Correlation between Intratumoral Cellular Microenvironment, Clinicopathological Parameters and Prognosis in Hodgkin Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2273-2273
Author(s):  
Peter Kamper ◽  
Anne-Sofie Hammer ◽  
Stephen Hamilton-Dutoit ◽  
Knud Bendix ◽  
Bent Honoré ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Hodgkin Lymphoma ◽  
Clinicopathological Parameters ◽  
Advanced Stage ◽  
Histological Subtypes ◽  
Cellular Microenvironment ◽  
Neoplastic Cells ◽  
Stage Disease ◽  
Cell Expression

Abstract Hodgkin lymphoma (HL) is characterized by a minority of neoplastic, Hodgkin, Reed-Sternberg (HRS) cells surrounded by a heterogeneous background of non-neoplastic cells. Previous studies have described a prognostic role of the cellular composition in HL. The aim of the present study was to correlate parameters related to the intratumoral cellular microenvironment with clinicopathological features and prognosis in a cohort of previously untreated HL patients. For this purpose a tissue microarray Array (TMA) consisting of pairs of representative cores (2mm) from each tissue specimen and from positive and negative controls was constructed. Immunohistochemical stains of cellular antigens were assessed and graded. Tissue samples and clinical record data from a total of 87 HL patients were analysed. Histological subtypes were distributed as follows: nodular sclerosis (NS)61 cases (71%), mixed cellularity (MC) 15 (17%), nodular lymphocyte- predominant (NLP) 9 (10%) and lymphocyte depleted 2 (2%). The median age was 36.7 yrs (range 5–83 yrs and the male to female ratio 1.6. 56 had localised (67%) 27 had advanced stage disease (32%). Anaemia and leukocytosis were present in 4 (5%) and 15 (17%) cases, respectively. All patients were treated according to standard guidelines (chemo- radiotherapy for localised disease and ABVD/COPP- based chemotherapy for advanced stage disease). Immunohistichemical stains were used to characterise and quantify the neoplastic and non-neoplastic cells within tumor lesions. Following antigens were studied: CD3, CD20, CD30, CD15, CD10, STAT-6, MUM-2, FAS, p53 and MIB-1. Among histological subtypes NLP HL was, as expected, the one most frequently displaying CD20 positivity, while CD15 and CD30 were more common in classical HL (cHL). A strong CD3 expression in the non-neoplastic by-stander population was inversely correlated with the presence of leukocytosis in the peripheral blood. An opposite pattern was found in cases, mostly cHL, with high expression of STAT-6 in the tumor cell population. In addition to leukocytosis STAT-6 expression also correlated to younger age (60 yrs or less) and presence of B-symptoms. Time-related endpoint analysis was restricted to NS, representing the largest subgroup (n=61). Interestingly, a significant adverse impact on overall survival (OS) was detected in cases with a strong tumor cell expression of STAT-6. Even more marked was the unfavorable prognostic value of low or lacking tumor cell expression of CD30 (p=0.0012) or by-stander cell expression of CD3 (p=0,0133). All these findings were far more evident in younger (≤ 60 yrs) NS-HL patients than in their elderly counterparts. These three parameters where not, or only minimally, influenced by classical clinical prognosticators such as clinical stage, B-symptoms or anemia. Moreover, the adverse prognostic influence of these factors was mutually increased in those cases, where they occurred in combination (high STAT6 + low CD30: p=0.0001; low CD30 + low CD3: p=0.0004; high STAT6 + low CD3: p=0.0017). The role of the STAT family of proteins and that of T-regulatory cells in the pathophysiology of HL should be further elucidated.

