Raloxifene for the treatment and prevention of breast cancer?

Raloxifene is a member of a family of drugs known as selective estrogen receptor modulators (SERMs). Raloxifene is currently approved by the FDA for the prevention and treatment of osteoporosis in postmenopausal women. SERMs hold the potential to treat and prevent breast cancer, osteoporosis and coronary heart disease. Ongoing clinical trials are in place to address the role of raloxifene and SERMs in each of these areas. We review the pharmacology, clinical utility, safety and tolerability of raloxifene and speculate on what the future holds for SERMs and their use in breast cancer.     

Raloxifene for the treatment and prevention of breast cancer?

Raloxifene is a member of a family of drugs known as selective estrogen receptor modulators (SERMs). Raloxifene is currently approved by the FDA for the prevention and treatment of osteoporosis in postmenopausal women. SERMs hold the potential to treat and prevent breast cancer, osteoporosis and coronary heart disease. Ongoing clinical trials are in place to address the role of raloxifene and SERMs in each of these areas. We review the pharmacology, clinical utility, safety and tolerability of raloxifene and speculate on what the future holds for SERMs and their use in breast cancer.     

Examining stools for colon cancer prevention: what are we really looking for?

Fecal immunochemical testing (FIT) is superior to guiac-based testing if we are looking for blood in stools, as it has better one-time colorectal cancer sensitivity and specificity and better patient acceptance. In this issue of the journal, Cai and colleagues (beginning on page 1572) and Khalid-de Bakker and colleagues (beginning on page 1563) present new information about the one-time test performance of FIT. FIT will have a growing appeal to providers and health care systems as resources for clinical preventive services shrink and as incentives to expand colorectal screening rates increase, but there are good reasons to be cautious about the temptation to organize new FIT screening programs. Colorectal screening has two potential objectives: To find cancers in an earlier, more-treatable stage and to find and remove adenomas to prevent cancers from forming in the first place. Because most adenomas, even advanced adenomas, do not bleed, tests designed to identify occult blood in the stool are better for detecting colorectal cancer, whereas direct endoscopic visualization of the colorectum is better for prevention. Even if advanced adenomas did commonly bleed, low compliance with repeat annual testing will seriously erode the benefit of FIT.     

Targeting of tamoxifen to enhance antitumour action for the treatment and prevention of breast cancer: The ‘personalised’ approach?

Tamoxifen is a standard endocrine therapy for the treatment of steroid receptor positive breast cancer. Tamoxifen efficacy depends on the formation of clinically active metabolites 4-hydroxytamoxifen and endoxifen which have a greater affinity to the oestrogen receptor and ability to control cell proliferation as compared to the parent drug. The cytochrome P450 2D6 enzyme plays a key role in this biotransformation and lack of tamoxifen efficacy has been linked to low activity. There is now considerable mechanistic, pharmacologic and clinical pharmacogenetic evidence in support of the notion that CYP2D6 genetic variants and phenocopying effects through drug interaction by CYP2D6 inhibitors influence plasma concentrations of active tamoxifen metabolites and negatively impact tamoxifen outcome. These interrelations are particularly critical for patients with non-functional (poor metaboliser) and severely impaired (intermediate metaboliser) CYP2D6 variants, and, moreover, for patients in need of co-medication such as serotonin re-uptake inhibitors to control adverse effects such as hot flashes and other menopausal symptoms. Therefore, in the future, a personalised approach for an optimal tamoxifen benefit should consider a CYP2D6 genotype guided adjuvant endocrine treatment strategy and avoid non-adherence as well as strong CYP2D6 inhibitors such as co-medications.     

Pancreatic cancer: promise for personalised medicine?

Sleeping Beauty (SB) is a genetically engineered insertional mutagenesis system. Its ability to rapidly induce cancer in SB-transgenic mice as well as the ease of identification of the mutated genes suggest important roles for SB in the discovery of novel cancer genes as well as the generation of models of human cancers where none currently exist. The range of SB-related tumors extends from haematopoietic to solid cancers such as hepatocellular carcinoma. This review follows the refinement of SB for different cancers and assesses its potential as a model for all cancers and a tool for cancer gene discovery.     

Patient education materials: are they readable?

The move toward discharging patients "quicker and sicker" does not allow patients sufficient time to receive the necessary education they need to provide for their self-care at home. Nurses are relying on printed materials to reinforce, or even supplement, hospital patient education programs. Many popular publications are available for the education of patients with cancer. However, a discrepancy exists between the reading level of the average adult and the reading level fo the printed materials. Many studies show that the average reading level of adults falls between the fifth- and eighth-grade levels. Common patient education materials reviewed tested between the eighth- and 12th-grade reading levels, with most materials falling at the upper range. An example of how to calculate one commonly used readability formula is presented in this article.     

Patient choice for cancer treatment: towards a shared-decision model?

The process of medical decision implies the elaboration of a choice between alternatives. Who has the choice? The doctor? The patient? Both? That depends on the particular characteristics of the patient and of the tumour, but also of the characteristics of the doctor and of his approach of medical discipline. For that reason, we planned first to remind some principles. In our analysis, the patient-doctor's relationship ties with environment, culture and habits. Philosophical principles, moral, and models of the relation between patient and doctor concern first part. In the second part, these ideas are compared with our routine practice: surveys about patients' needs, the obstacles for complete information and participation, studies on patients' preferences. The authors' analysis is that we are going inescapably towards shared decision-making taking into account the patients preferences. This evolution is not only tied with ethical principles, but with medical reason, i.e. the variability of patients' preferences led to tailor the treatment to the individual patient especially when benefit is limited. Of course, the applicability of a shared model depends on the particular situation of the patient and of his demand. It is all the easier as the consequences of the treatment are well known the riks tiny and distant. In the classical paternalistic model, there is no choice for the patient because the doctor(s) give the treatment. In the ideal model of the shared decision, doctor and patient progress together towards medical decision, in this case, the patient is not alone facing a choice, and in all cases, he is never alone.     

