The Challenging Estrogen Receptor-Negative/ Progesterone Receptor-Negative/HER-2-Negative Patient: A Promising Candidate for Epidermal Growth Factor Receptor-Targeted Therapy?

Siziopikou, Kalliopi P.; Ariga, Reshma; Proussaloglou, Kimon; Gattuso, Paolo; Cobleigh, Melody A.

doi:10.1111/j.1075-122x.2006.00276.x

Cited by 45 publications

(35 citation statements)

References 19 publications

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“…Increased HER1 protein expression is described in about 40% of BC, (ranging from 14% to 91% of all primary BC). High expression is described in triple negative breast cancer and metaplastic cancer (mostly basal-like) 7,14,[64][65][66][67][68][69][70][71][72] . HER1 overexpression was found in 30% of inflammatory breast cancer (IBC).…”

Section: The Her Familymentioning

confidence: 99%

Lapatinib in Breast Cancer - The Predictive Significance of Her1 (Egfr), Her2, Pten and Pik3ca Genes and Lapatinib Plasma Level Assessment

Bouchalová¹,

Cizkova²,

Cwiertka³

et al. 2010

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Breast cancer treatment trends are currently based on tailored therapies using tumor and patient biomarkers. Lapatinib is the first dual inhibitor of HER1 (EGFR, ErbB1) and HER2 (ErbB2, Neu) tyrosine kinases to be used in clinical practice. However, only HER2 is currently used for therapy indications and new predictors for the treatment with lapatinib are sought.Methods and results. This minireview focuses on lapatinib and its role in breast cancer treatment. Preclinical and clinical studies as well as pharmacological characteristics are briefly reviewed while the focus is on efficacy assessment including predictive factors for therapy outcome.Conclusion. Lapatinib (Tykerb/Tyverb) was Food and Drug Administration (FDA) approved in 2007 for use in combination with capecitabine for the treatment of HER2-positive advanced or metastatic breast cancer in patients who had received previous treatment (including anthracycline, taxane and trastuzumab containing regimens) and in 2010 for use in combination with letrozole for postmenopausal women with hormonal receptor positive and HER2-positive metastatic breast cancer. In contrast to trastuzumab (Herceptin), lapatinib is orally administered and it targets both HER2 and HER1 receptors. As a synthetic and oral tyrosine kinase inhibitor (TKI), it is convenient, cheaper and easier to produce than monoclonal antibodies. The recommended dosage is not dependent on body weight either. Lapatinib plasma level measurement could be an approach to tailored therapy for further optimizing the dose and prolonging this efficient therapy. New lapatinib response predictors are being evaluated. At this time, only HER2

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Section: The Her Familymentioning

confidence: 99%

Lapatinib in Breast Cancer - The Predictive Significance of Her1 (Egfr), Her2, Pten and Pik3ca Genes and Lapatinib Plasma Level Assessment

Bouchalová¹,

Cizkova²,

Cwiertka³

et al. 2010

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…In a recently reported analysis of participants in the Carolina Breast Cancer study 64% of Caucasian patients had a luminal A breast cancer subtype compared with only 48% of African-American patients, 11% of Caucasian patients had a luminal B breast cancer subtype compared with 8% of African-American patients, 5% of Caucasian patients had a HER2 overexpressing breast cancer subtype compared with 7% of African-American patients, and only 11% of Caucasian patients had a basal breast cancer subtype compared with a 22% of African-American patients [24]. We reported previously that 64% of ER negative/PR negative/HER2 negative breast tumors express epidermal growth factor receptor (EGFR) and that 67% of this group belongs to the basal subtype of breast carcinomas [15,20]. EGFR is a member of the human epidermal growth factor family of transmembrane tyrosine kinases that activate a number of signaling pathways involved in cell proliferation and carcinogenesis [15][16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

