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CCND1  is located on 11q13. Increased  CCND1  copy number (CN) in breast cancer (BC) is associated with high histopathological grade, high proliferation, and Luminal B subtype. In this study of  CCND1  in primary BCs and corresponding axillary lymph node metastases (LNM),we examine associations between  CCND1  CN in primary BCs and proliferation status, molecular subtype, and prognosis. Furthermore, we studied associations between  CCND1  CN and CNs of  FGFR1  and  ZNF703 , both of which are located on 8p12. Fluorescence in situ hybridization probes for  CCND1  and chromosome 11 centromere were used on tissue microarrays comprising 526 BCs and 123 LNM. We assessed associations between  CCND1  CN and tumour characteristics using Pearson’s χ 2  test, and estimated cumulative risks of death from BC and hazard ratios in analysis of prognosis. We found  CCND1  CN ≥ 4 &lt; 6 in 45 (8.6%) tumours, and ≥ 6 in 42 (8.0%).  CCND1  CN (≥ 6) was seen in all molecular subtypes, most frequently in Luminal B (HER2 − ) (20/126; 16%). Increased  CCND1  CN was associated with high histopathological grade, high Ki-67, and high mitotic count, but not prognosis.  CCND1  CN ≥ 6 was accompanied by CN increase of  FGFR1  in 6/40 cases (15.0%) and  ZNF703  in 5/38 cases (13.2%). Three cases showed CN increase of all three genes. High  CCND1  CN was most frequent in Luminal B (HER2 − ) tumours. Good correlation between  CCND1  CNs in BCs and LNM was observed. Despite associations between high  CCND1  CN and aggressive tumour characteristics, the prognostic impact of  CCND1  CN remains unresolved.

CCND1 Amplification in Breast Cancer -associations With Proliferation, Histopathological Grade, Molecular Subtype and Prognosis