scholarly journals Quantitative mRNA Expression Assays and Synchronous Breast Cancers: A Case Report

2019 ◽  
Vol 12 (2) ◽  
pp. 418-420
Author(s):  
Steven Sorscher
Keyword(s):  
Endocrine Therapy ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Oncotype Dx ◽  
The Other ◽  
Precision Oncology ◽  
Breast Cancers ◽  
Rt Pcr ◽  
Mrna Analysis ◽  
Cancer Network

Quantitative mRNA analysis of breast tumors represents a routinely applied example of precision oncology. Currently the National Comprehensive Cancer Network (NCCN) recommends quantitative mRNA profiling (e.g., 21-gene RT PCR or Oncotype Dx assay) for nearly all surgically resected lymph node (LN) negative hormone receptor (HR) positive, HER2 negative breast cancers in order to predict recurrence risk with endocrine therapy compared to chemotherapy followed by endocrine therapy after surgery. The incidence of synchronous breast cancers is low and evidence concerning distant recurrence risk is limited, but the risk of distant recurrence from one or the other of two primary breast cancers appears to be higher than the recurrence risk of the single largest of the two cancers. In this report, a woman with synchronous primary breast cancers is described. Oncotype Dx testing was done on each of her two cancers. By assuming that the recurrence risk from each with adjuvant endocrine therapy is an independent event, the recurrence likelihood from one or the other or both is calculated. I propose that this calculated value more accurately should predict the recurrence from one or the other or both tumors with endocrine therapy or chemotherapy followed by endocrine therapy compared with using only the higher of the two Oncotype Dx estimated risks.

scholarly journals Development and Validation of a Simulation Model–Based Clinical Decision Tool: Identifying Patients Where 21-Gene Recurrence Score Testing May Change Decisions

2021 ◽  
pp. JCO.21.00651
Author(s):  
Jinani Jayasekera ◽  
Joseph A. Sparano ◽  
Suzanne O'Neill ◽  
Young Chandler ◽  
Claudine Isaacs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Simulation Model ◽  
Endocrine Therapy ◽  
External Validation ◽  
Recurrence Score ◽  
Clinical Decision ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Decision Tool ◽  
Life Years

PURPOSE There is a need for industry-independent decision tools that integrate clinicopathologic features, comorbidities, and genomic information for women with node-negative, invasive, hormone receptor–positive, human epidermal growth factor receptor-2–negative (early-stage) breast cancer. METHODS We adapted an extant Cancer Intervention and Surveillance Modeling Network simulation model to estimate the 10-year risk of distant recurrence, breast cancer–specific mortality, other-cause mortality, and life-years gained with chemoendocrine versus endocrine therapy. We simulated outcomes for 1,512 unique patient subgroups based on all possible combinations of age, tumor size, grade, and comorbidity level; simulations were performed with and without 21-gene recurrence scores (RSs). Model inputs were derived from clinical trials, large US cohort studies, registry, and claims data. External validation was performed by comparing results to observed rates in two independent sources. We highlight results for one scenario where treatment choice may be uncertain. RESULTS Chemoendocrine versus endocrine therapy in a 65-69-year-old woman with a small (≤ 2 cm), intermediate-grade tumor, and mild comorbidities provides a 1.3% absolute reduction in 10-year distant recurrence risk, with 0.23 life-years gained. With these tumor features, a woman like this will have a 28% probability of having an RS 16-20, 18% RS 21-25, and 11% RS 26+. If testing is done, and her RS is 16-20, chemoendocrine therapy reduces 10-year distant recurrence risk to 1%, with 0.20 life-years gained, a similar result as without testing. The absolute benefits would increase to 4.8%-5.5% if the RS was 26+. The model closely reproduced observed rates in both independent data sets. CONCLUSION Our validated clinical decision tool is flexible, readily adaptable to include new therapies, and can support discussions about genomic testing and early breast cancer treatment.

