Differential response and survival across rare histologic subtypes of triple-negative breast cancer following neoadjuvant chemo-immunotherapy
Year: 2026
Type: article
Abstract: Special histologic subtypes of triple-negative breast cancer (TNBC) are biologically distinct, yet their outcomes in the immunotherapy era remain undefined. We analyzed 823 patients with early-stage TNBC treated with pembrolizumab plus chemotherapy in the multicenter real-world Neo-Real/GBECAM-0123 cohort. Histologies included invasive carcinoma of no special type (NST; n = 762, 92.6%), metaplastic carcinoma ( n = 26, 3.2%), triple-negative lobular carcinoma ( n = 17, 2.1%), and other rare variants ( n = 18, 2.2%). Metaplastic carcinoma demonstrated significantly lower pathological complete response (pCR) rates compared with NST (17.4% vs 65.4%; OR 0.14, 95% CI 0.04–0.44; p = 0.001), suggesting relative resistance to chemo-immunotherapy, with a numerical trend toward worse event-free survival (EFS) (HR 2.07, 95% CI 0.88–4.88; p = 0.094). Triple-negative lobular carcinoma achieved pCR rates comparable to NST (56.2%) but showed poorer 2-year EFS, with a significant association in the pre-surgical multivariable model (HR 4.25, 95% CI 1.50–12.06; p = 0.006), and a persistent trend after adjustment for pCR. This highlights the biological heterogeneity of TNBC and supports the investigation of histology-driven therapeutic strategies.
Source: npj Breast Cancer
Authors: Romualdo Barroso-Sousa, Mariana Carvalho Gouveia, Monica Varela, Natalia Cristina Cardoso Nunes, Laura Testa, Monique Celeste Tavares, Flávia Cavalcanti Balint, Zenaide Silva de Souza, Carlos Henrique dos Anjos, Débora de Melo Gagliato, Mayana Lopes de Brito, Melina Winocur, Carlos Gallina, Daniele Assad-Suzuki, Daniela Dornelles Rosa, Noele de Jesus Barros Gomes, Isadora Martins de Sousa, Matheus de Oliveira Andrade, Fernanda Madasi, Jose Bines, Rafael Dal Ponte Ferreira, Candice Lima Santos, Maira Tavares, Mariana Ribeiro Monteiro, Bruna M. Zucchetti, Anezka Ferrari, Maria Marcela Fernandes Monteiro, Gilmara Resende, Solange Sanches, Paulo M. Hoff, Gonzalo Gomez Abuin, Maria Del Pilar Estevez-Diz, Renata Colombo Bonadio
Institutions: Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, D’Or Institute for Research and Education, AC Camargo Hospital, Hospital Sírio-Libanês, Beneficência Portuguesa de São Paulo, Hospital Moinhos de Vento, Hospital de Clínicas de Porto Alegre, Hospital São Domingos, Hospital Samaritano de São Paulo, Hospital Haroldo Juaçaba, Hospital Santa Paula
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,790
OpenAlex ID: W7202266258
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