scholarly journals Effect of Estradiol as a Continuous Variable on Breast Cancer Survival by Menopausal Status: A Cohort Study in China

2021 ◽  
Author(s):  
Junxian Li ◽  
Chenyang Li ◽  
Ziwei Feng ◽  
Luyang Liu ◽  
Liwen Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survival ◽  
Menopausal Status ◽  
Continuous Variable ◽  
Breast Cancer Survival ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Menopausal Women ◽  
Post Menopausal

Abstract BackgroundHigh levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We studied the effect of E2 concentration on breast cancer survival among pre- menopausal and post- menopausal patients in China.MethodsWe evaluated this association among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints.ResultsA total of 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR=1.79, 95% CI: 1.17-2.75, P=0.008) and OS in post-menopausal women (HR=1.35, 95% CI: 1.04-1.74, P=0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation (“L-shaped” and “U-shaped”, respectively) with E2 levels. However, there was a linear relationship in post-menopausal women, among whom increasing E2 was associated with escalating risks of death and progression. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a “U-shaped” relationship with OS and PFS in pre-menopausal women.ConclusionsPre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.

scholarly journals Effect of Estradiol as a Continuous Variable on Breast Cancer Survival by Menopausal Status: a Cohort Study in China

2022 ◽  
Author(s):  
Junxian Li ◽  
Chenyang Li ◽  
Ziwei Feng ◽  
Luyang Liu ◽  
Liwen Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Menopausal Status ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Cancer Prognosis ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Menopausal Women ◽  
Survival Endpoints ◽  
Post Menopausal

Abstract High levels of circulating estradiol (E2) are associated with increased risk of breast cancer, whereas its relationship with breast cancer prognosis is still unclear. We evaluated the effect of E2 concentration on survival endpoints among 8766 breast cancer cases diagnosed between 2005 and 2017 from the Tianjin Breast Cancer Cases Cohort. Levels of serum E2 were measured in pre-menopausal and post-menopausal women. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between quartile of E2 levels and overall survival (OS) and progression-free survival (PFS) of breast cancer. The penalized spline was then used to test for non-linear relationships between E2 (continuous variable) and survival endpoints. 612 deaths and 982 progressions occurred over follow-up through 2017. Compared to women in the quartile 3, the highest quartile of E2 was associated with reduced risk of both PFS in pre-menopausal women (HR=1.79, 95% CI: 1.17-2.75, P=0.008) and OS in post-menopausal women (HR=1.35, 95% CI: 1.04-1.74, P=0.023). OS and PFS in pre-menopausal women exhibited a nonlinear relation (“L-shaped” and “U-shaped”, respectively) with E2 levels. However, there was a linear relationship in post-menopausal women. Moreover, patients with estrogen receptor-negative (ER-negative) breast cancer showed a “U-shaped” relationship with OS and PFS in pre-menopausal women. Pre-menopausal breast cancer patients have a plateau stage of prognosis at the intermediate concentrations of E2, whereas post-menopausal patients have no apparent threshold, and ER status may have an impact on this relationship.

scholarly journals Obesity Factors (Physical Activity and Usual Dietary Pattern) and Breast Cancer in Korea

2019 ◽  
Vol 26 (3) ◽  
pp. 29-34
Author(s):  
Myeong Seong Kim ◽  
Young Hee Nam
Keyword(s):  
Breast Cancer ◽  
Physical Activity ◽  
Cancer Patients ◽  
Nutrient Intake ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Animal Fat ◽  
Increased Risk ◽  
Menopausal Women ◽  
Post Menopausal

AbstractIntroduction. This study sought to evaluate the association between obesity factors (food consumption and physical activity) and breast cancer incidence in Korean women.Material and methods. The study included breast cancer patients (250 women) and normal participants undergoing medical checkups (250 women) who visited a specialized cancer research hospital between August 1, 2016 and February 15, 2017. Nutrient intake was assessed using a validated food frequency questionnaire (FFQ) covering 112 dishes and foods that Koreans often eat. Physical activity was assessed according to the International Physical Activity Questionnaire (IPAQ) guidelines and was quantified as metabolic equivalent (MET) scores.Results. The results for nutrient intake obtained using the FFQ showed that the control group had a higher consumption of dietary fiber (p < 0.004) and a lower intake of animal fat (p < 0.02) than the breast cancer group. Among breast cancer patients, pre-menopausal women consumed more animal fat (18.6 g ± 11.9 vs. 14.7 g ± 8.5, p < 0.03) than post-menopausal ones. An analysis of the MET scores with logistic regression revealed that lower physical activity among cancer patients was associated with an increased risk of breast cancer, and this association was greater among post-menopausal (OR = 2.11, p < 0.001) than pre-menopausal women (OR = 0.85, p < 0.02).Conclusion. Having a high-fat diet and doing less exercise increases the risk of breast cancer, so it is important to prevent the accumulation of fat and maintain proper weight through regular physical activity to lower the incidence of breast cancer.

scholarly journals Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

2021 ◽  
Author(s):  
Sandar Tin Tin ◽  
Gillian K. Reeves ◽  
Timothy J. Key
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Menopausal Status ◽  
Endogenous Hormones ◽  
Uk Biobank ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

scholarly journals Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

2013 ◽  
Vol 20 (2) ◽  
pp. 251-262 ◽  
Author(s):  
Catherine M Olsen ◽  
Christina M Nagle ◽  
David C Whiteman ◽  
Roberta Ness ◽  
Celeste Leigh Pearce ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Menopausal Status ◽  
Low Grade ◽  
Ovarian Cancer Risk ◽  
Histological Subtypes ◽  
Increased Risk ◽  
Modifiable Factors ◽  
Menopausal Women ◽  
Increase Risk ◽  
Post Menopausal

