PURPOSE: As survival in breast cancer patients is improving, brain metastases are becoming increasingly prevalent. The risk of brain metastases in newly diagnosed human epidermal growth factor receptor 2 (HER-2) -overexpressing breast cancer patients is not yet fully defined. We aimed to analyze the risk of brain metastasis in newly diagnosed HER-2-positive breast cancer patients in comparison with HER-2-negative patients. PATIENTS AND METHODS: To determine the incidence of brain metastases in HER-2-overexpressing patients, we analyzed a cohort of newly diagnosed 301 HER-2-positive and 363 HER-2-negative patients identified between January 1998 and December 2003. The association between histologic features and the occurrence of brain metastases was evaluated with univariate and multivariate Cox regression analysis. RESULTS: Median follow-up was 3.9 years. Brain metastases were identified in 9% (27 patients) with HER-2-overexpressing breast cancer compared with only 1.9% (7 patients) in the HER-2 negative patients (hazard ratio 4.23 [1.84-9.74], P = .0007). HER-2 overexpression, tumor size larger than 2 cm, at least one positive node, and grade 2/3 disease were predictors of brain metastases in univariate analysis. In multivariate analysis, HER-2 overexpression, tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective. CONCLUSION: Our study shows that newly diagnosed HER-2-overexpressing breast cancer patients are at increased risk for brain metastases. Because most brain metastases occur after the development of systemic disease, these findings prompt consideration of brain prophylaxis strategies with HER-2-inhibiting small molecules able to cross the blood-brain barrier and/or radiologic screening to detect asymptomatic brain metastases.
PURPOSE: As survival in breast cancerpatients is improving, brain metastases are becoming increasingly prevalent. The risk of brain metastases in newly diagnosed humanepidermal growth factor receptor 2 (HER-2) -overexpressing breast cancerpatients is not yet fully defined. We aimed to analyze the risk of brain metastasis in newly diagnosed HER-2-positive breast cancerpatients in comparison with HER-2-negative patients. PATIENTS AND METHODS: To determine the incidence of brain metastases in HER-2-overexpressing patients, we analyzed a cohort of newly diagnosed 301 HER-2-positive and 363 HER-2-negative patients identified between January 1998 and December 2003. The association between histologic features and the occurrence of brain metastases was evaluated with univariate and multivariate Cox regression analysis. RESULTS: Median follow-up was 3.9 years. Brain metastases were identified in 9% (27 patients) with HER-2-overexpressing breast cancer compared with only 1.9% (7 patients) in the HER-2 negative patients (hazard ratio 4.23 [1.84-9.74], P = .0007). HER-2 overexpression, tumor size larger than 2 cm, at least one positive node, and grade 2/3 disease were predictors of brain metastases in univariate analysis. In multivariate analysis, HER-2 overexpression, tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective. CONCLUSION: Our study shows that newly diagnosed HER-2-overexpressing breast cancerpatients are at increased risk for brain metastases. Because most brain metastases occur after the development of systemic disease, these findings prompt consideration of brain prophylaxis strategies with HER-2-inhibiting small molecules able to cross the blood-brain barrier and/or radiologic screening to detect asymptomatic brain metastases.
Authors: Taher Abu Hejleh; Barry R Deyoung; Eric Engelman; Jeremy M Deutsch; Bridget Zimmerman; Thorvardur R Halfdanarson; Daniel J Berg; Kalpaj R Parekh; William R Lynch; Mark D Iannettoni; Sudershan Bhatia; Gerald Clamon Journal: World J Gastrointest Oncol Date: 2012-05-15
Authors: Paul W Sperduto; Norbert Kased; David Roberge; Zhiyuan Xu; Ryan Shanley; Xianghua Luo; Penny K Sneed; Samuel T Chao; Robert J Weil; John Suh; Amit Bhatt; Ashley W Jensen; Paul D Brown; Helen A Shih; John Kirkpatrick; Laurie E Gaspar; John B Fiveash; Veronica Chiang; Jonathan P S Knisely; Christina Maria Sperduto; Nancy Lin; Minesh Mehta Journal: Int J Radiat Oncol Biol Phys Date: 2011-04-15 Impact factor: 7.038
Authors: Brunilde Gril; Diane Palmieri; Julie L Bronder; Jeanne M Herring; Eleazar Vega-Valle; Lionel Feigenbaum; David J Liewehr; Seth M Steinberg; Maria J Merino; Stephen D Rubin; Patricia S Steeg Journal: J Natl Cancer Inst Date: 2008-07-29 Impact factor: 13.506
Authors: C Bachmann; E M Grischke; T Fehm; A Staebler; J Schittenhelm; D Wallwiener Journal: J Cancer Res Clin Oncol Date: 2012-12-06 Impact factor: 4.553