Risk-reducing mastectomy (RRM) is one of key prevention strategies in female carriers of germline BRCA pathogenic/likely pathogenic variants (PV/LPV). We retrospectively investigated the rate, timing ...and longitudinal trends of bilateral RRM uptake and the incidence and types of cancers among unaffected BRCA carriers who underwent genetic counseling at the Institute of Oncology Ljubljana in Slovenia.
Female BRCA carriers without personal history of cancer were included in the study. Clinical data on PV/LPV type, date of RRM, type of reconstructive procedure, occult carcinoma and histopathology results was collected and analyzed.
Of the 346 unaffected BRCA carriers (median age 43 years, 70% BRCA1, 30% BRCA2, median follow-up 46 months) who underwent genetic testing between October 1999 and December 2019, 25.1% had a RRM (range 35–50 years, median age at surgery 38 years). A significant difference in time to prophylactic surgery between women undergoing RRM only vs. women undergoing RRM combined with risk-reducing salpingo-oophorectomy was observed (22.6 vs 8.7 months, p = 0.0009). We observed an upward trend in the annual uptake in line with the previously observed Angelina Jolie effect. In 5.7% of cases, occult breast cancer was detected. No women developed breast cancer after RRM. Women who did not opt for surgical prevention developed BRCA1/2-related cancers (9.3%).
The uptake of RRM among unaffected BRCA carriers is 25.1% and is similar to our neighboring countries. No women developed breast cancer after RRM while women who did not opt for surgical prevention developed BRCA1/2 related cancers in 9.3% of cases. The reported data may provide meaningful aid for carriers when deciding on an optimal prevention strategy.
Management of the radial scar (RS)/complex sclerosing lesion (CSL) diagnosed by core needle biopsy (CNB) in breast cancer screening population (BCSP) is controversial due to its intrinsic malignant ...potential. We aimed to determine (i) the rate of upgrade of the RS/CSL to malignant lesions and (ii) radiological characteristics and CNB histopathological findings of the lesions related to the upgrade of the RS/CSL to malignant lesions after surgical excision in our BCSP.
Database of Slovenian National Breast Cancer Screening Program was checked for terms RS/CSL in all patients who underwent CNB in the period 2008–2018. The ratios of upgrade from CNB RS/SCL to malignant lesions after surgical excision were calculated with specific interest to the radiological characteristics and the CNB patohistologically findings of the lesions.
Of 162 patients with diagnosis of RS/CSL on the CNB, 121/156 (78%) cases underwent surgical excision. 6 of 121 (5%) cases were upgraded to a malignant diagnosis in surgical specimen, 3 cases of invasive carcinoma and 3 cases of DCIS, respectively. Five of the upgraded cases (5/6, 83.3%) showed atypical epithelial proliferative lesions (AEPL) on CNB. In one upgraded case without AEPL the lesion presented as 33 mm architectural distortion with microcalcifications on the mammogram.
In BCSP setting RS/CSL without AEPL/papilloma and those measuring less than 2 cm in the largest diameter can be followed radiologically. Increasing the number of cores and adequate sampling of the periphery and the centre of the RS/CSL improves the pick-up rate of associated atypia/malignancy.
•Indications for radial scar/complex sclerosing lesions surgical excisions reduced.•Data from Slovenian national breast cancer screening program reviewed.•Radial scars/complex sclerosing lesions diagnosed by vacuum assisted core biopsy measuring less than 2 cm and without atypical epithelial proliferative lesions or papilloma can be followed radiologically.•Radial scars/complex sclerosing lesions larger than 2 cm, not adequately sampled in core needle biopsy and/or showing atypical epithelial proliferative lesions or papilloma should be excised.•Increasing the number of cores and adequate sampling of the periphery as well as the centre of the radial scars/complex sclerosing lesions improves the pick-up rate of associated atypia/malignancy.
Axillary ultrasound (US) with fine needle aspiration biopsy (FNAB) of suspicious lymph nodes helps identify patients with axillary metastases preoperatively avoiding a 2-step axillary procedure. ...However, it does not accurately differentiate between low and high axillary tumour burden. Our aim was to determine the rationale of preoperative axillary US in screen-detected breast cancer.
We retrospectively analysed patients, aged between 50 and 69 years, which had an invasive breast cancer diagnosed in the Slovenian National Breast Cancer Screening program between January 2012 and June 2017. Proportion of patients that proceeded directly to ALND and the proportion of patients with unnecessary ALND as a result of positive US-FNAB were calculated.
Altogether 892 patients were eligible for analysis. Preoperative US of the axilla was performed in 856/892 (96%) patients, while 36/892 patients (4%) did not undergo US of the axilla. We have found out that upfront ALND due to positive US-FNAB was performed in 91/856 (10.6%) patients. 116/856 patients (13.6%) had tumours in inner quadrants and maximal mammographic tumour size ≤ 2 cm. Among them only 1/116 (0.9%) proceeded directly to ALND due to positive US-FNAB.The final pathology of those who underwent upfront ALND due to positive US-FNAB showed low axillary tumour burden not meeting the indications for ALND in 13/91 (14.3%) patients.Among patients without preoperative axillary US, only 1/36 (2.8%) met the indications for ALND.
Our results showed that performing US of the axilla is not justified in screen detected breast cancer patients.
Purpose
New ultrafast view‐sharing sequences have enabled breast dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) to be performed at high spatial and temporal resolution. The aim of ...this study is to evaluate the diagnostic potential of textural features that quantify the spatiotemporal changes of the contrast‐agent uptake in computer‐aided diagnosis of malignant and benign breast lesions imaged with high spatial and temporal resolution DCE‐MRI.
