Prospektive Phase-III PlanB-Studie: 5 Jahres Daten zum prognostischen Stellenwert von 21-Gen Recurrence-Score, zentralpathologischem Grading, ER, PR, Ki-67 Review beim frühem Hochrisiko HR+/HER2-negativen Mammakarzinom

2016 ◽  
Vol 13 (02) ◽  
Author(s):  
T Reimer ◽  
O Gluz ◽  
U Nitz ◽  
M Christgen ◽  
RE Kates ◽  
...  
Keyword(s):  
Recurrence Score ◽  
Phase Iii ◽  
Ki 67

Prognostic impact of recurrence score, endocrine response and clinical-pathological factors in high-risk luminal breast cancer: Results from the WSG-ADAPT HR+/HER2- chemotherapy trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 504-504
Author(s):  
Oleg Gluz ◽  
Ulrike Nitz ◽  
Matthias Christgen ◽  
Michael Braun ◽  
Kerstin Luedtke-Heckenkamp ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
High Risk ◽  
Recurrence Score ◽  
Phase Iii ◽  
Luminal Breast Cancer ◽  
Prognostic Impact ◽  
Treatment Intensification ◽  
Ki 67 ◽  
Prospective Phase ◽  
High Risk Cohort

504 Background: In HR+/HER2- N0-1 early BC, postmenopausal patients (pts) with RS™ > 25 and a substantial proportion of premenopausal pts seem to benefit from addition of adjuvant chemotherapy (CT) to endocrine therapy (ET). However, the magnitude of absolute benefit from this treatment intensification seems to depend on clinical-pathological and biological prognostic factors. For the first time, we present outcome from the CT part of the prospective phase III WSG-ADAPT HR+/HER- trial combining both static (RS in baseline core biopsy (CB) and dynamic (Ki67 response) biomarkers to optimize adjuvant therapy in luminal EBC. Methods: Pts with clinically high-risk HR+/HER2- EBC (cT2-4 OR clinically N+ OR G3 OR Ki67>15%) were initially treated by 3 (+/-1) weeks of standard ET (postmenopausal: mostly AI; premenopausal: TAM) before surgery or sequential CB. Pts with cN2-3 or G3/Ki67>40% were randomized directly to the CT trial. pN0-1 pts with RS0-11 OR RS12-25/ET-response (central Ki67postendocrine<10%) received ET alone; the remaining high-risk cohort was randomized to the CT trial: (neo)adjuvant dose-dense CT (4xPaclitaxelà4xEC q2w vs. 8xNab-Paclitaxel q1wà4xEC q2w) followed by ET. Primary endpoint is efficacy comparison of CT schedules for survival; secondary endpoints reported here involve impacts of key prognostic factors on survival. Kaplan-Meier and Cox proportional hazard models were used to estimate survival curves and hazard ratios. For this analysis, subgroups free of selection bias by RS/ET-response were defined. Results: 5625 pts were screened and 4621 (ITT) entered the trial. After 4.9y median follow-up, higher baseline and post-endocrine Ki-67 levels were associated with poorer iDFS (both p < 0.001). In the CT cohort (n = 2331), higher RS, nodal status, and tumor size were generally associated with poorer iDFS. However, iDFS differed between N1 and N0 status only among younger pts (<50 years). In pts with >4 positive LN (n = 390), lower RS was associated with improved iDFS (RS0-11 vs RS > 25: plog-rank= 0.016, 5y-iDFS 90% vs. 64%). In pts with RS > 25 (n = 965), low Ki67postendocrine, N0 status, and c/pT1 status were associated with improved iDFS. In particular, ET-responders had higher 5y-iDFS (84%) than ET-non-responders (77%; plog-rank= 0.040). Younger patients (<50 years old) with N0-1 RS 12-25/ ET-non-responders treated by CT had non-significantly poorer 5-year iDFS (89%) compared to those with ET-response treated by ET only (92%) (plog-rank= 0.249). Conclusion: First results from the prospective high risk cohort from a large prospective phase III ADAPT trial provide evidence for good prognosis in some pts with >4 positive LN and e.g. low RS. Moreover combination of lower post-endocrine Ki-67 and limited tumor burden may be a promising criterion for CT de-escalation strategies even in patients with high RS. Clinical trial information: NCT01779206.

