Background: Screening guidelines for women at familial risk of breast cancer without a known causative gene mutation differ internationally. To our knowledge, no randomised controlled MRI-screening trial has been performed. The FaMRIsc-study aims to assess the efficacy of MRI versus mammography screening for familial risk and furthermore assesses the influence of breast density. Methods: In 12 Dutch hospitals, 1355 women aged 30-55 years with a cumulative lifetime risk of ≥20% without a BRCA1/2 mutation were randomised with a web-based computer generated hospital sequence, concealed for participants, physicians and researchers, in either the MRI-group with yearly MRI, clinical breast examination and mammography biennially, or the Mammography-group with yearly mammography and clinical breast examination. Breastfeeding, pregnancy, previous screening and previous ductal carcinoma in situ were permitted, but no previous invasive cancer. Primary outcomes were number, size and nodal-stage of breast cancers. Secondary outcomes were sensitivity, specificity and positive predictive value. Results were also stratified by mammographic density (BI-RADS AD). Intention to screen analyses were performed. This trial was registered with the Netherlands Trial Register, NTR2789. Findings: Between Jan 1 2011, and Dec 31 2017 in the MRI-group (674 women) compared to the Mammographygroup (680 women) with a median follow-up of 5.2 years for both groups, more breast cancers were detected (40 versus 15, p<0•001), invasive cancers were smaller (median size 9 versus 17 mm, p=0•010) and less frequently node positive (4/24, 17% versus 5/8, 63%, p=0•023). In the MRI-group, specificity was significantly lower compared to the Mammography-group (83•8% versus 91•0%, p<0•001), while sensitivity hardly differed (97•5% versus 86.7%, p=0.18). Clinical breast examination contributed hardly to detection (1/55). In incident cancers, tumour stage was better in the MRI-group (p=0•035), with lower numbers of node positive and ≥T2 tumours, while specificity improved in both arms (MRI-group: 87•4%, Mammography-group: 92•6%, p<0•001). All tumours ≥T2 were in the two highest density categories. In BI-RADS density A-C MRI was most effective. Interpretation: The earlier detection by MRI screening and especially the fewer late-stage cancers in incident rounds, may reduce adjuvant chemotherapy and mortality. However, especially for women with the highest breast density at the cost of more false positive results.

for the Familial MRI Screening (FaMRIsc) Study group IMPORTANCE For women with a 20% or more familial risk of breast cancer without a known BRCA1/2 (BRCA1, OMIM 113705; and BRCA2, OMIM 114480) or TP53 (OMIM 151623) variant, screening guidelines vary substantially, and cost-effectiveness analyses are scarce.OBJECTIVE To assess the cost-effectiveness of magnetic resonance imaging (MRI) screening strategies for women with a 20% or more familial risk for breast cancer without a known BRCA1/2 or TP53 variant. DESIGN, SETTING, AND PARTICIPANTSIn this economic evaluation, conducted from February 1, 2019, to May 25, 2020, microsimulation modeling was used to estimate costs and effectiveness on a lifetime horizon from age 25 years until death of MRI screening among a cohort of 10 million Dutch women with a 20% or more familial risk for breast cancer without a known BRCA1/2 or TP53 variant. A Dutch screening setting was modeled. Most data were obtained from the randomized Familial MRI Screening (FaMRIsc) trial, which included Dutch women aged 30 to 55 years. A health care payer perspective was applied.INTERVENTIONS Several screening protocols with varying ages and intervals including those of the randomized FaMRIsc trial, consisting of the mammography (Mx) protocol (annual mammography and clinical breast examination) and the MRI protocol (annual MRI and clinical breast examination plus biennial mammography). MAIN OUTCOMES AND MEASURESCosts, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated and discounted by 3%. A threshold of €22 000 (US $24 795.87) per QALY was applied.RESULTS This economic evaluation modeling study estimated that, on a lifetime horizon per 1000 women with the Mx protocol of the FaMRIsc trial, 346 breast cancers would be detected, and 49 women were estimated to die from breast cancer, resulting in 22 885 QALYs and total costs of €7 084 767 (US $7 985 134.61). The MRI protocol resulted in 79 additional QALYs and additional €2 657 266 (US $2 994 964.65). Magnetic resonance imaging performed only every 18 months between the ages of 35 and 60 years followed by the national screening program was considered optimal, with an ICER of €21 380 (US $24 097.08) compared with the previous nondominated strategy in the ranking, when applying the National Institute for Health and Care Excellence threshold. Annual screening alternating MRI and mammography between the ages of 35 and 60 years, followed by the national screening program, gave similar outcomes. Higher thresholds would favor annual MRI screening. The ICER was most sensitive to the unit cost of MRI and the utility value for ductal carcinoma in situ and localized breast cancer.CONCLUSIONS AND RELEVANCE This study suggests that MRI screening every 18 months between the ages of 35 and 60 years for women with a family history of breast cancer is cost-effective within the National Institute for Health and Care Excellence threshold for all densities. Higher thresholds would favor annual MRI screening. T...

After a mastectomy, there is a high probability of residual breast tissue. This tissue is predominantly located in the middle circle of the superficial dissection plane and in the lower outer quadrant. Surgeons should be aware of these locations so they may remove as much of the benign breast tissue as possible.

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Summary We investigated the effect of two doses of cytostatics, administered intraperitoneally during 5 consecutive days, on the healing of ileal and colonic anastomoses constructed on the third day. The cytostatics regimen consisted of a combination of 5-fluorouracil, bleomycin and cisplatin at 10, 2 and 0.35 mg kg-'d', respectively, or at twice higher doses. The lower dose was similar to that given intravenously in previous experiments. Rats were sacrificed 3 or 7 days after operation. No effects of cytostatics were observed after 3 days, neither on anastomotic bursting pressure nor on hydroxyproline concentration (jLg/mg dry weight) or content (ug cm-'). Profound effects were seen at 7 days. In the high dose group, bursting pressures in both anastomoses were greatly reduced with respect to the control group. Concurrently, collagen synthesis was severely impaired, as indicated by sustained decreased hydroxyproline concentrations and content. The lower dose of cytostatics showed essentially similar effects on hydroxyproline parameters, but affected anastomotic strength less dramatically. The data indicate that, while intraperitoneal chemotherapy may show less detrimental systemic toxicity and thus allow higher doses, its application as an adjunct to gastrointestinal surgery may be limited because of its severe effects on anastomotic repair.