Systematic review and meta-analysis of breast cancer brain metastasis and primary tumor receptor expression discordance

Rupesh Kotecha; Raees Tonse; Muni Rubens; Michael W McDermott; Yazmin Odia; Haley Appel; Minesh P Mehta

doi:10.1093/noajnl/vdab010

Systematic review and meta-analysis of breast cancer brain metastasis and primary tumor receptor expression discordance

Neurooncol Adv. 2021 Jan 16;3(1):vdab010. doi: 10.1093/noajnl/vdab010. eCollection 2021 Jan-Dec.

Authors

Rupesh Kotecha^{1

2}, Raees Tonse¹, Muni Rubens³, Michael W McDermott^{2

4}, Yazmin Odia^{2

4

5}, Haley Appel¹, Minesh P Mehta^{1

2}

Affiliations

¹ Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida, USA.
² Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, USA.
³ Office of Clinical Research, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida, USA.
⁴ Miami Neuroscience Institute, Baptist Health South Florida, Miami, Florida, USA.
⁵ Department of Neuro-Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida, USA.

Abstract

Background: Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or human epidermal growth factor receptor type 2 (HER2) status during the evolutionary course of metastatic breast cancer and the effect of tumor classification subtype switching remain understudied and underappreciated in brain metastasis patients.

Methods: Using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a systematic review of series published prior to April 2020 obtained from the Medline database of biopsied or resected breast cancer brain metastasis (BCBM) was performed. Weighted random effects models were used to calculate pooled estimates.

Results: 15 full-text articles were included with receptor expression analyses on 1373 patients who underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. Primary tumor receptor expression immunophenotypes were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding BCBM immunophenotypes were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. On primary/BCBM comparison, 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordant on ER, 23.0% (95% CI: 18.0%-30.0%) discordant on PR, and 12.0% (95% CI: 8.0%-16.0%) discordant on HER2 status. The most common receptor conversions found in BCBM were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%).

Conclusions: BCBM exhibits significant receptor expression discordance in comparison to primary tumors in approximately 40% of patients. Classification patterns need to be analyzed to determine factors predictive of BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.

Keywords: HER2; breast cancer; discordance; estrogen receptor; progesterone receptor.

Publication types

Review