The Breast Tumour Group of the BCCA has had a number of discussions regarding the use of hormone replacement therapy after a diagnosis of breast cancer. The traditional dogma has been that any use of hormones in patients with a personal history is contraindicated. This is based on the epidemiology of primary breast cancer, which reports an increased incidence of breast cancer in postmenopausal women exposed to long term estrogen replacement therapy (1). As well, a recent study has confirmed that HRT using a combination of progesterone and estrogen is also associated with an increased risk of developing breast cancer (2).
There is no direct evidence that estrogen causes recurrence in women with a previous history of cancer, but there is evidence of a decreased recurrence rate when women with a history of breast cancer are treated with Tamoxifen or after oophorectomy. Concerns about doing harm and contributing to incurable breast cancer recurrences have limited the use of estrogen replacement in these women. However, we are seeing an increased number of young women with early breast cancer and a relatively good prognosis, who are experiencing early menopause after adjuvant chemotherapy. As well, through screening mammography, we are identifying large numbers of older women with highly curable breast cancer.
At this time there is no good information on the risks of giving hormone replacement therapy to women after a diagnosis of breast cancer. There are a number of series reported in the literature which are not helpful because the studies are too small and have very short followup (3,4,5,6). Although there are plans for large randomized studies of women with a history of breast cancer to assess the risks and benefits of hormone replacement therapy, this data will not be available for many years.
Without evidence of safety our general policy has been to do no harm and therefore to not risk prescribing HRT to women with a previous history of any breast malignancy if there are other therapeutic options that can result in similar outcomes. Although there is evidence that HRT can improve bone health and conflicting evidence for cardiac health, there are often other therapies and lifestyle changes that can also be of benefit and should be considered as the first options in women with a history of breast cancer. In situations where there is a greater health risk from the non-breast cancer disease and there are no other options, the woman should be informed of the situation clearly and an individual decision to use HRT may be appropriate. Similarly, if there are symptoms that interfere significantly with a woman’s quality of life (i.e. troublesome hot flashes, vaginal dryness, vaginal atrophy, dyspareunia, sleep disturbances, depression) and there are no other therapeutic options, HRT should be considered. For vaginal complaints topical estrogens may be considered. In all situations the woman must be fully informed about the risks, benefits, and areas where we are lacking in clear information, and the use of HRT monitored and for a limited duration.
There is some confusion about many of the new SERMS and their role in HRT and breast cancer. At this time, tamoxifen has been shown to be of benefit in decreasing relapse and new cancers in women with a history of in-situ and invasive breast cancer. Based on an individual risk assessment, tamoxifen may be prescribed for women for a duration of 5 years. Similarly there is evidence of tamoxifen being of benefit for the prevention of breast cancer in high risk women and it may be appropriate to prescribe tamoxifen for selected, informed high-risk women. Provincial guidelines for its use are available. Raloxifene is currently being studied in a large randomized study comparing it to tamoxifen for prevention of breast cancer in postmenopausal women. Information on this study is available at (604) 822-7997. It is not approved or proven for use in women with a history of breast cancer, nor is it approved for prevention. Both these drugs can cause hot flushes and dyspareunia and are not appropriate to treat these menopausal symptoms. Both drugs are effective in improving heart and bone outcomes, and Raloxifene is licensed for use in osteoporosis.
Laboratory and clinical work suggest that tamoxifen may begin exerting its pro-estrogen effects rather than its antagonistic, anti-estrogenic effects after a period of time. It is therefore recommended for 5 years, as that appears to be the optimal duration of use. As Raloxifene acts very similarly to tamoxifen, it is presumed that it too will exert an agonist effect after a period of time. Therefore its safety for prolonged periods and its safety after 5 years of tamoxifen in women with a previous diagnosis of breast cancer is not known and until there is data, should be avoided if there are treatment options. A recent study in animals suggested that tumours may become tamoxifen or raloxifene dependent after prolonged exposure suggesting as well that there may be clinical concerns about more than 5 years of use.
There is continued controversy in the use of progestins as single agents for postmenopausal symptoms and health. A number of research studies are ongoing to clarify safety and risks in breast cancer. In contrast to the well established role progestins have in decreasing uterine cancer when used in combination with estrogens, they are associated with an increased risk of breast cancer when used in combination HRT. At this time, however, in the woman with an intact uterus who is receiving HRT, combination therapy should remain standard.
As well, research is ongoing in the role of soy proteins for symptom control after a diagnosis of breast cancer. Many other treatments are also under investigation.
The role of HRT in women with a known genetic mutation in BRCA1 or BRCA2 causing an increased risk of breast or ovarian cancer is also unknown. There is evidence that oral contraceptives may be of value in decreasing the incidence of ovarian cancer (7). It is not clear if either oral contraceptives or HRT affects the incidence of breast cancer in carriers of BRCA1 or BRCA2 mutations. There is one study suggesting that early and multiple pregnancies are not protective in these women, so more research is needed.
In summary, the role of HRT in women with a history of breast cancer is unknown. If there are options for other therapies they should be used. In individual informed cases HRT may be appropriate for some women (see post-menopausal replacement therapy). Research may give us new insights in the next few years. If there are patients that need further assessment, please consult their oncologist. If HRT is used, it may be advisable to prescribe the lowest dose of estrogen to relieve symptoms and to monitor the patient carefully and to consider short term use until long term data is available.
References
- Collaborative Group on Hormonal Factors in Breast Cancer. Breast Cancer and hormone replacement therapy: collaborative re-analysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997; 350: 1047-1058.
- Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000; 283: 485-491.
- Powles TJ, Hickish T, Casey S; Hormone replacement after breast cancer. Lancet: 1993; 342: 60-61.
- Stoll BA. Hormone replacement therapy in women treated for breast cancer. Eur J Cancer 1995; 25: 1909-1913.
- Disaia PJ. Estrogen replacement therapy for the breast cancer survivor; A reappraisal. J Surg Oncol 1997: 64; 175-80.
- Eden JA. A case controlled study of combined continuous estrogen-progestin replacement therapy among women with a personal history of breast cancer. Menopause 1995; 2: 67-72.
- Narod SA, Risch H, Moslehi R et al Oral contraceptives and the risk of hereditary ovarian cancer. NEJM 1998; 339: 424-427.