SAN FRANCISCO – Molecular subtyping of breast tumors with an 80-gene panel appears to be a better predictor of response or resistance to neoadjuvant therapy than do standard techniques and may identify patients who could benefit from dual HER-2 blockade, according to data presented by investigators.
In a prospective trial, molecular subtyping with the BluePrint 80-gene profile (Agendia) classified 23% of tumors into a different subgroup than did immunohistochemical staining and fluorescent in-situ hybridization (IHC/FISH) and identified a sub-group of so-called triple-positive tumors (positive for the HER-2, estrogen and progresterone receptors) with luminal features.
Dr. Peter Beitsch
“This triple-positive, 80-gene luminal subtype, is relatively resistant to neoadjuvant chemotherapy with trastuzumab [Herceptin] alone. Pertuzumab [Perjeta] overcame resistance to chemotherapy with trastuzumab in a substantial proportion of the triple-positive 80-gene luminal subtype,” said Dr. Peter Beitsch from the Dallas (Texas) Surgical group, in an oral session at a breast cancer meeting sponsored jointly by the American Society of Clinical Oncology, American Society of Radiation Oncology, and Society of Surgical Oncology. The data were also presented in a poster session.
“This trial was about 4 years long, and over the course of the trial, we saw the triple-positive luminal group get more and more pathologically complete responses, and we finally figured it out. What had happened was that about midway through the trial, pertuzumab became the standard,” Dr. Beitsch said in an interview.
The investigators used the gene profile to subtype tumors from 889 women from the ages of 18 years through 90 years with histologically proven breast cancer who had not yet undergone excision biopsy, axillary dissection, or breast cancer therapy.
Patients were treated with neoadjuvant therapy at the discretion of their oncologists, provided that the regimen was peer-reviewed or accepted by the National Comprehensive Cancer Network.
Dr. William Gradishar
As noted before, 23% of tumors were classified into a different subgroup than those assigned by ICH/FISH.
The gene profile re-classified 82 of 167 patients (49%) who were classified by IHC/FISH as triple-positive as BluePrint luminal instead. In this subgroup of patients, the pathologic complete response (pCR) rate was 17%. In contrast, of the 72 patients (43%) classified as triple-positive by IHC/FISH and as BluePrint HER2 by the gene profile, the pCR rate was 59%, a statistically significantly better response rate than patients with the BluePrint luminal designation (P = .0001).
The remaining 13 patients (8%) were reclassified as BluePrint basal.
“We looked at the patients who were triple-positive, luminal subtype, and they had an absymal [chance of achieving pathologic complete response] with just trastuzumab and chemotherapy, but, you add in pertuzumab, and it goes up 10-fold,” Dr. Beitsch said.
“Using this particular molecular platform may indeed allow us to better categorize patients over what ICH alone is able to do,” said Dr. William J. Gradishar from the Lurie Comprehensive Cancer Center at Northwestern University in Chicago, Illinois, the invited discussant.
He noted that therapy guided by intrinsic subtype could be even more potent and might result in superior outcomes.
“Of course, in the end, the only way we’re going to be able to definitively address this is by rigorously looking at this in a prospective manner,” he said.