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 ◽  
...  

<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.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 529-529
Author(s):  
Tanmayi Pai ◽  
Angelica Gil ◽  
Yaohua Ma ◽  
Zhuo Li ◽  
Pooja Advani ◽  
...  

529 Background: Multiple prognostic models exist to predict late relapse risk in early stage hormone receptor-positive (HR+) breast cancer (BC). The CTS5 is one such model that has been validated in HR+ HER2-negative BC. The value of this model in HR+ HER2+ has not been established. Here, we assessed CTS5 in patients (pts) with early stage HER2+ BC treated in the NCCTG N9831 (Alliance) trial. Methods: Pts with stage I-III HER2+ HR+ BC who survived ≥ 5 years were included. The online CTS5 calculator was used to determine CTS5 score and risk group (low, intermediate, and high) based on age, tumor size, grade, and number of involved nodes. Kaplan-Meier (KM) estimates, Cox regression models, and C index were used for analysis. Results: From 3,130 pts, 1,204 pts met the criteria and were included. Median age was 49 (22-79) years and median tumor size was 2.4 (0.1-12) cm. 63.6% had grade 3 tumors, 33.6% grade 2, and 2.8% grade 1. Median follow up was 10.89 (5.01-15.32) years. Based on CTS5, 821 (68.2%) pts were classified as high risk, 289 (24%) as intermediate risk, and 94 (7.8%) as low risk. Overall, using univariate Cox regression analysis, there was no statistically significant difference in recurrence free survival (RFS) among pts with intermediate vs. low (HR 0.47 95%CI 0.18-1.22, p = 0.12) and high vs. low (HR1.23 95%CI0.57-2.67, p = 0.6) with the C index of 0.58. Among pts who received concurrent trastuzumab (H) with HR+ BC, there was also no statistical difference in RFS between high vs. low (HR 0.68 95%CI0.24-1.97, p = 0.48) with the C index of 0.55. Paradoxically, pts with intermediate risk had better RFS than low risk (HR 0.18 95%CI0.03-0.97, p = 0.05). As a continuous variable, there is also no significant improvement in RFS per 1 unit increase in CTS5 score (HR 1.19 95%CI 0.73-1.96, p = 0.49) with the C index of 0.54. After 5 years, 7.06% (n = 30/425) of HR+ pts treated with concurrent H recurred. Conclusions: The CTS5 model is not prognostic in pts with early stage HR+ HER2+ BC receiving adjuvant H. While most HR+ HER2+ pts are classified as high risk by CTS5, the recurrence between years 5-10 was low in pts who received adjuvant H. This study highlights the need to develop a new predictive model for risk of late relapse in this specific group of pts to enable clinicians to determine which pts would benefit from extended adjuvant endocrine therapy. Support: BCRF-19-161, U10CA180821, Genentech. https://acknowledgments.alliancefound.org Clinical trial information: NCT00005970 .


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12561-e12561
Author(s):  
Parvaneh Fallah ◽  
Nasser Khleel Mulla ◽  
Raquel Aloyz ◽  
Olga Aleynikova ◽  
Anca Florea ◽  
...  

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.


2020 ◽  
Vol 06 (02) ◽  
pp. e135-e138
Author(s):  
T. M. Aherne ◽  
M. R. Boland ◽  
D. Catargiu ◽  
K. Bashar ◽  
T. P. McVeigh ◽  
...  

Abstract Introduction Routine utilization of multigene assays to inform operative decision-making in early breast cancer (EBC) treatment is yet to be established. In this pilot study, we sought to establish the potential benefits of surgical intervention in EBC based on recurrence risk quantification using the Oncotype DX (ODX) assay. Materials and Methods Consecutive ODX tests performed over a 9-year period from October 2007 to May 2016 were evaluated. Oncotype scores were classified into high (≥31), medium (18–30), or low-risk (0–17) groups. The primary outcome was breast cancer recurrence. Subgroup analysis offered assessment of the recurrence effect of mode of surgical intervention for patient groups as defined by the oncotype score. Results In total 361 patients underwent ODX testing. The mean age and follow-up were 55.25 (± 10.58) years and 38.59 (± 29.1) months, respectively. The majority of patients underwent wide local excision (86.7%) with 8.9 and 4.4% patients having a mastectomy or wide local excision with completion mastectomy, respectively. Fifty-one percent of patients fell into the low risk ODX category with a further 40.2 and 8.5% deemed to be of intermediate and high risk. Five patients (1.38%) had disease recurrence. Comparative analysis of operative groups in each oncotype group revealed no difference in recurrence scores in the low- (p = 0.84) and high-risk groups (p = 0.92) with a statistically significant difference identified in the intermediate risk group (p = 0.002). Conclusion To date we have been unable to definitively identify a role for ODX in guiding surgical approach in EBC. There is, however, a need for larger studies to examine this hypothesis.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11067-11067 ◽  
Author(s):  
H. Patel ◽  
K. Hook ◽  
C. Kaplan ◽  
R. Davidson ◽  
A. DeMichele ◽  
...  

11067 Background: The 21 gene RT-PCR assay Oncotype DX (Genomic Health, CA) stratifies patients into low, intermediate and high risk for systemic recurrence. The objective of this study was to examine the patterns of use of Oncotype DX in a single institution. Methods: All patients who had ODX testing requested by the University of Pennsylvania were identified and recurrence scores (RS) obtained. Patient and tumor characteristics, as well as treatment administered, were obtained by chart review for analysis. Results: 100 ODX tests were ordered between 1/1/05–11/30/06. RS results classified 51% of breast cancers as low risk, 38% intermediate risk, and 11% high risk. Characteristics of the tumors of the overall population and by RS group are shown in Table . 99% of patients received hormonal therapy. Of the low risk patients, only one patient was treated with chemotherapy (2%) while 34% of the intermediate risk group and 80% of the high risk group received chemotherapy. Notably, only 4/100 patients with ODX were under age 35 and 17/100 had tumors over 2cm. Conclusions: In this series, ODX use is accelerating. The results of the ODX tests appear to be used clinically as demonstrated by the very low use of chemotherapy in the low risk group. Comparison to the overall population of ER positive, node negative patients seen at this institution is underway. [Table: see text] No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 555-555
Author(s):  
Dennis Sgroi ◽  
Yi Zhang ◽  
Catherine A. Schnabel

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.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14723-e14723
Author(s):  
Saranya Kodali ◽  
Eswar Tipirneni ◽  
Kim Dittus

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]


2020 ◽  
Vol 10 ◽  
Author(s):  
Ming Li ◽  
Jinbo Yue ◽  
Xiangbo Wan ◽  
Bin Hua ◽  
Qiuan Yang ◽  
...  

PurposeThe aim of this study was to develop a widely accepted prognostic nomogram and establish a risk-adapted PMRT strategy based on locoregional recurrence for pT1-2N1M0 breast cancer.Methods and MaterialsA total of 3,033 patients with pT1-2N1M0 breast cancer treated at 6 participating institutions between 2000 and 2016 were retrospectively reviewed. A nomogram was developed to predicted locoregional recurrence-free survival (LRFS). A propensity score-matched (PSM) analyses was performed in risk-adapted model.ResultsWith the median follow-up of 65.0 months, the 5-year overall survival (OS), disease free survival (DFS) and LRFS were 93.0, 84.8, and 93.6%, respectively. There was no significant difference between patients who received PMRT or not for the entire group. A nomogram was developed and validated to estimate the probability of 5-year LRFS based on five independent factors including age, primary tumor site, positive lymph nodes number, pathological T stage, and molecular subtype that were selected by a multivariate analysis of patients who did not receive PMRT in the primary cohort. According to the total nomogram risk scores, the entire patients were classified into low- (40.0%), moderate- (42.4%), and high-risk group (17.6%). The 5-year outcomes were significantly different among these three groups (P&lt;0.001). In low-risk group, patients who received PMRT or not both achieved a favorable OS, DFS, and LRFS. In moderate-risk group, no differences in OS, DFS, and LRFS were observed between PMRT and no PMRT patients. In high-risk group, compared with no PMRT, PMRT resulted in significantly different OS (86.8 vs 83.9%, P = 0.050), DFS (77.2 vs 70.9%, P = 0.049), and LRFS (90.8 vs. 81.6%, P = 0.003). After PSM adjustment, there were no significant differences in OS, DFS, and LRFS in low-risk and moderate-risk groups. However, in the high-risk group, PMRT still resulted in significantly better OS, DFS and improved LRFS.ConclusionsThe proposed nomogram provides an individualized risk estimate of LRFS in patients with pT1-2N1M0 breast cancer. Risk-adapted PMRT for high-risk patients is a viable effective strategy.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 527-527
Author(s):  
Julia Foldi ◽  
Catherine A. Schnabel ◽  
Max Salganik ◽  
Lajos Pusztai ◽  
Tara B. Sanft

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.


2021 ◽  
Author(s):  
Lei Lei ◽  
Han-Ching Chan ◽  
Tzu-Pin Lu ◽  
Hung-Chun Skye Cheng

Abstract PURPOSE: To assess the prognostic value of the Dutch criteria for patients with early-stage hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer from the Taiwan Cancer Database. PATIENTS AND METHODS:We included 8,295 patients with early-stage node-negative breast cancer who underwent surgery during January 2008–December 2012. Patients were stratified into low- and high-risk groups based on the Dutch criteria. The Kaplan–Meier method and log-rank test were used to estimate the difference in breast cancer-specific survival (BCSS) and overall survival (OS) between groups. Multivariable analysis was used to evaluate the prognostic value of the Dutch criteria.RESULTS: Overall, the low-risk and high-risk groups comprised 5,375 and 2,920 patients, respectively. In the low- and high-risk groups, the 5-year BCSS rate was 99.6% and 98.2% (P<0.0001) and the 5-year OS rate was 98.3% and 96.8% (P<0.0001), respectively. The hazard ratio for BCSS was 4.18 (95% confidence interval [CI], 2.63–6.63, P<0.0001), and the hazard ratio for OS was 1.94 (95% CI, 1.48–2.55); both were significantly poorer in the high-risk group than in the low-risk group. In the low-risk group, the 5-year BCSS and OS of patients who did and did not receive adjuvant chemotherapy were similar (99.5% versus 99.6% [P=0.927] and 98.8% and 98.1% [P=0.0683], respectively). CONCLUSIONS: The prognosis of low-risk patients as classified using the Dutch criteria is excellent with or without adjuvant chemotherapy. The benefit of multi-gene testing for chemotherapy decision-making might be minimal in these patients.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2772
Author(s):  
Michael A. Jacobs ◽  
Christopher B. Umbricht ◽  
Vishwa S. Parekh ◽  
Riham H. El Khouli ◽  
Leslie Cope ◽  
...  

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained using the mpMRI, clinical, pathologic, and radiomic descriptors for prediction of the OncotypeDX risk score. The trained mpRad IRIS model had a 95% and specificity was 83% with an Area Under the Curve (AUC) of 0.89 for classifying low risk patients from the intermediate and high-risk groups. The lesion size was larger for the high-risk group (2.9 ± 1.7 mm) and lower for both low risk (1.9 ± 1.3 mm) and intermediate risk (1.7 ± 1.4 mm) groups. The lesion apparent diffusion coefficient (ADC) map values for high- and intermediate-risk groups were significantly (p < 0.05) lower than the low-risk group (1.14 vs. 1.49 × 10−3 mm2/s). These initial studies provide deeper insight into the clinical, pathological, quantitative imaging, and radiomic features, and provide the foundation to relate these features to the assessment of treatment response for improved personalized medicine.


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