S. Bhoriwal (New Delhi, India)

AIIMS - All India Institute of Medical Sciences

Author Of 1 Presentation

 On-Demand ePoster Display

155P - Profile of pathogenic mutations and evaluation of germline genetic testing criteria in consecutive breast cancer patients treated at a North Indian tertiary care center

Abstract

Background

The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (NCCN and MCG PLUS criteria) have never been validated in the Indian population.

Methods

All new female patients with invasive breast cancer attending our OPD from 1st March 2019 to 28th Feb 2020 were screened. Those without previous genetic testing and providing informed consent were recruited. Patients were divided into those qualifying or not qualifying NCCN/MCG PLUS criteria. Hereditary multigene panel testing by next generation sequencing with reflex MLPA from peripheral blood was performed after pre-test counselling. Frequency of P/LP mutations between two groups was compared and sensitivity of testing criteria was computed.

Results

236 patients were included (median age 45 years). Majority were Hindus (88.5%) and married (95%). 34 (14%) women had a family history suggestive of HBOC. Around 35% (83/236) had TNBC. 44/236 (18.64%) patients had a P/LP mutation with three patients having two mutations. Mutations in BRCA1 were most common (22/47=46.8%) followed by BRCA2 (9/47=19.1%). Only one patient had an Ashkenazi Jewish founder mutation. 34% mutations were seen in non BRCA genes. The difference in P/LP mutations was significant among patients qualifying and not qualifying NCCN and MCG PLUS criteria (23.6% vs 7.04%, P=0.03; 24.8% vs 7.2%, p=0.01 respectively). The sensitivity of NCCN and MCG Plus criteria for picking up patients with P/LP mutations were 88.6% (75.4-96.2) and 86.36% (72.65-94.83), respectively; 98% sensitivity was achieved if all women up-to age 60 years were tested. Among BRCA carriers, 10/27 (37.37%) patients underwent RRM and 7/27(29.1%) underwent RRBSO. Cascade testing was done in 31 previvors (16/44 families) and 23 previvors with P/LP mutations were detected.

Conclusions

Frequency of P/LP mutations among breast cancer patients is high in India with significant contribution of non-BRCA genes stressing the importance of multigene testing. Age cut off needs to be relaxed in testing criteria in order to expand access to testing. Uptake of risk-reducing interventions remains low and is an area of unmet need.

Legal entity responsible for the study

The authors.

Funding

Tata Center of Development, University of Chicago.

Disclosure

All authors have declared no conflicts of interest.

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