Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy

PurposeThere is no consensus on what constitutes adequate negative margins in breast-conserving therapy (BCT). We review the evidence on surgical margins in BCT for early-stage invasive breast cancer.MethodsMeta-analysis of studies reporting local recurrence (LR) relative to quantified final microscopic margin status and the threshold distance for negative margins. The proportion of LR was modelled using random effects logistic meta-regression.ResultsBased on 21 studies (LR in 1,026 of 14,571 subjects) the odds of LR were associated with margin status [model 1: odds ratio (OR) = 2.02 for positive/close versus negative; model 2: OR = 1.80 for close versus negative, 2.42 for positive versus negative (P < 0.001 both models)] but not with margin distance [1 mm versus 2 mm versus 5 mm (P > 0.10 both models)], adjusting for median follow-up time. However, there was weak evidence in both models that the odds of LR decreased as the threshold distance for declaring negative margins increased. This bordered significance in model 2 [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.75, 0.51 (P = 0.097 for trend)], and was not significant in model 1 [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.85, 0.58 (P = 0.11 for trend)] but was evident when one study (of women ? 40 years) was excluded from this model [OR for 1 mm, 2 mm, 5 mm: 1.0, 0.72, 0.52 (P = 0.058 for trend)]: this trend was rendered insignificant by adjustment for the proportion of subjects receiving a radiation boost or the proportion of subjects receiving endocrine therapy.ConclusionsMargin status has a prognostic effect in all women treated for invasive breast cancer; increasing the threshold distance for declaring negative margins is weakly associated with reduced odds of LR, however adjustment for covariates (adjuvant therapy) removes the significance of this effect. Adoption of wider margins, relative to narrower widths, for declaring negative margins is unlikely to a have substantial additional benefit for long-term local control in BCT.     

Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation

Hypoxia-inducible factor 1α (HIF-1α) and HIF-2α display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. Macrophages exposed to hypoxia accumulate both HIF-1α and HIF-2α, and overexpression of HIF-2α in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. However, the precise role of HIF-2α during macrophage-mediated inflammatory responses remains unclear. To fully characterize cellular hypoxic adaptations, distinct functions of HIF-1α versus HIF-2α must be elucidated. We demonstrate here that mice lacking HIF-2α in myeloid cells (Hif2a^Δ/Δ mice) are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2α directly regulated proinflammatory cytokine/chemokine expression in macrophages activated in vitro. Hif2a^Δ/Δ mice displayed reduced TAM infiltration in independent murine hepatocellular and colitis-associated colon carcinoma models, and this was associated with reduced tumor cell proliferation and progression. Notably, HIF-2α modulated macrophage migration by regulating the expression of the cytokine receptor M-CSFR and the chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2α as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer.     

The meaning of “control” for childbearing women in the US

Childbearing women, healthcare providers, and commentators on birth broadly identify control as an important issue during childbirth; however, control is rarely defined in literature on the topic. Here we seek to deconstruct the term control as used by childbearing women to better understand the issues and concepts underpinning it. Based on qualitative interviews with 101 parous women in the United States, we analyze meanings of control within the context of birth narratives. We find these meanings correspond to five distinct domains: self-determination, respect, personal security, attachment, and knowledge. We also find ambivalence about this term and concept, in that half our sample recognizes “you cannot control birth”. Together, these findings call into question the usefulness of the term for measuring quality or improving maternity care and highlight other concepts which may be more fruitfully explored.     

Public views of the uk media and government reaction to the 2009 swine flu pandemic

Background  

The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks.     

Enterolactone and breast cancer: methodological issues may contribute to conflicting results in observational studies

Lignans found in plant foods are converted by the intestinal microflora to enterolignans. The structure of enterolignans is similar to that of estrogens, which has inspired researchers to examine a potential protective association in relation to health outcomes. Numerous epidemiological studies have measured concentration of enterolignans, mainly enterolactone, in blood or urine as a biomarker of lignan exposure and studied its relation to breast cancer risk. Case-control studies have shown decreased breast cancer risk associated with high circulating enterolactone concentrations, but results demonstrated by prospective cohort studies are less clear. The purpose of this review is to discuss factors that may contribute to these contradictory findings obtained in epidemiological studies, including age distribution, enterolactone measurement error, heterogeneity of breast cancer subtypes, and genetic factors. Different sources of enterolactone precursors may also contribute to inconclusive results. In conclusion, to get robust evidence of the health effects of lignans and enterolactone, more effort has to be put on methodological problems, including reducing measurement errors in enterolactone estimation, and to identify factors that modify the effect.