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

Abstract

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). Methods: Of 77 consecutive TNBC patients, 23 received EC-D (4 cycles of epirubicin 1 cyclophosphamide followed by 4 cycles of docetaxel at conventional doses) and 55 received a dose-intensified, dose-dense concomitant regimen of epirubicin 1 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). Results: Of the 78 patients, 29 (37%) achieved pCR. The change in SUV max (ΔSUV max ) after 2 cycles was more pronounced in patients who achieved pCR (−72% vs. −42%; P , 0.0001). ΔSUV max was more pronounced under SIM than under EC-D (−68% vs. −35%, P 5 0.009), and there was a trend for a higher pCR rate (44% vs. 22%, P 5 0.078). Twenty-two patients relapsed and 10 of them died (median follow-up, 34 mo). pCR was associated with EFS (log-rank, P 5 0.001). ΔSUV max was also significantly associated with EFS both in patients receiving SIM (P 5 0.028) and in those receiving EC-D (P 5 0.021). The optimal ΔSUV max for predicting pCR and EFS was, however, specific to the treatment regimen. EFS was not associated with tumor grade (P 5 0.98), histologic subtype (P 5 0.17), or clinical stage (P 5 0.097). Conclusion: 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.

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

“…First, the sample size was small and the patient population was heterogeneous. Despite the small number, our cohort had representative distribution with subtype distribution and pCR frequency similar to other reports . Second, PET timing was variable.…”

“…In aggressive tumor subtypes (TNBC or HER2+), our findings on the prognostic role of PET parameter confirm and extend on previous reports. Despite contradicting results, the ability of SUV reduction to predict pCR and survival has been investigated in TNBC and HER2+ tumors. However, limited information is available on the relationship between survival and residual FDG uptake during or following NAC in these subtypes.…”

Now Is the Time to Use 18F-FDG PET/CT to Optimize Neoadjuvant Treatment in Triple-Negative Breast Cancer!

“…The current standard NAC in TNBC includes anthracycline-cyclophosmamide (AC) combination followed by taxanes, with dose-dense (dd) regimens suggested as potentially more efficient than standard doses (16). In TNBC patients treated by ddAC, we observed a pCR rate at surgery of 69% in patients predicted to be responders with 18 F-FDG PET/CT (decrease of the tumor SUV max after 2 cycles $ 65%) versus only 8% in predicted nonresponders (DSUV max , 65%) (14). Alternative treatment could be used in nonresponders with the aim to increase the pCR rate.…”

“…Early treatment response assessment could also be of help in the TNBC subgroup. Several reports highlighted the high accuracy of the early change in the SUV max to predict pCR (11,12) and outcome (13,14) in TNBC patients. In another recent study, DSUV max outperformed tumor blood flow (15).…”

A novel therapeutic target for triple negative breast cancer

“…Finding effective treatment targets for TNBC has proven difficult so far. TNBCs are reported to respond to neo-adjuvant chemotherapy, but overall, survival in patients with such tumors is still poor [2]. Next-generation sequencing of TNBC has suggested that actionable mutations occur in only a small subset of these cancers and do not completely predict survival [3].…”