Lymphocyte-predominant Hodgkin lymphoma: what is the optimal treatment?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 406-413 ◽  
Author(s):  
Michelle Fanale
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Radiation Treatment ◽  
Early Stage ◽  
B Cell Lymphoma ◽  
B Cell Lymphomas ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Relapsed Disease

AbstractNodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a unique diagnostic entity, with only ∼ 500 new cases in the United States per year with a similar infrequent incidence worldwide. NLPHL also has distinctive pathobiology and clinical characteristics compared with the more common classical Hodgkin lymphoma (cHL), including CD20 positivity of the pathognomic lymphocytic and histiocytic cells and an overall more indolent course with a higher likelihood of delayed relapses. Given the limited numbers of prospective NLPHL-focused trials, management algorithms historically have typically been centered on retrospective data with guidelines often adopted from cHL and indolent B-cell lymphoma treatment approaches. Key recent publications have delineated that NLPHL has a higher level of pathological overlap with cHL and the aggressive B-cell lymphomas than with indolent B-cell lymphomas. Over the past decade, there has been a series of NLPHL publications that evaluated the role of rituximab in the frontline and relapsed setting, described the relative incidence of transformation to aggressive B-cell lymphomas, weighed the benefit of addition of chemotherapy to radiation treatment for patients with early-stage disease, considered what should be the preferred chemotherapy regimen for advanced-stage disease, and even assessed the potential role of autologous stem cell transplantation for the management of relapsed disease. General themes within the consensus guidelines include the role for radiation treatment as a monotherapy for early-stage disease, the value of large B-cell lymphoma–directed regimens for transformed disease, the utility of rituximab for treatment of relapsed disease, and, in the pediatric setting, the role of surgical management alone for patients with early-stage disease.

Surgical Prevention in Ovarian Cancer

2021 ◽  
pp. 194-206
Author(s):  
Alexios Papanikolaou ◽  
Anastasios Liberis ◽  
Anastasia Vatopoulou
Keyword(s):  
Ovarian Cancer ◽  
Primary Prevention ◽  
Early Detection ◽  
Early Diagnosis ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Current Evidence ◽  
Advanced Stage ◽  
Stage Disease

Ovarian cancer is the second most common malignant disease of the female genital tract, but the first in mortality because it is usually diagnosed at an advanced stage. Options for early detection, diagnosis, and treatment are limited. Prevention of ovarian cancer relates to primary prevention by avoiding factors that are epidemiologically associated with an increased incidence of ovarian cancer and the adoption of protective habits. These include interventions to exclude the fallopian tubes and ovaries. Secondary prevention is related to early diagnosis. The chapter aims to summarize current evidence on prevention of ovarian cancer as well as role of surgery to prevent advanced-stage disease.

scholarly journals Optimal Therapy of Advanced Hodgkin Lymphoma

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 310-316 ◽  
Author(s):  
Ranjana Advani
Keyword(s):  
Hodgkin Lymphoma ◽  
Standard Of Care ◽  
Disease Status ◽  
Emission Tomography ◽  
Advanced Stage ◽  
Positron Emission ◽  
Frontline Therapy ◽  
Expanding Population

AbstractAdvanced-stage Hodgkin lymphoma (HL) has become a curable disease in the majority of patients. Research during the last decade has challenged chemotherapy with Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) as the standard of care and debates continue regarding the role of radiation therapy (RT) in this patient population. The incorporation of interim positron emission tomography (PET) imaging and, recently, further characterization of HL on cellular and molecular levels are emerging as tools for treatment stratification and predictors of disease status. Newer targeted therapies have emerged that are very effective in the relapsed setting and are actively being explored as frontline therapy. Lastly, the expanding population of survivors cured of HL outnumbers patients with the disease and needs to be monitored for therapy-related late effects.

Interim Absolute Lymphocyte Count (ALC) As a Predictor of Survival in Hodgkin Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2640-2640
Author(s):  
Tarsheen K. Sethi ◽  
Van T Nguyen ◽  
David S Morgan ◽  
John P. Greer ◽  
Nishitha M Reddy
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Lymphocyte Count ◽  
Absolute Lymphocyte Count ◽  
Disease Stage ◽  
Predictive Score ◽  
Advanced Stage ◽  
Bulky Disease ◽  
Nodular Sclerosis

