Impact of Neoadjuvant Chemotherapy on Breast Cancer Subtype: Does Subtype Change and, if so, How?

Lucy M. De La Cruz, Michael O. Harhay, Paul Zhang, Stacy Ugras

Breast cancer subtype, as determined by the expression of estrogen receptor (ER) and progesterone receptor (PR), together defined as hormone receptor (HR) status, and the HER2/neu receptor (HER2), is important in predicting prognosis and guiding therapy. Knowledge regarding how tumors evolve during treatment and whether subtype is influenced by neoadjuvant chemotherapy (nCT) is limited. The purpose of this study was to compare the HR and HER2 status between core needle biopsy and residual tumor after surgery of breast cancer patients treated with nCT and to evaluate the impact of status change on therapeutic management. After institutional review board approval, we performed a retrospective review of all patients with a diagnosis of breast cancer who received nCT and had their initial biopsy and post-nCT surgical specimens evaluated for tumor subtype between January 2009 and December 2014 at our institution. Immunohistochemistry (IHC) of ER, PR, HER2, and fluorescence in situ hybridization for HER2 expression, when indicated, was performed using identical technique and measured by a single pathologist who specializes in breast pathology. Pre- and post-nCT subtype was cross-tabulated to assess change. Standard diagnostic metrics were computed. Fifty-two patients with 54 cancers were identified to have their initial biopsy and post-nCT surgical specimens evaluated for tumor subtype in identical fashion. There was a complete pathologic response after nCT in 23 cancers (42.6%). Residual disease was noted in 31 cancers (57.4%). Five of these (16.1%) had a change in tumor subtype, of which four changes were based on IHC. HR status changed from positive to negative in two cases and from negative to positive in one case. HER2 status changed from positive to negative in one case and from negative to positive in one case. Subtype change led to treatment change in all five cases, with either the addition or discontinuation of adjuvant therapies. Patients with breast cancer may experience alterations in their tumor subtype after nCT. At our institution, this led to a change in adjuvant treatment in 100% of such patients. This implies that retesting receptor status of residual tumors after nCT should be routinely performed to tailor adjuvant therapy after nCT.