Correlation of Tumor-Infiltrative Lymphocyte Subtypes Alteration with Neoangiogenesis before and after Neoadjuvant Chemotherapy Treatment in Breast Cancer Patients

2014 ◽  
Vol 29 (3) ◽  
pp. 193-203 ◽  
Author(s):  
Monica SM Chan ◽  
Shi-Fan Chen ◽  
Saulo JA Felizola ◽  
Lin Wang ◽  
Noriko Nemoto ◽  
...  

The two most important factors in tumor-stromal interactions are tumor-infiltrating lymphocytes (TIL) and neoangiogenesis (NAng). While changes of these parameters in responders of neoadjuvant chemotherapy (NCTx) have been reported, their correlation with pathological response in breast cancer (BC) patients treated with NCTx have not been described. We therefore evaluated alterations of the TIL subtypes ratio and alterations of NAng using the vasohibin-1-positive ratio (VPR) in BC patients during the course of NCTx. To this aim we used: (i) double immunohistochemistry of CD8 cytotoxic T cells and T regulatory cells (Treg) with Foxp3, determining the CD8+/Foxp3 ratio; (ii) immunostaining of CD31 and vasohibin-1, yielding the VPR, which reflects the NAng status. Changes between the CD8+/Foxp3 ratio and VPR before and after therapy were then correlated with the pathological response of the patients. A concomitant significant decrement of Foxp3 and NAng, represented by VPR, were detected only in NCTx pathological responders (p<0.001 and p=0.044, respectively). The CD8+/Foxp3 ratio increased in both responders and non-responders, but to greater extent in responders (p=0.02). The changes of VPR in the NCTx-treated group differed from those recorded for the patients treated with aromatase inhibitors and shown in our earlier study; this indicates that the reactions of the tumor-stromal interaction to therapy were different among different treatments in BC patients. Changes in Foxp3 and VPR in responders may reflect the dynamic activity of tumor stroma and host immune response to tumor antigens in the tumor microenvironment in response to the NCTx. VPR can be a potential surrogate marker in BC specimens for predicting the response to NCTx, incorporating both features of carcinoma and stromal cells.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12654-e12654
Author(s):  
Katia MERCEDES Roque ◽  
Marco Galvez Nino ◽  
Carlos Arturo Castaneda Altamirano ◽  
Miluska Castillo Garcia ◽  
Joselyn Sanchez ◽  
...  

e12654 Background: The response after neoadjuvant chemotherapy (NAC) is the main prognostic factor in breast cancer (BC), likewise, malnutrition, anemia and systemic inflammation have also been associated to prognosis in breast cancer. We evaluated the association between pathological response (PR) and tumor infiltrating lymphocytes (TILs) post NAC with nutritional predictors as body mass index (BMI), prognostic nutritional index (PNI), anemia and neutrophil/lymphocyte index (N/L). Methods: This is a retrospective analysis of women diagnosed with BC between 2006 to 2017 at Instituto Nacional de Enfermedades (INEN) who received NAC. Pathological response was classified through residual cancer burden (RCB) and TILs post NAC which were prospectively evaluated by a pathologist. Clinical and pathological features as well as survival status were obtained from patient files. Results: We identified 439 women with BC who received NAC. Median age was 49 years, histological grade 3 was found in 245 patients (55.8%) and stage IIIB was the most frequent at diagnosis with 257 patients (58.5%). Luminal B subtype was the most frequent (43.7%). Rate of pCR was 10.5% and median TILs post NAC was 20%. About nutritional predictors, we use the median as a cutoff to discriminate between high and low values, for BMI was 27.5, for PNI was 56, for hemoglobin was 13.2 and for NLR was 1.84. There was no association for TILs post NAC with BMI (p = 0.38), PNI (p = 0.057) and hemoglobin (p = 0.43). We found a positive association between ILN and TILs post NAC (p = 0.001). On the other hand, we don’t found association for RCB with BMI (p = 0.45), PNI (p = 0.641), ILN (p = 0.2) and hemoglobin (p = 0.15). In the multivariate analysis, only RCB was an independent predictor for DFS (95 % CI, 87-100.5; p = 0.00001) and OS (95 % CI, 101.8-114.1; p = 0.00001). There was no association between BMI, PNI, ILN and anemia with OS and DFS. For the TILs post NAC there was a tendency to association with DFS (p = 0.07) and OS (p = 0.07). Conclusions: There are association between neutrophil/lymphocyte index with TILs after NAC. There was no association between nutritional and systemic predictors with long-term outcomes. The pathologic response is a biomarker for predicting the long-term outcomes of breast cancer patients.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Heba F. Taha ◽  
Ola M. Elfarargy ◽  
Reham A. Salem ◽  
Doaa Mandour ◽  
Amira A. Salem ◽  
...  

