Antiepileptic drug use improves overall survival in breast cancer patients with brain metastases in the setting of whole brain radiotherapy.
OBJECTIVE
There is mounting evidence that histone deacetylase (HDAC) inhibitors, e.g. valproic acid (VPA), synergize with radiation to improve outcomes in several cancers. This study was conducted to ascertain whether VPA affected outcomes in breast cancer patients with brain metastases treated with whole brain radiotherapy (WBRT).


METHODS
Records from 253 breast cancer patients with brain metastases treated with WBRT were reviewed. Data regarding use of all antiepileptic drugs (AEDs) were extracted. Kaplan-Meier survival times were calculated using the date of brain involvement as time zero. Cox proportional hazard models were used to determine the association between patient and tumor characteristics and overall survival (OS).


RESULTS
Median OS for the entire patient cohort was 6 months. Patients receiving VPA (n=20) had a median OS of 11 months versus 5 months for those not receiving VPA (p=0.028). Median OS was 9 months for patients taking any AED (n=101) versus 4 months for those not taking AEDs (p=0.0003). On multivariate analysis both VPA and AED use were associated with improved OS (HR 0.61, p=0.0419; HR 0.59, p=0.0002, respectively).


CONCLUSIONS
This study suggests the use of AEDs, including VPA, is associated with improved OS in breast cancer patients with brain metastases following WBRT.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
Jay P
JP
Reddy
Department of Medical Oncology, Dubai Hospital, United Arab Emirates.
Shaheenah
S
Dawood
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
Melissa
M
Mitchell
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
Bisrat G
BG
Debeb
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
Elizabeth
E
Bloom
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
Ana M
AM
Gonzalez-Angulo
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
Erik P
EP
Sulman
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States.
Thomas A
TA
Buchholz
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, United States. Electronic address: wwoodward@mdanderson.org.
Wendy A
WA
Woodward
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D015331:Cohort Studies; D016371:Cranial Irradiation; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D000927:Anticonvulsants; D056572:Histone Deacetylase Inhibitors
Anticonvulsants; Antiepileptic drugs; Brain metastases; Breast cancer; Radiation; Valproic acid