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Trastuzumab showed moderate benefit in HER-2–negative breast cancer
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Predictive models indicated that patients with HER-2–negative breast cancer receive a moderate benefit from trastuzumab, according to study results.
Researchers evaluated tumor blocks from 1,579 patients enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 to create a predictive model for degree of benefit from adjuvant trastuzumab (Herceptin, Genentech).
The patients were assigned to the discovery cohort (n=588) or the confirmation cohort (n=991).
Researchers used the nCounter assay (NanoString Technologies) to profile 462 genes of patients in the discovery cohort.
The genes selected for model building had expression levels that were correlated with ESR1 or ERBB2 mRNA.
ERBB2, c17orf37 and GRB7 — associated with HER-2 — and ESR1, NAT1, GATA3, CA12and IGF1R — associated with ER — were the final genes selected for model building.
The benefit groups created from the models included no benefit from trastuzumab (HR=1.56), large benefit (HR=0.27) and moderate benefit (HR=0.56).
Researchers then applied this model to the patients in the confirmation cohort.
One hundred patients were classified as having no benefit (HR=1.58; 95% CI, 0.67-3.69) from trastuzumab, 449 had moderate benefit (HR=0.6; 95% CI, 0.41-0.89) and 442 had large benefit (HR=0.28; 95% CI, 0.2-0.41).
Among 72 patients with HER-2–negative breast cancer in the discovery cohort, 66 were in the moderate benefit group. Among 107 patients with HER-2–negative breast cancer in the confirmation cohort, 101 were in the moderate benefit group.
The model also identified about 10% of HER-2–positive patients who may not benefit from adjuvant trastuzumab.
“Our data support the hypothesis based on central HER-2 testing results from B-31 that HER-2–negative patients may benefit from adjuvant trastuzumab,” the researchers wrote. “Because HER-2–negative patients belong to [the moderate benefit group, an approximate] 40% reduction in recurrences is expected from the addition of trastuzumab to adjuvant chemotherapy with minor side effects.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopJame Abraham, MD
This is a very interesting study by researchers from the NSABP group. They used tumor blocks from the NSABP B-31 trial to identify eight predictive genes associated with HER-2. Then, using multiplexed gene expression profiling, they were able to develop a predictive algorithm for degree of benefit from trastuzumab. There are two clinically relevant findings from this study. First, about 10% of HER-2–positive patients may not benefit from trastuzumab in adjuvant setting. Second, the majority of HER-2–negative patients by central testing actually fell into a moderate benefit group rather than the no benefit group. Further validation of these findings will have tremendous implications for patient care. It is important to identify the reasons for lack of response in the subset of HER-2–positive patients, and it is important to find out which subset of HER-2–negative patients will benefit from trastuzumab. The NSABP B-47 trial will be an important step in that direction.
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