No abstract

Purpose: The G 1 -S checkpoint of the cell cycle is frequently dysregulated in breast cancer. Palbociclib (PD0332991) is an oral inhibitor of CDK4/6. Based upon preclinical/phase I activity, we performed a phase II, single-arm trial of palbociclib in advanced breast cancer.Experimental Design: Eligible patients had histologically confirmed, metastatic breast cancer positive for retinoblastoma (Rb) protein and measureable disease. Palbociclib was given at 125 mg orally on days 1 to 21 of a 28-day cycle. Primary objectives were tumor response and tolerability. Secondary objectives included progression-free survival (PFS) and assessment of Rb expression/localization, KI-67, p16 loss, and CCND1 amplification.Results: Thirty-seven patients were enrolled; 84% hormonereceptor (HR) þ /Her2 À

This longitudinal study examined the association between three types of communication strategies couples may use to handle stressors they experience during and after breast cancer treatment and psychological distress and relationship satisfaction of women with early stage breast cancer and their partners. Mutual constructive communication, mutual avoidance, and demand-withdraw communication strategies as well as psychological distress and marital satisfaction were rated by 147 patients and 127 partners during cancer treatment and 9 months later. Mutual constructive communication was associated with less distress and more relationship satisfaction for both patient and partner. Demand-withdraw communication was associated with higher distress and lower relationship satisfaction for both patient and partner. Mutual avoidance was associated with more distress for patient and partner but was not associated with relationship satisfaction. The negative association between mutual constructive communication and patient distress was stronger for patients with more physical impairment. Patients' perceptions of mutual constructive communication and mutual avoidance were associated with partners' distress, and patients' perceptions of mutual constructive and demand/withdraw communication were associated with partners' marital satisfaction. Clinical implications for couple-focused communication skills training for cancer patients and their partners are discussed.

Overexpression of HER-2/neu (c-erbB2) is associated with increased risk of recurrent disease in ductal carcinoma in situ (DCIS) and a poorer prognosis in node-positive breast cancer. We therefore examined the early immunotherapeutic targeting of HER-2/neu in DCIS. Before surgical resection, HER-2/ neu pos DCIS patients (n = 13) received 4 weekly vaccinations of dendritic cells pulsed with HER-2/neu HLA class I and II peptides. The vaccine dendritic cells were activated in vitro with IFN-; and bacterial lipopolysaccharide to become highly polarized DC1-type dendritic cells that secrete high levels of interleukin-12p70 (IL-12p70). Intranodal delivery of dendritic cells supplied both antigenic stimulation and a synchronized preconditioned burst of IL-12p70 production directly to the anatomic site of T-cell sensitization. Before vaccination, many subjects possessed HER-2/neu-HLA-A2 tetramer-staining CD8 pos T cells that expressed low levels of CD28 and high levels of the inhibitory B7 ligand CTLA-4, but this ratio inverted after vaccination. The vaccinated subjects also showed high rates of peptide-specific sensitization for both IFN-;-secreting CD4 pos (85%) and CD8 pos (80%) T cells, with recognition of antigenically relevant breast cancer lines, accumulation of T and B lymphocytes in the breast, and induction of complement-dependent, tumor-lytic antibodies. Seven of 11 evaluable patients also showed markedly decreased HER-2/neu expression in surgical tumor specimens, often with measurable decreases in residual DCIS, suggesting an active process of ''immunoediting'' for HER-2/neuexpressing tumor cells following vaccination. DC1 vaccination strategies may therefore have potential for both the prevention and the treatment of early breast cancer. [Cancer Res 2007;67(4):1842-52]

In the SEER-Medicare database, differences in breast cancer survival between black and white women did not substantially change among women diagnosed between 1991 and 2005. These differences in survival appear primarily related to presentation characteristics at diagnosis rather than treatment differences.

Regulatory T cells (Tregs) are key mediators of immune tolerance and feature prominently in cancer. Depletion of CD25+ FoxP3+ Tregs in vivo may promote T cell cancer immunosurveillance, but no strategy to do so in humans while preserving immunity and preventing autoimmunity has been validated. We evaluated the Food and Drug Administration–approved CD25-blocking monoclonal antibody daclizumab with regard to human Treg survival and function. In vitro, daclizumab did not mediate antibody-dependent or complement-mediated cytotoxicity but rather resulted in the down-regulation of FoxP3 selectively among CD25high CD45RAneg Tregs. Moreover, daclizumab-treated CD45RAneg Tregs lost suppressive function and regained the ability to produce interferon-γ, consistent with reprogramming. To understand the impact of daclizumab on Tregs in vivo, we performed a clinical trial of daclizumab in combination with an experimental cancer vaccine in patients with metastatic breast cancer. Daclizumab administration led to a marked and prolonged decrease in Tregs in patients. Robust CD8 and CD4 T cell priming and boosting to all vaccine antigens were observed in the absence of autoimmunity. We conclude that CD25 blockade depletes and selectively reprograms Tregs in concert with active immune therapy in cancer patients. These results suggest a mechanism to target cancer-associated Tregs while avoiding autoimmunity.

Posttraumatic growth is reported by patients and by significant others. Cognitive and emotional processes predict growth. Patient growth is associated with the significant other's cognitive and emotional processing of breast cancer.

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.