Adherence to oral endocrine treatments in women with breast cancer: can it be improved?

There is a perception that women on oral endocrine treatments for oestrogen receptor-positive breast cancer will be adherent to these medicines, as they are facing a serious life-threatening disease, and the oral endocrine treatments are effective, easy to use and generally well tolerated. This is not in fact the case, and this is the basis of the first half of this review. The second half is of whether the changes/interventions to 'improve' adherence do actually increase adherence to the oral endocrine medicines. The review shows that better outcomes are achieved with good adherence to endocrine treatments in breast cancer. The rates of adherence to endocrine treatments range between 15 and 50%, and are influenced by a large number of factors (e.g. adverse effects, lack of belief in treatment, psychological problems and poor patient-health care provider relationship). Interventions to minimise the adverse effects have been used in an attempt to improve the adherence to the endocrine treatment therapies, but it is not known whether these do actually improve adherence. Similar, it has been assumed that interventions by health professionals (doctors, nurses and pharmacists) will improve the adherence, but this has not been tested. In conclusion, in women with breast cancer, we know there is a problem with adherence. There are also many approaches and suggestions about how to improve adherence to the oral endocrine treatments, but none of these approaches/suggestions have been scientifically tested, and they need to be.     

Targeting protein kinases in cancer therapy: a success?

The fundamental role of kinases in cancer progression has promoted the development of a plethora of therapeutic inhibitors. Despite the promise of effective treatment with little associated toxicity, the clinical experience with these agents has been mixed. This review will summarize recent advances made in the development of kinase inhibitors to highlight emerging issues and the strategies by which they being addressed.     

Targeting protein kinases in cancer therapy: a success?

The fundamental role of kinases in cancer progression has promoted the development of a plethora of therapeutic inhibitors. Despite the promise of effective treatment with little associated toxicity, the clinical experience with these agents has been mixed. This review will summarize recent advances made in the development of kinase inhibitors to highlight emerging issues and the strategies by which they being addressed.     

Screen-detected vs symptomatic breast cancer: is improved survival due to stage migration alone?

This paper examines whether screen-detected breast cancer confers additional prognostic benefit to the patient, over and above that expected by any shift in stage at presentation. In all, 5604 women (aged 50-70 years) diagnosed with invasive breast cancer between 1998 and 2003 were identified by the Eastern Cancer Registration and Information Centre (ECRIC) and mammographic screening status was determined. Using proportional hazards regression, we estimated the effect of screen detection compared with symptomatic diagnosis on 5-year survival unadjusted, then adjusted for age and Nottingham Prognostic Index (NPI). A total of 72% of the survival benefit associated with screen-detected breast cancer can be accounted for by age and shift in NPI. Survival analysis by continuous NPI showed a small but systematic survival benefit for screen-detected cancers at each NPI value. These data show that although most of the screen-detected survival advantage is due to a shift in NPI, the mode of detection does impact on survival in patients with equivalent NPI scores. This residual survival benefit is small but significant, and is likely to be due to differences in tumour biology. Current prognostication tools may, therefore, overestimate the benefit of systemic treatments in screen-detected cancers and lead to overtreatment of these patients.     

Targeting metabolism in breast cancer: How far we can go?

Adjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer.     

Targeting triple negative breast cancer: Is p53 the answer?

Triple negative breast cancers, which are defined by lack of expression of estrogen, progesterone, or HER2 receptors, represent approximately 15% of all breast cancers, although they account for a much higher proportional of breast cancer mortality. This is due both to their innate aggressive biological characteristics, but also to lack of effective therapies. Conventional chemotherapy is currently the only treatment option, thus there is a critical need to find new and effective targeted therapies in this disease. While investigation of agents such as poly (ADP-ribose) polymerase (PARP) inhibitors and EGFR inhibitors continues, results from recent clinical trials indicate that these therapies are not as active in sporadic triple negative breast cancers as initially hoped. It is important therefore to consider other emerging therapeutic agents. Mutation in p53 is found in the vast majority of triple negative breast cancers, and as such is a target of particular interest. Within this review, several agents with potential activity against aberrant p53 signaling have been considered, as a novel approach to finding an effective targeted therapy for this aggressive breast cancer subtype.     

Eradication of breast cancer cells in patients with distant metastasis: the finishing touches?

