Expression of breast cancer stem cell markers as predictors of prognosis and response to trastuzumab in HER2-positive breast cancer.

Abstract

BACKGROUND:

Breast cancer stem cells (BCSCs) have been suggested to have clinical implications for cancer therapeutics because of their proposed role in chemoresistance. The aim of this study was to investigate the impact of BCSC marker expression on clinical outcome and trastuzumab response in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

METHODS:

We analysed the expression of BCSC markers, CD44+/CD24- and aldehyde dehydrogenase 1 (ALDH1), and clinical outcomes in three sets of breast cancer cases: Set 1, 242 HER2-positive primary breast cancers treated by various modalities; Set 2, 447 HER2-positive primary breast cancers treated with surgery and chemotherapy plus adjuvant trastuzumab; Set 3, 112 metastatic HER2-positive breast cancers treated with trastuzumab.

RESULTS:

Expression of CD44+/CD24- and ALDH1 was detected in 30.7% and 10.0%, respectively, of the Set 1 cases, and was associated with hormone receptor negativity. In survival analyses, expression of CD44+/CD24-, but not ALDH1, was found to be an independent prognostic factor for poor disease-free and overall survival in whole patients and also in the subgroup not receiving adjuvant trastuzumab. In Set 2 cases treated with adjuvant trastuzumab, CD44+/CD24- expression was an independent prognostic factor for poor disease-free survival, but not for overall survival; expression of ALDH1 had no impact on disease-free or overall survival. In metastatic disease treated with trastuzumab (Set 3 cases), CD44+/CD24- and ALDH1 expression had no effect on trastuzumab response or survival.

CONCLUSIONS:

These results suggest that the CD44+/CD24- phenotype can be used as a prognostic factor for clinical outcome and a predictive factor of trastuzumab response in patients with HER2-positive primary breast cancer.

• Authors: An Na Seo, Hee Jin Lee, Eun Joo Kim, Min Hye Jang, Yu Jung Kim, Jee Hyun Kim, Sung-Won Kim, Han Suk Ryu, In Ae Park, Seock-Ah Im, Gyungyub Gong, Kyung Hae Jung, Hee Jeong Kim, So Yeon Park
• Journal: British journal of cancer (Br J Cancer) Vol. 114 Issue 10 Pg. 1109-16 (05 10 2016) ISSN: 1532-1827 [Electronic] England
• PMID: 27115469 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• CD24 Antigen
• CD24 protein, human
• CD44 protein, human
• Hyaluronan Receptors
• Isoenzymes
• Aldehyde Dehydrogenase 1 Family
• ALDH1A1 protein, human
• Retinal Dehydrogenase
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab

Topics

• Aldehyde Dehydrogenase 1 Family
• Antineoplastic Agents (administration & dosage, pharmacology)
• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (drug therapy, metabolism)
• CD24 Antigen (metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hyaluronan Receptors (metabolism)
• Isoenzymes (metabolism)
• Neoplastic Stem Cells (drug effects, metabolism)
• Prognosis
• Receptor, ErbB-2 (metabolism)
• Retinal Dehydrogenase (metabolism)
• Survival Analysis
• Trastuzumab (administration & dosage, pharmacology)
• Treatment Outcome