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Correlation of Her‐2/neu Gene Amplification with Other Prognostic and Predictive Factors in Female Breast Carcinoma

Abstract:   The purpose of this study was to determine if any relationship exists between Her‐2/neu gene amplification and estrogen receptor (ER), progesterone receptor (PR), MIB‐1, grade, size and age in female breast cancer. Five hundred and eighteen female patients with invasive breast carcinoma, 390 ductal and 128 lobular, in which assessment of Her‐2/neu amplification by fluorescence in‐situ hybridization (FISH) has been performed, were reviewed retrospectively. Each patient was further assessed for ER, PR, MIB‐1, grade, size and age at diagnosis. Chi‐square analysis was then used to correlate the above observations. Overall gene amplification was seen in 76 (15%) of the cases, 68 (17%) were ductal and 8 (6%) were lobular. Her‐2/neu gene was amplified in 37 (10%) out of 379 ER positive cases and in 39 (28%) out of 139 ER negative cases. Her‐2/neu was amplified in 22 (7%) out of 301 PR positive cases and in 54 (25%) out of 217 PR negative cases. Amplification occurred in 18 (8%) out of 222 negative MIB‐1 cases and amplified in 58 (20%) out of 296 positive cases. Amplification was seen in 5 (10%) out of 49 grade I tumors, 17 (12%) out of 143 grade II tumors and 54 (27%) out of 198 grade III tumors. Lobular carcinomas were not graded. Amplification was present in 52 (15%) out of 346 T1 lesions, in 17 (13%) out of 130 T2 lesions, in 5 (17%) out of 30 T3 lesions and in 2 (17%) out of 12 T4 lesions. Her‐2/neu was amplified in 67 (14%) out of 467 woman 41 years and older, and in 9 (18%) out of 51 women 40 years and younger. Comparison of these frequencies using chi‐square test revealed statistically significant correlation between Her‐2/neu amplification and ductal versus lobular carcinoma (p < 0.0003), ER (p = 0.0001) and PR (p < 0.0001) negative tumors, over‐expression of MIB‐1 (p < 0.0005) and high tumor grade (p = 0.0009), while size of the tumor (p = 0.08) and age of the patients (p = 0.67) were not statistically significant. Correlation was found between Her‐2/neu amplification and tumor type, high histological grade, ER and PR negative tumors, and high proliferative MIB‐1 index. No correlation was found between size of the tumor and age of the patient with Her‐2/neu amplification.