Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction.

BACKGROUND: Breast cancer (BC) risk prediction models consider cancer family history (FH) and germline pathogenic variants (PVs) in risk genes. It remains elusive to what extent complementation with polygenic risk score (PRS) and non-genetic risk factor (NGRFs) data affects individual intensified breast surveillance (IBS) recommendations according to European guidelines. METHODS: For 425 cancer-free women with cancer FH (mean age 40·6 years, range 21-74), recruited in France, Germany and the Netherlands, germline PV status, NGRFs, and a 306 variant-based PRS (PRS306) were assessed to calculate estimated lifetime risks (eLTR) and estimated 10-year risks (e10YR) using CanRisk. The proportions of women changing country-specific European risk categories for IBS recommendations, i.e. ≥20 % and ≥30 % eLTR, or ≥5 % e10YR were determined. FINDINGS: Of the women with non-informative PV status, including PRS306 and NGRFs changed clinical recommendations for 31·0 %, (57/184, 20 % eLTR), 15·8 % (29/184, 30 % eLTR) and 22·4 % (41/183, 5 % e10YR), respectively whereas of the women tested negative for a PV observed in their family, clinical recommendations changed for 16·7 % (25/150), 1·3 % (2/150) and 9·5 % (14/147). No change was observed for 82 women with PVs in high-risk genes (BRCA1/2, PALB2). Combined consideration of eLTRs and e10YRs identified BRCA1/2 PV carriers benefitting from IBS <30 years, and women tested non-informative/negative for whom IBS may be postponed. INTERPRETATION: For women who tested non-informative/negative, PRS and NGRFs have a considerable impact on IBS recommendations. Combined consideration of eLTRs and e10YRs allows personalizing IBS starting age. FUNDING: Horizon 2020, German Cancer Aid, Federal Ministry of Education and Research, Köln Fortune.

Improving Breast Conserving Surgery Using the Faxitron® OR Specimen Radiography System - A Complication Analysis, Cost Evaluation and Literature Review.

BACKGROUND/AIM: The combination of pre-surgical clip placement and hook-wire guided surgery is considered the gold standard for adequately locating non-palpable lesions during breast conserving surgery. After surgical removal of the segment, radiography is required to confirm clip removal, increasing surgical time, post-surgical complication rates, and cost. PATIENTS AND METHODS: We performed a retrospective analysis, using the Faxitron® in-theater specimen radiography system, of the following primary endpoints: surgical time and complication rates. The secondary endpoints were cost effectiveness and clip-location rates. The Control cohort included breast conserving surgery patients prior to May 2019 (n=150) and the Validation cohort included breast conserving surgery patients after May 2019 (n=53). RESULTS: The analysis showed an improvement in surgical time when using the Faxitron® system, which is directly linked to a benefit in cost effectiveness. A numerical benefit in complication rates was also shown. A subgroup analysis showed a significant advantage in surgical time for breast conserving surgery plus sentinel node biopsy and open breast biopsies. CONCLUSION: Use of the Faxitron® system significantly reduces surgical time, which increases cost efficiency while maintaining a low complication rate.