Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer

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Reproductive and Hormonal Risk Factors for Postmenopausal Luminal, HER-2-Overexpressing, and Triple-Negative Breast Cancer

We read with great interest the article by Phipps et al,1 in which they examined the risk factors for different subtypes of postmenopausal breast cancer. They found that certain reproductive factors have a greater effect on the risk of certain molecular subtypes of disease compared with others. However, the authors did not analyze oral contraceptive use as a risk factor. Oral contraceptive use has been associated with an increased risk of breast cancer in young women. Narod et al demonstrated that among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30 years, or who used them for ≥5 years may have an increased risk of developing breast cancer.2 Sporadic triple-negative breast cancers and tumors that are noted in carriers of the BRCA1 mutation share similar features, including estrogen receptor negativity, high nuclear grade, high Ki-67 staining, cytokeratin 5/6 expression, and epidermal growth factor receptor expression.3 Furthermore, BRCA1 is rarely mutated in sporadic breast cancers. However, the pathologic similarities suggest that BRCA1 or associated pathways can become inactivated in triple-negative tumors via other mechanisms, such as gene promoter methylation.4 We previously reported a positive association between oral contraceptive use and triple-negative breast cancer. Although we did not take into consideration the menopausal status of the patients, the frequency of oral contraceptive use in our small cohort was found to be higher in patients with the triple-negative subtype compared with patients with other subtypes of breast cancer (35.3% vs 12.2%; P=.02).5 Taken together, we propose that oral contraceptive use may be associated with an increased risk of developing triple-negative breast cancer. However, to identify the exact role of oral contraceptive use in the development of breast cancer, more preclinical and clinical studies are warranted.

Omer Dizdar MD*, Sercan Aksoy MD*, Kadri Altundag MD*, * Department of Medical Oncology, Hacettepe University, Institute of Oncology, Ankara, Turkey.

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