Study Shows Polygenic Risk Score (PGS) Could Predict Breast Cancer Survival Outcomes

Data from a large prospective cohort study reveal that a polygenic risk score has the potential to predict survival outcomes in patients with breast cancer. Arya Mariam Roy, MBBS, Hematology/Oncology Fellow (Class of 2024) at Roswell Park Comprehensive Cancer Center, will share the results of that study as the first and presenting author of “Breast cancer polygenic risk score and patient survival outcomes in the Pathways study” at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, May 31-June 4.

A polygenic risk score (PGS) helps estimate a person’s risk of developing specific diseases. It is based on a genome-wide association study (GWAS), which scans the individual’s DNA to identify variants, or mutations, associated with those diseases. “It is a mathematical value calculated by combining the effects of hundreds to thousands of genetic markers carried by each person to predict their risk,” explains Dr. Roy.

These include lower-penetrance gene variants, which individually may or may not lead to the disease. However, when several common, lower-penetrance gene variants are combined, they significantly increase the risk. A PGS is already a valuable tool for calculating the risk of developing breast cancer, and the current study indicates that it might be equally valuable for prognosis.

Conducted at Kaiser Permanente Northern California between 2006-2013, the Pathways Study provided genome-wide genotype data from 3,995 patients who enrolled shortly after a diagnosis of invasive breast cancer. It is led by Principal Investigators Christine Ambrosone, PhD, Distinguished Professor of Oncology, Senior Vice President for Population Sciences and Chair of Cancer Prevention and Control at Roswell Park, and Lawrence Kushi, ScD, Research Scientist and Director of Scientific Policy at the Kaiser Permanente Northern California Division of Research.

The Roswell Park study drew on the resulting data to compile four polygenic scores for each patient: PGS313 and PGS4k, PGS5k and PGS6m. Investigators then followed the participants to document their survival outcomes. By the end of the 2021 calendar year, the patients had been followed for a median of 10.5 years (0.2-14.2 years).

Investigators recorded the association between low (T1), medium (T2) and high (T3) polygenic scores within each self-reported racial and ethnic group to seven documented survival outcomes: overall survival, breast cancer-specific survival, recurrence-free survival, second primary cancer-free survival, disease-free survival, invasive disease-free survival and breast cancer event-free survival.

Of the four PGSs measured, only PGS313 was associated with the survival outcomes. Patients with medium (T2) and high (T3) PGS313 had a greater risk of recurrence, death from any cause, total breast cancer events and invasive disease compared with those who had low (T1) PGS313. Higher PGS313 was not associated with contralateral second primary breast cancer, breast cancer-specific death or any other second primary cancer.

“Our analysis showed that women with a higher PGS that was predictive of a higher risk of breast cancer also have an increased likelihood of experiencing a second breast-related event, such as cancer recurrence and death,” says Song Yao, MD, PhD, Professor of Oncology and Vice Chair of the Department of Cancer Prevention & Control at Roswell Park, and co-senior author of the study, along with Drs. Ambrosone and Kushi. He says the findings highlight the potential role of breast cancer PGS as a prognostic tool, warranting further exploration.

Dr. Roy will be honored at the annual meeting with a 2024 ASCO Merit Award, given to a student or trainee who is first author and presenter of a top-ranking abstract. She is also first author and presenter of “International Medical Graduates (IMG) representation at International Oncology Conference Meetings,” to be presented during a Clinical Science Symposium, “Conflicts (of Interest) and Conundrums: Perspectives from the Global Oncology Community,” during the ASCO Annual Meeting.

Presentation details

Breast cancer polygenic risk score and patient survival outcomes in the Pathways study

• Abstract 10502, Oral Abstract Session
• Saturday, June 1, 3:24-3:36 pm CDT

International medical graduates (IMG) representation at international oncology conference meetings

• Abstract 9000, Clinical Science Symposium
• Saturday, June 1, 1:27-1:39 pm CDT