Does endocrine therapy for the treatment and prevention of breast cancer affect memory and cognition?

Oestrogen receptors have been identified in several areas of the brain important in cognitive performance, including the prefrontal cortex (active during short-term working memory), the hippocampus and related cortical areas (learning and storage of information) and the amygdala (involved in the modulation of memory consolidation). There is much debate as to whether or not a reduction in oestrogen levels results in a corresponding decline in cognitive processing. Arguments for an effect are based on findings from laboratory and hormone replacement studies and the pharmacological actions of breast cancer drugs. However, there are few clinical data substantiating the claim that endocrine therapies used in the treatment and prevention of breast cancer could affect cognition. This paper examines the main evidence associated with this claim and discusses the importance of examining such issues within randomised trials.     

What are SNPs and haplotypes and how will they help us manage the prevention of adult cancer?

Human genetic variation data are now publicly available on a large scale, from public and private discovery efforts. Datasets from the International Haplotype Map Consortium and Perlegen Sciences provide a level of knowledge about human genetic variation that is unprecedented. In combination with novel high-throughput genotyping technologies, these new resources will allow cancer prevention investigators to identify in a more precise way which genetic subsets of patients are likely to benefit most from chemoprevention and screening interventions.     

Targeted therapies and radiation for the treatment of head and neck cancer: are we making progress?

Targeting specific biological pathways in tumor development has been heralded as a promising approach to the treatment of cancer. Familiar to most investigators are the studies done with epidermal growth factor receptor (EGFR) antagonists, but newer agents currently under development also target angiogenic or cell cycle pathways. EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Because EGFR overexpression portends for a worse outcome in patients with advanced head and neck cancer (HNC), selective targeting of this signaling pathway has gained attention. The agents selected for initial studies include monoclonal antibodies and tyrosine kinase inhibitors against EGFR. Encouraging laboratory findings in different xenografts resulted in rapid translation into the clinic. Results from initial clinical trials show rather surprisingly that only a minority of patients benefited from EGFR inhibition as monotherapy or in combination with chemotherapy. Current challenges for investigators are to determine (1). who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2). how to sequence these agents with radiation and/or cytotoxic compounds, (3). reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4). mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multiple targeted therapy. Well-integrated laboratory-clinical research programs are needed to address these issues.     

Symptoms after breast cancer treatment: are they influenced by patient characteristics?

PURPOSE: This study examines the burden of symptoms by treatment type and patient characteristics in a population-based sample of newly diagnosed breast cancer patients. METHODS: Using the Los Angeles County SEER Registry Rapid Case Ascertainment, we identified a cohort of breast cancer patients in 2000 and conducted telephone surveys in English and Spanish among participants. RESULTS: We completed interviews of 1,219 breast cancer patients and found almost half (46%) had at least one severe symptom (any of the following: nausea/vomiting, arm problems, hot flashes, vaginal dryness, difficulty sleeping) that interfered with her daily functioning or mood. Multi-variate analysis controlling for patient characteristics and treatment showed that older (OR=0.90; P<0.000), black (OR=0.50; P<0.000), Hispanic Spanish-speaking (OR=0.37; P<0.000), widowed or never married (OR=0.68; P=0.049), and working (OR=0.72; P=0.024) women were less likely to report severe symptoms than other women. Number of comorbid conditions (OR=1.21; P<0.000) and receipt of chemotherapy (OR=1.48; P=0.040) were positively associated with reporting symptoms. CONCLUSION: These findings estimate the prevalence of several mutable symptoms in breast cancer patients that can be addressed by appropriate treatments. Comorbidity is a significant predictor of symptoms, especially amongst those receiving chemotherapy. Variation in symptom reporting occurred by race/ethnicity and other sociodemographic characteristics, raising questions of different thresholds for reporting symptoms or truly fewer symptoms for some sociodemographic groups. Population-based estimates of the probability of symptoms in women with incident breast cancer can be used to provide patient education about potential outcomes following the treatment of breast cancer.     

Patient and physician reports of the information provided about illness and treatment: what matters for patients' adaptation to cancer during treatment?

Objective: The aim of this study was to examine (a) whether illness representations mediate the relation of the amount of information provided by physicians to patients' adaptation to illness; (b) whether patient–physician agreement on the information provided impacts the aforementioned relationship. The study focused on information that, according to the Common Sense Self‐Regulation Model, is essential for adaptation to illness. Methods: The sample consisted of 93 patients undergoing chemotherapy and their physicians. Indirect (mediation) effects and conditional (moderated) indirect effects were examined using bootstrapping. Results: The more illness and treatment‐related information was provided by physicians, the more positive illness representations (specifically, illness consequences, emotional representations, and personal control) were reported by patients. In turn, these illness representations were related to better physical functioning and better adjustment to cancer. The degree of the patient–physician agreement on the information provided did not affect this relationship. Conclusions: What seems to be more crucial for patients' adaptation to cancer during treatment is the amount of information provided by physicians rather than their agreement with patients on the information provided. Also, there is a need to thoroughly examine the pathways through which information provision impacts adaptation to illness. Copyright © 2015 John Wiley & Sons, Ltd.