PURPOSE Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating... Show morePURPOSE Triple-negative breast cancer (TNBC) is considered aggressive, and therefore, virtually all young patients with TNBC receive (neo)adjuvant chemotherapy. Increased stromal tumor-infiltrating lymphocytes (sTILs) have been associated with a favorable prognosis in TNBC. However, whether this association holds for patients who are node-negative (N0), young (< 40 years), and chemotherapy-naive, and thus can be used for chemotherapy de-escalation strategies, is unknown.METHODS We selected all patients with N0 TNBC diagnosed between 1989 and 2000 from a Dutch population-based registry. Patients were age < 40 years at diagnosis and had not received (neo)adjuvant systemic therapy, as was standard practice at the time. Formalin-fixed paraffin-embedded blocks were retrieved (PALGA: Dutch Pathology Registry), and a pathology review including sTILs was performed. Patients were categorized according to sTILs (< 30%, 30%-75%, and >= 75%). Multivariable Cox regression was performed for overall survival, with or without sTILs as a covariate. Cumulative incidence of distant metastasis or death was analyzed in a competing risk model, with second primary tumors as competing risk.RESULTS sTILs were scored for 441 patients. High sTILs (>= 75%; 21%) translated into an excellent prognosis with a 15-year cumulative incidence of a distant metastasis or death of only 2.1% (95% CI, 0 to 5.0), whereas low sTILs (< 30%; 52%) had an unfavorable prognosis with a 15-year cumulative incidence of a distant metastasis or death of 38.4% (32.1 to 44.6). In addition, every 10% increment of sTILs decreased the risk of death by 19% (adjusted hazard ratio: 0.81; 95% CI, 0.76 to 0.87), which are an independent predictor adding prognostic information to standard clinicopathologic variables (chi(2) = 46.7, P < .001).CONCLUSION Chemotherapy-naive, young patients with N0 TNBC with high sTILs (>= 75%) have an excellent long-term prognosis. Therefore, sTILs should be considered for prospective clinical trials investigating (neo)adjuvant chemotherapy de-escalation strategies. (c) 2022 by American Society of Clinical Oncology Show less
The objectives of this thesis, aimed to reduce overtreatment of ductal carcinoma in situ (DCIS) of the breast, were : 1) to evaluate the risk of underestimation after a diagnosis of DCIS and the... Show moreThe objectives of this thesis, aimed to reduce overtreatment of ductal carcinoma in situ (DCIS) of the breast, were : 1) to evaluate the risk of underestimation after a diagnosis of DCIS and the interrater reliability in the histopathological classification of DCIS, important conditions in order to safely adopt an active surveillance strategy for low-risk DCIS, 2) to investigate associations of clinicopathological factors with the risk of developing ipsilateral invasive breast cancer after treatment of DCIS and 3) to analyze the extent of response of DCIS, adjacent to HER2-positive breast cancer, to neoadjuvant systemic therapy and to investigate associations of clinicopathological factors with DCIS response.We have taken significant steps on the road towards conquering overtreatment of DCIS: by having identified several clinicopathological prognostic factors in pure DCIS, by providing reassuring evidence regarding underestimation in the context of active surveillance, by stressing the need for improvement of interrater reliability in histopathological classification, and by showing that the presence of DCIS adjacent to HER2-positive breast cancer should not preclude the option of breast conserving surgery. Show less
