scholarly journals Application of the 21-Gene Recurrence Score in Patients with Early HR-Positive/HER2-Negative Breast Cancer: Chemotherapy and Survival Rate According to Clinical Risk

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4003
Author(s):  
Soong June Bae ◽  
Sung Gwe Ahn ◽  
Jung Hwan Ji ◽  
Chihhao Chu ◽  
Dooreh Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Group ◽  
Recurrence Score ◽  
Rank Test ◽  
Breast Cancer Chemotherapy ◽  
Clinical Risk ◽  
Her2 Breast Cancer ◽  
Significant Difference ◽  
High Clinical Risk ◽  
The Impact

We assessed the impact of 21-gene Recurrence Score (RS) assay on chemotherapy decision-making according to binary clinical risk stratification in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. We included patients with tumors measuring 1–5 cm, N0-1, and HR+/HER2- breast cancer who underwent surgery followed by adjuvant treatment. The clinical risk was determined by a modified version of Adjuvant! Online. We performed propensity score matching (PSM) according to the application of 21-gene RS separately in the low and high clinical risk groups. Before PSM, 342 (39.0%) of 878 patients were classified as having high clinical risk. In the high clinical risk group, 21-gene RS showed a significantly reduced chemotherapy rate of 39.3%, without increasing the recurrence. After PSM, the 21-gene RS application significantly reduced chemotherapy rate by 34.0% in 200 patients with high clinical risk (21-gene RS application, 32.0% vs. no 21-gene RS application, 66.0%, p < 0.001). There was also no significant difference in RFS according to 21-gene RS status in the high clinical risk group (log-rank test, p = 0.467). These results support the usefulness of the 21-gene RS to reduce the chemotherapy rate without adversely affecting prognosis in a high clinical risk group.

scholarly journals Correlation of the pathological response rate with the global disease and survival of patients with sub type her2 breast cancer submitted to neoadjuvant chemotherapy at hospital de câncer de Pernambuco

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Juliana Beatriz de Oliveira Ferreira ◽  
Jose Peixoto ◽  
Carolina de Souza Vasconcelos ◽  
Tainan de Morais Bispo
Keyword(s):  
Breast Cancer ◽  
Response Rate ◽  
Statistical Significance ◽  
Pathological Response ◽  
Time Data ◽  
Recurrence Rates ◽  
Logrank Test ◽  
Her2 Breast Cancer ◽  
Significant Difference ◽  
The Impact

Introduction: QT NEO starts from the premise of tumor downstaging, enabling excision of previously unresectable tumors, reducing surgical extension and, consequently, enabling higher rates of conservative surgery. It also allows an in vivo assessment of the neoplastic response to systemic therapy. PCR is a powerful indicator of the benefit of QT NEO and is associated with better outcomes for relapse, DFS and OS. Objectives: This study aimed to evaluate the pathological response rate of patients with CM HER2 who underwent QT NEO, treated at HCP in the years 2014-2016 and to correlate with the recurrence rates, DFS and OS, observing whether the data are in agreement with those reported in the literature. Methods: The study evaluated patients with BC HER2, confirmed by IHC and/or FISH, who underwent QT NEO followed by surgery from 2014 to 2016, treated at the HCP. It is a retrospective, observational, and descriptive study. The information collected comes from a questionnaire formulated by the researcher with the relevant points to be analyzed in the project. The data were stored and analyzed using SPSS, version 20.0. The Kolmogorov-Smirnov test, χ2 test or Fisher’s exact test were used to assess the variables. The DFS and OS time data were represented by the Kapplan-Meier curves and the Logrank test was used to verify a significant difference between the categories with or nPRC. A significance level of 5% was assigned to it. Results: The medical records of 58 patients with BC subtype HER 2 who received QT NEO followed by surgery were analyzed. During a mean follow-up of 35 months, 5 (8.6%) local recurrences and 20 (34.5%) distant ones and 18 deaths from breast cancer (31%) were observed. A result of 50% of PRC was achieved, with no correlation of statistical significance between age, histological type, nuclear grade, staging prior to QT NEO and chemotherapy regimen used. The PRC group achieved lower recurrence rates (20.68 vs. 51.72%) with statistical significance. DFS in the PRC group is 75.9% and in the nPRC group it is 44.82%. OS of the group with PRC is 82.7 vs. 48.2% in the nPRC group. Patients with HR- and PRC were the ones that most benefited from obtaining PRC in the recurrence and DFS outcomes, reaching recurrence rates of 22% and DFS of 77.8% compared to the HR group – without PRC, which had recurrence rates of 72% and DFS of 27.3%. Conclusion: This study found significant data with lower recurrence rates and better rates of DFS and OS in patients who achieved PRC, thus evidencing the impact that PRC has on long-term outcomes, especially in the HR- subgroup of patients.

