Axel Stenmark Tullberg -The use of immunological biomarkers to improve individualization of postoperative radiotherapy in breast cancer

Link directly to the doctoral thesis

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ABSTRACT

Radiotherapy (RT) forms the cornerstone of most curative breast cancer treatment due to its well-established risk-reducing effect on local recurrences at the population level. However, there is heterogeneity regarding treatment benefits at the individual level, and research currently aims to better tailor treatment decisions based on tumorbiology. This thesis aimed to investigate if immunological biomarkers from the primary tumor can be used to predict the benefit from radiotherapy (RT) at the individual level and improve treatment individualization.

Tumor blocks were collected from the randomized SweBCG91RT cohort. Immunohistochemical and gene expression analyses of immunological biomarkers in the primary tumor were used to study if the benefit from RT could be predicted. An activated immune response was associated with a reduced risk of local recurrence and a reduced need for postoperative RT. The biological implications of an activated immune response depended on tumor-intrinsic characteristics. By integrating these two dimensions, tumors could be identified where a local immune infiltrate's risk-reducing effect was comparable to that obtained from RT.

Immunological biomarkers from the primary tumor provide independent information on the risk of local recurrence, which can be used to stratify patients according to the need for postoperative radiotherapy. An immune infiltrate's implications depend on tumor-intrinsic characteristics, and successful implementation of immunological biomarkers in clinical practice, therefore, requires a co-analysis of such factors. Tumors with an activated immune response may have a low risk of local recurrence and constitute a group where de-escalation of RT may be feasible.

Figure 7. from page 56 in thesis: Benefit from radiotherapy depending on TILs in the SweBCG91RT cohort.

Having TILs ≥10% was associated with an improved prognosis in multivariable analysis when adjusting for histological grade, age, and RT. Although not significant, the benefit from RT also appeared reduced among tumors with high TILs, compared to tumors with TILs <10%. First published in Kovács, A., Stenmark Tullberg, A., Werner-Rönnerman, E., et al. Journal of Clinical, Oncology (2019) 37:14. Reprinted with permission