BackgroundTumour-infiltrating lymphocytes (TILs) have been demonstrated to significantly influence prognosis and response to therapy of invasive breast cancer (IBC). Thus, it has been suggested that TIL density or/and immunophenotype could serve as biomarkers for selection of IBC patients for immunotherapy. However, much less is known about significance of TILs in breast ductal carcinoma in situ (DCIS).MethodsWe retrospectively investigated TIL density and immunophenotype in 96 pure DCIS and 35 microinvasive carcinomas (miCa). TIL density was assessed on H&E-stained breast biopsy sections as the percentage of tumour stromal area occupied by TILs, and classified into 4 grades: 0 (0%–9%), 1 (10–29%), 2 (30–49%) and 3 (50%–100%). TIL immunophenotype was assessed by immunohistochemistry for CD8, CD4, FoxP3, CD38 or CD20.ResultsCompared to pure DCIS, miCa contained significantly more cases with TIL density grade 3 (p = 0.028). Concordantly, CD8+, CD4+ and CD38+ cells were more numerous in miCa than in pure DCIS. In the pure DCIS subgroup with TIL density grades 2 and 3, all TIL subpopulations were more numerous than in the pure DCIS with TIL density grades 0 and 1, however the ratio between T-lymphocytes (CD8+ and CD4+) and B-lymphocytes (CD20+) was significantly lower (p = 0.029). On the other side, this ratio was significantly higher in miCa, in comparison with pure DCIS having TIL density grades 2 and 3 (p = 0.017). By cluster analysis of tumour cell pathobiological features we demonstrated similarity between miCa and the pure DCIS with TIL density grades 2 and 3. The only significant difference between those two categories was in the ratio of T- to B-TILs, higher in miCa.ConclusionResults indicate that TIL density level can distinguish 2 biologically different DCIS subgroups, one of which (DCIS with ≥30% TILs, the TIL-rich DCIS) is like miCa. Similarity of TIL-rich pure DCIS and miCa as well as the role of B-lymphocytes in DCIS invasiveness are worth further investigating with regards to the potential development of immunotherapy-based prevention of DCIS progression.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4013-6) contains supplementary material, which is available to authorized users.

BackgroundWhen invasive components are discovered at mastectomy for vacuum-assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option available is axillary lymph node dissection (ALND). The primary aim of this prospective multicenter trial was to determine the benefit of performing upfront sentinel lymph node (SLN) biopsy for these patients. The secondary aim was to determine DCIS factors associated with microinvasion or invasion.MethodsThe SLN procedure was performed during mastectomy, and for positive SLN an ALND was performed during the same intervention. A tissue microarray containing DCIS lesions from the mastectomy specimens was subsequently performed.ResultsFrom May 2008 to December 2010, 228 patients were enrolled from 14 French cancer centers, including 192 eligible patients with pure DCIS on VAB and successful SLN procedures. ALND was avoided for 51 [67 %; 95 % confidence interval (CI), 56–77 %] of all the patients who had microinvasive DCIS or DCIS associated with invasive carcinoma at mastectomy and a negative SLN. Of the 192 patients, 76 (39 %) with VAB-diagnosed DCIS were upgraded after mastectomy to micro (n = 20) or invasive disease (n = 56). The rate of positive SLN for patients with DCIS on VAB was 14 %. High nuclear grade of DCIS was associated with greater risk of microinvasion and invasion, and HER2-amplified DCIS was associated with greater risk of invasion.ConclusionsUnderestimation of invasive components is high when DCIS is diagnosed by VAB in patients undergoing mastectomy. Upfront SLN for patients with VAB-diagnosed extensive DCIS avoids unnecessary ALND for two-thirds of patients with micro or invasive disease on mastectomy.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-015-4476-5) contains supplementary material, which is available to authorized users.

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Para-aortic surgical staging in LACC is more deleterious for patients than clinical staging.

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