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case–control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m2; 95% CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

scholarly journals Research-based PAM50 signature and long-term breast cancer survival

2019 ◽  
Vol 179 (1) ◽  
pp. 197-206 ◽  
Author(s):  
Minya Pu ◽  
Karen Messer ◽  
Sherri R. Davies ◽  
Tammi L. Vickery ◽  
Emily Pittman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Stratification ◽  
Cancer Survival ◽  
Assessment Tool ◽  
Menopausal Status ◽  
Postmenopausal Breast Cancer ◽  
Breast Cancer Survival ◽  
Gene Signatures ◽  
Hypoxia Signature

Abstract Purpose Multi-gene signatures provide biological insight and risk stratification in breast cancer. Intrinsic molecular subtypes defined by mRNA expression of 50 genes (PAM50) are prognostic in hormone-receptor positive postmenopausal breast cancer. Yet, for 25–40% in the PAM50 intermediate risk group, long-term risk remains uncertain. Our study aimed to (i) test the long-term prognostic value of the PAM50 signature in pre- and post-menopausal breast cancer; (ii) investigate if the PAM50 model could be improved by addition of other mRNAs implicated in oncogenesis. Methods We used archived FFPE samples from 1723 breast cancer survivors; high quality reads were obtained on 1253 samples. Transcript expression was quantified using a custom codeset with probes for > 100 targets. Cox models assessed gene signatures for breast cancer relapse and survival. Results Over 15 + years of follow-up, PAM50 subtypes were (P < 0.01) associated with breast cancer outcomes after accounting for tumor stage, grade and age at diagnosis. Results did not differ by menopausal status at diagnosis. Women with Luminal B (versus Luminal A) subtype had a > 60% higher hazard. Addition of a 13-gene hypoxia signature improved prognostication with > 40% higher hazard in the highest vs lowest hypoxia tertiles. Conclusions PAM50 intrinsic subtypes were independently prognostic for long-term breast cancer survival, irrespective of menopausal status. Addition of hypoxia signatures improved risk prediction. If replicated, incorporating the 13-gene hypoxia signature into the existing PAM50 risk assessment tool, may refine risk stratification and further clarify treatment for breast cancer.

S-phase fraction is a prognostic factor in stage I breast carcinoma.

1993 ◽  
Vol 11 (9) ◽  
pp. 1717-1722 ◽  
Author(s):  
O Stål ◽  
M Dufmats ◽  
T Hatschek ◽  
J Carstensen ◽  
C Klintenberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Dna Content ◽  
Cancer Survival ◽  
Prognostic Significance ◽  
Breast Cancer Survival ◽  
S Phase ◽  
Stage I ◽  
Phase Fraction ◽  
Breast Cancer Patients

PURPOSE AND METHODS The prognostic significance of cell proliferation, estimated as cytometric S-phase fraction (SPF), was investigated in node-negative breast cancer patients with small tumors (T1, NO). The 219 stage I patients originated from two series and were diagnosed either from 1978 to 1981 or from 1981 to 1985. The tumors were analyzed for estrogen receptors (ERs) by isoelectric focusing and for cellular DNA content by static cytofluorometry or flow cytometry. RESULTS A high SPF correlated with the absence of ERs and abnormal DNA content, and was less often found in tumors smaller than 11 mm compared with those with a diameter between 11 and 20 mm. Among the variables age, tumor size, DNA ploidy, ER status, and SPF, only SPF showed a significant association with distant recurrence and breast cancer survival in systemically untreated patients. The relative recurrence rate for patients with an SPF of 10% or greater was three times that for patients with lower SPFs. Estimated 8-year breast cancer survival rates for the same groups were 72% and 91%, respectively. CONCLUSION This study suggests that cytometric SPF has prognostic significance in stage I breast carcinoma.

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 ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Peripheral Neuropathy ◽  
Cancer Patients ◽  
Neuroprotective Effect ◽  
Menopausal Status ◽  
Continuous Variable ◽  
Experimental Models ◽  
Multivariate Logistic Regression Model ◽  
Breast Cancer Patients ◽  
Retrospective Audit

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.

scholarly journals Identification and validation of prognostic signature for breast cancer based on genes potentially involved in autophagy

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9621
Author(s):  
Shanliang Zhong ◽  
Huanwen Chen ◽  
Sujin Yang ◽  
Jifeng Feng ◽  
Siying Zhou
Keyword(s):  
Breast Cancer ◽  
Cancer Survival ◽  
Cox Regression ◽  
Risk Group ◽  
Breast Cancer Survival ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Breast Cancer Patients ◽  
Prognostic Signature

We aimed to identify prognostic signature based on autophagy-related genes (ARGs) for breast cancer patients. The datasets of breast cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to construct multiple-ARG risk signature. In total, 32 ARGs were identified as differentially expressed between tumors and adjacent normal tissues based on TCGA. Six ARGs (IFNG, TP63, PPP1R15A, PTK6, EIF4EBP1 and NKX2-3) with non-zero coefficient were selected from the 32 ARGs using LASSO regression. The 6-ARG signature divided patients into high-and low-risk group. Survival analysis indicated that low-risk group had longer survival time than high-risk group. We further validated the 6-ARG signature using dataset from GEO and found similar results. We analyzed the associations between ARGs and breast cancer survival in TCGA and nine GEO datasets, and obtained 170 ARGs with significant associations. EIF4EBP1, FOS and FAS were the top three ARGs with highest numbers of significant associations. EIF4EBP1 may be a key ARG which had a higher expression level in patients with more malignant molecular subtypes and higher grade breast cancer. In conclusion, our 6-ARG signature was of significance in predicting of overall survival of patients with breast cancer. EIF4EBP1 may be a key ARG associated with breast cancer survival.

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