Complete Metabolic Response on Interim 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography to Predict Long-Term Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy

Abstract

Background: This study aims to investigate the prognostic role of complete metabolic response (CMR) on interim ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with breast cancer (BC) receiving neoadjuvant chemotherapy (NAC) according to tumor subtypes and PET timing.

Patients and methods: Eighty-six consecutive patients with stage II/III BC who received PET/CT during or following NAC were included. Time-dependent receiver operating characteristic analysis and Kaplan-Meier analysis were used to determine correlation between metabolic parameters and survival outcomes.

Results: The median follow-up duration was 71 months. Maximum standardized uptake value (SUV_max) on an interim PET/CT independently correlated with survival by multivariate analysis (overall survival [OS]: hazard ratio: 1.139, 95% confidence interval: 1.058-1.226, p = .001). By taking PET timing into account, best association of SUV_max with survival was obtained on PET after two to three cycles of NAC (area under the curve [AUC]: 0.941 at 1 year after initiation of NAC) and PET after four to five (AUC: 0.871 at 4 years), while PET after six to eight cycles of NAC had less prognostic value. CMR was obtained in 62% of patients (23/37) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) BC, in 48% (12/25) triple-negative BC (TNBC), and in 75% (18/24) HER2-positive (HER2+) tumors. Patients with CMR on an early-mid PET had 5-year OS rates of 92% for ER+/HER2- tumors and 80% for TNBC, respectively. Among HER2+ subtype, 89% patients (16/18) with CMR had no relapse.

Conclusion: CMR indicated a significantly better outcome in BC and may serve as a favorable imaging prognosticator. The Oncologist 2017;22:526-534 IMPLICATIONS FOR PRACTICE: This study shows a significantly better outcome for breast cancer (BC) patients who achieved complete metabolic response (CMR) on ¹⁸F-fluorodeoxyglucose emission tomography/computed tomography (PET/CT) during neoadjuvant chemotherapy, especially for hormone receptor-positive tumors and triple negative BC. Moreover, PET/CT performed during an early- or mid-course neoadjuvant therapy is more predictive for long-term survival outcome than a late PET/CT. These findings support that CMR may serve as a favorable imaging prognosticator for BC and has potential for application to daily clinical practice.

Keywords: 18F‐fluorodeoxyglucose positron emission tomography/computed tomography; Breast cancer; Complete metabolic response; Neoadjuvant chemotherapy; Prognosis.

Figure 1.

Kaplan‐Meier survival plots for event‐free survival and overall survival according to complete metabolic response (CMR) definitions: CMR_breast (A, B), CMR_liver (C, D), and CMR_2.5 (E, F). Log‐rank p values are provided.

Figure 2.

Time‐dependent receiver operating characteristic curves as a function of time for maximum standardized uptake values (SUV_max) on positron emission tomography (PET)/computed tomography of different timing to predict event‐free survival (A) and overall survival (B): black dashed line, SUV_max at PET performed after two to three cycles of NAC; black solid line, SUV_max at PET performed after four to five cycles of NAC; grey dashed line, SUV_max at PET_6‐7c; grey solid line, SUV_max at PET_8c. Abbreviations: AUC, area under the curve.

Figure 3.

Kaplan‐Meier survival curves of complete metabolic response with a maximum standardized uptake value of 2.5 according to positron emission tomography (PET) timing: PET_2‐3c (A, B); PET_4‐5c (C, D); PET_6‐7c (E, F); PET_8c (G, H). Log‐rank p values are provided.