Abstract Introduction: Patients with Hodgkin lymphoma (HL) have excellent response to current chemotherapy, however, up to 20% may have relapsed/refractory disease. Lymphocytopenia at diagnosis has been found to be predictive of survival in patients with advanced stage HL. An ALC of <600/μlat diagnosis as part of the Hasenclever predictive score is associated with a poorer prognosis. Furthermore, lymphocyte count at the time of apheresis and at day 15 after autologous SCT has been found to be predictive of survival in patients of HL. ALC is considered a surrogate indicator for the tumor microenvironment as well as immune recovery post treatment. There are no large studies evaluating the clinical significance of ALC recovery in patients with HL during initial chemotherapy treatment. In this study, we evaluated the role of lymphocyte recovery during and after standard chemotherapy in patients with HL. Patients and Methods: We analyzed 183 patients with Classical Hodgkin lymphoma treated at our institution between 1996 and 2014 following IRB approval. Complete data was available for 115 patients. We evaluated the absolute lymphocyte count at diagnosis, interim staging (after 2 cycles, Òinterim ALCÓ), at time of completion of chemotherapy and at 6 weeks and 3 months post completion of chemotherapy. Patients were categorized into two groups based on ALC where lymphocytopenia was defined as an ALC of <1x103/µl for adults based on standard criteria. Differences between the two groups were analyzed using Chi- square and t -Student tests. Statistical significance was set at P <0.05. Kaplan Meier method was used to calculate the Progression-free survival (PFS) and overall survival (OS). Log-rank test was used to determine the differences in survival. Statistical analysis was performed using SPSS.22 software. Results: The median age of patients was 31 years (yrs.) (range: 17-76 yrs.) and 53% of patients were male. 100% patients had an ECOG status of 0-1. 48% patients presented with B symptoms, 42% had advanced stage disease (Stage III and IV) and 22% had bulky disease (defined as a mass > 10 cm or mediastinal mass >1/3 of diameter of thorax at T5-T6). In terms of histology, 68% patients had classical nodular sclerosis HL, 19% syncytial variant of nodular sclerosis HL, 8% mixed cellularity HL and 5% Classical HL (NOS). 90% patients received ABVD as their initial chemotherapy, 2% received Stanford V and 1% received MOPP. The remaining patients were treated on a clinical trial. In the analysis of the 115 patients for whom the lymphocyte data was available, at a median follow up of 40 months, 57% in the ALC <1x103/µl group versus 66% in the ALC >1x103/µlgroup had not progressed. The median overall survival was not reached in the two groups. In the multivariate analysis, for PFS, interim ALC predicted survival independent of the interim staging response. The ALC at the time of interim staging scan (interim ALC) was associated with a significantly superior PFS in the group with ALC>1x103/µl(HR=4.16, 95% CI 2.37 to 7.28, P=0.024). There was no difference in overall survival between the groups (Fig. 1&2,P=0.28). For ALC at other time points, no statistically significant differences in PFS or OS were found in the two groups based on ALC at diagnosis, completion of therapy, six weeks and three months post therapy. Discussion: In summary, our results suggest that for patients across all stages and histopathologic subtypes of classical HL receiving first line chemotherapy, interim ALC >1x103/µl (after 2 cycles) is associated with a superior PFS as compared with ALC <1 x103/µl and this is independent of the interim staging response. This did not translate into a difference in OS. Further studies are underway to determine the role of immune effector cells in the context of newer therapeutic agents. Figure 1. PFS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 1. PFS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 2. OS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Figure 2. OS (months) in patients with interim ALC >1x103/ μlvs. <1x103/ μl Disclosures Reddy: Gilead: Other: Speaker; Seattle Genetics: Consultancy; ImmunoGen: Consultancy; PCYC: Consultancy; Celgene: Consultancy, Research Funding.

scholarly journals Relapse Risk and Loss in Expectation of Lifetime in Young Classical Hodgkin Lymphoma Patients - a Nordic Lymphoma Group Study of 2,582 Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 930-930
Author(s):  
Jorne Lionel Biccler ◽  
Ingrid Glimelius ◽  
Sandra Eloranta ◽  
Knut B. Smeland ◽  
Peter de Nully Brown ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Hodgkin Lymphoma ◽  
Relative Survival ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Event Free Survival ◽  
Free Survival ◽  
Relapse Risk ◽  
Limited Stage ◽  
Stage Disease

