scholarly journals Impact of Adjuvant Treatment on Heparanase Concentration in Invasive, Unilateral Breast Cancer Patients: Results of a Prospective Single-Centre Cohort Study

2021 ◽  
Vol 10 (10) ◽  
pp. 2184
Author(s):  
Barbara Ruszkowska-Ciastek ◽  
Kornel Bielawski ◽  
Elżbieta Zarychta ◽  
Piotr Rhone

Background: In recent years, great progress has been made in the treatment of breast cancer, but it is still one of the ten leading causes of death in women. The aim of the study was to evaluate the heparanase concentration of invasive breast cancer (IBrC) patients, before and after cancer adjuvant treatment. Methods: Eighty patients with stage IA to IIB IBrC receiving adjuvant treatment were included prospectively in this study. The heparanase concentrations were determined by an enzyme-linked immunosorbent assay. A univariate analysis was used to estimate the factors influencing the low or high pre-treatment concentration of heparanase and the low or high numerical decrease in heparanase concentration after completion of adjuvant treatment. Results: Treatment reduced the concentration of heparanase by almost four times in the general IBrC cohort. Higher levels of pre- and post-treatment heparanase were noted in oestrogen receptor-negative cancers than in positive ones. A higher post-treatment concentration of heparanase was found in patients with a triple-negative tumour compared to patients with a luminal B HER2 negative type of IBrC. Overweight IBrC subjects and those with a tumour diameter of ≥2 cm demonstrated a lower chance of a lower pre-treatment heparanase concentration. Interestingly, a pre-treatment heparanase concentration is the main predictor of the changes in heparanase concentration after adjuvant treatment. Follow-up revealed significantly lower progression-free survival (PFS) rates in IBrC patients with a pre-treatment concentration of heparanase higher than 181.46 pg/mL (PFS = 80%). Conclusions: Our findings provide supporting evidence that IBrC therapy reduced the heparanase levels, regardless of treatment patterns and a pre-treatment concentration of heparanase may serve as a prognostic indicator for future outcomes.

2005 ◽  
Vol 33 (03) ◽  
pp. 381-395 ◽  
Author(s):  
Chun-Kwok Wong ◽  
Yi-Xi Bao ◽  
Eliza Lai-Yi Wong ◽  
Ping-Chung Leung ◽  
Kwok Pui Fung ◽  
...  

Breast cancer is the most common cancer among women worldwide. Discomfort and fatigue are usually arisen from anticancer therapy such as surgery, radiotherapy, chemotherapy, hormonal therapy, or combination therapy, because of the suppressed immunological functions. Yunzhi (Coriolus versicolor) can modulate various immunological functions in vitro, in vivo, and in human clinical trials. Danshen (Salvia miltiorrhiza) has been shown to benefit the circulatory system by its vasodilating and anti-dementia activity. The purpose of this clinical trial was to evaluate the immunomodulatory effects of Yunzhi-Danshen capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer were recruited to take Yunzhi [50 mg/kg body weight, 100% polysaccharopeptide (PSP)] and Danshen (20 mg/kg body weight) capsules every day for a total of 6 months. EDTA blood samples were collected every 2 months for the investigation of immunological functions. Flow cytometry was used to assess the percentages and absolute counts of human lymphocyte subsets in whole blood. Plasma level of soluble interleukin-2 receptor (sIL-2R) was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that the absolute counts of T-helper lymphocytes (CD4+), the ratio of T-helper (CD4+)/T suppressor and cytotoxic lymphocytes (CD8+), and the percentage and the absolute counts of B-lymphocytes were significantly elevated in patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma sIL-2R concentration was significantly decreased (all p < 0.05). Therefore, the regular oral consumption of Yunzhi-Danshen capsules could be beneficial for promoting immunological function in post-treatment of breast cancer patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12623-e12623
Author(s):  
Osama Mosalem ◽  
Saud Alsubait ◽  
Shouq Kherallah ◽  
Venumadhavi Gogineni ◽  
Ling Wang ◽  
...  

