Abstract
BackgroundThe St Gallen surrogate molecular subtype definitions classify the oestrogen (ER) positive breast cancer into the luminal A and luminal B subtypes according to proliferation rate and/or expression of human epidermal growth factor receptor 2 (HER2) with differences in prognosis and chemo-responsiveness. Primary tumours and lymph node metastases might represent different malignant clones, but in the clinical setting only the biomarker profile of the primary tumour is used for selection of adjuvant systemic treatment. The present study aimed to classify primary breast tumours and matched lymph node metastases into luminal A, luminal B, HER2-positive and triple-negative subtypes and compare the distributions.MethodsEighty-five patients with available tumour tissue from both locations were classified. The distribution of molecular subtypes in primary tumours and corresponding lymph node metastases were compared, and related to 5-year distant disease-free survival (DDFS).ResultsThe St Gallen molecular subtypes were discordant between primary tumours and matched lymph node metastases in 11% of the patients (p = 0.06). The luminal A subtype in the primary tumour shifted to a subtype with a worse prognostic profile in the lymph node metastases in 7 of 45 cases (16%) whereas no shift in the opposite direction was observed (0/38) (p = 0.02). All subtypes had an increased hazard for developing distant metastasis during the first 5 years after diagnosis in both primary breast tumours and matched lymph node metastases, compared with the luminal A subtype.ConclusionThe classification according to the St Gallen molecular subtypes in primary tumours and matched lymph node metastases, implicates a shift to a more aggressive subtype in synchronous lymph node metastases compared to the primary breast tumour. The selection of systemic adjuvant therapy might benefit from taking the molecular subtypes in the metastatic node into account.
Highlights
The St Gallen surrogate molecular subtype definitions classify the oestrogen (ER) positive breast cancer into the luminal A and luminal B subtypes according to proliferation rate and/or expression of human epidermal growth factor receptor 2 (HER2) with differences in prognosis and chemo-responsiveness
The present study aimed to investigate whether classification into luminal A, luminal B, HER2-positive and triple-negative subtypes provides information beyond that of the individual analyses of Oestrogen receptor (ER), progesterone receptor (PR), HER2 and Ki67 when comparing the inherence between the primary tumour and matched lymph node metastases in terms of distribution and prognosis
16% (7/45) of the cases which were luminal A in the primary tumour shifted to a subtype with a worse prognosis according to the lymph node metastases, whereas not a single shift in the opposite direction was observed (0/38)
Summary
The St Gallen surrogate molecular subtype definitions classify the oestrogen (ER) positive breast cancer into the luminal A and luminal B subtypes according to proliferation rate and/or expression of human epidermal growth factor receptor 2 (HER2) with differences in prognosis and chemo-responsiveness. The present study aimed to classify primary breast tumours and matched lymph node metastases into luminal A, luminal B, HER2-positive and triple-negative subtypes and compare the distributions. Prognostic information for the individual patient is based on the analysis of biological markers in the primary tumour including oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67, together with age, tumour size, histological grade and lymph node engagement [1]. The luminal B subtype has a high proliferation rate and/or a high histological grade and systemic treatment with chemotherapy followed by endocrine therapy is recommended [10,11]
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