Introduction: Many patients with locally advanced breast cancer are proposed to neoadjuvant chemotherapy (NAT) before surgery. Only some of them achieve a pathological complete response (pCR). The determination of gene somatic alterations using next-generation sequencing (NGS) in the non-pCR tumors is important, in order to identify potential opportunities of treatment for the patients, if targeted therapies are available. Methods: Breast cancer tissue samples of 31 patients, collected before NAT, were analyzed by NGS using the Oncomine™ Comprehensive Assay Plus (OCA-Plus) panel. Results: Twelve patients achieved pCR after NAT. ERBB2 gene alterations were the most frequent in this cohort of pCR patients, followed by BRCA 1 and 2, MYC, TP53, PIK3CA, and MET alterations. Tumors that did not achieve a pCR were mainly triple negative. In this subgroup some BRCA 1 and 2 and PIK3CA gene alterations were identified, as well as TP53 mutations. The NGS panel employed in this study also allowed for the determination of tumor mutation burden (TMB). Conclusion: This study showcases the significance of employing comprehensive genomic testing in breast cancer cases, primarily due to the scarcity of specific target assays. The detection of somatic mutations, coupled with the availability of targeted therapies, holds promise as a potential therapeutic avenue to enhance tumor response rates during NAT, or as a complementary treatment following surgery. Moreover, evaluating the TMB in non-pCR samples could serve as a valuable criterion for selecting patients suitable for immunotherapy. Further exploration through clinical trials is imperative to investigate these prospects.

Jameson JL, Longo DL. Precision medicine-personalized, problematic, and promising. N Engl J Med. 2015 Jun 4;372(23):2229–34.
Hodson R. Precision medicine. Nature. 2016 Sep 8;537(7619):S49.
Hussen B, Abdullah ST, Salihi A, Sabir D, Sidiq K, Rasul MF, et al. The emerging roles of NGS in clinical oncology and personalized medicine. Pathol Res Pract. 2022 Feb;230:153760.
Desmedt C, Voet T, Sotiriou C, Campbell P. Next generation sequencing in breast cancer: first take home messages. Curr Opin Oncol. 2012 Nov;24(6):597–604.
Gianni L, Pienkowsky P, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab, trastuzumab in women wiith locally advanced, inflammatory or early Her2 positive breast cancer (Neosphere), a randomized multicenter phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25–32.
Gass P, Lux MP, Rauh C, Hein A, Bani M, Fiessler C, et al. Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple negative breast cancer. BMC Cancer. 2018 Oct 29;18(1):1051.
Tung N, Garber JE. BRCA1/2 testing: therapeutic implications for breast cancer management. Br J Cancer. 2018;119(2):141–52.
Byrski T, Dent R, Blecharz P, Foszczynska-Kloda M, Gronwald J, Huzarski T, et al. Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer. Breast Cancer Res. 2012;14(4):R110.
Robson MD, Im S, Senkus E, Xu B, Domchek S, Masuda N, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–33.
Montemorano L, Lightfoot M, Bixel K. Role of olaparib as maintenance treatment for ovarian cancer: the evidence to date. Onco Targets Ther. 2019;12:11497–506.
Maxwell KN, Wubbenhorst B, Wenz BM, De Sloover D, Pluta J, Emery L, et al. BRCA locus-specific loss of heterozygosity in germline BRCA1 and BRCA2 carriers. Nat Commun. 2017;8(1):319.
Popova T, Manie E, Rieunier G, Caux-Moncoutier V, Tirapo C, Dubois T, et al. Ploidy and large-scale genomic instability consistently identify basal-like breast carcinomas with BRCA1/2 inactivation. Cancer Res. 2012;72(21):5454–62.
Dong F, Davineni PK, Howitt BE, Beck AH. A BRCA1/2 mutational signature and survival in ovarian high-grade serous carcinoma. Cancer Epidemiol Biomarkers Prev. 2016;25(11):1511–6.
