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

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 N...

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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:
Anthracycline
Anthracyclines - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Breast cancer
Carboplatin
Carboplatin - adverse effects
Chemotherapy
Clinical medicine
Humans
Lymphocytes
Lymphocytes, Tumor-Infiltrating - metabolism
Metastases
Neoadjuvant Therapy
Paclitaxel
Paclitaxel - adverse effects
Triple Negative Breast Neoplasms - metabolism
Tumors
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Summary: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. 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. 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). 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.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-022-02050-8