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Doris Germain, PhD
Icahn School of Medicine at Mount Sinai
New York, New York
Goal: To develop a prevention intervention modeled on the risk-reducing effects of breastfeeding.
Impact: Breastfeeding is known to reduce the risk of future breast cancer, but the biology underlying this effect is not well understood. Based on discoveries from her lab, Dr. Germain is devising ways to leverage the protective effect of breastfeeding as a preventive strategy for breast cancers that occur after pregnancy.
What’s next: Dr. Germain’s group identified the hormones responsible for the risk-reducing benefit of breastfeeding. In the coming year, they will explore the possibility that the molecular mechanism underlying the protective role of breastfeeding can be exploited as a lactation replacement therapy for breast cancer prevention.
Breastfeeding is naturally protective against future breast cancer. Being able to mimic this effect for women who do not or cannot breastfeed could prevent the onset of aggressive, pregnancy-associated breast cancer. Dr. Germain’s group is the first to describe a mechanism underlying this protective effect. They will use this new knowledge to further unravel the details of this hormone-dependent mechanism so that they can develop lactation-replacement therapy as a strategy of precision prevention.
Full Research Summary
Research area: Identifying markers for risk assessment and stratification to develop interventions for precision prevention.
Impact: Breast cancers that arise after pregnancy (up to 6 years after pregnancy) are most frequently triple-negative breast cancers and are even more aggressive than non-pregnancy-associated triple-negative breast cancer. The risk of developing breast cancer can be reduced by breastfeeding. Dr. Germain’s BCRF research is exploring ways to mimic the protective effect of breastfeeding as a novel nontoxic strategy to prevent breast cancers that arise after pregnancy.
Current investigation: Dr. Germain’s team identified the hormones involved in the protective action of breastfeeding. In the next year, her team will explore the potential to mimic this effect in a laboratory model. If successful, it could lay the groundwork for a larger study to test a lactation-replacement therapy in new mothers to reduce the risk of pregnancy-associated breast cancers, as well as the risk of breast cancer in women with dense breasts.
Dr. Germain obtained her PhD at University of Montreal and trained as a postdoctoral fellow at Cold Spring Harbor Laboratories. She obtained her first faculty position at the Peter MacCallum Cancer Institute in Melbourne, headed by Dr. Joseph Sambrook. She joined Mount Sinai in 2002, where she is currently a tenured Professor.
The focus of her research is proteostasis, which refers to the management of the quality of proteins. Cancer cells are characterized by elevated rates of mutation and chromosomal abnormalities, which affect the folding of a vast array of proteins. In order to manage such changes, cancer cells rely heavily on chaperones, proteases and ubiquitin-proteasome pathway to maintain their proteomic landscape. So far, the Germain lab group has identified and characterized a novel gene implicated in the ubiquitin pathway, characterized a protease involved in pregnancy-associated breast cancer and pioneered the field of mitochondrial unfolded protein response (UPRmt).
Their laboratory was the first to describe a role of the estrogen receptor alpha (ER-alpha) in the UPRmt. Endocrine therapy of breast cancer aims at targeting the ER-alpha. Their unique combination of interest in the ER-alpha and ubiquitin-pathway has led to the establishment of scientific rationale for a new combination of drugs to enhance endocrine therapy. This effort was translated into a phase II clinical trial in metastatic ER-alpha+ breast cancer patients (NCI8457). Their group was also the first to establish a laboratory model of pregnancy-associated breast cancer and identify the mechanism by which breastfeeding is protective against breast cancer. Dr. Germain’s research has led to the discovery of novels pathways regulating metastasis and has led to two clinical trials to date.