Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer.

Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective.

Severe acute radiation dermatitis after palbociclib therapy in the setting of palliative radiotherapy.

Introduction: Cyclin-dependent-kinase 4/6(CDK4/6) inhibitors are widely used as a first-line systemic treatment for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer. Although many patients with metastatic breast cancer require palliative radiotherapy (RT), there are limited data on the safety of combining a CDK4/6 inhibitor with palliative RT.

Case Report: Presented is a case of acute high-grade radiation dermatitis with low-dose palliative RT following administration of palbociclib.

18F-FES PET/CT Improves the Detection of Intraorbital Metastases in Estrogen-Receptor-Positive Breast Cancer: Two Representative Cases and Review of the Literature.

Orbital metastases are a rare but life-altering complication in cancer. Most commonly seen in breast cancer, metastases to the optic nerves or extraocular muscles can have a devastating impact on visual acuity and quality of life. Hormone receptor status plays a central role in metastatic breast cancer treatment, with endocrine therapy often representing first-line therapy in hormone-receptor-positive cancers.

NCCN Guidelines® Insights: Breast Cancer, Version 4.2021.

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer-focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor-positive, HER2-negative breast cancer.

Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.

Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction.

Background We examined the longitudinal associations between changes in cardiovascular biomarkers and cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer treated with cardotoxic cancer therapy. Methods and Results Repeated measures of high-sensitivity cardiac troponin T (hs-cTnT), NT-proBNP (N-terminal pro-B-type natriuretic peptide), myeloperoxidase, placental growth factor, and growth differentiation factor 15 were assessed longitudinally in a prospective cohort of 323 patients treated with anthracyclines and/or trastuzumab followed over a maximum of 3.7 years with serial echocardiograms.

Refining the indications for neoadjuvant chemotherapy for patients with HER2+ breast cancer: A single institution experience.

Background: We aim to compare the clinical outcomes of patients with early-stage HER2+ breast cancer treated with adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC).

Methods: Patients with non-metastatic HER2+ breast cancer treated from 2009 to 2018 at our institution comprised our study cohort (n = 1254). Pathologic complete response (pCR) was defined as the absence of invasive disease in the breast and axilla after NAC.

Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy.

Objectives: This study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction.

Background: Doxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined.

Does time to adjuvant chemotherapy (TTC) affect outcomes in patients with triple-negative breast cancer?

Purpose: A recent study reported that time to adjuvant chemotherapy (TTC) > 30 days was significantly associated with worse OS and DFS in triple-negative breast cancer (TNBC). Earlier studies, however, found that worse outcomes were associated with TTC > 60 days or > 90 days. As the trend for mastectomy with reconstruction continues to rise, TTC of < 30 days is often not feasible due to wound-healing issues in some of these patients.

Safety and Efficacy of Intratumoral Injections of Chimeric Antigen Receptor (CAR) T Cells in Metastatic Breast Cancer.

Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule c-Met was expressed in ∼50% of breast tumors, prompting the construction of a CAR T cell specific for c-Met, which halted tumor growth in immune-incompetent mice with tumor xenografts.

Arginine-Nitric Oxide Metabolites and Cardiac Dysfunction in Patients With Breast Cancer.

Background: Oxidative/nitrosative stress and endothelial dysfunction are hypothesized to be central to cancer therapeutics-related cardiac dysfunction (CTRCD). However, the relationship between circulating arginine-nitric oxide (NO) metabolites and CTRCD remains unstudied.

Objectives: This study sought to examine the relationship between arginine-NO metabolites and CTRCD in a prospective cohort of 170 breast cancer patients treated with doxorubicin with or without trastuzumab.

Noninvasive Measures of Ventricular-Arterial Coupling and Circumferential Strain Predict Cancer Therapeutics-Related Cardiac Dysfunction.

Objectives: This study sought to determine the relationships between echocardiography-derived measures of myocardial mechanics and cancer therapeutics-related cardiac dysfunction (CTRCD).

