Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Abstract

Purpose: To investigate the value of the metabolic tumor response assessed with 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC).Experimental Design: Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (DSUV max ) were assessed using FDG-PET.Results: The pCR rate was 42%. High Ki-67 proliferation index (P ¼ 0.016), negative EGFR status (P ¼ 0.042), and high DSUV max (P ¼ 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P ¼ 0.043) and high DSUV max (OR, 7.1; P ¼ 0.014) were independent predictors of pCR. Using a threshold at À50%, tumor DSUV max predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low DSUV max and positive EGFR status could predict non-pCR with an accuracy of 92%.Conclusions: It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials.

18F-FDG PET/CT for the Early Evaluation of Response to Neoadjuvant Treatment in Triple-Negative Breast Cancer: Influence of the Chemotherapy Regimen

“…Two teams found that PET information was helpful in predicting pCR early (14,16), whereas in one other report PET was not predictive (17). Unlike their preliminary findings (15), Humbert et al recently reported that PET has high accuracy in predicting pCR (22). In a multicenter study (mixing TNBC and hormone-positive/HER2-negative breast cancer), PET was also predictive (23).…”

18F-FDG PET–Derived Tumor Blood Flow Changes After 1 Cycle of Neoadjuvant Chemotherapy Predicts Outcome in Triple-Negative Breast Cancer

“…Only women with TNBC were included. This population overlaps those of previous articles published by our team (7,16). Patients with high glycemia (.9 mmol/L), unwilling to undergo the complete PET examinations or with suspected metastasis on baseline 18 F-FDG PET, were excluded.…”

“…Previous studies found that early changes in tumor glucose metabolism, assessed with 18 F-FDG PET/CT after the first or second course of neoadjuvant chemotherapy, can indicate breast cancer response early (5,6), especially in the aggressive TNBC subtype (7,8).…”

Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with 99mTc using a peptide-based cysteine-containing chelator

“…High expression of EGFR in esophageal squamous cell carcinoma is a precondition for successful treatment with the TKI icotinib (22). High EGFR expression is a negative predicting biomarker for response of triple-negative breast cancer to neoadjuvant therapy using anthracyclines and taxanes (23). The main problem is that the expression level of EGFR can vary during the metastasis process, and the discordance rate between biopsy samples from primary NSCLC and metastases might be up to 50% (24).…”