Non-Invasive Assessment of Lactating Breasts of Asymptomatic BRCA mutation carriers

Kathleen and Brian at UMass Amherst

Our project with lactating BRCA mutation carriers to understand breast cancer risk and development

This project was developed by Dr. Kathleen Arcaro and Dr. Brian Pentecost and received funding  (2020-22) from the Breast Cancer Research Program (BCRP) of the Congressionally Directed Medical Research Program. See the section at the bottom of the page for our collaborators.  The formal project title is Non-Invasive Assessment of Lactating Breasts Using Somatic Mutations and DNA Methylation as a Pre-Symptomatic Test for BRCA Breast Cancer. That is kind of the entire project dumped on you in a sentence, but you can see the study incorporates several themes: BRCA mutation status, analysis during lactation, relevance to breast cancer risk and molecular analysis.  The description below is a trimmed version of the Lay abstract which eventually will be publically searchable on the BCRP website.  We currently recruit participants and collect samples under the auspices of the UMass IRB using UMass funds while awaiting human subjects review & approval in the BCRP program.  The project builds on more than a decade of funded research assessing risk using breastmilk samples.

The trimmed lay abstract for the BRCA breastmilk study, from the BCRP submission

BRCA1 and BRCA2 are genes encoding proteins involved in repairing damaged DNA. Women with defective BRCA genes have a reduced ability to repair DNA mutations, which leads to greatly elevated lifetime risk of breast and ovarian cancer.

Women with a germline BRCA mutation have a higher incidence of pregnancy-associated breast cancer (PABC), and an increased risk of developing breast cancer during their premenopausal years. An important reason for developing new screening methods for lactating BRCA mutation carriers is that the standard breast cancer screening methods do not work well for nursing mothers.

The elevated cancer incidence in BRCA mutation carriers is caused in part by accumulation of DNA damage (somatic mutations) due to failure of the DNA repair system which the intact BRCA genes support. Abnormal DNA methylation and somatic mutations underlie the development of all breast cancers, and are the most promising molecular biomarkers for both early detection and individual assessment of breast cancer risk.

In an effort to develop strategies to reduce breast cancer risk, we study breast milk. Breast milk provides a unique opportunity to non-invasively examine the breast, through sloughed cells, secreted proteins, and lipophilic environmental contaminants.

We propose, in this project, to recruit lactating women who have tested positive for a BRCA mutation associated with increased risk of developing cancer.

The sloughed epithelial cells present in the milk samples will be examined for DNA methylation and somatic mutations to uncover profiles that may identify breasts at increased risk of breast disease, as well as to shed light on breast cancer development in women with defects of DNA repair.

We will also attempt to recruit a small group of lactating women who already have breast cancer in order to understand what a positive signal looks like.

The study design provides a unique opportunity to examine breast cells from non-symptomatic BRCA carriers of reproductive-age in a critical period of breast development. We hope to convert the findings into a screening test for BRCA-related pathology during lactation, a period during which current screening methods are either not usable or are not fully effective, in addition to gaining further understanding of the development of BRCA-related breast cancers.

Meet other  members of the BRCA cancer biomarker project for nursing mothers

Much of the hands-on work for the study will be carried out by Kathleen’s grad student Vignesh Narayanaswamy.  Statistical analysis of data will be guided by Dr. Raji BalasubramanianDr. Elizabeth Cahn provides outreach to the BRCA carrier and breast cancer survivor communities in the Massachusetts region.  Our surgical collaborators, principally involved in recruiting lactating women with breast cancer, include Dr. Katrina B. Mitchell and Dr. Shannon Tierney.