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BackgroundWe examined the prognostic significance of circulating tumor cell (CTC) dynamics during treatment in metastatic breast cancer (MBC) patients receiving first-line chemotherapy.MethodsSerial CTC data from 469 patients (2202 samples) were used to build a novel latent mixture model to identify groups with similar CTC trajectory (tCTC) patterns during the course of treatment. Cox regression was used to estimate hazard ratios for progression-free survival (PFS) and overall survival (OS) in groups based on baseline CTCs, combined CTC status at baseline to the end of cycle 1, and tCTC. Akaike information criterion was used to select the model that best predicted PFS and OS.ResultsLatent mixture modeling revealed 4 distinct tCTC patterns: undetectable CTCs (56.9% ), low (23.7%), intermediate (14.5%), or high (4.9%). Patients with low, intermediate, and high tCTC patterns had statistically significant inferior PFS and OS compared with those with undetectable CTCs (P < .001). Akaike Information Criterion indicated that the tCTC model best predicted PFS and OS compared with baseline CTCs and combined CTC status at baseline to the end of cycle 1 models. Validation studies in an independent cohort of 1856 MBC patients confirmed these findings. Further validation using only a single pretreatment CTC measurement confirmed prognostic performance of the tCTC model.ConclusionsWe identified 4 novel prognostic groups in MBC based on similarities in tCTC patterns during chemotherapy. Prognostic groups included patients with very poor outcome (intermediate + high CTCs, 19.4%) who could benefit from more effective treatment. Our novel prognostic classification approach may be used for fine-tuning of CTC-based risk stratification strategies to guide future prospective clinical trials in MBC.

Cancer and cardiovascular diseases are the two major causes of mortality, morbidity, and disability worldwide. The improvement in effective therapeutic options for the management of breast cancer (BC) has led to an increased number of BC survivors, who can experience longterm toxicities from cancer treatments. Adverse events including cardiovascular toxicities must be considered in light of effectiveness of recently approved drugs for BC treatment, including elacestrant, tucatinib, neratinib, olaparib, the immune checkpoint inhibitors, trastuzumab deruxtecan, or sacituzumab govitecan. Many cancer drugs affect the cardiovascular system with a range of clinical manifestations. Prompt diagnosis and treatment as well as a multidisciplinary approach involving a cardio-oncologist is optimal for management of these cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a leading cause of morbidity, mortality, and disability for women worldwide. There is substantial variation in treatment outcomes, which is function of multiple variables, including access to treatment. Treatment standards can promote quality and improve survival; thus, their development should be a priority for the cancer-control planning., Methods: We extracted the guidelines for the treatment of BC from a systematic review of the literature. We evaluated the development process, the methodology, and the recommendations formulated and surveyed the country resource stratification. Metrics of health-system capacity were selected to study the guidelines context appropriateness., Results: We analyzed 49 distinct guidelines for BC, mostly in English language (n = 23), developed in upper-middle and high-income countries of the European and American regions (n = 39). A resource-stratified approach was identified in a quarter of the guidelines (n = 11), mostly from resource-constrained settings. Only one-half of the guidelines reached a gender balance of the authorship, and 10.2% were based on a multidisciplinary steering committee. A number of efforts and solutions of resource adaptations were recognized, mostly in low- and middle-income countries. Overall, the national guidelines appeared not sensitive enough of the local health-system capacity in formulating recommendations, with possible exception for the radiation therapy availability., Conclusion: This global landscape of treatment standards for BC demonstrates that the majority is not context appropriate. Research on the formulation of cancer treatment standards is highly warranted, along with novel platforms for developing and disseminating resource-appropriate guidance., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)