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Breast cancer, early stage

142P - Effectiveness and safety of pegylated liposomal doxorubicin- cyclophosphamide vs. epirubicin-cyclophosphamide as adjuvant chemotherapy for stage I and II HER2-negative breast cancer: An interim analysis of phase II randomized trial

Presentation Number
142P
Speakers
  • Ling-Ming Tseng (Taipei City, Taiwan)
Date
Sat, 10.09.2022

Abstract

Background

Doxorubicin is a cornerstone drug for breast cancer treatment. Epirubicin is an effective epimer of doxorubicin with less cardiotoxicity, and pegylated liposomal doxorubicin (PLD), is a liposomal formulation with lower toxicity than doxorubicin. We report the interim efficacy and safety results from the first phase II randomized trial aimed to compare PLD-based and epirubicin-based adjuvant chemotherapy for stage I-II Her2-negative breast cancer.

Methods

Eligible patients with Her2-negative stage I or II invasive breast adenocarcinoma were randomized 1:1 to receive adjuvant cyclophosphamide 600mg/m2 followed by pegylated liposomal-doxorubicin (Lipo-Dox®) 37.5mg/m2 Q3W, 5 cycles (LC arm) or epirubicin 90mg/m2 Q3W, 4 cycles (EC arm). Randomization was stratified by lymph node, ER & PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and quality of life (using EORTC QLQ-C30 & QLQ-BR23). The data cutoff date for the interim analysis was December 31, 2020.

Results

A total of 256 patients were randomized to LC (n=148) and EC (n=108). There was no difference in 2-year DFS rate between 2 arms (LC: 0.96; EC: 0.97, p=0.59), regardless of whether taxane was used. There was no difference in 2-year OS, mean change in LVEF, and BNP from screening to treatment after 3 weeks between the 2 arms. Compared to EC, there was less grade 3-4 AE in LC for: neutropenia (13.1% vs 34.3%), leukopenia (2.8% vs 24.8%), and vomiting (0 vs 3.8%) (All p<0.05). The major event in the LC arm are mucosal and dermal toxicities, whereas in the EC arm, the main toxicities are hematological and alopecia. The LC arm had a significantly better QoL score during and/or after treatment in symptoms including fatigue, nausea and vomiting, and systemic therapy side effects.

Conclusions

This interim analysis showed comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II Her2-negative breast cancer. In addition, less grade 3-4 AE and a trend of favorable QoL symptom scales were observed in the LC arm. Final analysis will be performed using longer survival data.

Clinical trial identification

NCT01210768. First posted: September 28, 2010.

Legal entity responsible for the study

TTY Biopharm Company Ltd.

Funding

TTY Biopharm Company Ltd.

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, early stage

143P - Efficacy and safety of anthracyclines in neoadjuvant therapy in HER2+ breast cancer. A systematic review and network meta-analysis (NMA)

Presentation Number
143P
Speakers
  • Guillermo Villacampa Javierre (Barcelona, Spain)
Date
Sat, 10.09.2022

Abstract

Background

Neoadjuvant therapy (NAT) is the recommended approach to early HER2+ breast cancer (BC). Anthracycline (ANTR)-polychemotherapy (CT) regimens have been the first choice but newer combinations with multiple anti-HER2 agents with or without ANTR have also shown efficacy. The questions of the optimal combination and whether ANTR could be omitted remain.

Methods

A systematic literature review in the Medline, Embase and Web of Science databases was performed.Randomised controlled trials (RCTs) evaluating NAT for HER2+ BC with at least one group with anti-HER2 targeted treatment, were selected. Primary endpoint was pathological complete response (pCR) and secondary endpoints were event-free survival (EFS), overall survival (OS) and toxicity incidence. A frequentist NMA was performed using random-effect models for the estimation of odds-ratio (OR) and hazard ratio (HR) along with the 95% confidence interval (95% CI).

Results

The literature search identified 3384 records; 67 articles corresponding to 48 RCTs met the eligibility criteria and additional 4 articles (3 RCTs) published during data analysis were included. A total of 16,245 patients with early HER2+ BC were included in the global network. For the pCR endpoint (n=10,906), three combinations performed significantly better than trastuzumab (TRA) + CT: i) pertuzumab (PER) + TRA + CT, ii) single T-DM1 and iii) Tyrosine Kinase Inhibitors (TKI) + TRA + CT. In the EFS analysis (n=6,657), PER + TRA + CT and TKI + TRA + CT demonstrated superiority against single T-DM1 (HR: 0.45; 0.26-0.78 and HR: 0.41; 0.19-0.87, respectively). In a more aggregated analysis, the combination of dual anti-HER2 + CT associated with significantly better EFS and OS than i) dual anti-HER2 alone, ii) anti-HER2 + CT and iii) single T-DM1. Comparison of regimens with or without ANTR demonstrated no significant differences in pCR rates, but all estimations were in favour of the non-ANTR group. There was no difference in EFS either (HR: 1.00, 0.62 - 1.62). Similar safety profiles were observed with or without ANTR, with the exception of higher risk of LVEF drop with ANTR and dual anti-HER2 (PRE + TRA).

Conclusions

The combination of dual anti-HER2 + CT provides the best efficacy results. Additionally, this study provides evidence that anthracyclines can be safely omitted in early HER2+ BC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

G. Villacampa Javierre: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly. A. Matikas: Non-Financial Interests, Advisory Role: Veracyte. All other authors have declared no conflicts of interest.

