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Next-Generation Sequencing of Breast Cancer in the Neoadjuvant Setting
Alexandra Mesquita1,2,3, Anabela Ferro3,4, José Carlos Machado2,3,4
1Medical Oncology Department, Local Health Unit Matosinhos, Matosinhos, Portugal.
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.
Insights
Genomic analysis of breast cancer tumors after neoadjuvant chemotherapy (NAT) reveals key gene alterations. Identifying these somatic mutations can guide targeted therapies and improve treatment response in non-pathological complete response (pCR) cases.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Neoadjuvant chemotherapy (NAT) is standard for locally advanced breast cancer, but pathological complete response (pCR) rates vary.
- Identifying non-pCR tumor characteristics is crucial for optimizing subsequent treatment strategies.
- Genomic profiling offers potential for discovering actionable targets in non-responders.
Purpose of the Study:
- To determine somatic gene alterations in breast cancer tumors that did not achieve pCR after NAT.
- To explore the utility of comprehensive genomic profiling for identifying therapeutic targets.
- To assess the potential of tumor mutation burden (TMB) as a biomarker.
Main Methods:
- Next-generation sequencing (NGS) using the Oncomine™ Comprehensive Assay Plus (OCA-Plus) panel.
- Analysis of 31 breast cancer tissue samples collected pre-NAT.
- Determination of gene alterations and tumor mutation burden (TMB).
Main Results:
- ERBB2, BRCA1/2, MYC, TP53, PIK3CA, and MET alterations were frequent in pCR tumors.
- Non-pCR tumors were predominantly triple-negative, with identified BRCA1/2, PIK3CA, and TP53 alterations.
- NGS successfully determined gene alterations and TMB in the analyzed samples.
Conclusions:
- Comprehensive genomic testing is significant for breast cancer, especially with limited targeted assays.
- Somatic mutation detection combined with targeted therapies may improve NAT response or aid post-surgical treatment.
- TMB evaluation in non-pCR samples could identify candidates for immunotherapy, warranting further clinical trials.
