HER-2-positive metastatic breast cancer: trastuzumab and beyond

Metro, Giulio; Mottolese, Marcella; Fabi, Alessandra

doi:10.1517/14656566.9.15.2583

Cited by 42 publications

(19 citation statements)

References 95 publications

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“…The introduction of trastuzumab (Herceptin, Genentech), the humanized monoclonal antibody (mAb) against HER2 into the metastatic setting and, more recently, also in the (neo)adjuvant setting (1,2) has completely changed the natural history of HER2 positive BC patients both in terms of time to recurrence and survival. Despite the benefits shown by trastuzumab, a percentage of these patients have demonstrated clinical resistance.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the benefits shown by trastuzumab, a percentage of these patients have demonstrated clinical resistance. In metastatic BC (MBC), 44% to 64% of patients show upfront resistance to trastuzumab as a single-agent therapy (2,3), whereas 12% to 22% of patients are primarily resistant to trastuzumab when given in combination with various cytotoxic drugs (2). Even though the efficacy of trastuzumab is first dependent on the accuracy in assessing HER2 status, various mechanisms are also involved in the resistance to the mAb.…”

Section: Introductionmentioning

confidence: 99%

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HER2 Protein and Gene Variation between Primary and Metastatic Breast Cancer: Significance and Impact on Patient Care

Fabi¹,

Benedetto²,

Metro³

et al. 2011

Clinical Cancer Research

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Purpose: To analyze HER2 status in primary breast cancer (PBC) compared with correspondent metachronous metastases and to investigate whether BC phenotype may be predictive of change in HER2 expression.Experimental Design: HER2 was investigated by immunohistochemistry, silver in situ hybridization (SISH), and FISH, in a series of 137 tumors, building up a tissue microarray to concurrently analyze each single PBC and metastatic (MBC) on the same slide.Results: HER2 status was discordant in 14 cases (10%): 12 negative in PBC and positive in metastases and two positive in PBC and negative in metastases (P ¼ 0.04). These findings were confirmed by a PCR based test termed Multiplex Ligation-dependent Probe Amplification (MLPA). HER2 status changed in hormone receptor-positive BC more frequently than in negative ones (P ¼ 0.002). In addition, we evaluated HER2 gene and chromosome 17 copy number by SISH in the 123 cases with unchanged HER2 status during progression. We found consistent HER2 gene copy number stability in the 100 nonamplified cases. Conversely, of the 23 amplified PBC, 13 (57%) demonstrated a significant increase in the HER2 gene and chromosome 17 copy number in their paired metastases (P ¼ 0.01), as defined by SISH (k ¼ 0.54, P < 0.0001) and MLPA. Patients who changed HER2 status from negative to positive, presented significant longer time to progression when treated with trastuzumab compared to those who were untreated (P ¼ 0.04).Conclusions: When feasible, HER2 reassessment in metastatic lesions should be carefully taken into account, especially for metastases coming from primary hormone receptor-positive BC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HER2 Protein and Gene Variation between Primary and Metastatic Breast Cancer: Significance and Impact on Patient Care

Fabi¹,

Benedetto²,

Metro³

et al. 2011

Clinical Cancer Research

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“…Local CerbB2 (2+) FISH (+) cases benefited from adjuvant herceptin treatment significantly, however central CerbB2(2+) FISH(+) cases didn't. No significant difference was found in the combination of two groups [9]. Again, for CerbB2 (2+) FISH (+) cases in the adjuvant studies, significant difference was found for DFS in NSABP B31 study, and was not found in NCCTG N9831 study [10][11].…”

Section: Resultsmentioning

confidence: 99%

“…CerbB2 positive tumors had poor prognosis. However the introduction of the anti-tumor agents that target this receptor and pathway have changed the poor prognosis of this tumor group as adjuvant or metastatic context [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Should FISH Test be Performed to all Patients With Breast Cancer?

