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Immunogenomic profiling and pathological response results from a clinical trial of docetaxel and carboplatin in triple-negative breast cancer
- Source :
- Breast Cancer Res Treat
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- PURPOSE: Patients with triple negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) following neoadjuvant chemotherapy have a high risk of recurrence and death. Molecular characterization may identify patients unlikely to achieve pCR. This neoadjuvant trial was conducted to determine the pCR rate with docetaxel and carboplatin, and to identify molecular alterations and/or immune gene signatures predicting pCR. EXPERIMENTAL DESIGN: Patients with clinical stages II/III TNBC received 6 cycles of docetaxel and carboplatin. The primary objective was to determine if neoadjuvant docetaxel and carboplatin would increase the pCR rate in TNBC compared to historical expectations. We performed whole exome sequencing (WES) and immune profiling on pre-treatment tumor samples to identify alterations that may predict pCR. Thirteen matching on-treatment samples were also analyzed to assess changes in molecular profiles. RESULTS: Fifty-eight of 127 (45.7%) patients achieved pCR. There was a non-significant trend towards higher mutation burden for patients with residual cancer burden (RCB) 0/I versus RCB II/III (median 80, versus 68 variants, p 0.88). TP53 was the most frequently mutated gene, observed in 85.7% of tumors. EGFR, RB1, RAD51AP2, SDK2, L1CAM, KPRP, PCDHA1, CACNA1S, CFAP58, COL22A1, and COL4A5 mutations were observed almost exclusively in pre-treatment samples from patients who achieved pCR. Seven mutations in PCDHA1 were observed in pre-treatment samples from patients who did not achieve pCR. Several immune gene signatures including IDO1, PD-L1, interferon gamma signaling, CTLA4, cytotoxicity, tumor inflammation signature, inflammatory chemokines, cytotoxic cells, lymphoid, PD-L2, exhausted CD8, Tregs, and immunoproteosome were upregulated in pre-treatment samples from patients who achieved pCR. CONCLUSIONS: Neoadjuvant docetaxel and carboplatin resulted in a pCR of 45.7%. WES and immune profiling differentiated patients with and without pCR. TRIAL REGISTRATION: Clinical trial information: NCT02124902, Registered 24 April 2014, & NCT02547987, Registered 10 September 2015.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
medicine.medical_treatment
Breast Neoplasms
Triple Negative Breast Neoplasms
Docetaxel
Article
Carboplatin
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Breast cancer
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Triple-negative breast cancer
Chemotherapy
business.industry
Combination chemotherapy
medicine.disease
Neoadjuvant Therapy
Clinical trial
Treatment Outcome
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Female
Neoplasm Recurrence, Local
business
CD8
medicine.drug
Subjects
Details
- ISSN :
- 15737217 and 01676806
- Volume :
- 189
- Database :
- OpenAIRE
- Journal :
- Breast Cancer Research and Treatment
- Accession number :
- edsair.doi.dedup.....91b661da2af17ded5021d46783c9e667