Harvard Catalyst Profiles

Harvard School of Public Health, Boston, MA	ScD	06/2004	Epidemiology
Harvard School of Public Health, Boston, MA	ScM	06/2001	Epidemiology
Dartmouth College, Hanover, NH	AB	06/1995	History

My research focuses on the associations between lifestyle factors, biomarkers of lifestyle and hormones, and breast cancer risk and survival after breast cancer. I have studied ways women may alter their lifestyle to reduce breast cancer risk, leveraging the rich resources of the NHS and NHSII cohorts. I have obtained funding from the NIH and Komen Foundation as an independent investigator, with a focus on carotenoids, oxidative stress, metabolomics, and breast cancer risk. My main administrative responsibilities include serving as co-PI of the NHS and NHSII cohorts, Director of the BWH/Harvard Cohorts Biorepository, Associate Director of the CDNM, and Director of the Chronic Disease Epidemiology unit in the CDNM. The remainder of my time is spent teaching and mentoring.

In my study of potentially preventive lifestyle factors, I showed that weight loss and increased physical activity after menopause reduced breast cancer risk, published in JAMA and Archives of Internal Medicine. As chair of an international collaborative group, I led a pooled analysis of 8 cohort studies and showed that higher blood levels of carotenoids, prominent in fruits and vegetables, significantly reduced breast cancer risk, published in the Journal of the National Cancer Institute. As a result, I obtained an NIH R01 to continue studying carotenoids and explore the role of oxidative stress in breast cancer etiology. In a more in-depth examination of carotenoids and breast cancer risk, I observed a significantly lower risk of lethal/recurrent breast cancer with higher carotenoid levels. Continuing the examination of biomarkers that reflect both diet and endogenous synthesis and breast cancer risk, I investigated the role of circulating fatty acids and breast cancer risk by tumor expression of inflammatory and immune markers, finding a positive association between circulating trans fatty acids and breast cancer risk, particularly among overweight and obese women and those with tumors expressing fatty acid synthase.

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, published in Cancer Research. 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 measurable 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.

I have several ongoing analyses of the role of metabolomics in the risk of breast and ovarian cancer, funded by an R01 and P01 on which I served as multi-PI. In analyses of a priori hypothesized lipid classes of metabolites, we observed several significant associations between circulating sphingomyelins and subsequent ovarian cancer, published in Cancer Research. In analyses of circulating branched-chain amino acids, we observed opposite associations with breast cancer risk depending on menopausal status, with inverse associations among premenopausal women but positive associations among postmenopausal women. Through agnostic analyses of metabolites, we identified several metabolites associated with higher risk of ovarian cancer, with pseudouridine as the top hit. Among premenopausal women in NHSII, we identified ten metabolites associated with subsequent breast cancer risk, including six metabolites associated with lower risk and four metabolites associated with higher risk, published in NPJ Breast Cancer. Additional agnostic analyses of metabolomic profiles and risk of breast and cancer in postmenopausal women are ongoing.

As the co-PI of NHS and NHSII, I have multiple leadership responsibilities. I serve as a senior scientific resource to others wishing to collaborate, help determine the scientific direction of the study, and lead students and fellows in their analyses of lifestyle factors and biomarkers in relation to breast cancer risk and survival. I also represent the cohort nationally and internationally, including election to the steering committee of the NCI Cohort Consortium, for which I will serve as Chair in 2022. My reputation in the breast cancer research community has led to invitations to serve on several grant study sections, including the DoD and several international research organizations, and to give talks at NCI seminars and workshops and cancer research institutions internationally. Our current infrastructure grant renewal application (U01 CA176726), on which Dr. Willett and I serve as multi-PIs, received a perfect priority score of 10 and is currently funded through 2023.

I am active in teaching at the HSPH, including as the primary instructor for Epi 246: Applied Biomarkers in Cancer Epidemiology and mentoring at HMS and the HSPH. I mentored three masters and two doctoral students in Epidemiology (HSPH) and three postdoctoral fellows (HMS and HSPH) as they conducted epidemiologic research. I currently mentor one master’s student and one doctoral student in Epidemiology and four postdoctoral fellows. I also served on oral exam and thesis committees for nine doctoral students.

Through my leadership of the NHS/NHSII cohorts, directing the BWH/Harvard Cohorts Biorepository and the CDNM’s Chronic Disease Epidemiology unit, applying the data obtained to study lifestyle factors and breast cancer etiology, collaborating with others in the field, and mentoring younger researchers, I intend to continue making meaningful contributions to the field of cancer epidemiology.