scholarly journals First Prospective Multicenter Italian Study on the Impact of the 21‐Gene Recurrence Score in Adjuvant Clinical Decisions for Patients with ER Positive/HER2 Negative Breast Cancer

2017 ◽  
Vol 23 (3) ◽  
pp. 297-305 ◽  
Author(s):  
Maria Vittoria Dieci ◽  
Valentina Guarneri ◽  
Tommaso Giarratano ◽  
Marta Mion ◽  
Giampaolo Tortora ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Score ◽  
Clinical Decisions ◽  
Italian Study ◽  
Er Positive ◽  
The Impact

scholarly journals Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah M. Bernhardt ◽  
Pallave Dasari ◽  
Danielle J. Glynn ◽  
Lucy Woolford ◽  
Lachlan M. Moldenhauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Menstrual Cycle ◽  
Recurrence Score ◽  
Gene Signature ◽  
Ovarian Cycle ◽  
Oncotype Dx ◽  
Mammary Tumours ◽  
Er Positive ◽  
The Impact

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.

A novel approach for 21-genes testing associated with prognosis in Chinese patients with ER-positive/HER2-negative breast cancer: A real-world study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12528-e12528
Author(s):  
Yinduo Zeng ◽  
Qian Li ◽  
Jiannan Wu ◽  
Heran Deng ◽  
Ying Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Recurrence Score ◽  
Risk Groups ◽  
Chinese Version ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Er Positive ◽  
The Impact

e12528 Background: We previously reported a Chinese version of 21-genes Recurrence Score (RS) provides reduction chemotherapy prescription in patients with ER-Positive/HER2-Negative node negative breast cancer, while Oncotype Dx was hardly to be reached. However, the impact on clinical outcome was not mentioned. Herein, we explored whether this 21-genes recurrence score (RS) impacted on prognosis in patients with this molecular subtype of breast cancer. Methods: From Jan 2013 to Aug 2018, 378 patients with ER-Positive/HER2-Negative early stage breast cancer were enrolled. All patients received a Chinese version of 21-genes RS test, which is a new method using RNA extracted from formalin-fixed paraffin-embedded tissue performed by SurExam Campany, Guangzhou, China. . The RS score for each patient was calculated based on expression level of 21-genes used in a prosperctively defined algorithm and calculate a recurrence score range from 0 to 100 and divided three risk groups according to TAILORs study.Distant metastases-free survival (DMFS) were correlated with the 21-genes RS by Kaplan-Meier (log-rank method), and Cox regression. Multivariable logistic regression was performed to determine factors correlated with RS testing and receipt of a high-risk RS. Results: Median patient age was 46 years (18 to 77 years). The Chinese version of 21-gene RS was generated for 378 patients: 61 (16.1%) low risk ( < 11), 241 (63.8%) intermediate risk (11 to 25), and 76 (20.1%) high risk (≥ 26). At a median follow-up of 40 months, the 4-year-rate of estimated DMFS was 100%, 98.7% and 92.9% in low risk, intermediate risk and high risk groups. Meanwhile, there was no difference in RFS among three risk groups. For all patients, 21-gene RS was associated with DMFS ( P = .021). In multivariable Cox regression models, 21-gene RS was independently prognostic factor of DMFS (hazard ratio, 5.375; 95% CI, 1.00 to 28.84; P = .05). Tumor size (>2cm vs ≤2cm, OR = 2.31, P = .005), high grade ( OR = 2.15, P = .013), ki67 index ( > 14% vs ≤14%, OR = 4.24, P = .002), progesterone receptor expression ( < 20% vs ≥20%, OR = 5.07, P < .001) were predictor of high risk of RS. Conclusions: The Chinese version of 21-genes RS is independently prognostic factor for DMFS patients with ER–positive/HER2-negative node negative breast cancer. Future study was needed to explore the impact of 21 gene RS on long-term prognosis.

Estrous cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

2020 ◽  
Author(s):  
Sarah M Bernhardt ◽  
Pallave Dasari ◽  
Danielle J Glynn ◽  
Lucy Woolford ◽  
Lachlan M Moldenhauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Menstrual Cycle ◽  
Recurrence Score ◽  
Premenopausal Women ◽  
Gene Signature ◽  
Ovarian Cycle ◽  
Oncotype Dx ◽  
Mammary Tumours ◽  
Er Positive ◽  
The Impact

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.

The effect of non-oncology drugs on clinical and genomic risk in early luminal breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12505-e12505
Author(s):  
Barliz Waissengrin ◽  
Ido Wolf ◽  
Tamar Zahavi ◽  
Mali Salmon‐Divon ◽  
Amir Sonnenblick
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Recurrence Score ◽  
Luminal Breast Cancer ◽  
Breast Cancer Patients ◽  
Clinical Risk ◽  
Er Positive ◽  
The Impact ◽  
Genomic Risk

e12505 Background: In women with ER-positive, HER2-negative early stage breast cancer (BC), treatment decisions for adjuvant chemotherapy are based on genomic risk and clinical risk. Recently, an effect of non-oncology medications on cancer cell lines and cancer outcome have been suggested. In this study we aimed to systematically examine the impact of non- oncology drugs on clinical risk and genomic risk (based on OncotypeDx recurrence score [RS]) in early BC. Methods: We collected data from 1385 files of ER positive HER2 negative breast cancer patients regarding their clinical risk (stage and grade), genomic risk (OncotypeDx RS) as well as data regarding medications the patients received during the month before their surgery. Statistical analysis was applied to identify the influence of various medications on OncotypeDx RS. Results: Out of the various medications we examined, we found that Levothyroxine was significantly associated with high median OncotypeDx RS (RS median = 25 ;p < 0.0001) and Metformin was associated with low median OncotypeDx RS (RS median = 12 p < 0.0011) in comparison to patients not receiving these medications (RS median = 17). By contrast there were no differences in the clinical risk between patients who received Metformin or Levothyroxine. Notably, Levothyroxine and metformin did not impact proliferation marker (Ki67) levels but did impact progesterone-related features, suggesting they influence genomic risk through estrogen dependent modules. Indeed, scores of other genomic tests (PAM50, Mammaprint), which are determined largely by proliferative features, were not influenced by Levothyroxine or Metformin. Finally, by using contemporary guidelines to recommend adjuvant chemotherapy based on clinical risk and genomic risk (OncotypeDx ) we show that patients (Age > 50) who received Metformin treatment had 14.5% chance to be recommended adjuvant chemotherapy while patients who received Levothyroxine had 49% (p = 0.0001). Conclusions: The results of this study indicate significant impact of Metformin and Levothyroxine on clinical decisions with potential impact on early BC patients.

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