scholarly journals Copy number heterogeneity identifies ER+ breast cancer patients with adverse outcome after adjuvant endocrine therapy

2021 ◽  
Author(s):  
Tom van den Bosch ◽  
Oscar M Rueda ◽  
Carlos Caldas ◽  
Louis Vermeulen ◽  
Daniël M Miedema
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Endocrine Therapy ◽  
Adjuvant Treatment ◽  
Copy Number ◽  
Adjuvant Endocrine Therapy ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Risk Patients

Background − Endocrine therapy forms the backbone of adjuvant treatment for estrogen-receptor positive (ER+) breast cancer. However, it remains unclear whether adjuvant treatment improves survival rates in low-risk patients . Low intra-tumor heterogeneity (ITH) has been shown to confer low-risk for recurrent disease. Here, it is studied if chromosomal copy number ITH (CNH) can identify low-risk ER+, lymph node-negative breast cancers patients who do not benefit from adjuvant endocrine therapy. Methods − Lymph node-negative ER+ patients from the METABRIC dataset were retrospectively analyzed (n=708). CNH was determined from a single bulk copy number measurement for each patient. Patients were stratified by CNH score as low, medium or high. Overall survival (OS) was compared between patients that did, or did not receive adjuvant endocrine therapy per CNH group with Cox proportional-hazards models, using propensity score weights to correct for confounders. Results − Adjuvant endocrine therapy improved the relapse free survival (RFS) for high-CNH/high-risk patients treatment (Hazard Ratio [HR] = 0.55, 95% Confidence Interval [CI] = 0.35 to 0.87), but not for low CNH/risk patients treatment (HR = 0.88, 95% CI = 0.50 to 1.55). For low-CNH/low-risk patients adjuvant endocrine therapy was associated with impaired OS (HR = 1.62, 95% CI = 1.10 to 2.40). Multivariable Cox analysis identified a significant interaction between CNH and endocrine therapy for OS (HR = 0.77, 95% CI = 0.62 to 0.96). Conclusions − This retrospective study of lymph node-negative, ER+ breast cancer finds that patients identified as low-risk using CNH display reduced OS when treated with adjuvant endocrine therapy.

The 70-gene profile and chemotherapy benefit in 1,600 breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
R. A. Bender ◽  
M. Knauer ◽  
E. J. Rutgers ◽  
A. M. Glas ◽  
F. A. de Snoo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Hormonal Therapy ◽  
Prognostic Indicator ◽  
Low Risk ◽  
Breast Cancer Patients ◽  
Node Negative

512 Background: The 70-gene expression profile (MammaPrint) is validated as an independent prognostic indicator for breast cancer patients with T1–2 node-negative and positive disease regardless of estrogen receptor status. Here we present the relationship between MammaPrint outcome and chemotherapy benefit in the adjuvant setting. Methods: We performed a pooled analysis of 1,637 patients with MammaPrint outcomes (T1–2, node-negative and positive invasive breast cancer and median FU 7.1 yrs) to determine the chemotherapy benefit of patients treated with adjuvant chemotherapy in addition to endocrine therapy. Patients were collected from 7 large datasets at multiple institutions across Europe. Results: In this meta-analysis, MammaPrint assigned 772 patients (47%) to “low risk” and 865 (53%) to “high risk”. In total 349 patients were treated with endocrine therapy alone, whereas 226 were treated with both chemo- and endocrine therapy. Patients with poor prognosis MammaPrint profile had a substantial benefit from chemotherapy: At 5 years, distant disease-free survival was improved from 69% to 88% (HR 0.28 (95% CI 0.14–0.56, p<0.001) when chemotherapy was added to hormonal therapy. The results remained significant in multivariate analysis including stratification by standard clinico-pathologic prognostic factors. Patients classified by MammaPrint as good prognosis (“low risk”) had no significant benefit from chemotherapy (p=0.962). Conclusions: The 70-gene MammaPrint profile is not only a strong and independent prognostic indicator for patients with early stage breast cancer, but it may also be predictive for the benefit of chemotherapy. While MammaPrint “high risk” classified patients demonstrate a clear benefit from adjuvant chemotherapy added to hormonal therapy, patients classified by MammaPrint as “low risk” for recurrence do not appear to benefit from the addition of chemotherapy to hormonal treatment alone. [Table: see text]

Are Breast Cancer Nomograms Still Valid to Predict the Need for Axillary Dissection?

Oncology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Vilma Madekivi ◽  
Antti Karlsson ◽  
Pia Boström ◽  
Eeva Salminen
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Axillary Dissection ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Axillary Lymph Node Metastases ◽  
Node Negative ◽  
Node Metastases ◽  
External Population

Background: Nomograms can help in estimating the nodal status among clinically node-negative patients. Yet their validity in external cohorts over time is unknown. If the nodal stage can be estimated preoperatively, the need for axillary dissection can be decided. Objectives: The aim of this study was to validate three existing nomograms predicting 4 or more axillary lymph node metastases. Method: The risk for ≥4 lymph node metastases was calculated for n = 529 eligible breast cancer patients using the nomograms of Chagpar et al. [Ann Surg Oncol. 2007;14:670–7], Katz et al. [J Clin Oncol. 2008;26(13):2093–8], and Meretoja et al. [Breast Cancer Res Treat. 2013;138(3):817–27]. Discrimination and calibration were calculated for each nomogram to determine their validity. Results: In this cohort, the AUC values for the Chagpar, Katz, and Meretoja models were 0.79 (95% CI 0.74–0.83), 0.87 (95% CI 0.83–0.91), and 0.82 (95% CI 0.76–0.86), respectively, showing good discrimination between patients with and without high nodal burdens. Conclusion: This study presents support for the use of older breast cancer nomograms and confirms their current validity in an external population.

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, &gt;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 &gt;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 &gt;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.

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