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Tedesco KL, Thor AD, Johnson DH, Shyr Y, Blum KA, Goldstein LJ, Gradishar WJ, Nicholson BP, Merkel DE, Murrey D, Edgerton S, Sledge GW. Docetaxel combined with trastuzumab is an active regimen in HER-2 3+overexpressing and fluorescent in situ hybridization-positive metastatic breast cancer: A multi-institutional phase II trial. J Clin Oncol. 2004 Mar;22(6):1071-7.
Purpose To determine the efficacy and safety of weekly docetaxel and trastuzumab as first- or second-line therapy in women with HER-2-overexpressing metastatic breast cancer and to correlate the efficacy of trastuzumab with HER-2 status as determined by immunohistochemistry assay and fluorescent in situ hybridization (FISH). Patients and Methods Twenty-six women with HER-2-positive (HercepTest [Dako Corp, Carpenteria, CA]2 to 3+) metastatic breast cancer were enrolled onto this study of trastuzumab (4 mg/kg load; 2 mg/kg/wk administered intravenously) and docetaxel (35 mg/m(2)/wk for 6 weeks). Results Using an intent-to-treat analysis, the overall response rate was 50% (13 of 26 patients). Eight patients (31%) had a period of stable disease posttherapy. Among HER-2 3+ patients, the overall response rate was 63% (12 of 19 patients) compared with a 14% response rate (one of seven patients) for HER-2 2+ patients (P = .07). Patients with FISH-positive tumors experienced an overall response rate of 64%. Median time to progression was 12.4 months for the entire cohort (HER-2 3+ tumors, 12.3 months, HER-2 2+ lesions, 9.5 months) and median survival was 22.1 months. All HEB-2 3+ patients were FISH-positive; the Only HER-2 2+ patient responding to treatment was also FISH-positive. Grade 4 toxicities occurred in four patients; most toxicties were mild. Conclusion Trastuzumab plus docetaxel is an active and well-tolerated regimen in women with HER-2 3+ overexpressing or FISH-positive metastatic breast cancer. (C) 2004 by American Society of Clinical Oncology.
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Goldstein
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Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. Oncologist. 2004;9 (6):606-16.
Breast cancer is the most common malignancy among American women. Due to increased screening, the majority of patients present with early-stage breast cancer. The Oxford Overview Analysis demonstrates that adjuvant hormonal therapy and polychemotherapy reduce the risk of recurrence and death from breast cancer. Adjuvant systemic therapy, however, has associated risks and it would be useful to be able to optimally select patients most likely to benefit. The purpose of adjuvant systemic therapy is to eradicate distant micrometastatic deposits. It is essential therefore to be able to estimate an individual patient's risk of harboring clinically silent micrometastatic disease using established prognostic factors. It is also beneficial to be able to select the optimal adjuvant therapy for an individual patient based on established predictive factors. It is standard practice to administer systemic therapy to all patients with lymph node-positive disease. However, there are clearly differences among node-positive women that may warrant a more aggressive therapeutic approach. Furthermore, there are many node-negative women who would also benefit from adjuvant systemic therapy. Prognostic factors therefore must be differentiated from predictive factors. A prognostic factor is any measurement available at the time of surgery that correlates with disease-free or overall survival in the absence of systemic adjuvant therapy and, as a result, is able to correlate with the natural history of the disease. In contrast, a predictive factor is any measurement associated with response to a given therapy. Some factors, such as hormone receptors and HER2/neu overexpression, are both prognostic and predictive.
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Goldstein
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Goldstein
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Goldstein
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Manne S, Ostroff J, Rini C, Fox K, Goldstein L, Grana G. The Interpersonal Process Model of Intimacy: The Role of Self-Disclosure, Partner Disclosure, and Partner Responsiveness in Interactions Between Breast Cancer Patients and Their Partners. Journal of Family Psychology. 2004;18(4):589-99.
