Jack Cuzick, PhD, discussed recent progress in breast cancer (BC) prevention in his McGuire Award Lecture at SABCS. “If there was ever a cancer that needed work on prevention, it’s breast cancer,” he said, noting that this most common cancer in women is increasing in incidence worldwide. A risk-adaptive approach to prevention should include identifying those at high risk as well as developing effective, minimally toxic prophylaxis.
Dr. Cuzick summarized research since adjuvant tamoxifen was shown to reduce the incidence of contralateral BC, which led to subsequent prevention trials with tamoxifen and other selective estrogen receptor modifiers (SERMs). Although the International Breast Cancer Intervention Study (IBIS)-I of tamoxifen versus placebo was stopped after four years, outcomes such as cumulative incidence for BC and number needed to treat continued to improve after 10 or more years of follow-up. Aromatase inhibitors, e.g., anastrozole, have been shown to be more effective than SERMs.
More recent research focuses on measuring serum estradiol and testosterone, both of which, particularly estradiol, are well-established risk factors although rarely measured, despite the low cost of assays. The IBIS-II prevention trial showed patients with higher estradiol levels who received placebo had increased risk for BC, whereas individuals with higher estradiol levels who received anastrozole had a lower risk for BC. Those in the lowest quartile of estradiol levels benefited little from anastrozole but risked side effects.
Therefore, measuring estradiol could identify those with higher levels who would benefit the most from aromatase inhibitor preventative therapy. Dr. Cuzick suggested that using the minimal dose needed to lower estradiol to a fixed level may improve the risk-benefit ratio. “We need to change treatment to use aromatase inhibitors in women who will benefit from them,” he said. Results of this analysis were published simultaneously with the presentation in Lancet Oncology.
Although women at increased risk for BC can benefit from taking tamoxifen, uptake of this preventative therapy has been low. A poster in the spotlight section on prevention reported the results of a Mayo Clinic study looking at patient understanding of BC risk and the role and uptake of preventative therapy with a “baby” tamoxifen dose of 5 mg/day rather than the standard 20 mg/day. Women with DCIS, high risk intraepithelial lesions (IEL), BC Risk Assessment Tool (BCRAT) 5-year risk >3%, or IBIS 10-year risk >8% were considered for prevention medication. Adherence and tolerability of baby tamoxifen were assessed at baseline and one year.
Most participants (37 of 41) had good or complete understanding of BC risk; 74% (n=23) chose to take baby tamoxifen. Those who initiated baby tamoxifen were more likely to have DCIS or high risk IEL (P<.001) and were more likely to continue medication at one year versus those who qualified based on BCRAT/IBIS score (P=.05). The 78% (n=18) still taking baby tamoxifen at one year had significantly higher estimated baseline BC risk than those who discontinued (IBIS 10-yesr risk 12.7% vs 7.6%; P=.027). Discontinuation was attributed to side effects, including hot flashes, night sweats, and fatigue.
Dr. Lederman has no conflicts of interest to report.
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