Association of clinicopathologic and sonographic features with stromal tumor-infiltrating lymphocytes in triple-negative breast cancer.

BACKGROUND: Increased level of stromal tumor-infiltrating lymphocytes (sTILs) are associated with therapeutic outcomes and prognosis in triple-negative breast cancer (TNBC). This study aimed to investigate the associations of clinicopathologic and sonographic features with sTILs level in TNBC. METHODS: This study included invasive TNBC patients with postoperative evaluation of sTILs after surgical resection. Tumor shape, margin, orientation, echo pattern, posterior features, calcification, and vascularity were retrospectively evaluated. The patients were categorized into high-sTILs (≥ 20%) and low-sTILs (< 20%) level groups. Chi-square or Fisher's exact tests were used to assess the association of clinicopathologic and sonographic features with sTILs level. RESULTS: The 171 patients (mean ± SD age, 54.7 ± 10.3 years [range, 22‒87 years]) included 58.5% (100/171) with low-sTILs level and 41.5% (71/171) with high-sTILs level. The TNBC tumors with high-sTILs level were more likely to be no special type invasive carcinoma (p = 0.008), higher histologic grade (p = 0.029), higher Ki-67 proliferation rate (all p < 0.05), and lower frequency of associated DCIS component (p = 0.026). In addition, the TNBC tumors with high-sTILs level were more likely to be an oval or round shape (p = 0.001), parallel orientation (p = 0.011), circumscribed or micro-lobulated margins (p < 0.001), complex cystic and solid echo patterns (p = 0.001), posterior enhancement (p = 0.002), and less likely to have a heterogeneous pattern (p = 0.001) and no posterior features (p = 0.002). CONCLUSIONS: This preliminary study showed that preoperative sonographic characteristics could be helpful in distinguishing high-sTILs from low-sTILs in TNBC patients.

Combining Analysis of Tumor-infiltrating Lymphocytes (TIL) and PD-L1 Refined the Prognostication of Breast Cancer Subtypes.

BACKGROUND: PD-L1 has been used as a biomarker to select patients for treatment of PD-1/PD-L1 inhibitors. MATERIALS AND METHODS: In this study, we assessed the clinicopathological features of breast cancers that are associated with PD-L1 expression, as well as its relationship with other immune components and its prognostic significance. RESULTS: Totally 1752 cases were included in this cohort. PD-L1 expression in tumor-infiltrating immune cells (PD-L1-IC) expression and in tumor cells (PD-L1-TC) expression were identified in 34.2% and 10.1% of cases, respectively, and they showed a positive correlation with higher tumor grade, morphological apocrine features, presence of necrosis, and higher stromal tumor-infiltrating lymphocytes (sTIL). PD-L1-IC and PD-L1-TC expression correlated positively with each other, and both of them were negatively associated with estrogen receptor and progesterone receptor and positively associated with Ki67, HER2, EGFR, p63, and p-cadherin. In survival analysis, PD-L1-IC expression was associated with better disease-free survival (DFS) and breast cancer-specific survival (BCSS) in HER2-overexpressed (HER2-OE) cancers and high-grade luminal B cancers. In triple-negative breast cancers (TNBC) and HER2-OE cancers, compared with sTIL low PD-L1-IC negative cases, sTIL high cases showed significantly better DFS independent of PD-L1-IC status. sTIL low PD-L1-IC positive cases also demonstrated a better DFS in HER2-OE cancers. In high-grade luminal B cancers, sTIL high PD-L1-IC positive cases showed the best BCSS. CONCLUSION: The data suggested that the combining analysis of sTIL and PD-L1-IC expression refined the prognostication of breast cancer subtypes. Cases with high TIL and PD-LI-IC expression appear to be more immune active.

Soluble B7H3 level in breast cancer and its relationship with clinicopathological variables and T cell infiltration.

