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Clinical Trial
. 2019 Nov 21;17(1):207.
doi: 10.1186/s12916-019-1445-z.

Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial

Maria Vittoria Dieci  1   2 , Giancarlo Bisagni  3 , Alba A Brandes  4 , Antonio Frassoldati  5 , Luigi Cavanna  6 , Francesco Giotta  7 , Michele Aieta  8 , Vittorio Gebbia  9 , Antonino Musolino  10 , Ornella Garrone  11 , Michela Donadio  12 , Anita Rimanti  13 , Alessandra Beano  12 , Claudio Zamagni  14 , Hector Soto Parra  15 , Federico Piacentini  16 , Saverio Danese  17 , Antonella Ferro  18 , Katia Cagossi  19 , Samanta Sarti  20 , Anna Rita Gambaro  21 , Sante Romito  22 , Viviana Bazan  23 , Laura Amaducci  24 , Gabriella Moretti  3 , Maria Pia Foschini  25 , Sara Balduzzi  26 , Roberto Vicini  27 , Roberto D'Amico  26   27 , Gaia Griguolo  1   2 , Valentina Guarneri  1   2 , Pier Franco Conte  28   29
Affiliations
Clinical Trial

Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial

Maria Vittoria Dieci et al. BMC Med. .

Abstract

Background: The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial.

Methods: The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death.

Results: A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category. Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P < 0.001). Five-year DDFS according to prognostic stage was as follows: IA 95.7%, IB 91.4%, IIA 86.9%, IIB 85.0%, IIIA 77.6%, IIIC 67.7% (P < 0.001). The C index was similar (0.69209 and 0.69249, P = 0.975). Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080).

Conclusions: The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment.

Trial registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

Keywords: 8th AJCC; Breast cancer; HER2-positive; Prognostic stage; Trastuzumab.

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Conflict of interest statement

MVD reports personal fees from Genomic Health, personal fees from EliLilly, personal fees from Celgene, outside the submitted work. AAB reports grants to organize courses from Devicor-Mammotome, Roche and Biocartis, outside the submitted work. AF reports personal fees from Roche, personal fees from Novartis, personal fees from Pfizer, outside the submitted work. AM reports grants, personal fees and non-financial support from Roche, personal fees and non-financial support from Lilly, personal fees from Pfizer, grants, personal fees and non-financial support from EISAI, personal fees from Macrogenics, grants from AstraZeneca, outside the submitted work. OG reports grants, personal fees, and non-financial support from Eisai, personal fees from Amgen, personal fees from Novartis, non-financial support from Celgene, outside the submitted work. CZ reports personal fees from Takeda, personal fees from Pierre Fabre, personal fees from TEVA, personal fees from Istituto Gentili, personal fees from Roche, personal fees from EISAI, personal fees from Novartis, personal fees from AstraZeneca, personal fees from Pfizer, personal fees from PharmaMar, personal fees from Celgene, personal fees from Lilly, personal fees from Amgen, personal fees from Tesaro, and personal fees from QuintilesIMS, outside the submitted work. FP reports personal fees from Eisai, outside the submitted work. MPF reports grants from Roche, grants from Devicor-Mammotome, personal fees from Biocartis, outside the submitted work, outside the submitted work. VG reports grants (Institution) and personal fees from Roche, personal fees from Novartis, personal fees from Eli Lilly, personal fees from Roche, outside the submitted work. PFC reports grants from Agenzia Italiana del Farmaco AIFA, during the conduct of the study; personal fees from Novartis, personal fees from EliLilly, personal fees from AstraZeneca, personal fees from Tesaro, personal fees from BMS, personal fees from Roche, grants (Institution) from Novartis, grants (Institution) from Roche, grants (Institution) from Merck KGa, grants (Institution) from BMS, outside the submitted work. All other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Kaplan-Meier DDFS curves by anatomic stage (a) and prognostic stage (b)
Fig. 2
Fig. 2
Kaplan-Meier DDFS curves for patients treated in the short (9 weeks trastuzumab) vs the long (1 year trastuzumab) arm according to stage categories: anatomic stage I patients (a), prognostic stage I patients (b), prognostic stage IA patients (c)
See this image and copyright information in PMC

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