Abstract Submission

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
L. J. Goldstein ◽  
R. Gray ◽  
B. H. Childs ◽  
D. Watson ◽  
S. G. Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Oncotype Dx ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Free Survival ◽  
Increased Risk

526 Background: Evidence suggests modern chemotherapy (CT) regimens are only marginally more effective in HR-pos breast cancer (Berry et al. JAMA 2006: 295: 1658). Genomic classifiers may be useful for selection of high-risk subjects for more aggressive CHT. Methods: A case-cohort sample of 776 patients enrolled on E2197 who did (N=179) or did not have a recurrence after CT (if HR-neg) or CHT (if HR-pos) and had available tissue were evaluated for Oncotype DX™ Recurrence Score (RS). E2197 included 2885 evaluable patients with 0–3 positive nodes treated with four 3-week cycles of doxorubicin (60 mg/m2) plus cyclophosphamide 600 mg/m2 (AC) or docetaxel 60 mg/m2 (AT) and hormonal therapy (if HR-pos). Median follow-up was 76 months. Results: There was no difference in DFS between treatment arms. In multivariate analysis, RS was a significant predictor of recurrence in HR-pos disease (p=0.0007, recurrence risk 21% lower for each 10 point drop in RS, 95% confidence intervals 9% to 31%). Recurrence risk was significantly elevated for an intermediate RS 18–30 (n=138, hazard ratio [HR] 2.96 [p=0.0002]) or a high RS ≥ 31 (n=108, HR 4.00, p=0.0001) compared with low RS < 18(n=196), but not for high compared with intermediate RS (HR 1.34, [p=0.32]); results were similar if only HER2-neg disease was included. The 5-year relapse free interval(RFI), breast cancer free survival (BCFS), disease-free survival (DFS), and overall survival (OS) for patients with HR-pos, HER2-neg disease are shown below (%); patients with both node-neg or node-pos breast cancers whose RS was < 18 had excellent outcomes. Conclusions: Oncotype DX™ RS identifies individuals with HR-pos, HER2-neg breast cancer with 0–3 positive axillary lymph nodes at 3–4-fold increased risk of relapse despite standard CHT, and may serve as a means to distinguish between those who do well with standard CHT (RS <18) from those who may be suitable candidates for clinical trials evaluating alternative CT regimens or other strategies (RS ≥ 18). [Table: see text] [Table: see text]

scholarly journals Ki67 Assessment by qRT-PCR in OncotypeDx ® Breast Recurrent Score®: Low Correlation With IHC Assessment of ki67 and Prognostic Impact of ki67 RNA Level of Expression.

2021 ◽  
Author(s):  
Zohair Selmani ◽  
Chloé Molimard ◽  
Alexis Overs ◽  
Fernando Bazan ◽  
Loic Chaigneau ◽  
...  
Keyword(s):  
Early Stage ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Oncotype Dx ◽  
Expression Level ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Event Free Survival ◽  
Free Survival ◽  
Qrt Pcr

