Anti-neutrophil antibodies (anti-MPO-ANCAs) are associated with poor prognosis in breast cancer patients

Anti-neutrophil antibodies are capable of activating neutrophils in sterile environments, releasing extracellular traps containing myeloperoxidase (MPO) and anti-MPO antibodies (MPO-ANCAs or anti-MPO-ANCAs), which have been implicated in the pathogenesis of several diseases. The present study evaluated systemic and tumor tissue levels of anti-MPO-ANCAs breast cancer patients, and its relation to clinicopathological characteristics. Anti-MPO-ANCAs were measured in serum and tissue samples of 150 patients by enzyme-linked immunoassay. Samples were pooled according to clinicopathological characteristics of patients. Higher anti-MPO-ANCAs levels were detected in groups presenting negative clinicopathological characteristics, such as high histological grade tumors and risk factors such as body mass index, menopausal status and early onset at diagnosis. The present data highlights anti-MPO-ANCAs as associated to poor prognosis in breast cancer, a role beyond its actually discussed role in autoimmunity and vasculitis.     

基于医院信息系统的乳腺癌临床特征及中西医用药特征分析

目的 解析真实世界中乳腺恶性肿瘤患者的人群特征、诊断特征、中西医用药特征，为乳腺癌的临床防治提供参考。方法 采集2002年2月至2015年5月全国60家三级甲等医 院信息系统（Hospital Information System，HIS）中，出院诊断为“乳腺癌”的患者用药信息，采用SAS9.3统计软件，对人口学信息、诊断信息、医嘱用药信息等进行描述性分析。结果 39798例乳腺癌患者，平均年龄（50.93者，平均年龄）岁；多以门诊入院，入院病情以“一般”为主;合并疾病主要为高血压，骨肿瘤，联用西药以抑制肿瘤细胞增殖、治疗并发症、缓解放化疗不良反应为主；中医辨证以痰瘀互结证，气阴两虚证，肝气淤滞证，脾气亏虚证型最为常见，临床清热解毒剂、益气扶正剂，活血化瘀剂应用较多。结论 乳腺癌中西医结合治疗，联用药物广泛，临床治疗基本符合临床指南。     

Idiopathic myointimal hyperplasia of mesenteric veins: Rare case of ischemic colitis mimicking inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76‐year‐old Japanese man presented to our hospital with a 1‐year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C‐reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.     

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.     

Post-neoadjuvant strategies in breast cancer: From risk assessment to treatment escalation

The post-neoadjuvant setting in early breast cancer represents an attractive scenario for adjuvant clinical trials, offering the opportunity to test new drugs or combinations in high-risk patients who did not achieve pathologic complete response after primary treatment. No standard therapies are routinely proposed to patients with residual disease after neoadjuvant chemotherapy and few trials have explored this setting. To date, only one randomized phase III study showed the benefit of additional capecitabine after neoadjuvant chemotherapy, and international guidelines recommend at least to consider its use, particularly for triple negative breast cancer. Therefore, the management of these patients is still a clinical challenge, with limited data supporting the use of an additional adjuvant non-cross-resistant chemotherapy. Escalation strategies are currently under evaluation, with new agents proposed as supplementary post-neoadjuvant treatment (e.g. platinum salts, capecitabine, poly ADP-ribose polymerase inhibitors, immune checkpoint inhibitors, cyclin-dependent kinase 4/6 inhibitors). Based on these premises, selection criteria are critical to identify patients who may benefit from post-neoadjuvant therapies, through the validation of prognostic and predictive biomarkers for a reliable risk assessment and estimation of benefit.The present review summarizes the efforts in introducing new therapeutic options for patients with breast cancer and residual disease after neoadjuvant treatment, with a particular focus on the ongoing clinical trials and useful biomarkers for risk stratification.     

Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. It is a cancer that originates from the mammary ducts and involves mutations in multiple genes. Recently, the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness, which gives rise to therapeutic resistance. Epidemiological, population-based, and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are the main allyl sulfur compounds present in garlic, and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation, tumor metastasis, and angiogenesis. The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer. This review discusses the potential anticancer activities of DADS and DATS, with emphasis on drug resistance in triple-negative breast cancer (TNBC). Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC, especially in clinical studies.     

