PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina.

PURPOSE: PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina. METHODS: We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines. RESULTS: The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country. CONCLUSION: This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.

Comparison between an abbreviated and full MRI protocol for detecting additional disease when doing breast cancer staging.

BACKGROUND: Previous studies have shown that abbreviated magnetic resonance imaging (aMRI) compares well to full-protocol MRI (fpMRI) in breast cancer (BC) screening, with the potential advantage of a less costly and complex examination. To our knowledge, the role for aMRI in staging BC has been poorly investigated, especially in assessing additional disease (ie, additional lesions compared to the index one prompting the examination). PURPOSE: To compare aMRI and fpMRI in detecting additional disease in BC staging. STUDY TYPE: Retrospective monocentric cohort study. POPULATION: In all, 87 patients with 89 biopsy-proven index lesions referred to staging fpMRI between January-June 2016. FIELD STRENGTH/SEQUENCE: A 1.5T magnet using short tau inversion recovery (STIR) T2 -weighted imaging, echoplanar diffusion-weighted imaging, and 3D fast long angle shot (FLASH) T1 -weighted imaging. ASSESSMENT: During independent sessions, four readers with 1.5-20 years of experience in breast imaging, blinded to the pathological examination and previous imaging, assessed multifocal, multicentric, and contralateral additional lesions on fpMRI and aMRI (including precontrast T1 -weighted 3D FLASH sequence, first postcontrast subtracted T1 -weighted 3D FLASH sequence, and a transverse maximum intensity projection reconstruction). STATISTICAL TESTS: We calculated the per-lesion cancer detection rate (CDR), positive predictive value (PPV), and false discovery rate (FDR) for additional disease, assessing the significance of intrareader differences in CDR with the McNemar test. RESULTS: Pathological analysis found 36 additional lesions (multifocal, multicentric, and contralateral in 20, 15, and 1 cases, respectively). Readers' CDR was comparably high using aMRI (range 88.9-94.4%) or fpMRI (range 91.7-94.4%) (P > 0.05). PPV and FDR of aMRI (ranges 76.2-84.6% and 15.4-23.8%, respectively), and fpMRI (ranges 76.7-82.9% and 17.2-23.3%, respectively) were comparable on an intrareader basis. Using aMRI, two out of four readers induced two false-negative cases (one case each) with presumably limited impact on surgical planning (multifocal cancers <1 cm in size). DATA CONCLUSION: aMRI was comparable to fpMRI in staging additional BC. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:e222-e230.

Interreader agreement of PI-RADS v. 2 in assessing prostate cancer with multiparametric MRI: A study using whole-mount histology as the standard of reference.

BACKGROUND: Most studies assessing interreader agreement of Prostate Imaging Reporting and Data System v. 2 (PI-RADS v2) have used biopsy as the standard of reference, thus carrying the risk of not definitively noting all existent cancers. PURPOSE: To evaluate the interreader agreement in assessing prostate cancer (PCa) of PI-RADS v2, using whole-mount histology as the standard of reference. STUDY TYPE: Monocentric prospective cohort study. POPULATION: In all, 48 patients with biopsy-proven PCa referred for radical prostatectomy, undergoing staging multiparametric magnetic resonance imaging (mpMRI) between May 2016 to February 2017. FIELD STRENGTH/SEQUENCE: 3.0T system using high-resolution T2 -weighted imaging, diffusion-weighted imaging (echo-planar imaging with maximum b-value 2000 sec/mm2 ), and dynamic contrast-enhanced imaging (T1 -weighted high resolution isotropic volume examination; THRIVE) ASSESSMENT: Three radiologists blinded to final histology (2-8 years of experience) analyzed mpMRI images independently, scoring imaging findings in accordance with PI-RADS v2. On a per-lesion basis, we calculated overall and pairwise interreader agreement in assigning PI-RADS categories, as well as assessing malignancy with categories ≥3 or ≥4, and stage ≥pT3. STATISTICAL TESTS: Cohen's kappa analysis of agreement. RESULTS: On 71 lesions found on histology, there was moderate agreement in assigning PI-RADS categories to all cancers (k = 0.53) and clinically significant cancers (csPCa) (k = 0.47). Assessing csPCa with PI-RADS ≥4 cutoff provided higher agreement than PI-RADS ≥3 cutoff (k = 0.63 vs. 0.57). Interreader agreement was higher between more experienced readers, with the most experienced one achieving the highest cancer detection rate (0.73 for csPCa using category ≥4). There was substantial agreement in assessing stage ≥pT3 (k = 0.72). DATA CONCLUSION: We found moderate to substantial agreement in assigning the PI-RADS v2 categories and assessing the spectrum of cancers found on whole-mount histology, with category 4 as the most reproducible cutoff for csPCa. Readers' experience influenced interreader agreement and cancer detection rate. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:546-555.