Abstract Estimates describing the survival and relapse risk for young classical Hodgkin lymphoma (cHL) patients are of considerable interest. A recent population-based study from British Columbia focused on the evolution of the relative survival and relapse risk given that patients reached certain milestones such as two years of relapse-free survival (Hapgood et al. 2016). The study included patients diagnosed before the year 2000 who were treated with regimens that have since been refined. Using register-data from Denmark, Sweden, and Norway, we investigated cHL survivorship in the era of contemporary treatment by inspecting the evolution of relapse risk and loss in life expectancy. Inclusion criteria were: age at diagnosis 18-49 years; diagnosis year between 2000 and 2013; and treatment with chemotherapy (CT) with or without involved node/field radiation therapy (RT). Event-free survival was measured as the time from diagnosis to progression, relapse, or death, whichever came first. The five-year relapse risks from diagnosis and conditional on reaching event-free survival (EFS) milestones were estimated while taking the censoring and competing risk, death, into account. As a measure of relative survival, we estimated the five-year restricted loss in expected lifetime (5y-RLEL), defined as the numeric difference in the number of days a healthy person and a patient with cHL are expected to survive within the next five years. The 5y-RLEL was estimated taking the censoring into account and was estimated for all patients and for those reaching one (EFS1), two (EFS2), or five (EFS5) years of event-free survival. In total, 2,582 cHL patients were included (Denmark n=863, Sweden n=1,236, Norway n=483). The majority were treated with ABVD (n=1,932). Most limited stage (IA-IIA) patients were treated with 2-4 courses of CT and RT with dosage up to 30Gy The majority of the advanced stage (IIB-IV) patients were treated with 6-8 courses of CT +/- RT. A fraction of the patients (n=306) were treated with 6-8 BEACOPP 14 or escalated BEACOPP. Advanced stage patients receiving BEACOPP more often had adverse risk criteria including involvement of the bone-marrow (27% vs 6%) and/or other extranodal sites (60% vs 34%) than advanced stage patients treated with 6-8 cycles of ABVD. The five-year OS was 95.2% (95% CI 94.4 - 96.1) and the five-year risk of relapse was 13.4% (95% CI 12.1-14.8). The dynamic evolution of the five-year relapse risk is shown in Figure 1A and the 5y-RLEL estimates in Figure 1B. For patients reaching the EFS2 and EFS5 milestones, five-year relapse risks were 4.2% (95% CI 3.8 - 4.6) and 0.8% (95% CI 0.8 - 0.9) (Figure 1A), respectively. From diagnosis, the five-year relapse risk for advanced stage patients was twice as high as for limited stage patients, however the difference decreased among patients reaching later EFS milestones and was small after EFS3 irrespective of stage (2.5% [95% CI 2.1 - 2.9] for advanced stage disease vs. 2.0% [95% CI 1.6 - 2.4] for limited stage disease) (Figure 1A). The five-year relapse risk for advanced stage patients treated with 6-8 courses of BEACOPP was comparable to that of advanced stage patients treated with 6-8 courses of ABVD despite more adverse risk criteria among the BEACOPP treated patients (Figure 1A). The 5y-RLEL was limited, e.g. within the first five years post-diagnosis the HL patients were expected to live 46 days (95% CI 35 - 54) less than what was expected for the background population (Figure 1B). Patients reaching the EFS2 milestone had a 5y-RLEL of 13 days (95% CI 7 - 20) and for patients reaching the EFS5 milestone, the 5y-RLEL was 8 days (95% CI 2 - 14) (Figure 1B). Limited stage patients who remained event-free two years post-diagnosis had a minimal 5y-RLEL of 2 days (95% CI -4 - 7) (Figure 1B). By reporting five-year relapse risk and loss of life expectancy overall and conditioned on years in remission, we provide relevant patient-centred prognostic measures for young contemporarily treated cHL patients. The results are reassuring and indicate that limited stage patients who remain event-free two years post-diagnosis have a future life expectancy in line with HL-free individuals. Additionally, irrespective of risk group, the five-year relapse risk was minimal once three years of event-free survival was reached. This information should be taken into account in future surveillance programs. Disclosures Eloranta: Janssen Pharmaceuticals: Other: S Eloranta is currently employed as a project coordinator and her salary is funded via a public-private real world evidence collaboration between Karolinska Institutet and Janssen Pharmaceuticals. Fosså:Janssen Pharmaceuticals, Inc.: Honoraria. Ekstroem Smedby:Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals.

