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

The diagnosis and management of breast cancer are undergoing a paradigm shift from a one-size-fits-all approach to an era of personalized medicine. Sophisticated diagnostics, including molecular imaging and genomic expression profiles, enable improved tumor characterization. These diagnostics, combined with newer surgical techniques and radiation therapies, result in a collaborative multidisciplinary approach to minimizing recurrence and reducing treatment-associated morbidity. This article reviews the diagnosis and treatment of breast cancer, including screening, staging, and multidisciplinary management. In this article, we address current approaches to breast cancer diagnosis and management. These approaches include screening recommendations; diagnostic imaging and pathologic assessment to determine the extent of disease; surgery and radiation treatment; and an array of systemic options, such as chemotherapy, endocrine therapy, and targeted agents (Fig. 1). We also consider the potential contribution of functional imaging to a new era of personalized, tumor-specific treatment. BREAST CANCER DIAGNOSIS ScreeningBreast cancer is generally diagnosed through either screening or a symptom (e.g., pain or a palpable mass) that prompts a diagnostic exam. Screening of healthy women is associated with the detection of tumors that are smaller, have lower odds of metastasis, are more amenable to breast-conserving and limited axillary surgery, and are less likely to require chemotherapy (1). This scenario translates to reduced treatment-related morbidity and improved survival.The only screening modality proven to reduce breast cancerspecific mortality is mammography (2). Screening mammography leads to a 19% overall reduction in breast cancer mortality (3), with less benefit for women in their 40s (15%) and more benefit for women in their 60s (32%). As a result, screening mammography is recommended by the American Cancer Society beginning at age 45, or sooner depending on individual preference. The potential negative aspects of screening mammography are falsepositive examinations, radiation exposure, pain, anxiety, and other negative psychologic effects. Mammography has a 61% chance of a false-positive result over a 10-y period for women commencing screening between the ages of 40 y and 50 y. The risk of a falsepositive examination decreases with older age (3). The US Preventative Task Force cited a 15% breast cancer-related mortality reduction for women who were 39-49 y old and a mortality-related benefit from screening between ages 39 and 69. However, the task force released a controversial report recommending only biennial screening mammography for women who were 50-74 y old, excluding younger women to a large extent because of the high rate of false-positive results (4). Mammography for women in the 39-to 49-y-old age group was recommended if indicated after the use of a risk-based model of breast cancer screening, such as the models developed by the Population-Based Research Optimizing Screening Through Personalized Re...

No enhancement and a smooth non-enhancing margin on MRI were predictive of longer PFS, while a smooth non-enhancing margin was a significant predictor of longer OS in LGGs. Textural analyses of MR imaging data predicted IDH1 mutation, 1p/19q codeletion, histological grade, and tumor progression with high accuracy.

Setting: Comprehensive cancer center.Patients: Fifty-one patients (21 men and 30 women) with biopsy-proven skin metastases and correlative clinical data.Interventions: Four dermatopathologists reviewed a random mixture of metastases and primary skin tumors. Immunohistochemical studies for 12 markers were performed on the metastases, with skin adnexal tumors as controls.Main Outcome Measures: Clinical characteristics of cutaneous lesions, clinical outcomes, histologic features, and immunohistochemical markers.Results: Eighty-six percent (43 of 50) of the patients had known stage IV cancer, and skin metastasis was the pre-

The role of estrogens in anti-tumor immunity remains poorly understood. Here we show that estrogen signaling accelerates the progression of different estrogen insensitive tumor models by contributing to deregulated myelopoiesis by both driving the mobilization of myeloid-derived suppressor cells (MDSCs) and enhancing their intrinsic immunosuppressive activity in vivo. Differences in tumor growth are dependent on blunted anti-tumor immunity and, correspondingly, disappear in immunodeficient hosts and upon MDSC depletion. Mechanistically, estrogen receptor alpha activates the STAT3 pathway in human and mouse bone marrow myeloid precursors by enhancing JAK2 and SRC activity. Therefore, estrogen signaling is a crucial mechanism underlying pathological myelopoiesis in cancer. Our work suggests that new anti-estrogen drugs that have no agonistic effects may have benefits in a wide range of cancers, independently of the expression of estrogen receptors in tumor cells, and may synergize with immunotherapies to significantly extend survival.