Weighing HRT use after breast cancer

The post-breast cancer patient

Since most breast cancers are estrogen-receptor positive, laboratory data suggest that cancer cells may be influenced by estradiol; epidemiologic studies note a slightly increased risk of breast cancer in HRT users, what rationale is there for giving a woman HRT after the diagnosis of breast cancer? The Physicians’ Desk Reference (PDR) notes that breast cancer is a contraindication to HRT. While this is the recognized dictum, there are no data to substantiate it. In the PDR, the contraindications listed do not include a history of breast cancer. Nor does the bibliography contain any references addressing the post-breast cancer patient.

If there are no data to support the non-use of HRT in the breast cancer patient, are there data to support its use? Indeed, studies do exist. But before reviewing these important research findings, consider a parallel scenario. For many years, a woman who was diagnosed with breast cancer during pregnancy was thought to have an extremely poor prognosis due to the high level of hormones produced. More than 50 years ago, Haagerson, the recognized surgical breast authority in the United States, suggested that the combination of breast cancer and pregnancy had such a poor outcome that surgical therapy was not indicated.⁸ Ten years later, more than 50 “recognized breast authorities” restated the recommendation against surgical therapy, noting the high levels of hormones from pregnancy (gas-on-the-fire theory).⁹ We now know that, when corrected for age and stage, survival in the pregnant and nonpregnant breast cancer patient is similar.^10,11 Carrying the pregnancy to term is not detrimental, nor is terminating the pregnancy beneficial.

Similarly, subsequent pregnancies after breast cancer were thought to be contraindicated because of the fear that the hormones elevated during pregnancy would reactivate dormant cancer cells. Data would suggest just the opposite. Subsequent pregnancies do not increase recurrences. Nor does the time of pregnancy (less than or greater than 2 years) after breast cancer appear to be a factor.¹²

For many years, part of the primary treatment for the pre-menopausal patient with breast cancer was bilateral salpingo-oophorectomy. Prospective randomized studies have shown that this was not beneficial with respect to survival and is no longer done.¹³ Endogenous estrogen appears to be acceptable in the premenopausal breast cancer patient, but exogenous estrogen in the postmenopausal patient is not. It is interesting to note that tamoxifen given to the premenopausal patient with breast cancer increases estradiol levels way beyond peak levels during the menstrual cycle. Still, it is indicated because of decreased breast cancer recurrence when compared to patients not taking tamoxifen. Thus, there is little rationale for denying the benefits of exogenous estrogen to the postmenopausal woman with breast cancer.

There have been several retrospective as well as case-controlled and cohort studies demonstrating that HRT can be given to the post-breast cancer patient without a negative impact on survival. The retrospective studies note very low recurrence and death rates ( Table 1).^14-19

Results from the case-controlled and cohort studies demonstrate no difference in the prognosis of patients who did or did not receive HRT post-cancer. Recently, in a cohort study, DiSaia and associates examined 125 breast cancer patients who received HRT after diagnosis,²⁰ along with 362 controls from the same geographic region. The risk of death was considerably lower in the HRT users compared to non-HRT users, with an odds ratio (OR) of 0.28 (CI 0.11–0.71).

We now know that, when corrected for age and stage, survival in the pregnant and non-pregnant breast cancer patient is similar.

The largest study to date evaluated 2,755 women with breast cancer who were enrolled in a large health maintenance organization (HMO).²¹ Medical and pharmacy records were reviewed and patients with breast cancer taking HRT were identified. Of these, 174 eligible HRT users were available for analysis. Four matched controls were identified for each of the breast cancer patients. Estrogen, as well as estrogen plus progesterone, was administered. Breast cancer recurrence was diagnosed in 16 hormone users (9%) compared with 101 (15%) nonusers. The rate of recurrence was 17 per 1,000 person-years in HRT users and 30 per 1,000 person-years in non-users. Comparison of rates adjusted for multiple factors noted an RR of 0.50 (CI 0.30–0.85). Five users (3%) and 59 non-users (8%) died of breast cancer (5 per 1,000 person-years versus 15 per 1,000 person-years). The adjusted RR was 0.34 (CI =0.13–0.91). Total mortality noted an RR (adjusted) of 0.48 (CI 0.29–0.78).

TABLE 1

HRT in women with breast cancer