Genomic Grade Index Is Associated With Response to Chemotherapy in Patients With Breast Cancer

Abstract

A B S T R A C T PurposeThe genomic grade index (GGI) is a 97-gene measure of histological tumor grade. High GGI is associated with decreased relapse-free survival in patients receiving either endocrine or no systemic adjuvant therapy. Herein we examined whether GGI predicts pathologic response to neoadjuvant chemotherapy in patients with HER-2-normal breast cancer. MethodsGene expression data (gene chips) was generated from fine-needle aspiration biopsies (n ϭ 229) prospectively collected before neoadjuvant paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Pathologic response was quantified using the residual cancer burden (RCB) method. The association between the GGI and pathologic response was assessed in univariate and multivariate analyses. The performance of a response predictor combining clinical variables and GGI was evaluated under cross-validation. ResultsEighty-five percent of grade 1 tumors had low GGI, 89% of grade 3 tumors had high GGI, and 63% of grade 2 tumors had low GGI. Among both estrogen receptor (ER)-positive and -negative cancers, high GGI score was associated with pathologic complete response (RCB-0) or minimal residual disease (RCB-1). A multivariate model combining GGI and clinical parameters had an overall accuracy of 71%, compared with 58% for the GGI alone, for prediction of pathologic response. However, high GGI score was also associated with significantly worse distant relapse-free survival in patients with ER-positive cancer (P ϭ .005), and was not associated with survival in patients with ER-negative cancer. ConclusionHigh GGI is associated with increased sensitivity to neoadjuvant paclitaxel plus fluorouracil, adriamycin, and cyclophosphamide chemotherapy in both ER-negative and ER-positive patients, but it remains a predictor of worse survival in ER-positive patients.

Effect of neoadjuvant anthracycline–taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study

“…Luminal Response Score (NLRS) [13,14]. The GGI compared to conventional parameters adds only modest but still independent predictive information.…”

High genomic grade index associated with poor prognosis for lymph node‐negative and estrogen receptor‐positive breast cancers and with good response to chemotherapy

“…These results are essentially consistent with those reported very recently by Liedtke et al, who have shown that high genomic grade index breast cancer tumors are associated with a high pathological CR rate to neoadjuvant chemotherapy consisting of paclitaxel followed by 5-fluorouracil/doxorubicin/cyclophosphamide. 4 All these results taken together indicate that, in the lymph node-negative and ER-positive subset, high genomic grade index tumors show a poor prognosis, but at the same time they are thought to have a relatively higher sensitivity to P-FEC. Therefore, it is speculated that prognosis of patients with such tumors can be improved by addition of adjuvant chemotherapy (P-FEC) to adjuvant hormonal therapy.…”

“…Interestingly, Liedtke et al reported that high genomic grade index tumors showed a worse prognosis than low genomic grade index tumors in the ER-positive subset. 4 Therefore, it is considered that genomic grade index modestly predicts chemosensitivity in patients who receive neoadjuvant chemotherapy, but its impact on prognosis still remains to be clarified.…”

“…Furthermore, it has been reported very recently that high genomic grade index tumors are associated with a better response to neoadjuvant chemotherapy as compared with low genomic grade index tumors. 4 In our study, we therefore also evaluated the relation between genomic grade index and pathological complete response (CR) to neoadjuvant chemotherapy.…”

Neoadjuvant systemic therapy for breast cancer

“…The ability of Genomic Grade Index (GGI) to predict response to neoadjuvant chemotherapy was evaluated in 229 tumor samples collected before neoadjuvant chemotherapy with paclitaxel, fluorouracil, doxorubicin and cyclophosphamide (T/FAC) (Liedtke et al, 2009). In general, pathologic complete response (pCR) is associated with better disease outcome regardless of hormone receptor status (Guarneri et al, 2006).…”