Breast cancer, artwork
Credit: ROGER HARRIS/ Getty Images

A team of researchers mapping a molecular atlas for ductal carcinoma in situ (DCIS) has made what they describe as “a major advance” toward distinguishing whether early pre-cancers in the breast will develop into invasive cancers or remain stable.

Analyzing samples from patients who had undergone surgery to remove DCIS, the team identified 812 genes associated with cancer progression over the patient’s next five years of life. Using their gene classifier, they were able to predict the risk of cancer progressing. They found that pathways associated with recurrence include proliferation, immune response, and metabolism.

The study, which published this week in Cancer Cell, was led by E. Shelley Hwang, MD, of the Duke Cancer Institute, and Rob West, MD, PhD, of the Stanford University Medical Center. Their work is part of the Human Tumor Atlas Network under the Moonshot Initiative funded by the National Cancer Institute.

“There has been a long-standing debate over whether DCIS is cancer or a high-risk condition,” Hwang said. “In the absence of a way to make that determination, we currently treat everyone with surgery, radiation, or both.”

DCIS is the most common precursor of invasive breast cancer, but it is unclear why it sometimes leads to cancer and sometimes not. The adoption of screening mammography led to an epidemic of diagnoses DCIS because it is rarely clinically palpable or symptomatic. So, the condition was seldom diagnosed before the advent of modern mammography. However, by 2009 DCIS accounted for about 20%–25% of all newly diagnosed cases of breast cancer in the United States and from 17% to 34% of mammography-detected cases.

“DCIS is diagnosed in more than 50,000 women a year, and about a third of those women have a mastectomy, so we are increasingly concerned that we might be overtreating many women,” Hwang added. “We need to understand the biology of DCIS better, and that’s what our research has been designed to do.”

Hwang, West, and colleagues analyzed 774 DCIS samples from 542 patients who were about seven years post-treatment. The team identified 812 genes associated with cancer recurrence.

The gene classifier was able to predict both recurrence and invasive progression of cancer. The team found that progression was dependent on interactions between invasive DCIS cells and specific features of the tumor environment.

Hwang said most of the DCIS cancers analyzed in the study were identified to be at low risk for cancer progression or recurrence, which underscores the need to have an accurate predictive test to guide care.

“We’ve made great progress in our understanding of DCIS, and this work gives us a real path forward to being able to personalize care by scaling treatments to the risk of cancer progression. The real goal is diminishing treatment-related harms without compromising outcomes, and we are excited to be getting closer to achieving this for our patients with DCIS,” says Hwang.

New technologies are helping other researchers determine how normal tissues become cancerous. A team at Oxford University and KTH Royal Institute of Technology recently used spatial genomics to examine the transition from benign to malignant tissue.

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