Analysis of factors related to adjuvant chemotherapy decision in early breast cancer patients with intermediate recurrence score.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12032-e12032
Author(s):  
Feilin Qu ◽  
Jiayi Wu ◽  
Xiaosong Chen ◽  
Ou Huang ◽  
Jianrong He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Predictive Factors ◽  
Molecular Subtype ◽  
Recurrence Score ◽  
Tumor Grade ◽  
Clinical Risk ◽  
Gene Assay ◽  
High Clinical Risk

e12032 Background: The 21-gene Recurrence Score (RS) assay has been routinely used to guide systemic chemotherapy in patients (pts) with estrogen receptor positive, node-negative early breast cancer (EBC). However, there has been less clarity in recommendation of adjuvant chemotherapy (ACT) in pts with intermediate RS (IRS). According to the definitions of IRS in retrospective NSABP B14, B20 trials and prospective validation of TAILORx trial, we adopted the broaden cut-offs of 11-30 in our study. We sought to analyze the factors related to ACT decision in this subset of pts. Additionally, the role of Adjuvant!Online (AOL) was evaluated in ACT decision. Methods: A cohort of 564 pts with RS of 11-30 was retrospectively analyzed from January 2014 to October 2016 in Ruijin Hospital Shanghai Jiaotong University School of Medicine. The Oncotype DX RS, a RT-PCR 21-gene assay, was performed on RNA extracted from formalin-fixed paraffin-embedded tissue. The AOL was used to determine pts’ clinical risk. Predictive factors of chemotherapy usage in different clinical risk catogories were also assessed. Results: 267 (47.3%) pts received chemotherapy. Age, tumor grade, pathologic type, pT, pN, molecular subtype and RS were significantly correlated with ACT decision ( p <0.05). These factors were all independent predictors of ACT usage ( p<0.05) in mutivariable model. AOL was successfully measured in 504 (89.4%) pts, of whom 279 (49.5%) were at low clinical risk and 225 (39.9%) had high clinical risk. The distribution of RS correlated significantly with AOL clinical risk catogories. The predictive factors of ACT administration in high and low clinical risk subgroups were highly consistent with the overall population, except pT in high clinical risk pts. Discordances between clinical risk and ACT decision were found in 158 pts (28.0%), probably due to different age, molecular subtype and RS. Conclusions: Age, tumor grade, pathologic type, pT, pN, molecular subtype and RS were independent predictors of ACT administration in EBC pts with IRS. AOL should not be used alone to aid chemotherapy decision in this subset of pts.

Prospective WSG phase III PlanB trial: Final analysis of adjuvant 4xEC→4x doc vs. 6x docetaxel/cyclophosphamide in patients with high clinical risk and intermediate-to-high genomic risk HER2-negative, early breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 504-504 ◽  
Author(s):  
Nadia Harbeck ◽  
Oleg Gluz ◽  
Michael R. Clemens ◽  
Wolfram Malter ◽  
Toralf Reimer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Triple Negative ◽  
Recurrence Score ◽  
Final Analysis ◽  
Clinical Risk ◽  
Central Pathology ◽  
High Clinical Risk

