Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia.

The present study aimed to determine the safety and activity of the histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia (WM). Eligibility criteria included patients with relapsed/refractory WM with any number of prior therapies. Patients received panobinostat at 30 mg 3 times a week; 12 of 36 (33%) patients were enrolled at 25 mg dose. A total of 36 patients received therapy. The median age was 62 years (range, 47-80) and the median number of prior therapies was 3 (range, 1-8). All of the patients had received prior rituximab. Minimal response (MR) or better was achieved in 47% of patients (90% confidence interval [CI], 33-62), with 22% partial remissions and 25% MR. In addition, 18 (50%) patients achieved stable disease and none showed progression while on therapy. The median time to first response was 1.8 months (range, 1.7-3.2). The median progression-free survival was 6.6 months(90% CI, 5.5-14.8). Grade 3 and 4 toxicities included thrombocytopenia (67%), neutropenia (36%), anemia (28%), leukopenia (22%), and fatigue (11%). We conclude that panobinostat is an active therapeutic agent in patients with relapsed/ refractory WM. This study (www.clinicaltrials.gov identifier: NCT00936611) establishes a role for histone deacetylase inhibitors as an active class of therapeutic agents in WM.

Breast cancer in elderly women: outcome as affected by age, tumor features, comorbidities, and treatment approach.

PURPOSE: The current work assessed the independent contributions of age, comorbidities, tumor features, and treatment approach to the outcome of elderly patients with breast cancer. PATIENTS AND METHODS: Records of consecutive women aged > or = 70 years with a histologic diagnosis of first invasive breast cancer between 1971 and 2001 and available medical information were reviewed. Restaging to the 2002 TNM system and comorbidity data abstraction were performed. Primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: There were 992 patients with a median diagnosis age of 76 years, of whom 840 were approached with a curative intent. Significant comorbidities were recorded as none and > or = 3 in 13% and 44% of patients, respectively. The 5- and 10-year OS rates were 59% and 34%; corresponding BCSS rates were 74% and 62%, respectively. Of 693 patients who died during the study period, only 298 (43%) died from their tumors. Stage emerged as the strongest predictor determining OS and BCSS (P = 0.001). In curatively approached patients, age was the next dominant factor affecting survival length (P = 0.001). The comorbidities with significant effect on OS differed by stage and included heart failure, diabetes, and other common comorbidities in early tumors but only extremely debilitating ones in advanced-stage disease (P < 0.05). Significant favorable effect of systemic therapy emerged only in the univariate model. CONCLUSION: This study confirms tumor stage as the strongest predictor of survival in elderly patients with breast cancer. It also indicates a significant role for age and comorbidities that varies by stage. Treatment effect should be interpreted with caution because of the retrospective study nature.

Primary pure squamous cell carcinoma of the breast.

Primary squamous cell carcinoma (SCC) of the breast is an extremely rare tumor. It is diagnosed when the malignant cells are entirely of squamous type, the tumor is independent from overlying skin, and other primary SCC sites are excluded. This report presents clinical, radiologic, and histologic correlative findings of a patient diagnosed with pure SCC of the breast. Literature review suggests that primary SCC tumors of the breast are large, often cystic lesions, with a low rate of nodal involvement, no expression of estrogen and progesterone receptors, and resistance to the chemotherapy regimens commonly used in breast cancer.

Correlation of single-lumen silicone implant integrity with chemical shift artifact on T2-weighted magnetic resonance images.

PURPOSE: To correlate the integrity of single-lumen silicone gel implants with chemical shift artifact (CSA) associated with infolding of the elastomer shell. MATERIALS AND METHODS: The T2-weighted images of presurgical MRI examinations of 54 implants were retrospectively reviewed by two breast radiologists blinded to the operative and pathologic findings. CSA associated with intraluminal membranes was quantified by determining the fraction of membranes with it and categorized as minimal (0-1/3 of membranes involved), moderate (>1/3- <2/3), and marked (2/3 to all). CSA was qualified by noting whether CSA intensity of the membranes was less than or similar to that of blood vessels. The CSA was correlated with the surgical or pathology findings to judge integrity of the implant. RESULTS: Nineteen implants were intact, 35 were dysfunctional (gel leakage or rupture). Twenty-eight of 29 (97%) with a minimal fraction of membranes with CSA were dysfunctional; 17/21 (81%) with CSA associated with a marked fraction of membranes were intact (P < 0.001). All 28 implants with CSA intensity less than vessels were dysfunctional, 19/26 (73%) with CSA equal to vessels were intact (P < 0.001). All 25 implants with minimal CSA and intensity less than vessels were dysfunctional. Seventeen of 19 (89%) implants with CSA associated with a marked fraction of membranes and intensity equal to vessels were intact (P = 0.02). The magnetic resonance imaging (MRI) signs were combined with strong CSA as a predictor of integrity, and 22 of 26 (85%) implants were correctly diagnosed, 4 dysfunctional and 18 intact (P < 0.0001). CONCLUSION: CSA correlates with integrity of silicone gel implants on T2-weighted images and can be used with other MRI signs to improve diagnosis.