Abstract
Purpose
The role of established breast cancer risk factors and clinical characteristics of the first breast cancer in the development of contralateral breast cancer (CBC) among postmenopausal women is unclear.
Methods
We identified 10,934 postmenopausal women diagnosed with a first primary breast cancer between 1995 and 2011 in the NIH-AARP Diet and Health Study. CBC was defined as a second primary breast cancer diagnosed in the contralateral breast ≥ 3 months after the first breast cancer. Exposures included pre-diagnosis risk factors (lifestyle, reproductive, family history) and clinical characteristics of the first breast cancer. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results
Over a median follow-up of 6.8 years, 436 women developed CBC. We observed an increasing trend in CBC risk by age (p-trend = 0.002) and decreasing trend by year of diagnosis (p-trend = 0.001) of the first breast cancer. Additional risk factor associations were most pronounced for endocrine therapy (HR 0.68, 95% CI 0.53–0.87) and family history of breast cancer (HR 1.38, 95% CI 1.06–1.80, restricted to invasive first breast cancer). No associations were found for lifestyle (body mass index, physical activity, smoking, alcohol) or reproductive factors (age at menarche, parity, age at first birth, age at menopause).
Conclusions
This study suggests that clinical characteristics of the first breast cancer and family history of breast cancer, but not pre-diagnosis lifestyle and reproductive factors, are strongly associated with CBC risk among postmenopausal women. Future studies are needed to understand how these factors contribute to CBC etiology and to identify further opportunities for prevention.
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Data availability
The datasets analyzed during the current study were obtained from the NIH-AARP Diet and Health Study at the National Cancer Institute. The data used in this study are available with the submission of a proposal and approval from the NIH-AARP Steering Committee (https://dietandhealth.cancer.gov/).
Code availability
Code is available upon request.
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Funding
This study was funded by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health. MM is funded by the Health Research Board in Ireland.
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CR, ABdG conceived and designed the study and conducted and reviewed statistical analysis. All authors substantially contributed to the preparation and critical review of the manuscript. All authors read and approved the final manuscript.
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The NIH-AARP Diet and Health Study (Protocol Number: OH95CN025) was approved by the Special Studies Institutional Review Board (SSIRB) of the US National Cancer Institute. This study was conducted in accordance with the ethical standards of the institutional review board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Ramin, C., Mullooly, M., Schonfeld, S.J. et al. Risk factors for contralateral breast cancer in postmenopausal breast cancer survivors in the NIH-AARP Diet and Health Study. Cancer Causes Control 32, 803–813 (2021). https://doi.org/10.1007/s10552-021-01432-2
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DOI: https://doi.org/10.1007/s10552-021-01432-2