OBJECTIVES The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. BACKGROUND Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. METHODS A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. RESULTS At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (β = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 - ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. CONCLUSIONS A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036) (J Am Coll Cardiol Img 2018;11:1045–55) © 2018 by the American College of Cardiology Foundation.
BACKGROUND. Although invasive lobular carcinoma (ILC) is the second most common histotype of breast cancer, the prognostic implications of its clinicopathologic characteristics remain controversial. METHODS.The authors undertook a retrospective analysis of a large series of cases treated and followed at a single institution, with the objective of assessing the prognostic/predictive value of distinct clinicopathologic features of the tumors, after revision of the original histopathologic preparations and statistical analyses. RESULTS.Overall, 530 patients with pure ILC (57% with the classic type; 19% with the alveolar type; 11% with the solid type; and the remaining 13% characterized by pleomorphic, signet ring cell, histiocytoid, or apocrine features) were included in the study. Tumor size, lymph node metastatic involvement, and hormonal status were confirmed to be significant prognostic factors. In addition, statistically significant correlations were demonstrated between the 'classic' histotype of ILC and a lower risk of axillary lymph node metastases (P 5 .0005), a reduced number of metastatic lymph nodes (P 5 .04), and lower tumor grade (P < .0001). Patients with ILC of the 'nonclassic' subtype demonstrated significantly increased breast-related events (hazards ratio of 1.80; 95% confidence interval, 1.04-3.10) and a trend toward reduced disease-free survival and overall survival. CONCLUSIONS.The results of the current study confirm the clinical usefulness of several traditional clinicopathologic features of ILC as prognostic parameters but also emphasize the prognostic role of the histopathologic subtyping of these tumors, documenting the more favorable outcome of the classic subtype of ILC.
PurposeIndications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion.MethodsThe panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology.ResultsConsensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference.ConclusionsIn case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.Electronic supplementary materialThe online version of this article (10.1007/s10549-018-4937-1) contains supplementary material, which is available to authorized users.
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