Breast Cancer Prevention: Time for Change

Abstract

Agency breast cancer prevention guidelines for other than hereditary cancers have not materially changed in 20 years; endocrine-targeted agents (then, tamoxifen; now, adding raloxifene and aromatase inhibitors) reduce good prognosis estrogen receptor (ER)–positive, progesterone receptor (PR)–positive cancers without reducing deaths from breast cancer. Across three tamoxifen placebo-controlled prevention trials (N = 23,360) begun almost 30 years ago, although there were 226 fewer breast cancer cases, there were nine more deaths from breast cancer in the tamoxifen groups. Following clinical advances, currently more than half of breast cancer cases are solved problems with extremely low risk of death. As endocrine-targeted agents commonly prevent these cancers, widespread implementation of current prevention strategies may not reduce deaths from breast cancer. Compared with other breast cancers, ER-positive, PR-negative cancers and triple-negative cancers have inferior survival (90.6% v 83.8% v 78.1%, respectively; P < .001). Against this background, in the Women's Health Initiative Dietary Modification randomized trial (N = 48,835), ER-positive, PR-negative cancers were statistically significantly reduced in the intervention group (hazard ratio, 0.77; 95% CI, 0.64 to 0.94) and deaths from breast cancer were reduced 21% ( P = .02). In the Women's Health Initiative randomized, placebo-controlled trial evaluating conjugated equine estrogen (N = 10,739), ER-positive, PR-negative cancers were statistically significantly reduced in the intervention group (hazard ratio, 0.44; 95% CI, 0.27 to 0.74) and deaths from breast cancer were reduced 40% ( P = .04). These findings suggest that reexamination of breast cancer risk reduction strategies and clinical practice is needed.

Mechanistic Effects of Estrogens on Breast Cancer

“…98,118 Congruent with this concept, the greatest reduction is in tumors with these therapies that are ERα + . 126…”

Introduction

“…• Postmenopausal women randomized to estrogen alone in the WHI's prospective, randomized, double-blind study were reported to have a persistent 23% reduced risk of breast cancer after 20 years of follow-up 16 and a 40% reduced risk of breast cancer mortality. 17 Among women with no prior HRT exposure (constituting the majority of perimenopausal women taking HRT as part of the study), the WHI reported no increased risk of breast cancer associated even with combination HRT (conjugated equine estrogen [CEE] + medroxyprogesterone acetate [MPA]) administration. 18 • A full-term pregnancy, which floods the body with both estrogen and progestogen, before age 20 years reduces the risk of subsequent breast cancer by 70%.…”

Breast Cancer Prevention: Where Are We?

“…In the companion to this article, Chlebowski et al 3 present a review of breast cancer prevention and eloquently summarize the decades of work that his group has spent researching this topic through the Women's Health Initiative (WHI). 4 To date, the only medications well-studied for breast cancer prevention are endocrine therapy, which includes selective estrogen receptor modulators and aromatase inhibitors, and there is no known survival benefit from this approach.…”