Aim of the study: Although early diagnosis of breast cancer (BC) is often associated with a good prognosis, there is currently no biomarker with high sensitivity serving this purpose. B7H3, a recently identified member of the B7 family, appears to inhibit antitumor immunity. We investigated the soluble B7H3 (sB7H3) level in BC and its relationship with clinicopathological variables and stromal tumor-infiltrating lymphocytes (sTILs). Material and methods: The study, which was designed as a cross-sectional trial between January 2020 and September 2021, included 93 BC patients, 20 patients with benign breast disease (BBD) and 14 healthy volunteers as the control group. Serum sB7H3 levels were measured using the ELISA (enzyme-linked immunosorbent assay) method and sTILs were measured by immunohistochemistry using Tru-cut biopsy materials. Results: sB7H3 levels in BC patients were significantly higher than those in patients with BBD and healthy volunteers. Receiver operating characteristic curve analysis results showed that sB7H3 level may be a potential biomarker for distinguishing patients with BC from those with BBD (AUC: 0.807; sensitivity: 0.786; specificity: 0.706) and from healthy volunteers (AUC: 0.731; sensitivity: 0.700; specificity: 0.692). Conclusions: To the best of our knowledge, the present study is the first to investigate the relationship between sB7H3 and disease parameters in BC. We found that sB7H3 may be a clinically practical and meaningful biomarker in differentiating BC from BBD. In order to evaluate the relationship of B7H3 with clinical variables in BC, and especially with sTILs, tissue-based studies with higher numbers of patients are needed.

Total metabolic tumor volume and spleen metabolism on baseline [18F]-FDG PET/CT as independent prognostic biomarkers of recurrence in resected breast cancer.

PURPOSE: We evaluated whether biomarkers on baseline [18F]-FDG PET/CT are associated with recurrence after surgery in patients with invasive breast cancer of no special type (NST). METHODS: In this retrospective single-center study, we included consecutive patients with non-metastatic breast cancer of NST who underwent [18F]-FDG PET/CT before treatment, including surgery, between 2011 and 2016. Clinicopathological data were collected. Tumor SUVmax, total metabolic tumor volume (TMTV), and spleen- and bone marrow-to-liver SUVmax ratios (SLR, BLR) were measured from the PET images. Cut-off values were determined using predictiveness curves to predict 5-year recurrence-free survival (5y-RFS). A multivariable prediction model was developed using Cox regression. The association with stromal tumor-infiltrating lymphocytes (TILs) levels (low if <50%) was studied by logistic regression. RESULTS: Three hundred and three women were eligible, including 93 (31%) with triple-negative breast carcinoma. After a median follow-up of 6.2 years, 56 and 35 patients experienced recurrence and death, respectively. The 5y-RFS rate was 86%. In multivariable analyses, high TMTV (>20 cm3) and high SLR (>0.76) were associated with shorter 5y-RFS (HR 2.4, 95%CI 1.3-4.5, and HR 1.9, 95%CI 1.0-3.6). In logistic regression, high SLR was the only independent factor associated with low stromal TILs (OR 2.8, 95%CI 1.4-5.7). CONCLUSION: High total metabolic tumor volume and high spleen glucose metabolism on baseline [18F]-FDG PET/CT were associated with poor 5y-RFS after surgical resection in patients with breast cancer of NST. Spleen metabolism was inversely correlated with stromal TILs and might be a surrogate for an immunosuppressive tumor microenvironment.

The integration of proportion and cell counts of stromal, not intratumoral, PD-1+ tumor-infiltrating lymphocytes has prognostic significance in esophageal squamous cell carcinoma.

The present study aimed to investigate the prognostic effect of intratumoral and stromal exhausted tumor-infiltrating lymphocytes (TILs) on operable esophageal cancer patients. We performed a retrospective cohort study by consecutively recruiting 142 patients with esophageal cancer. The proportion and cell counts of intratumoral and stromal PD-1+ TILs in tumor microenvironment were independently evaluated by two pathologists. Neither proportion nor cell counts of intratumoral PD-1+ TILs was associated with prognosis (p > 0.05). However, patients with the proportion of stromal PD1+ TILs >20% had the median overall survival (OS) at 19 months, significantly longer than those with the proportion = 20%. The adjusted hazard ratio (HR) was 1.49 (95%CI 0.82, 2.69). Patients with cell counts of stromal PD1+ TILs = 18/ high-power field (HPF) had the median disease-free survival (DFS) at 10 months. However, patients with cell counts>18/HPF had the median DFS at 48 months (p = 0.037), and the adjusted HR was 0.59 (95%CI 0.35, 1.01). Compared with patients with proportion = 20% and cell counts >18/HPF of stromal PD1+ TILs, patients with proportion = 20% and cell counts = 18/HPF, proportion >20% and cell counts >18/HPF, and proportion >20% and cell counts = 18/HPF, had the adjusted HRs increased to 3.73, 3.36 and 3.99 for DFS (p for trend being 0.030) and the adjusted HRs increased to 2.95, 3.64 and 3.82 (p for trend being 0.015) for OS, respectively. The integration of proportion and cell counts of PD-1+ stromal TILs has a significant association with the relapse and overall survival of esophageal cancer patients. Further prospective studies are warranted.

