Does progesterone protect from chemotherapy-induced peripheral neuropathy? A retrospective audit of breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11552-e11552
Author(s):  
Aruna Laxman Prabhu ◽  
Akshita Singh ◽  
Rucha Vishal Kaushik ◽  
Nita S. Nair ◽  
Rohini W Hawaldar ◽  
...  

e11552 Background: Paclitaxel is an integral component of chemotherapy for breast cancer but its benefit comes at the risk of peripheral neuropathy. There are experimental models of peripheral nerve injury in which progesterone is protective, possibly through remyelination and other mechanisms. Methods: We evaluated the effect of menopausal status, as a surrogate for circulating progesterone levels, on the risk of developing paclitaxel induced peripheral neuropathy, in a retrospective audit of breast cancer patients. Patients who had received paclitaxel chemotherapy for breast cancer were characterized as having CIPN or not by clinical history/examination. Results: 256 women treated with paclitaxel at our institution were assessed for CIPN. Of these 133(52%) were premenopausal and 123(48%) postmenopausal at diagnosis. 22(8.6%) had preexisting diabetes mellitus. Of the 133 premenopausal women 97(72.9%) developed chemotherapy induced amenorrhea (CIA). The incidence of CIPN was 23.1% in persistently premenopausal patients 47.4% in patients with CIA and 57.7% in postmenopausal patients. In patients with DM 81.8% had CIPN. In a multivariate logistic regression model, increasing age (continuous variable RR=1.04 95%CI 1.02-1.08 p=0.001) DM (RR=4.39 95% CI 1.42-13.38 p=0.01) and postmenopausal/CIA status (RR=2.48 95% CI 1.05-5.88 p=0.03) were risk factors for CIPN. Because patients developed CIA at variable times and circulating progesterone levels at the time of neurotoxin insult maybe variable in them such patients were excluded in the second model, which included only patients with continuing menses (n=36) and postmenopausal at diagnosis (n=123). In the latter model postmenopausal status (RR=3.5 95%CI 1.18-10.39 p=0.02) and DM (RR=6.8 95%CI 1.44-31.82 p=0.01) were associated with CIPN but increasing age (RR=1.03 95% CI 0.98-1.07 p=0.21) was not. Conclusions: These results suggest a neuroprotective effect of premenopausal status, possibly related to higher circulating levels of progesterone. We hypothesize that progesterone administration prior to taxane chemotherapy may protect against CIPN. This will be tested in a RCT.

2014 ◽  
Vol 40 (5) ◽  
pp. 612
Author(s):  
Muhammd Noor Chauhan ◽  
Selene Chew ◽  
Metin Nizamoglu ◽  
Kryjak Zbigniew ◽  
Deedar Ali

2018 ◽  
Vol 8 (3) ◽  
pp. 154-161
Author(s):  
Jasmina Gubaljevic ◽  
Nahida Srabović ◽  
Adlija Jevrić-Čaušević ◽  
Adaleta Softić ◽  
Adi Rifatbegović ◽  
...  

Introduction: The aim of this study was to determine the serum levels of malondialdehyde (MDA) in patients with invasive breast cancer in relation to its serum levels in patients with benign breast disease, and to investigate correlation between MDA serum levels with pathohistological prognostic factors (tumor size, lymph node involvement, and histologic grade [HG]), estrogen receptor (ER) status, and with breast cancer patient’s age and menopausal status. Methods: A total of 43 with well-documented invasive breast cancer were included in this study: 27 with positive axillary’s lymph nodes, and 16 with negative axillary’s lymph nodes, and 39 patients with findings of benign breast diseases. MDA determination in serum of breast cancer and benign breast disease patients was performed by the fluorimetric method, immunohistochemical staining was performed for ER, and routine pathohistological examination was conducted for pathohistological factors. Results: MDA serum levels in breast cancer patients were significantly higher than MDA serum levels in benign breast disease patients (p = 0.042). No statistically significant difference between MDA serum levels in breast cancer patients with and without lymph node metastases was found (p = 0.238). No statistically significant correlations between MDA serum levels and tumor size (p = 0.256), HG (p = 0.124), or number of positive lymph nodes (0.113) were found. A statistically significant correlation between serum MDA levels and ages of breast cancer patients with lymph node metastases was found (p = 0.006). Conclusion: Obtained results support the importance of MDA in the carcinogenesis of breast cancer. According to our findings, serum level of MDA could not be a useful prognostic factor in breast cancer.


2020 ◽  
Vol 26 (6) ◽  
pp. 1421-1428
Author(s):  
Ebrahim Salehifar ◽  
Ghasem Janbabaei ◽  
Abbas Alipour ◽  
Nasim Tabrizi ◽  
Razieh Avan

Purpose Taxane-induced peripheral neuropathy (TIPN) is a common and bothersome toxicity. This study aimed to determine the incidence and severity of TIPN in patients with breast cancer and to investigate the relationship between TIPN and quality of life. Methods A total of 82 breast cancer patients with TIPN symptoms were included in this study. The criteria of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30, version 3.0) were used to evaluate grading of sensory neuropathy and quality of life, respectively. Analysis of the data was done by IBM SPSS statistics version 23. Results A total of 346 patients received taxane-based chemotherapy and 82 patients (23.7%) experience TIPN. The mean (SD) global health status/quality of life, physical functioning, role functioning, and pain subscales were 60.63 (5.26), 80.64 (9.05), 81.77 (10.41), and 43.88 (11.27), respectively. There were significant negative correlations between global health status/quality of life, physical functioning, and role functioning subscales with the grade of neuropathy (r = −0.33, −0.80, and −0.61, respectively) and positive correlation between pain subscale and the grade of neuropathy (r = 0.70). Conclusion This study shows a clear association between TIPN and worsened quality of life. These findings emphasize on detecting and management of TIPN in an effort to improve the quality of life of breast cancer patients.


