Despite efforts for laboratory and method harmonization, discordant clinical subtypes for ER/PgR/HER2 that determine treatment selection for breast cancer patients in clinical practice, still pose a challenge.
We investigated the clinical relevance of discordant clinical subtypes and their clinicopathological and genotype characteristics (60-gene panel) in a series of 1427 breast cancer patients treated within 4 adjuvant trials (2 in the pre- and 2 in the post-trastuzumab era; recruitment period 1997 – 2012). Treatment decisions were based on local laboratory typing; all tumors were re-typed centrally. Disease-free survival was assessed.
We observed 340 (23.8%) discordant tumors for ER/PgR and/or HER2, ranging from 30% in the oldest to 19% in the most recent trial (p = 0.004); Cohen’s K was 0.512 for all subtypes, 0.583 for ER/PgR and 0.687 for HER2. ER/PgR discordance was associated with ER (p
Apart from technical considerations, clinical subtype discordance may reflect the genetic background of breast cancers, which appear to evolve by deviating from the ER+/PgR+ status. Development and reporting of phenotypic surrogates predictive of discordance is needed for increasing diagnostic accuracy and appropriate treatment selection.
Clinical trial identification
Legal entity responsible for the study
Hellenic Cooperative Oncology Group (HeCOG)
H. Gogas: Advisory or consultancy role: Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche. C. Papandreou: Honoraria and/or Advisory Role: Astellas Pharmaceuticals, AstraZeneca, Janssen Pharmaceutical, Merck S.A., Roche (Hellas) S.A., Sanofi-Aventis, Pfizer Hellas S.A., Merck Sharp & Dohme. G. Fountzilas: Honoraria: AstraZeneca. Consulting or Advisory Role: Pfizer, Sanofi, Roche. Stock ownership (an immediate family member): Ariad. All other authors have declared no conflicts of interest.