Preoperative lymphocyte/C-reactive protein ratio and its correlation with CD8+ tumor-infiltrating lymphocytes as a predictor of prognosis after resection of intrahepatic cholangiocarcinoma.

PURPOSE: To clarify whether the preoperative lymphocyte/C-reactive protein (CRP) ratio (LCR) is a prognostic factor for patients with intrahepatic cholangiocarcinoma (IHCC), and investigate its mechanism via tumor-infiltrating lymphocytes. METHODS: The subjects of this retrospective study were 42 patients who had undergone hepatectomy for IHCC. We divided the patients into low LCR and high LCR groups (cutoff value: 8780) and analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated the levels of stromal tumor-infiltrating lymphocytes (TILs) and CD8+ TILs in surgical specimens, and the relationship between LCR and TILs. RESULTS: A low LCR was identified in 21 patients and was significantly correlated with older age, a high CRP-albumin ratio, and advanced disease stage, and was a prognostic factor for OS and DFS. Multivariate analysis revealed that a low LCR was an independent prognostic factor for worse OS (HR 10.40, P = 0.0077). Although the LCR and levels of stromal TILs were not significantly related, LCR and levels of CD8+ TILs were significantly related (P = 0.0297). CONCLUSION: The preoperative LCR may predict the postsurgical prognosis of patients with IHCC and reflect the CD8+ TILs.

Development and validation of nomograms predicting survival in Chinese patients with triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Nomograms predicting outcomes of TNBC are needed for risk management. METHODS: Nomograms were based on an analysis of 296 non-metastatic TNBC patients treated at Sun Yat-sen Memorial Hospital from 2002 to 2014. The end points were disease-free survival (DFS) and overall survival (OS). Predictive accuracy and discriminative ability were evaluated by concordance index (C-index), area under the curve (AUC) and calibration curve, and compared with the American Joint Committee on Cancer (AJCC) staging system, PREDICT and CancerMath. Models were subjected to bootstrap internal validation and external validation using independent cohorts of 191 patients from the second Xiangya Hospital and Peking University Shenzhen Hospital between 2007 and 2012. RESULTS: On multivariable analysis of training cohort, independent prognostic factors were stromal tumor-infiltrating lymphocytes (TILs), tumor size, node status, and Ki67 index, which were then selected into the nomograms. The calibration curves for probability of DFS and OS showed optimal agreement between nomogram prediction and actual observation. The C-index of nomograms was significantly higher than that of the seventh and eighth AJCC staging system for predicting DFS (training: 0.743 vs 0.666 (P = 0.003) and 0.664 (P = 0.024); validation: 0.784 vs 0.632 (P = 0.02) and 0.607 (P = 0.002)) and OS (training: 0.791 vs 0.683 (P = 0.004) and 0.677 (P < 0.001); validation: 0.783 vs 0.656 (P = 0.006) and 0.606 (P = 0.001)). Our nomograms had larger AUCs compared with PREDICT and CancerMath. In addition, the nomograms showed good performance in stratifying different risk groups of patients both in the training and validation cohorts. CONCLUSION: We have developed novel and practical nomograms that can provide individual prediction of DFS and OS for TNBC based on stromal TILs, tumor size, node status, and Ki67 index. Our nomograms may help clinicians in risk consulting and selection of long term survivors.

Incorporation of stromal tumor-infiltrating lymphocytes into an early death prediction model significantly improves net reclassification for outcome estimation in advanced buccal cancer.