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Breast cancer, early stage

144P - Neoadjuvant giredestrant (GDC-9545) + palbociclib (P) vs anastrozole (A) + P in postmenopausal women with oestrogen receptor-positive, HER2-negative, untreated early breast cancer (ER+/HER2– eBC): Biomarker subgroup analysis of the randomised, phase II coopERA BC study

Presentation Number
144P
Speakers
  • Aditya Bardia (Boston, United States of America)
Date
Sat, 10.09.2022

Abstract

Background

Giredestrant, a highly potent, non-steroidal, oral, selective ER antagonist and degrader (SERD), has shown encouraging antitumour activity as monotherapy and + P in metastatic BC. In coopERA BC (NCT04436744), the primary endpoint of superior suppression of Ki67 with single-agent giredestrant vs A from baseline (BL) after 2 weeks of treatment for ER+/HER2– eBC was met. Here, we report biomarker subgroup analyses of potential associations between BL characteristics, clinical features and Ki67 reduction.

Methods

221 patients with cT1c (≥1.5 cm)–cT4a–c ER+/HER2– eBC and BL Ki67 score ≥5% were randomised 1:1 to receive giredestrant or A alone for 14 days (D), then + P for four 28-D cycles. The primary outcome of Ki67 change from BL to Week 2 was analysed based on AJCC stage, primary tumour stage, nodal (N) status, histological grade or subtype and progesterone receptor (PgR) status. Changes in ER/PgR protein levels were assessed by H-score.

Results

This analysis included 201 Ki67-evaluable patients at BL and Week 2. Greater Ki67 reduction was observed with giredestrant vs A across AJCC stages, almost all tumour stages, in patients with N+ disease and regardless of ductal or lobular subtype (Table). Giredestrant treatment also resulted in a markedly larger Ki67 decrease vs A in PgR-negative tumours, a poor prognostic feature. As expected, a strong decrease in ER protein levels was observed after 2 weeks of treatment with giredestrant, with a trend for greater reduction in protein levels of PgR at Week 2 with giredestrant vs A. Data on gene expression changes in ER signalling will be presented.

% Ki67 reduction
A Giredestrant
AJCC stage I 66 75
II 68 75
III 62 74
Primary tumour stage T1 64 73
T2 68 76
T3 65 80
T4 69 65
N status cN0 59 72
cN+ 59 79
Histological grade 1/2 67 76
3 66 68
Histological subtype Ductal 65 76
Lobular 68 71
PgR status + 70 77
39 60

Conclusions

Giredestrant induced greater suppression of Ki67 than A in ER+/HER2– eBC regardless of stage, histological subtype and PgR status, providing rationale for further evaluation in the adjuvant setting.

Clinical trial identification

NCT04436744 (June 18, 2020).

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics, Taiho, Sanofi, Daiichi Pharma/AstraZeneca, Puma, Biotheranostics Inc., Phillips, Eli Lilly, Foundation Medicine; Financial Interests, Institutional, Research Grant: Genetech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics, Daiichi Pharma/AstraZeneca; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. T.M. Fernando: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. P.A. Fasching: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, SeaGen, F. Hoffmann-La Roche Ltd, Hexal, Agendia, Gilead; Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, SeaGen, F. Hoffmann-La Roche Ltd, Gilead; Financial Interests, Institutional, Research Grant: Biontech, Cepheid; Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. V. Quiroga Garcia: Financial Interests, Personal, Other, Honoraria: F. Hoffmann-La Roche Ltd, Pfizer; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Personal, Other, Travel/accommodation/ expenses: Novartis, F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Funding: Celgene; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. Y.H. Park: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd, Novartis, Eisai, Lilly; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd, Merck; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd, Novartis; Financial Interests, Personal, Other, Speaker fee: F. Hoffmann-La Roche Ltd, Novartis; Financial Interests, Institutional, Principal Investigator, Contracted research: Daiichi Sankyo, Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Research Grant: Gencurix; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. J.M. Giltnane: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. C. Xue: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. V. Lopez Valverde: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. J. Steinseifer-Szabo: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. P.D. Pérez-Moreno: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. H.M. Moore: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.; Financial Interests, Personal, Full or part-time Employment, Spouse: Pfizer; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd. S.A. Hurvitz: Financial Interests, Institutional, Research Grant, Contracted research: Ambrx, Amgen, AstraZeneca, Arvinas, Bayer, Cytomx, Daiichi Sankyo, Dignitana, Genentech/F. Hoffmann-La Roche Ltd, Gilead, GSK, Immunomedics, Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Orinove, Pieris, PUMA, Radius, Sanofi, Seattle Genetics/Seagen, Zymeworks, Phoenix Molecular Designs, Ltd; Financial Interests, Personal, Other, Travel accommodations, expenses (2019): Lilly; Financial Interests, Personal, Stocks/Shares, Spouse: Ideal Plant; Financial Interests, Personal, Stocks/Shares: NKMax; Financial Interests, Personal, Advisory Board: Daiichi Sankyo/ AstraZeneca, Genentech/F. Hoffmann-La Roche Ltd, Novartis, Sanofi; Non-Financial Interests, Personal, Research Grant, Medical writing support for this abstract, furnished by Martin Cadogan, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd.: F. Hoffmann-La Roche Ltd.

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Breast cancer, early stage

145P - Prognostic value of tumor-infiltrating lymphocytes in HER2-positive breast cancer treated with neoadjuvant chemotherapy and dual HER2-blockade: A TRAIN-2 sub study

Presentation Number
145P
Speakers
  • Marte C. Liefaard (Amsterdam, Netherlands)
Date
Sat, 10.09.2022

Abstract

Background

Previously, it has been demonstrated that stromal tumor-infiltrating lymphocytes (sTILs) provide independent prognostic information in early-stage HER2-positive breast cancer. The aim of our study was to validate these findings by studying sTILs and outcome measures in early-stage HER2-positive breast cancer patients who were randomized to receive neoadjuvant chemotherapy with or without anthracyclines plus trastuzumab and pertuzumab in the TRAIN-2 study.

