scholarly journals Metformin diminishes the unfavourable impact of Nrf2 in breast cancer patients with type 2 diabetes

Tumor Biology ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 101042831881541 ◽  
Author(s):  
Elina Urpilainen ◽  
Jenni Kangaskokko ◽  
Ulla Puistola ◽  
Peeter Karihtala
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Overall Survival ◽  
Critical Role ◽  
Breast Cancer Surgery ◽  
Breast Cancer Specific Survival ◽  
Breast Cancer Patients ◽  
Cancer Specific Survival ◽  
High Level

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a major regulator of the oxidative stress response and it is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). The Keap1–Nrf2 axis has a fundamental role in carcinogenesis. In previous studies, the widely used diabetes drug metformin has appeared to have a critical role in the regulation of Nrf2 function. In this study, we assessed the expression of Nrf2 and Keap1 immunohistochemically in 157 patients with type 2 diabetes who underwent breast cancer surgery with curative intent. In total, 78 (49.7%) of these patients were taking metformin alone or combined with other oral anti-diabetic medication at the time of breast cancer diagnosis. We found that high-level cytoplasmic Nrf2 expression predicted dismal overall survival and breast cancer–specific survival, but only in the patients who were not taking metformin at the time of diagnosis. Similarly, low-level nuclear Keap1 expression had an adverse prognostic value in terms of overall survival and breast cancer–specific survival in patients without metformin. On the other hand, high-level nuclear Keap1 expression was associated with prolonged overall survival and breast cancer–specific survival. The results may be explained in terms of non-functioning or displaced Keap1, although more mechanistic pre-clinical and prospective clinical studies are warranted.

Prognosis of BRCA1/2-negative breast cancer patients with HBOC risk factors compared with sporadic breast cancer patients without HBOC risk factors

2020 ◽  
Vol 50 (2) ◽  
pp. 104-113
Author(s):  
Jai Min Ryu ◽  
Seok Jin Nam ◽  
Seok Won Kim ◽  
Jeong Eon Lee ◽  
Byung Joo Chae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Specific Survival ◽  
Breast Cancer Patients ◽  
Cancer Specific Survival ◽  
Free Survival

Abstract Objective Demands for genetic counseling with BRCA1/2 examination have markedly increased. Accordingly, the incidence of uninformative results on BRCA1/2 mutation status has also increased. Because most patients examined for BRCA1/2 mutation have a high risk of hereditary breast and/or ovarian cancer, many patients suffer psychological distress even when the BRCA1/2 result is negative. We compared oncological outcomes between BRCA1/2-negative breast cancer with high risk of hereditary breast and/or ovarian cancer and sporadic breast cancer without risk of hereditary breast and/or ovarian cancer. Methods The criteria for high risk for hereditary breast and/or ovarian cancer were defined as family history of breast and/or ovarian cancer in first- or second-degree relative, early onset breast cancer at <35 years old and bilateral breast cancer. Patients were matched maximally 1:3 into those who identified as negative for BRCA1/2 mutation with risk of hereditary breast and/or ovarian cancer (study group) and those who were not examined for BRCA1/2 mutation without risk for hereditary breast and/or ovarian cancer (control group). Matched variables were pathologic stage, estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status. Results All matching variables were successfully matched. Median follow-up duration was 57.8 months. There was no significant difference between the groups in disease-free survival (log-rank P = 0.197); however, the study group showed significantly better overall survival and breast cancer-specific survival (both P < 0.0001). We conducted subgroup analysis in the middle-aged group (36–54) and showed no significant difference for disease-free survival (P = 0.072) but significantly better overall survival and breast cancer-specific survival in the study group (P = 0.002 and P < 0.0001). Conclusions BRCA1/2-negative breast cancer patients who had hereditary breast and/or ovarian cancer risk factors showed similar disease-free survival and better overall survival and breast cancer-specific survival compared with those with sporadic breast cancer without hereditary breast and/or ovarian cancer risk factors.

