PURPOSE: Human epidermal growth factor receptor 2 (HER-2) expression is associated with increased risk of high-grade disease, nodal metastasis, and absence of estrogen receptors (ERs) in early breast cancer. We tested interactions between ER and HER-2 to determine if they may modulate breast cancer nodal metastasis and proliferation. PATIENTS AND METHODS: Tumors from the Cancer Research UK Taxotere as Adjuvant Chemotherapy phase III trial were tested for HER-2 using current diagnostic procedures. ER status, progesterone status, clinicopathologic characteristics, and patient age were included in a logistic regression analysis to identify associations with HER-2 status (positive v negative). RESULTS: A total of 841 (23.6%) of 3,565 samples were HER-2 positive (3+ by immunohistochemistry or positive by fluorescent in situ hybridization). ER-negative tumors were more likely to be HER-2 positive than were ER-positive tumors (odds ratio [OR] = 1.87, ER negative v ER positive; P < .001). For ER-positive tumors, risk of HER-2 positivity increased by grade (OR = 7.6, grade 3 v grade 1; P < .001) but not nodal status (OR = 1.3, four or more positive nodes v node negative; P = .08). Conversely, ER negative node-positive tumors were markedly more frequently HER-2 positive than node-negative cases (OR = 3.05, four or more positive nodes v node negative; P < .001) but independent of grade (OR = 0.82, grade 3 v grade 1; P = .76). CONCLUSION: In early breast cancer patients selected for cytotoxic chemotherapy, we identified significant interactions between HER-2 and ER expression that correlate with tumor pathology. In ER-positive breast cancers, HER-2 expression correlates with grade, not nodal metastasis. In ER-negative breast cancers, HER-2 expression correlates with increased nodal positivity, not grade. ER and HER-2 expression may modify tumor pathology via ER/HER-2-mediated cross talk.
PURPOSE:Human epidermal growth factor receptor 2 (HER-2) expression is associated with increased risk of high-grade disease, nodal metastasis, and absence of estrogen receptors (ERs) in early breast cancer. We tested interactions between ER and HER-2 to determine if they may modulate breast cancer nodal metastasis and proliferation. PATIENTS AND METHODS: Tumors from the Cancer Research UK Taxotere as Adjuvant Chemotherapy phase III trial were tested for HER-2 using current diagnostic procedures. ER status, progesterone status, clinicopathologic characteristics, and patient age were included in a logistic regression analysis to identify associations with HER-2 status (positive v negative). RESULTS: A total of 841 (23.6%) of 3,565 samples were HER-2 positive (3+ by immunohistochemistry or positive by fluorescent in situ hybridization). ER-negative tumors were more likely to be HER-2 positive than were ER-positive tumors (odds ratio [OR] = 1.87, ER negative v ER positive; P < .001). For ER-positive tumors, risk of HER-2 positivity increased by grade (OR = 7.6, grade 3 v grade 1; P < .001) but not nodal status (OR = 1.3, four or more positive nodes v node negative; P = .08). Conversely, ER negative node-positive tumors were markedly more frequently HER-2 positive than node-negative cases (OR = 3.05, four or more positive nodes v node negative; P < .001) but independent of grade (OR = 0.82, grade 3 v grade 1; P = .76). CONCLUSION: In early breast cancerpatients selected for cytotoxic chemotherapy, we identified significant interactions between HER-2 and ER expression that correlate with tumor pathology. In ER-positive breast cancers, HER-2 expression correlates with grade, not nodal metastasis. In ER-negative breast cancers, HER-2 expression correlates with increased nodal positivity, not grade. ER and HER-2 expression may modify tumor pathology via ER/HER-2-mediated cross talk.
Authors: Kimberly Noonan; Lakshmi Rudraraju; Anna Ferguson; Amy Emerling; Marcela F Pasetti; Carol A Huff; Ivan Borrello Journal: Clin Cancer Res Date: 2012-01-12 Impact factor: 12.531
Authors: Ana P Ortiz; Orquídea Frías; Carmen González-Keelan; Erick Suárez; David Capó; Javier Pérez; Fernando Cabanillas; Edna Mora Journal: P R Health Sci J Date: 2010-09 Impact factor: 0.705
Authors: Mitch Dowsett; Marion Procter; Worta McCaskill-Stevens; Evandro de Azambuja; Urania Dafni; Josef Rueschoff; Bruce Jordan; Stella Dolci; Mark Abramovitz; Oliver Stoss; Giuseppe Viale; Richard D Gelber; Martine Piccart-Gebhart; Brian Leyland-Jones Journal: J Clin Oncol Date: 2009-04-13 Impact factor: 44.544
Authors: Antonio C Wolff; M Elizabeth H Hammond; David G Hicks; Mitch Dowsett; Lisa M McShane; Kimberly H Allison; Donald C Allred; John M S Bartlett; Michael Bilous; Patrick Fitzgibbons; Wedad Hanna; Robert B Jenkins; Pamela B Mangu; Soonmyung Paik; Edith A Perez; Michael F Press; Patricia A Spears; Gail H Vance; Giuseppe Viale; Daniel F Hayes Journal: Arch Pathol Lab Med Date: 2013-10-07 Impact factor: 5.534