Lactate dehydrogenase B: a metabolic marker of response to neoadjuvant chemotherapy in breast cancer.

Dennison JB, Molina JR, Mitra S, González-Angulo AM, Balko JM, Kuba MG, Sanders ME, Pinto JA, Gómez HL, Arteaga CL, Brown RE, Mills GB
Clin Cancer Res. 2013 19 (13): 3703-13

PMID: 23697991 · PMCID: PMC3727144 · DOI:10.1158/1078-0432.CCR-13-0623

PURPOSE - Although breast cancers are known to be molecularly heterogeneous, their metabolic phenotype is less well-understood and may predict response to chemotherapy. This study aimed to evaluate metabolic genes as individual predictive biomarkers in breast cancer.

EXPERIMENTAL DESIGN - mRNA microarray data from breast cancer cell lines were used to identify bimodal genes-those with highest potential for robust high/low classification in clinical assays. Metabolic function was evaluated in vitro for the highest scoring metabolic gene, lactate dehydrogenase B (LDHB). Its expression was associated with neoadjuvant chemotherapy response and relapse within clinical and PAM50-derived subtypes.

RESULTS - LDHB was highly expressed in cell lines with glycolytic, basal-like phenotypes. Stable knockdown of LDHB in cell lines reduced glycolytic dependence, linking LDHB expression directly to metabolic function. Using patient datasets, LDHB was highly expressed in basal-like cancers and could predict basal-like subtype within clinical groups [OR = 21 for hormone receptor (HR)-positive/HER2-negative; OR = 10 for triple-negative]. Furthermore, high LDHB predicted pathologic complete response (pCR) to neoadjuvant chemotherapy for both HR-positive/HER2-negative (OR = 4.1, P < 0.001) and triple-negative (OR = 3.0, P = 0.003) cancers. For triple-negative tumors without pCR, high LDHB posttreatment also identified proliferative tumors with increased risk of recurrence (HR = 2.2, P = 0.006).

CONCLUSIONS - Expression of LDHB predicted response to neoadjuvant chemotherapy within clinical subtypes independently of standard prognostic markers and PAM50 subtyping. These observations support prospective clinical evaluation of LDHB as a predictive marker of response for patients with breast cancer receiving neoadjuvant chemotherapy.

©2013 AACR.

MeSH Terms (20)

Adult Aged Biomarkers, Tumor Breast Neoplasms Cell Line, Tumor Female Gene Expression Glycolysis Humans Isoenzymes L-Lactate Dehydrogenase Middle Aged Neoadjuvant Therapy Oxygen Consumption Phenotype Prognosis RNA, Messenger Transcriptome Treatment Outcome Triple Negative Breast Neoplasms

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