Second breast cancer: recurrence score results, clinicopathologic characteristics, adjuvant treatments, and outcomes-exploratory analysis of the Clalit registry.

Data on using the 21-gene Recurrence Score (RS) testing on second breast cancer (BC; second primary or local recurrence) are lacking. This cohort study examined patients with first and second BC, who underwent 21-gene testing both times. It included a 'study-cohort' (60 N0/N1mi/N1 ER + HER2‒ BC patients with ≥2 RS results >1 year apart) and a 'general 21-gene-tested BC-cohort' (2044 previously described N0/N1mi/N1 patients).

Epithelial cell-expressed type II IL-4 receptor mediates eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, food-driven allergic disease, characterized by eosinophil-rich inflammation in the esophagus. The histopathological and clinical features of EoE have been attributed to overproduction of the type 2 cytokines IL-4 and IL-13, which mediate profound alterations in the esophageal epithelium and neutralizing of their shared receptor component (IL-4Rα) with a human antibody drug (dupilumab) demonstrates clinical efficacy. Yet, the relative contribution of IL-4 and IL-13 and whether the type II IL-4 receptor (comprised of the IL-4Rα chain in association with IL-13Rα1) mediates this effect has not been determined.

Oncology Treatments during the COVID-19 Pandemic in Israel: the ONCOR Study.

Background: The increased susceptibility of cancer patients to coronavirus disease-2019 (COVID-19) infections and complications calls for special precautions while treating cancer patients during COVID-19 pandemics. Thus, oncology departments have had to implement a wide array of prevention measures.

Objectives: To address issues associated with cancer care during the COVID-19 pandemic and to assess the implementation of measures aimed at containment of COVID-19 diffusion while allowing continuation of quality cancer care.

The Place of Chemotherapy in The Evolving Treatment Landscape for Patients With HR-positive/HER2-negative MBC.

Endocrine therapy (ET) for the treatment of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR-positive/HER2-negative) metastatic breast cancer (MBC) has changed markedly over recent years with the emergence of new ETs and the use of molecularly targeted agents. Cytotoxic chemotherapy continues, however, to have an important role in these patients and it is important to maximize its efficacy while minimizing toxicity to optimize outcomes. This review examines current HR-positive/HER2-negative MBC clinical guidelines and addresses key questions around the use of chemotherapy in the face of emerging therapeutic options.

Advanced Breast Cancer at Diagnosis: Over One Third Adherent to Screening Recommendations.

Advanced breast cancer (ABC) at diagnosis carries a worse prognosis, and can be attributed to delay in diagnosis, failure of screening tests, or aggressive biology. Better understanding of factors related with ABC at diagnosis could help decrease the proportion of such cases. This is a retrospective study of all patients diagnosed and treated for breast cancer (BC) at a single institution between 2012 and 2015.

Safety and tolerability of subcutaneous trastuzumab at home administration, results of the phase IIIb open-label BELIS study in HER2-positive early breast cancer.

Purpose: The subcutaneous (SC) administration of trastuzumab is highly preferred by patients. At home, administration of trastuzumab SC might further improve patient benefit. The aims of the BELIS study are to evaluate the safety and tolerability of trastuzumab SC when administered at home by a healthcare professional (HCP) and to evaluate patient-reported outcomes for treatment experience of at home cancer therapy.

Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy.

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan-Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort.

Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial.

Background: We report longitudinal health-related quality-of-life (HRQoL) data from the international, randomized, double-blind, placebo-controlled phase III ExteNET study, which demonstrated an invasive disease-free survival benefit of extended adjuvant therapy with neratinib over placebo in human epidermal growth factor receptor-2-positive early-stage breast cancer.

Patients And Methods: Women (N  = 2840) with early-stage HER2-positive breast cancer who had completed trastuzumab-based adjuvant therapy were randomly assigned to neratinib 240  mg/day or placebo for 12  months. HRQoL was an exploratory end point.

Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry.

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 ( = 709). Medical records were reviewed to verify treatments/recurrences/survival.

Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.

Background: Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.

Methods: In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily.

Identification and Characterization of a Novel Aspergillus fumigatus Rhomboid Family Putative Protease, RbdA, Involved in Hypoxia Sensing and Virulence.

Aspergillus fumigatus is the most common pathogenic mold infecting humans and a significant cause of morbidity and mortality in immunocompromised patients. In invasive pulmonary aspergillosis, A. fumigatus spores are inhaled into the lungs, undergoing germination and invasive hyphal growth.

HER2-Mutated Breast Cancer Responds to Treatment With Single-Agent Neratinib, a Second-Generation HER2/EGFR Tyrosine Kinase Inhibitor.

Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2-targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. This case report describes a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2.

D538G mutation in estrogen receptor-α: A novel mechanism for acquired endocrine resistance in breast cancer.

