Abstract P1-08-03: Prediction of response to neoadjuvant chemotherapy in estrogen receptor positive (ER+) breast cancer by IHC4 or Ki67 alone

Abstract

Abstract Aims To determine whether IHC4 score assessed on pre-treatment core biopsies (i) predicts response to neoadjuvant chemotherapy in ER positive breast cancer; (ii) provides more predictive information than Ki67 alone. Background The IHC4 score, a composite of ER, PgR, Ki67 and HER2 scores provides prognostic information similar to the OncotypeDx 21-gene Recurrence Score in ER + primary breast cancer treated with endocrine therapy but it is unknown if it also predicts response to chemotherapy. Pathological complete response (pCR) following neoadjuvant chemotherapy is established as an intermediate marker of long-term outcome. More recently the residual cancer burden (RCB) has also been shown to be prognostic, with those patients with minimal residual disease (RCB1) following neoadjuvant chemotherapy having a similar prognosis to those with a pCR (RCB0). The development of these intermediate markers provides an opportunity to study the predictive role of pre-treatment biomarkers for benefit to a particular therapy. Methods A total of 114 ER+ patients treated with neoadjuvant chemotherapy at the Royal Marsden Hospital between 2002-2010 were included in the study. An assessment of the excision specimen was made for residual disease. IHC4 was determined on pre-treatment core biopsies, blinded to clinical outcome, by immunohistochemistry using quantitative scoring of ER (H-score), PgR (%) and Ki67 (%). Determination of HER2 status was made by immunohistochemistry and fluorescent in situ hybridization for 2+ cases. IHC4 and Ki67 scores were tested for their association with pCR rate and RCB score. Results 19 (17%) of the 114 patients and 9 (10%) of the 90 HER2-ve cases showed a pCR. Ki67 and the IHC4 score were both positively associated with achievement of pCR (P<10-7 and P<10-9 respectively) and RCB0+1 (P<10-5 and P<10-9 respectively) following neoadjuvant chemotherapy in all patients. Rates of RCB0+1 were 45% and 66% in the highest quartiles of Ki67 and IHC4 scores respectively. In ER + HER2-ve cases pCR and RCB0+ 1 rates were 35% and 39%, respectively in the highest quartile of IHC4 and 30% and 39%, respectively in the highest quartile of Ki67 (Table 1). There were no pCRs in the lower half of IHC4 or Ki67 scores. Conclusions A high IHC4 was strongly predictive of a pCR or near pCR in ER + breast cancers following neoadjuvant chemotherapy. Ki67 was an important component of this predictive ability. Response according to IHC4 and Ki67 quartile in HER2 negative, ER+ breast cancersIntermediate endpointpCRpCRRCB0+RCB1RCB0+RCB1ScoreIHC4Ki67IHC4Ki67Quartile 10% (0/22)0% (0/22)5% (1/22)9% (2/22)Quartile 20% (0/23)0% (0/23)4% (1/23)0% (0/23)Quartile 35%(1/22)9% (2/23)9% (2/22)9% (2/23)Quartile 435% (8/23)30% (7/23)39% (9/23)39% (9/23) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-03.