Methods

Following sTIL scoring on pre-treatment biopsies by two pathologists, the geometric mean was calculated. When the two scores differed by more than 10%, a final score was assigned after revision by one pathologist. The association between sTILs and pathological complete response (pCR) was studied using logistic regression analyses adjusted for age, hormone receptor (HR) status, clinical T-stage, clinical N-stage, tumor grade and treatment arm. Similarly, the relation between sTILs and event-free survival (EFS) was evaluated by Cox regression analyses.

Results

sTIL score was available for 389/438 patients and was associated with age, HR-status, grade and N-stage. sTIL score was associated with pCR in univariable, but not in multivariable analysis (OR 1.01, 95% CI 1.00-1.02). Similarly, sTIL score was prognostic for EFS in univariable analysis, but not in multivariable analysis (HR 0.98, 95% CI 0.97-1.00). Patients with high sTILs (above the median) and who reached pCR had excellent 5-year EFS rates (Table).

Stromal TILs, pathological complete response and 5-year event-free survival rates

Group Number of events 5-year EFS (%) 95% CI
Low sTILs, no pCR 11/73 83.8 75.3 - 93.2
High sTILs, no pCR 8/45 81.7 71.0 - 94.1
Low sTILs, pCR 13/129 81.5 69.7 - 95.2
High sTILs, pCR 3/123 97.5 94.7 - 100

Conclusions

We did not observe a significant association between sTILs and pCR or EFS after adjustment for clinical variables. However, patients with pCR and high sTILs show excellent 5-year EFS rates compared to patients with no pCR or low sTILs. Early-stage HER2-positive breast cancer patients with high sTILs and pCR may be candidates for de-escalated adjuvant treatment, whereas patients with low sTILs may benefit of additional treatment.

Clinical trial identification

NCT01996267.

Legal entity responsible for the study

BOOG Study Center.

Funding

Roche.

Disclosure

A.E. van Leeuwen-Stok: Financial Interests, Institutional, Funding, Roche funding for the TRAIN-2 study: Roche. H. Horlings: Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Institutional, Advisory Role: SlideScore.com. R.F. Salgado: Non-Financial Interests, Institutional, Other: Merck, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Puma Biotechnology, Merck, Roche; Financial Interests, Personal, Advisory Board: Roche, Exact Sciences, Bristol Myers Squibb. G.S. Sonke: Financial Interests, Institutional, Funding: Roche, Merck, Novartis, Agendia, AstraZeneca, Seagen; Financial Interests, Institutional, Advisory Role: Seagen, Biovica. All other authors have declared no conflicts of interest.

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Breast cancer, early stage

146P - HRD/TIL-low high-risk breast cancer is characterized by good prognosis (the RADIMMUNE trial)

Presentation Number
146P
Speakers
  • Benedetta Pellegrino (Parma, Italy)
Date
Sat, 10.09.2022

Abstract

Background

Early stage tumor-infiltrating lymphocytes (TIL)-low triple-negative breast cancers (TNBC) are characterized by bad prognosis. The RAD51 test can identify Homologous Recombination Repair (HRR)-deficient (HRD) tumors and may add prognostic value in this subset of patients, potentially guiding post-neoadjuvant treatments in order to improve survival.

Methods

We quantified functional HRD detecting RAD51 and BRCA1 nuclear foci by immunofluorescence, content of TIL by H&E and IHC and expression of immune markers on diagnostic tumor biopsies of 148 high-risk BC patients, namely histologically confirmed TNBC or early onset BC (≤ 35 years old) or gBRCA1/2-mutated BC. Patients were admitted at 6 Italian Hospitals of the “Gruppo Oncologico Italiano di Ricerca Clinica” (GOIRC) and at the Bordet Institute in Brussels and treated with (neo)adjuvant chemotherapy based on anthracyclines, taxanes and cyclophosphamide. Functional HRD was predefined as RAD51 score ≤10% (RAD51-low).

Results

RAD51 was successfully scored in 123/148 (83%) samples. 43/123 (35%) patients presented HRR mutations: 35 gBRCA1 (28%), 6 gBRCA2 (5%), and 2 gPALB2 (2%) mutations. 99/123 (81%) tumors were HRD by RAD51: 41/43 (95%) HRR-mutated and 58/80 (72%) HRR-WT tumors. 39/80 (49%) HRR-WT tumors presented BRCA1-low nuclear foci, surrogate of lack of BRCA1 function likely due to epigenetic silencing. pCR rates, TIL extent and PD-L1 Combined Positive Score (CPS) did not correlate with HRD status. DFS did not differ between HRD and HRR proficient (HRP)-tumors. Instead, patients with HRD tumors had a statistically significant higher 5y-OS than patients with HRP-tumors (88% vs 59%, p=0.032). Within TIL-low tumors, the 5y-OS benefit was greater in HRD vs HRP (92% vs 49%, p=0.004). In support, HRD/TIL-low tumors showed lower PD-L1 CPS compared to others (p=0.0011); no statistically significant differences were found in CD3+ and CD20+ TIL.

Conclusions

The RAD51 test is able to identify HRR-altered tumors, beyond gBRCA1/2 mutations, and to select a cohort of HRD/TIL-low patients with good prognosis in a platinum-free (neo)adjuvant chemotherapy setting. Biomarker analyses on a larger cohort of patients are ongoing. Results will be available for the congress.

Legal entity responsible for the study

Azienda Ospedaliero-Universitaria di Parma.

Funding

EraPerMed (Horizon 2020 Program).

