Discordance of biomarkers in multifocal and lymph node positive breast cancer

Histological, molecular, and genetic characterisation of the tumour can guide tailored adjuvant treatment of breast cancer. However, characteristics can differ between different foci in multifocal cancers [1].

Tailored adjuvant therapy according to histological grade, biomarkers ER, PR, and Her2, and proliferative indicators like Ki67 has been one of the most important factors improving survival in breast cancer. However, a number of reports show that in a small proportion of cases characteristics differ between primary tumour and lymph node metastasis and between different foci in multifocal cancers. Usually, assessment of biomarkers is performed on one primary only. This might lead to some patients receiving suboptimal treatment.

In Sweden, about 9,000 women are diagnosed with breast cancer each year, Dr Marie Sundquist (Kalmar County Hospital, Sweden) and colleagues showed. About 20% have more than one primary tumour and approximately 30% have lymph node metastases. Sundquist et al. explored concordance regarding tumour biology between different primary foci and between lymph node metastases and primary tumour in these patients. From 3 Swedish breast units, they included all consecutive breast cancer patients with more than one primary tumour and/or lymph node metastasis. In these patients, assessments of ER, PR, Her2, and Ki67 were performed with immunohistochemistry and in situ hybridisation on at least two lesions in multifocal cases and on one to two metastatic lymph nodes.

Dr Sundquist presented interim results of the study (74 patients with more than one primary tumour and 58 patients with lymph node metastases). In about 17% of cases there was discordance in tumour biology between foci. In 8 cases, Ki67 scored high in one lesion and low in another. Five of those also differed in histological grade between Nottingham histological grade 3 and 1–2. Three had different ER/PR status, two had Her2 amplification in one foci while the other was normal. In metastatic lymph nodes, the biology differed between primary and metastases in 5 of 58 cases (8,6%). ER/PR nodal status was different from the primary in two cases. One triple-negative tumour had an ER/PR-positive metastasis and one ER/PR-positive primary had an ER/PR-negative metastasis. In three cases, Her2 normal primaries had an amplified lymph node metastasis.

Based on these (interim) results, Sundquist et al. concluded that biomarker status is relatively consistent between foci in multifocal tumours and between lymph node metastases and primaries. However, the results indicate that there is a risk of suboptimal treatment that might have important consequences on the outcome for this subgroup.

1. Sundquist M, et al. The Breast 2019;44(suppl 1):abstract P225.

Posted on 21 May 201924 March 2021