Narrowing the focus: Therapeutic cell surface targets for refractory triple-negative breast cancer

Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2 protein. In comparison to other types of breast cancer, TNBC characterizes for its aggressive behavior, more prone to early recurrence and a disease with poor response to molecular target therapy. Although TNBC is identified in only 25%-30% of American breast cancer cases annually, these tumors continue to be a therapeutic challenge for clinicians for several reasons: Tumor heterogeneity, limited and toxic systemic therapy options, and often resistance to current standard therapy, characterized by progressive disease on treatment, residual tumor after cytotoxic chemotherapy, and early recurrence after complete surgical excision. Cell-surface targeted therapies have been successful for breast cancer in general, however there are currently no approved cell-surface targeted therapies specifically indicated for TNBC. Recently, several cell-surface targets have been identified as candidates for treatment of TNBC and associated targeted therapies are in development. The purpose of this work is to review the current clinical challenges posed by TNBC, the therapeutic approaches currently in use, and provide an overview of developing cell surface targeting approaches to improve outcomes for treatment resistant TNBC.     

Disorders of sex development

Disorders of sex development (DSD) occur in 1–2/10,000 live births, with a specific molecular diagnosis only possible in 20% of cases. Presentation is usually at birth, and gender assignment must be avoided before review by an expert multidisciplinary team. Initial investigations allow a working diagnosis to be made within 48 hr. In 46,XY DSD, surgery may be necessary to correct hypospadias, reposition or remove undescended testes, and remove symptomatic Müllerian remnants. In 46,XX DSD, feminizing surgery is performed less frequently than in the past, but genitoplasty may still be indicated. Psychosocial support is required to promote positive adaptation as gender dissatisfaction can occur in certain conditions. Long-term outcome data are sparse.     

Effect of the COVID-19 Pandemic on Surgical Breast Cancer Care in the Netherlands: A Multicenter Retrospective Cohort Study

BackgroundCoronavirus disease 2019 (COVID-19) has put a strain on regular healthcare worldwide. In the Netherlands, the national screening programs, including for breast cancer, were halted temporarily. This posed a challenge to breast cancer care, because ∼40% of cases are detected through national screening. Therefore, the aim of the present study was to evaluate the effects of the COVID-19 pandemic on the surgical care of patients with breast cancer in the Netherlands.Materials and MethodsThe present multicenter retrospective cohort study investigated the effects of COVID-19 on patients with breast cancer who had undergone surgery from March 9 to May 17, 2020. The primary endpoints were the number of surgical procedures performed during the study period, tumor characteristics, surgery type, and route of referral. The secondary endpoint was the incidence of postoperative complications during the study period.ResultsA total of 217 consecutive patients with breast cancer requiring surgery were included. We found an overall decrease in the number of patients with breast cancer who were undergoing surgery. The most significant decline was seen in surgery for T1-T2 and N0 tumors. A decline in the number of referrals from both the national screening program and general practitioners was observed. The incidence of postoperative complications remained stable during the study period.ConclusionsThe temporary halt of the national screening program for breast cancer resulted in fewer surgical procedures during the study period and a pronounced decrease in surgery of the lower tumor stages.     

New and important changes in breast cancer TNM: incorporation of biologic factors into staging

Introduction: Cancer staging has historically been based solely on the anatomic extent of the tumor (T), spread to lymph nodes (N), and the presence of distant metastases (M). More recently biologic factors have been added to modify TNM stage groups to provide more accurate prognosis for patients.

Areas covered: The American Joint Committee on Cancer (AJCC) updated breast cancer staging in 2016 to include T, N, M, tumor grade and expression of estrogen and progesterone receptors and HER2. Addition of these factors changed the stage group for a large fraction of cases compared to prior TNM stage groupings. This updated ‘prognostic stage’ provides more robust and precise prognosis information.

Expert opinion: Inclusion of biological information in staging changes the meaning and the use of stage in clinical practice. This paper reviews the evidence supporting these changes, limitations affecting staging, and discusses the implications for clinical practice and the future of breast cancer staging.