The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting.

Tamoxifen treatment was associated with reduction in breast density, most of which occurred during the first 18 months of treatment.

Determination of survival time among persons with screen-detected cancer is subject to lead time and length biases. The authors propose a simple correction for lead time, assuming an exponential distribution of the preclinical screen-detectable period. Assuming two latent categories of tumors, one of which is more prone to screen detection and correspondingly less prone to death from the cancer in question, the authors have developed a strategy of sensitivity analysis for various magnitudes of length bias. Here they demonstrate these methods using a series of 25,962 breast cancer cases (1988-2004) from the West Midlands, United Kingdom.

BackgroundTreatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality.MethodsParticipants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.5 mg ± perindopril 2 to 4 mg or to matching placebo. Data relating to blood pressure, comorbidities, cognitive function, depression, and quality of life were collected at entry into the study and at subsequent follow-up visits. The FI was calculated at entry, based on 60 potential deficits. The distribution of FI was similar to that seen in population studies of adults aged 80 years and above (median FI, 0.17; IQR, 0.11–0.24). Cox regression was used to assess the impact of FI at entry to the study on subsequent risk of stroke, total mortality, and cardiovascular events. Models were stratified by region of recruitment and adjusted for sex and age at entry. Extending these models to include a term for a possible interaction between treatment for hypertension and FI provided a formula for the treatment effect as a function of FI. For all three models, the point estimates of the hazard ratios for the treatment effect decreased as FI increased, although to varying degrees and with varying certainty.ResultsWe found no evidence of an interaction between effect of treatment for hypertension and frailty as measured by the FI. Both the frailer and the fitter older adults with hypertension appeared to gain from treatment.ConclusionsFurther work to examine whether antihypertensive treatment modifies frailty as measured by the FI should be explored.Trial registrationClinicalTrials.gov NCT00122811 (July 2005)Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0328-1) contains supplementary material, which is available to authorized users.

Early endovenous ablation of superficial venous reflux resulted in faster healing of venous leg ulcers and more time free from ulcers than deferred endovenous ablation. (Funded by the National Institute for Health Research Health Technology Assessment Program; EVRA Current Controlled Trials number, ISRCTN02335796 .).

BACKGROUNDAlthough there is evidence for a reduction in breast carcinoma mortality with mammographic screening, some doubts have been expressed, and there is still uncertainty regarding the age specific effects.METHODSThe authors report on a randomized, controlled trial of mammographic screening for breast carcinoma that was conducted among 51,611 women (21,650 women who were invited to a screening [the study group] and 29,961 women in a control group) ages 39–59 years in Gothenburg, Sweden. Among women in the study group, the screening interval was 18 months. The screening phase of the trial took place in 1982–1991, and follow‐up for breast carcinoma mortality continued until December 31, 1996. Mortality from breast carcinoma was analyzed using a Poisson regression model. Overall and age specific effects of invitation to mammography screening on breast carcinoma mortality were calculated. Three mortality effects were estimated: the effect on deaths from breast tumors diagnosed during the screening phase of the trial, as assessed by an independent Endpoint Committee (the EPC evaluation model); the effect on deaths from breast carcinoma diagnosed during the screening phase of the trial, as determined by data from the National Cancer Registry and the National Cause of Death Register (the SCB evaluation model); and the effect on deaths from all breast carcinomas diagnosed up to December 31, 1996, as determined by the National Cancer Registry and the National Cause of Death Register (the SCB follow‐up model).RESULTSA nonsignificant, 21% reduction in the rate of mortality from breast carcinoma with invitation to screening was observed using the EPC evaluation model (relative risk [RR], 0.79; 95% confidence interval [95% CI], 0.58–1.08; P = 0.14); and a borderline significant, 23% rate reduction was observed using the SCB follow‐up model (RR, 0.77; 95% CI, 0.60–1.00; P = 0.05). Age specific analyses yielded greater mortality rate reductions for the groups of women ages 39–44 years, 45–49 years, and 55–59 years, but there was no mortality rate reduction in the group of women ages 50–54 years. The effects of invitation to mammographic screening on the incidence of lymph node‐positive disease closely paralleled the effects of invitation on breast carcinoma mortality. The effect on breast carcinoma mortality was consistent with the effect on all‐cause mortality, suggesting no bias in classification of cause of death. Breast carcinoma incidence in the study group was almost identical to the incidence in the control group after trial by screening had ended in the control group (RR, 0.98; 95% CI, 0.88–1.09; P = 0.7).CONCLUSIONSThe current results support the commonly observed 20–30% reduction in breast carcinoma mortality with invitation to screening. The impression that screening is less effective in women younger than 50 years may be an oversimplification. Age specific effects should be a target for further research. Cancer 2003;10:2387–96. © 2003 American Cancer Society.DOI 10.1002/cncr.11361

METHODS.Following superovulation with recombinant follicle-stimulating hormone and administration of gonadotropinreleasing hormone antagonist to prevent premature ovulation, 53 women were administered a single subcutaneous injection of kisspeptin-54 (1.6 nmol/kg, n = 2; 3.2 nmol/kg, n = 3; 6.4 nmol/kg, n = 24; 12.8 nmol/kg, n = 24) to induce a luteinizing hormone surge and egg maturation. Eggs were retrieved transvaginally 36 hours after kisspeptin injection, assessed for maturation (primary outcome), and fertilized by intracytoplasmic sperm injection with subsequent transfer of one or two embryos. RESULTS.Egg maturation was observed in response to each tested dose of kisspeptin-54, and the mean number of mature eggs per patient generally increased in a dose-dependent manner. Fertilization of eggs and transfer of embryos to the uterus occurred in 92% (49/53) of kisspeptin-54-treated patients. Biochemical and clinical pregnancy rates were 40% (21/53) and 23% (12/53), respectively. CONCLUSION.This study demonstrates that a single injection of kisspeptin-54 can induce egg maturation in women with subfertility undergoing in vitro fertilization therapy. Subsequent fertilization of eggs matured following kisspeptin-54 administration and transfer of resulting embryos can lead to successful human pregnancy.

BackgroundIntegrin αvβ6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of αvβ6 has yet to be elucidated in breast cancer.MethodsProtein expression of integrin subunit beta6 (β6) was measured in breast cancers by immunohistochemistry (n > 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of β6 in breast cell lines, the role of αvβ6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ≥ 3), respectively. A student’s t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni’s Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.ResultsHigh expression of either the mRNA or protein for the integrin subunit β6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of β6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P < .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.ConclusionsTargeting αvβ6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.