Fluorescence in situ hybridization (FISH) may accurately select patients likely to benefit from herceptin monotherapy

Cobleigh, M.; Vogel, Charles-André; Tripathy, Debu; Mass, R.; Murphy, Maureen; Press, Macmillan

doi:10.1016/s0959-8049(01)81193-x

Cited by 4 publications

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“…Furthermore, retrospective analyses revealed that patients who tested HER-2 positive by FISH experienced significantly better response rates and improved survival with trastuzumab than those patients whose tumors were FISH negative. This suggests that FISH may predict more accurately which patients will obtain the most clinical benefit from trastuzumab therapy in the metastatic setting (36).…”

Section: Discussionmentioning

confidence: 99%

Pathologic Complete Response to Trastuzumab-Based Neoadjuvant Therapy Is Related to the Level of HER-2 Amplification

Arnould́

Arveux

Couturier

et al. 2007

Clinical Cancer Research

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Purpose: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer. Experimental Design: Breastbiopsies from 93 HER-2^positivepatients treatedwithtrastuzumabbased neoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+. Results: HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low-and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low-plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen,Tor N stage, tumor grade, or hormonal receptors. Conclusions: This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.The human epidermal growth factor receptor-2 (HER-2) gene, which plays an important role in tumor formation and growth processes, is amplified in approximately 20% to 30% of all breast cancers (1, 2). Patients whose tumors overexpress HER-2 are more likely to experience a shorter time to relapse and a significantly lower overall survival rate (1, 2). Treatment with trastuzumab (Herceptin), a recombinant monoclonal antibody against HER-2, results in significant clinical benefits in patients diagnosed with HER-2 -positive disease. In phase II/III trials, trastuzumab significantly improved survival by up to 8.5 months when given as first-line treatment in combination with a taxane (3, 4) in women with HER-2 -positive metastatic breast cancer. In five major adjuvant clinical trials involving >13,000 women with HER-2 -positive early breast cancer, trastuzumab significantly reduced the risk of recurrence and improved overall survival by one third (5 -8).In the neoadjuvant setting, primary systemic therapy with trastuzumab-based combination chemotherapy has also shown clinical benefit in terms of both overall response and pathologic complete response rates (9 -13). The goals of primary systemic therapy are to treat occult system...

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Section: Discussionmentioning

confidence: 99%

Pathologic Complete Response to Trastuzumab-Based Neoadjuvant Therapy Is Related to the Level of HER-2 Amplification

Arnould́

Arveux

Couturier

et al. 2007

Clinical Cancer Research

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“…More importantly, clinical trials have established the significance of ERBB2 gene amplification and overexpression in predicting tumor response to the humanized anti‐ERBB2 antibody trastuzumab (Pegram et al, 1998a, b; Cobleigh et al, 1999; Slamon et al, 2001; Vogel et al, 2001), the first targeted antineoplastic drug. Breast carcinomas lacking ERBB2 gene amplification rarely respond to trastuzumab, whereas 20–40% of tumors with ERBB2 amplification have good response (Cobleigh et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Effects of ERBB2 amplicon size and genomic alterations of chromosomes 1, 3, and 10 on patient response to trastuzumab in metastatic breast cancer

Morrison

Jewell

Usha

et al. 2007

Genes Chromosomes & Cancer

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Trastuzumab is widely used for advanced breast cancer patients with ERBB2-amplified tumors. Nevertheless, over half of these patients do not have an objective response. One reason may be altered expression of genes that might compensate for ERBB2 inhibition. We previously mapped the gene-rich region of chromosome 17 telomeric to ERBB2, and reported considerable variability in the telomeric extent of the ERBB2 amplicon. Here we examined whether the variable amplicon size may be associated with patient response to trastuzumab. In addition, we looked at associations between response and several signaling pathway-related genes unrelated to the ERBB2 amplicon, including AKT3, PTEN, PIK3CA, and PTGS2. In 35 patients with ERBB2-amplified metastatic breast cancer, with 40% overall response to trastuzumab, fluorescence in situ hybridization identified the telomeric extent of the ERBB2 amplicon and the status of the several pathway-related genes. Objective response strongly correlated with the telomeric amplicon size, with 62% of patients with shorter amplicons responding, compared with only 7% of patients with longer amplicons (P = 0.0015). Abnormal copy number of PTGS2 was marginally associated with objective response (P = 0.066), while abnormal copy numbers of two reference loci, 1q25 and the chromosome 10 centromere, were significantly associated with response. Pairwise combinations of copy number status of these loci and ERBB2 amplicon size provided stronger associations and identified a group of patients without responders. These results suggest that patient selection for trastuzumab may be improved by considering ERBB2 amplicon size and genomic status of the 1q25, PTGS2, and centromere 10 loci.

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“…Η ενίσχυση γονίδιου HER2 θα πρέπει να ανιχνεύεται με τη χρήση φθορίζοντος in situ υβριδισμού (FISH) ή χρωμογενικού in situ υβριδισμού (CISH) σε σταθερά τμήματα του όγκου. Οι αθενείς είναι κατάληλοι για θεραπεία με Herceptin εφόσον παρουσιάζουν ισχυρή υπερέκφραση του HER2, όπως περιγράφεται από αποτέλεσμα 3+ κατά IHC ή θετκό αποτέλεσμα FISH ή CISH 175,176 .…”

Section: ανίχνευση της Her2 υπερέκφρασης ή της ενίσχυσης γονιδίου Her2unclassified

Το Herceptin (trastuzumab) στη θεραπεία του μεταστατικού καρκίνου του μαστού

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Fluorescence in situ hybridization (FISH) may accurately select patients likely to benefit from herceptin monotherapy

Cited by 4 publications

References 0 publications

Pathologic Complete Response to Trastuzumab-Based Neoadjuvant Therapy Is Related to the Level of HER-2 Amplification

Pathologic Complete Response to Trastuzumab-Based Neoadjuvant Therapy Is Related to the Level of HER-2 Amplification

Effects of ERBB2 amplicon size and genomic alterations of chromosomes 1, 3, and 10 on patient response to trastuzumab in metastatic breast cancer

Το Herceptin (trastuzumab) στη θεραπεία του μεταστατικού καρκίνου του μαστού

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