scholarly journals Metformin improves the outcomes in Chinese invasive breast cancer patients with type 2 diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tianli Hui ◽  
Chao Shang ◽  
Liu Yang ◽  
Meiqi Wang ◽  
Ruoyang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cancer Patients ◽  
Invasive Breast Cancer ◽  
Breast Cancer Patients ◽  
Diabetes Group ◽  
Metformin Group

AbstractEarly reports indicate that metformin, a clinical drug administered to treat type 2 diabetes mellitus (T2DM), was found to be associated with a better prognosis of cancer. The objective of this study was retrospectively analyzed the effect of metformin on the outcomes of Chinese breast cancer patients with T2DM. A total of 3757 primary invasive breast cancer patients who underwent surgery from January 2010 to December 2013 were enrolled. According to the medication treatment, all the patients were divided as non-diabetes group, metformin group and insulin group. The follow-up data for disease-free survival (DFS) and overall survival (OS) were obtained from 3553 patients (median follow up of 85 months) and estimated with the Kaplan–Meier method followed by a log-rank test. Multivariate Cox proportional hazards regression model was applied. The results showed that there was a significant survival difference among non-diabetes group, metformin group and insulin group, 5-year DFS was 85.8%, 96.1%, 73.0%, and 5-year OS was 87.3%, 97.1%, 73.3% respectively (P < 0.05). Prognostic analysis showed metformin was significantly associated with better DFS and OS. Our results suggested that metformin may have a good effect on the survival of invasive breast cancer patients with T2DM.

scholarly journals A cukorbetegség és a daganatos thrombocytosis túlélésre gyakorolt hatásának vizsgálata emlőtumoros nőkben

2019 ◽  
Vol 160 (51) ◽  
pp. 2012-2020
Author(s):  
Anikó Somogyi ◽  
Magdolna Herold ◽  
Júlia Lohinszky ◽  
László Harsányi ◽  
Zoltán Herold
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Joint Effect ◽  
Diabetic Patients ◽  
Breast Cancer Patients ◽  
Negative Effect ◽  
T1 Stage ◽  
The University ◽  
Study Participants

Abstract: Introduction: Thrombocytosis and type 2 diabetes have negative effect on the survival of tumor patients. Previously, their joint effect has not been studied in breast cancer. Aim: The aim of our retrospective study was to investigate the occurrence and effects of thrombocytosis and/or type 2 diabetes in breast cancer patients who attended the 2nd Department of Internal Medicine or the 1st Department of Surgery, Semmelweis University, between 2014 and 2017. Laboratory and anamnestic data were compared at the time of tumor diagnosis between diabetic and non-diabetic groups. Survival analysis was performed to study the effects of thrombocytosis and/or type 2 diabetes. Method: 274 study participants were followed until 31 December 2018, or until their last appearance at the University, or until their death. Results: 5% of the patients had elevated platelet counts (over 400 G/L), and 52 were diabetics. Diabetics were significantly older (non-diabetics: 56.8 ± 13.8 years, diabetics: 67.8 ± 11.0 years, p<0.0001). Triple negative subtype (p = 0.0366), and T1 stage (50%) were present more often in non-diabetics. Stage T2 was more common in diabetic patients (51.9%). Type 2 diabetes was associated with a shorter survival time (p = 0.0032). Thrombocytosis did not affect patient survival. Conclusion: At the diagnosis of breast cancer, existing type 2 diabetes is associated with a more severe clinicopathological stage and shorter survival. We recommend that during routine diabetes controls, women should be made aware of the importance of mammography screening. Moreover, diabetes should be considered as a risk factor; after 30 years of age, diabetics should be screened at least every two years. Orv Hetil. 2019; 160(51): 2012–2020.

scholarly journals Survival After Early-Stage Breast Cancer of Women Previously Treated for Depression: A Nationwide Danish Cohort Study

2017 ◽  
Vol 35 (3) ◽  
pp. 334-342 ◽  
Author(s):  
Nis P. Suppli ◽  
Christoffer Johansen ◽  
Lars V. Kessing ◽  
Anita Toender ◽  
Niels Kroman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cohort Study ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Specific Survival ◽  
Regression Analyses ◽  
Cancer Specific Survival ◽  
Increased Risk ◽  
Previously Treated

