Trastuzumab Plus Chemo Behaves as a Vaccine in HER2-Positive Metastatic Breast Cancer

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CHICAGO ― In HER2-positive metastatic breast cancer, the combination of trastuzumab and chemotherapy may behave as a vaccine by inducing adaptive immunity to antigens released by the tumor, allowing patients to respond immunologically, a study reported at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Alternatively, combination therapy could be acting as a general immune stimulant boosting preexistent immunity,” reported Raphael Clynes, MD, PhD, of Columbia University, New York, NY, on behalf of the North Central Cancer Treatment Group (NCCTG).

The study sought to determine whether the immunity induced was “due to complexing of non–tumor-derived HER2 or antigen derived from the tumor site,” Dr. Clynes noted. “We addressed this question by assessing whether the combination therapy induced epitope spreading to tumor antigens other than HER2.”

They obtained pre- and post-treatment sera from 56 women with HER2-positive metastatic breast cancer enrolled in two NCCTG clinical trials, N0337 and 98-32-52, and using enzyme-linked immunosorbent assays, examined immunoglobulin G (IgG) antibodies to HER2 intracellular domain (HER2), p53, IGFBP2, carcinoembryonic antigen (CEA), and tetanus toxoid. Also examined were sera from an age-matched group of controls (n=56) and patients treated in the adjuvant setting (n=12).

Prior to treatment, patients with HER2-positive metastatic breast cancer had higher IgG levels (≥ 2-fold) to p53 and HER2 but not CEA, IGFBP2, or tetanus toxoid compared with the controls. Similarly, patients treated in the adjuvant setting had elevated IgG levels to multiple tumor antigens prior to therapy, relative to controls.

Post-treatment, “levels of IgG to IGFBP2, HER2, and p53 increased in 81% of metastatic patients, with mean increases of 3.2 (±0.6 sem), 6.2 (±2.7), and 2.7 (±0.7) fold, respectively (P<0.05),” they noted. “Levels of antibodies to tetanus toxoid and CEA were not elevated by treatment.”

They found that in contrast, IgGs “were not significantly increased post-treatment in patients in the adjuvant setting, in keeping with the idea that immunity depends on the presence of high level of tumor antigens, which are reduced after resection of the primary tumor.”

Patients treated in the adjuvant setting had more limited immune responses, reflecting reduced levels of tumor antigen.

“Our data suggest that the induction of adaptive immunity to HER2 in patients with metastatic breast cancer is associated with favorable clinical response to combination trastuzumab and chemotherapy,” they concluded. “The potential for therapeutic vaccinal effects of trastuzumab therapy should be further explored clinically.”

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