Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast.
ABSTRACT Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality.
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ABSTRACT: Objectives: To describe trends in breast cancer mortality in 14 Italian regions representing 90% of the Italian population, and in the country overall, in relation to the diffusion of organized or opportunistic breast cancer screening programmes. Settings: Breast cancer mortality figures from 1980-2008 in Italy and 14 Italian regions were retrieved from the National Statistics Institute. Methods: Estimated annual percent change (EAPC) was calculated for three time-periods (1980-1989, 1990-1999, 2000-2008). To estimate the age-adjusted and age-specific EAPC, trends in mortality based on annual data were examined using a log-linear regression model, and the year of death as a regressor variable. Results: In the period 1980-1989 an increasing trend was observed in Italy overall (EAPC = +1.1%; 95% confidence interval [95%CI]: +0.9%; +1.3%) and in the 14 regions. In the second decade a decreasing trend was recorded both overall in Italy (EAPC = -1.6%; 95CI: -1.8%; -1.4%) and in all the regions. Between 2000-2008 a slightly decreasing trend was observed in Italy overall (EAPC = -0.8%; 95%CI: -1.0%; -0.5%). A steeper and earlier decrease compared with the rest of Italy was observed in 1990-1999 in Liguria (EAPC = -3.1%; 95%CI: -4.0%, -2.1%), Lombardy (EAPC = -2.3%; 95%CI: -2.8%; -1.9%), and Tuscany (EAPC = -3.0%; 95%CI: -3.7%; -2.2%), mainly due to the 55-64 age-group. There were significant EAPCs between -4.1% and -3.7% in these three regions, 2.5-3.0 times greater than in the rest of Italy (EAPC = -1.4%). Conclusions: This earlier decline in three Italian regions could be partially attributable to local organized screening programmes implemented earlier than in the rest of Italy, and to opportunistic screening that became more common in 1990s.Journal of Medical Screening 09/2014; 21(4). DOI:10.1177/0969141314549368 · 2.72 Impact Factor
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ABSTRACT: A series of recent studies have demonstrated that the retinoblastoma tumor suppressor (RB) pathway plays a critical role in multiple clinically relevant aspects of breast cancer biology, spanning early stage lesions to targeted treatment of metastatic disease. In ductal carcinoma in situ, multiple groups have shown that dysregulation of the RB pathway is critically associated with recurrence and disease progression. Functional models have similarly illustrated key roles for RB in regulating epithelial-mesenchymal transition and other features contributing to aggressive disease. Invasive breast cancers are treated in distinct fashions, and heterogeneity within the RB pathway relates to prognosis and response to commonly used therapeutics. Luminal B breast cancers that have a poor prognosis amongst estrogen receptor-positive disease are defined based on the expression of RB-regulated genes. Such findings have led to clinical interventions that directly target the RB pathway through CDK4/6 inhibition which have promise in both estrogen receptor-positive and Her2-positive disease. In contrast, RB loss results in improved response to chemotherapy in triple-negative breast cancer, where ongoing research is attempting to define intrinsic vulnerabilities for targeted intervention. These findings support a wide-reaching impact of the RB pathway on disease that could be harnessed for improved clinical interventions.Breast cancer research: BCR 05/2014; 16(3):207. DOI:10.1186/bcr3652 · 5.88 Impact Factor
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ABSTRACT: Recent concerns about potential overdiagnosis and overtreatment of ductal carcinoma in situ of the breast (DCIS) render evaluation of late effects of treatment, such as cardiovascular disease (CVD), of great importance. We studied cardiovascular morbidity and mortality in a large population-based cohort of DCIS patients.JNCI Journal of the National Cancer Institute 08/2014; 106(8). DOI:10.1093/jnci/dju156 · 15.16 Impact Factor