“…We reported previously that 64% of ER negative/PR negative/HER2 negative breast tumors express epidermal growth factor receptor (EGFR) and that 67% of this group belongs to the basal subtype of breast carcinomas [15,20]. EGFR is a member of the human epidermal growth factor family of transmembrane tyrosine kinases that activate a number of signaling pathways involved in cell proliferation and carcinogenesis [15][16][17][18][19]. Despite initial absence of promising results with the use of EGFR-targeted therapies in breast cancer, a growing number of studies suggested interactions of EGFR-mediated signaling and endocrine pathways [35,36].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the majority of the BRCA1 associated breast carcinomas are thought to belong to the basal subtype of breast tumors [12][13][14]. We, and others, recently reported that ER-negative/ PR-negative/HER-2 negative (so called "triple negative") breast tumors express epidermal growth factor receptor (EGFR), a member of the human epidermal growth factor family of transmembrane tyrosine kinases that activate a number of signaling pathways involved in cell proliferation and carcinogenesis [15][16][17][18][19]. Furthermore, a number of studies including our own, have suggested that the majority of these "triple negative", EGFR positive tumors belong to the basal subtype and hypothesized that these tumors may be the subtype of breast carcinomas that could potentially benefit from EGFR-targeted therapeutic approaches [7,18,[20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Race and Triple Negative Breast Cancer

Siziopikou¹

2011

J Clinic Experiment Pathol

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Breast cancer is understood to represent not a single disease but a heterogeneous group of tumors with different biologic behavior, prognosis and response to treatment. Luminal A, luminal B, HER2 overexpressing, triple negative and basal subtypes of breast carcinomas are now considered distinct entities with unique biologic characteristics and clinical outcomes. Classic epidemiologic studies have also shown that race plays a role in the incidence and ultimate prognosis of breast cancer; specifically while the incidence of breast carcinomas is higher in Caucasian women, African-American patients have worse overall prognosis with higher breast cancer mortality rates. While the impact of socioeconomic and health care access factors is not to be dismissed, unique biologic characteristics in this patient population may play an important role in the difference in patient outcome. In this report we evaluated possible racial differences in the incidence of the basal subtype of triple negative breast carcinomas in a large cohort of consecutive breast cancer patients.

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“…Triple-negative breast cancer (TNBC), which represents approximately 15% of all breast cancers (3) and shows high recurrence and poor survival rates (4), is defined by the lack of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/cerbB2/ EGFR2) expression (5). Thus, to date, TNBC lacks effective targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression

Sun

Liu

Huang

2012

Molecular Medicine Reports

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Abstract. Curcumin is the major component of the spice turmeric, extracted from the rhizomes of the plant Curcuma longa. It exerts a number of therapeutic effects, including the inhibition of cancer cell proliferation. However, the anti-carcinogenic mechanism of curcumin has not been fully elucidated. Triple-negative breast cancer (TNBC), which lacks expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2/EGFR2), is an aggressive breast cancer phenotype with a poor prognosis. In this study, we investigated the effects of curcumin on triple-negative breast cancer cells and the possible molecular mechanisms. The MDA-MB-231 TNBC cells were treated with curcumin, the growth inhibition ratio of the cells was measured by MTT assay, apoptosis was detected by flow cytometry and the expression levels of extracellular regulated protein kinase (ERK1/2), pERK1/2, EGFR and pEGFR were detected by western blotting. After treatment with different concentrations of curcumin, the growth inhibition rates of the MDA-MB-231 breast cancer cells of the 30 µmol/ml curcumin-treated group were significantly different from those of the other groups. The level of apoptosis of the curcumin-treated group (26.34%) was significantly different from that of the control group (2.76%). The expression levels of pERK1/2 and pEGFR in the curcumin-treated group were significantly decreased compared with those of the control group. These results indicate that curcumin is able to inhibit the proliferation of TNBC cells. Inhibition of the EGFR signaling pathway is the likely underlying molecular mechanism.

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The Challenging Estrogen Receptor-Negative/ Progesterone Receptor-Negative/HER-2-Negative Patient: A Promising Candidate for Epidermal Growth Factor Receptor-Targeted Therapy?

Cited by 45 publications

References 19 publications

Lapatinib in Breast Cancer - The Predictive Significance of Her1 (Egfr), Her2, Pten and Pik3ca Genes and Lapatinib Plasma Level Assessment

Lapatinib in Breast Cancer - The Predictive Significance of Her1 (Egfr), Her2, Pten and Pik3ca Genes and Lapatinib Plasma Level Assessment

Race and Triple Negative Breast Cancer

Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression

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