scholarly journals The Prognostic Role of Interim PET after First Chemotherapy Cycle and PET Sequential Evaluation of Response to ABVD in Hodgkin Lymphoma Patients - the Polish Lymphoma Research Group (PLRG) Observational Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3943-3943 ◽  
Author(s):  
Jan M Zaucha ◽  
Bogdan Malkowski ◽  
Edyta Subocz ◽  
Stephane Chauvie ◽  
Joanna Tajer ◽  
...  
Keyword(s):  
Observational Study ◽  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Early Stage ◽  
Advanced Stage ◽  
Prognostic Role ◽  
Interim Pet ◽  
Pet Scans

Abstract Background: Several studies confirmed the predictive role on treatment outcome of interim-PET after 2nd ABVD cycle (iPET2) in Hodgkin lymphoma (HL). We hypothesized that interim PET after 1st cycle (iPET1) might define chemosensitivity with a better accuracy than iPET-2. To test this hypothesis, PLRG launched in 2008 a prospective multicenter observational study aiming at assessing the prognostic role of iPET1 and the dynamic of sequential PET response to ABVD. Methods: Adult pts with newly diagnosed early (stage I-IIA) and advanced (stage IIB-IV) consecutively enrolled in 11 Polish centers were risk-stratified by the EORTC/GELA criteria and treated according to the ESMO guidelines: ABVD x 3-4 cycles + IFRT in early stage, ABVD x 6 ± consolidation RT in advanced stage disease. Patients were scanned with iPET1 and iPET2 and no treatment change was permitted based solely on iPET results, with the exception of clinical or radiological evidence of overt HL progression. After the first interim analysis (52 pts enrolled, 2010), which demonstrated that all the iPET1 negative patients had also a negative iPET2, the protocol was amended, limiting the iPET2 scans only to pts with iPET1 Deauville score 5,4,3. Quality control for PET-CT was supervised by the Italian-Polish core lab using a standard methodology. PET scans were interpreted locally according to the Deauville 5-point scale: Score 1 to 3, was considered a negative (-), score 4 to 5 a positive (+) scan. Subsequently all PET scans were uploaded to the web platform WIDEN® for central review and Italian-Polish expert panel (EP) scored them afresh. Discorcondant cases were discussed in a joint review session with all the five EP members. Binary and overall concordance rates were calculated using k Cohen's and alpha Krippendorf's coefficients, respectively. Negative (NPV) and positive predictive values (PPV) of iPET1 were calculated using time to progression free survival (PFS) event. Results: Between 2008 and 2014, 346 pts were registered. 35 pts were excluded from the analysis for absence/poor quality of images resulting in 108(35%) assessable pts with early and 203(65%) with advanced HL. Median age at diagnosis was 31(18-80) years. iPET1 was scored 1-3 in 87/108(81%), and 4-5 in 21/108(19%) of pts with early and in 133/203(65%), and 70/203(35%) with advanced stage, respectively. Out of 91pts with positive iPET1, 83 pts underwent iPET2, which remained (+) in 41/83(49,4%) pts. In 22 pts treatment was escalated. 11 of those pts, in whom the treatment escalation was decided solely on positive iPET were excluded from the analysis; the remaining had symptoms or CT evidence of progression. After a median follow-up of 40,2 (3,2-90,2) months 300 pts (103 "early" and 197 "advanced") were evaluable. 65(21,7%) of them (9 in early and 56 in advanced group) had a PFS event: in "early" group 9(9%) showed disease progression (4 with iPET1(-) and 5 with IPET1(+)) and 1 of them died. In advanced stage 49(25%) pts showed disease progression (16 with iPET1(-) and 33 withiPET1(+)) out of whom 13 died; 7 additional pts died without HL progression: 4 from toxicity and 3 from unrelated events. At 36 months NPV and PPV of iPET1 was 93% and 45% in "early" and 81% and 52% in "advanced" group, respectively. The dynamic of response to ABVD was assessed in 189 pts who underwent both iPETs. All 116 pts with iPET1(-) remained (-) in iPET2-(fast-responders). Out of 83pts with IPET1(+) 39 (47%) became iPET2(-)-(slow responders); the rest (34pts: 41%) remained iPET2(+)-(no responders). PFS for fast-responders @36 months was 85%, for slow-responders 80% (log rank p=0,36) and for no-responders 25% (log rank p=0,0000). The EP changed the local iPET1 score in 27 cases: in 14 from (+) to (-) in 13 from (-) to (+). The inter-observer-agreement among reviewers on evaluating a positive vs. negative interim PET scans was good, Fleiss' kappa = 0.73, comparable to that found in analogous studies (IVS, HD0607). Conclusion: iPET1 fails to better identify chemosensitivity in ABVD-treated HL compared to iPET2. PPV of iPET1 is substantially inferior to the published results for iPET2. However NPV of iPET1 is comparable to iPET2 and therefore might guide early treatment de-escalation strategies. Disclosures Zaucha: Roche: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Knopinska-Posluszny:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Teva: Other: travel, accommodation, Speakers Bureau. Walewski:Mundipharma; Roche; Takeda: Honoraria, Other: Travel expenses; Amgen; Boehringer Ingelheim; Celgene; Janssen-Cilag; Mundipharma; Roche; Takeda; Teva: Consultancy; Bayer (Inst); Bayer/Onyx (Inst); Boehringer Ingelheim (Inst); Celgene (Inst); Celltrion (Inst); Gilead Sciences (Inst); GlaxoSmithKline (Inst); GlaxoSmithKline (Inst); Mundipharma (Inst); Pfizer (Inst); Roche (Inst); Roche/Genentech (Inst); Seattle Geneti: Research Funding.

