Risk-Reducing Medication in Patients With High-Risk, ER-Positive Breast Cancer: Benefits and Harms

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In a study reported in the Journal of Clinical Oncology, Jayasekera et al identified the benefits and harms of using risk-reducing medication in addition to screening in patients with high-risk, estrogen receptor (ER)-positive breast cancer.

As stated by the investigators, “Recent studies, including a meta-analysis of 88 trials, have shown higher-than-expected rates of recurrence and death in [patients with] hormone receptor–positive breast cancer. These new findings suggest a need to reevaluate the use of risk-reducing medication to avoid invasive breast cancer and breast cancer death in high-risk women.”

Study Details

The study used an adapted established Cancer Intervention and Surveillance Modeling Network model to evaluate lifetime benefits and harms of risk-reducing medication in women with a ≥ 3% 5-year risk of developing breast cancer, according to the Breast Cancer Surveillance Consortium risk calculator. Model inputs were derived from meta-analyses, clinical trials, and data from large observational studies. The model was used to assess the effects of 5 years of risk-reducing medication (tamoxifen or aromatase inhibitors [AIs]) with annual screening mammography ± magnetic resonance imaging (MRI) compared with no screening, MRI, or risk-reducing medication.

Key Findings

Tamoxifen with annual screening (±MRI) reduced the risk of invasive breast cancer by 40% and breast cancer death by 57% vs no tamoxifen or screening; the finding is equivalent to an absolute reduction of 95 invasive breast cancers and 42 breast cancer deaths per 1,000 high-risk women. The estimated benefit attributable to tamoxifen alone was avoidance of 58 to 59 invasive breast cancers and 13 breast cancer deaths per 1,000 women. Harms included the association of tamoxifen with 11 cases of endometrial cancer per 1,000 women over a 5-year period.

In subgroup analyses including such individual risk factors as age, family history, and prior biopsy, benefits and harms of risk-reducing medication were found to vary according to individual characteristics.

In an analysis of use of AIs vs tamoxifen in women at age 50 years and at age 65 years, AIs were associated with greater benefits and reduced harms. The absolute reductions attributable to AIs alone in women aged 50 years and 65 years were 133 to 134 and 84 invasive breast cancers and 54 to 55 and 14 breast cancer deaths per 1,000 women, respectively.

The investigators concluded, “The addition of risk-reducing medication to screening could further decrease the risk of breast cancer death. Clinical guidelines for high-risk women should consider integrating shared decision-making for risk-reducing medication and screening on the basis of individual risk factors.”

Jinani Jayasekera, PhD, of the Population and Community Health Sciences Branch, Intramural Research Program, National Institutes of Health, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Institutes of Health and National Cancer Institute. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.