Poster Presentation NSW State Cancer Conference 2023

Differences in tumour infiltrating immune cells in BRCA1/BRCA2 mutant ovarian and breast cancer to predict response to immunotherapy (#106)

Michelle WY Brown 1 2 3 , Martin Hong 4 , Andre van der Westhuizen 1 2 5 , Nikola A Bowden 1 2 3
  1. University of Newcastle, New Lambton Heights, NEW SOUTH WALES, Australia
  2. Centre for Drug Repurposing and Medicines Research, Hunter Medical Research Institute, New Lambton Heights, NSW , Australia
  3. NSW Regional Cancer Research Network, Newcastle, NSW, Australia
  4. Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, Australia
  5. Department of Medical Oncology, Calvary Mater Newcastle, Newcastle, NSW, Australia

Background

Breast cancer is the number one most commonly diagnosed cancer in females, with an estimated incidence of 275 cases per 100,000 women.  Ovarian cancer is 9th with respect to incidence, but 6th most common cause of death. BRCA1 and BRCA2 have an important role in the DNA repair process. Approximately 20% of ovarian cancers and 5% of breast cancers have mutations in BRCA1 or BRCA2, leading to negative effects on homologous recombination DNA repair. A recent study in mice showed differences in the populations of tumour infiltrating immune cells in mouse BRCA1-mutant breast cancer tumours compared to BRCA2-mutant breast cancer tumours, and BRCA2-mutant tumours had improved response to ICIs. A retrospective analysis in a pan-cancer cohort of patients showed that those with BRCA2 truncating mutations had improved overall survival after treatment with ICIs compared to those with BRCA1 truncating mutations. 

 

Aims

  1. Characterise the tumour infiltrating immune cell populations in ovarian and breast tumours with germline homologous recombination deficiency (BRCA1, BRCA2, and PALB2 mutations)
  2. Assess if any patients received immune checkpoint inhibitor therapy, and compare outcomes between those who received ICI vs those who did not receive ICI therapy

  

Methods

Diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples from 66 patients with breast or ovarian cancer and known germline BRCA1 and BRCA2 mutations were obtained from NSW Regional Biospecimen and Research Services. Whole tissue sections were assessed for tumour infiltrating lymphocytes by immunohistochemistry labelling of CD3, CD4, and CD8, and analysed on HALO software.

 

Results

Tumour infiltrating immune cells were observed in all tumours. There is no significant difference in tumour infiltrating CD8+ T-cells between BRCA1- and BRCA2-mutated tumours. There is no significant difference in CD4+ T-cells between BRCA1- and BRCA2-mutated tumours. However, there is significantly lower densities of CD8+ and CD4+ T-cells between PALB-mutated tumours and BRCA1- or BRCA2-mutated tumours. None of the patients in this cohort received immunotherapy.

 

Discussion and Conclusion

Our preliminary analyses show that tumour infiltrating immune cells are present in all homologous recombination deficient ovarian and breast tumours. A larger sample size is necessary to assess whether the differences in tumour infiltrating immune cells between BRCA1- and BRCA2-mutated tumours observed in mouse models in also present in patient cohorts.