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Showing content from https://pubmed.ncbi.nlm.nih.gov/36455167/ below:

Reassessing the Benefits and Harms of Risk-Reducing Medication Considering the Persistent Risk of Breast Cancer Mortality in Estrogen Receptor-Positive Breast Cancer

Meta-Analysis

Affiliations

• ¹ Population and Community Health Sciences Branch, Intramural Research Program, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD.
• ² Department of Oncology, Georgetown University Medical Center and Cancer Prevention and Control Program, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC.
• ³ Departments of Family and Social Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
• ⁴ Department of Radiology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA.
• ⁵ Department of Pediatrics, Harvard Medical School, Boston Children's Hospital, Boston, MA.
• ⁶ Kaiser Permanente Washington Health Research Institute, Seattle, WA.
• ⁷ Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Healthcare Institute, Boston, MA.
• ⁸ Departments of Medicine and of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA.

• PMID: 36455167
• PMCID: PMC9901948
• DOI: 10.1200/JCO.22.01342

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Meta-Analysis

Jinani Jayasekera et al. J Clin Oncol. 2023.

• ¹ Population and Community Health Sciences Branch, Intramural Research Program, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD.
• ² Department of Oncology, Georgetown University Medical Center and Cancer Prevention and Control Program, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC.
• ³ Departments of Family and Social Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
• ⁴ Department of Radiology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA.
• ⁵ Department of Pediatrics, Harvard Medical School, Boston Children's Hospital, Boston, MA.
• ⁶ Kaiser Permanente Washington Health Research Institute, Seattle, WA.
• ⁷ Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Healthcare Institute, Boston, MA.
• ⁸ Departments of Medicine and of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA.

• PMID: 36455167
• PMCID: PMC9901948
• DOI: 10.1200/JCO.22.01342

Item in Clipboard

Purpose: Recent studies, including a meta-analysis of 88 trials, have shown higher than expected rates of recurrence and death in hormone receptor-positive breast cancer. These new findings suggest a need to re-evaluate the use of risk-reducing medication to avoid invasive breast cancer and breast cancer death in high-risk women.

Methods: We adapted an established Cancer Intervention and Surveillance Modeling Network model to evaluate the 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 input parameters were derived from meta-analyses, clinical trials, and large observational data. We evaluated the effects of 5 years of risk-reducing medication (tamoxifen/aromatase inhibitors) with annual screening mammography ± magnetic resonance imaging (MRI) compared with no screening, MRI, or risk-reducing medication. The modeled outcomes included invasive breast cancer, breast cancer death, side effects, false positives, and overdiagnosis. We conducted subgroup analyses for individual risk factors such as age, family history, and prior biopsy.

Results: Risk-reducing tamoxifen with annual screening (± MRI) decreased the risk of invasive breast cancer by 40% and breast cancer death by 57%, compared with no tamoxifen or screening. This is equivalent to an absolute reduction of 95 invasive breast cancers, and 42 breast cancer deaths per 1,000 high-risk women. However, these drugs are associated with side effects. For example, tamoxifen could increase the number of endometrial cancers up to 11 per 1,000 high-risk women. Benefits and harms varied by individual characteristics.

Conclusion: 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.

PubMed Disclaimer

Claudine Isaacs

Consulting or Advisory Role: Pfizer, Genentech/Roche, Novartis, Puma Biotechnology, Seattle Genetics, Sanofi/Aventis, Eisai, Ion Solutions, bioTheranostics, AstraZeneca/MedImmune, Gilead Sciences

Research Funding: Tesaro (Inst), Merck (Inst), Seattle Genetics (Inst), Pfizer (Inst), GlaxoSmithKline (Inst), AstraZeneca (Inst), Novartis (Inst), Genentech/Roche (Inst), Bristol Myers Squibb/Celgene (Inst)

Patents, Royalties, Other Intellectual Property: McGraw Hill Publishing, UpToDate—Wolters Kluwer—Author of chapters, Elsevier—Editor of Book

Other Relationship: Side-Out Foundation

No other potential conflicts of interest were reported.

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• Opportunities, challenges, and future directions for simulation modeling the effects of structural racism on cancer mortality in the United States: a scoping review.

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