Abstract Background: Breast cancers expressing high levels of Ki67 are associated with poor outcomes. To provide individualized patient care, reliability of prognostic and predictive information deriving from Ki67 assessment is essential. Oncotype DX® test was designed for ER+/HER2- early-stage breast cancers to help adjuvant chemotherapy decision by providing a Recurrent Score® (RS®). RS® measures the expression of 21 specific genes from tumor tissue, including Ki67, and aim to predict the benefit of chemotherapy and the risk of distant recurrence. The primary aim of this study was to assess the agreement between Ki67RNA obtained with Oncotype DX® RS® and Ki67IHC. Other objectives were to analyze the association between the event free survival (EFS) and the expression level of Ki67RNA; and association between RS® and Ki67RNA.Methods: In a cohort of 98 patients with early ER+/HER2- breast cancers, we obtained: Recurrence score®, RNA level of Ki67 expression measured when assessing RS® and Ki67 tumor labelling by immunohistochemistry (Ki67IHC). The Ki67RNA was compared to the Ki67IHC by Kappa Cohen test. With a mean follow-up of 57 months, the association between the event free survival (EFS) and Ki67 status was measured using R package survival. Results: This population was essentially composed of no special type tumor (91%), N0 or Nmic (71%), grade 1 (62%), and tumor size pT1c (1-2 cm) (58%). The RS® values were <18 in 38% (n=37), 18-30 in 51% (n=50) and >30 in 11% (n=11) of the patients. A low agreement of 0.24 was found by Cohen’s kappa test between Ki67IHC and Ki67RNA. Moreover, Ki67RNAhigh tumors were significantly associated with the occurrence of events (p=0.02). On the other hand, we did not find any association between Ki67IHC and EFS (p=0.25).Conclusion: We observed of low agreement between expression level of Ki67RNA and Ki67 protein labelling by IHC. Unlike Ki67IHC and independently of the RS®, Ki67RNA could have a prognostic value. It would be interesting to better assess the prognosis and predictive value of Ki67RNA measured by qRT-PCR. The Ki67RNA in medical routine could be a good support in countries where Oncotype DX® is not accessible.

Female breast cancers (T1-2, N0, M0, HR+, HER2−) with an intermediate genetic-based recurrence risk: a real-world estimate in Italy

2019 ◽  
Vol 105 (6) ◽  
pp. 483-487
Author(s):  
Emanuele Crocetti ◽  
Alessandra Ravaioli ◽  
Dino Amadori ◽  
Silvia Mancini ◽  
Rosa Vattiato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Incidence ◽  
Risk Groups ◽  
Recurrence Risk ◽  
Oncotype Dx ◽  
Intermediate Risk ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Inclusion Criteria ◽  
Recent Trial

Objectives: Prognostic definition and treatment of breast cancer are supported by multigene testing. A recent trial (TAILORx) provided evidence against the use of adjuvant chemotherapy in early breast cancer (HR+ HER2−) with an intermediate result (11–25) in a multigene test (Oncotype DX). These results consequently fueled great discussion among oncologists. We aimed to estimate the burden of Italian incident breast cancer patients who, each year, may be involved in such decision-making. Methods: We used the data collected in the Romagna Cancer Registry to estimate the number of cases with the inclusion criteria of the TAILORx trial. Adjustments based on geographical variability in breast cancer incidence in Italy were applied to national estimates. Cases were estimated by Oncotype DX recurrence risk groups: ⩽10, 11–25, ⩾26. We also estimated the proportion of grade 1, 2, or 3 disease among breast cancer cases. Results: An overall 52,300 breast cancer cases were estimated to be diagnosed in Italy in 2018. Of these, 18,225 fit the TAILORx inclusion criteria: 3,025 were expected to have a low risk of recurrence (⩽10), 11,536 (63.3% of all cases) an intermediate risk (11–25), and 3,664 a high risk (⩾26). Among the group at intermediate risk, who may benefit from less aggressive therapy, 2,414 were estimated to have grade 1 disease, 7,618 grade 2, and 1,983 grade 3. Conclusions: This article provides reliable estimates on the burden of Italian women with breast cancer who, once tested with multigene testing, could potentially have their treatment changed to hormone therapy only.

Analysis of recurrence risk by subtype in ≤1 cm breast tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1034-1034
Author(s):  
Sarah V. Colonna ◽  
Ashantice K. Higgins ◽  
JoAnn Alvarez ◽  
Benjamin R. Saville ◽  
Julia Lawrence ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Tumor Grade ◽  
Breast Tumors ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Receptor Subtype ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Chi Square ◽  
Increased Risk

1034 Background: Triple-negative breast cancers (TNBC) comprise 15% of breast cancers and lack ER, PR, and HER2 expression. TNBC is biologically aggressive with high rates of recurrence, but little is known about the prognosis of small (≤1cm) TNBCs compared to similarly sized breast cancers with other receptor profiles. The role of adjuvant chemotherapy for TNBC that is ≤1cm remains unclear. Methods: Electronic medical records of all women aged ≥ 18 years with ≤1 cm, node negative, invasive breast cancer from 1997-2007 diagnosed or treated at Vanderbilt or Wake Forest were reviewed. Tumor grade, receptor status, treatment details, and follow up and recurrence information were tabulated. Rates of local and distant recurrence among three different receptor subtype categories, ER+ or PR+, HER2 negative; ER-/PR-, HER2 negative; or any ER/PR, HER2 positive were compared using chi-square tests. Results: 437 women with ≤1cm breast tumors were identified. Women with TNBC not given chemotherapy were more likely to have distant recurrence at 9% compared to 2% for ER+ or PR+, HER2 negative and 4% for any ER/PR, HER2 positive. There were no recurrences among the 14 women with ≤1cm TNBC who received chemotherapy. Conclusions: Based on our two institution review, women with ≤1 cm TNBC are at an increased risk for distant recurrence compared to other subtypes when not treated with adjuvant chemotherapy. Further studies to determine the benefit of adjuvant chemotherapy in this population are needed. [Table: see text]

Characterization of weakly hormone receptor (HR)-positive, HER- negative breast cancer (BC) and current treatment strategies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12621-e12621
Author(s):  
Johanna Poterala ◽  
Kari Braun Wisinski
Keyword(s):  
Endocrine Therapy ◽  
Ductal Carcinoma ◽  
Pathologic Complete Response ◽  
Treatment Strategies ◽  
Distant Recurrence ◽  
Axillary Node ◽  
Her2 Status ◽  
Breast Cancers ◽  
Nodal Disease ◽  
Prognostic Information

e12621 Background: HR and HER2 status is critical for determining initial management of BC. Current guidelines define estrogen receptor (ER) and progesterone receptor (PR)+ as ≥1%. Previous reports of small cohorts with low HR+/HER2- disease showed similar rates of pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) as triple negative BC (TNBC). This study aims to further characterize this group of patients (pts), focusing on modern management and breast/axillary pCR rates following NAC. Methods: Pts with newly diagnosed stage I-III, HR+/HER2- BC from 1/1/2009–4/1/2019 were found using the University of Wisconsin Hospital and Clinics Cancer Registry. Medical records were reviewed for demographics, tumor characteristics with quantification level of ER and PR ( < 33%), treatments including NAC and adjuvant chemotherapy (chemo), endocrine therapy, surgery and radiation, and follow-up clinical data. Results: Data reviewed from 2,905 pts: 2,604 (89.6%) were HR+/HER2-, 282 (9.7%) were ER+/PR-, and 19 (0.7%) were ER-/ PR+. A total of 64 pts [median age 54 (22-87), 100% female] met inclusion criteria. At diagnosis, 23 (36%) were anatomic stage 1, 30 (47%) stage II, and 11 (17%) stage III; 18 (28%) had biopsy (bx) proven nodal disease. 57 (89%) had invasive ductal carcinoma; 9 (14%) were ER+/PR+, 43 (67%) ER+/PR-, and 12 (19%) ER-/ PR+. The majority [51 (80%)] received chemo, ~ half with NAC 30 (48%), 1 pt chemo plan was unknown. NAC regimens included an anthracycline (A) and taxane (T) [26 (41%)], a sole A regimen [1 (1%)], and an A+T and platinum regimen [3 (5%)]. 4 pts received capecitabine after NAC. 50 (78%) pts had a sentinel lymph node bx, but 13 (20%) had an axillary node dissection (ALND). 10 (16%) pts did not receive any endocrine therapy, 28 (44%) got tamoxifen, 22 (34%) an aromatase inhibitor, and 4 (6%) unknown. Of 28 pts who had NAC followed by breast and axillary surgery, 12 (43%) had pCR (ypT0/Tis/ypN0). Of the 12 pts who had bx proven nodal disease at diagnosis and NAC, 7 (64%) pts had pCR at the axilla. One pt had progressive disease on NAC, 1 had local recurrence and 8 (13%) pts had distant recurrence. Median time to recurrence was 13.6 (5.6 – 48.7) months. Only 2 pts with pCR had distant recurrence. Conclusions: BC that are HER2- and weakly HR+ treated with NAC demonstrated an axillary and overall pCR rate more similar to TNBC than breast cancers with strong HR+. Neoadjuvant approaches may reduce need for ALND and pCR may provide important prognostic information. Clinical trials should be developed to focus on this unique patient cohort.

