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. 2023 Mar 29;15(7):2030.
doi: 10.3390/cancers15072030.

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

Nhu Hanh To  1   2   3 , Isabelle Gabelle-Flandin  4 , Thi My Hanh Luong  5 , Gokoulakrichenane Loganadane  1 , Nabila Ouidir  6 , Chahrazed Boukhobza  1 , Noémie Grellier  1 , Camille Verry  4 , Allan Thiolat  2 , José L Cohen  2 , Nina Radosevic-Robin  7 , Yazid Belkacemi  1   2   3
Affiliations

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

Nhu Hanh To et al. Cancers (Basel). .

Abstract

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.

Keywords: luminal B; neoadjuvant; neutrophils-to-lymphocytes ratio; radiotherapy; triple negative breast cancer; tumor-infiltrating lymphocytes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic overview of the study. Patients were randomized to receive either standard treatment consisting of anthracycline/taxane-based NACT or experimental treatment with the same NACT and the addition of a short course tumor-directed APBI between two chemotherapy cycles. Abbreviation: A: anthracycline-based chemotherapy (FEC or EC: fluorouracil, epirubicin, cyclophosphamide), APBI: accelerated partial breast irradiation, LABC: locally advanced breast cancer, LB: luminal B, R: randomization, RT: radiation therapy, T: taxane, TN: triple-negative, WBI: whole breast irradiation (or parietal irradiation), ∆: blood test, ◊: histological analysis (biopsy before randomization and operative piece after breast surgery).
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