Disclosure

B. Pellegrino: Non-Financial Interests, Institutional, Other, meeting grant: Pfizer, Lilly; Financial Interests, Personal and Institutional, Writing Engagements: MSD. A. Frassoldati: Financial Interests, Personal, Advisory Board, and travel grant: Roche, Novartis, AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board: Daichii, Seagen, Gilead; Non-Financial Interests, Personal, Other, travel grant: Pfizer, Amgen. M. Lambertini: Financial Interests, Personal, Other, Consultant and speaker honoraria: Roche, Novartis, Lilly, MSD; Financial Interests, Personal, Other, Consultant: AstraZeneca, Exact Sciences, Pfizer, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: Takeda, Ipsen, Knight, Sandoz, Libbs. M.V. Dieci: Financial Interests, Personal, Other, Personal Fees: Eli Lilly, MSD, Exact Sciences, Novartis, Pfizer, Seagen. L. Cortesi: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Gilead; Financial Interests, Personal, Other, Honoraria and consulting: Novartis, Pfizer, MSD. J. Balmaña: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer; Financial Interests, Institutional, Other, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Principal Investigator: MedSir, Pfizer. V. Serra: Financial Interests, Personal, Research Grant, and personal fees: AstraZeneca; Financial Interests, Personal, Research Grant: Tesaro; Financial Interests, Personal, Other, Personal Fees: AbbVie; Financial Interests, Personal and Institutional, Other, Patent WO2019122411A1: Other. A. Musolino: Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Research Grant, and personal fees: Lilly; Financial Interests, Personal, Other, Personal Fees: Eisai, Seagen, Daiichi Sankyo. All other authors have declared no conflicts of interest.

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Breast cancer, early stage

147P - Blind validation of an AI-based tool for predicting distant relapse from breast cancer HES stained slides

Presentation Number
147P
Speakers
  • Ingrid J. Garberis (Villejuif, France)
Date
Sat, 10.09.2022

Abstract

Background

Correctly classifying early invasive breast cancer (eiBC) cases into high-risk and low-risk is considered a key issue in breast cancer treatment. This classification is notably crucial in determining the treatment regimen: chemo-endocrine therapy versus, endocrine therapy alone. Last year, we presented RACE, an AI-based tool for assessing the risk of distant relapse at 5 years of ER+HER2- eiBC patients from HES (hematoxylin-eosin-safran) whole slide images (WSI). In the present study, we performed a one-shot blind validation of RACE on an independent cohort of 676 HES WSI.

Methods

HES WSI of 676 ER+/HER2- eiBC diagnosed at Gustave Roussy from 2012 to 2017 included in the CANTO cohort, constituted the validation dataset (19 patients relapsed at 5 years). We compared RACE performance to the two most relevant clinical scores: Predict Breast and CTS0. To assess performance, we proceeded as follows. The scores were first compared in terms of both cumulative sensitivity and dynamic specificity at 5 years to assess the accuracy of the scores to identify relapses. For this purpose, each score has been binarized (low risk/high risk) with respect to a threshold that has been set beforehand.

Results

The cumulative sensitivity (resp. dynamic specificity) at 5 years is 64% (resp. 78%) for Race, 61% (resp. 77%) for CTS0 and 43% (resp. 80%) for Predict Breast. Further analyses showed that among the low risk population treated with endocrine therapy alone, the distant relapse rate was 0.3% (1 out of 324).

Conclusions

We performed a first fully blind validation of Race, an AI-based tool for assessing the risk of distant relapse. First, the obtained results showed the ability of RACE to generalize on independent data and thus endorse the soundness of the method. Furthermore, additional analysis brings to light the clinical value of Race and that it could be used for therapeutic de-escalation purposes. This validation will be extended to multi-site and multi-scanner eiBC WSI from the CANTO cohort under completion.

Legal entity responsible for the study

Gustave Roussy.

Funding

Owkin.

Disclosure

V. Gaury, V. Aubert, C. Saillard, K. Elgui: Financial Interests, Personal, Stocks/Shares: Owkin. F. André: Financial Interests, Personal, Advisory Role: Owkin. All other authors have declared no conflicts of interest.

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Breast cancer, early stage

148P - Serum metabolomics based risk assessment of disease recurrence in elderly patients with early breast cancer (eBC)

Presentation Number
148P
Speakers
  • Emanuela Risi (Prato, Italy)
Date
Sat, 10.09.2022

Abstract

Background

Metabolomics studies metabolites in biological samples. Cancer can impair metabolism, so the pattern of altered metabolites could reproduce a “cancer signature”. This analysis aimed at identifying a “metabolic signature” that could differentiate elderly eBC patients (pts) from elderly advanced breast cancer (aBC) pts, as well as at investigating its prognostic role in terms of disease recurrence (DR).

Methods

Serum samples from elderly BC pts enrolled in 3 onco-geriatric trials coordinated by the Medical Oncology Division of Prato, were retrospectively analyzed via proton nuclear magnetic resonance (NMR) spectroscopy. Three NMR spectra were acquired for each serum sample (NOESY1D, CPMG and Diffusion-edited). Random Forest (RF) models were calculated. The ability of metabolomics to predict BC relapses was assessed using Kaplan–Meier curves with calculation of the hazard ratio (HR) and p-value by Log-Rank test.

Results

Serum samples from 140 pts with eBC and 27 with aBC were collected between 2008 and 2018. In the aBC cohort, median age was 79 years (95% CI, 70-88); 25.9% of pts were hormone receptor positive HER2 negative (HR+HER2-), 29.6% HER2 positive (HER2+), 11.1% triple negative (TN); data missing in 33.3% of cases. In the eBC cohort, median age was 76 years (95% CI, 70-91); 30.7% of pts were HR+HER2-, 48.6% HER2+, 11.4% TN; data missing in 3.6% of cases. In this cohort, 39.3% of pts had tumors larger than 2 cm, and 41.4% had positive axillary lymph nodes. Using NOESY1D spectra, the RF classifier discriminated free from recurrance eBC from aBC with a sensitivity, specificity and accuracy of 81.5%, 66.7% and 70% respectively, performing better than the other spectra. Therefore, we tested the NOESY1D spectra of each eBC pt on the RF models already calculated. If the RF model classified the sample as relapsed, it was considered at “high risk” of DR. Our analysis showed that pts classified as "high risk” had a higher risk of DR (HR 3.39, 95% CI 1.59-7.24, p=0.00084).