We explored the impact of stromal tumor-infiltrating lymphocytes (sTILs) on the prognostic value of an early death model for advanced buccal cancer. We assessed 121 patients with advanced buccal cancer who underwent primary tumor resection at a medical center. Predictors of early death and 5-year overall survival (OS) were analyzed using Cox regression models. Performance of models was evaluated with the Harrell C and Akaike information criterion. The net reclassification improvement of the early death model was also calculated relative to the 5-year OS model for one-year all-cause mortality. A total of 121 patients with advanced buccal cancer were recruited. Mean age was 56.1 ± 9.8 years; 117 (96.7%) patients were male. sTILs ≤30%, clinical nodal disease, pathological nodal disease, poor differentiation, lymphovascular invasion, perineural invasion, WPOI 5, and no adjuvant radiotherapy were risk factors for early death in univariate analysis. In multivariate analysis, clinical TNM, sTILs, clinical nodal disease, poor differentiation, lymphovascular invasion, and no adjuvant RT were independent factors for early death. sTILs, pathological nodal disease, poor differentiation, lymphovascular invasion, and no adjuvant RT were independent factors for early death in the multivariate model with pathological TNM. The discriminatory ability was better for early death model for 1-year all-cause mortality. Finally, incorporation of sTILs into the early death model increased net reclassification by 21% for the clinical TNM model and 28% for the pathological TNM model. Addition of sTILs improved the early death model, which may help physicians to identify high-risk patients for more intensive treatment and follow-up.

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Stromal Tumor-Infiltrating Lymphocytes Associated with Immunohistopathology and Molecular Subtypes of Breast Cancer in Vietnam.

OBJECTIVE: Breast cancer is a heterogeneous disease with varied symptoms and pathogenesis, as well as variable prognosis and therapeutic outcomes. Stromal tumor-infiltrating lymphocytes, one of the tumor microenvironment factors, has been recognized as an important immunological biomarker that reflected the antitumor immune response in breast cancer. METHODS: We analyzed 207 invasive breast cancer patients who had lumpectomy or mastectomy and have not received any pre-operative treatment. Clinicopathological characteristics, immunohistochemistry characteristics, molecular subtypes classification and stromal TILs evaluation were investigated. RESULT: Stromal TILs correlated with well-established prognostic markers. Tumor grade showed significantly higher sTILs percentages in high-grade tumors than in low-grade tumors (p<0.001). There was a statistically significant association between intermediate and high levels of sTILs and a high Ki-67 index (p< 0.001). ER/PR negative was significantly related to high sTILs. Mean sTILs score was significantly higher in TNBC (40.1±31.6%) compared to others, statistically significant (p<0.001). In HER2-negative breast cancer, sTILs were significantly associated with histologic grade, ER status, PR status, and Ki67 index. CONCLUSION: sTILs played an important role, associated with unfavorable factors in breast cancer. Our findings support the use of stromal sTILs to identify a more aggressive phenotype of tumors.

Characterization and spatial distribution of the immune cell infiltrate in triple-negative breast cancer: a novel classification based on plasma cells and CD8+ T cells.

Stromal tumor-infiltrating lymphocytes (sTILs) are a robust prognostic and predictive biomarker in triple-negative breast carcinoma. However, the sTIL compartment comprises different cell populations. The aim of the study is to characterize the distribution of T cells (CD3+ and CD8+), B cells, and plasma cells and explore their association with outcome in the surgical specimen of 62 patients. Furthermore, programmed death ligand 1 expression and the presence of tertiary lymphoid structures (TLSs) are explored. Patients with higher sTILs achieve better progression-free survival (PFS) (P = .0013), and tumors have more plasma cells in the infiltrate. Specifically, higher counts of T cells (both CD3+ and CD8+) have better PFS (P = .002 and P = .0086, respectively) as it is observed in tumors with higher infiltration of CD8+ T cells in the tumor core (P = .035). Higher infiltration by B cells and plasma cells shows a positive tendency toward increased PFS (P = .06 and P = .058). Programmed death ligand 1 (SP142) is positive in 56% of tumors. Tumors with at least 1 TLS (42%) show higher CD8+ T cell infiltration in the tumor core and the sTIL value doubles compared to tumors devoid of TLSs [sTIL mean: 36 ± 11% and 18 ± 5% (CI [Confidence Interval]: 95%), respectively]. Our study demonstrates that the characterization of the immune cell infiltration is as relevant as its distribution. Moreover, the importance of considering different immune cell types for classification is emphasized. Therefore, a new classification of triple-negative breast carcinoma immune infiltration with CD8+ T cell and plasma cell densities in the tumor core and infiltrative margin is proposed.

BI-RADS Ultrasound Lexicon Descriptors and Stromal Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.

PURPOSE: Increased levels of stromal tumor-infiltrating lymphocytes (sTILs) have recently been considered a favorable independent prognostic and predictive biomarker in triple-negative breast cancer (TNBC). The purpose of this study was to determine the relationship between BI-RADS (Breast Imaging Reporting and Data System) ultrasound lexicon descriptors and sTILs in TNBC. MATERIALS AND METHODS: Patients with stage I-III TNBC were evaluated within a single-institution neoadjuvant clinical trial. Two fellowship-trained breast radiologists used the BI-RADS ultrasound lexicon to assess pretreatment tumor shape, margin, echo pattern, orientation, posterior features, and vascularity. sTILs were defined as low <20 or high ≥20 on the pretreatment biopsy. Fisher's exact tests were used to assess the association between lexicon descriptors and sTIL levels. RESULTS: The 284 patients (mean age 52 years, range 24-79 years) were comprised of 68% (193/284) with low-sTIL tumors and 32% (91/284) with high-sTIL tumors. TNBC tumors with high sTILs were more likely to have the following features: (1) oval/round shape than irregular shape (p = 0.003), (2) circumscribed or microlobulated margins than spiculated, indistinct, or angular margins (p = 0.0005); (3) complex cystic and solid pattern than heterogeneous pattern (p = 0.006); and (4) posterior enhancement than shadowing (p = 0.002). There was no significant association between sTILs and descriptors for orientation and vascularity (p = 0.06 and p = 0.49, respectively). CONCLUSION: BI-RADS ultrasound descriptors of the pretreatment appearance of a TNBC tumor can be useful in discriminating between tumors with low and high sTIL levels. Therefore, there is a potential use of ultrasound tumor characteristics to complement sTILs when used as stratification factors in treatment algorithms for TNBC.

Prognostic significance of tumor-infiltrating lymphocytes in premenopausal, luminal breast cancer treated with adjuvant endocrine therapy.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) have strong prognostic value in triple-negative and HER2-enriched breast cancer, but their prognostic role in luminal breast cancer (LBC) is less clear. Here, we assessed the overall TIL levels and CD8+ T-cells in relation to the prognosis of LBC patients from China. METHODS AND RESULTS: A total of 596 patients with LBC who were premenopausal and treated with adjuvant endocrine therapy were included. Among them, 160 cases were evaluated for CD8 by immunohistochemical (IHC) staining. Whole-section hematoxylin and eosin and IHC staining were visually assessed for stromal TILs (sTILs), stromal CD8+ T-cells (sCD8), and intratumoral CD8+ T-cells (iCD8). Multivariable analyses were used to test the associations between TILs and disease-free survival (DFS) and overall survival (OS) with the adjustment for clinicopathologic characteristics and treatment. High sTILs (≥10%) were associated with high histologic grade (P<0.001), luminal B/HER2- (P<0.001), luminal B/HER2+ subtype (P=0.002), and high Ki67 expression (≥25%; P=0.014). Similar associations were observed for sCD8 but not for iCD8. While sTILs and sCD8 were not associated with either DFS or OS, the presence of iCD8 (≥1%) was associated with better DFS in both univariate (HR=0.51, 95% CI 0.26-0.96, P=0.042) and multivariate (HR=0.48, 95% CI 0.25-0.92, P=0.027) analyses. Similar but less significant associations were found for iCD8 and OS (adjusted HR=0.35, 95% CI 0.11-1.10, P=0.073). CONCLUSIONS: Among Chinese premenopausal patients with LBC, iCD8 demonstrated suggestive associations with favorable outcome. In contrast, although sTILs and sCD8 were associated with more aggressive tumor features, they did not appear to be associated with clinical outcome.

