A new study has reported that women with breast tenderness who start combined hormone replacement therapy (estrogen plus progestin) have twice the risk of developing breast cancer as those without breast tenderness when starting combined HRT. Women who develop breast tenderness after beginning combined HRT are also at higher risk of breast cancer.
HRT is also known as menopausal hormone therapy. To conduct the study, the authors analyzed data from the Women’s Health Initiative Estrogen plus Progestin clinical trials until trial close-out in Spring 2005.
The trials included 16,608 postmenopausal women who had not had hysterectomies and were randomly assigned to receive either daily combined HRT (conjugated equine estrogen (estrogen) and medroxyprogesterone (progestin)) or a placebo, as well as 10,739 women who received estrogen alone or a placebo.
The women underwent mammography and clinical breast examination at the outset of the study (baseline) and annually thereafter. Self-reported breast tenderness was recorded at baseline and at the end of one year. New cases of invasive breast cancer were confirmed by medical record review.
The risk of newly reported breast tenderness after 12 months was two to three times higher among women assigned to either type of HRT than placebo. Use of combined estrogen plus progestin was found to double the risk of invasive breast cancer among women who had reported breast tenderness at baseline (before starting HRT). Combined HRT had a much smaller effect on breast cancer risk in women without baseline breast tenderness. However, women who developed breast tenderness after starting combined HRT also had a higher risk of breast cancer.
On the other hand, the authors found no significant associations between breast tenderness and risk of breast cancer among women taking estrogen-only HRT. The authors conclude use of combined HRT is associated with increased risk of breast cancer, especially among those with baseline breast tenderness.
Comments regarding hormone replacement therapy
Some of the benefits once thought to be associated with combined HRT, such as reductions in heart disease and dementia, have been found to be non-existent. In addition, combined HRT has been found to be associated with increased risk of breast cancer, especially estrogen receptor positive (ER+/PR+ and ER+/PR-) and lobular breast cancer. Strong evidence that combined HRT use could increase the risk of breast cancer was first published in 2002, when it was reported that participants in the Women’s Health Initiative trial who were taking combined HRT had higher rates of breast cancer than those who did not. Subsequent studies have confirmed the finding that combined HRT promotes breast cancer.
The picture is less clear for estrogen-only HRT; some but not all studies have concluded that estrogen-only HRT is also associated with increased breast cancer risk, although lower than that of combined HRT. While combined HRT is effective in reducing menopausal symptoms such as hot flashes, women are advised to use this treatment for the shortest possible period for the relief of severe menopause-related symptoms.
Women with severe menopausal symptoms who use combined HRT should be aware of the following study findings:
- Use of combined HRT appears to increase risk of breast cancer by at least 25%. This might not be an acceptable increase for women who are already at high risk
- The immediate reduction in breast cancer incidence after a decline in combined HRT usage indicates that combined HRT is a strong promoter of tiny, mammographically and clinically undetectable cancers, which in turn suggests that combined HRT use is especially dangerous for breast cancer survivors who may have micrometastases that otherwise might not develop into deadly recurrences
- Generally speaking, the increase in breast cancer risk from HRT increases with years of use and disappears within five years of cessation of treatment.
Bioidentical hormone formulations, which have been described by some health practitioners as more natural and safer than conventional HRT, have been welcomed by many women who seek relief from menopause-related symptoms. Bioidentical hormones are plant-derived hormones that are biochemically identical or similar to those produced in the body, especially those produced by the ovaries. Some prescription products that contain bioidentical hormones are FDA approved. However, bioidentical hormones that are custom-compounded have not been tested for purity, potency, efficacy, and safety. Although many people think of bioidentical as more natural hormones, they are often derived from some of the same precursors as HRT, namely soy or wild yam, and a great deal of processing is required to extract them.
Unfortunately, large-scale and carefully designed population studies comparing HRT with bioidentical hormone treatments are simply not available. There is some evidence that HRT formulations different from the estrogen plus progestin combinations normally used in the U.S. might result in smaller increases in breast cancer risk. There are also some responsible physicians who are using a “bioidentical hormone” approach using FDA-approved bioidentical hormones to treat women with menopausal symptoms.
However, the term “bioidentical hormone treatment” is also used by some nontraditional health care providers in ways that might be unsafe for any women, but especially those who are breast cancer survivors or are at high risk for breast cancer. The hallmarks of such practices are the use of saliva tests to determine dosage, the use of compounded products, and the sale of bioidentical hormone formulations directly to patients.
Estriol is commonly used in compounded products. It is promoted as a superior form of estrogen that may produce fewer risks commonly associated with estrogens. However, it still carries risks associated with estrogen, and has been found to stimulate the growth of hormone receptor positive breast cancer cells. In addition, it is not known how estriol and other hormones are absorbed from compounded gels and creams. While estriol may be described as a weak estrogen, there is no evidence that, if given at a dosage high enough to relieve symptoms, it is any safer than other estrogens.
In fact, the main danger of unregulated bioidentical hormone treatments is that women may be exposed to high levels of estrogen (potentially far higher than HRT) that could promote breast cancer. The sense of well being that some women report while using bioidentical hormones may in fact be the result of dangerous levels of estrogen and other hormones. The promises that were once made for combined HRT, including various aspects of youthfulness in addition to the relief of symptoms such as hot flashes and vaginal dryness, are now being made for compounded bioidentical hormone treatments. Neither combined HRT nor bioidentical hormones are safe for women at high risk for breast cancer or its recurrence.
Selected breast cancer studies
Breast Cancer Risk by Breast Density, Menopause, and Postmenopausal Hormone Therapy Use
Kerlikowske K, Cook AJ, Buist DS, Cummings SR, Vachon C, Vacek P, et al. Breast Cancer Risk by Breast Density, Menopause, and Postmenopausal Hormone Therapy Use. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2010; 28:3830-3837 10.1200/jco.2009.26.4770
Abstract 5741: Change in mammographic density with estrogen and progestin therapy: A measure of breast cancer risk in the Women's Health Initiative
Byrne C, Ursin G, Martin CF, Peck JD, Cole EB, Heiss G, et al. Abstract 5741: Change in mammographic density with estrogen and progestin therapy: A measure of breast cancer risk in the Women's Health Initiative. Epidemiology. American Association for Cancer Research; 2010; 10.1158/1538-7445.am10-5741
Menopausal hormone therapy and breast cancer risk: Impact of different treatments. The European Prospective Investigation into Cancer and Nutrition
Bakken K, Fournier A, Lund E, Waaseth M, Dumeaux V, Clavel-Chapelon F, et al. Menopausal hormone therapy and breast cancer risk: Impact of different treatments. The European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer. Wiley; 2010; 128:144-156 10.1002/ijc.25314
Dietary β-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Nagel G, Linseisen J, van Gils CH, Peeters PH, Boutron-Ruault MC, Clavel-Chapelon F, et al. Dietary β-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Breast Cancer Research and Treatment. Springer Science and Business Media LLC; 2009; 119:753-765 10.1007/s10549-009-0444-8