The focus of my research is the etiology of breast cancer, examining associations between lifestyle factors, biomarkers of lifestyle and hormones, and breast cancer risk. I study ways in which women may alter their lifestyle to reduce breast cancer risk, and much of my work has been conducted within the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII). I serve as co-PI of the NHSII, founded in 1989 by Dr. Walter Willett, that includes over 116,000 women. We continue to follow the Nurses’ Health Studies participants, collecting exposure information and disease diagnoses every two years, and have initiated a new biospecimen collection of stool samples for future examination of the role of the microbiome in human health and disease. I am also Director of the BWH/Harvard Cohort Biorepository, which houses more than three million biospecimens from 200,000 cohort participants, and co-lead of the Cancer Epidemiology Program at the Dana-Farber/Harvard Cancer Center.
In my investigations of potentially preventive lifestyle factors, I showed that weight loss and increased physical activity, even if initiated after menopause, reduced breast cancer risk. As chair of an international collaborative group, I led a pooled analysis of eight cohort studies and showed that higher blood levels of carotenoids, prominent in fruits and vegetables, significantly reduced breast cancer risk. In this and a subsequent paper, we observed stronger inverse associations with carotenoids for tumors that lack estrogen receptor expression and tumors that recurred or caused death. Contributing to our understanding of the importance of timing of exposure, we have found that dietary intake of carotenoid-containing fruits and vegetables in both adolescence and adulthood is important, with adolescent fruit intake associated with lower risk of benign breast disease and adult fruit and vegetable intake associated with lower risk of both premenopausal and postmenopausal breast cancer risk. Intake during adulthood is associated with lower risk of breast tumors that do not express the estrogen receptor, including those that are enriched for HER2 expression and basal-like tumors. Continuing the examination of biomarkers that reflect both diet and endogenous synthesis, I have ongoing projects examining circulating fatty acids and breast cancer risk by tumor expression of inflammatory and immune markers, and am co-PI of the main scientific R01 of the NHSII cohort, in which we are investigating metabolomics and breast cancer risk.
I also have expanded our understanding of the role of hormones in breast cancer etiology, and the intersection between hormones and lifestyle factors. I led the first extensive analysis of urinary estrogen metabolites with risk of breast cancer in premenopausal women, finding unexpected inverse associations. Building upon these findings, I have overseen several analyses to understand how lifestyle factors may impact patterns of estrogen metabolism. In addition, a marker of ovarian reserve, anti-Müllerian hormone, which is measureable in premenopausal women and is inversely associated with subsequent age at menopause, is associated with higher risk of breast cancer. The association is apparent in cancers diagnosed before menopause and independent of its strong association with age at menopause. Our next step is to consider if these premenopausal hormones could be used to identify women at risk of breast cancer, potentially providing a risk assessment at younger ages.
In addition to my research interests, I teach classes and mentor doctoral students and postdoctoral fellows at the Harvard T.H. Chan School of Public Health. Through my efforts supporting the framework of the NHS/NHSII cohorts, directing the BWH/Harvard Cohorts Biorepository, applying the data obtained to study lifestyle factors and biomarkers with breast cancer etiology, collaborating with others in the field, and mentoring younger researchers, my goal is to continue making meaningful contributions to the field of breast cancer epidemiology.