Conclusions

This analysis suggests that a “metabolic signature”, identified employing NMR spectral profiling, is able to predict the risk of DR in elderly pts with eBC. Further studies are needed to confirm these data.

Legal entity responsible for the study

Azienda USL Toscana Centro.

Funding

"Sandro Pitigliani” Foundation.

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, early stage

149P - Clinical outcomes in ER+ breast cancer patients with recurrence score 26-30-guided therapy: Real-world data

Presentation Number
149P
Speakers
  • Ofer Rotem (Petah Tikva, Israel)
Date
Sat, 10.09.2022

Abstract

Background

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive HER2-negative breast cancer (BC). Based on previous retrospective trials, in patients with RS<31, chemoendocrine therapy (CET) was not superior to endocrine therapy (ET) alone. Recent prospective trials confirmed non-inferiority of ET vs CET in patients with RS<26. Data regarding CT benefit in the RS 26-30 group are sparse.

Methods

This exploratory analysis of the Clalit Health Services (CHS) registry included all CHS patients with ER+ HER2-negative BC and RS 26-30 who underwent RS testing between 1/2006 and 12/2016, and determined 7-year Kaplan-Meier (KM) estimates for overall survival (OS), distant recurrence free survival (DRFS), and BC-specific mortality (BCSM).

Results

The analysis included 394 node-negative patients (49% CET-treated, 51% ET-treated) and 140 node-positive patients (62% CET-treated, 38% ET-treated). For node-negative patients, with a median (IQR) follow up of 7.8 (5.8-11.1) years, KM estimates for OS, DRFS, and BCSM were not statistically significantly different between the CET and ET groups; 7-year rates (95% CI) in the CET vs the ET group, were 97.9% (94.4-99.2%) vs 97.9% (94.6-99.2%) for OS, 91.5% (86.6-94.7%) vs 91.2% (86.0-94.6%) for DRFS, and 0.5% (0.1-3.7%) vs 1.6% (0.5-4.7%) for BCSM. For node-positive patients, with a median (IQR) follow up of 8.2 (5.8-11.1) years, KM estimates were not statistically significantly different between the CET and ET groups for OS and DRFS; 7-year rates (95% CI) in these respective groups were 96.3% (89.2-98.8%) vs 93.8% (82.3-98.0%) for OS, and 89.4% (80.9-94.4%) vs 78.0% (64.3-87.5%) for DRFS. The BCSM KM estimates differed significantly between the treatment groups (P=0.024, log-rank test); the 7-year BCSM rate (95% CI) was 1.3% (0.2-8.6%) in the CET group and 6.2% (2.0-17.7%) in the ET group.

Conclusions

In node-negative ER+ HER2-negative BC patients with RS 26-30, CT had no significant effect on clinical outcomes; however, in node-positive ER+ HER2-negative BC patients, CT was associated with a statistically significant reduction in BCSM, without a statistically significant effect on OS and DRFS.

Legal entity responsible for the study

Rotem and Stemmer.

Funding

Oncotest, Exact Sciences.

Disclosure

O. Rotem: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Novartis, Pfizer, Roche, Takeda, Teva; Financial Interests, Personal, Advisory Role: NucleaiMD, Edocate. I. Kuchuk: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Medison; Financial Interests, Personal, Sponsor/Funding, Travel support: Roche, Medison, Pfizer. S. Paluch-Shimon: Financial Interests, Institutional, Advisory Board, Advisory board invited speaker honoraria: Roche, Exact sciences, Eli Lilly; Financial Interests, Institutional, Other, Advisory board invited speaker honoraria: Pfizer, Novartis, AstraZeneca; Financial Interests, Institutional, Other, Advisory board, speaker's bureau, consultancy: Medison; Financial Interests, Personal and Institutional, Research Grant, Research grant for an RFP independent research put out by SPCC and Pfizer: SPCC (Shared Progress in Cancer Care). R. Yerushalmi: Financial Interests, Personal, Principal Investigator: Roche, AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Medison, MSD, AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Role: Roche, Pfizer, Novartis, Medison, Gilead Sciences, Eli Lilly, AstraZeneca. A. Sonnenblick: Financial Interests, Personal, Advisory Role: Eli Lilly, Pfizer, Novartis, Roche, Gilead, MSD, AstraZeneca, Progenetics; Financial Interests, Personal, Other, travel/accommodation expensess: Neopharm, Celgene, Medison; Financial Interests, Personal, Other, travel/accommodation expenses: Roche; Financial Interests, Personal, Invited Speaker: Teva, Roche, Pfizer, Novartis, Eli Lilly; Financial Interests, Personal, Research Grant: Novartis, Roche. E. Nili Gal Yam: Financial Interests, Personal, Other, Honorarium: Roche, Novartis, Eli Lilly, Pfizer, MSD, AstraZeneca. H. Goldvaser: Financial Interests, Personal, Other, Honorarium: Roche, Rhenium, Oncotest, Novartis, Pfizer, MSD; Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Eli Lilly, Gilead. A. Bareket-Samish: Financial Interests, Personal, Writing Engagements: Can-Fite, Teva, Rhenium, Exact Sciences, Pfizer. L. Soussan-Gutman: Financial Interests, Personal, Full or part-time Employment: Oncotest, Genomic Health. S. Stemmer: Financial Interests, Institutional, Research Grant: Can-Fite, AstraZeneca, BioLine RX, BMS, Halozyme, Clovis Oncology, CTG Pharma, Exelexis, Geican, Lilly, Moderna, Teva, Roche; Financial Interests, Personal, Stocks/Shares, stocks/options: CTG Pharma, DocBox MD, Tyrnovo, VYPE, Cytora, Can-Fite. All other authors have declared no conflicts of interest.