504 Background: Optimal chemotherapy in HER2-negative, particularly HR-positive, early breast cancer (EBC), especially the survival impact of anthracyclines, is still a matter of debate. Retrospective analyses saw most benefit of 6xCEF vs. 6xCMF in HER2+ EBC. Prospective trials have shown conflicting results; no predictive molecular factors have been validated so far, particularly for HR+ EBC. The WSG PlanB trial is the first trial that randomized only patients with high clinical risk or with Recurrence Score >11 in the HR+/HER2- subgroup (pN0-1). Patients with RS<11 (pN0-1) had an excellent prognosis (five-year DFS of 94%) with endocrine therapy alone (Gluz et al. ASCO 2016). Methods: The WSG PlanB trial was originally planned as a non-inferiority study for comparison of 6 cycles of anthracycline-free TC (Arm A) vs. standard anthracycline-taxane based chemotherapy (4xEC→4xDoc) (Arm B) in patients with high-risk pN0 (T2-4, G2-3, <35 years, or high uPA/PAI-1) or pN+ HER2- EBC. Following an early amendment, Oncotype DX was performed in all HR+ tumors, and omission of chemotherapy (CT) was recommended in RS≤11 HR+ pN0-1 disease. Primary endpoint was DFS, defined as time to any recurrence, secondary cancer or death. Final analysis for the CT randomization was planned after completed 5-year follow-up in all patients. Results: From 2009 to 2011, PlanB enrolled 3198 patients (n=3073 with central pathology review). In 348 patients (15.3%), CT was omitted based on RS≤11. 2449 patients were randomized to 6xTC (n=1222) and 4xEC→4xDoc (n=1227). Within this cohort, 41% were pN+, 42% had G3 tumors and 18% HR-negative tumors by central pathology. After median follow-up of 61 months, very similar five-year DFS of 89.9% [88.1%-91.7%] vs. 90.2% [88.4%-92.0%] and five-year OS of 94.7% [93.4%-96.1%] vs. 94.6% [93.2%-96.0%] were observed in Arms A vs. B. Five treatment-related deaths were observed in Arm A (TC) vs. one in Arm B (EC-Doc) (0.4% vs. 0.1%), despite a trend to more SAE’s in Arm B vs. Arm A (n=397 vs. 358). Although recurrence score is a strong prognostic factor, it was not predictive for anthracycline efficacy; no efficacy differences between the study arms were observed in (locally) triple-negative patients or in those with >4 involved lymph nodes, despite the prognostic impact of these factors. Conclusion: In the WSG PlanB trial, patients with early HER2-negative BC seem to be sufficiently treated by six cycles of docetaxel/cyclophosphamide compared to four cycles of EC followed by four cycles of docetaxel -- no efficacy differences are evident in high-risk subgroups defined by triple-negative status, nodal status, or high Recurrence Score. Further prospective studies are urgently needed before final conclusions for impact of anthracyclines in HER2-negative BC can be drawn. Clinical trial information: NCT01049425.

Impact of clinical risk category on prognosis and prediction of chemotherapy benefit in early breast cancer (EBC) by age and the 21-gene recurrence score (RS) in TAILORx.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 503-503
Author(s):  
Joseph A. Sparano ◽  
Robert James Gray ◽  
Della F. Makower ◽  
Tracy G. Lively ◽  
Thomas James Saphner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Risk Category ◽  
Low Grade ◽  
Prognostic Information ◽  
Clinical Risk ◽  
Prognosis And Prediction ◽  
High Clinical Risk ◽  
Clinical Trial Information

503 Background: TAILORx established that endocrine therapy (ET) alone is non-inferior to adjuvant chemotherapy (CT) plus ET in EBC and a 21-gene RS of 11-25, with some benefit if ≤50 years (y) with RS 16-25 (PMID: 29860917). We evaluated whether clinical risk (tumor size & histologic grade) provides additional prognostic information to RS, a secondary trial objective. Methods: Clinical risk by was assessed by Adjuvant! (version 8.0) using MINDACT criteria (PMID 27557300), defined as low clinical risk (LCR - tumor ≤3 cm and low grade, <2 cm and intermediate grade, or ≤1 cm and high grade) or high clinical risk (HCR -not meeting LCR criteria). Results: Of 9427 women with RS and clinical risk information, 70% were LCR and 30% HCR, with comparable distribution by age ( ≤50 vs. >50). The RS was 26-100 in 9% of LCR and 27% of HCR patients, with similar distributions by age. Although LCR/HCR provided additional prognostic information in each RS category for iDFS, including RS 0-10 (9-year rates 86.7% vs. 75.7% LCR vs. HCR), 11-25 (85.4% vs. 78.9%), and 26-100 (82.0% vs. 70.4%), iDFS rates were similar irrespective of CT (no vs. yes) in the entire RS 11-25 cohort whether LCR (85.8% vs. 85.1%) or HCR (79.8% vs. 77.9%). DRFI rates were also similar irrespective of CT in the RS 11-25 cohort or > 50y group whether LCR (96.0% vs. 96.1% overall; 96.5% vs. 96.0% > 50y) or HCR (92.3% vs. 89.9% overall; 91.7% vs. 90.7% >50y). For women ≤50y, the absolute reduction in distant recurrence from CT with a RS of 16-20 (N=923) was -0.2% (standard error [SE]±2.1%) for LCR vs. 6.5%(SE±4.9%) for HCR (vs. 1.6%[SE±1.9%] overall), whereas for a RS 21-25 (N=492) it was 6.4% (SE±4.9%) for LCR vs. 8.6% (SE±6.2%) for HCR (vs. 6.5%[SE±3.7%] overall). Conclusions: Clinical risk stratification provides additional prognostic information to the 21-gene RS, but not prediction of CT benefit in the overall TAILORx population or those > 50y, and facilitates more refined estimates of absolute CT benefit for women ≤50y with a RS 16-25. (Funded by National Cancer Institute, Komen Foundation, Breast Cancer Research Foundation). Clinical trial information: NCT00310180.