2012 ◽  
Vol 27 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Heena Dave ◽  
Manoj Shah ◽  
Sunil Trivedi ◽  
Shilin Shukla

Transforming growth factor betas (TGF-βs) are multifunctional cytokines with a biphasic role in breast tumorigenesis, acting as tumor suppressors at early stages while stimulating tumor progression at later stages (TGF-β switch). Among the 3 human isoforms, TGF-β1 is known to be overexpressed in several tumor types including breast tumors. TGF-β signaling and “crosstalk” in the tumor microenvironment presents a unique challenge and an opportunity to develop novel therapies. We assessed circulating TGF-β1 levels by ELISA in blood samples from 117 previously untreated breast cancer patients in this prospective study to explore the TGF-β switch at the forefront. The levels were correlated with clinicopathological prognosticators like age, menopausal status, nodal status, histological type, histological grade, necrosis, stromal involvement, and survival. Higher mean preoperative serum TGF-β1 was observed in early-stage patients than controls (p=0.05) as revealed by receiver operating characteristic (ROC) analysis. Elevation of TGF-β1 was evident in patients with advanced-stage breast cancer compared with those having early-stage disease (p=0.0001). Prognosticators of an aggressive phenotype were associated with higher TGF-β1 levels, and higher levels thus announced the likelihood of relapse, marking the role of TGF-β1 as a tumor promoter and evidencing the existence of a TGF-β switch. Moreover, higher levels of TGF-β1 shortened the overall survival in breast cancer patients (p=0.010). The results indicate that circulating TGF-β1 may be used as a predictive and prognostic marker in breast carcinoma.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1107-1107
Author(s):  
D. Karacetin ◽  
O. Maral ◽  
O. Aksakal ◽  
B. Okten ◽  
B. Yalçın ◽  
...  

1107 Background: No standart chemotherapy regimen has been estabilished for the treatment of patients with metastatic breast cancer. The gemcitabine and docetaxel combination has been shown to be synergistic . This study is conducted to verify the clinical efficacy and safety of gemcitabine and docetaxel combination therapy in metastatic breast cancer. Methods: 27 metastatic breast cancer patients were treated with gemcitabine-docetaxel combination . Gemcitabine 1,250 mg/m2 IV infusion, on day 1 and 8, and docetaxel 70 mg/m2 on day 1 in 21 day cycles. 4–6 cycles of chemotherapy were repeated every 3 weeks. The primary endpoint was response rate, and survival. Results: The median age was 50 years (range,32–77). Performans status (ECOG) was 0–1. Hormone receptor status: ER+/ER-; 11/16, PR+/PR-; 14/13. Menopausal status were: 11 premenopausal, 16 postmenopausal. Of the 27 evaluable patients, there were 11 (40.7%) partial responses and no complete response. Overall response rate was 40.7%. Median time to progression was 7 months, and median survival was 14 months. Toxicities included grade 3–4 neutropenia in 9 (30%), thrombocytopenia in 6 (22%), anemia in 3(9%). There were no treatment releated deaths Conclusions: The combination of gemcitabine and docetaxel has shown favorable toxicity profile and promising activity in metastatic breast cancer patients. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21702-e21702
Author(s):  
David Azoulay ◽  
Anca Leibovici ◽  
Rivka Sharoni ◽  
Hadassah Goldberg

e21702 Background: We previously published preliminary results suggesting an association between the met-BDNF allele and vulnerability to paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients. Here we present updated data obtained from our extended study. Methods: 35 patients; 34 women (33 with breast cancer and 1 with ovarian cancer) and one man (breast cancer) completed their follow-up. Peripheral neuropathy (PN) was assessed at diagnosis and along the treatment protocol, using the reduced version of Total Neuropathy Score (TNSr). Patients with TNSr≥2 at diagnosis were determined with pre-existing PN (Pre-PN). Allelic discrimination of BDNF polymorphism (rs6265) was determined by Sanger sequencing. Results: BDNF genotype Val/Val was found in 20 patients (57.14%), Val/Met in 15 patients (42.86%). No patient had the Met/Met genotype. 10 patients (28.57%) were diagnosed with Pre-PN, 3 of them with diabetic-related neuropathy. A higher incidences of the Met-BDNF allele was found in patients with Pre-PN as compared to patients with no Pre-PN (7/10 (70%) vs. 8/25 (32%) Val/Met in Pre-PN and no Pre-PN respectively, prob > ChiSq < 0.05). The three patients with diabetic related Pre-PN were genotyped Met-BDNF. The maximal TNSr scores developed by each patient during follow-up were higher in Met-BDNF patients compare to Val/Val patients. (Maximal TNSr mean ± SEM in Val/Val 4.80±0.62 vs. 7.73±1.34 in Val/Met BDNF, prob < t 0.04). No difference in the maximal TNSr scores between Met-BDNF and Val/Val patients were shown after excluding the patients with Pre-PN (Maximal TNSr mean ± SEM in Val/Val 5.05±0.78 vs. 5.25±0.62 in Val/Met BDNF, prob < t 0.44). Conclusions: Our data demonstrate an association between met-BDNF and Pre-PN. Higher maximal TNSr scores in our met-BDNF patients is generally the consequence of their higher Pre-PN.


Sign in / Sign up

Export Citation Format

Share Document