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Estrogen Receptor Status in BRCA1- and BRCA2-Related Breast Cancer

The Influence of Age, Grade, and Histological Type

¹ Program in Cancer Genetics, Departments of Oncology and Human Genetics, and Cancer Prevention Centre, Sir M. B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec, Canada; ² Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada; ³ Centre for Research on Women’s Health and Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; ⁴ Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska; ⁵ Epidemiology Research Unit, Centre de Recherché du CHUM, Pavillon Masson de l’Hôtel-Dieu, Montreal, Quebec, Canada; ⁶ Beth Israel Deaconess Hospital, Boston, Massachusetts; ⁷ Department of Medicine, University of Chicago, Illinois; ⁸ Departments of Medicine and Genetics and Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania; ⁹ Cancer Risk Program, University of California-San Francisco Comprehensive Cancer Center, San Francisco, California; ¹⁰ British Columbia Cancer Agency, Victoria, British Columbia, Canada; and ¹¹ Department of Pathology, Sacré Coeur Hospital, Montreal, Quebec, Canada

Purpose: BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied.

Experimental Design: ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America. There were 208 BRCA1 mutation carriers, 88 BRCA2 carriers, and 804 women without a known mutation. We stratified the patients by mutation status, grade, age, and histological type and calculated the percentage of ER-positive tumors within each stratum.

Results: BRCA1 mutation carriers were more likely to have ER-negative breast cancers than were women in other groups, after adjustment for age, grade, and histological subtype (P < 0.001). Only 3.9% of BRCA1-related breast cancers were ER-positive cancers occurring in women in their postmenopausal years. The direction and magnitude of the change in ER status with increasing age at diagnosis in BRCA1 carriers was significantly different from in BRCA2 carriers (P_intercept = 0.0002, P_slope = 0.04). Notably, changes in ER status with age at diagnosis for BRCA1 carriers and noncarriers were almost identical (P_slope = 0.98).

Conclusions: The strong relationship between the presence of a BRCA1 mutation and the ER-negative status of the breast cancers is neither a consequence of the young age at onset nor the high grade but is an intrinsic property of BRCA1-related cancers. The ER-negative status of these cancers may reflect the cell of origin of BRCA1-related cancers.

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