TY - JOUR
T1 - Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics
T2 - implications for tumor biology and research
AU - Alqaisi, Abeer
AU - Chen, Li
AU - Romond, Edward
AU - Chambers, Mara
AU - Stevens, Mark
AU - Pasley, Grace
AU - Awasthi, Mukta
AU - Massarweh, Suleiman
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2014/11/7
Y1 - 2014/11/7
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Co-expression
KW - Estrogen receptor
KW - Human epidermal growth factor receptor
KW - Progesterone receptor
KW - Triple positive breast cancer
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U2 - 10.1007/s10549-014-3145-x
DO - 10.1007/s10549-014-3145-x
M3 - Article
C2 - 25257728
AN - SCOPUS:84911961587
SN - 0167-6806
VL - 148
SP - 437
EP - 444
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -