scholarly journals Trastuzumab-induced cardiotoxicity: testing a clinical risk score in a real-world cardio-oncology population

2017 ◽  
Vol 24 (3) ◽  
pp. 176 ◽  
Author(s):  
M. Rushton ◽  
C. Johnson ◽  
S. Dent
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Real World ◽  
Predictive Value ◽  
Low Risk ◽  
Clinical Risk Score ◽  
Breast Cancer Patients ◽  
Risk Patients

Background Trastuzumab has improved survival for women with her2-positive breast cancer, but its use is associated with an increased risk of cardiotoxicity. With increased survivorship, the long-term effects of cancer treatment are an important consideration for clinicians and patients. We reviewed the current literature on predicting trastuzumab-related cardiotoxicity and tested a clinical risk score (crs) in a real-world breast cancer population to assess its utility in predicting permanent cardiotoxicity.Methods In this retrospective exploratory cohort study of breast cancer patients referred to a cardio-oncology clinic at a tertiary care centre between October 2008 and August 2014, a crs was calculated for each patient, and a sensitivity analysis was performed.Results Of the 143 patients included in the study, 62 (43%) experienced a cardiac event, and of those 62 patients, 43 (69%) experienced full recovery of cardiac function. In applying the crs, 119 patients (83%) would be considered at low risk, 14 (10%) at moderate risk, and 10 (7%) at high risk to develop heart failure or cardiomyopathy. When applied to the study population, the high-risk cut-off score had a sensitivity of 0.13 [95% confidence interval (ci): 0.08 to 0.20] and a specificity of 0.94 (95% ci: 0.87 to 0.97). The positive predictive value was 0.07 (95% ci: 0.03 to 0.13), and the negative predictive value was 0.93 (95% ci: 0.87 to 0.96).Conclusions The crs demonstrated good specificity and negative predictive value for the development of permanent cardiotoxicity in a real-world population of breast cancer patients, suggesting that intensive cardiac monitoring might not be warranted in low-risk patients, but that high-risk patients might benefit from early referral to cardio-oncology for optimization. Further study using the crs in a larger breast cancer population is warranted to identify patients at low risk of long-term trastuzumab-related cardiotoxicity.

scholarly journals Impact of Different Modules of 21-Gene Assay in Early Breast Cancer Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengdi Chen ◽  
Deyue Liu ◽  
Weilin Chen ◽  
Weiguo Chen ◽  
Kunwei Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Younger Patients ◽  
Gene Assay ◽  
Risk Patients ◽  
Gene Modules ◽  
The Impact

BackgroundThe 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages.MethodsA total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal (n = 97); Group B, >40 years and premenopausal (n = 284); Group C, postmenopausal (n = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules.ResultsIn patients >40 years, RS had a strong negative correlation with its estrogen module (ρ = −0.76 and −0.79 in Groups B and C) and a weak positive correlation with its invasion module (ρ = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS >25) group, the proliferation module was the leading driver in all patients (ρ = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients.ConclusionsRS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks.

scholarly journals Impact of Oncotype DX testing on ER+ breast cancer treatment and survival in the first decade of use

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Evelien Schaafsma ◽  
Baoyi Zhang ◽  
Merit Schaafsma ◽  
Chun-Yip Tong ◽  
Lanjing Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Temporal Trends ◽  
Recurrence Score ◽  
Low Risk ◽  
Oncotype Dx ◽  
Risk Scores ◽  
Breast Cancer Patients ◽  
Risk Patients

Abstract Background The Oncotype DX breast recurrence score has been introduced more than a decade ago to aid physicians in determining the need for systemic adjuvant chemotherapy in patients with early-stage, estrogen receptor (ER)+, lymph node-negative breast cancer. Methods In this study, we utilized data from The Surveillance, Epidemiology, and End Results (SEER) Program to investigate temporal trends in Oncotype DX usage among US breast cancer patients in the first decade after the introduction of the Oncotype DX assay. Results We found that the use of Oncotype DX has steadily increased in the first decade of use and that this increase is associated with a decreased usage of chemotherapy. Patients who utilized the Oncotype DX test tended to have improved survival compared to patients who did not use the assay even after adjusting for clinical variables associated with prognosis. In addition, chemotherapy usage in patients with high-risk scores is associated with significantly longer overall and breast cancer-specific survival compared to high-risk patients who did not receive chemotherapy. On the contrary, patients with low-risk scores who were treated with chemotherapy tended to have shorter overall survival compared to low-risk patients who forwent chemotherapy. Conclusion We have provided a comprehensive temporal overview of the use of Oncotype DX in breast cancer patients in the first decade after Oncotype DX was introduced. Our results suggest that the use of Oncotype DX is increasing in ER+ breast cancer and that the Oncotype DX test results provide valuable information for patient treatment and prognosis.