Impact of exogenous female hormone use (EHU) on breast cancer (BC) recurrence as assessed by the 21-gene assay (Oncotype DX).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 563-563
Author(s):  
Wendy M. Ledesma ◽  
Adedayo A. Onitilo ◽  
Chong Zhang ◽  
KyungMann Kim ◽  
Molly Andreason ◽  
...  
Keyword(s):  
Early Stage ◽  
Hormone Replacement ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
T Test ◽  
Oncotype Dx ◽  
Her2 Receptor ◽  
Significance Level ◽  
Gene Assay ◽  
Hormone Use

563 Background: Observational studies suggest that EHU, such as oral contraceptive (OCPs) or postmenopausal hormone replacement therapy (HRT), increases the risk of developing BC. However, the prognosis of women taking EHU compared to nonusers remains controversial. The Oncotype Dx 21-gene assay RS predicts the distant recurrence risk for early stage, HR+ BC. We assessed RS in patients (pts) on EHU at diagnosis (users) vs nonusers. Methods: Retrospective chart review was conducted on BC pts with a RS, diagnosed 2005–2010. Stage, grade, estrogen (ER), progesterone (PR) and HER2 receptor status were abstracted. Manual review of medications, as well as electronic data pull within ≤5yrs of diagnosis, defined users as pts on EHU within 1 yr of diagnosis for ≥1 yr. Nonusers had been on EHU > 5 yrs before diagnosis or never. Comparisons between EHU users and nonusers were made using two-sample tests; chi-square or Fisher’s exact test for discrete data such as stage and ER status and t-test or Wilcoxon rank sum test for continuous data such as RS. All tests were at a two-sided significance level of 0.05. Results: 495 pts had RS. EHU was documentable for 475, 77 were using exogenous hormone at diagnosis. Type of hormone use included systemic HRT (48%), OCPs (36%), other (4%), and unknown (12%). For users vs nonusers, mean RS was 17 vs 19, (p=0.007, t-test). See table for other predictors. Conclusions: Prior study shows21-gene assay predict distant recurrence risk for HR+BC. In our study, an association existed between EHU and lower RS, suggesting that BC developing on EHU may have less risk of recurrence. Prospective evaluation is warranted. [Table: see text]

A comparative analysis of distant recurrence risk assessments by Oncotype DX recurrence score alone and integrated with clinicopathologic factors in early-stage breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 598-598 ◽  
Author(s):  
Ciara Marie Kelly ◽  
Rose Beamish ◽  
John McCaffrey ◽  
Martina SMITH ◽  
John Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Score ◽  
Risk Groups ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Oncotype Dx ◽  
Node Negative ◽  
Er Positive ◽  
Clinicopathologic Factors ◽  
Oncotype Dx Recurrence Score

