A team of researchers compiling the Molecular Atlas of Ductal Carcinoma in Situ (DCIS) has made major advances in determining whether early breast precancerous lesions will develop into invasive cancers or remain stable.
Analyzing samples from patients who underwent surgery to remove areas of DCIS, the team identified 812 genes associated with cancer progression. Using this gene classifier, they were able to predict the risk of recurrence or progression of cancer cells.
The study, published this week in the journal Cancer cell, was led by E. Shelley Hwang, MD, of Duke Cancer Institute, and Rob West, MD, PhD, of Stanford University Medical Center. Their work is part of the National Cancer Institute-funded Moonshot Initiative’s Human Tumor Atlas Network.
“There has been a long debate about whether DCIS is a cancer or a high-risk disease,” Hwang said. “Because there is no way to make that determination, we currently treat everyone with surgery, radiation, or both.
“DCIS is diagnosed in more than 50,000 women a year, and about a third of those women have a mastectomy, so we’re increasingly concerned that we may be oversaturating many women,” Hwang said. “We need to better understand the biology of DCIS, and that’s what our study was designed to do.”
Hwang, West and colleagues analyzed 774 DCIS samples from 542 patients, an average of 7.4 years after treatment. They identified 812 genes associated with relapse within five years of treatment.
The gene classifier was able to predict both cancer recurrence and invasive progression, with progression appearing to depend on a process that requires interactions between invasive DCIS cells and unique features of the tumor environment.
Most of the DCIS cancers analyzed in the study were found to be at low risk of cancer progression or recurrence, Hwang said, a factor that underscores the need to have an accurate prediction model that can be used during clinic visits to provide care.
“We have made great progress in understanding DCIS, and this work gives us a real path to being able to personalize care by scaling treatment based on the risk of cancer progression,” Hwang said. “The real goal is to reduce treatment-related harm without compromising outcomes, and we’re very excited to be one step closer to achieving that for our DCIS patients.”
In addition to Hwang and West, the study’s authors include principal investigator Carla Malley, Ph.D., of the Arizona State School of Life Sciences, and Graham Colditz, Ph.D., of the Washington University in St. Louis Breast Pre-Cancer Atlas Center, as well as collaborators from 12 other institutions are members of the Translational Breast Cancer Consortium.
The study is part of the National Cancer Institute Human Tumor Atlas Network Consortium, which is part of the National Institutes of Health (R01 CA185138-01, U2C CA-17-035, UO1 CA214183, R01CA193694). Other financial support was from the Department of Defense (BC132057); Breast Cancer Research Foundation (19-074, 19-028, 18-006); PRECISION CRUK Grand Challenge (AEI RYC2019- 026576-I); “la Caixa” Foundation (LCF/PR/PR17/51120011); Lundbeck Foundation (R288-2018-35); Danish Cancer Society (R229-A13616); and Susan G. Komen.