Breast cancer subtypes and the risk of local and regional relapse.

Abstract

PURPOSE:

The risk of local and regional relapse associated with each breast cancer molecular subtype was determined in a large cohort of patients with breast cancer. Subtype assignment was accomplished using a validated six-marker immunohistochemical panel applied to tissue microarrays.

PATIENTS AND METHODS:

Semiquantitative analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin (CK) 5/6 was performed on tissue microarrays constructed from 2,985 patients with early invasive breast cancer. Patients were classified into the following categories: luminal A, luminal B, luminal-HER2, HER2 enriched, basal-like, or triple-negative phenotype-nonbasal. Multivariable Cox analysis was used to determine the risk of local or regional relapse associated the intrinsic subtypes, adjusting for standard clinicopathologic factors.

RESULTS:

The intrinsic molecular subtype was successfully determined in 2,985 tumors. The median follow-up time was 12 years, and there have been a total of 325 local recurrences and 227 regional lymph node recurrences. Luminal A tumors (ER or PR positive, HER2 negative, Ki-67 < 1%) had the best prognosis and the lowest rate of local or regional relapse. For patients undergoing breast conservation, HER2-enriched and basal subtypes demonstrated an increased risk of regional recurrence, and this was statistically significant on multivariable analysis. After mastectomy, luminal B, luminal-HER2, HER2-enriched, and basal subtypes were all associated with an increased risk of local and regional relapse on multivariable analysis.

CONCLUSION:

Luminal A tumors are associated with a low risk of local or regional recurrence. Molecular subtyping of breast tumors using a six-marker immunohistochemical panel can identify patients at increased risk of local and regional recurrence.

• Authors: K David Voduc, Maggie C U Cheang, Scott Tyldesley, Karen Gelmon, Torsten O Nielsen, Hagen Kennecke
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 10 Pg. 1684-91 (Apr 01 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20194857 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Ki-67 Antigen
• Receptors, Estrogen
• Receptors, Progesterone
• ErbB Receptors

Topics

• Adult
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (mortality, pathology)
• ErbB Receptors (metabolism)
• Female
• Humans
• Ki-67 Antigen (metabolism)
• Lymphatic Metastasis
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Recurrence, Local
• Neoplasms, Hormone-Dependent
• Receptors, Estrogen (analysis)
• Receptors, Progesterone (analysis)
• Tissue Array Analysis