Women with a history of breast cancer have been advised to avoid estrogen replacement therapy (ERT). A reassessment of this approach has been initiated by several authors and clinical reports to date have not supported this tenet. The only prospective randomized trial reported to date is that of Vassilopoulou-Sellin et al. The authors conducted a prospective clinical trial to assess the safety and efficacy of prolonged ERT in a group of menopausal women with localized (Stage I or II) breast carcinoma and a minimum disease-free interval of 2 years, if the estrogen receptor (ER) was negative, or 10 years if the ER status is unknown. For 5 years, the authors followed 77 trial participants and 222 other women with clinical and prognostic characteristics comparable to those of the trial participants. Overall, 56 women were on ERT, and 243 women were not on ERT. Patient and disease characteristics, such as tumor size, number of lymph nodes involved, ER status, menopausal status, and disease-free interval were comparable for women who were on ERT and women who were not on ERT. Two of the 56 women on ERT (3.6%) developed a contralateral, new breast carcinoma. In the group that was not on ERT, 33 of the 243 women (13.5%) developed new or recurrent breast carcinoma. There were no differences in the development of other carcinomas with respect to ERT. Thus, ERT did not compromise disease-free survival in select patients who were treated previously for localized breast carcinoma.
Additionally, observational studies reported by DiSaia, O’Meara, and Peters have supported this same conclusion. O’Meara assembled data from 2,755 women ages 35 to 74 years who were diagnosed with incident invasive breast cancer while they were enrolled in a large health maintenance organization from 1977 to 1994. Pharmacy data identified 174 users of hormone replacement therapy (HRT) after diagnosis. Each HRT user was matched to four randomly selected non-users of HRT with similar age, disease stage, and year of diagnosis. The rate of breast cancer recurrence was 17 per 1,000 person-years in women who used HRT after diagnosis and 30 per 1,000 person-years in non-users (adjusted relative risk for users, compared with non-users was equivalent to 0.50; 95% confidence interval was 0.30-0.85). Total mortality rates were 16 per 1,000 person-years in the HRT users and 30 per 1,000 person-years in the non-users.
DiSaia et al reported on 125 women who were breast cancer survivors with and without positive nodes, both ER positive and ER negative, who elected to take ERT or HRT. These patients were matched to 362 control patients from the same population base with the approximate ratio of four controls to one patient taking ERT or HRT. The risk of death was lower among the HRT survivors; odds ratio 0.28 (95% Cl 0.11-0.71). This analysis also did not suggest an adverse outcome with HRT use.
Peters interviewed 607 breast cancer survivors concerning ERT usage. Sixty-four patients indicated they had received some form of ERT after their breast cancer diagnosis. Eight patients were excluded because they had used only vaginal cream ERT. The remaining 56 received ERT as conjugated estrogens, an estradiol patch, or birth control pills. The median follow-up from diagnosis was 12.8 years and the median time on ERT since diagnosis was 6.4 years. One local recurrence and one contralateral breast cancer occurred during the follow-up period at 13.5 and 9.6 years respectively. There were no breast cancer deaths. The author also concluded that the use of ERT in a cohort of breast cancer survivors with tumors of generally good prognosis was not associated with increased breast cancer events compared with non-ERT users, even after a long follow-up period.
The question then remains as to whether all patients who have had breast cancer should be denied the benefits of estrogen replacement therapy. This is particularly relevant in the patient who has serious quality of life issues before her. At present, therapy with ERT/HRT is indicated in the management of quality of life issues, using lowest possible dose of hormone for shortest duration of time possible. Is it appropriate to deny a woman the option of taking replacement therapy for relief of her symptoms when there is no clinical evidence that it adversely affects outcome?