A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients

• Published in: Radiotherapy and oncology Vol. 156; pp. 127 - 135
• Main Authors: Bosma, Sophie C.J., Hoogstraat, Marlous, van Werkhoven, Erik, de Maaker, Michiel, van der Leij, Femke, Elkhuizen, Paula H.M., Fourquet, Alain, Poortmans, Philip, Boersma, Liesbeth J., Bartelink, Harry, van de Vijver, Marc J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-03-2021
• Subjects: Breast conserving therapy; Breast Neoplasms - pathology; Case-Control Studies; DNA Copy Number Variations; Early-stage breast cancer; Humans; Local control; Mastectomy, Segmental; Middle Aged; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Risk Factors; Local control; Breast conserving therapy; Early-stage breast cancer
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2020.11.025

•Primary tumours and local recurrences showed similar genomic profiles.•Several differences between recurring and non-recurring tumors were observed.•No genomic classifier for LR could be identified.•Basal subtype is a strong risk factor for local recurrence.
To investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancer patients randomized in the “Young Boost Trial”.
In the “Young Boost Trial” 2421 patients ≤50 years old were randomized between a 16 Gy and 26 Gy boost after breast conserving surgery and whole breast radiation (50 Gy). We performed a case-control study comparing patients who developed a LR (cases) and for each of them three control patients free of recurrence (controls). Clinicopathological factors, copy number- and gene expression profiles of primary tumors were compared between cases and controls, and between primary tumors and local recurrences.
The cumulative 5-year LR rate was 1.07% (95% CI 0.72-1.59%) and 10-year LR rate 2.56% (1.81–3.62%). Analysis of a subset of primary tumors and local recurrences showed similar histopathological characteristics (n = 15), copy number (n = 13) and gene expression profiles (n = 14). Basal subtype was strongly associated with LR in univariable and multivariable analysis. Gains of CCND1 were identified more frequently among controls, while more frequent gains of FGFR1 and IGF1R were observed among cases. Upregulation of genes involved in the p53-pathway was observed in recurring tumors compared to non-recurring tumors. We could not identify a genomic classifier for LR.
All investigated local recurrences were true genomic recurrences. Although differences in copy number variation and gene expression pathways were observed in recurring tumors compared to non-recurring tumors, no genomic classifier for LR could be identified.