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Breast cancer, early stage

150P - Assessment of high Ki67 (≥20%) ER+HER2- breast cancer with a 21-gene multigene assay

Presentation Number
150P
Speakers
  • Sung Gwe Ahn (Seoul, Korea, Republic of)
Date
Sat, 10.09.2022

Abstract

Background

Ki67 immunohistochemistry (IHC) with a cut-off of 20% by MIB-1 PharmDx assay has been approved as a companion diagnostic for adjuvant abemaciclib in high-risk ER+HER2- breast cancer. We addressed the genomic risk profile of high Ki67 (≥20%) ER+HER2- breast cancer using a 21-gene multigene assay (Oncotype DX test). In addition, we investigated survival outcomes and identified factors associated with low genomic risk in the high Ki67 group.

Methods

We collected clinical and pathologic information in 2,295 patients who underwent Oncotype DX testing. High genomic risk was defined by the 21-gene recurrence score (RS ≥26). Ki67 IHC examination with a cut-off of 20% was performed locally using MIB-1.

Results

The Ki67 IHC assigned 870 (38%) to the high and 1,425 (62%) to the low groups, while 21-gene RS assigned 347 (15%) to the genomic-high and 1,948 (85%) to the genomic-low. Of these, 263 of 870 (30%) of the high Ki67 had high genomic risk, whereas 84 of 1424 (6%) of the low Ki67 had it (p<0.0001). Average 21-gene recurrence score was significantly higher in the high Ki67 than in the low Ki67. In survival analyses, high Ki67 and 21-gene RS were significant prognostic factors. When the patients were classified into three groups (genomic-high, high-Ki67/genomic-low, low-Ki67/genomic-low), survival outcome of the high-Ki67/genomic-low was better than the genomic-high, whereas it was worse than the low-Ki67/genomic-low. Within the high Ki67 group, a multivariable analysis demonstrated that PR+, age ≤50, and histologic grade I-II were associated with low genomic risk.

Conclusions

Although about 60% of tumors with high Ki67 expression had low genomic risk by 21-gene multigene assay, the patients with high Ki67 have a substantial risk of relapse regardless of genomic risk. In high Ki67 tumors with PR+ and/or lower histologic grade, the multigene assay would be useful to evaluate their genomic risk.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Breast cancer, early stage

151P - Tumor biology and immunology in patients (pts) with breast cancer occurring during pregnancy (BCP) compared to non-pregnant breast cancer pts

Presentation Number
151P
Speakers
  • Kristin Galas (Neu-Isenburg, Germany)
Date
Sat, 10.09.2022

Abstract

Background

Breast cancer (BC) is one of the most common malignancies during pregnancy. The incidence is likely to increase as more women tend to delay childbearing into later life and the overall lifetime cancer risk increases with age. Pregnancy presents a complex and unique immunological condition. This study investigated the tumour biology and immunology of BCP cohort compared to non-pregnant BC cohort.

Methods

Tissue microarrays (TMA) of formalin-fixed paraffin embedded core biopsies or surgical specimens from 125 pregnant BC pts treated with (neo-) adjuvant chemotherapy were constructed. The BCP cohort was matched to an appropriate non-pregnant BC cohort with existing TMAs from the GAIN study by variables age, tumour stage, nodal status (N0 patients were not eligible in the GAIN study), grading and subtype. TMAs were stained via IHC to assess oestrogen and progesterone receptor (ER, PgR), human epidermal growth factor receptor 2 (HER2), Ki-67 (≤20% vs >20%), and immune response relevant markers, such as HLA class I (EMR8-5, MHC I), HLA-G (4H84), PD-L1 (<1% vs ≥1%), TIGIT (BLR047F), Nectin-4 (EPR15613-68) and tumour-infiltrating lymphocytes (TILs, ≤25% vs 26-60% vs >60%). PD-L1 expression was evaluated in tumour and immune cells using the 22C3 antibody. H-scores of HLA class I, HLA-G, TIGIT and Nectin-4 were calculated.

Results

Pregnant BC pts were younger than non-pregnant (median 34 [26-47] vs 37 [27-47] years) and had higher Ki-67 expression (>20%: 53.3% vs 38.1%, p=0.025). The H-score of HLA-G was significantly lower (median 4.9 vs 10.6, p=0.012), while the H-scores of HLA class I (median: 27.7 vs 13.8, p=0.029) and Nectin-4 (median: 156 vs 113, p≤0.001) were significantly higher in the BCP compared to the non-pregnant BC cohort. No significant differences were found for TILs, PD-L1 or H-score of TIGIT.

Conclusions

The significantly higher Ki-67 expression in the BCP cohort suggests an increased proliferation in BC cells during pregnancy. Higher Nectin-4 expression in the BCP cohort could be a sign of an altered anti-tumour response. These results suggest differences in tumour proliferation and tumour/host immunogenicity in BCP cohort vs non-pregnant BC cohort.

Legal entity responsible for the study

GBG Forschungs GmbH.

Funding

This study was financially supported by GBG and Philipps-Universität Marburg.

