Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials

Polychemotherapy for early breast cancer: an overview of the randomised trials

Objective. —To evaluate the effect of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients with symptomatic congestive heart failure. Data Sources and Study Selection. —Data were obtained for all completed, published or unpublished, randomized, placebo-controlled trials of ACE inhibitors that were at least 8 weeks in duration and had determined total mortality by intention to treat, regardless of sample size. Trials were identified based on literature review and correspondence with investigators and pharmaceutical firms. Data Extraction. —Using standard tables, data were extracted by one author and confirmed where necessary by the other author or the principal investigator of the trial. Unpublished data were obtained by direct correspondence with the principal investigator of each study or pharmaceutical firm. Data Synthesis. —The data for each outcome were combined using the Yusuf-Peto adaptation of the Mantel-Haenszel method. Overall, there was a statistically significant reduction in total mortality (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.67 to 0.88;P Conclusions. —Total mortality and hospitalization for congestive heart failure are significantly reduced by ACE inhibitors with consistent effects in a broad range of patients. (JAMA. 1995;273:1450-1456)

https://jamanetwork.com/journals/jama/articlepdf/388358/jama_273_18_040.pdf

Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure

Screening with mammography uses X-ray imaging to find breast cancer before a lump can be felt. The goal is to treat cancer earlier, when a cure is more likely. The review includes seven trials that involved 600,000 women in the age range 39 to 74 years who were randomly assigned to receive screening mammograms or not. The studies which provided the most reliable information showed that screening did not reduce breast cancer mortality. Studies that were potentially more biased (less carefully done) found that screening reduced breast cancer mortality. However, screening will result in some women getting a cancer diagnosis even though their cancer would not have led to death or sickness. Currently, it is not possible to tell which women these are, and they are therefore likely to have breasts or lumps removed and to receive radiotherapy unnecessarily. If we assume that screening reduces breast cancer mortality by 15% after 13 years of follow-up and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings.
Women invited to screening should be fully informed of both the benefits and harms. To help ensure that the requirements for informed choice for women contemplating whether or not to attend a screening programme can be met, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.

/pdf/screening-for-breast-cancer-with-mammography-36k7l5kzia.pdf

Screening for breast cancer with mammography.

https://amstar.ca/docs/Publication%20-%20AMSTAR%20is%20reliable.pdf

AMSTAR is a reliable and valid measurement tool to assess the methodological quality of systematic reviews.

We sought information worldwide on mortality according to assigned treatment in all randomized trials that began before 1985 of adjuvant tamoxifen or cytotoxic therapy for early breast cancer (with or without regional lymph-node involvement). Coverage was reasonably complete for most countries. In 28 trials of tamoxifen nearly 4000 of 16,513 women had died, and in 40 chemotherapy trials slightly more than 4000 of 13,442 women had died. The 8106 deaths were approximately evenly distributed over years 1, 2, 3, 4, and 5+ of follow-up, with little useful information beyond year 5. Systematic overviews of the results of these trials demonstrated reductions in mortality due to treatment that were significant when tamoxifen was compared with no tamoxifen (P less than 0.0001), any chemotherapy with no chemotherapy (P = 0.003), and polychemotherapy with single-agent chemotherapy (P = 0.001). In tamoxifen trials, there was a clear reduction in mortality only among women 50 or older, for whom assignment to tamoxifen reduced the annual odds of death during the first five years by about one fifth. In chemotherapy trials there was a clear reduction only among women under 50, for whom assignment to polychemotherapy reduced the annual odds of death during the first five years by about one quarter. Direct comparisons showed that combination chemotherapy was significantly more effective than single-agent therapy, but suggested that administration of chemotherapy for 8 to 24 months may offer no survival advantage over administration of the same chemotherapy for 4 to 6 months. Because it involved several thousand women, this overview was able to demonstrate particularly clearly that both tamoxifen and cytotoxic therapy can reduce five-year mortality.

G. Bonadonna

Papers

Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. An overview of 61 randomized trials among 28,896 women