İnvaziv Duktal Meme Kanseri Hastalarında Eşlik Eden İn Situ Duktal Karsinomun Prognoza ve Sağkalıma Etkisi

Abstract

Koray F. N. The effect on prognosis and survival of co-existence ductal carcinoma in situ in invasive ductal breast cancer. Hacettepe University Faculty of Medicine, Internal Diseases Specialty Thesis, ANKARA, 2022. Breast cancer is the most commonly diagnosed cancer and it is the second most common cause of cancer related death in women. The most common histopathological type of breast cancer is invasive ductal carcinoma (IDC). Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. Some researches showed that there are biological differences between pure IDC and IDC+DCIS tumors. The purpose of the present study was to evaluate the effect of co-existence DCIS in IDC on tumor microenvironment, clinical and pathological features of the tumor, prognosis and survival. A total of 165 IDC and 404 IDC+DCIS patients were enrolled in this study. Furthermore 164 pure IDC patients were matched with 164 IDC+DCIS patients to form a matched cohort. They were exactly matched for age decade, the AJCC version 8 TNM stage, grade of invasive component, hormone receptor and Her2 status. In the whole cohort compared with pure IDC patients, those with IDC+DCIS patients were more likely to be ER and PR positivite (p< 0.001 for each) and to be received hormonal therapy (p< 0.001). In the whole cohort, compared with IDC+DCIS patients, those with pure IDC patients were more likely to have higher percentage of ki-67 (p< 0.001). In the whole cohort and matched cohort, the co-existence of DCIS was associated with significantly improved overall survival (OS) (log rank p= 0.001 and p= 0.01, respectively). Also in the whole cohort and matched cohort, the co-existence of DCIS was associated with significantly improved disease free survival (DFS) (log rank p< 0.001 and p= 0.04, respectively). Furhermore, in the whole cohort, we found that patients with pure IDC had a 2.14 fold higher probability of death and 2.44 fold higher probability of disease (recurrence or distant metastasis or death) than did those patients with IDC+DCIS. In the matched cohort, a 1% increase in stromal TILs was associated longer OS and DFS (Hazard ratio (HR) 0,87 (%95 CI 0,81-0,93), p<0,001 and HR 0,89 (%95 CI 0,86-0,93), p<0,001, respectively). Finally, we utilized the ROC curve analyses in the whole cohort and the matched cohort to predict the cut-off value of the stromal TILs affecting survival. The cut-off value for the optimal stromal TILs that could be used to predict OS of pure IDC patients in the whole cohort and matched cohort was 7.5% (AUC: 0.832 and 0.834, respectively; sensitivity 95%, specificity 67% for both cohorts). The cut-off value for the optimal stromal TILs that could be used to predict DFS of pure IDC patients in the whole cohort and matched cohort was 12.5% (AUC: 0.806; sensitivity 97%, specificity 58% for both cohorts). In ROC analyses utilizing for OS and DFS of IDC+DCIS patients in the whole cohort and matched cohort, the AUC was found to be around 0.5 and the optimal cut-off value for the stromal TILs could not be determined. According to these findings the stromal TILs can use to predict survival in the pure IDC patients, but not the IDC+DCIS patients. Recent studies showed that pure IDC and IDC+DCIS tumors behave biologically different, these two groups of tumor may also behave differently from each other in terms of antitumoral immune response. In this respect, further studies are needed.

Keywords: Breast cancer, invasive ductal carcinoma, ductal carcinoma in situ, tumor infiltrating lymphocyte.