FISH DETECTION OF HER-2 NEU ONCOGENE AMPLIFICATION IN EARLY-ONSET BREAST-CANCER/

HER-2/neu (c-erbB-2) gene amplification based on Southern blotting or immunohistochemistry has been shown to be predictive of poor outcome i n breast cancer occurring in women over 40, but there is little data o n the role of HER-2/neu in young women with breast cancer, many of who m may have inherited BRCA1 or other predisposing genes. The present st udy used fluorescent in situ hybridization (FISH) on archival specimen s of breast cancer from 37 women under the age of 40 to evaluate the r ole of HER-2/neu amplification in this cohort, and to also evaluate th e efficacy of FISH for quantifying amplification. The frequency of pri mary tumors with a greater than fourfold increase in gene copy number was found to be 38%, which is similar to the frequency of amplificatio n reported in Southern blot studies in older women. However, the great er sensitivity of FISH enabled detection of low level amplification (m ore than 2 but less than 8 gene copies), which was found in an additio nal 30% of the tumors. Patients with low level amplification demonstra ted a 54% recurrence rate, compared to 86% in those with high amplific ation and 17% in those with no amplification. HER-2/neu amplification appeared to be more prognostic of recurrence than nodal status, with 4 5% of node negative tumors recurring compared to 62% of those which we re node positive, nor was tumor size predictive of recurrence in this cohort since tumors of 2 cm or less recurred in 44% of cases compared to 57% of those larger than 2 cm. Thus, this study demonstrates that F ISH is a reproducible and sensitive technique for detecting HER-2/neu amplification, and that amplification of the oncogene is the strongest independent indicator of recurrence of breast cancer in young women.