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Discovering the causes of cancer and the means of prevention

Evidence for Familial Clustering of Breast Cancer Age at Onset - Dr. Weinberg

DCEG Events

October 3, 2019 | 10:30 AM – 11:30 AM

NCI Shady Grove Seminar TE406 Rockville M.D.

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Sholom Wacholder Distinguished Lecture


Clarice R. Weinberg, Ph.D., Principal Investigator, 
Biostatistics & Computational Biology Branch, 
National Institute of Environmental Health Sciences


This talk will describe ongoing work that has not yet been published, so feedback is welcome! Familial clustering of age at onset would have implications for both screening and etiology, but has not been well studied for breast cancer. We used Cox models applied to a cohort of prospectively-followed sisters of cases to explore whether breast cancer risk over age-time is influenced by the age at diagnosis of a previously-affected sister. We created a ‘closeness’ covariate to quantify how similar the participant’s current age was to her sister’s age at diagnosis. This variable updates over follow-up time so that the hazard ratio can peak (or dip) when the participant’s age reaches the sister’s diagnosis age. When restricted to women with a single proband, who was older (to optimize inclusion of proximal follow-up ages), the hazard ratio was estimated as 1.7 (95% CI (1.26, 2.19) at the sister’s diagnosis age, consistent with a sizable increase in the hazard near the age when the older sister had previously been diagnosed. We performed a sensitivity analysis to rule out increased vigilance as an artifactual explanation. This familial clustering suggests that there may be important shared genetic and/or early environmental contributions to risk for subtypes of breast cancer, even when onset is late in life.


Hormuzd A. Katki, Ph.D., Senior Investigator, 
Biostatistics Branch, Division of Cancer Epidemiology & Genetics, 
National Cancer Institute

This lectureship is named in memory of Sholom Wacholder, Ph.D., senior investigator in the Biostatistics Branch (BB), a brilliant, multidisciplinary and critical thinker who worked at the intersection of quantitative reasoning and science. 


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