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

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. 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. The median follow-up duration was 71 months. Maximum standardized uptake value (SUVmax) 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 SUVmax 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. 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.

Chen S ，Ibrahim NK ，Yan Y ，Wong ST ，Wang H ，Wong FC ... -  《-》

Role of (18)F-PET/CT in Predicting Prognosis of Patients With Breast Cancer After Neoadjuvant Chemotherapy.

Breast cancer can be assessed preoperatively and postoperatively using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). We prospectively analyzed the maximum baseline standardized uptake value (SUVmax) derived from FDG PET/CT to predict the outcomes after neoadjuvant chemotherapy (NAC) for breast cancer. We assessed 130 consecutive female patients with primary breast cancer (mean age, 53.9 years) using PET/CT before and after NAC. The SUVmax before (pre-SUVmax) and after (post-SUVmax) NAC and the SUVmax reduction rates (ΔSUVmax) after NAC with sequential anthracyclines and a taxane were assessed to predict the pathologic complete response (pCR) and prognosis. Of the 130 patients, 30 (23.1%) achieved a pCR. The pCR rate of the patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative (TN) breast cancer was 52.8% and 40.0%, respectively. In contrast, only 1.4% of those with estrogen receptor-positive and HER2- cancer achieved a pCR. The post-SUVmax correlated closely with the pCR (area under the curve, 0.700) but not with the pre-SUVmax and ΔSUVmax (area under the curve, 0.414 and 0.589, respectively) in patients with HER2+ and TN breast cancer. The post-SUVmax was associated with the pCR (P = .019), and multivariate analysis selected post-SUVmax as a significant prognostic factor (P = .014). The post-SUVmax correlated significantly with recurrence-free survival and recurrence (P = .026, log-rank test). The SUVmax determined after NAC using FDG PET/CT can predict for the pCR and the prognosis of patients with operable HER2+ and TN breast cancer. In the future, additional chemotherapy will be applied according to the post-SUVmax after standard NAC to achieve a pCR or omit surgery.

Akimoto E ，Kadoya T ，Kajitani K ，Emi A ，Shigematsu H ，Ohara M ，Masumoto N ，Okada M ... -  《-》

Early assessment with 18F-fluorodeoxyglucose positron emission tomography/computed tomography can help predict the outcome of neoadjuvant chemotherapy in triple negative breast cancer.

In patients with triple-negative breast cancer (TNBC), pathology complete response (pCR) to neoadjuvant chemotherapy (NAC) is associated with improved prognosis. This prospective study was designed and powered to investigate the ability of interim (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT) to predict pathology outcomes to NAC early during treatment. Consecutive TNBC women underwent (18)FDG-PET/CT at baseline and after two courses of NAC. Maximum standardised uptake value (SUV(max)) in the primary tumour and lymph nodes at each examination and the evolution (ΔSUV(max)) between the two scans were measured. NAC was continued irrespective of PET results. Correlations between PET parameters and pathology response, and between PET parameters and event-free survival (EFS), were examined. Fifty patients without distant metastases were enroled. At completion of NAC, surgery showed pCR in 19 patients, while 31 had residual tumour. Mean follow-up was 30.3 months. Thirteen patients, all with residual tumour, experienced relapse. Of all assessed clinical, biological and PET parameters, ΔSUV(max) in the primary tumour was the most predictive of pathology results (p<0.0001; Mann-Whitney-U test) and EFS (p=0.02; log rank test). A threshold of 42% decrease in SUV was identified because it offered the best accuracy in predicting EFS. There were 32 metabolic responders (⩾ 42% decrease in SUV(max)) and 18 non-responders. Within responders, the pCR rate was 59% and the 3-year EFS 77.5%. In non-responders, the pCR rate was 0% and the 3-year EFS 47.1%. Interim (18)FDG can early predict the inefficacy of NAC in TNBC patients. It shows promise as a potential contributory biomarker in these patients.

Groheux D ，Hindié E ，Giacchetti S ，Hamy AS ，Berger F ，Merlet P ，de Roquancourt A ，de Cremoux P ，Marty M ，Hatt M ，Espié M ... -  《-》

FDG PET/CT during neoadjuvant chemotherapy may predict response in ER-positive/HER2-negative and triple negative, but not in HER2-positive breast cancer.