Disclosure

C. Solbach: Financial Interests, Personal, Advisory Board: MSD, Roche; Financial Interests, Personal, Other, Lecture: Pfizer, Lilly. A. Schneeweiss: Financial Interests, Personal and Institutional, Research Grant, Travel expenses, Honoraria: Celgene, Roche; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Personal, Other, Honoraria, Travel expenses: Pfizer; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen, Pierre Fabre. C. Denkert: Other, Institutional, Research Grant, Consulting fees: Myriad, Roche; Financial Interests, Personal and Institutional, Royalties, Consulting fees: VmScope digital pathology software; Financial Interests, Personal and Institutional, Advisory Role, Consulting fees: MSD Oncology, Daiichi Sankyo, Merck, Lilly, AstraZeneca, Molecular Health; Financial Interests, Personal and Institutional, Advisory Role, Consulting fees, Support for attending meetings and/or travel: Roche; Other, Personal and Institutional, Other, Paten for Therapy response: WO2015114146A1, WO2010076322A1; Other, Personal and Institutional, Other, Paten for cancer immunotherapy: WO2020109570A1; Non-Financial Interests, Personal, Ownership Interest, cofounder and shareholder until 2016: Sividon Diagnostics. P. Jank: Financial Interests, Institutional, Other, stock ownership: Myriad Genetics, Inc. S. Loibl: Financial Interests, Institutional, Research Grant, honorarium for Ad Boards, paid to institute: AbbVie; Financial Interests, Institutional, Other, honorarium for Ad Boards, paid to institute: Amgen, BMS, Lilly, Merck; Financial Interests, Institutional, Research Grant, honorarium for Ad Boards & Lectures, paid to institute: AstraZeneca; Financial Interests, Institutional, Research Grant, honorarium for Ad Board, paid to institute: Celgene; Financial Interests, Institutional, Other, honorarium for Ad Board, paid to institute: Eirgenix, GSK, Sanofi; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board, paid to institute / Medical Writing: Gilead; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board & Lectures, paid to institute / Medical Writing: Novartis, Pfizer; Financial Interests, Institutional, Other, honorarium for Ad Board & Lecture, paid to institute: Pierre Fabre; Non-Financial Interests, Institutional, Other, honorarium for Ad Boards, paid to institute / Medical Writing: Seagen, Roche; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Boards, paid to institute / Medical Writing: Daiichi Sankyo; Other, Institutional, Other, Patent for Immunsignature in TNBC, paid to institute: EP14153692.0; Other, Institutional, Other, Patent for Signature for CDK 4/6 Inhibitor, paid to institute: EP21152186.9; Other, Institutional, Other, Patent for Predicting response to an Anti-HER2 containing therapy, paid to institute: EP15702464.7; Other, Institutional, Other, Patent for GeparNuevo, paid to institute: EP19808852.8; Other, Institutional, Royalties, Paten for VM Scope GmbH, paid to institute: Digital Ki67 Evaluator. All other authors have declared no conflicts of interest.

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Breast cancer, early stage

152P - Molecular characterization by the 21-gene breast cancer (BC) Recurrence Score (RS) test of BRCA1/2 mutation carriers (mBRCA1/2) versus the general BC patient (pt) population

Presentation Number
152P
Speakers
  • Rinat Yerushalmi (Petah Tikva, Israel)
Date
Sat, 10.09.2022

Abstract

Background

The RS assay is a validated test used to guide treatment decisions in ER+ HER2-negative early-stage BC. We compared RS distribution and expression of the single genes/gene groups within this assay between mBRCA1/2 carriers ER+ HER2-negative BC pts vs the general BC pt population undergoing RS testing.

Methods

This retrospective cohort study included consecutive female ER+ HER2-negative BC pts with germline mBRCA1/2 who were RS-tested in 2004-2015. Their RS and gene expression data were compared to the commercial use database (DB) described by Jakubowski et al (J Surg Oncol. 2020;122:611). Chi-square test and 1-sample t-test were used to compare RS distribution and single gene/gene group scores, respectively, between the cohort and the DB.

Results

The mBRCA1/2 cohort included 81 pts; the DB included 799,986 BC samples. Age at diagnosis was younger in the mBRCA1/2 cohort vs the DB (median [IQR], 56 [47-61.5] vs 60 [51-67] yrs; P<.0001). In the mBRCA1/2 cohort, RS distribution shifted towards the high RS category (Table). Expression of 12 of the 16 cancer genes in the RS assay and the ER, proliferation, and invasion gene group scores differed significantly between the mBRCA1/2 cohort and the DB, all in a direction that contributed to higher RS results (Table).

mBRCA1/2 carriers N = 81 Commercial use DB N = 799,986 P
RS group, %
0-10 9% 22% <.0001
11-25 42% 62%
26-100 49% 16%
Gene expression, mean (SD)
ER group
ESR 9.8 (1.4) 10.0 NS
PGR 6.3 (1.7) 7.3 <.0001
BCL2 8.6 (1.0) 8.5 NS
SCUBE2 8.2 (1.8) 8.8 .0023
Group score 8.0 (1.1) 8.5 <.0001
Proliferation group
CCNB1 5.9 (0.5) 5.7 .0001
KI67 7.1 (0.8) 6.4 <.0001
STK15 6.4 (0.8) 5.6 <.0001
SURV 6.1 (1.1) 5.0 <.0001
MYBL2 5. 6 (1.0) 4.5 <.0001
Group score 6.2 (0.7) 5.4 <.0001
HER2 group
ERBB2 9.1 (0.7) 9.2 NS
GRB7 6.8 (0.7) 6.7 .049
Group score 7.1 (0.7) 6.9 NS
Invasion group
STMY3 9.8 (1.4) 10.0 NS
CTSL2 4.4 (0. 9) 3.8 <.0001
Group score 7.1 (0.8) 6.9 .043
Individual
CD68 9.0 (0.6) 8.8 .0070
GSTM1 6.9 (1.4) 7.8 <.0001
BAG1 8.2 (0.6) 8.5 .0001

Conclusions

mBRCA1/2 carriers are characterized by higher RS results that stem from a distinct gene expression profile of most genes in the RS assay.