598 Background: Treatment planning for patients with node negative, ER-positive, HER-2 negative breast cancer often incorporates the use of prognostic and predictive tools like Oncotype DX. Prior to the availabilty of Oncotype DX, clinicopathologic factors such as age, nodal status, tumour size and grade were used to determine risk of recurrence (ROR). RSPC represents a validated formal integration of oncotype DX recurrence score (RS) and clinicopathologic factors that further refines prognostic accuracy. RSPC does not improve the prediction of likelihood of chemotherapy benefit. The objective of this study was to compare distant recurrence risk assessment by RS and RSPC. Methods: We included patients with node negative, ER-positive, HER2-negative breast cancer who had Oncotype DX testing routinely or on clinical trial. We retrospectively reviewed patient charts and extracted clinicopathological and RS data. We calculated the RSPC using the RSPC educational tool. A comparative analysis was performed looking at the statification of patients into low (LR), intermediate (IR) and high (HR) ROR groups by RS and RSPC. The cut offs for low, intermediate and high risk by the RSPC were set to less than 12%, 12-20% and more than 20% risk of distant recurrence at 10yrs, corresponding to the risks of recurrence associated with the RS categories. Results: We identified 658 patients from 5 academic hospitals in Ireland and the US. Oncotype DX RS classified the following proportions of patients into three risk groups for distant recurrence: LR, n=334 (50.5%), IR, n=259 (39.4%), HR, n=67 (10.1%). RSPC classified the following proportion of patients into the three risk groups for recurrence: LR, n= 455 (69.1%), IR, n=110 (16.7%), HR, n=93 (14.1%). RSPC reclassified 72.6% (n=188) of the IR group (59.1% (n=153) from IR to LR and 13.5% (n=35) from IR to HR). RPSC reclassified 10.5% (n=35) of the LR group (8.1% (n=27) from LR to IR, and 2.4% (n=8) from LR to HR). RSPC reclassified 25.3% (n=17) of the HR group (17.9% (n=12) from HR to IR, and 7.4% (n=5) from HR to LR). Conclusions: RSPC reclassified 240 patients (36.5%) and was most helpful reassigning the IR group.

Performance of Oncotype Dx test in patients with T1bN0, grade 1, hormone receptor-positive, HER2-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12043-e12043
Author(s):  
Vinay K. Gudena ◽  
Lindsey Causey ◽  
Dawn Stuart ◽  
Keisha Martini
Keyword(s):  
Hormone Receptor ◽  
Oncotype Dx ◽  
Cancer Center ◽  
Breast Cancers ◽  
Ki 67 ◽  
Tumor Registry ◽  
Hormone Receptor Positive ◽  
Stage Ia ◽  
Her 2 ◽  
Cancer Network

e12043 Background: NCCN (National comprehensive cancer network) recommends to consider Oncotype DX testing for patients diagnosed with T1bN0 stage 1A breast cancers that are hormone receptor positive and HER-2 negative. This study is a retrospective review of these patients diagnosed at Cone Health Cancer Center between 2012 and 2018 who had Oncotype DX testing. Methods: Patients with T1b hormone receptor positive and HER-2 negative breast cancers, who had Oncotype DX testing performed were queried from tumor registry from 2012 to 2018. Registry provided data on the patients ER/PR and Her 2 neu as well as whether they received chemotherapy. Patient charts were reviewed for grade, Ki 67 and their Oncotype Dx scores. Results: A total of 104 patients with T1b N0 (stage IA ) invasive breast cancers that were ER and PR positive and HER-2 negative between 2012 and 2018 had Oncotype DX test performed. Grade 1 tumors comprised 75 patients. Among these, four patients received adjuvant chemotherapy who had Oncotype scores of 22, 27, 29 and 38. Among patients with Ki 67 ≤ 10% and grade 1, only one patient out of 104 required chemotherapy. Conclusions: This retrospective analysis suggests that 97% of patients with T1b, grade 1, ER/PR positive, HER-2 negative breast cancers had Oncotype scores of less than 25. Hence Oncotype testing may be safely omitted for this group. Grade along with Ki 67 can identify a subset of T1bN0 ER/PR positive and Her 2 negative patients who do not need Oncotype testing.[Table: see text]

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