Study Identifies Potential Biomarkers for De-escalating Chemotherapy in HER2-Positive Breast Cancer

Certain human epidermal growth factor receptor 2 (HER2)-positive breast cancer tumors may be more sensitive to treatment with anti-HER2 therapy alone, potentially eliminating the need for additional chemotherapy, according to a study published in the Journal of the National Cancer Institute.

Approximately 1 in 5 patients with breast cancer have high levels of HER2 proteins, according to the study authors. These tumors are typically aggressive in nature with a higher likelihood of metastasis, relapse, and decreased patient survival. According to the findings, identifying patients with HER2-positive breast cancers with high anti-HER2 sensitivity can help de-escalate chemotherapy, reducing the associated toxicity and cost burden.

Since the approval of trastuzumab, outcomes have improved for patients with HER2-positive breast cancer, but treatment with trastuzumab is still combined with chemotherapy. Further, the use of dual anti-HER2 therapy has increased efficacy even more. To determine whether the dual anti-HER2 therapies could eliminate the need for chemotherapy in some patients, the researchers evaluated treatment with lapatinib and trastuzumab in patients with HER2-positive breast cancer in a clinical trial.

The study included 305 patients with early HER2-positive disease and 117 patients with advanced disease. Patients were treated for 12 weeks with the dual anti-HER2 therapy, without chemotherapy. According to the data, 27% of the patients with HER2-positive breast cancer achieved pathologic complete response (pCR), meaning that their tumors disappeared despite a median tumor size of 6 cm. This pCR rate has been confirmed in 2 similar clinical trials, according to the researchers.

Additionally, the study showed that 44% of patients with high HER2 levels and an intact PI3K pathway achieved pCR. Conversely, only 4% of the patients who did not meet these criteria achieved pCR. These findings indicate that both high levels of HER2 and PI3K pathway status may signal how patients will respond to anti-HER2 therapies.

“Our and others’ results showed that not all HER2-positive breast cancers benefit from the de-escalation strategy,” study author Jamunarani Veeraraghavan, PhD, assistant professor at the Lester and Sue Smith Breast Cancer at Baylor College of Medicine, said in a press release. “We needed a plan to differentiate patients who are candidates for de-escalation approach from those needed additional therapy.”

A similar study that analyzed tissue specimens supported the approach of combining 2 biomarkers, HER2 RNA and HER2 signaling, to predict which patients would most likely benefit from dual anti-HER2 therapy.

“Our findings suggest that there is a clinical subtype of breast cancer with high HER2 levels and intact PI3K pathway that is especially sensitive to HER2-targeted therapies without chemotherapy,” study author Rachel Schiff, PhD, associate professor in the Lester and Sue Smith Breast Cancer and in the departments of molecular and cellular biology and medicine at Baylor College of Medicine, said in a press release. “Identifying these tumors by measuring the levels of HER2 gene amplification and PI3K pathway status warrants validation.”

This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer, the researchers concluded.

Reference

Prat A, Pascual T, De Angelis C, et al. HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade. JNCI: Journal of the National Cancer Institute. 2019. https://doi.org/10.1093/jnci/djz042

De-escalating breast cancer therapy; can some patients be spared chemotherapy? [news release] Baylor College of Medicine. https://blogs.bcm.edu/2019/06/25/from-the-labs-de-escalating-breast-cancer-therapy-can-some-patients-be-spared-chemotherapy/. Accessed June 25, 2019.