Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

Biochem Biophys Res Commun. 2014 Aug 15;451(1):54-61. doi: 10.1016/j.bbrc.2014.07.050. Epub 2014 Jul 21.


Background: (18)Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer.

Methods: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively.

Results: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR=0.47, P=0.02) and overall-survival (HR=0.38, P=0.002). These results were confirmed in the independent cohort of 127 cancer patients.

Conclusion: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H(+) symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

Keywords: Glycolysis; Hypoxia; MCT4; Monocarboxylate transporters; Triple negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism
  • Female
  • Glucose Transporter Type 1 / metabolism
  • Glycolysis
  • Humans
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lactate Dehydrogenase 5
  • Middle Aged
  • Monocarboxylic Acid Transporters / metabolism*
  • Muscle Proteins / metabolism*
  • Positron-Emission Tomography / methods
  • Predictive Value of Tests
  • Prognosis
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / mortality*
  • Triple Negative Breast Neoplasms / pathology


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • Isoenzymes
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • SLC16A4 protein, human
  • SLC2A1 protein, human
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases