Adherence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor (HR)-positive breast cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 527-527
Author(s):  
Julia Foldi ◽  
Catherine A. Schnabel ◽  
Max Salganik ◽  
Lajos Pusztai ◽  
Tara B. Sanft
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Endocrine Therapy ◽  
Risk Group ◽  
Early Stage ◽  
Distant Recurrence ◽  
Breast Cancers ◽  
High Likelihood ◽  
Dxa Scans

527 Background: Evidence suggests continuing endocrine therapy (ET) beyond 5 years (yr) may reduce breast cancer recurrence in early stage HR+ breast cancers. Given the modest benefit and potentially serious adverse effects of extended ET (EET), improved approaches to identify patients who are at increased risk of late distant recurrence and who derive benefit from EET are critical. Guidelines recommend shared decision-making between oncologists and patients. The adherence rate to EET by 5 yr is only 50-60%. BCI is a gene-expression assay used to predict late distant recurrence and is predictive of benefit from EET. We assessed adherence to EET in women who had BCI testing. Methods: Women with stage I-III HR+ breast cancer s/p 3.5 yr of adjuvant ET and had BCI testing at our institution (8/2013-7/2015) were included. Pts who had < 4 yr of follow-up since BCI testing were excluded. Information including demographics, tumor characteristics, treatment history, number DXA scans, history of osteopenia/osteoporosis were collected. Data on medication adherence was based on prescriptions in the electronic health record. Results: 102 pts were included in our analysis. The median age was 61yr (46-89 yr). The majority of pts had stage I (63%), N0 (77%) and HER2- (90%) disease. 50 pts (46%) received chemotherapy. 44 (43%) received tamoxifen and 79 (77%) had an aromatase inhibitor. BCI categorized 61 (60%) pts as low risk, 26 (25%) as intermediate, and 15 (15%) as high risk for late distant recurrence. 61 (60%) and 41 (40%) pts were predicted to have low and high likelihood of benefit from EET, respectively. All 15 (100%) pts categorized as high risk for late recurrence were predicted to have a high likelihood to benefit from EET; all were recommended to continue EET by their oncologist and all 15 elected EET. 11 (73%) completed 10 yr or were on EET at last follow-up. Of the 4 (27%) pts who stopped before 10 yr, 1 pt had metastatic recurrence and 3 had intolerable side effects. Pts on EET underwent an avg of 1.91 DXA scans, compared with 1.23 for those who stopped ET at 5 yr (p = 0.003). At a median follow-up of 10 yr from diagnosis, there were 2 metastatic (1/15 in the high risk and 1/26 in the intermediate risk group) and 1 local recurrence (1/61 in the low risk group). Conclusions: In pts who continued ET beyond 5 years based on BCI testing and discussion with their oncologist, the rates of adherence and persistence to EET were higher than those previously published. EET may increase the number of DXA scans performed.

Can high Ki67 predict distant recurrence in early-stage breast cancer with low Oncotype Dx score?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12561-e12561
Author(s):  
Parvaneh Fallah ◽  
Nasser Khleel Mulla ◽  
Raquel Aloyz ◽  
Olga Aleynikova ◽  
Anca Florea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Group ◽  
Early Stage ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
High Risk Group ◽  
Low Risk ◽  
Oncotype Dx ◽  
Early Stage Breast Cancer

e12561 Background: Ki-67 is a marker of proliferating cells. The recurrence score based on the 21-gene breast cancer assay also called Oncotype Dx provides prognostic and predictive information for recurrence in early stage breast cancer patients. We previously showed that there is a moderate correlation between Ki67 and oncotype Dx recurrence score. In this retrospective study, we aimed to examine whether high Ki67 could predict the distant recurrence in early stage breast cancer with low oncotype Dx scores ( < 25). Methods: This retrospective study included 278 consecutive cases of hormone receptor-positive, HER2 negative (T1-2 N0 M0) breast cancer who were diagnosed between 2008 and 2015 with low oncotype Dx ( < 25). Patients’ clinical outcome in terms of distant recurrence after breast surgery was determined up to December 2020 (median follow-up of 7 years). Patients were divided in to low risk (Ki67 < 15%) and high risk (Ki67 > = 15%) groups. Results: Of 278 cases with average and median age of 59 and 60 respectively, 148 (53%) were in Ki67 low risk and 130 (47%) were in Ki67 high risk group. Average and median oncotype Dx were 13.86 and 15 respectively in Ki67 low risk versus 15.23 and 16 respectively in Ki67 high risk group. 13 patients (4%) experienced distant metastasis in lung, liver, bone and skin. Of these 13 cases with average and median oncotype Dx 15.84 and 19 respectively, 12 (92%) were in the Ki67 high risk group and only 1 (8%) belonged to the low risk category. High Ki67 patients were overrepresented in group with recurrent distant metastasis compare to group without recurrent disease (Pearson Chi-Square = 51.18 with 1 degree of freedom and P = < 0.001). Conclusions: Ki67 high patients in the low risk oncotype Dx group are relapsing at a significantly higher rate suggesting that Ki67 combined with low oncotype Dx further refines the risk of distant relapse.

Secondary Invasive Breast Events among Patients with Hormone-Positive Breast Cancer and High-Risk Oncotype DX Recurrence Scores 26–30 and ≥31

Oncology ◽  
2021 ◽  
pp. 1-4
Author(s):  
Natalie F. Berger ◽  
Brittney S. Zimmerman ◽  
Serena Tharakan ◽  
Kelly Suchman ◽  
Krystal P. Cascetta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Endocrine Therapy ◽  
Risk Group ◽  
Early Stage ◽  
Low Risk ◽  
Oncotype Dx ◽  
Intermediate Risk ◽  
Ovarian Suppression ◽  
Significant Difference

<b><i>Background:</i></b> The Oncotype DX Recurrence Score (ODx RS) is the most widely adopted genomic assay used to guide treatment for patients with early-stage, hormone-positive (HR+) breast cancer (BC), with higher scores predicting greater risk of recurrence and benefit from chemotherapy. Patients with ODx RS &#x3e;25 typically recieve adjuvant chemotherapy; however, data regarding efficacy of chemotherapy for reducing recurrence in this population have been mixed. <b><i>Objectives:</i></b> This study aimed to evaluate outcomes of patients with early-stage HR+ BC with high-risk ODx RS (26–30 and ≥31) in order to assess treatment patterns and outcomes. We hypothesized that the benefit of chemotherapy in these groups may be minimal and that select patients may forgo chemotherapy in favor of more aggressive endocrine therapy and ovarian suppression. <b><i>Methods:</i></b> We performed a retrospective analysis of 515 patients with early-stage, HR+ BC with high-risk ODx RS 26–30 and ≥31 treated between 2006 and 2018. Patients were stratified by RS: low-risk (≤10), intermediate-risk (11–25), and high-risk (≥26). The Kaplan-Meier method was used to estimate the time to secondary invasive breast events (SIBE) or distributions overall and among different RS groups with the log rank test used to compare distributions between groups. <b><i>Results:</i></b> Rates of chemotherapy administration were 7% among the low-risk group, 18% among the intermediate-risk group, and 83% among high-risk patients with 41 SIBE (8%) reported. When stratified by ODx RS, 5-year rates of SIBE were 4%, 6%, and 16% for low-risk, intermediate-risk, and high-risk RS, respectively. Among the 27 lymph node (LN)-negative patients with ODx RS 26–30, 74% received chemotherapy. The 5-year rate of SIBE was 25% among patients who received chemotherapy and 33% among those who did not (<i>p</i> = 0.5489). Among the 23 LN-negative patients with ODx RS ≥31, 91% of patients received chemotherapy. The 5-year rate of SIBE was 0% both with and without chemotherapy. <b><i>Conclusions:</i></b> There was no statistically significant difference in SIBE for patients with high-risk ODx RS based on chemotherapy treatment. More aggressive endocrine therapy with ovarian suppression has become an alternative to chemotherapy among patients with intermediate-risk ODx RS (16–25). This approach may be useful among patients with high-risk ODx RS, with additional studies needed in this patient population.

scholarly journals Endocrine Therapy in Premenopausal Hormone Receptor–Positive Breast Cancer

2016 ◽  
Vol 12 (11) ◽  
pp. 1148-1156 ◽  
Author(s):  
Amye J. Tevaarwerk ◽  
Kari B. Wisinski ◽  
Ruth M. O’Regan
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Systemic Therapy ◽  
Hormone Receptor ◽  
Randomized Trials ◽  
Early Stage ◽  
Premenopausal Women ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

Systemic therapy for premenopausal women with hormone receptor–positive breast cancer has evolved in the last 5 years, but critical questions remain. Recent randomized trials have demonstrated a benefit for the addition of ovarian suppression to endocrine therapy in patients with breast cancers considered to be at high risk for recurrence, whereas those with lower-risk cancers seem to have a favorable outcome with tamoxifen alone. Two large randomized trials have demonstrated a benefit for extending adjuvant tamoxifen beyond 5 years. Currently the choice of systemic therapy is selected empirically but molecular profiling may, in the near future, provide a more conclusive means of selecting an endocrine therapeutic approach for premenopausal patients. Given that a significant subset of hormone receptor–positive cancers are intrinsically resistant to endocrine agents, as well as the finding that inhibiting cyclin-dependent kinases 4 and 6 and mammalian target of rapamycin appears to potentially reverse this resistance in patients with metastatic disease, evaluation of these agents in the early-stage setting is ongoing.

Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study

2017 ◽  
Vol 35 (11) ◽  
pp. 1179-1188 ◽  
Author(s):  
Signe Borgquist ◽  
Anita Giobbie-Hurder ◽  
Thomas P. Ahern ◽  
Judy E. Garber ◽  
Marco Colleoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Distant Recurrence ◽  
Cholesterol Lowering ◽  
Hormone Receptor Positive ◽  
Cholesterol Levels ◽  
Free Interval

Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer–free interval, and distant recurrence–free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer–free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence–free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor–positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.

Correlation of Breast Cancer Index (BCI) prognostic and predictive results to Ki67 and tumor grade in early stage HR+ breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12075-e12075
Author(s):  
Carla Isadora Falkson ◽  
Jeffrey Kepes ◽  
Graham M. Poage ◽  
Junmei Liu ◽  
Catherine A. Schnabel
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Stage ◽  
Tumor Biology ◽  
Tumor Grade ◽  
Distant Recurrence ◽  
Wide Distribution ◽  
Individual Risk ◽  
Chi Squared ◽  
Extended Endocrine Therapy

e12075 Background: Markers of tumor proliferative status, e.g., Ki67 and grade (G), are prognostic for early distant recurrence (DR) in HR+ breast cancer and integrated in adjuvant chemotherapy decisions; however, their impact on late DR and extended endocrine therapy (EET) decisions is less clear. BCI is a genomic assay that provides 2 results: BCI Predictive, based on HoxB13/IL17BR (H/I ratio), reports a prediction of likelihood of benefit from EET; BCI Prognostic, based on the algorithmic combination of H/I and proliferation genes, reports risk of late DR. In this study, BCI results were examined within clinicopathologic risk categories based on Ki67 and G. Methods: The BCI Clinical Database for Correlative Studies is an IRB-approved de-identified database that contains > 50 clinicopathologic and molecular variables from cases submitted for BCI testing in clinical practice (N = 14,463). Clinicopathologic variables were abstracted from pathology reports, and were available for a subset of cases. High Ki67 was defined as ≥14%. Chi-squared tests were used to compare BCI results between Ki67 and G subgroups. Results: Analyses included 3395 LN- pts (median age 59.1y; 73% ≥ 50y). BCI Prognostic showed a wide distribution of individual risk assessments in pts with high or low Ki67. A greater proportion of pts with high Ki67 was classified by BCI as high risk of late DR compared to low Ki67 (68.2% vs 26.5%; P < 0.0001); however, substantial proportions of high Ki67 pts were classified as BCI low risk (31.8%) and pts with low Ki67 classified as BCI high risk (26.5%). Overall, there was a moderate correlation between individual BCI Scores and individual Ki67 scores (Correlation = 0.519). 45.5% of pts with high Ki67 were classified as High BCI Predictive (H/I) compared to 35.5% of pts with low Ki67 (p < 0.001). Both BCI Prognostic and BCI Predictive (H/I) classified increasing proportions of pts as high risk or high benefit with increasing G (P < 0.0001). Conclusions: These findings help characterize differential stratification based on tumor biology vs Ki67/G for pts considering EET. While moderately correlated, both BCI Prognostic and BCI Predictive (H/I) identified distinct populations compared to Ki67 and G.

Utility of the Breast Cancer Index (BCI) in the clinical practice.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14723-e14723
Author(s):  
Saranya Kodali ◽  
Eswar Tipirneni ◽  
Kim Dittus
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
High Risk ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Late Recurrence ◽  
Low Risk ◽  
Breast Cancer Index ◽  
Pathologic Features ◽  
Poor Tolerance

e14723 Background: Extended endocrine therapy (EET) greater than 5 years in early stage hormone receptor positive (HR+) breast cancer (BC) patients has shown benefit. However, EET is associated with side effects and there is no validated assay to determine which group of patients would derive benefit. Breast Cancer Index (BCI) is a validated bio-marker test that incorporates 2 distinct genomic assays and is prognostic/predictive. The objective of this study is to assess patient characteristics, pathologic features and patient preferences with regards to extending endocrine therapy after reviewing the BCI results. Methods: We performed a retrospective chart review on early stage HR+ BC patients from Jan, 2016 to Jan, 2017 at the University of Vermont Medical Center. We identified 25 cases on whom BCI was submitted. Results: Median age was 68 years. Majority of the patients were stage IA (64%). 56% of the tumors were moderately differentiated. All patients were ER +ve and 12% were HER2+. Median tumor size was 1.4 cm (0.3-4). 76% had poor tolerance to the ET and preferred the test to be sent. In LN-patients, BCI identified 42% as high risk and 52% as low risk for late recurrence and 32% who derive high benefit from EET. In LN+ patients, BCI identified 75% as high risk for late recurrence and 25% as low risk for late recurrence. 40% of the entire group were identified to highly benefit from EET (70% agreed to continue ET and 30% denied due to side effects). Conclusions: BCI is a reasonable test to consider in early stage HR+ BC, especially in patients with poor tolerance to ET. This test might aid in decision making with tolerability/compliance challenges to EET. [Table: see text]

scholarly journals Development a Prognostic Model Integrating lncRNA/ mRNA novel Biomarkers Identified by Bioinformatics Analysis and Experiments in Breast Cancer

2021 ◽  
Author(s):  
Jinrong Wei ◽  
Qianshu Dou ◽  
Futing Ba ◽  
Guo-Qin Jiang
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
High Risk ◽  
Risk Score ◽  
Risk Group ◽  
Low Risk ◽  
Breast Cancers ◽  
Rt Pcr ◽  
Cerna Network ◽  
Prognosis Model

