Hormone Receptor Expression in HER2+ Breast Cancer and Relationship to Ki67 and p53 Expression
Debra Smith, Diane Xiang, Alana Christie, George John, Yan Peng, Sunati Sahoo, Yisheng Fang, Venetia Sarode. UT Southwestern Medical Center, Dallas, TX
Background: HER2+ invasive breast cancer (IBCA) is a heterogeneous group less likely to be estrogen receptor (ER) positive than HER2- IBCA. Bidirectional crosstalk between HER2 and ER signaling pathways has been demonstrated in vivo, and a subset of HER2+ IBCA appears to be driven by ER. In addition to ER, PR and HER2, proliferation and p53 alteration play important roles in defining molecular subtypes. Further characterization of the HER2+ subset is important for appropriate targeted therapies. The relationship between HER2 and ER, PR, Ki67 and p53 expression has not been well documented.
Design: Using a set of 482 HER2-amplified IBCA tumors, we examined the relationship between ER, PR, Ki67 and p53 expression and HER2 amplification. Estimation of biomarkers was performed using routine immunohistochemistry. HER2 FISH assay was performed with a PathVysion kit according to manufacturer's guidelines. Biomarker semi-quantification was performed by image analysis. Positive cut-offs were as follows: ≥1% for ER, PR; FISH ratio >2.2 for HER2. For each parameter among the subgroups, 1-way ANOVA was used for overall mean comparison and Tukey-Kramer tests were used for pairwise comparisons.
Results: Of the HER2+ tumors, 200/482 (41.49%) were ER+ and PR+; 193 (40.04%) were hormone receptor (HR) negative; and 89 (18.46%) were ER+ (85) or PR+ (4). HER2 amplification was lower in triple positive compared to double positive and HR- tumors. ER and PR expression levels were higher in triple positive than in double positive tumors. HR- tumors showed higher Ki-67 and p53 expression compared to HR+ tumors. Mean values for each parameter in each of the subgroups are shown below.
|Variable||ER+/PR+/HER2+||ER+ or PR+/HER2+||ER-/PR-/HER2+||p-value|
|HER2 Amplification (FISH Ratio)∗§||4.60||5.45||5.38||0.0027|