Cyclin D1 differential activation and its prognostic impact in patients with advanced breast cancer treated with trastuzumab.

We sought to determine the level of activation of the critical components of the cyclin D1-mediated pathway and to evaluate their prognostic significance across the different molecular subtypes of advanced breast cancer. The study population comprised 219 female patients with advanced breast cancer who had been found to have human epidermal growth factor receptor 2 (HER2)-positive disease by local testing and were all treated with trastuzumab-based regimens. For all tumours, central testing for HER2 was performed, and cyclin D1 gene ( After central testing, only 134 (61.2%) of 219 patients were confirmed to have HER2 gene amplification by FISH and/or 3+ HER2 protein expression by immunohistochemistry. After a median follow-up time of 136.0 months (95% CI 123.3 to 148.9), 105 (78.4%) HER2-positive patients and 76 (89.4%) HER2-negative patients had died, while 80% of the former and 87.1% of the latter had experienced a disease relapse. Patients with positive oestrogen receptor/progesterone receptor status presented with higher cyclin D1 mRNA expression. In the HER2-negative subgroup, patients with negative cyclin D1 protein expression were at higher risk of progression (HR= 1.66, 95%CI 1.01 to 2.72, Wald's p=0.045). Among de novo metastatic patients, the risk of progression was higher for patients with non-amplified Aberrant activation of the cyclin D1-mediated pathway appears to reduce the risk of progression in HER2-negative tumours, but not in HER2-positive ones.

Déclaration de conflit d'intérêts

Competing interests: GM: honoraria: Roche, AstraZeneca, Bristol-Myers Squibb; consulting or advisory role: MSD, Pfizer, Roche, Boehringer Ingelheim. GL: honoraria: BMS, MSD, Roche, Amgen, LEO Pharma; consultant, advisory role: Merck. CC: advisory role: Merck, Genesis Pharmaceuticals, Pfizer, Novartis, Roche, AstraZeneca, Bristol-Myers Squibb; honoraria: Roche, Bristol-Myers Squibb; travel: AZ, Sanofi. GP: advisory role: Roche; honoraria: Roche; speaker bureau: Roche; grants: Amgen. AK: consulting fees (eg, advisory boards): AstraZeneca; other, travel: Sanofi-Aventis, Astellas, Genesis, BMS, Amgen. ER: consulting fees (eg, advisory boards): Novartis; other, travel: Genesis Pharmaceuticals, Pfizer, Roche, Bristol-Myers Squibb, Genekor; honoraria: Novartis. PP: advisory role: Roche, Merck, Genesis Pharmaceuticals; honoraria: Roche, Merck. GA: advisory boards: Novartis, BMS, Roche Hellas, AstraZeneca, Sanofi, Amgen, Genesis Pharma, Merck, Pfizer. GF: advisory board: Pfizer, Sanofi and Roche; honoraria from AstraZeneca.