Prognostic Roles of Neutrophil-to-Lymphocyte Ratio and Stromal Tumor-Infiltrating Lymphocytes and Their Relationship in Locally Advanced Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) and stromal tumor-infiltrating lymphocytes (sTILs) are associated with immunogenicity and prognosis of patients with triple-negative breast cancer (TNBC). OBJECTIVE: To investigated the prognostic roles of NLR and sTILs and their rela-tionship of TNBC patients treated with neoadjuvant chemotherapy (NAC). METHODS: The clinical data of 170 patients with locally advanced TNBC who received NAC from January 2010 to December 2014 were collected. The difference among variables was calculated by χ2 test. The association between essential clinicopathological characteristics, pathological complete response (pCR), NLR, and sTILs with disease-free survival (DFS) was analyzed. Kaplan-Meier and Cox analysis were performed to address the effects of clinical parameters on prognosis. RESULTS: There was a trend that TNBC patients with lower baseline NLR (NLR1) or higher sTILs scoring would obtain a better pCR rate. NLR1 and sTILs were not associated (p > 0.05). Patients with low NLR1 or high sTILs scoring had a significantly improved DFS compared to those with high NLR1 or low sTILs scoring (p = 0.002 and p = 0.001, respectively). The increased lymphocyte count in peripheral blood after NAC was associated with the improved DFS outcome in both high and low NLR1 groups. Cox analysis revealed that NLR1 and sTILs were independent prognostic predictors of DFS outcome (p < 0.001). CONCLUSION: Low NLR1 and high sTILs were associated with better DFS outcome in locally advanced TNBC patients treated with NAC. Further studies are needed to explore the connection between systemic and local inflammatory/immune markers.

A high neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with a worse outcome in inflammatory breast cancer.

INTRODUCTION: Inflammatory breast cancer (IBC) is an uncommon, but aggressive form of breast cancer that accounts for a disproportionally high fraction of breast cancer related mortality. The aim of this study was to explore the peripheral immune response and the prognostic value of blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), in a large IBC cohort. PATIENTS & METHODS: We retrospectively identified 127 IBC patients and collected lab results from in-hospital medical records. The differential count of leukocytes was determined at the moment of diagnosis, before any therapeutic intervention. A cohort of early stage (n = 108), locally advanced (n = 74) and metastatic breast cancer patients (n = 41) served as a control population. RESULTS: The NLR was significantly higher in IBC compared to an early stage breast cancer cohort, but no difference between IBC patients and locally advanced breast cancer patients was noted. In the metastatic setting, there was also no significant difference between IBC and nIBC. However, a high NLR (>4.0) remained a significant predictor of worse outcome in IBC patients (HR: 0.49; 95% CI: 0.24-1.00; P = .05) and a lower platelet-lymphocyte ratio (PLR) (≤210) correlated with a better disease-free survival (DFS) (HR: 0.51; 95% CI: 0.28-0.93; P = .03). CONCLUSION: Patients with a high NLR (>4.0) have a worse overall prognosis in IBC, while the PLR correlated with relapse free survival (RFS). Since NLR and PLR were not specifically associated with IBC disease, they can be seen as markers of more extensive disease.

Locally advanced breast cancer: Tumor-infiltrating lymphocytes as a predictive factor of response to neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the pathologic response after neoadjuvant chemotherapy in patients with breast cancer according to the stromal tumor-infiltrating lymphocytes (TILs) as well as the evaluation of overall and disease-free survival according to TILs. METHODS: A six years (2008-2013) review was done including patients with locally advanced breast cancer that received neoadjuvant therapy and then surgery. An evaluation of the percentage of TILs was done in the pretreatment biopsies and a correlation analysis and survival curves were done. RESULTS: 187 patients were evaluated. The pathological complete response (pCR) in patients with TILs ≥30% was 58.5%, and in patients with TILs < 30% was 11% (p <0.001). An Odds Ratio of 8.85 was obtained in patients with TILs ≥30% to achieve a pCR. This relationship was seen in patients with HER2-enriched and triple-negative subtypes. No correlation between TILs and survival was obtained (OS: log-rank; p = 0.834; DFS: log-rank; p = 0.937). CONCLUSIONS: The study of TILs is important because they represent an additional tool to predict the response to neoadjuvant treatment mostly in HER2-enriched and triple-negative subtypes of breast cancer.