“While the sample size and power are limited, these results suggest that a higher HER2 FISH ratio at baseline core biopsy may be a potential biomarker to select patients for neoadjuvant dual anti-HER2 therapy without chemotherapy."
The HER2/CEP17 fluorescence in situ hybridization (FISH) ratio was associated with a pathologic complete response (pCR) with the use of dual anti-HER2 therapy in patients with HER2-positive breast cancer without the use of chemotherapy, suggesting that FISH may be a predictive biomarker of anti-HER2 response, according to the CLO20-042 study.
The median HER2 FISH ratio values were 10.3 (IQ range, 8.1-13.1) in those who achieved a pCR (n = 29) versus 5.9 (IQ range, 3.5-12.8) in those who did not achieve a pCR (n = 27; P =.04). Among patients who achieved a pCR in the upper versus lower quartile of HER2 FISH ratio, the unadjusted odds ratio was 2.28 (95% CI, 0.96-5.42), and the multivariate odds ratio when adjusted for treatment regimen or estrogen receptor (ER) status was 1.40 (95% CI, 0.0-32.51).
“While the sample size and power are limited, these results suggest that a higher HER2 FISH ratio at baseline core biopsy may be a potential biomarker to select patients for neoadjuvant dual anti-HER2 therapy without chemotherapy,” Eric M. Lander, MD, Vanderbilt University Medical Center, et al, wrote.
The upper quartile of HER2 FISH ratio appeared to be more likely to have a pCR compared with the lower quartile, but the association was not seen when the investigators adjusted for treatment regimen and ER status.
HER2 FISH ratios up to 11 were associated with higher pCR rates with the neoadjuvant HER2-targeted doublets (P =.001), but there was no additional increase in the likelihood of achieving a pCR when HER2 FISH ratios were greater than 11, though it was positively associated with pCR (P =.0150).
The objective of this single-center, cross-sectional study was to assess whether a higher HER2/CEP17 FISH ratio is associated with a pCR in patients with HER2-positive breast cancer who receive neoadjuvant dual HER2-directed targeted therapy without the use of chemotherapy. The study analyzed findings from 3 clinical trials being conducted at the Vanderbilt-Ingram Cancer Center between May 2009 and April 2017. Fifty-six patients with HER2-positive breast cancer were included, and patients had a HER2/CEP17 FISH ratio ≥2 and stage II to III disease.
Patients received either lapatinib (Tykerb) plus trastuzumab (Herceptin) for 12 to 24 weeks, pertuzumab (Perjeta) plus trastuzumab for 6 cycles, or pertuzumab plus trastuzumab emtansine (Kadcyla) for 6 cycles. The study compared patients who achieved a pCR who had no residual disease at the time of surgery and those with no pCR who had residual disease at the time of surgery.
Recent phase 2 and 3 clinical trials have demonstrated that a subgroup of patients with HER2-positive breast cancer achieved a pCR when treated with neoadjuvant dual HER2-targeted therapy with or without chemotherapy, but there is no current optimal approach to identifying this subgroup that may benefit from the de-escalation treatment strategy. The purpose of this study was to determine if higher levels of HER2 amplification is associated with increased rates of response to neoadjuvant dual HER2-targeted therapy.
These findings are encouraging for future evaluation of identifying a subtype in breast cancer with higher HER2 FISH amplification that may be more sensitive to the doublet regimen without chemotherapy.
Lander EM, Huang LC, Hu JR, et al. CLO20-042: The HER2 FISH Ratio is a Predictor of Pathologic Complete Response Among Patients With HER2+ Breast Cancer Receiving Neoadjuvant Anti-HER2 Doublet Therapy Without Chemotherapy. JCCN. 2020 18:3.5. doi:10.6004/jnccn.2019.7511