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New Prognostic Markers Guide Triple-Negative Breast Cancer Treatment Decisions

December 18, 2019

Triple-negative breast cancer is unique because it lacks estrogen receptors, progesterone receptors and excess HER2 protein – the drivers of other breast cancer subtypes. It is more aggressive and has a poorer prognosis, primarily because there are fewer targeted medicines that treat it. As many as 20 percent of breast cancer cases are triple-negative, underscoring the need for more research that identifies effective therapies.

A team comprising members of the SWOG Cancer Research Network, a cancer clinical trials network funded by the National Cancer Institute, has identified two new markers to predict which triple-negative breast cancer patients may benefit from AC chemotherapy, a combination of doxorubicin and cyclophosphamide. The study findings were published in the Journal of Clinical Oncology.

According to Priyanka Sharma, MD, principal investigator and physician-scientist at The University of Kansas Cancer Center, these tests may help personalize treatment for triple-negative breast cancer.

"This moves us a little closer to basing triple-negative breast cancer treatment on the biology of individual patients," Dr. Sharma said in a news release issued by SWOG. "If you knew, up front, which women would respond well to AC chemotherapy, we could preferentially pick this treatment - and spare them other treatment. With other patients, we would want to investigate different strategies such as immunotherapies or targeted drugs."

Utilizing SWOG’s biospecimen bank, the team gathered previous samples from a previous clinical trial that studied the effectiveness of AC chemotherapy in breast cancer patients. The set was then filtered to include triple-negative breast cancer cases, a total of 425 samples.

Dr. Sharma and her team studied the samples to assess 44-gene DNA Damage Response (DDIR) signature status and stromal tumor-infiltrating lymphocytes (sTILs) density. A positive DDIR status and a high sTILs density indicate the body has a DNA repair deficiency. AC chemotherapy works best in tumors where DNA repair functionality is reduced.

Of the samples tested, 62% were DDIR-positive, and data from the previous clinical trial indicated those patients had better outcomes from the AC chemotherapy. The researchers also found that patients with higher sTIL density had better outcomes from the chemotherapy. Those with a positive DDIR signature and higher sTIL density who were treated for AC chemotherapy were cancer-free longer and lived longer.

“Triple-negative breast cancer is notoriously difficult to treat,” Dr. Sharma said. “Now we have two new ways to predict how a patient with triple-negative breast cancer will respond to treatment.”

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