A population-based study of the relationships between synchronous breast cancers: opportunities for personalised surgery

Abstract

1-3% of women diagnosed with breast cancer also have a cancer in their opposite breast - synchronous breast cancer (SBC). It is not known whether SBCs represent spread from a first breast cancer to the other breast or whether they are unrelated second tumours.

This project identified a cohort of women in Northern Ireland who have been diagnosed with SBC through the Northern Ireland Cancer Registry (NICR). Clinical & pathological data was collated, and tumour blocks recalled so that DNA samples can be taken from both tumours. The somatic DNA of these tumours were examined using high throughput targeted gene panel sequencing to look for shared somatic mutations which can indicate a shared clonal origin between the tumours i.e. whether they are independent cancers or cancers that have spread from one breast to the other. Germline DNA from each patient was examined in the same way, to identify pathogenic variants that may indicate a genetic predisposition that lead to the development of SBC.

A final study cohort of 200 patient diagnosed with SBC in Northern Ireland 2000-2014 was identified. 142 SBC patients had germline DNA sequenced for pathogenic germline mutations in all know breast cancer risk predisposition genes. Pathogenic variants were found in 16 cases (11.3%). Shared somatic variants between paired SBCs was found in 11.5% of 129 cases that had sufficient DNA for comparison.

The clinical and pathological features of the SBC cohort in Northern Ireland are in keeping with those reported elsewhere in the literature. The SBC cohort is found to be moderately enriched for the presence of pathogenic mutations in known risk redisposition genes. Should this finding be replicated in study of other SBC populations it may influence the genetic testing guidelines in women diagnosed with SBC, especially those in occurring in younger women. Furthermore, the detection of shared somatic mutations in a proportion of tumour pairs indicate the presence of metastatic disease. As such a case may be made of the routine genomic characterisation of SBCs at the point of diagnosis in order to better inform clinical management.

Thesis is embargoed until 31 December 2028.

Date of Award	Dec 2023
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Kienan Savage (Supervisor) & Stuart McIntosh (Supervisor)