Pharmacodynamics and antitumor activity
multifocal disease, tumors, tumor
BREAST CANCER, RESIDUAL CANCER, TUMOR, RESIDUAL TUMOR, TUMORS, INFILTRATING, RESIDUAL DISEASE, PATHOLOGY, STROMAL TUMOR
All patients underwent definitive surgery with curative intent. One patient with a basal-like intrinsic molecular subtype (see below) progressed clinically and radiographically and she transitioned to preoperative chemotherapy. All patients had residual disease on surgical pathology; pCR was achieved in one of two sites in a patient with multifocal disease. To capture treatment effect, we also assessed pathologic response by means of Residual Cancer Burden (RCB) scoring [Antitumor activity. To characterize gene expression changes induced by the investigational therapy, we performed genomic analyses on a NanoString nCounter platform (Breast Cancer 360 panel) of paired macrodissected tumor samples obtained at the time of diagnosis and on cycle 2 day 1. We successfully tested and analyzed 10 paired samples; one on-treatment sample did not pass quality control.By Correlative Studies and Relapse-free Survival. The presence of non-luminal intrinsic subtypes in the immunophenotypically HR+/Her2− subgroup has been well recognized [CD105 (endoglin) was predominantly expressed in the vessels (Fig. Semiquantitative assessment of the residual tumors for stromal tumor infiltrating lymphocytes (TILs) was consistent with no or minimal levels of TILs in 15/17 tumors (patient who progressed and transitioned to chemotherapy excluded; 88.2%; 95% CI 63.6–98.5) [The protocol left postoperative treatment decisions at the discretion of the treating physicians. None of 4 patients whose tumors downstaged with the investigational therapy received adjuvant chemotherapy; 4/7 (57%) and 2/3 (66%) patients whose tumors did not change stage or were upstaged, respectively, received adjuvant chemotherapy. With a median follow up of 45.6 months after surgery for curative intent (53.4 months from cycle 1 day 1), 3 patients relapsed (Fig. 