Abstract 187P
Background
In ER+/HER2- early breast cancer (eBC), oncologists frequently disagree on chemotherapy (CT) recommendation due to the subjective interpretation of classical clinicopathological variables, including Ki67. We aimed to evaluate whether and how Oncotype DX adoption improves the agreement and confidence among oncologists of different countries and experience.
Methods
We randomly selected 30 patients (pts) with pT1c-2 N0, grade 2-3, Ki67>15%, ER+/HER2- eBC and RS available from the database of San Raffaele Hospital. We asked 16 breast oncologists in Italy (IT) and US (seniors [Sr]: 6 IT, 4 US; juniors [Jr, within 2 years from end of residency]: 3 IT, 3 US) to provide recommendation for addition of CT to endocrine therapy with a degree of confidence twice: firstly based on clinicopathological features only (pre-RS), then with also the RS result available (post-RS). Intra- and inter- observer agreement was assessed by Cohen's kappa (K).
Results
Patients’ characteristics: median age 50.5 years (30-75), 40% premenopausal, 27% G3, 50% pT2, 70% Ki67>25%. In pre-RS, the average rate of CT recommendation was 50.8% (range 27.7%-76.7%) and was higher in Jr (61.7% vs 44.3%; p<0.001), but similar by country. Oncologists were uncertain in 39.0% of cases and provided discordant indications in 26.7% (3.3% - 53.3%, interobserver agreement K 0.47, range -0.14 - 0.93). Comparing pre- and post-RS, the average change of treatment indication was 29.6% (19.6% less CT; 10.0% more CT) (intraobserver agreement K 0.40; range 0.05-0.60), with no differences by group. In post-RS, both confidence and agreement in recommendation increased significantly: confidence increased in 65.2% with only 5.6% of oncologists uncertain. Average interobserver agreement was near perfect (K 0.85, range 0.47 – 1.00), especially in US (K 0.93) and Jr (K 0.93) (p<0.001). This corresponded to only 6.7% (0% - 26.7%) discordancy.
Conclusions
Subjective interpretation of clinicopathological features resulted in 1 out of 4 pts receiving discordant indications and higher uncertainty. Oncotype DX decreased the discordancy to only 1 out of 15 pts with lower uncertainty. The increased consensus among oncologists is an underappreciated benefit from using genomic tests in breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Criscitiello: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. A. Giordano: Advisory/Consultancy: Pfizer. M. Chavez-MacGregor: Full/Part-time employment: MD Anderson Physician’s Network ; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony: Abbot Laboratories; Honoraria (self): Eisai. G. Curigliano: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche/Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Foundation Medicine; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Samsung; Speaker Bureau/Expert testimony: Daiichi Sankyo; Honoraria (self): Ellipses Pharma. M. Giuliano: Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis pharma SAS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer Pharmaceuticals Israel; Speaker Bureau/Expert testimony: Gentili; Speaker Bureau/Expert testimony: Eisai Europe Ltd; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. R.J. Collins: Full/Part-time employment: South Carolina Oncology Associates. L. Del Mastro: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer ; Advisory/Consultancy: Ipsen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Lilly; Travel/Accommodation/Expenses: Celgene. F. Puglisi: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (self): Eisai; Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy: Pierre Fabre; Travel/Accommodation/Expenses: Servier Laboratories Ltd. F. Montemurro: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Daiichi Sankyo. C. Vernieri: Licensing/Royalties: P06242/IT ; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Gentili; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Roche. L. Gerratana: Advisory/Consultancy: Lilly; Travel/Accommodation/Expenses: Menarini Silicon Biosystems. S. Barnato Giordano: Advisory/Consultancy: Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis. L. Sica: Travel/Accommodation/Expenses: Pfizer. L. Pusztai: Advisory/Consultancy: H3 Biomedicine; Advisory/Consultancy, Research grant/Funding (institution): Merk; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: Syndax; Advisory/Consultancy: Athenex; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Almac Diagnostics; Research grant/Funding (institution): Genentech; Non-remunerated activity/ies: NanoString Technologies. G. Bianchini: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca ; Advisory/Consultancy: Lilly; Advisory/Consultancy: NeoPharm; Advisory/Consultancy: Amgen; Advisory/Consultancy: Chugai Pharma ; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: MSD Brazil; Advisory/Consultancy: Novartis pharma SAS; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer Pharmaceuticals Israel; Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai Europe Ltd; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Licensing/Royalties: European Patent Application N. 12195182.6 and 12196177.5. All other authors have declared no conflicts of interest.