China is one of the countries with the highest incidence of gastric cancer. There are differences in epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selection between gastric cancer patients from the Eastern and Western countries. Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients. The Chinese Society of Clinical Oncology (CSCO) arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile, discuss, and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad. By referring to the opinions of industry experts, taking into account of regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted experts’ consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes. This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis, comprehensive treatment, and follow-up visits for gastric cancer.

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The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer.

Cancer remains a leading causes of death worldwide and an elevated systemic inflammatory response (SIR) is associated with reduced survival in patients with operable cancer. This review aims to examine the evidence for the role of systemic inflammation based prognostic scores in patients with operable cancers. A wide-ranging literature review using targeted medical subject headings for human studies in English was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. The SIR has independent prognostic value, across tumour types and geographical locations. In particular neutrophil lymphocyte ratio (NLR) (n = 158), platelet lymphocyte ratio (PLR) (n = 68), lymphocyte monocyte ratio (LMR) (n = 21) and Glasgow Prognostic Score/ modified Glasgow Prognostic Score (GPS/mGPS) (n = 60) were consistently validated. On meta-analysis there was a significant relationship between elevated NLR and overall survival (OS) (p < 0.00001)/ cancer specific survival (CSS) (p < 0.00001), between elevated LMR and OS (p < 0.00001)/CSS (p < 0.00001), and elevated PLR and OS (p < 0.00001)/CSS (p = 0.005). There was also a significant relationship between elevated GPS/mGPS and OS (p < 0.00001)/CSS (p < 0.00001). These results consolidate the prognostic value of the NLR, PLR, LMR and GPS/mGPS in patients with resectable cancers. This is particularly true for the NLR/GPS/mGPS which should form part of the routine preoperative and postoperative workup.

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The role of the systemic inflammatory response in predicting outcomes in patients with operable cancer: Systematic review and meta-analysis.

Chemotherapy is More Effective in Patients With Breast Cancer Not Expressing Steroid Hormone Receptors: A Study of Preoperative Treatment

Purpose: Endocrine therapy, using tamoxifen or an aromatase inhibitor, remains first-line therapy for the management of estrogen receptor (ESR1)–positive breast cancer However, ESR1 mutations or other ligand-independent ESR1 activation mechanisms limit the duration of response The clinical efficacy of fulvestrant, a selective estrogen receptor downregulator (SERD) that competitively inhibits agonist binding to ESR1 and triggers receptor downregulation, has confirmed that ESR1 frequently remains engaged in endocrine therapy–resistant cancers We evaluated the activity of a new class of selective estrogen receptor modulators (SERM)/SERD hybrids (SSH) that downregulate ESR1 in relevant models of endocrine-resistant breast cancer Building on the observation that concurrent inhibition of ESR1 and the cyclin-dependent kinases 4 and 6 (CDK4/6) significantly increased progression-free survival in advanced patients, we explored the activity of different SERD– or SSH–CDK4/6 inhibitor combinations in models of endocrine therapy–resistant ESR1 + breast cancer Experimental Design: SERDs, SSHs, and the CDK4/6 inhibitor palbociclib were evaluated as single agents or in combination in established cellular and animal models of endocrine therapy–resistant ESR1 + breast cancer Results: The combination of palbociclib with a SERD or an SSH was shown to effectively inhibit the growth of MCF7 cell or ESR1-mutant patient-derived tumor xenografts In tamoxifen-resistant MCF7 xenografts, the palbociclib/SERD or SSH combination resulted in an increased duration of response as compared with either drug alone Conclusions: A SERD– or SSH–palbociclib combination has therapeutic potential in breast tumors resistant to endocrine therapies or those expressing ESR1 mutations Clin Cancer Res; 21(22); 5121–30 ©2015 AACR  See related commentary by DeMichele and Chodosh, p 4999

