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Trastuzumab-based chemotherapy most effective among HER-2–enriched tumor cancers
Researchers in Spain identified as many as four subgroups of HER-2–positive breast cancer, revealing one subtype to be particularly responsive to chemotherapy.
The retrospective exploratory study assessed the utility of the research-based prediction analysis of microarray 50 (PAM50) subtype predictor in gauging pathologic complete response (pCR) and event-free survival in women enrolled in the Neoadjuvant Herceptin (NOAH) trial.
The researchers performed gene Q8 expression profiling on biopsies from 114 patients with HER-2–positive tumors. Of these patients, 15 were randomly assigned to a regimen of neoadjuvant doxorubicin/paclitaxel followed by cyclophosphamide/methotrexate/fluorouracil, or the same treatment combined with trastuzumab (Herceptin, Genentech) for a year.
The study also included a control group of 42 patients with HER-2–negative tumors treated with the combination of cyclophosphamide/methotrexate/fluorouracil and neoadjuvant doxorubicin/paclitaxel.
The researchers investigated the PAM50 subtypes, the PAM50 proliferation score and the PAM50 risk of relapse score based on subtype.
They found that the four genomic subtypes in breast cancer (luminal A, luminal B, HER-2–enriched and basal-like) also are found in HER-2–positive breast cancer. The PAM50 analysis found that HER-2–enriched tumors demonstrated increased pCR rates after trastuzumab-based chemotherapy compared with luminal A, luminal B, basal-like and normal-like tumors.
“Specifically, we have found that HER-2–positive tumors in the HER-2–enriched subtype have a highly activated HER-2 signaling pathway, thereby making them especially sensitive to anti-HER-2 targeted therapies such as trastuzumab,” Aleix Prat, MD, PhD, principal investigator of Vall d’Hebron Institute of Oncology Translational Genomics Group, said in a press release.
Among patients classified in the group at high risk for relapse based on subtype and proliferation, the OR for pCR with trastuzumab compared with chemotherapy only was 8.469 in all patients (pCR rates of 75% vs. 37.5%) and 13.914 in patients with hormone receptor-negative disease (78.6 vs. 30.8%).
The researchers said they hope the findings will lead to more targeted and customized approaches to HER-2–positive breast cancer, which is currently treated as a single subgroup.
“There is no doubt that gene expression in breast cancer provides us with essential biological information to better determine the diagnosis, treatment, relapse risk and possibilities of survival,” Prat said. “From this moment on, treatment strategies should be based on prior molecular characterization of the tumor.”
Disclosure: The researchers report consultant/advisory board roles with, employment relationships with and ownership interests in Bayer, Genentech, GlaxoSmithKline, Hoffmann-La Roche, Novartis, Roche and other companies.