WINDBER, PA — Every year, 60,000 women in the United States receive a diagnosis of ductal carcinoma in situ (DCIS), a noninvasive form of breast cancer. Accounting for one in five breast cancer diagnoses, DCIS has increased with the adoption of routine mammography, but it is far more than just an artifact of imaging.
DCIS, also called stage 0 breast cancer, intraepithelial neoplasia or intraductal carcinoma, occupies an unusual territory in the cancer environment. While the cancerous epithelial cells of the breast’s milk ducts have not spread beyond the breast, DCIS, in some cases, can recur and spread into the surrounding breast tissue.
DCIS patients with germline pathogenic variants (PV) in genes that predispose to cancer have the highest risk for breast cancer recurrence, but most women with DCIS do not meet the criteria recommended by the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing to find out whether they have high-risk variants. As a result, physicians and patients lack critical information for determining whether a risk-reducing surgery such as bilateral mastectomy or breast-conserving surgery, or lumpectomy is more appropriate.
Researchers led by Rachel Ellsworth, PhD, director of Translational Breast Research at the Henry M. Jackson Foundation for the Advancement of Military Medicine and Murtha Cancer Center Research Program, Uniformed Services University of the Health Sciences, conducted a study to determine how often women with DCIS have pathogenic variants.1
The team identified all women diagnosed with unilateral DCIS between 2001 and 2020 who were enrolled in the Clinical Breast Care Project and pulled information on demographics, genetic test results, and surgical procedures from the database. Based on the NCCN criteria, women were assigned test eligibility. Panel genetic testing was performed using DNA from 465 patients in the research setting.
Among all 465 women with DCIS, 39 or 8.1% had pathogenic variants. Of those eligible for testing using NCCN criteria, 35.1% chose to proceed with genetic testing, although 13.2% only did so following a second breast cancer occurrence.
Pathogenic variants were detected in more than half of the women with these high-risk mutations (20 out of 39) only in the research setting, and more than one-quarter (28.2%) of the women with PV were not eligible for genetic testing based on NCCN criteria.
The failure to identify PV in women with DCIS likely affected the treatment decisions made by physicians and their patients. Among the 419 women who did not proceed to bilateral mastectomy, those with PV had three times the risk of breast cancer recurrence compared to those without pathogenic variants, 33.3% vs. 11.6%.
“Genetic testing is suboptimal in women with a primary diagnosis of DCIS,” Ellsworth and her colleagues said. “Twenty percent of women with PV, who may have benefited from [bilateral mastectomy], did not undergo genetic testing at the time of diagnosis and recurred.” Consequently, they recommended that all women with DCIS should receive genetic testing as a standard component of care.
- Ellsworth RE, Turza L, Lovejoy LA, Turner CE, Shriver CD. Impact of germline mutations on surgical decision-making in women with DCIS. J Clin Oncol. 2022; 40 (suppl 16; abstr 10576).
