ecancermedicalscience

Short Communication

Spectrum and management of breast cancer patients with variant of uncertain significance mutations at a tertiary care centre in North India

1 Aug 2022
Abhenil Mittal, S V S Deo, Ajay Gogia, Atul Batra, Akash Kumar, Sandeep Bhoriwal, Koushik Sinha Deb, Ekta Dhamija, V L Ramprasad, Olufunmilayo Olopade, Raja Pramanik

Background: The spectrum and significance of Variants of Uncertain Significance (VUS) mutations in breast cancer predisposition genes is poorly defined in the Indian population.

Methods: All new female breast cancer patients from 1 March 2019 to 28 February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited. Multigene panel testing (107 genes) by next-generation sequencing was performed for all patients. Descriptive statistics was used to describe the spectrum of VUS mutations.

Results: Out of 236 patients recruited in the study, a VUS was detected in 89 patients (37.71%). VUS pathogenic ratio was 2.02. A total of 121 different VUS mutations in 40 different genes were detected. Fourteen patients (15.7%) had a VUS in high penetrance genes and 36 VUS mutations (29.8%) were detected in one of the genes involved in homologous recombination repair pathway. No therapeutic interventions were done based on VUS.

Conclusions: In this large prospective study of genetic determinants of breast cancer from India, a high prevalence of VUS (37.71%) was detected with 15.7% patients having a VUS in high penetrance genes. More evidence needs to be generated from larger multicentric studies to better understand the implications of these genetic variants and enable their reclassification.

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