(from the journal abstract) This study evaluated H. Reis and P. Shaver's (1988) interpersonal process model of intimacy in a sample of 98 women with breast cancer and their partners. Couples engaged in two discussions and rated self- and partner disclosure, perceived partner responsiveness, and intimacy experienced. A mediational model was tested in which partner responsiveness mediated the association between disclosure and intimacy. For patients, perceived responsiveness partially mediated the association between partner disclosure and intimacy, but self-disclosure was not significantly associated with responsiveness or intimacy. For partners, perceived responsiveness mediated the association between self-disclosure and perceived partner disclosure and intimacy. For breast cancer patients, partner disclosure predicted patient feelings of intimacy, because this type of disclosure was associated with greater feelings of acceptance, understanding, and caring. These findings may have implications for interventions to improve relationship closeness among couples coping with breast cancer. (PsycINFO Database Record (c) 2004 APA, all rights reserved).
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Goldstein
Manne
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Manne S, Ostroff J, Winkel G, Goldstein L, Fox K, Grana G. Posttraumatic growth after breast cancer: Patient, partner, and couple perspectives. Psychosom Med. 2004 May-Jun;66(3):442-54.
The purpose of this study was to evaluate posttraumatic growth among breast cancer patients and their significant others over a 1(1)/(2)-year time span after diagnosis and to examine cognitive and emotional processes in posttraumatic growth. Methods: One hundred sixty-two women with breast cancer and their partners completed surveys assessing postraumatic growth, cognitive and emotional processing, and marital satisfaction at 3 time points spaced 9 months apart. Results: Posttraumatic growth increased for both partners during this period. Patient posttraumatic growth was predicted by younger age, contemplating reasons for cancer, and more emotional expression at time 1. Partner posttraumatic growth was predicted by younger age, more intrusive thoughts, and greater use of positive reappraisal and emotional processing at time 1. Conclusion: Posttraumatic growth is reported by patients and by significant others. Cognitive and emotional processes predict growth. Patient growth i! s associated with the significant other's cognitive and emotional processing of breast cancer.
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Goldstein
Manne
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Fracasso PM, Goldstein LJ, de Alwis DP, Rader JS, Arquette MA, Goodner SA, Wright LP, Fears CL, Gazak RJ, Andre VA, Burgess MF, Slapak CA, Schellens JH. Phase I study of docetaxel in combination with the P-glycoprotein inhibitor, zosuquidar, in resistant malignancies. Clin Cancer Res. 2004 Nov 1;10(21):7220-8.
Purpose: To determine the maximum tolerated dose, dose-limiting toxicity, and pharmacokinetics of docetaxel infused over I hour when given in combination with oral zosuquidar to patients with resistant solid tumors. Experimental Design: In cycle 1, patients received docetaxel alone. In subsequent cycles, zosuquidar was administered with docetaxel, which was escalated from 75 to 100 mg/m(2). Zosuquidar was escalated from 100 to 300 mg/m(2) every 8 hours on days 1 to 3 for a total of 7 doses, or from 400 to 500 mg every 12 hours for 2 doses administered 2 hours before docetaxel. The pharmacokinetics of docetaxel with and without zosuquidar administration were obtained. Results: Thirty-six of 41 patients completed at least one cycle of docetaxel and zosuquidar. The maximum tolerated dose was docetaxel 100 mg/m(2) and zosuquidar 500 mg every 12 hours for 2 doses. The most common toxicity was neutropenia. In 35 patients, zosuquidar produced minimal increases in the docetaxel peak plasma concentrations and area under the curve. Dosing over 3 days with zosuquidar (7 doses) did not show benefit over the 1-day dosing. Of the 36 patients, one patient had a partial response, and 14 patients had disease stabilization. Conclusions: Docetaxel at 75 or 100 mg/m(2) and zosuquidar 500 mg 2 hours before docetaxel and 12 hours later is well tolerated. Zosuquidar minimally alters the pharmacokinetics of docetaxel, allowing full dose docetaxel to be given with this P-glycoprotein modulator. A Phase II study with this combination in advanced breast carcinoma is underway.
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Goldstein
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