Abstract Purpose: The purpose of this study is to established a prognosis model based on the expression profiles of lncRNAs and mRNAs for breast cancers.Methods: Single Variable Cox Proportional Risk Regression analysis and difference analysis were applied to screen survival-related and differently expressed lncRNAs and mRNAs between tumor and normal tissues from TCGA data. GO and KEGG analysis were applied for top 30 survival-related genes. LncRNA/mRNA co-expressed network was constructed based on correlation analysis. LASSO analysis and Multivariate Stepwise Cox Regression analysis were applied to establish the prognosis model. RT-PCR experiments were applied to verify the correctness of the analysis results. Relative components of the TME in breast cancers with high and low risk groups were analysed by xCell and Cox proportional risk regression analysis. The ceRNA network was constructed by calculating the Pearson correlation coefficient (PCC) for miRNA-mRNA and miRNA-lncRNA using paired miRNA, mRNA, and lncRNA expression profile data.Results:Venn diagrams showed that there were 60 genes and 54 lncRNAs that were differently expressed and related with survival. Through lncRNA/mRNA co-expressed network construction, 19 lncRNA and 16 mRNA hub genes were gained. The genes were then included in LASSO and multivariate Cox proportional hazard regression analysis, and finally, 3 lncRNAs (LINC01497, LINC02766, LINC02528) and 2 mRNAs (C20orf85, CST1) were selected as prognosis predictive genes. According to the median risk score of the 5 candidates, patients were divided into high-risk group and low-risk group. The results of RT-PCR were consistent with the analysis results. The proportions of Adipocytes, Endothelial cells, HSCs, Fibroblasts were significantly lower in low risk score tissues compared with the high risk score tissues, while the proportions of M1 macrophages, MSCs, Th2 cells were significantly higher. A lncRNA-miRNA-mRNA ceRNA network containing 3 lncRNAs, 2 mRNAs, and 158 miRNAs was finally constructed, preliminarily revealed a proper mechanism of the 5 molecules playing important roles in breast cancer progression and prognosis prediction.Conclusion: We found that LINC01497, LINC02766, LINC02528 and C20orf85, CST1 may serve as a powerful prognostic tool to optimize the prognosis evaluation system of breast cancer.

scholarly journals Prospective Validation of a Genomic Assay in Breast Cancer: The 70-gene MammaPrint Assay and the MINDACT Trial

2019 ◽  
Vol 48 (1) ◽  
pp. 18
Author(s):  
William Audeh ◽  
Lisa Blumencranz ◽  
Heather Kling ◽  
Harsha Trivedi ◽  
Gordan Srkalovic
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
High Risk ◽  
Expression Analysis ◽  
Clinical Utility ◽  
Gene Expression Analysis ◽  
Early Stage ◽  
Significant Proportion ◽  
Breast Cancers ◽  
Gene Assay

<p>MammaPrint was the first genomic assay in breast cancer to be validated with a prospective randomized trial, the MINDACT trial. The 70 gene MammaPrint assay was developed to determine the risk of distant metastasis in early stage breast cancer through gene expression analysis and was the first FDA cleared genomic assay for breast cancer. The assay identifies primary breast cancers likely to metastasize within the first five years of diagnosis and has clinical utility for helping to determine the expected benefit from adjuvant chemotherapy. The MINDACT Trial was the first trial of a genomic assay in breast cancer to provide prospective, randomized evidence of clinical utility for this important clinical question, identifying a significant proportion of patients who could safely forgo chemotherapy within a cohort of patients with high risk clinical characteristics. Nearly half of all patients (46%) who would have been advised chemotherapy according to clinical guidelines were identified genomically by MammaPrint as being low risk and found to have equivalent rates of freedom from metastasis at 5 years with or without chemotherapy. Based upon the MINDACT trial, the ASCO Biomarker Guidelines now approve the use of MammaPrint to inform decisions regarding chemotherapy for women with clinically high-risk ER+ breast cancer, and as the only approved assay for use in women with 1-3 involved lymph nodes. Recent studies suggest information obtained from the 70-gene assay may also help inform decisions regarding endocrine therapy, as well as chemotherapy, targeted therapy and immunotherapy.</p><p><strong>Conclusion. </strong>The power of gene expression analysis in breast cancer, effectively illustrated with MammaPrint in the MINDACT trial, is now being explored through examination of the full transcriptome in breast cancer.</p>

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