Prediction and clinical utility of a contralateral breast cancer risk model

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Quality improvement in surgical breast cancer care: a decrease in positive surgical margins after first breast conserving surgery

Background: In recent years there has been a growing awareness of the quality of breast cancer care. In the Netherlands the completeness of breast conserving surgery (BCS) was introduced as a quality parameter, and hospitals are obliged to report on the proportion of patients with positive margins after first BCS since 2007. Increasing national mastectomy rates during the last decade for the treatment of early breast cancer have recently been published from the US. This study describes trends in BCS over time in relation to positive margin rates after BCS. Materials and Methods: All breast cancer patients T1–2, any N, M0 diagnosed between July 1, 2008, and December 31, 2012 who underwent surgical resection were selected from the Netherlands Cancer Registry. Type of first surgery was coded as BCS or mastectomy. Margin status was coded as clear, focally positive margins (tumor in a limited area of the inked surface, i.e. one or two foci of tumor, with a maximum of 4 mm), more than focally positive margins (MFP) or unknown. BCS rates were available in the NCR for the period 1995–2012. Results: The percentage of BCS as first surgery increased over time (48% and 64% in 1995 and 2012 respectively; χ2-test: p = 0.000), with a temporary decline in the period 2008–2009. Of the 49,570 included patients over the period 2008–2012, 62% (30,790 patients) received BCS in 89 hospitals in the Netherlands. The percentage of MFP-margins significantly decreased since the introduction of the indicator; 9.7% in 2008 versus 5.4% in 2012 (Table 1; χ2-test: p = 0.000). After case mix correction for age, tumor size, grade, lobular subtype, multifocality, hormone receptor status and HER2 status, hospital variance was substantial: corrected MFP-margin rates varied from 0% to 19%. Thirty-seven hospitals (42%) had margin rates significantly lower than 10%, while 3% showed significantly higher rates. Conclusions: The percentage of patients with positive surgical margins after first BCS for breast cancer decreased between 2008 and 2012. This decrease in positive margins was accompanied by a increase in the national BCS rates in the Netherlands during this period

Richtlijn 'screening en diagnostiek van het mammacarcinoom' (herziening).

Revised practice guideline 'Screening and diagnosis of breast cancer' The evidence-based revision of the practice guideline 'Screening and diagnosis of breast cancer' was necessitated by new insights, for instance on the cost-effectiveness of screening modalities other than mammography. Mammography is the only screening modality that is recommended for the general population. In the Netherlands, women from 50-75 years of age are invited for screening. However, in view of the ongoing increase in the incidence of breast cancer and of the image quality advantages of radiological digitalization, a study on the decrease of the lower age limit--preferably 45 years--is recommended. Screening with MRI is indicated for carriers of breast cancer gene mutations. Evaluation of risk factors has resulted in a rearrangement of screening recommendations, based on relative risks (RRs): screening apart from the population screening is only recommended in case the RRis 4 or more and in patients with a positive family history in case of a RR of 2 or more. Additional risks require further genetic evaluation. The 'Breast imaging reporting and data system' (BI-RADS) is now recommended for both screening and diagnostic imaging. Its application has had an impact on the triple diagnostic approach, which has now evolved into a consensus between surgeon, radiologist and pathologist. Axillary ultrasound should be carried out ifa sentinel node procedure is being considered. MRI should be included if the cancer cannot be reliably delineated on mammography or ultrasound. The increased complexity of the diagnostic work-up often means that the final diagnosis is not arrived within one day. Every effort should be made to achieve this goal within 5 working days. Ned Tijdschr Geneeskd. 2008;I52:2336-

Risk of metachronous contralateral breast cancer in patients with primary invasive lobular breast cancer: Results from a nationwide cohort

Lobular primary breast cancer (PBC) histology has been proposed as a risk factor for contralateral breast cancer (CBC), but results have been inconsistent. We investigated CBC risk and the impact of systemic therapy in lobular versus ductal PBC. Further, CBC characteristics following these histologic subtypes were explored. We selected 74,373 women diagnosed between 2003 and 2010 with stage I-III invasive PBC from the nationwide Netherlands Cancer Registry. We assessed absolute risk of CBC taking into account competing risks among those with lobular (n = 8903), lobular mixed with other types (n = 3512), versus ductal (n = 62,230) histology. Hazard ratios (HR) for CBC were estimated in a cause-specific Cox model, adjusting for age at PBC diagnosis, radiotherapy, chemotherapy and/or endocrine therapy. Multivariable HRs for CBC were 1.18 (95% CI: 1.04-1.33) for lobular and 1.37 (95% CI: 1.16-1.63) for lobular mixed versus ductal PBC. Ten-year cumulative CBC incidences in patients with lobular, lobular mixed versus ductal PBC were 3.2%, 3.6% versus 2.8% when treated with systemic therapy and 6.6%, 7.7% versus 5.6% in patients without systemic therapy, respectively. Metachronous CBCs were diagnosed in a less favourable stage in 19%, 26% and 23% and less favourable differentiation grade in 22%, 33% and 27% than the PBCs of patients with lobular, lobular mixed and ductal PBC, respectively. In conclusion, lobular and lobular mixed PBC histology are associated with modestly increased CBC risk. Personalised CBC risk assessment needs to consider PBC histology, including systemic treatment administration. The impact on prognosis of CBCs with unfavourable characteristics warrants further evaluation.Development and application of statistical models for medical scientific researc

Steelman

To determine the diagnostic test characteristics and inter-observer variation of pathology features for identifying high microsatellite instability (MSI-H) colorectal cancer (CRC). Six pathologists blindly evaluated 177 CRC for the presence of MSI-H associated pathology features. Inter-observer agreement was determined by using Kappa-statistics. In the first random 88/177 cases, mucinous carcinoma, tumor-infiltrating lymphocytes (TIL) and Crohns-like infiltrate (CLI) were the best discriminators between MSI-H and microsatellite stable CRC [OR 5.6 (95 % CI 1.7-19), 5.4 (1.8-17) and 3.5 (1.1-11), respectively], with high specificity (89-91 %). The sensitivities for MSI-H, however, were low (31-41 %). In addition, inter-observer agreement was moderate for TIL and CLI (kappa 0.38 and 0.48, respectively), but very good for mucinous carcinoma (kappa 0.86). Interpretation of overall histopathology as suggestive for MSI-H performed better than any individual feature; OR 15 (5.2-44), and area under the curve 0.79. However, inter-observer agreement was moderate (kappa 0.53). In the second set, TIL and CLI were scored according to updated scoring systems. Although both remained the best individual discriminators, test characteristics and inter-observer agreement did not improve. MSI-H pathology features have moderate accuracy for identifying MSI-H CRC, and are identified with moderate inter-observer agreement. These findings highlight the limitations of clinical strategies, such as the revised Bethesda guidelines, which incorporate the MSI-H associated pathology features in their strategy to identify persons with lynch syndrome