Credit: Nicola Tree / Getty Images
Researchers at King’s College London have shown that an existing genetic test for breast cancer can also predict future breast cancer in women with ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS), two conditions characterized by lesions in breast tissue that can progress into breast cancer. Results of the study, published in Cancer Epidemiology, Biomarker & Prevention, show early potential for this genetic test to inform a more personalized approach when treating these patients.
“Predicting who is most likely to develop invasive breast cancer is vital to offering the best possible treatment options for women, as not all with DCIS or LCIS will go on to develop invasive cancer,” said Jasmine Timbres, clinical information analyst at King’s College London and lead author of the study. “In some cases, this could avoid unnecessary invasive treatments altogether, which can take a toll on patients both physically and emotionally. Focusing more on individual risk could improve overall well-being and help reduce the stress that comes with being overtreated.”
DCIS and LCIS are the most common forms of pre-invasive abnormal cells found in the breast. Women diagnosed with these conditions are often treated with preventive surgery, and potentially also radiotherapy, but more than half of them will never develop breast cancer if untreated.
The current study looked at the 313-SNP breast cancer polygenic risk score (PRS313), one of the most commonly used genetic tests for breast cancer prevention. By quantifying 313 single nucleotide polymorphisms (SNPs) known to be associated with breast cancer, this test can predict breast cancer risk in women with no cancer history, especially cases of estrogen receptor-positive (ER+) breast cancer.
While genetic risk factors for these three conditions are similar, no previous studies had shown whether the same factors also influence the risk of developing breast cancer after a DCIS or LCIS diagnosis. To determine if a potential link exists, Timbres and colleagues conducted a retrospective study using data from the ICICLE and GLACIER studies, including a total of 2,169 patients with DCIS and 185 with LCIS, with a median follow up of 11 years.
Results showed that DCIS patients with PRS313 scores in the highest quartile were twice as likely to develop cancer in the breast opposite to where their lesions were located. No association was drawn with developing breast cancer on the same side, most likely due to most patients with this diagnosis undergoing preventive surgery. Further examination determined that only 20% of these recurrence cases were caused by a new primary tumor.
In women with LCIS, higher PRS313 scores were generally associated with a higher risk of developing breast cancer in either breast, but due to the lower number of patients in this category, results were not statistically significant for all patients. However, for women with a family history of breast cancer a high PRS313 score was found to result in a more than threefold increase in breast cancer risk.
“LCIS is not always surgically removed or treated with hormone therapies, as it is considered lower risk than DCIS,” said Timbres. “However, these results indicate that those with a family history may benefit from such additional treatments, which could reduce their risk of further cancer.”
Altogether, these finds indicate that the PRS313 test could play an important role in identifying patients at higher risk of developing breast cancer. In some of these cases, the researchers write in the study, preventive treatment with tamoxifen or an aromatase inhibitor could be effective, especially since most of the tumors developed from these lesions are ER+.
“In my clinical practice, I see many women diagnosed with DCIS or LCIS,” said Elinor J. Sawyer, PhD, professor of clinical oncology at King’s College London and senior author of the study. “Until now, treatment decisions have mostly been based on how the cells look under a microscope…By looking at the full picture, we can give women more accurate information about their personal risk of recurrence. This helps them make more informed choices about their treatment options and what’s right for them.”