Genetic Test May Predict Risk of Invasive Breast Cancer After DCIS or LCIS

Being diagnosed with either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) ups a person's risk of developing invasive breast cancer in the future. But doctors don't have a good way to figure out who will go on to develop invasive disease. So some people may receive more treatment than they need to try to prevent it. A certain type of genetic test could change that.

In a recent study, researchers used a test looking for small DNA changes to estimate a person's risk of developing invasive breast cancer after DCIS or LCIS. The test calculates a score, called a polygenic risk score. People with a higher polygenic risk score have a higher risk of invasive cancer after DCIS or LCIS.

A polygenic risk score is a number that estimates a person's risk of a disease, based on small changes to DNA called single nucleotide polymorphisms (SNPs). SNPs are single changes to the molecules that make up DNA, and they're very common. Some SNPs don't do anything. Others can increase the risk of diseases, including breast cancer. Each SNP that raises breast cancer risk only has a tiny effect by itself. But if someone has a high number of SNPs that raise breast cancer risk, the total increase in risk can be large enough to affect a person's health.

The test used in the study, called the PRS₃₁₃ test, measures which of 313 SNPs linked to breast cancer a person has. Researchers found that people with a high PRS₃₁₃ score were more likely to develop invasive breast cancer after DCIS or LCIS.

In this episode of The Breastcancer.org Podcast, Drs. Holly Pederson and Elisha Hughes explain what a polygenic risk score is.

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Researchers used the PRS₃₁₃ test to analyze DNA samples from more than 2,100 people diagnosed with DCIS and nearly 200 people diagnosed with LCIS who were part of two studies, known as the ICICLE and GLACIER studies.

Among those with DCIS, people with PRS₃₁₃ scores in the highest 25% were more than twice as likely to develop invasive cancer in the opposite breast compared to people with PRS₃₁₃ scores in the lowest 25%. There was no link between a higher PRS₃₁₃ score and developing invasive disease in the same breast.

In people with LCIS, a higher PRS₃₁₃ score was linked to more than double the risk of developing invasive disease in the same breast. A higher PRS₃₁₃ score didn't increase the risk of invasive disease in the opposite breast.

A person's family history also seemed to play a role in the risk of invasive disease after LCIS. People with both a family history of breast cancer and higher PRS₃₁₃ scores had more than triple the risk of invasive disease in the same breast after LCIS compared to people with a family history and lower PRS₃₁₃ scores. The risk quadrupled when researchers excluded people who had mastectomy and radiation therapy for LCIS from the analysis because these treatments reduce the risk of developing invasive disease later. Still, the number of people with LCIS who had mastectomy and radiation was very small, so these results should be interpreted with caution.

"This research provides strong evidence that PRS₃₁₃ can serve as a valuable predictor of future breast cancer events in women with in situ breast cancer, specifically [cancer in the opposite breast] after DCIS and [cancer in the same breast] after LCIS," the researchers concluded.

"Our initial results are very promising," Jasmine Timbres, first author and clinical information analyst at King's College London, said in a statement. "The results of this study show that the genetic risk score could be useful in [predicting who will go on to develop invasive cancer], meaning that treatments could be more personalized, rather than giving everyone the same treatment approach."