Mission Statement: To design and implement a breast cancer prevention strategy based on naturally occurring protective changes identified in breast tissue of normal women.
The need for this project has never been greater. With almost 2 million new cases of breast cancer worldwide every year, the impact from this disease on patients and their families is devastating. Yet less than 10% of a decreasing amount of government research funding is directed toward prevention.
The project addresses a complex problem with a simple premise. We have the opportunity to devise a breast cancer prevention strategy by copying the breast cancer protection that occurs naturally in some women. Research completed within the Marin Women’s Study, a large CDC and Avon Foundation-funded breast cancer study housed in the Marin County Department of Health & Human Services, has identified a subgroup of women with naturally occurring breast cancer protection. This dramatic and powerful finding could not be pursued optimally in the County government environment and has led to the formation of this project, in which the study's Principal Investigator and many original research team members will move this promising research forward. The ultimate goal is to fully identify the mechanism of the protection, allowing its application to all women. We have developed a novel biological hypothesis to explain this observation and will first expand our findings in the statewide California Teachers Study, and then use normal breast biopsy samples to prove our mechanistic hypothesis and generate the necessary information to launch an entirely new breast cancer prevention strategy.
Despite the complexity of the human body and of a disease like breast cancer, there is a certain simplicity in identifying a phenomenon that is occurring naturally, and then duplicating that process in others. As Albert Einstein said, “Look deep into nature and you will understand everything better.” The execution of this strategy is clearly not a simple process, but can be accomplished following a series of defined steps by a multidisciplinary team of many dedicated and talented collaborators.
It has long been known that events surrounding pregnancy are critical to the developing breast. It is thought that this is due to changes in the breast cells themselves, such as mammary stem cells becoming less susceptible to future cancer transformation, a down-regulation of growth factors and expression of critical genes, or final cell differentiation.
Our research has found that women who develop hypertension in pregnancy and carry a common normal gene variation have very high levels of breast cancer protection, in fact, none of the women in our initial study went on to develop breast cancer later in life. The hypertension these women develop in pregnancy is not thought to play a direct role, but is a marker for pregnancies in which the placenta does not develop properly. This results in an outpouring of metabolic and growth factors designed to save the pregnancy. These substances, in the presence of the specific gene variation, have a critical effect on breast tissue, rendering it resistant to developing breast cancer later in life. These findings are consistent with extensive previous research which has shown that developing hypertension in pregnancy is associated with both a lower subsequent risk of breast cancer and with a smaller, more poorly developed placenta. The identification of the critical gene variant has created a window of opportunity to identify the specific process, and could explain why some women develop protection from pregnancies while others do not.