title: Breast cancer subtype affects patterns of failure of brain metastases after treatment with stereotactic radiosurgery.
abstract: We investigate the variance in patterns of failure after Gamma Knife™ radiosurgery (GKRS) for patients with brain metastases based on the subtype of the primary breast cancer. Between 2000 and 2010, 154 breast cancer patients were treated with GKRS for brain metastases. Tumor subtypes were approximated based on hormone receptor (HR) and HER2 status of the primary cancer: Luminal A/B (HR+/HER2(-)); HER2 (HER2+/HR(-)); Luminal HER2 (HR+/HER2+), Basal (HR(-)/HER2(-)), and then based on HER2 status alone. The median follow-up period was 54 months. Kaplan-Meier method was used to estimate survival times. Multivariable analysis was performed using Cox regression models. Median number of lesions treated was two (range 1-15) with a median dose of 20 Gy (range 9-24 Gy). Median overall survival (OS) was 7, 9, 11 and 22 months for Basal, Luminal A/B, HER2, and Luminal HER2, respectively (p = 0.001), and was 17 and 8 months for HER2+ and HER(-) patients, respectively (p < 0.001). Breast cancer subtype did not predict time to local failure (p = 0.554), but did predict distant brain failure rate (76, 47, 47, 36 % at 1 year for Basal, Luminal A/B, HER2, and Luminal HER2 respectively, p < 0.001). An increased proportion of HER2+ patients experienced neurologic death (46 vs 31 %, p = 0.066). Multivariate analysis revealed that HER2+ patients (p = 0.007) independently predicted for improved survival. Women with basal subtype have high rates of distant brain failure and worsened survival. Our data suggest that differences in biologic behavior of brain metastasis occur across breast cancer subtypes.
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, Baptist Medical Center, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157, USA. tvern@wfubmc.edu
authors.forename: Tamara Z
authors.initials: TZ
authors.lastname: Vern-Gross
authors.forename: Julia A
authors.initials: JA
authors.lastname: Lawrence
authors.forename: L Douglas
authors.initials: LD
authors.lastname: Case
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McMullen
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Bourland
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Metheny-Barlow
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ellis
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Tatter
authors.forename: Edward G
authors.initials: EG
authors.lastname: Shaw
authors.forename: James J
authors.initials: JJ
authors.lastname: Urbanic
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chan
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000145:classification / Q000401:mortality* / Q000556:secondary / Q000601:surgery; D001943:Breast Neoplasms / Q000145:classification / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D002280:Basal Cell Carcinoma / Q000145:classification / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D016634:Radiosurgery; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016879:Salvage Therapy; D015996:Survival Rate; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone