356PD - The molecular profile of matched primary breast cancer and resected or biopsied brain metastases

Date 28 September 2014
Event ESMO 2014
Session Metastatic and locally advanced breast cancer: Facing with heterogeneity and endpoints in clinical trials
Topics Breast Cancer, Metastatic
Pathology/Molecular Biology
Presenter Alastair Thomson
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors A. Thomson1, G. Purvis1, J. McGrane1, J. Palmer2, J. Mathew3
  • 1Oncology- Sunrise Centre, Royal Cornwall Hospital, TR1 3LJ - Truro/GB
  • 2Oncology, Royal Cornwall Hospital, Truro/GB
  • 3Pathology, Royal Cornwall Hospital, Truro/GB

 

Abstract

Aim

Over 10% of patients with metastatic breast cancer will develop symptomatic brain metastases. Limited treatment options can result in significant morbidity and a poor prognosis for such patients. Little is known about the molecular profile of these brain secondaries and whether there are differences compared with the breast primary, researched in this study.

Methods

Patients with resected or biopsied brain metastases from a breast cancer primary were identified from an electronic multidisciplinary database at Derriford Hospital. Clinical data was collected from hospital notes at the Royal Cornwall, Royal Devon and Exeter, North Devon and Derriford Hospitals in the United Kingdom. Patients were included in the study if tissue from the primary breast cancer and brain metastasis were available for testing. Immunohistochemical analysis was performed for oestrogen receptor (ER), progesterone receptor (PR), p27kip1, cyclin D1 and HER 2 receptor on both the brain and breast samples, with borderline HER 2 results analysed by fluorescent in situ hybridisation. Correlations between levels of expression in the breast primary and resected brain metastases were analysed using the Wilcoxon signed ranks test.

Results

40 patients were identified. For breast primary tumours ER, PR, p27kip1, cyclin D1 and HER 2 positivity was identified in 37.5%, 27.5%, 47.5%, 52.5% and 32.5% respectively. For ER, 3 patients were found to have a positive brain metastasis with a negative breast primary, with no patients developing an ER negative brain lesion having been positive in the breast primary. 4 patients (10%) acquired a new HER 2 amplification in the brain metastasis, 1 brain metastasis was HER 2 negative with a positive primary. Cyclin D1 levels were high in the breast in 47.5%, rising to 70% of brain samples (12 patients increased, 3 decreased). 65% of patients had a rise in p27kip1, 30% having a statistically significant change (p = 0.023) from low (breast) to high (brain).

Conclusions

In this cohort there were demonstrable phenotypic differences in the expression levels of HER2, p27Kip1 and cyclin D1 in metastatic brain tumours compared with primary breast tumours of the same patients. There was a statistically significant increase for p27Kip1. 8 patients (20%) had a change in ER or HER 2 that could impact on therapeutic decisions.

Disclosure

All authors have declared no conflicts of interest.