e12623 Background: Hematologic markers have been looked at as potential prognostic biomarkers in a variety of cancers. Ni and colleagues (2014) have shown that an elevated pre-treatment lymphocyte-to-monocyte ratio (LMR) was significantly associated with improved disease-free survival (DFS) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NACT). Given the prognostic implications of hematologic inflammatory parameters, we sought to understand if such biomarkers will predict response to neoadjuvant chemotherapy (NACT) in patients with breast cancer. Methods: We conducted a retrospective review of breast cancer patients treated with NACT at our institution (2008-2018). Data on patient characteristics, stage, pathologic characteristics, and blood counts were collected. Blood parameters prior to NACT were used to calculate LMR and neutrophil-to-lymphocyte ratio (NLR). To test the impact of LMR and NLR on pathologic response, a two sample mean test was used first as univariate analysis. Next, logistic regression was employed for multivariate analysis controlling for patient characteristics with interaction of LMR and NLR with ER, PR and HER2 status. Results: A total of 50 patients were included. 38% of patients achieved a pathologic complete response (pCR). The mean LMR was 3.69 (1.4-12.5), and the mean NLR was 2.55 (0.66 – 9.31). On univariate analysis, a high NLR was associated with a higher likelihood of achieving a pCR (OR = 1.64, 95% CI = 1.01-2.63). A high LMR was associated with a higher likelihood of pCR; however, this was not statistically significant (OR = 1.08, 95% CI = 0.78-1.47). On multivariate analysis, patients with HER-2 positive disease with a high LMR had a significantly higher chance of having a pCR (OR = 1.72, 95% CI = 1.06-2.78). Conclusions: Our study showed that NLR was a predictor of pCR in breast cancer patients receiving neoadjuvant chemotherapy. A high NLR was associated with achieving a pCR on univariate analysis. Multivariate analysis suggested that HER-2 positive disease with a high LMR had a significantly higher chance of achieving a pCR. The results of this cohort correlate with previous reports by others showing that pre-NACT LMR and NLR provide prognostic information in patients with breast cancer. Although limited by sample size, this adds to the growing body of literature supporting peripheral blood counts as a biomarker for outcomes in breast cancer.


2004 ◽  
Vol 19 (1) ◽  
pp. 14-22 ◽  
Author(s):  
M. Saghatchian ◽  
S. Guepratte ◽  
K. Hacene ◽  
R. Neumann ◽  
J.-L. Floiras ◽  
...  

Purpose To determine the clinical correlations and prognostic value of serum HER-2 (sHER-2) before and after primary breast cancer treatment. Methods sHER-2 from 701 consecutive patients with stage I-III tumors (median follow-up 7.7 years) was assayed by an enzyme-linked immunosorbent assay (Immuno 1, Bayer Diagnostics). Results The median pretreatment sHER-2 concentration was 8.30 ng/mL (range 3.15–82.00 ng/mL). Forty-seven patients (6.7%) had sHER-2 concentrations >12 ng/mL (cutoff level). Pretreatment sHER-2 correlated positively with CA 15.3 (p=0.0169), pathological tumor size (p=0.0082), number of invaded lymph nodes (pN, p=0.0160) and histological grading (p=0.0086). Kaplan-Meier analyses indicated that pretreatment sHER-2 was of prognostic value for contralateral breast cancer (p=0.0018), metastasis-free survival (MFS) (p=0.0008) – particularly lung (p=0.0082) and liver metastases (p=0.0035) – and overall disease-specific survival (DSS) (p=0.0020). According to pN status, pretreatment sHER-2 was of prognostic value only for pN-positive patients (p=0.0017). When combined with estradiol or progesterone receptor status, patients with elevated sHER-2 and receptor-negative tumors had a significantly shorter DSS (p<0.0001 for both receptors). Post-treatment sHER-2 also had individual prognostic value for MFS (p=0.0144) and DSS (p=0.0212). In multivariate analysis, only sHER-2 after primary treatment was an independent prognostic variable for MFS and DSS (p=0.0078 and p=0.0058, respectively). Conclusion sHER-2 elevation in early breast cancer correlates with the principal criteria of tumor aggressiveness, thus permitting selection of patients with a high risk of visceral metastases and contralateral breast tumors. Post-treatment sHER-2 is an independent prognostic factor enabling to identify patients likely to benefit from aggressive adjuvant treatments.