Validation of the 21-Gene Recurrence Score Assay in Patients with Hormone Receptor-Positive, HER2-Negative Breast Cancer and 0 to 3 Positive Lymph Nodes – Risk Pattern and Outcomes on a Community Level

Breast Care ◽  
2021 ◽  
Author(s):  
Michael Braun ◽  
Antonia Kriegmair ◽  
Nina Szeterlak ◽  
Anne Andrulat ◽  
Simone Schrodi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Endocrine Therapy ◽  
Disease Free Survival ◽  
Recurrence Score ◽  
Nodal Status ◽  
World Population ◽  
Her2 Breast Cancer ◽  
Significant Difference ◽  
Positive Lymph Nodes

Introduction The aim of the present study was to analyze the performance of Oncotype DX® multigene assay (ODX) in patients with 0-3 lymph nodes in a high volume community hospital. Methods Patients with non-metastatic HR+/HER2- EBC and 0-3 positive lymph nodes, who underwent primary surgery at the Red Cross Hospital Munich, Germany and consecutively had ODX testing were included in this retrospective study. The distribution of clinico-pathologic characteristics, recurrence score (RS) risk and use of systemic therapy were compared among patients without positive lymph nodes (N0) and patients with micrometastases or 1 to 3 positive lymph nodes (N1). Disease free survival (DFS) and overall survival (OS) were estimated. Results From 2012 to2017 ODX was consecutively performed in 575 (16.4%) of 3492 women with HR+/ HER- EBC, of which 553 were eligible for this analysis (N0: 60.8%; N1: 39.2%). Among the patients included, 441 (79.7%) had a RS of 0 to 25 and 112 (20.3%) had a RS of 26 or higher. In patients with RS 0 to 25 the rate of chemotherapy use was low, independent from nodal status (N0: 17.1% and N1: 19.1%) and 5y-DFS was 90.5% and 91.7% for N0 and N1 patients, respectively. There was no significant difference in DFS (90.5% vs. 93.3%; p= 0.101) or OS (97.2% vs. 96.0%; p= 0.737) for patients with a RS 0 to 25 when treated with chemo-endocrine therapy or endocrine therapy alone, independent from nodal status. Conclusions The results of the study confirm the observations from randomized studies on the use of the ODX in a real world population in terms of risk distribution and patient outcome. Adjuvant chemotherapy could be safely omitted in patients with HR+/HER2- breast cancer with 0-3 positive lymph nodes and RS<25.

scholarly journals Carboplatin dose capping affects pCR rate in HER2-positive breast cancer patients treated with neoadjuvant Docetaxel, Carboplatin, Trastuzumab, Pertuzumab (TCHP)

2020 ◽  
Vol 184 (2) ◽  
pp. 481-489
Author(s):  
Sacha J. Howell ◽  
Faye Coe ◽  
Xin Wang ◽  
Laura Horsley ◽  
Maria Ekholm
Keyword(s):  
Breast Cancer ◽  
Area Under The Curve ◽  
Dose Intensity ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Significant Difference ◽  
The Impact ◽  
Carboplatin Dose