Resistance to endocrine therapy occurs in virtually all patients with estrogen receptor α (ERα)-positive metastatic breast cancer, and is attributed to various mechanisms including loss of ERα expression, altered activity of coregulators, and cross-talk between the ERα and growth factor signaling pathways. To our knowledge, acquired mutations of the ERα have not been described as mediating endocrine resistance. Samples of 13 patients with metastatic breast cancer were analyzed for mutations in cancer-related genes.

The impact of the 21-gene Recurrence Score assay on clinical decision-making in node-positive (up to 3 positive nodes) estrogen receptor-positive breast cancer patients.

Oncotype DX testing is reimbursed in Israel for node-negative and node-positive (N1+; up to 3 positive nodes including micrometastases), estrogen receptor positive (ER+), breast cancer patients. This retrospective study evaluated the impact of Oncotype DX testing on treatment decisions in N1+/ER+ breast cancer patients. To this end, we compared treatments for all N+ patients for whom testing had been ordered with treatments for patients with similar characteristics where the test had not been available.

Pretreatment CA 15-3 levels do not predict disease-free survival in patients with advanced epithelial ovarian cancer.

Aims: To evaluate the role of pretreatment CA 15-3 levels as a predictor of disease-free survival in patients with advanced epithelial ovarian cancer.

Methods: A cohort of 65 patients with FIGO stage III or IV epithelial ovarian cancer was evaluated. Patients were treated either with primary cytoreductive surgery followed by adjuvant platinum-based chemotherapy or with neoadjuvant chemotherapy with interval debulking surgery.

Germline mutations in BRCA1 and BRCA2 genes in ethnically diverse high risk families in Israel.

Three mutations in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT) predominate among high risk breast ovarian cancer Ashkenazi Jewish families, with few "private" mutations described. Additionally, the spectrum of BRCA1 and BRCA2 germline mutations among high risk Jewish non Ashkenazi and non Jewish Israelis is undetermined. Genotyping by exon-specific sequencing or heteroduplex analysis using enhanced mismatch mutation analysis was applied to 250 high risk, predominantly cancer affected, unrelated Israeli women of Ashkenazi (n = 72), non Ashkenazi (n = 90), Moslem (n = 45), Christian Arabs (n = 21), Druze (n = 17), and non Jewish Caucasians (n = 5).

Hormone receptor expression is associated with a unique pattern of metastatic spread and increased survival among HER2-overexpressing breast cancer patients.

Objectives: HER2/neu (HER2) overexpression occurs in approximately 20% of breast cancers and is associated with aggressive disease. Although a significant number of HER2-positive tumors also express hormone receptors (HR), the effects HR expression has on clinical characteristics, including response to trastuzumab among HER2-positive breast cancer, has not been elucidated yet.

Methods: A retrospective analysis of consecutive metastatic HER2-positive breast cancer patients was conducted in 2 medical centers.

Association between standard clinical and pathologic characteristics and the 21-gene recurrence score in breast cancer patients: a population-based study.

Background: The 21-gene recurrence score (RS) assay has been reported to accurately predict the risk of disease recurrence and chemotherapy benefit in women with estrogen receptor (ER)-positive, lymph node (LN)-negative breast cancer who are treated with tamoxifen. To the authors' knowledge, the association between the RS and clinicopathologic characteristics has been studied in randomized and case-control trials, but not in the general population.

Methods: The authors analyzed the correlation between clinicopathologic breast cancer characteristics and RS among 300 consecutive Israeli patients who were referred to undergo the test between October 2004 and October 2006.

Postoperative loco-regional radiation therapy for breast cancer patients with four or more involved lymph nodes or extracapsular extension.

Background: Post-mastectomy loco-regional radiation to the chest wall and draining lymphatics, combined with adjuvant chemotherapy and hormonal therapy, significantly improve survival in patients with node-positive breast cancer. However, the actual benefit of post-mastectomy radiotherapy and the desired extent of treatment are still debatable.

Objectives: To examine the effect of postoperative loco-regional radiotherapy on local and regional recurrence and survival in breast cancer patients with four or more involved lymph nodes or extracapsular tumor extension.

Prenatal diagnosis in Li-Fraumeni syndrome.

Purpose: The hallmark of Li-Fraumeni syndrome (LFS), a familial cancer syndrome, is constitutional TP53 mutation. The authors addressed the complex question of predictive prenatal genetic testing for cancer risk associated with inheritance of TP53 mutation.

Methods: A classic LFS family including the proband (a 20-month-old boy with rhabdomyosarcoma), his 36-year-old father with osteosarcoma, and his 40-year-old paternal aunt with bilateral breast cancer were identified as carriers of a TP53 germline mutation, a novel 1 base pair deletion in exon 5.