2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 29-29 ◽  
Author(s):  
Hae-na Shin ◽  
Jisun Kim ◽  
Hee Jeong Kim

29 Background: Inflammatory response exacerbates mechanisms linked to tumor growth and dissemination. As an index of systemic inflammatory status, neutrophil lymphocyte ratio (NLR) may be a predictive biomarker of both prognosis and response to therapy. We evaluated initial pre-treatment NLR and post-treatment NLR change to assess whether initial and change in NLR would be predictive of disease outcome in stage IV breast cancer patients. Methods: This study included 250 stage IV breast cancer patients diagnosed at Asan Medical Center between 1997 and 2012. The NLR was calculated from the differential count by dividing neutrophil percentage by lymphocyte percentage. All initial (pre-treatment) NLR was evaluated at the first visit day in Asan medical center. Post-treatment NLR was obtained at the first follow-up visit at the outpatient department after first treatment (chemotherapy first: about after 3weeks/endocrine therapy: after 3~6 months). The initial (pre-treatment) NLR was divided by quartile, and the NLR change was calculated by dividing post-treatment NLR by pre-treatment NLR. If the value was ≥ 1.2, NLR change was increased; if not, it was not changed or decreased. We evaluated prognostic value of NLR by comparison with Cancer Specific Survival (CSS). Results: When comparing pre-treatment NLR and post-treatment NLR, the NLR was increased in 85 patients (34%) and stationary or decreased in 165 patients (66%). There was no significant difference between two groups in baseline characteristics. On the other hand, in CSS, the difference between two groups are shown, but does not have statistical significance (log rank p = 0.052). The 1, 3, 5 year CSS rate was 78.8%, 35.7%, 20.5% in increased NLR group, and 87.1%, 49.3%, 26.9% in the other group. Multivariate analysis suggested that increased NLR change (Post/Pre NLR ≥ 1.2) had statistical significance as prognostic factor of stage IV breast cancer patients after treatment (HR = 1.750, 95% CI 1.130-2.709, p-value = 0.012). Conclusions: After start of treatment, increased NLR can be correlated with poor cancer specific survival in stage IV breast cancer. The NLR change might be an index of response of systemic treatment.


2009 ◽  
Vol 32 (3) ◽  
pp. 250 ◽  
Author(s):  
Wen-sheng Qui ◽  
Lu Yue ◽  
Ai-ping Ding ◽  
Jian Sun ◽  
Yang Yao ◽  
...  

Purpose: To assess the prognostic value of co-expression of estrogen receptor (ER)-beta and human epidermal growth factor receptor 2 (HER2) in primary breast cancer patients in China. Methods: Tumour specimens from 308 patients undergoing surgery for primary breast cancer were evaluated. Expression of ER-beta and HER-2 was investigated by the immunohistochemistry. Results: 123 patients (40%) were ER-beta positive and 58 (18.5 %) were HER2 positive. Among the 58 HER2 positive patients, 44 were ER-beta positive and 14 were ER-beta negative. ER-beta positive was associated with HER2 positive (75.9%, P=0.018) as well as ER-alpha positive (79.7%, P=0.023), poor cell differentiation (77.2% grade 2 or 3, P=0.010) and menopause age < 45 yr (55.3%, P=0.031). HER2 positive was associated with poor cell differentiation (93.1%, P=0.001), ?3cm tumour size (67.2%, P=0.011). Conclusion: Both ER-beta positive and HER2 positive status was associated with poorer overall survival (OS) by univariate analysis. In both HER2 positive and HER2 negative subgroups, ER-beta positive was associated with poorer distant disease free survival (DDFS) but not OS, which implied that ER-beta might relate to metastasis in breast cancer.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1685
Author(s):  
Antonino Grassadonia ◽  
Vincenzo Graziano ◽  
Laura Iezzi ◽  
Patrizia Vici ◽  
Maddalena Barba ◽  
...  

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.


Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 2
Author(s):  
Lee D. Gibbs ◽  
Kelsey Mansheim ◽  
Sayantan Maji ◽  
Rajesh Nandy ◽  
Cheryl M. Lewis ◽  
...  

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.


2018 ◽  
Vol 14 (2) ◽  
pp. 102-107
Author(s):  
Hong Bae Choi ◽  
Sangchul Yun ◽  
Sung Woo Cho ◽  
Min Hyuk Lee ◽  
Jihyoun Lee ◽  
...  

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