Prospective comparison of recurrence score and independent central pathology assessment of prognostic tools in early breast cancer (BC): Focus on HER2, ER, PR, Ki-67 results from the phase III WSG-Plan B trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 552-552 ◽  
Author(s):  
Oleg Gluz ◽  
Hans Heinrich Kreipe ◽  
Matthias Christgen ◽  
Tom Degenhardt ◽  
Ronald E. Kates ◽  
...  
Keyword(s):  
High Risk ◽  
Recurrence Score ◽  
Phase Iii ◽  
Rt Pcr ◽  
Ki 67 ◽  
Negative Results ◽  
Prospective Comparison ◽  
Plan B ◽  
Central Pathology ◽  
Pai 1

552 Background: Use of multi-gene real-time PCR (RT-PCR) based assays e.g. Recurrence Score (RS) and single markers (grade, uPA/PAI-1, ER/PR, HER2, KI-67) is currently controversially discussed in early BC. Here, we present the final WSG-planB trial correlation analysis of risk assessment tools and first prospective comparison of independent central pathology IHC/FISH assessment and RT-PCR for single markers. Methods: Plan B trial (n=2,448 randomized for 6xTC vs. 4xEC-4xDOC in locally HER2- BC). RS has been used as selection criterion for cht omission in HR+ BC (if RS<11 in pN0 or pN1). uPA/PAI-1 was optionally obtained. Grade, ER/PR, HER2 (IHC/FISH), Ki-67 were evaluated by the independent trial pathologist in all tumors. Results: From 04/09 to 11/11, 3196 patients have been recruited and 2448 randomized. RS distribution in 2551 HR+ tumors: 0-11 (18%), 12-25 (60%), >25 (22%). In 354 pN0-1 patients, cht was omitted based on low risk RS (88% compliance). Central grade for n=3038 and IHC/FISH results are currently available in n=1476. Moderately significant correlations were only found between RS and both central grade (rs=0.313; p<0.001) as well as Ki-67 (rs=0.374; p<0.001) and a weak one for uPA/PAI-1, particularly due to poor correlations within the RS group <26. In 1476 locally HER2- cases, n=9 were found as 3+ and/or FISH+ by central analysis. In 6 HR+/HER2+ cases, RS revealed 2 positive, 2 equivocal and 2 negative results. In 7 cases positive for HER2 by RT-PCR central pathology revealed 4 negative results. 24 locally HR+ cases are assessed as HR- in central pathology (2%). Among these, 6 were ER positive by RT-PCR. Final correlation analyses will be presented at the meeting. Conclusions: These first prospective data demonstrate that high-risk status according to RS is predictive of high risk by other factors, but the converse is not true. Regarding controversial HER2 and HR status by RT-PCR and IHC/FISH, we found few cases with false-negative or positive RT-PCR results in HER2- BC by local pathology. However, these discrepancies could potentially have a substantial impact on clinical patient management.

West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment

2016 ◽  
Vol 34 (20) ◽  
pp. 2341-2349 ◽  
Author(s):  
Oleg Gluz ◽  
Ulrike A. Nitz ◽  
Matthias Christgen ◽  
Ronald E. Kates ◽  
Steven Shak ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Prognostic Markers ◽  
Disease Free Survival ◽  
Recurrence Score ◽  
Outcome Data ◽  
Phase Iii ◽  
Ki 67 ◽  
Free Survival ◽  
Hormone Receptor Positive ◽  
Disease Free

