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Type and Duration of Exogenous Hormone Use A3ects Breast Cancer Histology

¹ Department of Surgery, Kaiser Permanente Oakland Medical Center, Oakland, California 94602, USA
² Department of Surgery, University of California San Francisco—East Bay, Oakland, California 94602, USA
³ Department of Surgery, University of California San Francisco, Comprehensive Cancer Center, San Francisco, California 94143, USA
⁴ Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
⁵ Department of Medicine, Division of Hematology and Oncology, University of California San Francisco, San Francisco, California, USA
⁶ Buck Institute for Age Research, Novato, California 94945, USA

Correspondence: Address correspondence and reprint requests to: E. Shelley Hwang, MD, MPH, E-mail: shelley.hwang{at}ucsfmedctr.org

Background: It is unclear whether hormone replacement therapy (HRT), in addition to increasing risk for breast cancer, affects the type of breast cancer diagnosed. We conducted this investigation to assess whether the type of hormone used (none, estrogen, progesterone, or combined) and duration of use influences subsequent breast cancer histology.

Methods: We performed a retrospective cohort analysis among women listed as incident cases of breast malignancy in the Kaiser Permanente Northern California Cancer Registry during 2003 (n = 2830). Type and duration of hormone used (none, estrogen, progesterone, or combined) before breast cancer diagnosis was obtained from electronic pharmacy records. The association between type and duration of hormone use with characteristics of subsequent breast cancers was examined.

Results: Among women aged >50 years (n = 1701), any use of estrogen, progesterone, or combination therapy was not associated with an increased risk of estrogen receptor (ER)-positive disease. However, >6 months’ use of combined HRT increased the odds of ER-positive tumors (odds ratio, 1.65; 95% confidence interval, 1.07–2.5; P = .02). Estrogen HRT patients were more likely than nonusers to present with low-grade (P = .05), and early-stage tumors (P = .03). This trend was not seen in combined HRT users.

Conclusions: Short-duration HRT did not increase the likelihood of ER-positive breast cancer. However, prolonged duration of combined HRT, but not estrogen or progesterone alone, resulted in a marked increase in ER-positive disease. Our findings suggest that the effect of combined HRT on breast cancer incidence or progression is not immediate and that long-term use is more likely to affect breast cancer histology.

Key Words: Breast cancer • Hormone replacement therapy • Estrogen receptor