Salivary Duct Carcinoma - A Highly Aggressive Salivary Gland Tumor with HER-2/neu Oncoprotein Overexpression

Skálová, Alena; Stárek, Ivo; Kučerová, V.; Szépe, P; Plank, L

doi:10.1078/0344-0338-00136

Cited by 82 publications

(37 citation statements)

References 16 publications

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“…The HER2 gene encodes for a receptor tyrosine kinase often amplified and overexpressed in SDC (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Using FISH, we detected HER2 gene amplification in 8 of 27 cases (30%).…”

Section: Clinical Characteristics Of the Cohortmentioning

confidence: 99%

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Detection of Novel Actionable Genetic Changes in Salivary Duct Carcinoma Helps Direct Patient Treatment

Nardi

Sadow

Juric

et al. 2013

Clinical Cancer Research

105

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Purpose: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland cancers for which cytotoxic chemotherapy has limited efficacy. We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents.Experimental Design: We genotyped 27 SDC archival specimens from patients followed at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2011. These included the tumors of 8 patients who were tested prospectively. Targeted mutational analysis of 13 clinically relevant cancer genes was conducted using SNaPshot multiplexed genotyping. FISH was conducted to detect HER2 gene amplification. Patient medical records and tumor histopathologic features were retrospectively reviewed.Results: Mutually exclusive genetic aberrations were detected in 15 of 27 (56%) tumors, including 2 (7%) mutations in BRAF, 5 (19%) mutations in PIK3CA, and 8 (30%) cases of HER2 gene amplification. To our knowledge, this is the first time that BRAF and PIK3CA mutations have been reported in this tumor type. Prospective clinical testing of 8 patients with SDC identified actionable genetic alterations in 6 tumors and influenced therapeutic decisions for all 6 patients.Conclusion: SNaPshot molecular profiling identified novel genetic changes in SDCs, expanded the therapeutic options for patients with this rare tumor, and is changing SDC management at our institution. These findings highlight the importance of using broad-based genetic profiling to expedite the identification of effective-targeted therapies for patients with rare malignancies. Clin Cancer Res; 19(2); 480-90. Ó2012 AACR.

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Section: Clinical Characteristics Of the Cohortmentioning

confidence: 99%

“…In addition to the histologic resemblance between SDC and breast ductal carcinoma, overexpression of the HER2/ neu is also a feature shared by both tumor types (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Detection of Novel Actionable Genetic Changes in Salivary Duct Carcinoma Helps Direct Patient Treatment

Nardi

Sadow

Juric

et al. 2013

Clinical Cancer Research

105

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“…Yet these carcinomas frequently express an amplification of the ErbB-2 (HER-2) oncogene, and the membrane overexpression of its protein product (p185) 4 is common and correlates with a poor prognosis (4 -7). p185 is a receptor tyrosine kinase related to the epidermal growth factor receptor family.…”

mentioning

confidence: 99%

Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent ofHER-2/neuExpression

Pannellini

Spadaro

Carlo

et al. 2006

The Journal of Immunology

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Double transgenic mice overexpressing the transforming rat HER-2/neu oncogene and the mutated p53, with both dominant-negative and a gain-of-function properties, display early aggressive and metastasizing parotid tumors. Multiple acinar and ductal hyperplasia foci overexpressing the HER-2/neu gene product are evident at wk 5 and progress to poorly differentiated carcinoma by wk 7. Mice die before wk 18 with invasive carcinomas and multiple metastases that no longer express HER-2/neu. A combination of repeated electroporations of plasmids coding for the extracellular and transmembrane domains of the rat HER-2/neu receptor with systemic IL-12 administrations started when the parotids that present diffuse hyperplasia protected all female and 50% of the male mice until the close of the experiment at wk 40. This combined treatment began when multifocal in situ carcinomas that were already present cured 33% of the females and 25% of the males. The most prominent immunologic features associated with the antitumor protection were the production of high titers of anti-HER-2/neu Abs and the nonappearance of cell-mediated cytotoxic reactivity. In conclusion, anti-HER-2/neu vaccination combined with systemic IL-12 control parotid carcinomas as far as p53 mutation makes their growth independent of HER-2/neu expression.

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“…Although amplification of the HER2 gene was first described in human breast cancer, the gene is amplified in other human tumor types, including ovarian, endometrial, salivary gland, gastric, bladder and pancreatic cancers [24][25][26][27][28][29][30].…”

Section: Her2 Amplification and Overexpressionmentioning

confidence: 99%

Anti-erbB-2 antibody trastuzumab in the treatment of HER2-amplified breast cancer

Yeon

Pegram

2005

Invest New Drugs

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Human epidermal growth factor receptor-2 (HER2/erbB-2) is a member of a family of four transmembrane receptor tyrosine kinases that regulate cell growth, survival and differentiation via multiple signal transduction pathways. Amplification of the HER2 gene occurs in 20-25% of human breast cancers. This amplification event is an independent adverse prognostic factor as well as a predictive factor for increased response to doxorubicin-based combination chemotherapy, response to trastuzumab and decreased response to hormonal therapy. Methods for detecting protein overexpression or gene amplification in clinical tumor specimens include immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques, with the latter considered by some to be more accurate. Trastuzumab (Herceptin) is a recombinant humanized monoclonal antibody which targets an epitope in the extracellular domain of the HER2 protein. Preclinical models demonstrated that this antibody has significant anti-tumor activity as a single agent and has synergy with certain chemotherapeutic drugs. Phase II and III clinical trials performed in women with metastatic breast cancer that overexpress HER2 have shown that trastuzumab has clinical activity when used as first-, second- or third-line monotherapy, and improves survival when used as first-line therapy in combination with chemotherapy. Newer combinations with numerous chemotherapeutic drugs have also shown significant clinical activity in phase II studies. In all of these trials, trastuzumab was generally well-tolerated, but cardiac toxicity (particularly when the antibody was combined with anthracyclines) was an unexpected adverse effect. Although trastuzumab is currently usually administered on a weekly intravenous schedule, evidence suggests that a triple dose of the drug given once every three weeks has a pharmacokinetic profile expected to be equally efficacious. Neither the optimal schedule nor the optimal duration of trastuzumab therapy has yet been clearly defined in controlled clinical trials. Current clinical investigations of trastuzumab include its use in both the adjuvant and neoadjuvant settings as well as in combination with other chemotherapy drugs or new biologic targeted agents.

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Salivary Duct Carcinoma - A Highly Aggressive Salivary Gland Tumor with HER-2/neu Oncoprotein Overexpression

Cited by 82 publications

References 16 publications

Detection of Novel Actionable Genetic Changes in Salivary Duct Carcinoma Helps Direct Patient Treatment

Detection of Novel Actionable Genetic Changes in Salivary Duct Carcinoma Helps Direct Patient Treatment

Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent ofHER-2/neuExpression

Anti-erbB-2 antibody trastuzumab in the treatment of HER2-amplified breast cancer

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