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Nguyen 07-31-2019 05:35 PM

Association between HER2 positivity by HER2/CEP17 ratio
I was rereading my wife's pathology report today and saw the Her2/Cep17 ratio. Too late for us, but might be of help to some.



Association between HER2 positivity by HER2/CEP17 ratio and response to neoadjuvant HER2 targeted therapy.
Katherine Cynthia Rappazzo, Heidi Chen, Tarah Jean Ballinger, Vandana Gupta Abramson
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Abstract Disclosures



Background: Human epidermal growth factor receptor gene 2 (HER2) amplification status in breast cancers provides prognostic information and predicts response to HER2 targeted therapies. Breast cancers undergo HER2 testing by immunohistochemistry (IHC) or florescent in situ hybridization (FISH), with a positive result by dual-probe FISH if the HER2/CEP17 ratio is ≥ 2.0. Patients who are positive for HER2 amplification respond well to HER2 targeted therapies, but no correlation has been made between the quantitative level of HER/CEP17 ratio and tumor response. We aimed to determine whether increasing quantitative levels of HER2/CEP17 ratio lead to increasing rates of pathologic response to neoadjuvant HER2 targeted therapy.

Methods: Patients (n = 125) with locally advanced HER2+ breast cancer who received neoadjuvant HER2 targeted therapies including trastuzumab, pertuzumab, ado-trastuzumab, and lapatinib without cytotoxic chemotherapy were studied retrospectively. The HER2/CEP17 ratio at diagnosis was correlated to pathological complete response (pCR), residual tumor < 0.5cm (pCR0.5), and residual tumor < 1cm (pCR1) and adjusted for ER status.

Results: Data from 125 patients were analyzed. Using logistic regression, there was a statistically significant nonlinear association between HER2/CEP17 ratio and pCR ( p < 0.01). Increasing HER2/CEP17 ratio positively correlated with pCR from HER2/CEP17 ratios between 2 and 11. As HER2/CEP17 ratios increased to beyond 11, the curve had a slight downward concavity. The same pattern was seen for HER2/CEP17 ratio correlating with pCR0.5 (p = 0.0055), and pCR1 (p = 0.0126). ER status was not correlated to HER2 ratio using a Wilcoxon rank sum test with continuity correction (p = 0.8505).

Conclusions: Quantitative increases in HER2/CEP17 ratio are positively correlated to degree of pathologic response to neoadjuvant HER2 targeted therapies without cytotoxic chemotherapy for HER2/CEP17 ratios up to 11. Above HER2/CEP17 ratios of 11, response rates remain high, but do not have an additive benefit in response to HER2 targeted therapy.

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