My goal is to better understand breast cancer risk and prognosis by utilizing molecular markers in epidemiologic studies. Specifically, my research has focused on intermediate markers of breast cancer risk including mammographic density and benign breast diseases (BBD). Many of these studies are based within the Nurses Health Study (NHS) and Nurses Health Study II (NHSII).
Mammographic Density Studies
Mammographic density is one of the strongest risk factors for breast cancer, yet the mechanisms underlying this are not well elucidated. I have multiple grants to examine lifestyle, genetic, and molecular predictors of mammographic density. We demonstrated for the first time that circulating hormones and mammographic density were independent predictors of breast cancer risk, and that women with high levels of both were at a particularly high risk of subsequent breast cancer in the NHS. These data suggest that incorporating both hormones and mammographic density into risk prediction models may identify high risk women for targeted interventions.
Mammographic density is a highly heritable trait, more so than breast cancer. Given the high heritability of mammographic density, understanding the genetic predictors of breast density may help to identify novel genes and pathways related to breast density and breast cancer. To better identify genetic predictors of mammographic density, I lead the Markers of Density (MODE) consortium, an international consortium to pool genome-wide association studies of mammographic density.
I have also leveraged randomized control trials, to study the effects of specific interventions on change in breast density. We have an ancillary breast health study within the Kronos Early Estrogen Prevention Study (KEEPS) randomized control trial to evaluate the effect of newer low-dose hormone therapies on breast density. Similarly, we have just been funded to conduct an ancillary study within the VITamin D and omega-3 trial (VITAL), to study association between vitamin D supplementation on breast density and breast tissue molecular and morphologic features.
Additionally, I have initiated a multi-ethnic pilot study of mammographic density enrolling women coming in for routine screening mammograms at the Lee Bell Center for Breast Imaging at Brigham and Women's Hospital.
Benign Breast Disease Studies
Benign breast diseases are also thought of as general markers of breast cancer risk. Within the Nurses Health Studies my group has examined exposures associated with early proliferative changes in the breast, and how morphologic and molecular changes in benign breast tissue are related to subsequent risk of breast cancer. Recently, we found that early adolescent exposures influence later proliferative breast disease risk. Although it had been hypothesized that adolescence may be an important time period for breast cancer, these projects are critical for identifying the modifiable exposures that may influence long-term breast health. Most recently, we have identified molecular alterations in benign breast tissue that predict long-term risk of subsequent breast cancer. These projects have important public health implications for identifying early opportunities for cancer prevention.
Breast cancer is a heterogeneous disease. Characterization of breast tumors by hormone receptor status has been important in understanding the mechanisms by which certain breast cancer risk factors operate, but also for determining treatment and prognosis. I have worked closely with collaborating pathologists to create breast cancer tissue microarrays within the Nurses Health Study. This will allow us to examine how lifestyle factors, and genetic and plasma markers influence the molecular characteristics of the breast tumor. Better molecular classification of breast tumors may provide important clues as to the biology and underlying mechanisms of breast carcinogenesis. My long-term goals are to incorporate the full spectrum of resources including genetic variation, early life exposures, circulating markers, tissue markers and intermediate endpoints to fully develop and address hypotheses about breast cancer risk.
In addition to my research interests, I have enjoyed a number of local teaching and mentoring opportunities at the Harvard School of Public Health, and Harvard Medical School.