Breast Cancer Prevention: Time for Change
Rowan T Chlebowski1, Aaron K Aragaki2, Kathy Pan1
1Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
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.
Insights
Current breast cancer prevention strategies, like tamoxifen, don't reduce deaths. New approaches are needed to effectively lower breast cancer mortality and improve survival rates.
Area of Science:
- Oncology
- Preventive Medicine
- Clinical Trials
Background:
- Established breast cancer prevention guidelines have remained static for two decades.
- Endocrine-targeted agents, such as tamoxifen, raloxifene, and aromatase inhibitors, primarily prevent estrogen receptor (ER)-positive, progesterone receptor (PR)-positive breast cancers.
- These agents have not demonstrated a reduction in breast cancer-related mortality, despite preventing certain cancer subtypes.
Purpose of the Study:
- To evaluate the effectiveness of current breast cancer prevention strategies in reducing mortality.
- To investigate alternative approaches for breast cancer risk reduction, particularly for subtypes with inferior survival rates.
- To determine if specific interventions can decrease deaths from breast cancer.
Main Methods:
- Analysis of three tamoxifen placebo-controlled prevention trials (N=23,360) to assess tamoxifen's impact on breast cancer incidence and mortality.
- Examination of data from the Women's Health Initiative Dietary Modification trial (N=48,835) focusing on ER-positive, PR-negative cancers and breast cancer deaths.
- Review of findings from the Women's Health Initiative trial on conjugated equine estrogen (N=10,739) regarding ER-positive, PR-negative cancers and mortality.
Main Results:
- Tamoxifen trials showed 226 fewer breast cancer cases but nine more deaths.
- The Women's Health Initiative Dietary Modification trial found a significant reduction in ER-positive, PR-negative cancers (HR, 0.77) and a 21% decrease in breast cancer deaths.
- The Women's Health Initiative conjugated equine estrogen trial demonstrated a significant reduction in ER-positive, PR-negative cancers (HR, 0.44) and a 40% decrease in breast cancer deaths.
Conclusions:
- Current endocrine-targeted agents may not be effective in reducing overall breast cancer mortality.
- ER-positive, PR-negative breast cancers and triple-negative cancers exhibit poorer survival rates.
- Interventions in the Women's Health Initiative trials suggest potential for reducing specific breast cancer subtypes and associated mortality, warranting a reevaluation of prevention strategies.
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