Atypical responses to neoadjuvant chemotherapy combined with accelerated partial breast tumor-directed radiotherapy: two cases and considerations for future clinical trials

To, Nhu Hanh; Ouidir, Nabila; Grellier, N.; Assaf, Elias; Gabelle-Flandin, Isabelle; Belkacémi, Yazid; Radosevic‐Robin, Nina

doi:10.5603/rpor.a2022.0112

Cited by 1 publication

(4 citation statements)

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“…The lack of the immunity-boosting effect of RT could have been even greater in the LB than in the TN tumors, as the former typically contained less TIL than the latter [ 15 ]. Interestingly, the only LB tumor that responded by pCR in our NACRT cohort was much richer in TILs than the other tumors of this subtype [ 45 ]. A fraction of TIL-rich BCs, greater in the TN than in the LB subtype, have defects in the DNA repair pathway and are more chemo/radiosensitive.…”

Section: Discussionmentioning

confidence: 99%

“…Most of these tumors had a missense TP53 mutation*. None of the TP53 -mutated tumors had the ID phenotype, whereas among the ID tumors (all non-pCR), only one was TP53 -mutated* [ 45 ]. The association between the missense TP53 mutation and higher TIL levels has been recently described [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…The pRb status, assessed by IHC, was not associated with response in this small cohort of patients. However, the only patient with a null-type TP53 mutation and absent pRb (corresponding to the p53 loss/pRb loss status) among the 21 treated by NACRT was primo-resistant to the treatment and experienced a rapid fatal metastatic relapse [ 25 ]. As in the case of TP53 mutations, an IHC-based assessment of the pRb status seems worth further evaluation in the NACRT trials.…”

Section: Discussionmentioning

confidence: 99%

“…The analysis was carried out on the first 42 patients included in the trial, triggered by the unusual behavior observed in some patients receiving NACRT [ 25 ]. The objective is to identify potential biomarkers predicting pCR after NACRT.…”

Section: Methodsmentioning

confidence: 99%

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Pathologic Response to Neoadjuvant Sequential Chemoradiation Therapy in Locally Advanced Breast Cancer: Preliminary, Translational Results from the French Neo-APBI-01 Trial

Gabelle-Flandin

Luong

et al. 2023

Cancers

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Background: Radiation therapy (RT), a novel approach to boost the anticancer immune response, has been progressively evaluated in the neoadjuvant setting in breast cancer (BC). Purpose: We aimed to evaluate immunity-related indicators of response to neoadjuvant chemoradiation therapy (NACRT) in BC for better treatment personalization. Patients and Methods: We analyzed data of the first 42 patients included in the randomized phase 2 Neo-APBI-01 trial comparing standard neoadjuvant chemotherapy (NACT) and NACRT regimen in locally advanced triple-negative (TN) and luminal B (LB) subtype BC. Clinicopathological parameters, blood counts and the derived parameters, total tumor-infiltrating lymphocytes (TILs) and their subpopulation, as well as TP53 mutation status, were assessed as predictors of response. Results: Twenty-one patients were equally assigned to each group. The pathologic complete response (pCR) was 33% and 38% in the NACT and NACRT groups, respectively, with a dose-response effect. Only one LB tumor reached pCR after NACRT. Numerous parameters associated with response were identified, which differed according to the assigned treatment. In the NACRT group, baseline hemoglobin of ≥13 g/dL and body mass index of <26 were strongly associated with pCR. Higher baseline neutrophils-to-lymphocytes ratio, total TILs, and T-effector cell counts were favorable for pCR. Conclusion: This preliminary analysis identified LB and low-TIL tumors as poor responders to the NACRT protocol, which delivered RT after several cycles of chemotherapy. These findings will allow for amending the selection of patients for the trial and help better design future trials of NACRT in BC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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