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High Levels of Immune Cells in Tumors May Identify Breast Cancer Patients Most Likely to Benefit From Trastuzumab

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Key Points

  • For every 10% increase in the levels of tumor-infiltrating lymphocytes there was a 16% increase in the number of patients with HER2-positive tumors who had a pathologic complete response after neoadjuvant trastuzumab and chemotherapy.
  • In a mouse model of HER2-positive breast cancer, combining trastuzumab with PD-1 or PD-L1 inhibitors resulted in greater tumor regression compared with trastuzumab alone.

Women with HER2-positive breast cancer who had the highest levels of immune cells in their tumors gained the most benefit from presurgery treatment with chemotherapy and trastuzumab (Herceptin), according to results presented today at the 2013 San Antonio Breast Cancer Symposium (Abstract S1-05).

“We have previously shown that high levels of tumor-infiltrating lymphocytes are predictive of response to trastuzumab and chemotherapy administered after surgery for early-stage, HER2-positive breast cancer using samples from patients enrolled on the randomized, adjuvant phase III clinical trial called the FinHER study,” said Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia. “Our new data further support the positive relationship between tumor-infiltrating lymphocytes and better outcomes with trastuzumab therapy, this time in a cohort of patients with newly diagnosed HER2-positive breast cancer who received the therapy before surgery," she added.

“It seems, therefore, that levels of tumor-infiltrating lymphocytes may be a good biomarker of response to trastuzumab in primary breast cancer, something that researchers have been looking for with little success for some time,” Dr. Loi noted.

Study Details

Dr. Loi and colleagues evaluated breast tumor samples from 156 patients with operable or locally advanced HER2-positive breast cancer enrolled in the GeparQuattro trial. All participants received chemotherapy and trastuzumab prior to surgery as part of the trial, which showed that women who received the combination were more likely to have a pathologic complete response.

The study revealed that for every 10% increase in the levels of tumor-infiltrating lymphocytes, there was a 16% increase in the number of patients who had a pathologic complete response.

“These data indicate that a patient’s immune system influences outcome and trastuzumab response,” said Dr. Loi. “What we don’t know is why some patients have tumor-infiltrating lymphocytes in their breast tumor at diagnosis and others do not. Currently, we are actively investigating this and trying to understand why there is a positive relationship between tumor-infiltrating lymphocytes and better outcomes with trastuzumab therapy.”

Immune Checkpoint Inhibitors Enhance Response

To address the second point, the researchers analyzed breast tumor samples from patients enrolled in the FinHER study, in which patients with HER2-positive primary breast cancer were randomly assigned to trastuzumab or no trastuzumab with their postsurgery chemotherapy agents. The researchers found evidence that trastuzumab modulates the immune microenvironment, probably by relieving tumor-mediated immunosuppression through multiple immune-related factors, including the programmed death 1 protein (PD-1).

They also found in a mouse model of HER2-positive breast cancer that combining trastuzumab with either an agent that blocks PD-1 or its ligand (PD-L1) resulted in greater tumor regression compared with trastuzumab alone. “Thus, we suggest that adding an inhibitor that can block factors that suppress patient antitumor immune responses to trastuzumab therapy could potentially improve clinical outcomes,” said Dr. Loi.

This study was funded by the European Union Seventh Framework Program RESPONSIFY project, the Breast Cancer Research Foundation, and the Fonds J.C. Heuson. Dr. Loi declared no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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