Purpose The 21-gene Recurrence Score (RS) assay is a validated prognostic/predictive tool in early hormone receptor–positive breast cancer (BC); however, only a few prospective outcome results have been available so far. In the phase III PlanB trial, RS was prospectively used to define a subset of patients who received only endocrine therapy. We present 3-year outcome data and concordance analysis (among biomarkers/RS). Patients and Methods Central tumor bank was established prospectively from PlanB (intermediate and high-risk, locally human epidermal growth factor receptor 2–negative BC). After an early amendment, HR-positive, pN0-1 patients with RS ≤ 11 were recommended to omit chemotherapy. Results From 2009 to 2011, PlanB enrolled 3,198 patients with a median age of 56 years; 41.1% had node-positive and 32.5% grade 3 disease. In 348 patients (15.3%), chemotherapy was omitted based on RS ≤ 11. After 35 months median follow-up, 3-year disease-free survival in patients with RS ≤ 11 and endocrine therapy alone was 98% versus 92% and 98% in RS > 25 and RS 12 to 25 in chemotherapy-treated patients, respectively. Nodal status, central and local grade, the Ki-67 protein encoded by the MKI67 gene, estrogen receptor, progesterone receptor, tumor size, and RS were univariate prognostic factors for disease-free survival; only nodal status, both central and local grade, and RS were independent multivariate factors. Histologic grade was discordant between central and local laboratories in 44%. RS was positively but moderately correlated with the Ki-67 protein encoded by the MKI67 gene and grade and negatively correlated with progesterone receptor and estrogen receptor. Conclusion In this prospective trial, patients with enhanced clinical risk and omitted chemotherapy on the basis of RS ≤ 11 had excellent 3-year survival. The substantial discordance observed between traditional prognostic markers and RS emphasizes the need for standardized assessment and supports the potential integration of standardized, well-validated genomic assays such as RS with clinicopathologic prognostic factors for chemotherapy indication in early hormone receptor–positive BC.

Association between androgen receptor expression, Ki-67 and the 21-gene recurrence score in non-metastatic, lymph node-negative, estrogen receptor-positive and HER2-negative breast cancer

2015 ◽  
Vol 68 (10) ◽  
pp. 839-843 ◽  
Author(s):  
Francisco E Vera-Badillo ◽  
Martin C Chang ◽  
Gordana Kuruzar ◽  
Alberto Ocana ◽  
Arnoud J Templeton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Lymph Node ◽  
Androgen Receptor ◽  
Statistical Significance ◽  
Multivariable Analysis ◽  
Recurrence Score ◽  
Receptor Expression ◽  
Ki 67 ◽  
Node Negative

BackgroundThe mechanisms underlying the favourable prognosis of androgen receptor (AR) expression in breast cancer are unknown.MethodsThe associations between the 21-gene recurrence score (RS), AR, grade, mitotic score, Ki-67 and estrogen receptor (ER) and progesterone receptor (PgR) expression were explored in sequential women with lymph node-negative, ER-positive and HER2-negative breast cancer. Statistical significance of this exploratory study was defined as p<0.10.ResultsAnalysis comprised 70 women. Most tumours had high AR expression (97% had scores >3). Median RS was 15 (range 1–53). AR expression showed a minimally significant positive correlation with ER (R=0.37), but no correlation with Ki-67 (R=−0.18). In univariable analysis, AR (p=0.01), ER (p<0.001) and PgR (p<0.001) had significant negative associations with RS. Ki-67 (p=0.16), grade (p=0.40) and mitotic score (p=0.23) showed no association with RS. Multivariable analysis showed similar associations.ConclusionsAR is associated with lower RS, but not with Ki-67.

Correlation of manual semi-quantitative and automated quantitative Ki-67 proliferative index with OncotypeDXTM recurrence score in invasive breast carcinoma

2021 ◽  
pp. 1-11
Author(s):  
Brian S. Finkelman ◽  
Amanda Meindl ◽  
Carissa LaBoy ◽  
Brannan Griffin ◽  
Suguna Narayan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Hot Spot ◽  
Recurrence Score ◽  
Invasive Breast Carcinoma ◽  
Chemotherapy Response ◽  
Scoring Method ◽  
Cancer Proliferation ◽  
Ki 67 ◽  
Breast Cancer Chemotherapy

BACKGROUND: Ki-67 immunohistochemistry (IHC) staining is a widely used cancer proliferation assay; however, its limitations could be improved with automated scoring. The OncotypeDXTM Recurrence Score (ORS), which primarily evaluates cancer proliferation genes, is a prognostic indicator for breast cancer chemotherapy response; however, it is more expensive and slower than Ki-67. OBJECTIVE: To compare manual Ki-67 (mKi-67) with automated Ki-67 (aKi-67) algorithm results based on manually selected Ki-67 “hot spots” in breast cancer, and correlate both with ORS. METHODS: 105 invasive breast carcinoma cases from 100 patients at our institution (2011–2013) with available ORS were evaluated. Concordance was assessed via Cohen’s Kappa (κ). RESULTS: 57/105 cases showed agreement between mKi-67 and aKi-67 (κ 0.31, 95% CI 0.18–0.45), with 41 cases overestimated by aKi-67. Concordance was higher when estimated on the same image (κ 0.53, 95% CI 0.37–0.69). Concordance between mKi-67 score and ORS was fair (κ 0.27, 95% CI 0.11–0.42), and concordance between aKi-67 and ORS was poor (κ 0.10, 95% CI −0.03–0.23). CONCLUSIONS: These results highlight the limits of Ki-67 algorithms that use manual “hot spot” selection. Due to suboptimal concordance, Ki-67 is likely most useful as a complement to, rather than a surrogate for ORS, regardless of scoring method.