scholarly journals Potential prognostic value of PD-L1 and FOXP3 as predictors of relapse in breast cancer

2019 ◽  
Vol 9 (2) ◽  
pp. 38
Author(s):  
Reham Nagib ◽  
Sherine Refat ◽  
Ahmed E. Eladl ◽  
Ziad Emarah ◽  
Khaled Elnaghi
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Treg Cells ◽  
Clinicopathological Parameters ◽  
Advanced Stage ◽  
Breast Cancer Patients ◽  
Duct Carcinoma ◽  
Free Survival ◽  
Cancer Management

Background: Expression of PD-L1 detected by immunohistochemistry can represent a new hope for cancer management. The role of PD L1 in breast cancer is still unclear. Similarly, is the role of tumor-infiltrating FOXP3 +ve regulatory T (Treg) cells where literature data are conflicting. Our study aimed to evaluate the immunohistochemical expression of PD L1 and FOXP3 in breast cancer, correlate them with clinicopathological parameters as well as evaluating their relation.Methods: This is a retrospective study carried out on 136 breast cancer specimens. Only cases with proved pathological diagnosis of infiltrating duct carcinoma of no special type (NST) were included. Tissue microarray blocks were constructed and immunostained with the polyclonal antibody for PDL1 and monoclonal antibody for FOXP3.Results: Statistically significant correlation was found between high FOXP3 and nearly all adverse prognostic factors including; grade III tumors (p = .003), basal-like subtype(p = .001), high Ki67(p = .001), negative ER status(p = .001), negative PR(p = .028), HER2 expression(p = .04), advanced stage (p = .001), and LN metastases(p = .001). For PDL1, only statistically significant correlation with high Ki67 (p = .018) and advanced stage(p = .03) was found. A statistically significant positive correlation was found between PD L1 and FOXP3(p= .001). No statistically significant correlation was found between both PDL1 and FOXP3 in relation to disease-free survival (DFS) (p = .054). PDL1, age (≥ 50 years), nodal metastases were significant predictors of relapse in breast cancer.Conclusion: The current study supports PDL1 as a predictor of relapse in breast cancer. Additionally, it highlights the synergistic role between PDL1 and FOXP3 in breast cancer microenvironment. Each can be considered as a poor prognostic marker in breast cancer. This raises a concern about the benefit of breast cancer patients from blocking of PDL1 pathway.

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