Purpose The aim of this nationwide, register-based cohort study was to determine whether women treated for depression before primary early-stage breast cancer are at increased risk for receiving treatment that is not in accordance with national guidelines and for poorer survival. Material and Methods We identified 45,325 women with early breast cancer diagnosed in Denmark from 1998 to 2011. Of these, 744 women (2%) had had a previous hospital contact (as an inpatient or outpatient) for depression and another 6,068 (13%) had been treated with antidepressants. Associations between previous treatment of depression and risk of receiving nonguideline treatment of breast cancer were assessed in multivariable logistic regression analyses. We compared the overall survival, breast cancer–specific survival, and risk of death by suicide of women who were and were not treated for depression before breast cancer in multivariable Cox regression analyses. Results Tumor stage did not indicate a delay in diagnosis of breast cancer in women previously treated for depression; however, those given antidepressants before breast cancer had a significantly increased risk of receiving nonguideline treatment (odds ratio, 1.14; 95% CI, 1.03 to 1.27) and significantly worse overall survival (hazard ratio, 1.21; 95% CI, 1.14 to 1.28) and breast cancer–specific survival (hazard ratio, 1.11; 95% CI, 1.03 to 1.20). Increased but nonsignificant estimated risks were also found for women with previous hospital contacts for depression. In subgroup analyses, the association of depression with poor survival was particularly strong among women who did not receive the indicated adjuvant systemic therapy. Conclusion Women previously treated for depression constitute a large subgroup of patients with breast cancer who are at risk for receiving nonguideline breast cancer treatment, which probably contributes to poorer overall and breast cancer–specific survival.

Long-term outcomes of preoperative radiotherapy in locally advanced breast cancer: Analysis of Surveillance, Epidemiology, and End Results (SEER) database.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12600-e12600
Author(s):  
Zhe Pan ◽  
Zhiyuan Yao ◽  
Mingkai Huang ◽  
Junfeng Huang ◽  
Xiang Ao
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Multimodality Therapy ◽  
Breast Cancer Specific Survival ◽  
Seer Database ◽  
Cancer Specific Survival

e12600 Background: Currently the treatment paradigm for locally advanced breast cancer (LABC) is multimodality therapy with neoadjuvant systematic treatment, surgery and postoperative radiation therapy (RT). However, with improving outcomes from systematic therapy, the survival rates remain unpromising, which leads to the investigation of the concept of preoperative RT in LABC due to the potential advantages including a possible tumor downstaging and better cosmetic outcomes. We evaluated the overall survival (OS) and breast cancer specific survival (BCSS) of preoperative versus postoperative RT in LABC patients. Methods: Patients diagnosed with non-inflammatory LABC (defined as T3 N1, T4 N0, any N2 or N3, and M0) who received RT before or after surgery between 2010 and 2015 were identified using the SEER database. OS and BCSS were analyzed using Kaplan-Meier method and multivariate Cox proportional hazards model. Results: Among 19249 patients with LABC, 140 (0.7%) received preoperative RT and 19109 (99.3%) received postoperative RT. Overall, 5-year survival and BCSS are 59% and 63% in the preoperative RT group while 77% and 80% in the postoperative RT group. In all patients, treatment with preoperative RT was significantly associated with poor OS (HR 1.82, 95%CI 1.25 to 2.45, P < 0.001) and BCSS (HR 2.00, 95%CI 1.46 to 2.73, P < 0.001) after adjustment for other clinically relevant factors. However, there were no significant difference in terms of both OS and BCSS in ER+ (OS: HR 1.44, 95%CI 0.91 to 2.27, P = 0.12; BCSS: HR 1.55, 95%CI 0.94 to 2.54, P = 0.08) and HER2+ patients (OS: HR 1.33, 95%CI 0.55 to 3.22, P = 0.53; BCSS: HR 1.64, 95%CI 0.67 to 3.97, P = 0.28). Conclusions: Overall, preoperative RT in LABC may reduce overall survival and breast cancer specific survival. However, OS and BCSS were independent of radiation sequence for ER+ and HER2+ patients. This finding warrants further exploration of potential mechanisms of the disparity and the definitive role of preoperative RT in the multimodality therapy of LABC patients.

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