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Hormone Replacement Therapy After Breast Cancer: A Systematic Review and Quantitative Assessment of Risk

From the Division of General Medicine and Decision Systems Group, Brigham and Women’s Hospital and Harvard Medical School, and Divisions of Clinical Decision Making, Informatics, and Telemedicine, Hematology/Oncology, and Clinical Care Research, and Department of Medicine, New England Medical Center and Tufts University School of Medicine, Boston, MA; and Department of Surgery, Spartanburg Medical Center, Spartanburg, SC.

Address reprint requests to Nananda Col, MD, Brigham and Women’s Hospital, Harvard Medical School, Decision Systems Group, Ste 200, 850 Boylston St, Chestnut Hill, MA 02467; email: ncol{at}Dsg.harvard.edu

PURPOSE: Hormone replacement therapy (HRT) is typically withheld from women with breast cancer because of concern that it might increase the risk of recurrence. The purpose of this study was to quantify the risk of recurrent breast cancer associated with HRT among breast cancer survivors.

METHODS: We performed a systematic literature review through May 1999, calculating the relative risk (RR) of breast cancer recurrence in each study by comparing the number of recurrences in the HRT group to those in the control group. In studies that did not contain a control group, we constructed one by estimating the expected number of recurrences based on data from the Early Breast Cancer Trialists’ Collaborative Group, adjusting for nodal status and disease-free interval. RRs across all studies were combined using random-effects models.

RESULTS: Of the 11 eligible studies, four had control groups and included 214 breast cancer survivors who began HRT after a mean disease-free interval of 52 months. Over a mean follow-up of 30 months, 17 of 214 HRT users experienced recurrence (4.2% per year), compared with 66 of 623 controls (5.4% per year). HRT did not seem to affect breast cancer recurrence risk (RR = 0.64, 95% confidence interval [CI], 0.36 to 1.15). Including all 11 studies in the analyses (669 HRT users), using estimated control groups for the seven uncontrolled trials, the combined RR was 0.82 (95% CI, 0.58 to 1.15).

CONCLUSION: Although our analyses suggest that HRT has no significant effect on breast cancer recurrence, these findings were based on observational data subject to a variety of biases.

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