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Estrogen replacement therapy in breast cancer survivors: a matched-controlled series

Decker, David A. MD1; Pettinga, Jane E. MD2; VanderVelde, Nancy MD1; Huang, Raywin R. PhD4; Kestin, Larry MD3; Burdakin, John H. MD1


Objective: We prospectively administered estrogen replacement therapy (ERT) to control estrogen deficiency symptoms in breast cancer survivors as part of our clinical practice. We report the consequences of ERT compared with a historical matched-control group.

Design: Two hundred seventy-seven disease-free survivors received ERT. Controls were matched for exact stage, a recurrence-free period similar to the period to ERT initiation in the ERT group, approximate age, and duration of follow-up. The mean time from breast cancer diagnosis to initiation of ERT was 3.61 (± 0.25) years, with a median of 1.88 years. The mean duration of ERT was 3.7 (± 3.01) years, with a median of 3.05 years.

Results: Hot flashes were relieved in 206 of 223 women (92%), dyspareunia/vaginal dryness in 149 of 167 women (89%), and reactive depression/anxiety/mood change in 111 of 126 women (88%). Univariate analysis demonstrated no statistical differences between the groups for age, stage, pathology at diagnosis, progesterone receptor status, local therapy, breast at risk, prior chemotherapy, and duration of follow-up. The ERT group was more likely to be estrogen receptor negative (P = 0.01), to have received prior ERT (P < 0.001), and to have received no adjuvant tamoxifen (P < 0.001). There was no significant difference between the ERT and control groups in ipsilateral primary/recurrence (5/155 v 5/143; P = 0.85), contralateral breast cancers (10/258 v 9/260; P = 0.99), or systemic metastasis (8/277 v 15/277; P = 0.13). Noncause-specific deaths in the control group numbered 15 (of 277), and in the ERT group, 7 (of 277) (P = 0.03). Overall survival favored the ERT group (P = 0.02).

Conclusions: In these selected patients, ERT relieved estrogen deficiency symptoms and did not increase the rate or time to an ipsilateral recurrence/new primary, contralateral new primary, local-regional recurrence, or systemic metastases.

Estrogen deficiency symptoms (EDS) are a major problem for breast cancer survivors and can have a significant impact on quality of life. Hot flashes have been reported in 65% of patients, vaginal dryness in 48%, night sweats in 44%, difficulty sleeping in 44%, feeling depressed in 44%, and dyspareunia in 26%. 1 Concerns about osteoporosis and heart disease are also common. 2 Nonhormonal interventions to control hot flashes and vaginal dryness offer modest clinical benefit. 3–7 For some women, the only means of controlling EDS is estrogen replacement therapy (ERT).

Estrogens have traditionally not been administered to breast cancer survivors. It has been assumed that ERT would increase a breast cancer survivor's rate of relapse and decrease the time to relapse. This assumption is based on estrogen deprivation therapy in premenopausal breast cancer patients, laboratory evidence, epidemiological studies, and recently, a randomized trial of ERT in healthy women. 8–11 On the other hand, conjugated equine estrogen (CEE) was the treatment of choice for postmenopausal women with estrogen receptor-positive metastatic breast cancer before the antiestrogen era. 12 The use of estrogens to control EDS is also supported by several small, published series of survivors receiving ERT without a subsequent increase in recurrences. 13–25

For breast cancer survivors in our clinical practice who have uncontrolled EDS, we have administered ERT and followed them prospectively. We have published an uncontrolled series of these patients and subsequently presented a smaller series with a matched control group. 26,27 This paper reports the consequences of ERT in 277 patients with comparison to a historically matched-control group.

From the Departments of 1Medicine, 2Surgery, 3Radiation Therapy, and 4Biostatistics, William Beaumont Hospital, Royal Oak-Troy, MI.

Received November 25, 2002; revised and accepted January 30, 2003.

Address reprint requests to David A. Decker, MD, 3577 West 13 Mile Road, Suite 404, Royal Oak, MI 48073. E-mail:

©2003The North American Menopause Society