In Iceland, genetic testing for the majority of patients (historical cohort) was done using paraffin- embedded tumour specimens from pathology archives, based on permission from the National Bioethics Committee of Iceland. The remaining Icelandic patients consented to the study.

Consent to publish

Our paper does not contain any individual person’s data in any form.

Data availability

The datasets generated and/or analysed during the current study are not publicly available, due to protection of the privacy of BRCA2 mutation carrier patients, but are available from the corresponding author on reasonable request.

Competing interests

Steven A. Narod is an Editorial board member to British Journal of Cancer.

Funding information

The study was funded by the Nordic Cancer Union and the Icelandic Cancer Society. S.A.N. is supported by the Peter Gilgan Centre for Cancer in Women.

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Olafsdottir, E.J., Borg, A., Jensen, MB. et al. Breast cancer survival in Nordic BRCA2 mutation carriers—unconventional association with oestrogen receptor status. Br J Cancer 123, 1608–1615 (2020). https://doi.org/10.1038/s41416-020-01056-4

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