scholarly journals Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay—Results From the SAFIA Phase III Trial

2021 ◽  
pp. 811-819
Author(s):  
Khalid AlSaleh ◽  
Heba Al Zahwahry ◽  
Adda Bounedjar ◽  
Mohammed Oukkal ◽  
Ahmed Saadeddine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Interim Analysis ◽  
Growth Factor Receptor ◽  
Recurrence Score ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Hormone Sensitivity ◽  
Epidermal Growth ◽  
Breast Recurrence

PURPOSE Luminal, human epidermal growth factor receptor 2–negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2–negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate ( P = .05). CONCLUSION The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Verteilung des 21-Gen-Rezidiv-Scores bei Patientinnen mit primärem Mammakarzinom in Deutschland

2021 ◽  
Vol 18 (03) ◽  
pp. 285-293
Author(s):  
Vincent P. Walter ◽  
Florin-Andrei Taran ◽  
Markus Wallwiener ◽  
Armin Bauer ◽  
Eva-Maria Grischke ◽  
...  
Keyword(s):  
Recurrence Score ◽  
Oncotype Dx ◽  
Ki 67

Zusammenfassung Einleitung Multigen-Assays werden zunehmend als Entscheidungshilfe für eine Chemotherapie beim Mammakarzinom verwendet. Wir stellen hier den 21-Gen-Recurrence-Score (RS) von Patientinnen mit Brustkrebs vor, die routinemäßig in Deutschland untersucht wurden. Patientinnen und Methoden 4695 Patientinnen mit hormonrezeptorpositivem und HER2-negativem Brustkrebs im Frühstadium (pT1–3, pN0–1, M0) wurden einer retrospektiven Analyse unterzogen. Bei diesen Patientinnen wurde in Deutschland zwischen November 2015 und Juli 2018 der Genexpressionstest Oncotype DX zur Ermittlung des Recurrence-Scores durchgeführt. Die Klassifikation der RS-Gruppen erfolgte gemäß der TAILORx Studie (RS: 0–10; 11–25; 26–100). Ergebnisse Von diesen Patientinnen wurden 21 % in die niedrige RS-Gruppe, 63 % in die mittlere RS-Gruppe, und 15 % in die hohe RS-Gruppe eingeteilt. 1772 (81 %) von 2175 Patientinnen im Alter von über 50 Jahren und ohne Lymphknotenbefall wurden entweder in die niedrige oder die mittlere RS-Gruppe eingeteilt. Der Prozentsatz an Patientinnen mit einem niedrigen oder mittleren RS betrug 90 % bei Patientinnen ohne Lymphknotenbefall (1284 von 1432 Patientinnen), 79 % bei Patientinnen mit einem hohen (≥ 20 %) Ki-67-Wert (1829 von 2310 Patientinnen), 86 % bzw. 70 % bei Patientinnen mit G2- bzw. G3-Tumoren (3244 von 3762 Patientinnen bzw. 368 von 522 Patientinnen), 88 % bei Patientinnen mit einem Tumordurchmesser von > 5 cm (140 von 159 Patientinnen) und 82 % bei Patientinnen ohne Lymphknotenbefall, aber mit einem hohen klinischen Risiko (1110 von 1352). Schlussfolgerung Die Verteilung des 21-Gens RS bei deutschen Patientinnen, die in der klinischen Routinepraxis getestet wurden, deutet darauf hin, dass gemäß den Ergebnissen der TAILORx-Studie die Chemotherapie bei den meisten dieser Patientinnen keinen Nutzen hat.

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