ASCO24 Updates: Arya Roy on Polygenic Risk Scores and Breast Cancer Survival

The American Society of Clinical Oncology (ASCO) Annual Meeting is one of the largest and most prestigious conferences in the field of oncology. This year, the meeting took place from May 31 to June 4 in Chicago, Illinois. The event gathers oncologists, researchers, and healthcare professionals from around the world to discuss the latest advancements in cancer research, treatment, and patient care. Keynote sessions, research presentations, and panel discussions are typically part of the agenda, providing attendees with valuable insights into emerging trends and innovations in oncology.

This year, OncoDaily was at ASCO 2024 for the first time covering the meeting on-site. We had the pleasure of interviewing researchers who summarized the highlights of their work.

In this video, Dr. Arya Roy, a third-year hematology and oncology fellow at Roswell Park Comprehensive Cancer Center, shared insights on ‘Breast cancer polygenic risk score and patient survival outcomes in the Pathways study.‘

Hi everyone, I am Arya Roy, I am a third year hematology and oncology fellow from Roswell Park Comprehensive Cancer Center and I am an incoming breast medical oncology assistant professor at the Ohio State University, Ohio State Comprehensive Cancer Center. In our study, we evaluated the polygenic risk scoring in breast cancer and its association with the survival outcomes in breast cancer. We know that breast cancer is the most common malignancy in women in the US and also it is the second most common cause of mortality in women in the US.

And there are several high penetrance and moderate penetrance genes which are associated with the heritability of breast cancer such as BRCA1, BRCA2 or TP53, ATM etc. Although there are the high and moderate penetrance genes, there are several other low penetrance genes which are commonly seen in the population than when compared to the pathogenic variants which in combination has a higher risk for breast cancer development. And there is very little that is known about this low penetrance genes and most of the time these low penetrance genes are actually single nucleated polymorphisms or called as SNPs.

These are DNA variants usually seen in people. So, we can identify the gene variants through GWAS testing and there is a score called as polygenic risk score. So, polygenic risk score is a mathematical value that is calculated by combining the effects of hundreds of or thousands of genetic markers in an individual which would help us to identify the individual’s risk for certain type of diseases especially in breast cancer.

So, in our study we looked at the polygenic risk score and we know that polygenic risk score is usually associated with the incidence of breast cancer, but the association of polygenic risk score with the survival outcomes in breast cancer is not very well studied. Therefore, in our study we hypothesized that in patients with higher polygenic risk score they have higher chance of secondary cancers or recurrence of cancer and also higher mortality rates. For our study we looked at the pathway study which is a large prospective cohort of cancer survivor patients who were enrolled from 2006 to 2013 at the Kaiser Permanente in Northern California.

We had a total of 4505 patients enrolled in this study so far and out of that 3980 patients they had genome wide genotype data available. We looked into the polygenic risk scoring and we looked into 4 different polygenic risk scoring PGS 313 which is a 313 variant scoring, then PGS 4000, PGS 5000 and PGS 6 million. And in our study we mainly observed that those who have higher polygenic risk scoring which is the PGS 313 they have higher risk for recurrence of disease and also they have higher risk of mortality rates.

We divided the groups into 3 different groups T1, T2 and T3 with T1 is the group of patients which have low PGS scores, T2 is the group of the patients which have medium PGS scores and T3 is the group of the patients who have higher PGS scores. And we observed that when compared to the patients who have low scores which is the T1 group, T2 and T3 groups they had higher chance of recurrence and also higher chance for overall mortality and also higher chance of invasive breast cancer events.

So, this study actually tells us that in addition to the risk of association of development of cancer breast cancer in patients with higher polygenic risk score, there is higher polygenic risk score is also associated with the survival outcomes in breast cancer.

So, this study is definitely important in the cancer prevention and also prevention area because when we know that if a patient has higher polygenic risk score that means that this patient has higher chance of recurrence and we need to follow up the patient very closely and also we need to make sure that the patient is adherent to strict screening guidelines even after they are cured from their cancer. 

More videos and content from ASCO 2024 on OncoDaily.