Patients with human epidermal growth factor 2 (HER2)-positive breast cancer who undergo induction chemotherapy are likely to convert to HER2-negative disease if residual disease occurs, prompting further systemic therapy, according to research presented at the 2017 ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).
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Neoadjuvant chemotherapy coupled with HER2-directed therapy is considered standard of care for most patients with potentially curable HER2-positive breast cancer. Induction chemotherapy is also associated with a high pathologic complete response rate, but HER2 status of residual disease after induction chemotherapy is not well researched. A common belief is that HER2 status post-neoadjuvant therapy could help inform clinical decisions about systemic therapy.
Nicholas Manguso, MD, Cedars-Sinai Medical Center (Los Angeles, CA), and colleagues examined breast cancer HER2 status before and after neoadjuvant chemotherapy with HER2-directed therapy. Researchers screened an institutional database to sample patients between 2011 and 2015 with stage I-III HER2-positive breast cancer by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) who underwent neoadjuvant chemotherapy with HER2-directed therapy, followed by resection. Clinicopathologic data were collected, as well as changes in HER2 status by FISH and IHC after treatment.
Researchers identified 99 patients (median age, 49; range, 26-85). Prior to treatment initiation, median HER2 and CEP17 copy number ratio for all tumors was 6.3 (range, 1.9-20.7) by FISH and 84 (84.8%) tumors were IHC 3+.
Results of the analysis showed a total of 44 patients achieved pathologic complete response. Among the 55 remaining patients with residual disease, 35 demonstrated sufficient residual tumor with which to evaluate HER2 status. Fourteen of these 35 patients (40%) showed HER2-negative status by FISH and IHC.
Researchers reported that tumors converting from HER2-positive to HER2-negative status had lower pre-treatment median HER2 copy numbers compared with tumors that remained HER2-positive after neoadjuvant chemotherapy. Furthermore, pre-treatment median HER2 and CEP17 copy number ratio was lower among tumors that converted from HER2-positive to HER2-negative status compared with tumors that remained HER2-positive after induction therapy.
Authors of the study concluded that while pathologic complete response rates are high with neoadjuvant chemotherapy and HER2-directed therapy, many patients still exhibit residual disease. Among these patients with residual disease, a significantly high percentage demonstrated status conversion, which may have clinical significance and biological implications for further systemic therapy.—Zachary Bessette
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