Progestin + Estrogen Multiplies Breast Ca Risk.

SAN ANTONIO -- Adding a progestin to estrogen replacement therapy markedly increases breast cancer risk over that with estrogen alone, Dr. Ronald K. Ross reported at a breast cancer symposium sponsored by the San Antonio Cancer Institute.

In a recent, large population-based case-control study, investigators analyzed data on 1,860 women who developed breast cancer during a 4 1/2-year period in Los Angeles County as well as 1,605 neighborhood controls. Use of estrogen replacement therapy for 5 years was associated with a modest 7% increase in breast cancer risk. In contrast, 5 years of combination hormone replacement therapy (HRT) increased breast cancer risk by 29%--more than fourfold greater than with estrogen replacement therapy alone (J. Natl. Cancer Inst. 92[4]:328-32, 2000).

These cancers were disproportionately of the progesterone receptor-positive type, suggesting that women on combination HRT who develop breast cancer should have a relatively favorable prognosis, said study investigator Dr. Ross, professor and chairman of the department of preventive medicine and deputy director of the Norris Cancer Center at the University of Southern California, Los Angeles.

"We have to figure out a way to get progestins to the only organ that likes it postmenopausally, and that's the endometrium. The brain doesn't like it, the liver doesn't like it, the heart doesn't like it, and the breast sure as heck doesn't like it. The only organ that wants anything whatsoever to do with progestins is the endometrium," he said.

Ultimately, the answer will be to develop novel selective estrogen receptor modulators (SERMs) to serve as a sort of designer HRT. In the meantime, less-frequent administration of progestins is worth exploring.

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