Fertility Drugs and the Risk of Breast and Gynecologic Cancers

Abstract

The evaluation of cancer risk among patients treated for infertility is complex, given the need to consider indications for use, treatment details, and the effects of other factors (including parity status) that independently affect cancer risk. Many studies have had methodologic limitations. Recent studies that have overcome some of these limitations have not confirmed a link between drug use and invasive ovarian cancers, although there is still a lingering question as to whether borderline tumors might be increased. It is unclear whether this merely reflects increased surveillance. Investigations regarding breast cancer risk have produced inconsistent results. In contrast, an increasing number of studies suggest that fertility drugs may have a special predisposition for the development of uterine cancers, of interest given that these tumors are recognized as particularly hormonally responsive. Additional studies are needed to clarify the effects on cancer risk of fertility drugs, especially those used in conjunction with in vitro fertilization. Because many women who have received such treatments are still relatively young, further monitoring should be pursued in large well-designed studies that enable assessment of effects within a variety of subgroups defined by both patient and disease characteristics.

In vitro fertilization and risk of breast and gynecologic cancers: a retrospective cohort study within the Israeli Maccabi Healthcare Services

“…This resulted in the elimination of the following numbers of cases: breast (3 cases within 1 year, 31 within 2 years), endometrial (0,0), ovarian (0,3), in situ cervix (3, 17), invasive cervix (2, 5). These eliminations did not substantially change the interpretation of risks associated with different fertility treatments.…”

“…We also had incomplete information on some risk factors (e.g., BMI) and did not have any information on other recognized risk factors (e.g., family history of cancer, oral contraceptive use), which could have affected our risks. However, the most important factor to control for is likely parity (3), for which we had documented (rather than self-reported) information from registry linkages.…”

“…Although early studies suggested large increases in ovarian cancer risk related to fertility medications (1;2), this relationship has not been confirmed by subsequent studies (3). Whether there could be residual smaller risks, particularly among subgroups of users, such as nulligravidous or nulliparous women (2;4–7), is still an open question.…”

Breast cancer risk after exposure to fertility drugs

“…In recent years, several literature reviews [73][74][75] and one meta-analysis [44] have addressed this topic, but they did not observe a clear relationship, particularly for breast cancer. As discussed earlier, this event may be due to a number of limitations inherent in the studies.…”

The Histopathological Changes in Rat Ovary and Endometrium Following Long Term Clomiphene Treatment

“…20 Breast cancer risk associated with CC has been studied in details. 21,22 However, investigations regarding breast cancer risk produced inconsistent results. Additional studies are needed to clarify the effects of fertility drugs on cancer risk, especially those used in conjunction with in vitro fertilization.…”