A Phase II Study of the Efficacy and Safety of Chloroquine in Combination With Taxanes in the Treatment of Patients With Advanced or Metastatic Anthracycline-refractory Breast Cancer

IntroductionChemotherapy eliminates most of the cancer cells except those with potential for self-renewal and tumor initiation, called cancer stem cells (CSCs). Chloroquine, through bioinformatics, was found to be a potential agent to target CSCs. We designed a phase II trial to test the efficacy and safety of chloroquine in combination with taxane or taxane-like chemotherapy agents in patients with advanced or metastatic breast cancer who are refractory to anthracycline-based chemotherapy.Patients and MethodsFemale patients ≥ 18 years of age who had received prior anthracycline chemotherapy were enrolled in this study. Chloroquine 250 mg was given daily orally with either docetaxel or paclitaxel or nab-paclitaxel or ixabepilone every 3 weeks. The maximum number of 3-week cycles allowed was 6. The primary efficacy endpoint was the objective response rate (ORR). The secondary efficacy endpoints included progression-free survival (PFS) and safety analysis.ResultsThirty-eight patients were enrolled in the study, and 31 patients were evaluated for response. The median age was 54.1 years (range, 31.7-78.1 years). The ORR was 45.16% (95% confidence interval [CI], 29.2%-62.2%), which was higher than the expected ORR of 30% (P = .03). Patients were followed for a median of 25.4 months and experienced a median PFS of 12.4 months (95% CI, 4.9-24.6 months) and a median OS of 25.4 months (95% CI, 13.7-83.5 months). The combination was well-tolerated, with only 13.15% of patients experiencing grade ≥ 3 adverse events.ConclusionA combination of chloroquine with taxane or taxane-like chemotherapy was efficacious in patients with locally advanced or metastatic breast cancer with prior anthracycline-based chemotherapy.     

CASC15 Polymorphisms are Correlated With Breast Cancer Susceptibility in Chinese Han Women

IntroductionBreast cancer (BC) is a prevalent malignant tumor among women. Numerous studies have been reported that long noncoding RNAs (lncRNAs) were associated with various human diseases.Materials and MethodsIn the current study, 681 patients with BC and 680 unrelated controls were recruited to investigate the correlation between lncRNA cancer susceptibility candidate 15 (CASC15) polymorphisms and BC risk in Chinese Han women. We performed single-nucleotide polymorphism genotyping using the Agena MassARRAY platform. The relationship between lncRNA CASC15 polymorphisms and the risk of BC were evaluated through odds ratios and 95% confidence intervals.ResultsOur results suggested that the lncRNA CASC15 rs7740084 “G/G” genotype and rs1928168 “T/C” genotype significantly reduced BC risk in different genetic models (P = .045, P = .029, and P = .047, respectively). However, rs9393266 “C/T” and “C/T-T/T” genotypes were correlated with the risk of BC (P = .021 and P = .048). In addition, we also observed that rs1928168 was related to the risk of BC in patients with age > 50 years (P = .025), body mass index > 24 (P = .006), and tumor size (P = .035). For rs9393266, it was revealed that the “C/T” and “C/T-T/T” genotypes were related to BC risk in people with age ≤ 50 years (P = .005) and body mass index > 24 (P = .023).ConclusionIn summary, our results revealed a potential interaction between lncRNA CASC15 polymorphisms and BC susceptibility. The results provided an important insight into lncRNA CASC15 function in the development of BC.     

Beyond Teenage and Young Adult Cancer Care: Care Experiences of Patients Aged 25–39 Years Old in the UK National Health Service

AimsAdolescents and young adults aged 15–39 years with cancer face unique medical, practical and psychosocial issues. In the UK, principal treatment centres and programmes have been designed to care for teenage and young adult patients aged 13–24 years in an age-appropriate manner. However, for young adults (YAs) aged 25–39 years with cancer, little access to age-specific support is available. The aim of this study was to examine this possible gap by qualitatively exploring YA care experiences, involving patients as research partners in the analysis to ensure robust results.Materials and methodsWe conducted a phenomenological qualitative study with YAs diagnosed with any cancer type between ages 25 and 39 years old in the last 5 years. Participants took part in interviews or focus groups and data were analysed using inductive thematic analysis. Results were shaped in an iterative process with the initial coders and four YA patients who did not participate in the study to improve the rigor of the results.ResultsSixty-five YAs with a range of tumour types participated. We identified seven themes and 13 subthemes. YAs found navigating the healthcare system difficult and commonly experienced prolonged diagnostic pathways. Participants felt under-informed about clinical details and the long-term implications of side-effects on daily life. YAs found online resources overwhelming but also a source of information and treatment support. Some patients regretted not discussing fertility before cancer treatment or felt uninformed or rushed when making fertility preservation decisions. A lack of age-tailored content or age-specific groups deterred YAs from accessing psychological support and rehabilitation services.ConclusionsYAs with cancer may miss some benefits provided to teenagers and young adults in age-tailored cancer services. Improving services for YAs in adult settings should focus on provision of age-specific information and access to existing relevant support.     

Microbiome and colorectal cancer: A review of the past,present, and future

The gastrointestinal tract is home to diverse and abundant microorganisms, collectively referred to as the microbiome. This ecosystem typically contains trillions of microbial cells that play an important role in regulation of human health. The microbiome has been implicated in host immunity, nutrient absorption, digestion, and metabolism. In recent years, researchers have shown that alteration of the microbiome is associated with disease development, such as obesity, inflammatory bowel disease, and cancer.This review discusses the five decades of research into the human microbiome and the development of colorectal cancer – the historical context including experiments that sparked interest, the explosion of research that has occurred in the last decade, and finally the future of testing and treatment.