Xu J, Chen Y, Olapade O. MYC and breast cancer. Genes Cancer. 2010 Jun;1(6):629–40.
Andrikopoulou A, Terpos E, Chatzinikolaou S, Apostolidou K, Ntanasis-Stathopoulos I, Gavriatopoulou M, et al. TP53 mutations determined by targeted NGS in breast cancer: a case-control study. Oncotarget. 2021;12(21):2206–14.
Shimoi T, Hamada A, Yamagishi M, Hirai M, Yoshida M, Nishikawa T, et al. PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system. Cancer Sci. 2018;109(8):2558–66.
André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019 May 16;380(20):1929–40.
Tovar EA, Graveel C. MET in human cancer: germline and somatic mutations. Ann Transl Med. 2017;5(10):205.
Wood G, Hockings H, Hilton D, Kermorgant S. The role of MET in chemotherapy resistance. Oncogene. 2021;40(11):1927–41.
Gu J, Zhang R, Yang Z, Duan Z, Yin D, Zhou Y. Biological roles and therapeutic applications of IDH2 mutations in human cancer. Front Oncol. 2021;11:644857.
Mitri Z, Abuhadra N, Goodyear SM, Hobbs E, Kaempf A, Thompson AM, et al. Impact of TP53 mutations in triple negative breast cancer. NPJ Precis Oncol. 2022;6(1):64.
Foroughizadeh M, Mozdarani H, Majidzadeh-A K, Kaviani A. Variation of ATM gene expression in peripheral blood cells of sporadic breast carcinomas in Iranian patients. Avicenna J Med Biotechnol. 2012 Apr–Jun;4(2):95–101.
Stucci L, Interno V, Tucci M, Perrone M, Mannavola F, Palmirotta R, et al. The ATM gene in breast cancer: its relevance in clinical practice. Genes. 2021;12(5):727.
Haricharan S, Punturi N, Singh P, Holloway KR, Anurag M, Schmelz J, et al. Loss of MutL disrupts CHK2-dependent cell-cycle control through CDK4/6 to promote intrinsic endocrine therapy resistance in primary breast cancer. Cancer Discov. 2017;7(10):1168–83.
Nakai K, Hung MC, Yamaguchi H. A perspective on anti-EGFR therapies targeting triple-negative breast cancer. Am J Cancer Res. 2016;6(8):1609–23.
Galie M. RAS as supporting actor in breast cancer. Front Oncol. 2019;9:1199.
Helsten T, Elkin S, Arthur E, Tomson BN, Carter J, Kurzrock R. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res. 2016;22(1):259–67.
Kommalapati A, Tella S, Borad M, Javle M, Mahipal A. FGFR inhibitors in oncology: insight on the management of toxicities in clinical practice. Cancers. 2021;13(12):2968.
Miknyoczki SJ, Wan W, Chang H, Dobrzanski P, Ruggeri BA, Dionne CA, et al. The neurotrophin-trk receptor axes are critical for the growth and progression of human prostatic carcinoma and pancreatic ductal adenocarcinoma xenografts in nude mice. Clin Cancer Res. 2002;8(6):1924–31.
Griffin N, Marsland M, Roselli S, Oldmeadow C, Attia J, Walker MM, et al. The receptor Tyrosine kinase, TrKa is increased and targetable in Her2 positive breast cancer. Biomolecules. 2020;10(9):1329.
Lu J, Blakely CM, Barve M, et al. Entrectinib in NTRK fusion-positive (NTRK-fp) breast cancer: updated data from STARTRK-2. Presented at: 2022 ESMO Breast Cancer Congress; May 3–5, 2022. Berlin, Germany. Poster 173P.
Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9(1):34.
McGrail DJ, Pilie PG, Rashid NU, Voorwerk L, Slagter M, Kok M, et al. High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types. Ann Oncol. 2021;32(5):661–72.
You do not currently have access to this content.