Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years’ follow-up
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Molecular profiles of asynchronous breast cancer metastases are of clinical relevance to individual patients’ treatment, whereas the role of profiles in synchronous lymph node metastases is not defined. The present study aimed to assess individual biomarkers and molecular subtypes according to the St Gallen classification in primary breast tumours, synchronous lymph node metastases and asynchronous relapses and relate the results to 10-year breast cancer mortality (BCM). Tissue microarrays were constructed from archived tissue blocks of primary tumours (N = 524), synchronous lymph node metastases (N = 147) and asynchronous relapses (N = 36). The samples were evaluated by two independent pathologists according to oestrogen receptor (ER), progesterone receptor (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and in situ hybridisation. The expression of biomarkers and molecular subtypes in the primary tumour was compared with that in the synchronous lymph node metastases and relapses, and related to 10-year BCM. Discordances were found between primary tumours and relapses (ER: p = 0.006, PR: p = 0.04, Ki67: p = 0.02, HER2: p = 0.02, St Gallen subtypes: p = 0.07) but not between primary tumours and metastatic lymph node. Prognostic information was gained by the molecular subtype classification in primary tumours and nodal metastases; triple negative subtype had the highest BCM compared with the luminal A subtype (primary tumours: HR 4.0; 95 % CI 2.0–8.2, p < 0.001, lymph node metastases: HR 3.5; 95 % CI 1.3–9.7, p = 0.02). When a shift in subtype inherence between primary tumour and metastatic lymph node was identified, the prognosis seemed to follow the subtype of the lymph node. Molecular profiles are not stable throughout tumour progression in breast cancer. Prognostic information for individual patients appears to be available from the analysis of biomarker expression in synchronous metastatic lymph nodes. The study supports biomarker analysis also in asynchronous relapses.
KeywordsBreast cancer Lymph node metastases Relapse Prognosis Tumour progression St Gallen molecular subtypes
The study was supported by funds from the Swedish Breast Cancer Organisation (BRO), the Swedish Cancer Society, Swedish Research Council, the Gunnar Nilsson Cancer Foundation, the Mrs. Berta Kamprad Foundation, Stig and Ragna Gorthons Stiftelse, Skåne County Council’s Research and Development Foundation and Governmental Funding of Clinical Research within the National Health Service (ALF). The authors would like to acknowledge Kristina Lövgren, Division of Oncology, Department of Clinical Sciences Lund, for technical support in the construction of TMAs and Sara Baker, Division of Oncology, Department of Clinical Sciences Lund, for technical support in the scanning procedure.
Conflict of interest
The authors declare no conflict of interest.
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