Potential Biomarker Found for HER2+ Breast Cancer Recurrence

A new study indicates that T-cells that recognize HER2 receptor may be key to developing an immune signature test to identify and monitor HER2-positive breast cancer (HER2-BC) patients at high risk of treatment failure and recurrence.

Recurrence of HER2-BC after treatment may be due to a specific, and possibly cancer-induced, weakness in the patient’s immune system—a weakness that in principle could be corrected with a HER2-targeted vaccine—according to a new study by researchers at the Perelman School of Medicine, University of Pennsylvania (Philadelphia, PA, USA). T-cells from patients whose breast cancer had recently recurred showed far weaker response to the HER2 receptor protein, compared to T-cells from patients whose breast cancer had not recurred over a long period following treatment. The study suggests that patients with HER2-BC—which accounts for roughly 20% of the 260,000 invasive breast cancers diagnosed yearly in the US—might someday undergo immune status monitoring with blood tests before, during, and after treatment, to help gauge the risk of recurrence, and possibly to reduce that risk with therapies that boost anti-HER2 immunity.

“We know that it’s not a fixed immune defect, because we have several clinical trials open where we’re vaccinating people and can restore anti-HER2 responsivity,” said senior author Prof. Brian J. Czerniecki, MD, PhD.

Czerniecki and colleagues have long been investigating the role of the immune system in breast cancer, and the potential of cancer vaccines. Their recent focus has been on the T-helper type 1 (Th1) immune response. In the new study, the team isolated immune cells from 95 women with invasive HER2-BC, and analyzed the cells’ ability to mount a Th1 response against the HER2 growth factor receptor protein. HER2-BC cells overexpress the HER2 receptor, which helps drive their rapid proliferation. The cells from women with recently recurrent cancer that had not yet been re-treated had only about 10% of the anti-HER2 responsivity compared to that seen in women whose HER2-BC had not recurred for at least 2 years following treatment. Across all the patients, the researchers found that patients with the least amount of responsivity had experienced only 47 disease-free months after treatment, on average, compared to 113 disease-free months for the patients in with the most responsivity.

The low anti-HER2 responsivity seen in the women with recurrent cancer was not part of a broader immune suppression. “We detected no other immune deficit – just the deficit in the anti-HER2 response,” said Prof. Czerniecki.

The findings complement those from two studies published earlier by Czerniecki and colleagues. In one, Th1 responsivity against HER2 tended to vary strikingly from high responsivity in cancer-free and early-stage HER2-BC patients, to low responsivity in advanced HER2-BC patients. In the other study, patients whose tumors shrank during standard pre-surgery drug treatment had much stronger anti-HER2 responsivity, compared to patients whose tumors responded less completely to that drug treatment.

How patients lose anti-HER2 responsivity during formation and growth of a HER2-BC tumor is not yet clear. “We’re trying to determine the mechanism, but we already know that we can ‘fill the tank’ with vaccines to restore that specific responsivity to HER2,” said Prof. Czerniecki. In addition, the team hopes to confirm the association between anti-HER2 responsivity and cancer recurrence risk in larger clinical trials that would track patient immune status over time.

The study, by Datta J. et al., was published online December 30, 2015, in the journal JAMA Oncology.

Related Links:
Perelman School of Medicine at the University of Pennsylvania
Penn Medicine / University of Pennsylvania Health System