Tamoxifen and uterine cancer

Tamoxifen is a venerable drug that revolutionized breast cancer care when it was first introduced. More recently, it has been largely supplanted by aromatase inhibitors(AI), such as Arimidex and Femara, but tamoxifen is still useful in pre-menopausal women, in whom AIs do not work. Recently, an authoitative body( USPTF) recommended ten years of adjuvant tamoxifen instead of five. This greatly increases concern for the development of endometrial cancer over this longer period.

A common complication of tamoxifen is uterine lining overgrowth, which can proceed to endometrial bleeding. Abnormal uterine bleeding occurs in more than 50% of premenopausal women taking tamoxifen and in this group of women, up to 23% will have an underlying endometrial abnormality such as polyps, hyperplasia, or EC. However, the incidence of endometrial disease is not markedly different compared with that in premenopausal women with breast cancer and uterine bleeding who are not taking tamoxifen. Still,  two meta-analyses found the risk of uterine/endometrial cancer, while still very low, nearly doubled with tamoxifen use. In the great majority of the cases, these are early stage cancers that are curable with hysterectomy. Unfortunately, there are no effective or generally accepted ways to monitor endometrial overgrowth or to predict uterine cancer.  Given the higher rate of endometrial disease in premenopausal women taking tamoxifen who have development of  uterine bleeding, further evaluation is warranted via endometrial sampling with an office biopsy or with operative curettage (with or without hysteroscopy). There are no guidelines that recommend preventative hysterectomy or cystoscopy.

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