Legal entity responsible for the study

Yerushalmi, Kaduri.

Funding

Oncotest, Exact Sciences.

Disclosure

R. Yerushalmi: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Medison, MSD, AstraZeneca, Eli Lilly; Financial Interests, Personal, Principal Investigator: Roche, Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Role: Roche, Novartis, Medison, AstraZeneca, Gilead, Eli Lilly, Pfizer. S. Paluch-Shimon: Financial Interests, Personal, Advisory Role: Roche, Novartis, Eli Lilly, Gilead, MSD, Pfizer, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Exact Sciences, NanoString, Novartis; Financial Interests, Personal, Speaker’s Bureau, And travel: Roche; Financial Interests, Personal, Speaker’s Bureau, and travel: Pfizer. L. Soussan-Gutman: Financial Interests, Personal, Full or part-time Employment: Oncotest, Genomic Health. F.L. Baehner: Financial Interests, Personal, Full or part-time Employment: Exact Sciences; Financial Interests, Personal, Stocks/Shares: Exact Sciecnes. H. Voet: Financial Interests, Personal, Advisory Role: BioInsight. A. Bareket-Samish: Financial Interests, Personal, Writing Engagements: Exact Sciences, Can-Fite BioPharma Ltd, Pfizer, Oncotest, Teva. L. Kaduri: Financial Interests, Personal, Research Grant: Hoffman la roche; Financial Interests, Personal, Principal Investigator: Eli Lilly, Bayer, Novartis. All other authors have declared no conflicts of interest.

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Breast cancer, early stage

153P - HER2DX risk-score in the context of the PREDICT online-tool: A correlative analysis of the Short-HER clinical trial in early-stage HER2-positive (HER2+) breast cancer (BC)

Presentation Number
153P
Speakers
  • Pier Franco Conte (Padova, Italy)
Date
Sat, 10.09.2022

Abstract

Background

PREDICT is an online tool (https://breast.predict.nhs.uk/) designed to help make informed decisions about treatment following surgery for early invasive BC and estimates overall survival (OS). HER2DX is a prognostic test that integrates clinical data and gene expression from immune, proliferation, luminal differentiation and HER2 amplicon processes. Here, we explored the prognostic ability of HER2DX beyond the PREDICT tool.

Methods

HER2DX and PREDICT tool were evaluated on 427 FFPE surgical specimens from patients (pts) enrolled at Short-HER trial a phase III, multicentric study for pts with HER2+ BC. All pts received multi-agent chemotherapy (CT) and were randomized to 9 weeks of trastuzumab (T) or 1 year (y). PREDICT included all variables except for ki67 and mode of cancer detection. Distant metastasis-free survival (DMFS) and OS were evaluated. The median follow-up was 7.3 y. Survival Cox model likelihood ratios evaluated the contribution of each variable (i.e: HER2DX risk-score, HER2DX risk-score with biological variables-only (HER2DX-bio) and PREDICT 5-y and 10-y OS estimates).

Results

PREDICT tool 5-y and 10-y OS estimates were significantly associated with DMFS (p<0.001) and OS (p<0.001) in Short-HER. PREDICT 10-y OS provided more prognostic information for DMFS and OS than 5-y OS and was used for further analysis. Pts with a PREDICT 10-y OS of ≥90% (low-risk) represented 12% and the actual 8-y DMFS and 8-y OS were 98% and 100%, respectively. 88% of pts had a high risk with a PREDICT 10-y OS and the actual 8-y DMFS and 8-y OS were 84% and 89%, respectively. The concordance rate between PREDICT and HER2DX was 66%. PREDICT did not add significant prognostic information beyond HER2DX for DMFS (c2=2.5; p=0.118) but did for OS (c2=12.6; p<0.001), whereas HER2DX was the opposite (c2=18.4; p<0.001 for DMFS and c2=0.9; p=0.334 for OS). HER2DX-bio provided 21% of prognostic information obtained with combined HER2DX and PREDICT (c2=6.8; p=0.009).

Conclusions

HER2DX provides more DMFS information than PREDICT in early-stage HER2+ BC treated with adjuvant CT and T. PREDICT is a strong predictor of OS.

Legal entity responsible for the study

Reveal Genomics, S.L.

Funding

Has not received any funding.

Disclosure

L. Pare Brunet: Financial Interests, Full or part-time Employment: Reveal Genomics, S.L. F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. O. Martinez Saez: Financial Interests, Personal, Invited Speaker: Novartis, Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Medical advisory: Reveal Genomics. M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Seagen, Exact Science; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Institutional, Research Grant: Veneto Institute of Oncology IOV-IRCCS, Italian Ministry of health, University of Padova. M. Marin: Financial Interests, Full or part-time Employment: Reveal Genomics. V. Guarneri: Financial Interests, Personal, Advisory Board: Roche, Eli Lilly, Novartis, MSD, Gilead; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck. A. Vivancos: Financial Interests, Personal, Advisory Board: Roche, Bristol Meyers Squibb, Guardant Health, Bayer, Incyte; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Meyers Squibb, ROCHE, Incyte. P. Villagrasa Gonzalez: Financial Interests, Full or part-time Employment: Reveal Genomics, S.L; Financial Interests, Other, Equity stock holder and consultant of Reveal Genomics: Reveal Genomics, S.L. J. Parker: Financial Interests, Other, Equity stock holder and consultant of Reveal Genomics: Reveal Genomics, S.L. C.M. Perou: Financial Interests, Other, Equity stock holder and consultant of Reveal Genomics: Reveal Genomics, S.L. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, BMS, Puma, Oncolytics Biotech, MSD, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation. All other authors have declared no conflicts of interest.

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