Abstract Purpose Estimated glomerular filtration rate (eGFR) is commonly used to calculate carboplatin doses and capping the eGFR may be used to reduce the risk of excessive dosing and toxicity. We sought to retrospectively examine the impact of our carboplatin guidelines on pathological complete response rates (pCR) and toxicity in women with HER2+ breast cancer receiving neoadjuvant docetaxel, carboplatin, trastuzumab and pertuzumab (TCHP). Methods The delivered area under the curve (dAUC) was calculated [(actual carboplatin dose at cycle 1 ÷ dose calculated with uncapped/unbanded eGFR) × 6] and dichotomized at the median value. The impact of this and other clinical factors on pCR rate, dose intensity (DI) and toxicity was assessed. Results 124 eligible patients were identified of whom 63.7% (79/124) achieved pCR. The median dAUC at cycle 1 was 5.75 mg × ml/min. Those with lower dAUC were more frequently younger and overweight/obese. Patients with lower dAUC had significantly inferior pCR rates of 54.8% (34/62) vs 72.6% (45/62), respectively (p = 0.040). Similar results were seen in the ER+ subgroup; 45.2% (19/42) vs 68.3% (28/41), p = 0.037%, whereas no significant difference was seen among ER- patients; 75.0% (15/20) vs 81.0% (17/21), p = 0.72. DI and toxicity were comparable between the two dAUC groups. Conclusions The overall pCR rate was high in patients with HER2+ breast cancer receiving the TCHP regimen; however, carboplatin dose capping resulted in inferior pCR rates, particularly in the ER+ subgroup. To ensure optimal dosing, isotopic measurement of renal function is warranted in patients who would otherwise have their eGFR and dose capped.

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.

Practice-changing use of 21-gene oncotype DX breast recurrence score assay in a public hospital in Brazil: Results of 155 cases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12518-e12518
Author(s):  
Andre Mattar ◽  
Guilherme Ribeiro Fonseca ◽  
Murilo Barato Agudo Romão ◽  
Jorge Yoshinori Shida ◽  
Monica Maria Agata Stiepcich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Public Hospital ◽  
Recurrence Score ◽  
Treatment Recommendations ◽  
Clinical Risk ◽  
Post Surgery ◽  
Gene Assay ◽  
Gene Test ◽  
Score Result ◽  
The Impact

e12518 Background: The 21-gene assay estimates risk of recurrence expressed as a Recurrence Score result between 0 and 100. The assay is clinically validated to predict chemotherapy (CT) benefit in node-negative (N0) and node-positive (up to three axillary nodes, N1) hormone receptor-positive (HR+) early-stage breast cancer (ESBC). The TAILORx study, which randomized 6711 women with N0 ESBC and Recurrence Score result 11-25 to hormonal therapy (HT) ± CT, demonstrated that patients older than 50 years derived no benefit from CT+HT, although younger patients with Recurrence Score result 16-25 may derive some benefit. The 21-gene assay has been incorporated in practice guidelines worldwide, based on evidence of clinical utility in N0 and N1 ESBC. We evaluated the impact of the 21-gene test on treatment decisions for patients with N0 and N1 ESBC at Sistema Único de Saúde in Brazil. Methods: Eligible patients were post-surgery with T1/T2 tumors, had HR+, HER2−, N0 or N1 ESBC, and were candidates for adjuvant systemic therapy. Treatment recommendations, CT+HT or HT alone, were captured before and after 21-gene test results. All patients were seen at Pérola Byington Hospital, a public hospital in São Paulo, Brazil. TAILORx results were used to guide decisions for or against CT for each patient. Results: From 08/2018 to 04/2019, 155 women were enrolled. Patient mean age was 57.6 years (29-78), 116 (75%) were postmenopausal, and 53 (34%) had N1 breast cancer. Based on clinical data alone, 151 patients had pre-assay recommendations of CT. Post-assay, 106 of 151 patients (70%) had changes in CT recommendation: 104 (69%) initially recommended CT received HT alone, and 2 (1%) initially recommended HT alone received CT+HT (Table). Using the modified Adjuvant!Online criteria for clinical risk classification, 109 of 155 patients (70%) had high risk, 48 (44%) of whom received CT. Of 46 patients with low clinical risk, 10 (22%) received CT. CT use trended with histologic grade: 11% with grade 1, 69% with grade 2, and 61% with grade 3. Most of our patients had tumor bigger than 2 cm (61%) with 8% bigger than 4 cm. Conclusions: The change in clinical practice at this public hospital was greater than expected: 69% of initial treatment recommendations were changed with the Recurrence Score result to omit CT. Clinicopathologic criteria did not correlate well with Recurrence Score results and did not identify those most likely to benefit from CT. A cost-effectiveness study is underway at our institution. [Table: see text]

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.

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