Mutlu¹,

Karaca²,

Akca³

et al. 2013

Med-Science

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CerbB2 receptor determination is very important for the prognosis and treatment of breast cancer. The most used two methods for CerbB2 receptor determination are immunohistochemistry and FISH methods. FISH method is recommended for immunohistochemically CerbB2 (++) patient group. Therefore, even though the immunohistochemically CerbB2 (++) patients are in the same group, FISH test divides the results into two separate groups. Our study compared these two groups in terms of relaps duration. Total of 85 patients from The Kayseri Research and Training Hospital in Kayseri, Kayseri Erciyes University Hospital and Mersin State Hospital were included in this study. The relaps duration of the patients were determined and then compared statistically. When the mean disease free survival was compared for FISH(+) and FISH(−) groups, the mean DFS was 46±5 and 73±8 months. However, the median DFS was 38±9 months for the FISH positive group. No median PFS was reached for FISH (−) group. Immunohistochemically CerbB2 (++) breast cancer patients are considered as in the same group, however actually they have different prognostic features. Similarly, when the immunohistochemical tests and FISH tests are compared for CerbB2 positivity, different results are obtained. As a consequence of that, the therapy alternatives will be changed. Therefore, we conclude that the FISH test should be performed to all patients.

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“…Amplification or overexpression of HER2 has been detected in approximately 20% of invasive BCs and is associated with increased tumor aggressiveness, resistance to therapies, and increased mortality (2). The introduction of trastuzumab, the humanized monoclonal antibody directed against the extracellular domain of HER2, resulted in an increasing time to recurrence and overall improvement in survival in patients whose tumors overexpressed HER2 (3). However, despite the presence of HER2 overexpression, 44%-64% of patients with metastatic BC show upfront resistance to trastuzumab as a single-agent therapy, whereas only 12%-22% of patients are primarily resistant to trastuzumab when it is given in combination with cytotoxic chemotherapy (4).…”

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confidence: 99%

PET of HER2-Positive Pulmonary Metastases with ¹⁸F-Z_HER2:342 Affibody in a Murine Model of Breast Cancer: Comparison with ¹⁸F-FDG

et al. 2012

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Targeted therapies often depend on the expression of the target present in the tumor. This expression can be difficult to ascertain in widespread metastases. 18 F-FDG PET/CT, although sensitive, is nonspecific for particular tumor markers. Here, we compare the use of a human epidermal growth factor receptor 2 (HER2)-specific 18 F-Z HER2:342 -Affibody and 18 F-FDG in HER2-expressing pulmonary metastases in a murine model of breast cancer. Methods: The lung metastasis model was established by intravenous injection of MDA-MB-231 HER2 -Luc human breast cancer cells into the tail vein. Bioluminescence imaging was used to evaluate metastasis progression. Uptake of 18 F-Z HER2:342 -Affibody and 18 F-FDG was confirmed by coregistration of the PET images with MR and CT images. At the end of the study, the presence of neoplastic cells and HER2 expression in lung tissues, and distribution of the tracer, were assessed ex vivo by immunohistochemistry and autoradiography. Results: 18 F-Z HER2:342 -Affibody successfully targeted HER2-positive lesions in the lung and allowed detection of metastases as early as 9 wk after injection of cells. In contrast, 18 F-FDG uptake was often masked by surrounding inflammatory changes and was nonspecific for HER2 expression. HER2 expression at a cellular level correlated well with tracer uptake on autoradiography. Conclusion: 18 F-Z HER2:342 -Affibody is a promising tracer for evaluation of HER2 status of breast cancer metastases and is more specific for detecting HER2-positive lesions than 18 F-FDG.

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HER-2-positive metastatic breast cancer: trastuzumab and beyond

Cited by 42 publications

References 95 publications

HER2 Protein and Gene Variation between Primary and Metastatic Breast Cancer: Significance and Impact on Patient Care

HER2 Protein and Gene Variation between Primary and Metastatic Breast Cancer: Significance and Impact on Patient Care

Should FISH Test be Performed to all Patients With Breast Cancer?

PET of HER2-Positive Pulmonary Metastases with ¹⁸F-Z_HER2:342 Affibody in a Murine Model of Breast Cancer: Comparison with ¹⁸F-FDG

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HER-2-positive metastatic breast cancer: trastuzumab and beyond

Cited by 42 publications

References 95 publications

HER2 Protein and Gene Variation between Primary and Metastatic Breast Cancer: Significance and Impact on Patient Care

HER2 Protein and Gene Variation between Primary and Metastatic Breast Cancer: Significance and Impact on Patient Care

Should FISH Test be Performed to all Patients With Breast Cancer?

PET of HER2-Positive Pulmonary Metastases with 18F-ZHER2:342 Affibody in a Murine Model of Breast Cancer: Comparison with 18F-FDG

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PET of HER2-Positive Pulmonary Metastases with ¹⁸F-Z_HER2:342 Affibody in a Murine Model of Breast Cancer: Comparison with ¹⁸F-FDG