Breast and Gynecological Cancers by Mahesh K. Shetty

Author:Mahesh K. Shetty
Language: eng
Format: epub
Publisher: Springer New York, New York, NY

Pharmaceutical Agents and Vaccines

Results from clinical trials have shown that two selective estrogen receptor modulators (SERMs)—tamoxifen and raloxifene—are effective in preventing breast cancer among high-risk persons. The FDA approved the two drugs in October 1998 and September 2007, respectively. SERMs act by blocking the action of estrogen in breast tissue and are effective in preventing estrogen receptor (ER) positive cancers but not ER negative cancers. In an overview of seven randomized controlled trials (RCTs), tamoxifen achieved an overall reduction of invasive cancers by 38% after 10 years of follow up and a 50% reduction in the incidence of ER-positive cancers [82, 83]. Raloxifene has similar effects to tamoxifen but has the advantage of a better safety profile. In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, a 3-year treatment with raloxifene reduced the risk of invasive breast cancer among postmenopausal women with osteoporosis by 76% and of ER-positive breast cancer by 90%, but it did not reduce ER-negative breast cancer [84]. Breast experts recommend tamoxifen as the drug of choice because of the long history of use, and it can be used in premenopausal and postmenopausal women. Raloxifene is only approved as a breast cancer prevention treatment for postmenopausal women. A recent analysis of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) data at a median follow-up of 81 months revealed a significant difference in invasive breast cancer between the two treatment groups, with a 24% higher rate with raloxifene compared to tamoxifen (RR, 1.24; 95% CI, 1.05–1.47) [85]. However, raloxifene continued to be associated with fewer cancers than expected in the absence of a preventive intervention, such that raloxifene would reduce the risk of invasive breast cancer by approximately 38% when compared to placebo.

The main adverse effects of tamoxifen are invasive endometrial cancer and venous thromboembolic events (VTE) such as stroke, pulmonary embolism, or deep venous thrombosis. Women <50 years are at low risk of these effects [86]. In the MORE trial, raloxifene increased the risk of VTE but not of endometrial cancer [84].

The choice for each patient who might benefit from tamoxifen chemoprevention must be based on a careful assessment of risk, benefit, patient preference, and complication management capability. The risk of breast cancer can be assessed using online assessment tools (based on older age, number of first-degree relatives with breast cancer, age at first menstrual period, age at first live birth, medical history of any breast cancer, a history of atypical hyperplasia on a breast biopsy, and the woman’s race) or the Gail index [87]. The US Preventive Services Task Force (USPSTF) recommends tamoxifen for women at high risk of breast cancer in their 40s or in their 50s without a uterus who also have a low risk for thromboembolic events. The American Society of Clinical Oncology recommends tamoxifen for women with a 5-year projected risk for breast cancer greater than or equal to 1.66%.

Despite the FDA approval and public interest, there has been low uptake of tamoxifen by patients [48, 88].

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