Abstract
Abstract Introduction In primary ductal carcinoma in situ of the breast (DCIS) tumour biological features associated with risk of invasive recurrence and metastasis may already be present at the pre-invasive stage. The aim of this study was to investigate the correlation of biological markers in DCIS and the risk of subsequent breast cancer death. Patients and methods A nested case-control study was conducted in a population based cohort of women diagnosed with primary DCIS between 1992 and 2012. Women who later died from breast cancer were identified. Four controls per case were selected randomly by incidence density sampling from the same cohort. Tumour blocks were retrieved for histopathological reevaluation and immunohistochemical analysis (IHC) of Oestrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Receptor 2 (HER2) and Ki67 expression. Odds ratios (OR) for risk of breast cancer death with 95% CI was calculated using conditional logistic regression. Results From a cohort of 6964 women with primary DCIS, tumour specimens were available for 66 patients who died from breast cancer and these were compared to samples from 195 controls. DCIS with intense lymphocytic infiltration was associated with an increased risk of breast cancer related death in univariate analysis (OR 2.25; 95%CI 1.02-4.99). None of the biomarkers were individually related to increased risk. In multivariable analysis and stepwise adjusting for age, tumour size and treatment; PR negativity in combination with lymphocytic infiltration (OR 4.40; 95%CI 1.20-16.14), PR negativity, lymphocytic infiltration and presence of comedonecrosis (OR 5.48; 95%CI 1.71-17.57) and the combination of PR negativity, lymphocytic infiltration, comedonecrosis and HER2 positivity (OR 7.54; 95%CI 2.00-28.43) were all independently associated with increased risk of breast cancer related death. Conclusion In the present study, the combination of PR negativity and periductal lymphocytic infiltration was associated with risk of breast cancer related death after primary DCIS. Combining biomarker expressions in DCIS with features in the peritumoural stroma may be useful tools for prognostication. Citation Format: Charlotta Wadsten, Johan Hartman, Irma Fredriksson, Hans Garmo, Fredrik Wärnberg, Malin Sund. Biomarkers associated with dcis related breast cancer death [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-19.
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