Molecular subtyping in breast carcinoma,
How should molecular subtyping and molecular tumor markers in breast cancer care be implemented and would it give patients a better treatment? SCAN-B (Sweden Cancerome Analysis Network – Breast cancer) got ethical and biobank approvals in 2010 and the collecting of fresh tumor tissue started in October the same year. Until September 2016, 9000 patients have been included from hospitals in the southern part of Sweden and tissue have been sampled from 6500 tumors. In Helsingborg a pilot study started in November 2015 with the aim to develop the flow of information and to look at differences in the Nottingham histologic grade (NHG), the immunohistochemistry markers ER, PR, HER2 and Ki67 and molecular subtypes (St Gallen) compared with RNA sequenced markers. Is it possible to have the gene expression report completed to the breast conference which is held within 10 days after surgery? How often would RNA sequencing potentially have an effect on treatment? E.g. turn Luminal A into Luminal B or vice versa. In the pilot study 113 surgery cases and 21 core needle biopsy cases were included. The SCAN-B report include molecular subtype, GGI (genomic grade index), ER, PR, HER2 and Ki67. Molecular subtype is based on PAM50. GGI gene expression is based on a previously published gene signature of 97 genes. ER, PR, HER2 and Ki67 are classified using a multigene classifier from the validation project in SCAN-B based on immunohistochemistry in approximately 400 tumors. In the pilot study the SCAN-B report did not have any impact on treatment decisions. In surgery cases 27 changed molecular subtypes when comparing St Gallen with PAM50. GGI divides NHG 2 in low and high. Three grade 1 cases changed to high and one grade 3 case changed to low. For ER there were 12 discordant cases, for PR 30 cases, for HER2 9 and Ki67 13. To determine the reason for the difference, discordant cases will be reanalyzed. Pitfalls may be not representative tissue, small tumors, heterogeneity or in situ component.
Viktoria Gaspar, MD, specialist in pathology since 2013, Department of Pathology, University and Regional Laboratories of Region Skåne, Sweden. Assessor in NordiQC general module and breast module since 2011.