title: Lactate dehydrogenase B: a metabolic marker of response to neoadjuvant chemotherapy in breast cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dennison
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Molina
authors.forename: Shreya
authors.initials: S
authors.lastname: Mitra
authors.forename: Ana M
authors.initials: AM
authors.lastname: González-Angulo
authors.forename: Justin M
authors.initials: JM
authors.lastname: Balko
authors.forename: María G
authors.initials: MG
authors.lastname: Kuba
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Sanders
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Pinto
authors.forename: Henry L
authors.initials: HL
authors.lastname: Gómez
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Arteaga
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010101:Oxygen Consumption; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D012333:RNA, Messenger; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1