Abstract Background Introducing neoadjuvant chemotherapy (NCT) in a breast cancer patient may be associated with changes in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) status. Method In our prospective cohort study, we evaluated the impact of change in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth hormone receptor 2 (HER2) on the prognosis of breast cancer patients treated with neoadjuvant chemotherapy (NCT). We investigated 110 patients with locally advanced breast cancer for ER, PR and HER2 status of their lesions before and after NCT. Result For hormone receptor status (HR) (which include ER, PR) of the residual tumor of the patients after receiving NCT, 12 (10.9%) of them changed from HR (+) to HR (−) and 15 (13.6%) changed from HR (−) to HR (+). For HER2 status after NCT, 8 (7.3%) patients changed from HER2 (+) to HER2 (−) and 9 (8.2%) patients changed from HER2 (−) to HER2 (+). Triple negative (TN) tumor phenotype changes occurred in 17 (15.5%) patients. Patients for whom the HR status changed from positive to negative had poor prognosis for both disease-free survival (DFS) and overall survival (OS) in univariate survival analysis. Conclusion Changes in ER, PR, HER2 status and tumor phenotype in breast cancer patients after NCT had a negative prognostic impact and were associated with a poor prognosis.


2002 ◽  
Vol 12 (6) ◽  
pp. 773-776 ◽  
Author(s):  
C. R. R. Miranda ◽  
C. N. De Resende ◽  
C. F. E. Melo ◽  
A. L. Costa ◽  
H. Friedman

Depression in cancer patients is common and may affect treatment outcome either directly (by lowering defenses) or indirectly (by lowering compliance). Neoadjuvant chemotherapy for advanced uterine cervix or breast cancer is a strenuous undertaking and may lead to depression and impair patients' willingness to comply with the rest of the treatment (eg, surgery or radiotherapy).We compare Beck Depression Inventory (BDI) scores both before and after neoadjuvant chemotherapy in order to verify if depression influences treatment outcome. We studied 22 advanced uterine cervix and 20 breast cancer patients submitted to three courses of neoadjuvant chemotherapy. We used cisplatin and ifosfamide for cervix, and fluorouracil, adriamycin, and cyclophosphamide for breast cancer. We did not identify significant differences in the number of depressed patients, before and after treatment. Cognitive affective, somatic-performance, and total BDI scores were not significantly different from before to after chemotherapy for both breast and uterine cervix cancer. After treatment, the number of depressive breast cancer patients increased while the number of uterine cervix cancer patients decreased. This trend to depression was found more often in less responsive breast cancer patients than in the more responsive cervix cancer patients. We were not able to link depression to treatment failure or success, but patients who responded to treatment were less depressed at the end of treatment.


2018 ◽  
Vol 225 ◽  
pp. 175-180 ◽  
Author(s):  
Hiroshi Kaise ◽  
Fumika Shimizu ◽  
Kohei Akazawa ◽  
Yoshie Hasegawa ◽  
Jun Horiguchi ◽  
...  

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 138-138 ◽  
Author(s):  
Yan Mao ◽  
Qing Qu ◽  
Yuzi Zhang ◽  
Junjun Liu ◽  
Kunwei Shen

138 Background: Whether tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) remains elusive. Methods: A systematic review and meta-analysis was undertook to establish the relationship between TIL and pathological complete response (pCR) rate in NAC of breast cancer. A PubMed and Web of Science literature search was designed. Studies were included, in which the predictive significance of intratumoral and/or stromal TIL, and/or CD3+, CD4+, CD8+, and FOXP3+ lymphocytes were determined . Pooled ORs and publication bias was evaluated by STATA software. Results: A total of 13 published studies (including 3,555 patients) were eligible. In pooled analysis, higher number of TIL in pre-treatment biopsy was correlated with higher pCR rate of neoadjuvant chemotherapy, and odds ratio (OR) was 3.82 (95% confidence interval (CI), 3.10-4.70), no matter tested in intratumor (OR=3.32, 95% CI: 2.52-4.37), in stroma (OR=4.15,95% CI: 2.94-5.86), or in combined sites (OR=8.98, 95% CI: 3.79,21.30). Moreover, TIL predicts higher pCR rate in triple negative (OR=5.03,95% CI: 2.31-10.97) and HER2+ (OR=5.54,95% CI: 1.39-22.12) patients, but not in hormonal receptor (HR) +/HER2- patients (OR=2.57, 95% CI: 0.20-33.24). For TIL subsets, CD8+ T-lymphocytes predict better pathological response to NAC no matter in pre- (OR=3.36,95%CI: 1.15-9.85) or post-NAC (OR=4.71,95%CI: 1.29-17.27) tissue, while FOXP3+ T-lymphocytes have similar predictive roles only when tested after NAC (OR=4.26, 95%CI: 1.83-9.92).With limited study, the predictive role of CD3+ and CD4+T-lymphoctes were unclear, more perspective studies were needed in future to establish the relationship. Conclusions: High level of TIL in pre-treatment biopsy could be a good marker indicates better pathological response to NAC in triple-negative and HER2+ breast cancer patients. Different subsets have different predictive roles in the pCR rate to NAC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes and different subtypes of breast cancer to increase the robustness of the analyses.


Sign in / Sign up

Export Citation Format

Share Document