The method of detection of ductal carcinoma in situ has no therapeutic implications: results of a population-based cohort study

Multivariable-adjusted Cox regression analysis of ipsilateral and contralateral invasive breast cancer in women aged 49–75 years at DCIS diagnosis (DCIS diagnostic period 1989–2004). Age was the primary time scale, time since DCIS diagnosis (0–5, 5–10, and ≥10 years) the secondary time scale, and DCIS treatment a time-varying covariable (DOCX 22 kb

Cause-specific Mortality in a Population-based Cohort of 9799 Women Treated for Ductal Carcinoma in Situ

Objective: To assess cause-specific mortality in women treated for ductal carcinoma in situ (DCIS). Background: From screening and treatment perspective, it is relevant to weigh the low breast cancer mortality after DCIS against mortality from other causes and expected mortality in the general population. Methods: We conducted a population-based cohort study comprising 9799 Dutch women treated for primary DCIS between 1989 and 2004 and estimated standardized mortality ratios (SMRs). Results: After a median follow up of 9.8 years, 1429 patients had died of whom 284 caused by breast cancer (2.9% of total cohort). DCIS patients 50 had significantly lower mortality (SMR 0.9; 95% CI: 0.8-0.9). Overall, the risk of dying from general diseases and cancer other than breast cancer was lower than in the general population, whereas breast cancer mortality was increased. The SMR for breast cancer decreased from 7.5 (95% CI: 5.9-9.3) to 2.8 (95% CI: 2.4-3.2) for women aged 50 years, respectively. The cumulative breast cancer mortality 10 years after DCIS was 2.3% for women 50 years treated for DCIS between 1999 and 2004. Conclusions: DCIS patients >50 years had lower risk of dying from all causes combined compared with the general female population, which may reflect differences in health behavior. Women with DCIS had higher risk of dying from breast cancer than the general population, but absolute 10-year risks were low

A practical approach to manage additional lesions at preoperative breast MRI in patients eligible for breast conserving therapy: results

The aim of this prospective study was to evaluate the efficacy of directives, established to handle additional lesions at preoperative contrast-enhanced magnetic resonance imaging (MRI). Six-hundred-and-ninety consecutive patients with pathology-proven breast cancer planned for BCT based on clinical examination and conventional imaging underwent preoperative breast MRI. The incidence of additional lesions detected at MRI and impact on management were evaluated. Additional findings were pathology-proven or considered benign by follow-up. Findings for which no pathology proof was available prior to surgery, were defined as Unidentified Breast Objects (UBOs). Patients with multicentric or contralateral UBOs underwent BCT as planned with annual follow-up. Multifocal UBOs in the vicinity of the index cancer were excised with wider local margins. Preoperative MRI detected 141 additional lesions in 121 patients (17.5%). Of these lesions, 44.0% were proven malignant. Additional findings classified as UBOs were found in 81 patients (11.7%). None of the UBOs outside the primary tumour region resulted in malignant disease at follow-up after BCT (mean follow-up time: 57.1 months). However, most multifocal UBOs (in the vicinity of the primary) were malignant (77.5%). The strategy to pursue BCT with larger wide-local excisions for multifocal UBOs and to follow-up multicentric and contralateral UBOs with conventional imaging is effective to exclude malignancy at follow-up. After second-look targeted ultrasound has been performed, MRI-guided biopsy of BIRADS-3 multicentric and contralateral additional findings may have limited complementary clinical valu

Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study

Background: The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non-to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS. Design: This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged P45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research. Feasibility: To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres. (C) 2015 The Authors. Published by Elsevier Ltd

Discordant marker expression between invasive breast carcinoma and corresponding synchronous and preceding DCIS

Ductal carcinoma in situ (DCIS) is considered a potential precursor of invasive breast carcinoma (IBC). Studies aiming to find markers involved in DCIS progression generally have compared characteristics of IBC lesions with those of adjacent synchronous DCIS lesions. The question remains whether synchronous DCIS and IBC comparisons are a good surrogate for primary DCIS and subsequent IBC. In this study, we compared both primary DCIS and synchronous DCIS with the associated IBC lesion, on the basis of immunohistochemical marker expression. Immunohistochemical analysis of ER, PR, HER2, p53, and cyclo-oxygenase 2 (COX-2) was performed for 143 primary DCIS and subsequent IBC lesions, including 81 IBC lesions with synchronous DCIS. Agreement between DCIS and IBC was assessed using kappa, and symmetry tests were performed to assess the pattern in marker conversion. The primary DCIS and subsequent IBC more often showed discordant marker expression than synchronous DCIS and IBC. Strikingly, 18 of 49 (36%) women with HER2-positive primary DCIS developed an HER2-negative IBC. Such a difference in HER2 expression was not observed when comparing synchronous DCIS and IBC. The frequency of discordant marker expression did not increase with longer time between primary DCIS and IBC. In conclusion, comparison of primary DCIS and subsequent IBC yields different results than a comparison of synchronous DCIS and IBC, in particular with regard to HER2 status. To gain more insight into the progression of DCIS to IBC, it is essential to focus on the relationship between primary DCIS and subsequent IBC, rather than comparing IBC with synchronous DCIS