Level of HER2/neu gene amplification as a predictive factor of response to trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer

Gullo, Giuseppe; Bettio, Daniela; Torri, Valter; Masci, Giovanna; Salvini, P.; Santoro, Armando

doi:10.1007/s10637-008-9155-y

Cited by 22 publications

(17 citation statements)

References 23 publications

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“…In recent studies, a positive correlation was even shown between the level of HER-2 amplification assessed by FISH and the rate of pathologic complete response to trastuzumab-based neoadjuvant treatment [36,37]. Also in gastric cancer, tumors with both amplification and overexpression recently showed better response to trastuzumab than cancers with overexpression alone.…”

Section: Discussionmentioning

confidence: 98%

Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers

et al. 2010

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Section: Discussionmentioning

confidence: 98%

Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers

et al. 2010

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“…31 Surprisingly, however, the level of amplification has been proven so far to be truly outcome predictive only for neoadjuvant therapy. [32][33][34] With gastric cancer in the ToGA trial, a trastuzumab-based regimen was found more effective in patients with tumors highly expressing the ERBB2 protein. 4 A positive correlation between levels of gene amplification and overall survival after trastuzumabbased therapy has also been recently established.…”

Section: Discussionmentioning

confidence: 99%

Assessment of a HER2 scoring system for colorectal cancer: results from a validation study

et al. 2015

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We sought to develop criteria for ERBB2-positivity (HER2) in colorectal cancer to ensure accurate identification of ERBB2-amplified metastatic colorectal cancer patients suitable for enrolment in a phase II trial of ERBB2-targeted therapy (HERACLES trial). A two-step approach was used. In step 1, a consensus panel of pathologists adapted existing protocols for use in colorectal cancer to test ERBB2 expression and amplification. Collegial revision of an archival test cohort of colorectal cancer samples led to specific recommendations for adapting current breast and gastric cancer criteria for scoring ERBB2 in colorectal cancer. In step 2, from September 2012 to January 2015, colorectal-specific ERBB2 testing protocols and ERBB2 scoring criteria were used to centrally screen for ERBB2-positive KRAS wild-type colorectal cancer patients to be enrolled in the HERACLES trial (clinical validation cohort). In both archival test (N = 256) and clinical validation (N = 830) cohorts, a clinically sizeable 5% fraction of KRAS wild-type colorectal cancer patients was found to be ERBB2-positive according to the colorectal cancer-specific ERBB2 scoring criteria. ERBB2-positive tumors showed ERBB2 immunostaining consisting of intense membranous ERBB2 protein expression, corresponding to homogenous ERBB2 amplification, in 450% of cells. None of the immunohistochemistry 0 or 1+ cases was amplified. Concordance between SISH and FISH was 100%. In conclusion, we propose specific criteria for defining ERBB2-positivity in colorectal cancer (HERACLES Diagnostic Criteria). In a phase II trial of trastuzumab and lapatinib in a cetuximabresistant population, HERACLES Diagnostic Criteria shaped the selection of patients and defined ERBB2 as a predictive marker for response to ERBB2-targeted therapy in metastatic colorectal cancer.

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“…23 However, the role of HER2/neu in urinary bladder cancer is still unclear. A wide variability of HER2/neu gene amplification and of protein overexpression has been observed in TCC, associated with most advanced tumors and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

et al. 2009

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This study investigates the potential clinical significance of c-erbB-2 gene and chromosome 17 alterations by fluorescence in situ hybridization (FISH) analysis and HER2/neu overexpression by immunohistochemical staining in transitional cell carcinoma (TCC) of urinary bladder correlating the results with tumor stage and grade categories and with clinical behavior. Sixty-three cases of TCC retrieved from the files of 2 institutions were analyzed for chromosome 17 aberrations and c-erbB-2 amplification by FISH analysis and evaluated immunohistochemically for HER2/neu overexpression. Five tumors were G1, 29 intermediate grade (G2), and 29 tumors high grade (G3); 32 tumors had stage Ta, 18 tumors T1, and 13 tumors T2. We found polysomy of chromosome 17 in 58.7% of TCC with average chromosome copy number >2.26; increased number of HER2/neu gene copy was observed in 66.7% of tumors. C-erbB-2 amplification occurred in 6.3% of tumors. Immunohistochemically, 60.3% of TCC overexpressed HER2/neu and 39.7% of tumors were negative. All tumors with polysomy showed simultaneously increase of HER2/neu gene copy number of which 34/37 with protein overexpression. A statistically significant correlation between polysomy of chromosome 17 and tumor stage (P = .0003) and tumor grade (P < .0001) was found; polysomy was not seen in G1 tumors; however, 8/29 G2 tumors and 29/29 G3 tumors revealed polysomy of chromosome 17; in 8/32 Ta tumors, 14/18 T1 and 13/13 of deeply invasive tumors (T2) polysomy 17 was observed. Moreover, it was found that 7 superficial tumors (1 Ta and 6 T1) showed high polysomy with average of chromosome 17 copy number > or =3.76 as observed in all invasive tumors. The data suggest that although HER2/neu amplification, found in high grade and invasive tumors, is a rare event in TCC, polysomy of chromosome 17 is an important factor correlated with tumor stage and grade categories and could be considered a molecular marker of tumor progression with interesting diagnostic implications.

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Level of HER2/neu gene amplification as a predictive factor of response to trastuzumab-based therapy in patients with HER2-positive metastatic breast cancer

Cited by 22 publications

References 23 publications

Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers

Heterogenous high-level HER-2 amplification in a small subset of colorectal cancers

Assessment of a HER2 scoring system for colorectal cancer: results from a validation study

Role of Polysomy 17 in Transitional Cell Carcinoma of the Bladder: Immunohistochemical Study of HER2/neu Expression and FISH Analysis of c-erbB-2 Gene and Chromosome 17

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