Prediction of pathologic complete response to sequential paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide therapy using a 70-gene classifier for breast cancers

Abstract

BACKGROUND. Sequential administration of paclitaxel plus combined fluorouracil, epirubicin, and cyclophosphamide (P-FEC) is 1 of the most common neoadjuvant chemotherapies for patients with primary breast cancer and produces pathologic complete response (pCR) rates of 20% to 30%. However, a predictor of pCR to this chemotherapy has yet to be developed. The authors developed such a predictor by using a proprietary DNA microarray for gene expression analysis of breast tumor tissues. METHODS. Tumor samples were obtained from 84 patients with breast cancer by core-needle biopsy before the patients received P-FEC, and the gene expression profile was analyzed in those samples to construct a classifier for predicting pCR to P-FEC. In addition, the authors analyzed the gene expression profile of tumor tissues that were obtained at surgery from 105 patients with lymph node-negative and estrogen receptor-positive breast cancer who received adjuvant hormone therapy alone to determine the prognostic significance of the classifier. RESULTS. The 70-gene classifier for predicting pCR to P-FEC was constructed by using the training set (n ¼ 50) and subsequently was validated successfully in the validation set (n ¼ 34), revealing high sensitivity (88%; 95% confidence interval [CI], 47%-100%) and high negative predictive value (93%; 95% CI, 68%-100%). Specificity and positive predictive value were 54% (95% CI, 33%-73%) and 37% (95% CI, 16%-62%), respectively. Among the various parameters (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 status, etc), the 70-gene classifier had the strongest association with pCR (P ¼ .015). In an additional study, genetically assumed complete responders were associated significantly (P ¼ .047) with a poor prognosis. CONCLUSIONS. The 70-gene classifier that was constructed for predicting pCR to P-FEC for breast tumors was successful, with high sensitivity and high negative predictive value. The classifier also appeared to be useful for predicting the prognosis of patients with lymph node-negative and estrogen receptor-positive breast cancer who receive adjuvant hormone therapy alone. Cancer 2011;117:3682-

Functional Heterogeneity within the CD44 High Human Breast Cancer Stem Cell-Like Compartment Reveals a Gene Signature Predictive of Distant Metastasis

“…Thus, the prognostic profiles should be subtype specific. The specificity of 97% is substantially higher than generally reported (54,55) and demonstrates that this signature is a highly accurate indication of those patients with triple-negative breast cancer who will not experience recurrence. This assay may, when further developed, be clinically useful in avoiding the deleterious side effects of overtreatment.…”

The impact of Oncotype DX® recurrence score of paraffin-embedded core biopsy tissues in predicting response to neoadjuvant chemotherapy in women with breast cancer

“…In contrast, Gianni et al determined that Recurrence Score did, in fact, predict for pCR [7]. A finding common to many studies is the ability of lower ER expression by RT-PCR to predict tumor volume reduction and/or pCR [7,8,16].…”

“…Literature on the topic varies according to the assay used. While some support the use of assays in this capacity [2,7,8,14,16,22,24], others question their validity in predicting response to NCT [20]. Few studies concentrate only on ER+ patients and the ability to predict NCT response in this subset [7,14].…”

Biomarker Analysis of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early-Stage Breast Cancer

“…Pathologic complete response (pCR) after neoadjuvant therapy is associated with favorable disease-free survival and overall survival (11)(12)(13) and is thus a valid endpoint for correlation with biomarker expression. Indeed, various gene expression profiles have been shown to correlate with pCR after neoadjuvant chemotherapy regimens in patients with breast cancer (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”