Peter Beitsch, MD/

Her2 Status in Non Path Complete Responders to Neo-Adj Chemo

Spoiler alert - Her2 status can change after Neo-Adjuvant chemotherapy (NAC).  In this retorspective study from Cedars Sinai, researchers identified 99 patients with HER2 breast cancer ( copy number ratio for all tumors was 6.3 (range, 1.9-20.7) by FISH and 84 (84.8%) tumors were IHC 3+) who underwent NAC.  Only 44 patients achieved pathologic complete response (pCR). Among the 55 remaining patients with residual disease, 35 had sufficient residual tumor with which to evaluate HER2 status. Fourteen of these 35 patients (40%) showed HER2-negative status by FISH and IHC!

Explanation could be tumor heterogeneity (Her2 neg cells not killed by the given chemo) or chemotherapy induced mutagenesis (chemo changes cells into Her2 neg).

We know non pCR is a marker for poor prognosis and at least for a subset of these, this may be an explanation.

Implications of this trial - ALL patients with residual disease should have the tumor's genomics analyzed and targeted adjuvant chemotherapy (in addition to their remaining year of Herceptin).

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