Adjuvant Chemotherapy Guidance for pT1-3N0-1 Breast Cancer Patients with HR+, HER2- subtype: a study based on SEER database

2021 ◽  
Author(s):  
juanjuan Qiu ◽  
Li Xu ◽  
Yu Wang ◽  
Jia Zhang ◽  
Jiqiao Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
High Risk ◽  
Cancer Patients ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Group Score

Abstract Background Although the results of gene testing can guide early breast cancer patients with HR+, HER2- to decide whether they need chemotherapy, there are still many patients worldwide whose problems cannot be solved well by genetic testing. Methods 144 735 patients with HR+, HER2-, pT1-3N0-1 breast cancer from the Surveillance, Epidemiology, and End Results database were included from 2010 to 2015. They were divided into chemotherapy (n = 38 392) and no chemotherapy (n = 106 343) group, and after propensity score matching, 23 297 pairs of patients were left. Overall survival (OS) and breast cancer-specific survival (BCSS) were tested by Kaplan–Meier plot and log-rank test and Cox proportional hazards regression model was used to identify independent prognostic factors. A nomogram was constructed and validated by C-index and calibrate curves. Patients were divided into high- or low-risk group according to their nomogram score using X-tile. Results Patients receiving chemotherapy had better OS before and after matching (p < 0.05) but BCSS was not significantly different between patients with and without chemotherapy after matching: hazard ratio (HR) 1.005 (95%CI 0.897, 1.126). Independent prognostic factors were included to construct the nomogram to predict BCSS of patients without chemotherapy. Patients in the high-risk group (score > 238) can get better OS HR 0.583 (0.507, 0.671) and BCSS HR 0.791 (0.663, 0.944) from chemotherapy but the low-risk group (score ≤ 238) cannot. Conclusion The well-validated nomogram and a risk stratification model was built. Patients in the high-risk group should receive chemotherapy while patients in low-risk group may be exempt from chemotherapy.

Impact of the EndoPredict-clin score on risk stratification in ER-positive, HER2-negative breast cancer after considering clinical guidelines.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 542-542
Author(s):  
Martin Filipits ◽  
Peter Christian Dubsky ◽  
Margaretha Rudas ◽  
Jan C. Brase ◽  
Ralf Kronenwett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Clinical Guidelines ◽  
Risk Groups ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Er Positive

542 Background: Many ER-positive, HER2-negative breast cancer patients are treated by adjuvant chemotherapy according to current clinical guidelines. We retrospectively assessed whether the combined gene expression/ clinicopathological EndoPredict-clin (EPclin) score improved the accuracy of risk classification in addition to considering clinical guidelines. Methods: Three clinical breast cancer guidelines (National Comprehensive Cancer Center Network (NCCN), German S3 and St. Gallen 2011), and the EPclin score - assessed by quantitative RT-PCR in formalin-fixed paraffin-embedded tissue - were used to assign risk groups in 1,702 ER-positive, HER2-negative breast cancer patients from two randomized phase III trials (Austrian Breast and Colorectal Cancer Study Group 6 and 8) treated with endocrine therapy only. Results: Although all analyzed clinical guidelines identified a low-risk group with improved metastasis-free survival, the overwhelming majority of all patients (81-94%) were classified as intermediate / high risk. In contrast to that, the EPclin classified only 37% of all patients as high risk and that stratification resulted in the best separation between low and high risk groups (p < 0.001, HR = 5.11 (3.48-7.51). Consequently, the majority of all patients deemed intermediate / high risk by the clinical guidelines was re-classified as low risk by the EPclin score. Kaplan Meier analyses demonstrated that the re-classified subgroups (47 to 57% of all patients) had an excellent 10-year metastasis-free survival of 95% comparable to the clinical assigned low-risk groups although encompassing a higher proportion of the trial patients. Conclusions: The EPclin score predicted distant recurrence more accurately than all three clinical guidelines and is especially useful to reclassify patients considered as intermediate / high risk by the guidelines. The data suggests that the EPclin score provides clinically useful prognostic information beyond common clinical guidelines and can be used to accurately identify the clinically relevant group of patients who are adequately and sufficiently treated with adjuvant endocrine therapy alone.

