Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation

• Published in: British journal of cancer 2023-01, Vol.128 (2), p.266-274
• Main Authors: Dieci, Maria Vittoria, Carbognin, Luisa, Miglietta, Federica, Canino, Fabio, Giorgi, Carlo Alberto, Cumerlato, Enrico, Amato, Ottavia, Massa, Davide, Griguolo, Gaia, Genovesi, Elisa, Garufi, Giovanna, Giannarelli, Diana, Tornincasa, Antonio, Trudu, Lucia, Michieletto, Silvia, Saibene, Tania, Lo Mele, Marcello, Fassan, Matteo, Zarrilli, Giovanni, Piacentini, Federico, Bria, Emilio, Guarneri, Valentina
• Format: Article
• Language: English
• Subjects: 631/250/2503; 631/67/1347; 692/4028/67/1347; 692/4028/67/580; 692/53/2422; Anthracycline; Anthracyclines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Carboplatin; Carboplatin - adverse effects; Chemotherapy; Clinical medicine; Drug Resistance; Epidemiology; Humans; Lymphocytes; Lymphocytes, Tumor-Infiltrating - metabolism; Metastases; Molecular Medicine; Neoadjuvant Therapy; Oncology; Paclitaxel; Paclitaxel - adverse effects; Triple Negative Breast Neoplasms - metabolism; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-022-02050-8

Background The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. Methods Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/− Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. Results In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P  = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P  = 0.05). Conclusions We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/− Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.