scholarly journals The impact of Oncotype DX® recurrence score of paraffin-embedded core biopsy tissues in predicting response to neoadjuvant chemotherapy in women with breast cancer

2016 ◽  
Vol 36 (2-3) ◽  
pp. 65-71 ◽  
Author(s):  
Atilla Soran ◽  
Rohit Bhargava ◽  
Ronald Johnson ◽  
Gretchen Ahrendt ◽  
Marguerite Bonaventura ◽  
...  
BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah M. Bernhardt ◽  
Pallave Dasari ◽  
Danielle J. Glynn ◽  
Lucy Woolford ◽  
Lachlan M. Moldenhauer ◽  
...  

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 568-568 ◽  
Author(s):  
Joseph Gligorov ◽  
Xavier B. Pivot ◽  
Herve L. Naman ◽  
William Jacot ◽  
Dominique Spaeth ◽  
...  

568^ Background: The 21-gene Oncotype DX Recurrence Score (RS) is a validated assay to help inform the appropriate treatment of estrogen receptor-positive (ER+), early stage breast cancer in the adjuvant setting. Treatment traditions regarding choice of adjuvant treatment vary significantly in different countries. This prospective multicenter study is the first to assess the impact of using the Oncotype DX assay in the French clinical setting. Methods: A total of 100 consecutive patients with ER+, HER2-negative, node negative or pN1 (mi) breast cancer were enrolled. Overall treatment recommendation change, change from chemoendocrine to endocrine alone and change from endocrine alone to chemoendocrine treatment were recorded. Medical oncologists completed questionnaires regarding their confidence in their recommendation before and after knowing the patient’s RS. A preliminary analysis was conducted on the first 92 evaluable patients with data available at the time of abstract submission. Final data will be presented at the meeting. Results: Prior to Oncotype DX 49% of patients were recommended chemoendocrine treatment and 51% endocrine treatment alone. After having the RS, 26% were recommended chemoendocrine treatment and 74% endocrine treatment alone. The overall reduction in chemotherapy recommendation from 49% to 26% was significant (p<0.001). Of patients originally recommended chemoendocrine treatment, 58% were changed to endocrine treatment alone after having the RS. Of patients originally recommended endocrine treatment, 11% were changed to chemoendocrine treatment after receiving the RS. There was a significant improvement in physician confidence in treatment recommendations (p=0.002) when using Oncotype DX. Conclusions: These are the first prospective data regarding the impact of using Oncotype DX in France. Using Oncotype DX was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. The data are consistent with those presented from Germany, Spain, the UK and the US.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 565-565
Author(s):  
Jeffrey L. Vacirca ◽  
Michaela L. Tsai ◽  
Adam Brufsky ◽  
Richard Alan Michaelson ◽  
Frederick P. Smith ◽  
...  

565 Background: Genomic assays such as the 21-gene breast cancer assay (Oncotype DX), have improved the ability to individualize pt treatment based on their individual tumor’s biology. Since 2004, when the 21-gene assay became commercially available, more than 300K assays have been ordered. While several studies have been conducted assessing the impact of having the Recurrence Score (Score) result on treatment decisions, most have been retrospective or evaluating the treatment recommendation. The Oncotype DX Breast Cancer Registry is a large prospective study conducted in clinical practices evaluating the types of pts having the assay ordered and the actual treatments delivered. We report here the first set of analyses. Methods: Pts with ER+ EBC were eligible to enroll. Data collected at baseline (BL) included age, size, grade, ER, PR and HER2 status. Data collected at the 6-month visit included Score and treatment given. Pt demographics, Score distribution, and associations with clinicopathologic (CP) factors are described. Results: A total of 890 pts were enrolled at 15 U.S. sites between 11/09-3/12. 803 eligible pts were included in the analyses. The Table shows BL characteristics, Score distribution and %CT given. Distribution of Score values across the CP factors was similar to the cohort overall. 30% of pts received CT. Among low Score patients, CT was given in 17% of pts <50y, 9% of Grade 3 tumors and 11% of tumors >2cm. Conclusions: A large, prospective registry for pts with EBC receiving the 21-gene breast cancer assay examined the application of the Score to treatment. The Score distribution is consistent with other retrospective cohorts. The association between the Score and the CP factors was modest. The CP factors did not predict the Score. In general, CT decisions followed the Score with the exception of younger pts; 17% received CT despite a low Score. These findings from a real-world cohort underscore the importance of understanding breast cancer biology in order to make more informed and individualized treatment decisions. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12630-e12630
Author(s):  
Serafin Morales Murillo ◽  
Ariadna Gasol Cudós ◽  
Alvaro Rodriguez ◽  
Carles Canosa Morales ◽  
Jordi Melé Olivé ◽  
...  