Comparative performance of Breast Cancer Index (BCIN+) and CTS5 in hormone receptor-positive (HR+) lymph node-positive (N+) breast cancer patients with one to three positive nodes (N1).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 555-555
Author(s):  
Dennis Sgroi ◽  
Yi Zhang ◽  
Catherine A. Schnabel
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Tumor Size ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Low Risk ◽  
Intermediate Risk ◽  
Breast Cancer Patients

555 Background: Identification of N+ breast cancer patients with a limited risk of recurrence improves selection of those for which chemotherapy and/or extended endocrine therapy (EET) may be most appropriate to reduce overtreatment. BCIN+ integrates gene expression with tumor size and grade, and is highly prognostic for overall (0-10yr) and late (5-10yr) distant recurrence (DR) in N1 patients. Clinical Treatment Score post-5-years (CTS5) is a prognostic model based on clinicopathological factors (nodes, age, tumor size and grade) and significantly prognostic for late DR. The current analysis compares BCIN+ and CTS5 for risk of late DR in N1 patients. Methods: 349 women with HR+, N1 disease and recurrence-free for ≥5 years were included. BCIN+ results were determined blinded to clinical outcome. CTS5 was calculated as previously described (Dowsett et al, JCO 2018; 36:1941). Kaplan-Meier analysis and Cox proportional hazards regression for late DR (5-15y) were evaluated. Results: 64% of patients were > 50 years old, 34% with tumors > 2cm, 79% received adjuvant chemotherapy and 64% received up to 5 years of ET. BCIN+ stratified 23% of patients as low-risk with 1.3% risk for late DR vs those classified as high-risk with 16.1% [HR 12.4 (1.7-90.4), p = 0.0014]. CTS5 classified patients into 3 risk groups: 29% of patients as low-risk (4.2% DR), 37% as intermediate-risk (10.6% DR), and 34% as high-risk (22.1% DR) [HR intermediate vs. low: 2.3 (0.7-7.0), p = 0.16; high vs. low: 5.3 (1.8-15.5), p = 0.002]. In a subset of patients who completed 5 years of ET (N = 223), BCIN+ identified 22% of patients as low-risk with a late DR rate of 2.1%, while CTS5 identified 29% and 37% of patients as low- and intermediate-risk with late DR rates of 5.2% and 10.3%, respectively. Conclusions: BCIN+ classified N1 patients into binary risk groups and identified 20% patients with limited risk of late DR ( < 2%) that may be advised to forego EET and its attendant toxicities/side effects. In comparison, CTS5 classified patients into 3 risk groups, with low- and intermediate-risk of late DR of 4-5% and 10%, wherein the risk-benefit profile for extension of endocrine therapy is less clear.

Application of MammaPrint test on Chinese patient with breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13671-e13671
Author(s):  
Chen Tian ◽  
Lili Fu ◽  
Jiyu Wei ◽  
Pengfei Yin ◽  
Henghui Zhang
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Clinical Pathology ◽  
Low Risk ◽  
Chinese Patients ◽  
Her2 Status ◽  
Clinical High Risk ◽  
Breast Cancer Patients

e13671 Background: A 70-gene prognosis-signature, known as MammaPrint (MP), is validated as a good predictor of recurrence in patients with ER+/HER2- early stage breast cancer in Europe and America. Previous studies on Japanese and Korean breast cancer patients showed that the proportion of MP Low-Risk tumours is significantly lower than the percentage which reported in previous studies. Here we use MammaPrint to determine the gene profiles of breast cancer tumours from Chinese patients and investigate the test’s potential clinical applications. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumour samples or fresh tumour samples from 594 eligible breast cancer patients were collected from 97 hospitals in China. Tumor RNAs were isolated from samples and analyzed using RNA sequencing technology. Clinical risk was categorized based on the Adjuvant! algorithm as used in the MINDACT trial. Concordance between risk predicted by the MammaPrint and clinical characteristics were evaluated. We also analyzed the clinical-pathology features of patients and compared them to previous studies. Results: Overall, 315 patients were categorized as clinical high risk (182 were MP Low-Risk and 133 MP High-Risk), while 279 patients were categorized as clinical low risk (203 were MP Low-Risk and 76 MP High-Risk). The concordance rate between risk predicted by the MammaPrint and clinical characteristics was 56.57%. Among the clinical-pathology features, age, ER/PR/HER2 status, tumour grade and tumour size were significantly related to the genomic risk (p = 0.009, 0.003, < 0.001, 0.001, < 0.001, and 0.007 respectively). Conclusions: The proportion of MP Low-Risk tumours was 64.81%, which is similar to previous validated studies in Europe and America. Of the patients that were clinical high risk, 58% was categorized as MP Low-Risk, and this group of patients may have limited benefit from chemotherapy. Our results indicate that MammaPrint is applicable to Chinese patients and has potential value in clinical practice to avoid over-treatment.

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