Response monitoring with MRI during neoadjuvant chemotherapy (NAC) in breast cancer is promising, but knowledge of breast cancer subtype is essential. The aim of the present study was to evaluate the relevance of breast cancer subtypes for monitoring of therapy response during NAC with 18F-FDG PET/CT. Evaluation included 98 women with stages II and III breast cancer. PET/CTs were performed before and after six or eight weeks of NAC. FDG uptake was quantified using maximum standardized uptake values (SUVmax). Tumors were divided into three subtypes: HER2-positive, ER-positive/HER2-negative, and triple negative. Tumor response at surgery was assessed dichotomously (presence or absence of residual disease) and ordinally (breast response index, representing relative change in tumor stage). Multivariate regression and receiver operating characteristic (ROC) analyses were employed to determine associations with pathological response. A (near) complete pathological response was seen in 19 (76%) of 25 HER2-positive, 7 (16%) of 45 ER-positive/HER2-negative, and 20 (71%) of 28 triple negative tumors. Multivariate regression of pathological response indicated a significant interaction between change in FDG uptake and breast cancer subtype. The area under the ROC curve was 0.35 (0.12-0.64) for HER2-positive, 0.90 (0.76-1.00) for ER-positive/HER2-negative, and 0.96 (0.86-1.00) for triple negative tumors. We found no association between age, stage, histology, or baseline SUVmax and pathological response. Response monitoring with PET/CT during NAC in breast cancer seems feasible, but is dependent on the breast cancer subtype. PET/CT may predict response in ER-positive/HER2-negative and triple negative tumors, but seems less accurate in HER2-positive tumors.

Koolen BB ，Pengel KE ，Wesseling J ，Vogel WV ，Vrancken Peeters MJ ，Vincent AD ，Gilhuijs KG ，Rodenhuis S ，Rutgers EJ ，Valdés Olmos RA ... -  《-》

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

Patients with triple-negative breast cancer (TNBC) have poor outcome when pathologic complete response (pCR) is not reached after neoadjuvant chemotherapy. Early prediction would be helpful. We evaluated the association between metabolic response after 2 cycles of neoadjuvant chemotherapy, pCR, and outcome in patients receiving 2 different anthracycline-based regimens (conventional and intensified). Of 77 consecutive TNBC patients, 23 received EC-D (4 cycles of epirubicin + cyclophosphamide followed by 4 cycles of docetaxel at conventional doses) and 55 received a dose-intensified, dose-dense concomitant regimen of epirubicin + cyclophosphamide (historically called SIM) for 6 cycles. PET/CT with (18)F-FDG was performed at baseline and after 2 cycles of neoadjuvant chemotherapy. The associations between clinical factors, biologic factors, early metabolic change, pCR, and event-free survival (EFS) were examined (log-rank test). Of the 78 patients, 29 (37%) achieved pCR. The change in SUVmax (∆SUVmax) after 2 cycles was more pronounced in patients who achieved pCR (-72% vs. -42%;P< 0.0001). ∆SUVmax was more pronounced under SIM than under EC-D (-68% vs. -35%, P= 0.009), and there was a trend for a higher pCR rate (44% vs. 22%, P= 0.078). Twenty-two patients relapsed and 10 of them died (median follow-up, 34 mo). pCR was associated with EFS (log-rank, P= 0.001). ∆SUVmax was also significantly associated with EFS both in patients receiving SIM (P= 0.028) and in those receiving EC-D (P= 0.021). The optimal ∆SUVmax for predicting pCR and EFS was, however, specific to the treatment regimen. EFS was not associated with tumor grade (P= 0.98), histologic subtype (P= 0.17), or clinical stage (P= 0.097). Early metabolic change during neoadjuvant chemotherapy can predict pathologic response and EFS in TNBC patients under different chemotherapy regimens. However, the metabolic response varies with the type of chemotherapy.

Groheux D ，Biard L ，Giacchetti S ，Teixeira L ，Hindié E ，Cuvier C ，Vercellino L ，Merlet P ，de Roquancourt A ，de Cremoux P ，Resche-Rigon M ，Espié M ... -  《-》