Standard Ovulation Induction May Promote Ca in Predisposed Women


MONTREAL — Ovulation induction for in vitro fertilization may promote the growth of breast cancer in patients who are predisposed to the disease, suggest results of a case series of seven IVF patients later diagnosed with the disease.

“A breast cancer family history should be included in the pre-IVF work-up, and women with a positive history should be considered candidates for an alternate IVF stimulation protocol,” recommended Kutluk Oktay, M.D., who reported the findings in a poster at the joint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

In a case series of seven breast cancer patients who had undergone ovarian stimulation for in vitro fertilization (IVF), Dr. Oktay's team found more than half (57%) had a family history of breast cancer. It is normally expected that only about 10% of breast cancer patients will have a family history of the disease.

All women had estrogen- and progesterone-receptor-positive breast cancer, when normally it is expected that about 40% of breast cancer patients will have this type of disease, said Dr. Oktay, of Cornell University in New York.

Ovulation induction exposes women to supraphysiologic levels of estrogen, which may be problematic in women with a family history of breast cancer, Dr. Oktay suggested.

“Not that IVF necessarily causes their cancer, but it may promote it,” he said in an interview. “Counseling should include the fact that if you have a family history of breast cancer, this may increase your risk—but it may simply facilitate the appearance of the disease and so patients should be closely examined before IVF and followed after.”

The mean age of the patients was 39.8, and the mean duration from the time of their IVF treatment until their breast cancer diagnosis was 8.5 months.

One patient had a breast lesion biopsied before undergoing IVF, and it was initially negative for malignancy. However, after her IVF treatment, the mass grew, and a second biopsy revealed stage I invasive ductal carcinoma.

One other patient had stage I invasive ductal carcinoma, three had stage IIA disease, and two had carcinoma in situ. Tumor size was less than or equal to 1.5 cm in all except one patient.

Dr. Oktay, also of the Center for Reproductive Medicine and Infertility of New York-Presbyterian Hospital/Weill Cornell Medical Center, recommends that IVF patients who face an elevated risk of breast cancer based on their family history should undergo ovulation induction with a letrozole/FSH protocol instead of standard ovulation induction, which exposes patients to high levels of estrogen. Letrozole, an aromatase inhibitor that also is used to treat breast cancer, can stimulate oocyte production without raising estrogen levels, making it ideal for this patient population, he said.

“Obviously, if they conceive, they are going to be exposed to high levels of estrogen anyway—but there will be an increase in many other hormones as well—and the studies so far don't suggest that pregnancy necessarily increases the risk of cancer.”

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