Method
The proposed approach is based on the textural analysis quantifying the spatial variation of six dynamic features of the early‐phase contrast‐agent uptake of a lesion's largest cross‐sectional area. The textural analysis is performed by means of the second‐order gray‐level co‐occurrence matrix, gray‐level run‐length matrix and gray‐level difference matrix. This yields 35 textural features to quantify the spatial variation of each of the six dynamic features, providing a feature set of 210 features in total. The proposed feature set is evaluated based on receiver operating characteristic (ROC) curve analysis in a cross‐validation scheme for random forests (RF) and two support vector machine classifiers, with linear and radial basis function (RBF) kernel. Evaluation is done on a dataset with 154 breast lesions (83 malignant and 71 benign) and compared to a previous approach based on 3D morphological features and the average and standard deviation of the same dynamic features over the entire lesion volume as well as their average for the smaller region of the strongest uptake rate.
Result
The area under the ROC curve (AUC) obtained by the proposed approach with the RF classifier was 0.8997, which was significantly higher (P = 0.0198) than the performance achieved by the previous approach (AUC = 0.8704) on the same dataset. Similarly, the proposed approach obtained a significantly higher result for both SVM classifiers with RBF (P = 0.0096) and linear kernel (P = 0.0417) obtaining AUC of 0.8876 and 0.8548, respectively, compared to AUC values of previous approach of 0.8562 and 0.8311, respectively.
Conclusion
The proposed approach based on 2D textural features quantifying spatiotemporal changes of the contrast‐agent uptake significantly outperforms the previous approach based on 3D morphology and dynamic analysis in differentiating the malignant and benign breast lesions, showing its potential to aid clinical decision making.
GOALSTo determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a ...Central European population with BC incidence below EU average.METHODS502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18.RESULTSThe AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included.CONCLUSIONBC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.
The organised, population-based breast cancer screening programme in Slovenia began providing biennial mammography screening for women aged 50-69 in 2008. The programme has taken a comprehensive ...approach to quality assurance as recommended by the European guidelines for quality assurance in breast cancer screening and diagnosis (4th edition), including centralized assessment, training and supervision, and proactive monitoring of performance indicators. This report describes the progress of implementation and rollout from 2003 through 2019. The screening protocol and key quality assurance procedures initiated during the planning from 2003 and rollout from 2008 of the screening programme, including training of the professional staff, are described. The organisational structure, gradual geographical rollout, and coverage by invitation and examination are presented. The nationwide programme was up and running in all screening regions by the end of 2017, at which time the nationwide coverage by invitation and examination had reached 70% and 50%, respectively. Nationwide rollout of the population-based programme was complete by the end of 2019. By this time, coverage by invitation and examination had reached 98% and 76%, respectively. The participation rates consistently exceeded 70% from 2014 to 2019. The successful implementation of the screening programme can be attributed to an independent central management, external guidance, and strict adherence to quality assurance procedures, all of which contributed to increasing governmental and popular support. The benefits of quality assurance have influenced all aspects of breast care and have provided a successful model for multidisciplinary management of other diseases.
Several tools for predicting the likelihood of non-sentinel lymph node (non-SLN) involvement in SLN-positive breast cancer patients have been created so far. The aim of our study was to create and ...validate different nomograms for predicting the likelihood of non-SLN involvement that would be applicable in different institutions and that would also include the results of the preoperative US examination of the axilla. From January 2000 to January 2009, 534 breast cancer patients underwent axillary lymph node dissection (ALND) due to metastatic SLN at our institution. Using logistic regression results three nomograms differing in the inclusion of the results of intraoperative examination of SLN were created. The nomograms were validated using bootstrap methods. In all three nomograms, US examination of the axilla was a powerful independent variable. Other variables included (different in different nomograms) were tumor size, lymphovascular invasion, metastasis size in SLN, number of negative and number of positive SLNs. Mean absolute error and mean area under the ROC curve equals to 0.016 and 0.77 for the first, 0.023 and 0.75 for the second and 0.014 and 0.79 for the third nomogram. Three nomograms for predicting the likelihood of non-SLN metastases including the results of the preoperative US examination of the axilla were created at our institution. They differ in the inclusion of the results of intraoperative examination of SLNs and are thus applicable in different institutions. The validation results seem promising and omission of completion ALND might be considered in patients with the probability of having non-SLN metastases of 10% or less.
Summary Background For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, ...axillary dissection might be overtreatment. We designed IBCSG trial 23–01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. Methods In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov , NCT00072293. Findings Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6–7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4–91·2) in the group without axillary dissection and 84·4% (80·7–88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55–1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3–4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. Interpretation Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. Funding None.
Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different ...tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study. DNA extracted from blood and FFPE tumor tissue were genotyped using NGS panels TruSightCancer/Hereditary and TruSight Tumor 170. Among 170 EOC patients, 21.8% had BRCA germline or somatic PV/LPV, and additionally 6.4% had PV/LPV in other HBOC genes. Sensitivity of tumor genotyping for detection of germline PV/LPV was 96.2% for BRCA genes and 93.3% for HBOC genes. With germline genotyping-only strategy, 58.8% of HBOC PV/LPV and 68.4% of BRCA PV/LPV were detected. By tumor genotyping-only strategy, 96.1% of HBOC PV/LPV and 97.4% of BRCA PV/LPV were detected. Genotyping of tumor first, followed by germline genotyping seems to be a reasonable approach for detection of PV/LPV in breast and/or ovarian cancer susceptibility genes in non-mucinous EOC patients.