Background: Doxorubicin and trastuzumab are highly effective breast cancer therapies, but have a substantial risk of CTRCD. There is a critical need for the early detection of patients at increased risk of toxicity.

Identifying patients at high risk of breast cancer recurrence: strategies to improve patient outcomes.

Identifying patients at high risk of breast cancer recurrence has important implications not only for enabling the ability to provide accurate information to patients but also the potential to improve patient outcomes. Patients at high recurrence risk can be offered appropriate treatment to improve the overall survival. However, the major challenge is identifying patients with early-stage breast cancer at lower risk who may be spared potentially toxic therapy.

Inflammatory breast cancer management in the national comprehensive cancer network: the disease, recurrence pattern, and outcome.

Background: Inflammatory breast cancer (IBC) is an uncommon clinicopathologic entity characterized by rapid progression and aggressive behavior. We used the National Comprehensive Cancer Network (NCCN) Outcomes Database to characterize recurrence patterns and outcomes.

Methods: Patients with newly diagnosed IBC treated between 1999 and 2009 at 12 NCCN institutions were identified, and baseline characteristics were obtained.

Cost sharing and hereditary cancer risk: predictors of willingness-to-pay for genetic testing.

Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history.

How do I follow patients with early breast cancer after completing adjuvant therapy.

With improvements in the detection and treatment of breast cancer, more women are surviving after diagnosis. Patients who complete adjuvant therapy require ongoing follow-up to manage toxicities, to detect recurrences early, and to provide ongoing physical and psychosocial support. Routine surveillance should be implemented, with attention to educating patients about symptoms of recurrence, such as weight loss, cough, and bone pain.

Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive-aged breast cancer survivors.

Background: In late reproductive-aged breast cancer survivors, there is a need for real-time biomarkers of postchemotherapy ovarian function. The objective was to determine whether antimullerian hormone (AMH) and inhibin B are such biomarkers. The authors tested whether AMH and inhibin B were impacted by breast cancer treatment by comparing cancer survivors to age-matched control women and determined the association between these hormones and postchemotherapy menstrual pattern.

Association of cyclophosphamide drug-metabolizing enzyme polymorphisms and chemotherapy-related ovarian failure in breast cancer survivors.

Objective: To determine if genetic variation in chemotherapy metabolism are associated with risk of ovarian failure in breast cancer patients after adjuvant chemotherapy.

Design: Prospective cohort study.

Setting: Comprehensive cancer center.

Risk factors for mediastinitis following median sternotomy in children.

Background: Mediastinitis is a devastating complication of pediatric cardiothoracic surgery. However, risk factors for the development of mediastinitis are poorly characterized. The objective of this study was to identify risk factors for mediastinitis in a cohort of children undergoing cardiothoracic surgery at a tertiary care children's hospital.

Bloodstream infections after median sternotomy at a children's hospital.

Objectives: Postoperative bloodstream infections are a major source of morbidity and increased health care costs. In adults, mediastinitis has been described as a risk factor for bloodstream infections. The objectives of this retrospective cohort study were to determine the incidence and to identify risk factors for postoperative bloodstream infections among children after median sternotomy in an urban tertiary care children's hospital.

Recombinant, live-attenuated tetravalent dengue virus vaccine formulations induce a balanced, broad, and protective neutralizing antibody response against each of the four serotypes in rhesus monkeys.

Three tetravalent vaccine (TV) formulations of previously described monovalent dengue (DEN) virus vaccine candidates were compared to a tetravalent formulation of wild-type DEN viruses (T-wt) for replication in SCID mice transplanted with human liver cells (SCID-HuH-7) or for replication and immunogenicity in rhesus monkeys. TV-1 consists of recombinant DEN1, -2, -3, and -4, each with a 30-nucleotide deletion in the 3' untranslated region (Delta30). TV-2 consists of rDEN1Delta30, rDEN4Delta30, and two antigenic chimeric viruses, rDEN2/4Delta30 and rDEN3/4Delta30, both also bearing the Delta30 mutation.