What is the association between breast cancer risk and HRT for menopause?

Updated: Jun 06, 2018
  • Author: PonJola Coney, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Estrogen therapy is known to benefit postmenopausal women in a multitude of ways, mostly through the relief of vasomotor symptoms associated with postmenopause. Estrogen is also beneficial for the prevention and treatment of osteoporosis.

Much controversy exists about the use of estrogen and breast cancer. Some studies show an increased risk of breast cancer with postmenopausal estrogen use; others show a decrease. A possible link to cancer is also suggested by the finding that breast cancer risk is increased in women with an earlier age at menarche and a later age at menopause. However, a reduction in risk is observed with early age at pregnancy and the interruption of menstrual hormonal changes. The role of estrogen in the development of breast cancer continues to be studied.

In the Women’s Health Initiative (WHI), the incidence of breast cancer increased in the estrogen-plus-progestin versus placebo arm of the study (38 vs 30 per 10,000 person years); however, the incidence of breast cancer decreased in the estrogen-only versus placebo arm of the study (26 vs 33 per 10,000 person years). [39, 40]

Additional follow-up in patients from the WHI suggested similar results: Breast cancer incidence and mortality were increased in the estrogen-plus-progestin group as compared with the placebo group. [58] The role of combined estrogen-plus-progesterone therapy (associated with most of the breast cancer risk) continues to be puzzling in the development of breast cancer. 

Data suggest a slightly increased relative risk with estrogen use, approximately 1.1-1.3, [59, 60] but not all of the evidence supports this finding. [61] The risk appears to be related to duration of use, with longer-term users being more affected. [62]

Data suggest that the addition of sequential progestin to the regime increases the RR of subsequently developing breast cancer beyond the risk associated with estrogen alone, though some believe that continuous combined hormone therapy using much smaller doses of progestin may attenuate this risk. [63] Most earlier studies evaluating breast cancer risk and estrogen therapy were conducted at a time when the progestin in hormone therapy was administered on a cyclical basis.

Notably, women with a history of using hormone therapy have more localized tumors, as well as better survival rates. That is, women receiving hormone therapy who are diagnosed with breast cancer are found to have more favorable staging at the time of diagnosis, [60] including smaller tumor size, negative lymph node involvement, and better-differentiated tumor histology. [64, 65, 66, 67, 68, 69, 70, 71, 72]

Breast cancer survivors (BCSs) may suffer genitourinary syndrome of menopause (GSM) (vaginal and urinary symptoms related to menopause) after receiving aromatase inhibitor therapy for hormone-dependent tumors. [73] BCS are typically not candidates for conventional menopause therapies (eg, systemic hormonal therapy, vaginal estrogens at standard doses) and nonhormonal vaginal moisturizers/lubricants have limited use over the long term, newer management options have become available including the use of androgens, low-dose/ultra low-dose estrogens, or selective estrogen receptor modulators, vaginal laser therapy, and psychosocial interventions. [73]

A beneficial effect on breast cancer mortality has been documented in postmenopausal women who have received hormone therapy as compared with controls who have no prior history of hormone therapy use. [59] Study findings do not agree on whether the benefit is due to earlier detection or to effects of the therapy itself on breast tissue.

The general belief is that any increase in risk is small and that each patient should be evaluated as a candidate for estrogen therapy or hormone therapy on an individual basis, with the overall balance of risks and benefits taken into account. An essential precept in the management of menopause is that each individual is unique and that therapy should be tailored accordingly. At present, the main indication for hormone therapy and estrogen therapy remains the relief of vasomotor symptoms.

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