Cytotoxic agents are significantly active in breast cancer cells, but their usefulness has been limited in treating metastatic breast cancer (MBC). This has facilitated the development of an approach using molecular-targeted agents. Intrinsic subtypes including luminal A, luminal B, human epidermal growth factor receptor type 2 (HER2)-enriched, basal-like, and claudin-low tumors exhibit original drug responsiveness and clinical prognosis. Anti-HER2 treatments, trastuzumab or lapatinib, have demonstrated clinically significant efficacy. Poly ADP-ribose polymerase-1 inhibitors act against BRCA1-disabled breast cancer. Cancer stem cells could be the major obstacle to achieving a cure in systemic treatment. Extensive investigations are underway to develop novel agents that act on the genes or signaling of Hedgehog, Wnt, and Notch, which regulate cancer stem cells. Cancer cells undergo epithelial?Cmesenchymal transition (EMT) and acquire invasive properties. Breast cancer cells alter their phenotype in blood and bone marrow, e.g., circulating tumor cells or disseminated tumor cells. Cancer stem cells, like normal stem cells, may exist at niches in bone marrow. To achieve a cure for MBC, it is necessary to disrupt cancer stem cell?Cniche interactions or eradicate cancer stem cells. Traditional treatments with cytotoxic or endocrine agents require development in relation to intrinsic subtypes, stem cells, or EMT.     

Radiation-induced cell death and dendritic cells: potential for cancer immunotherapy?

Dendritic cells are key orchestrators of the immune system. There is considerable interest in their use for treating cancer. Whether they initiate an effective cytotoxic response against antigen-bearing cells, or produce tolerance, depends on the context in which those antigens are presented. Ionising radiation, and the cell death it causes, has several properties that may facilitate such an effective response. A range of in-vitro and in-vivo data supports this, although potential problems exist that may require concurrent strategies.     

Hypothesis: is antibiotic use associated with breast cancer?

The hypothesis that antibiotic use may increase cancer risk was first proposed several decades ago and some research suggests an increased risk of breast cancer among women with conditions likely to require long-term antibiotic use (e.g., acne, recurrent urinary-tract infections, UTI). However, this hypothesis has not been verified and the possible biological mechanisms are not entirely clear. A recent cohort study in Finland reported an increased risk of breast-cancer associated with antibiotic use for UTI. The effect of antibiotics on the ability of intestinal microflora to metabolise phytochemicals from edible plants into compounds that may protect against cancer was proposed as a potential mechanism. We extend this hypothesis by proposing that antibiotic use may be associated with breast-cancer risk through effects on immune and inflammatory factors, such as cytokines, T lymphocytes, prostaglandins, and matrix metalloproteinases, as well as disruption of phytochemical and oestrogen metabolism by intestinal microflora. We suggest that some mechanisms may increase breast-cancer risk, while others may decrease risk, depending on the antibiotic classification.     

Has racial difference in cause-specific death improved in older patients with late-stage breast cancer?

BackgroundResearch on temporal mortality trends for stage IV breast cancer is limited, especially among older patients by race. We evaluated factors associated with overall, breast cancer-specific and other-cause mortalities using contemporary population data.Patients and methodsUsing the Surveillance, Epidemiology, and End Results–Medicare linked data, we identified older women (≥66 years) with stage IV breast cancer diagnosed in 2002–2009. Overall mortality was estimated by the Kaplan–Meier method, compared by log-rank tests, and modeled by Cox models. Competing risk analysis was used to evaluate breast cancer-specific and other-cause mortalities.ResultsThe median overall survival time for non-Hispanic blacks improved from 8.6 months in 2002–2003 to 9.9 months in 2007–2009, whereas that for non-Hispanic whites improved from 12.1 to 14.8 months. In the multivariate model, the risk of breast cancer-specific death for patients diagnosed in 2007–2009 was significantly lower (P = 0.02), whereas the risk of other-cause mortality changed little (P = 0.88) compared with those risks for patients diagnosed in 2002–2003. Non-Hispanic blacks had the higher risk of both mortality types compared with non-Hispanic whites; a diagnosis time–race interaction term was not statistically significant for either cause of death.ConclusionBreast cancer-specific mortality among older women modestly improved from 2002 to 2009 across all races, but not other-cause mortality. Racial disparity in mortality persisted, but did not widen in this period. Efforts should be devoted to improving other-cause mortality for all women, with special attention toward decreasing breast cancer mortality for non-Hispanic black women.