Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis

Olga Caramelo; Cristina Silva; Francisco Caramelo; Cristina Frutuoso; Leonor Pinto; Teresa Almeida-Santos

doi:10.1186/s13053-022-00242-0

Efficacy of different neoadjuvant treatment regimens in BRCA-mutated triple negative breast cancer: a systematic review and meta-analysis

Hered Cancer Clin Pract. 2022 Sep 9;20(1):34. doi: 10.1186/s13053-022-00242-0.

Authors

Olga Caramelo¹, Cristina Silva², Francisco Caramelo³, Cristina Frutuoso⁴, Leonor Pinto⁵, Teresa Almeida-Santos^{6

7}

Affiliations

¹ Gynecology Department, Coimbra Hospital and University Centre (CHUC), EPE, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. olgalgcaramelo@gmail.com.
² Faculty of Pharmacy of the University of Coimbra, Rua Filipe Simões n° 33, 3000-186, Coimbra, Portugal.
³ Laboratory of Biostatistics and Medical Informatics, iCBR - Faculty of Medicine, University of Coimbra, 3000-354, Coimbra, Portugal.
⁴ Gynecology Department, Coimbra Hospital and University Centre (CHUC), EPE, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
⁵ Oncology Department, Coimbra Hospital and University Centre (CHUC), EPE, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
⁶ Centre for Fertility Preservation, Human Reproduction Department, Coimbra Hospital and University Centre (CHUC), EPE, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
⁷ Faculty of Medicine of the University of Coimbra, Azinhaga de Santa Comba - Celas, 3000-548, Coimbra, Portugal.

Abstract

Purpose: Triple negative breast cancer (TNBC) is an aggressive breast cancer strongly associated with BRCA mutation. Standard neoadjuvant chemotherapy remains the standard of care for early stage TNBC, the optimal chemotherapy regimen is still a matter of discussion. Other agents, such as poly-ADP-ribosyl polymerase inhibitors (PARPi) and anti-vascular endothelial growth factor (VEGF) antibodies were evaluated in the neoadjuvant setting. This systematic review and meta-analysis intend to evaluate the impact of neoadjuvant treatments in pCR rates in TNBC gBRCA mutation, beyond traditional standard chemotherapy.

Methods: PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase and key oncological meetings for trials were searched for studies reporting neoadjuvant chemo-immunotherapy in BRCA positive TNBC.

Results: Out of 1238 records reviewed, thirty-one trials were included, resulting in a total 619 BRCA-mutated TNBC patients. In BRCA mutated TNBC patients who received cisplatin in monotherapy the proportion of patients who achieved pCR was 0.53 (95%CI [0.30, 0.76]), and when treatment combined standard chemotherapy and platin derivatives the proportion of pCR increased to 0.62 (95% CI [0.48, 0.76]). The group of patients treated with platin derivatives, anthracyclines ± taxanes achieved the highest proportion of pCR, 0.66. Patients treated with PARPi alone show a pCR proportion of 0.55 (95% CI [0.30, 0.81]); and when standard chemotherapy and platin derivatives were combined with PARPi the proportion of pCR did not vary.

Conclusions: Patients with BRCA mutated TNBC treated with cisplatin in monotherapy demonstrate inferior proportion in the pCR achievement when compared with standard chemotherapy plus platin derivates. The best pCR was achieved with platin derivates in association with anthracyclines ± taxanes. No difference in pCR was found between PARPi alone vs PARPi with standard chemotherapy.

Keywords: BRCA; Carboplatin; Cisplatin; Neoadjuvant chemotherapy; PARPi; Triple negative breast cancer.

Publication types

Review