Validation of the American Joint Committee on Cancer new prognostic stage groups for HER2-positive breast cancer patients treated with adjuvant chemotherapy and trastuzumab in the prospective ShortHER trial
Authors: M.V. Dieci, G. Bisagni, A.A. Brandes, A. Frassoldati, M. Donadio, O. Garrone, F. Piacentini, S. Balduzzi, V. Guarneri, P.F. Conte
Journal: Annals of Oncology (2019)

Background: The American Joint Committee on Cancer (AJCC) 8th edition staging system introduced prognostic stage groups based on anatomic stage combined with biologic factors. We aimed to validate the AJCC prognostic classification in a large cohort of patients with HER2-positive breast cancer enrolled in the prospective ShortHER trial. Methods: The ShortHER trial randomized 1253 HER2-positive patients to receive 9 weeks or 1 year of trastuzumab in combination with anthracycline and taxane chemotherapy. Patients were classified according to the classic AJCC anatomic groups and the AJCC prognostic groups (8th edition). Distant disease-free survival (DDFS) was calculated as the time from randomization to relapse at a distant site or death. The Harrell's C-index was used to compare the prognostic performance of the two staging systems. Results: 1244 patients had complete clinicopathological data for both AJCC anatomic and AJCC prognostic stage classifications. Compared with the anatomic AJCC, the prognostic AJCC moved 41.6% (n = 517) of the patients to a more favorable stage category: 100% of IB to IA (n = 40), 61.6% of IIA to IB or IA (n = 246), 63.0% of IIB to IB or IA (N = 94), 58.7% of IIIA to IIA or IB (n = 71) and 100% of IIIC to IIIB or IIIA (n = 66). Table shows the 5-years DDFS rates according to the two staging systems. The c-index was similar: 0.69209 for anatomic stage and 0.69249 for prognostic stage (P = 0.975). Table88OAJCC anatomicAJCC prognosticN (%)5-years DDFS %Log-rank PN (%)5-years DDFS %Log-rank PIA469 (37.7)96.6P < 0.001733 (58.9)95.7P < 0.001IB40 (3.2)94.1139 (11.2)91.4IIA400 (32.1)92.4201 (16.2)86.9IIB149 (12.0)87.355 (4.4)85.0IIIA121 (9.7)81.359 (4.7)77.6IIIB0–57 (4.6)67.7IIIC66 (5.3)70.500 Open table in a new tab Conclusions: The AJCC prognostic classification reallocated 41.6% of HER2-positive patients to a more favorable stage category, while maintaining a similar prognostic performance as compared to the classic anatomic stage. With the AJCC prognostic staging, 59% of patients were classified as IA and showed an excellent prognosis after adjuvant treatment. Clinical trial identification: EUDRACT number: 2007-004326-25 NCI; NCT00629278. Legal entity responsible for the study: University of Modena and Reggio Emilia; University of Padua. Funding: Agenzia Italiana del Farmaco (AIFA, grant FARM62MC97). Disclosure: M.V. Dieci: Fees for consultancy role and participation on advisory boards: Eli Lilly; Fees for consultancy role: Genomic Health; Fees for participation on advisory boards: Celgene. A. Frassoldati: Advisory board: Roche, Novartis; Sponsored lectures: Pfizer, Novartis, Eli Lilly. O. Garrone: Fees for participation on advisory boards: Celgene, Eisai. V. Guarneri: Institutional research grant: Roche; Advisory boards: Eli Lilly, Roche, Novartis; Speaker's bureau: Eli Lilly, Novartis. P.F. Conte: Fees and honoraria for participation on advisory boards: Eli Lilly, Novartis, Roche, AstraZeneca. All other authors have declared no conflicts of interest.