e12630 Background: Neoadjuvant chemotherapy (NAC) is an optimal option in early breast cancer, but in ER-positive/HER2-negative (luminal) is still controversial, although a survival benefit has recently been observed when a histological response by symmands method type 0 or I is achieved. The 21-Gene recurrence score assay (Oncotype DX) is a validated test to assess the survival benefit of adjuvant chemotherapy in these patients but its role in neoadjuvant setting is not yet well established unknown. We analyze the correlation between Oncotype DX Recurrence Score result and the pathological response assessed by symmands method. Methods: We analyzed a prospective cohort of 63 early luminal breast cancer patients who received NAC after performing an Oncotype DX test. Patients with an Oncotype DX Recurrence Score result lower 11 were excluded. The median age was 54 years (31-84), initial tumor size was 37 mm (12 -97), 41 patients (65%) had initial nodal involvement and the median Ki67 index was 34% (8 – 85). Results: An Oncotype DX results inferior or equal to 25 (considered as a limited benefit of chemotherapy treatment) was observed in 25 patients (40%) and a Recurrence Score higher than 25 in 38 (60%). Pathological response type 0 was achieved in 5 patients (8%) and type I in 16 (25%). A strong correlation between pathological response type 0 and I and Recurrence Score result in the univariate and multivariate analysis (OR 0,946 p:0,023) was found. We have performed a threshold analysis finding the Oncotype DX the most significant predictor of pathological response (AUC:0,75 p:0,0 01 ) compared to Ki67 (AUC:0,61 p:171), Estrogen receptor (AUC:0,41 p:0,21) and initial tumor size (AUC:0,671 p:0,028). All the patients who achieved a complete pathological response had a Recurrence Score result ≥ 26. Conclusions: The Oncotype DX Recurrence Score could be a useful tool to select early breast cancer patients who will benefit from neoadjuvant chemotherapy. Oncotype DX is the most significant predictor variable of pathological response and patients with a Recurrence Score of 25 or greater are five times more likely to obtain a histological response type 0-1 (OR: 5,3 p < 0,016). In our series the Oncotype DX test reaches the highest rate of complete pathological responses in this group of patients.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 514-514
Author(s):  
Tal Sella ◽  
Shari I. Gelber ◽  
Philip Daniel Poorvu ◽  
Hee Jeong Kim ◽  
Yaileen D Guzman Arocho ◽  
...  

514 Background: The 21- gene Breast Recurrence Score predicts benefit from adjuvant chemotherapy in estrogen receptor positive (ER+), HER-2 negative (-) breast cancer (BC). We aimed to examine whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NAC). Methods: We identified patients with stage I-III ER+/HER2− BC treated with NAC from the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤ 40 years. The 21-gene assay was performed on tumor specimens removed prior to NAC either as part of clinical care or retrospectively for research. Pathologic complete response (pCR) was defined as no residual invasive tumor (ypT0/is ypN0). The relationship between Recurrence Score result (RS) and pCR was evaluated using logistic regression modeling. Results: 76 women in the cohort had undergone NAC for ER+, HER2- BC and were eligible for this analysis: 5 had undergone clinical 21-gene assay testing, 71 had banked specimens retrospectively tested. Median age at diagnosis was 36.7 (24.3-40). Most tumors were of ductal histology (78%), high grade (51%), progesterone receptor (PgR) positive (86%), ≥T2 (88%), clinically node positive (74%), and anthracycline and taxane containing protocols were administered in 86% of cases. RS ranged between 5-75 with 50% > 25 and only 4 < 11. Mean RS was significantly higher among tumors achieving pCR vs. non-pCR response (51.9 vs. 26.6, pwilcoxon= 0.0005). pCR rate in patients with RS > 25 was 21% (8/38) vs. 5% in patients with RS < 25 (2/38), with both pCRs in the <25 group in patients with RS 21-25. In univariable analysis, PgR negativity (odds ratio (OR) 5.62, 95% confidence interval (CI) 1.27-24.89, p = 0.02), high grade (OR 9.03, 95%CI 1.07-76.32, p = 0.04) and higher RS as a continuous variable (OR 1.08, 95%CI 1.04-1.13, p = 0.0003) were associated with a greater likelihood of pCR. In multivariable analysis only RS remained significantly associated with pCR (OR: 1.07, 95%CI 1.01-1.12, p = 0.01): a 7% increase in the odds of pCR for every 1-point increase in RS. Conclusions: In young women with ER+, HER2- BC who received NAC, higher pretreatment RS was associated with an increased likelihood of pCR. Genomic expression profiling assays may have a role in decision-making in young women in need of neoadjuvant therapy. For women with low likelihood of benefiting from NAC, alternative approaches are clearly warranted. Given the demonstrated efficacy of neoadjuvant endocrine therapy in post-menopausal women, further evaluation in young women should be pursued.


2020 ◽  
Author(s):  
Sarah M Bernhardt ◽  
Pallave Dasari ◽  
Danielle J Glynn ◽  
Lucy Woolford ◽  
Lachlan M Moldenhauer ◽  
...  

Abstract Background: The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods: ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results: Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p≤0.05) and a significant increase in 21-gene recurrence score (21.8±2.4; mean±SEM) compared to tumours dissected at estrus (15.5±1.9; p=0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p<0.001) and invasion-group (p=0.01) genes, and increased 21-gene recurrence score (p=0.01). These tumours also exhibited higher expression of estrogen-group genes (p=0.005) suggesting increased sensitivity to hormonal fluctuations during the ovarian cycle. Conclusions: Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature and recurrence scores in Mmtv-Pymt murine mammary tumours. Whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage is not yet known. To address this question and ensure young breast cancer patients receive optimal treatment advice, future prospective studies using breast cancer samples from premenopausal women with known cycle stage are required.


2018 ◽  
Vol 26 (2) ◽  
pp. 366-371 ◽  
Author(s):  
Alison M. Pease ◽  
Luis A. Riba ◽  
Ryan A. Gruner ◽  
Nadine M. Tung ◽  
Ted A. James

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