Abstract P6-17-07: Changing molecular profile of brain metastases compared with matched breast primaries and impact on clinical outcomes
Authors: Thomson AH , Purvis G , McGrane J , Palmer J , Jenkins R 
Published: May 2016

Background

Over 10% of patients with metastatic breast cancer develop symptomatic brain metastases. Limited treatment options can result in significant morbidity and a dismal prognosis. Little is known about the molecular profile of brain secondaries, differences compared with the patient's breast primary and whether any changes impact on prognosis.

Methods

Patients with resected or biopsied brain metastases from a breast cancer were identified from an electronic database, with clinical data collected from hospital notes for patients in the south west of the UK. Patients were included 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, epidermal growth factor receptor (EGFR), insulin like growth factor 1 (IGF1) and receptor (IGF1-R), vascular endothelial growth factor A (VEGF A), vascular endothelial growth factor receptor (VEGFR-2), transforming growth factor beta (TGFB) and Her 2 receptor on both the brain and breast samples. Borderline Her 2 results were analysed by fluorescent in situ hybridisation.

Results

41 patients were identified. Median age of patients was 49, with a 26 month interval between breast cancer diagnosis and development of brain metastases. Median time from brain metastases to death was 15 months. 13 patients (32%) had a HER2 positive breast primary, 12 receiving HER2 directed therapy prior to development of brain metastases. 15 patients (37%) had an ER positive breast cancer at initial diagnosis. 11 patients had a biopsy of their brain secondary, 30 more extensive surgical resection. 28 patients received whole brain radiotherapy (WBRT), 1 patient stereotactic radiotherapy (SRT) alone, 6 patients both WBRT and SRT, 6 unknown.

Changes in the molecular profile of the breast primary compared with the brain secondary are illustrated in Table 1.

Number of patients with a change in molecular profile from breast primary to brain metastasis Breast positive to brain negativeBreast negative to brain positiveER03PR01Her214EGFR16IGF 1312IGF1-R34TGFB11p27 kip 1515cyclin D1312VEGF00VEGFR-211

There was a change in more than 10% of patients from a positive breast primary to a negative brain secondary for p27kip1 and from a negative breast cancer to a positive brain metastasis for EGFR, IGF1, cyclin D1 and p27kip1. These alterations did not have a significant impact on time from brain metastasis to death. However, there was a significant improvement in survival from brain metastasis diagnosis for secondary lesions that were ER positive (p=0.005) or PR positive (p=0.013). Survival from time of brain metastasis improved with a longer time to brain metastasis from initial diagnosis (p=0.001).

Conclusions

In this cohort there were demonstrable phenotypic differences in the expression levels of EGFR, IGF1, p27Kip1 and cyclin D1 in metastatic brain tumours compared with primary breast tumours of the same patient, although survival was not affected. 8 patients (20%) had a change in ER or Her 2 that could impact on current therapeutic decisions. Hormone receptor positive brain metastases had superior survival compared with negative lesions.

Citation Format: Thomson AH, Purvis G, McGrane J, Palmer J, Jenkins R. Changing molecular profile of brain metastases compared with matched breast primaries and impact on clinical outcomes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-07.