19P - Genetic profiling of early triple-negative breast cancer patients with an indication for neoadjuvant pembrolizumab

Background

Triple-negaive breast cancer (TNBC) is a highly aggressive subtype with neoadjuvant options historically limited to chemotherapy until the recent success of the KEYNOTE-522 trial. Although TNBC is well known for being associated with constitutional pathogenic BRCA mutations when compared to other types of breast cancer, the genetic profiles of the patients in the KEYNOTE-522 trial are unknown and no subgroup analysis has assessed a possible relationship with treatment efficacy.

Methods

We analysed consecutive index-case genetic consults of TNBC patients (N = 170) between January 2020 and July 2024 in our oncogenetics department. Only patients with treatment history in our center were included. Tumor characteristics, pCR status and the type of chemotherapy agents used were collected. We compared the pCR and non pCR rates according to the genetic status and survival probability distribution stratified by the presence or not of Pembrolizumab and Carboplatin using Fisher’s exact test and the Kaplan-Meier method. A significance threshold of 5% was applied to all statistical analyses.

Results

A total of 132 patients were identified for the analysis. Significant benefits were observed in patients with pCR in terms of EFS (p = 0.001, HR = 0.07 CI 95% 0.02 – 0.21) and OS (p = 0.012, HR = 0.12 CI 95% 0.03 – 0.50), respectively. When comparing patients treated by a neoadjuvant chemotherapy regimen to those treated by pembrolizumab plus chemotherapy, a significantly higher pCR rate was observed with the latter group (p = 0.01). Regarding the presence of pathogenic variants (PV), the following were identified: BRCA1 (N = 10), BRCA2 (N = 3), PALB 2 (N = 1), PMS2 (N = 1), RAD51C (N = 3) and RAD51D (N = 1). 30 patients carried various variants of unknown significance. Notably, all patients carrying a BRCA PV treated with pembrolizumab achieved pCR but results were not statistically significant (p = 0.14).

Conclusions

To our knowledge this is the first descriptive analysis of the genetic landscape of patients with an indication for neoadjuvant Pembrolizumab. Interestingly, all patients carrying pathogenic variants of BRCA treated with pembrolizumab had pCR although results were not statistically significant compared to patients not presenting BRCA PV.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.