The impact of germline BRCA pathogenic variants in locally advanced, triple negative breast cancer treated with platinum-based neoadjuvant chemotherapy

Raz Mutai; Iryna Kuchuk; Alexandra Goldshtein; Rinat Yerushalmi; Ofer Rotem; Adi Maisel Lotan; Tali Bdolah-Abram; Alberto Gabizon; Hadar Goldvaser

doi:10.1007/s10549-024-07247-4

The impact of germline BRCA pathogenic variants in locally advanced, triple negative breast cancer treated with platinum-based neoadjuvant chemotherapy

Breast Cancer Res Treat. 2024 Feb 12. doi: 10.1007/s10549-024-07247-4. Online ahead of print.

Authors

Raz Mutai^{1

2}, Iryna Kuchuk^{2

3}, Alexandra Goldshtein^{4

5}, Rinat Yerushalmi^{1

2}, Ofer Rotem^{1

2}, Adi Maisel Lotan⁶, Tali Bdolah-Abram⁷, Alberto Gabizon⁸, Hadar Goldvaser⁹

Affiliations

¹ Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.
² Faculty of Medicine Tel-Aviv University, Tel-Aviv, Israel.
³ The Oncology Institute, Meir Medical Center, Kfar Saba, Israel.
⁴ Department of Military Medicine and "Tzameret", Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
⁵ Medical Corps, Israel Defense Forces, Ramat Gan, Israel.
⁶ Plastic Surgery Department, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
⁷ Faculty of Medicine, Hebrew University, Jerusalem, Israel.
⁸ The Helmsley Cancer Center, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University, 9103102, Jerusalem, Israel.
⁹ The Helmsley Cancer Center, Shaare Zedek Medical Center, Faculty of Medicine, Hebrew University, 9103102, Jerusalem, Israel. hadar7g@gmail.com.

PMID: 38345692
DOI: 10.1007/s10549-024-07247-4

Abstract

Background: Whether germline BRCA (gBRCA) pathogenic variants (PV) affect prognosis of women with triple negative breast cancer (TNBC) and whether it has implications for treatment decisions in the neoadjuvant setting is unclear.

Methods: This is a retrospective two-center cohort study comprising all women with early stage TNBC who have completed genetic testing and were treated with neoadjuvant dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin. All eligible patients treated between 10.2014 and 3.2020 were included. Data on clinico-pathological, pathological response, overall survival (OS) and disease-free survival (DFS) were evaluated. Differences in clinico-pathological features and outcomes were analyzed according to gBRCA status.

Results: Sixty-four women were included in the final analysis, of which 31 had gBRCA PV (gBRCA carriers) and 33 were gBRCA wild-type. Clinico-pathological characteristics were similar between both groups. The odds for pathological complete response (pCR) were significantly higher in gBRCA carriers (74.2%) compared to BRCA wild-type women (48.5%), p = 0.035. At a median follow-up of 30 months, gBRCA carriers had significantly favorable OS (HR = 8.64, 95% CI 1.08-69.21, p = 0.042). The difference in DFS did not reach statistical significance (HR = 7.4, 95% CI 0.91-60.27, p = 0.062). The favorable OS for gBRCA carriers remained significant in multivariate analysis (p = 0.029) and was noted regardless of pathological response (p = 0.018).

Conclusion: Compared to wild-type, gBRCA carriers with locally advanced TNBC treated with neoadjuvant chemotherapy containing carboplatin had a higher pCR rate and better outcomes. These results strengthen the contention that gBRCA status should be considered when tailoring treatment decisions in women with locally advanced TNBC.

Keywords: BRCA mutation; Breast cancer; Neoadjuvant chemotherapy; Triple negative.