What is the role of estrogen therapy in the etiology of breast cancer?

Updated: Oct 16, 2018
  • Author: Janice L Bacon, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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The association of hormone therapy with breast cancer may have different potential based on estrogen alone, estrogen and a progestin or conjugated estrogen plus bazedoxifene. Different medication formulations and dosages, timing of initiation and length of use may also affect occurrence of malignancy. Individual patient characteristics, combined with medical comorbidities and genetic risk factors and the interactions with hormone therapy are important but not yet clearly elucidated.

While the WHI confirmed an increased risk of breast cancer in users of CEE and MPA, the women in the estrogen (CEE) alone arm had a nonsignificant reduction in breast cancer at 7.2 and 13 years. Smaller trials have also shown a nonsignificant reduction in breast cancer in women taking estrogen alone but observational studies have demonstrated increased risk

There are no RCT for assessing breast cancer in long- term users of estrogen therapy, but one small, randomized, non-blinded trial found no increased breast cancer risk at 10 and 16 years of use (though the trial was addressing cardiovascular risks in recently postmenopausal women using HT. [122] Observational studies and meta-analyses considering risks of breast cancer in women using estrogen for long duration (> 5 years) have shown mixed results

The effects of progestogen therapy with estrogens suggest micronized progesterone (MP) may have less risk on the development of breast cancer than the more potent medroxyprogesterone acetate (MPA). Randomized trials are needed.

Oral CEE and bazedoxifene prescribed to menopausal women followed for up to 2 years did not show an increased risk of breast cancer

Mammographic breast-density may increase in women taking hormone therapy. Although the biologic importance of this finding has not been established, mammographic abnormalities require additional medical evaluation and may lead to more breast biopsies. [123]

The potential risk of breast cancer in women using HT should be addressed prior to beginning therapy.

Hormone therapy is not recommended for breast cancer survivors. Women who have a family history of breast cancer do not appear to be at increased risk themselves while using HT, nor has increased risk for women post-oophorectomy for BRCA1 or 2 gene mutations been noted. [113] The use of vaginal preparations for genitourinary symptoms is an exception and when used as prescribed does not result in an increase of systemic hormone levels.

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