https://clincancerres.aacrjournals.org/content/clincanres/21/22/5121.full.pdf

Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy–Resistant Breast Cancer

Human endometrial anatomy Human endometrium as an estrogen-receptive organ † Methods † Estrogen receptors ERb structure ERb receptor activation † ERb expression in normal endometrium Evidence from transgenic mice: ERbKO mice Primate studies ERb in the endometrial vasculature ERb in endometrial immune cells ERb in the human uterus Role of ERb in endometrial regeneration ERb expression in the healthy human post-menopausal endometrium † ERb in endometrial pathology Endometriosis and adenomyosis Polycystic ovary syndrome Endometrial polyps Endometrial hyperplasia Endometrial cancer † Pharmacological regulation of endometrial ERb expression Evidence for regulation of endometrial ERb expression by exogenous hormone treatment Evidence for SERMs (ERb selective pharmacological agents) in endometrium † Summary/conclusion background: The endometrium is the primary target organ for the 'female' sex steroid hormone estrogen, which exerts effects in the endo- metrium via two main classical estrogen receptor (ER) isoforms, ERa and ERb. The main function of the endometrium, embryo implantation, appears unperturbed in ERb knockout mice, which has led researchers to disregard other potentially important functional roles that ERb may have in endometrium. This review focuses on ERb in the human endometrium and its protective role from the undesired effects of ERa.

Estrogen receptor β: the guardian of the endometrium

The aim of this study was to evaluate the frequency and prognostic impact of changes in the estrogen (ER), progesterone (PR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent/metastatic lesions (RML). We investigated 133 breast cancer patients for ER, PR and HER2 status of primary and RML and their follow-up records. Among 133 patients with RML, discordance rate for ER, PR, and HER2 was 18.8, 33.8, and 6.8%, respectively. ER, PR and HER2 discordance were observed in 20.0, 38.1 and 6.7% of the patients with distant metastasis, and in 14.3, 17.9 and 7.1% of the patients with locoregional recurrence. The mean time between the primary diagnosis and last contact or death was 57 (range 22-78) months and between the recurrence biopsy and last contact or death was 17 (range 1-33) months. Among 133 patients with RML, the ER-discordant cases and ER-loss cases experienced a worse overall survival (OS) (p=0.001 and p=0.016, respectively) and post-recurrence survival (PRS) (p=0.001 and p=0.018, respectively), compared with the respective concordant cases. The HER2-discordant patients and HER2-loss patients had a poorer OS (p=0.008 and p=0.001, respectively) and PRS (p=0.004 and p=0.000, respectively) than the respective concordant cases. Among 105 patients with distant metastasis, ER discordance, ER loss, HER2 discordance and HER2 loss, compared with the respective concordant cases, resulted in a worse OS and PRS (p<0.05 for all). Our findings show an evident change in ER, PR and HER2 between breast primary tumors and relapsing tumors. The unstable status for ER or HER2 in breast cancer seems to be clinically significant and to correlate with a worse prognosis.

Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast cancer patients

// Jian-Hong Zhong 1, 2, * , Ning-Fu Peng 1, 2, * , Xue-Mei You 1, 2, * , Liang Ma 1, 2, * , Xiao Xiang 1 , Yan-Yan Wang 1 , Wen-Feng Gong 1, 2 , Fei-Xiang Wu 1, 2 , Bang-De Xiang 1, 2 , Le-Qun Li 1, 2 1 Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China 2 Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China * These authors have contributed equally to this work Correspondence to: Le-Qun Li, email: xitongpingjia@163.com Bang-De Xiang, email: xiangbangde@gmail.com Keywords: hepatic resection, hepatocellular carcinoma, transarterial chemoembolization, treatment selection, tumor stage Received: December 01, 2016      Accepted: January 18, 2017      Published: February 17, 2017 ABSTRACT The current clinical reality of tumor stages and primary treatments of hepatocellular carcinoma (HCC) is poorly understood. This study reviewed the distribution of tumor stages and primary treatment modalities among a large population of patients with primary HCC. Medical records of patients treated between January 2003 and October 2013 for primary HCC at our tertiary hospital in China were retrospectively reviewed. A total of 6241 patients were analyzed. The distribution of Barcelona Clinic Liver Cancer (BCLC) stages was as follows: stage 0/A, 28.9%; stage B, 16.2%; stage C, 53.6%; stage D, 1.3%. The distribution of Hong Kong Liver Cancer (HKLC) stages was as follows: stage I, 8.4%; stage IIa, 1.5%; stage IIb, 29.0%; stage IIIa, 10.0%; stage IIIb, 33.6%; stage IVa, 3.4%; stage IVb, 2.5%; stage Va, 0.2%; stage Vb, 11.4%. The most frequent therapy was hepatic resection for patients with BCLC-0/A/B disease, and transarterial chemoembolization for patients with BCLC-C disease. Both these treatments were the most frequent for patients with HKLC I to IIIb disease, while systemic chemotherapy was the most frequent first-line therapy for patients with HKLC IVa or IVb disease. The most frequent treatment for patients with HKLC Va/Vb disease was traditional Chinese medicine. In conclusion, Prevalences of BCLC-B and -C disease, and of HKLC I to IIIb disease, were relatively high in our patient population. Hepatic resection and transarterial chemoembolization were frequent first-line therapies.

Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: A real-world study.

Previous studies have reported conflicting results regarding the impact of neoadjuvant chemotherapy (NAC) on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status in breast cancer. Our aim was to investigate whether NAC induces some selective change in the breast biomarkers. We retrospectively detected the immunohistochemical results of ER, PR and HER2 between the core biopsy and surgical excision specimens in 113 patients with NAC. As a control group, we analyzed sample pairs from 102 patients without NAC. Fourteen (12.4%) of 113 patients undergoing NAC showed the ER status modulation in the surgically removed specimen as compared with only 4 (3.9%) of 102 women without NAC (p=0.025). Eighteen (15.9%) of 113 patients given NAC appeared in the PR status alteration in the final surgical specimen, whereas only 7 (6.9%) of 102 patients without NAC did (p=0.038). The HER2 status shift was found in 17 (15.0%) of 113 patients with NAC and in 6 (5.9%) of 102 patients without NAC, respectively (p=0.030). Neoadjuvant chemotherapy does change ER, PR and HER2 status in a statistically significant manner. Retesting these biomarkers of the residual tumor should be considered to improve future tailored adjuvant therapies.

Changes in ER, PR and HER2 receptors status after neoadjuvant chemotherapy in breast cancer

Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma.

Official guidelines recommend palliative treatments for patients with liver metastases from gastric cancer. However, many case series reported that hepatectomy for such cases is safe and effective. This systematic review compares the overall survival between hepatectomy and palliative therapy in patients with liver metastases from gastric cancer. Two independent reviewers performed a systematic search of literature in EMBASE and PubMed, updated until 26 October 2016. The Newcastle-Ottawa score for cohort studies was used for quality assessment of included studies. A total of eight cohort studies involving 196 patients in the hepatectomy arm and 481 in the palliative arm were included. Median overall survival of patients in the two arms was 23.7 (range, 13.0 to 48.0) and 7.6 (range, 5.5 to 15.2), respectively. Median rates of overall survival of the two arms were 69, 40, 33 and 27, 8, 4% at 1, 2, and 3 years, respectively. Comparing with palliative therapy, hepatectomy was associated with significantly lower mortality at 1 year (odds ratio 0.17, P < 0.001) and 2 years (odds ratio 0.15, P < 0.001). Among the patients who underwent hepatectomy, Asian cohorts showed higher median rates of overall survival than Western cohorts at 1 year (76 vs. 60%), 2 years (47 vs. 30%) and 3 years (39 vs. 23%). Hepatectomy in the management of liver metastases from gastric cancer can be considered effective. In the elective setting, hepatectomy provides a potential alternative to palliative therapy.

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Ning-Fu Peng

Papers

Discordances in ER, PR and HER2 receptors between primary and recurrent/metastatic lesions and their impact on survival in breast cancer patients

Tumor stage and primary treatment of hepatocellular carcinoma at a large tertiary hospital in China: A real-world study.

Changes in ER, PR and HER2 receptors status after neoadjuvant chemotherapy in breast cancer

Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma.

Hepatectomy for liver metastases from gastric cancer: a systematic review