Cancer Treatment Today

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), but tamoxifen is still useful in pre-menopausal women, in whom AIs do not work.

Tamoxifen has a variety of bothersome side effects, related mostly to forced early menopause.
In addition, a rare 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 tamoxife 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 AUB who are not taking tamoxifen. However, two meta-analyses found the risk of uterine/endometrial cancer 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. 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.

Recently, USPTF recommended ten years of adjuvant tamoxifen instead of five. This greatly increases concern for the development of endometrial caner over this longer period. The ASCO guideline* (Visvanathan et al) has this to say: “Follow-up should include a baseline gynecologic examination before initiation of treatment and annually thereafter, with a timely work-up for abnormal vaginal bleeding.”
H.F. Kennecke,New guidelines for treatment of early hormone-positive breast cancer with tamoxifen and aromatase inhibitors, BCMJ, Vol. 48, No. 3, April 2006,  121-126

Kala Visvanathanet al, American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Pharmacologic Interventions Including Tamoxifen, Raloxifene, and Aromatase Inhibition for Breast Cancer Risk Reduction, JCO July 1, 2009 vol. 27 no. 19 3235-3258

Bushnell CD wt al, (2004) Risk of ischemic stroke with tamoxifen treatment for breast cancer: A meta-analysis. Neurology 63:12301233.

Jamie N. Bakkum-Gamez et al, Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer, Mayo Clin Proc. 2011 March; 86(3): 229–240.

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