Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for tumor biology and research

Abeer Alqaisi, Li Chen, Edward Romond, Mara Chambers, Mark Stevens, Grace Pasley, Mukta Awasthi, Suleiman Massarweh

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


ER and HER2 are critical drivers of breast cancer biology and can interact when co-expressed, but less data describe the impact of ER/HER2 co-expression on clinical disease characteristics. We studied the impact of ER and HER2 (co)-expression in a cohort of 1,187 patients with invasive breast cancer and compared disease characteristics among different groups according to ER and HER2 status. Age, tumor size, grade, nodal status, TNM stage, and metastatic sites were compared and significance determined using the appropriate t tests. All p values were two-tailed. Compared to ER-negative/HER2-negative disease as the control group, ER expression was associated with older age, smaller tumors, lower grade, earlier TNM stage, and increased bone involvement in de novo metastasis, while HER2 had no significant impact on these characteristics. ER and HER2 co-expression was associated with lower grade and higher bone involvement in de novo metastasis, reflecting a retained impact for ER. HER2 impact on ER-positive disease was reflected by younger age, higher grade and TNM stage, and increased frequency of visceral involvement in de novo metastasis. Within the ER-positive/HER2-positive group, triple positive breast cancer (ER+/PgR+/HER2+) was associated with younger age compared to ER+/PgR−/HER2+ disease (mean age of 50.8 vs. 56 years, p = 0.0226). PgR was also associated with younger age in ER+/HER2− disease with a mean age of 57.6 years in ER+/PgR+/HER2− disease vs. 63.4 years in ER+/PgR−/HER2− disease (p < 0.0001). In conclusion, ER has a profound impact on breast cancer characteristics, including a retained impact when co-expressed with HER2. Similarly, HER2 dramatically modulates ER-positive breast cancer making it more aggressive. PgR association with young age may be related to hormonal levels of the premenopausal state, with HER2 providing an earlier growth advantage in triple positive disease, suggesting a specific dependence for this subset on high estrogen levels.

Original languageEnglish
Pages (from-to)437-444
Number of pages8
JournalBreast Cancer Research and Treatment
Issue number2
StatePublished - Nov 7 2014

Bibliographical note

Funding Information:
Acknowledgments This work was supported by the Biostatistics and Bioinformatics Shared Resource and Cancer Research Informatics Shared Resource facilities of the Markey Cancer Center (P30CA177558). Presented at the 36th annual San Antonio Breast Cancer Symposium held in San Antonio, TX, December 2011 (Cancer Res, 2013 73; P3-07-04).

Publisher Copyright:
© 2014, Springer Science+Business Media New York.


  • Breast cancer
  • Co-expression
  • Estrogen receptor
  • Human epidermal growth factor receptor
  • Progesterone receptor
  • Triple positive breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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