[Lani]

based on the number of copies of her2 and its amplicon as well as based on what other genes are included in the amplicon and whether they are mutated and deleted.

An amplicon is a stretch of DNA including the gene of interest (here her2). Some her2 amplified bcs have a longer amplicon than others ie, the part that is overcopied (like a paper in a xerox machine that just won't stop making extra copies) has more other genes on it than in some other her2+ bc tumors.

It is as if the xerox copier is stuck and the question is how many paragraphs are on the piece of paper. The fewer the paragraphs the less likely overcopying of the other info (paragraphs) will effect the tumors behavior.

But sometimes deletion or mutation is more important than amplification

I told you cancer was complicated!

Breast Cancer Res. 2011 Feb 2;13(1):R15. [Epub ahead of print]
Quantification and clinical relevance of gene amplification at chromosome 17q12-q21 in human epidermal growth factor receptor 2-amplified breast cancers.
Lamy PJ, Fina F, Bascoul-Mollevi C, Laberenne AC, Martin PM, Ouafik L, Jacot W.

Abstract
ABSTRACT:

INTRODUCTION: Human epidermal growth factor receptor 2 (HER2)-amplified breast cancers represent a tumor subtype with chromosome 17q rearrangements that lead to frequent gene amplifications. The aim of this study was to quantify the amplification of genes located on chromosome 17q and to analyze the relations between the pattern of gene amplifications and the patients' characteristics and survival.

METHODS: Patients with HER2-positive breast tumors (HER2 score of 3+ by immunohistochemistry or positive for HER2 amplification by fluorescence in situ hybridization (FISH)) (n = 86) and with HER2-negative breast tumors (n = 40) (negative control) were included in this study. Using a quantitative PCR method and DNA extracted from frozen tumor specimens, 11 genes (MED1, STARD3, HER2, GRB7, THRA, RARA, TOP2A, IGFBP4, CCR7, KRT20, KRT19 and GAS), which are localized within Chr17q12-q21 and have a putative role in breast cancer development, were quantified. Relapse-free and overall survival rates were estimated from the date of surgery to the date of the event of interest (recurrence or death) using the Kaplan-Meier method.

RESULTS: Gene amplification was observed only in HER2-positive tumors and the frequency of amplification decreased with the distance of the gene from HER2. HER2 presented the highest level of amplification. TOP2A was not included in the smallest region of amplification (SRA) involving HER2. Amplification of RARA, KRT20 and KRT19 was significantly associated with node-positive breast cancer (P=0.030, 0.002 and 0.033, respectively). During a median follow-up of 55 months (range 6 to 81 months), the subgroup of patients with hormone receptor-negative cancer and without TOP2A amplification showed the worst survival (relapse-free survival: HR=0.29 with 95% confidence interval [CI]: 0.13 to 0.65, P=0.001; and overall survival: HR=0.28 with 95% confidence interval [CI]: 0.10 to 0.76, P=0.008).

CONCLUSIONS: HER2 amplification seems to drive genomic instability along chromosome17q leading to different patterns of gene amplification. The study confirms the clinical importance of identifying, among the patients with HER2-positive breast tumors, the subgroup of patients with hormone receptor-negative and non-amplified TOP2A cancers as they have the worst prognosis.

PMID: 21288332