Preventing breast cancer after childbirth

Women who inherit a mutation in the BRCA1 gene face a much higher risk of developing aggressive breast cancer during their lifetime – including during pregnancy and after giving birth. Researchers have long known that breastfeeding is linked to a lower risk of certain breast cancers, but they do not fully understand why. Even less is known about how BRCA1 mutations affect the normal changes that happen in the breast during and after pregnancy. 

Research Training Award recipient and PhD student Ryan Ghorayeb, working with CCS-funded researcher Dr Christopher Maxwell at the University of British Columbia, is investigating how the BRCA1 gene influences mammary gland development during pregnancy, breastfeeding and as the glands return to their pre-pregnancy state. He hopes to learn how these changes may affect breast cancer risk. 

Working with collaborators in Spain, the team identified a potential way to reduce BRCA1-related breast cancer risk: a drug called cabergoline that is normally used to stop milk production. Their findings, published in the journal Cancer Discovery, showed that cabergoline reduced mammary tumours in laboratory models of breast cancer. By analyzing real-world data, they also found that women who took cabergoline after giving birth were associated with a lower risk of developing breast cancer.  

Using organoids (miniature breast tissues grown in the lab), Ryan and Dr Maxwell found that the BRCA1 protein plays a critical role in helping cells divide and develop into milk-producing cells. They also found that mammary glands with BRCA1 gene mutations took longer to return to their pre-pregnancy state.  

“Discovering changes that occur in the mammary gland prior to the formation of tumours helps us come up with strategies to prevent cancer altogether rather than treat it,” Ryan says. “This is important for BRCA1 mutation carriers because breast cancers in these women are aggressive and difficult to treat.”  

Along with other research teams in Canada, the UK and Spain, the team has started a clinical trial to test whether cabergoline can speed up the mammary glands’ return to a pre-pregnancy state and reduce breast cancer risk in people with BRCA1 mutations.  Ryan says, “We are excited about the possibility of a new, non-surgical prevention approach for women born with BRCA1 mutations, which may also prove to be effective more broadly.”  

Inspired by conversations with people affected by cancer through CCS’s IGNITE program – which supports trainees with learning, networking and sharing knowledge – Ryan expanded the project last year to include studying human samples. This year, the team collected unique human breast tissue samples from people during pregnancy and after birth, then partnered with other researchers to analyze large population-based datasets. 

 “CCS has directly funded my research for the past 3 years and provided me with an additional training budget,” Ryan explains. “With these funds, I have been able to attend both national and international conferences where I learned about new research in breast cancer biology and fostered collaborations with labs within and outside Canada.”