OBJECTIVES: To assess the expression of DDR1 and DVL1 and their association with histological type, grading and hormonal status of IDC and ILC.
MATERIALS AND METHODS: This cross sectional study was conducted on IDC and ILC breast tumours. Tumours were immunohistochemically stained for (DDR1) and (DVL1) as well as estrogen receptor (ER), progesterone receptor (PR) and C-erbB2 receptor. Demographic data including age and ethnicity were obtained from patient records.
RESULTS: A total of 51 cases (30 IDCs and 21 ILCs) were assessed. DDR1 and DVL1 expression was not significantly associated with histological type (p=0.57 and p=0.66 respectively). There was no association between DDR1 and DVL1 expression and tumour grade (p=0.32 and p=1.00 respectively), ER (p=0.62 and 0.50 respectively), PR (p=0.38 and p=0.63 respectively) and C-erbB2 expression (p=0.19 and p=0.33 respectively) in IDC. There was no association between DDR1 and DVL1 expression and tumour grade (p=0.52 and p=0.33 respectively), ER (p=0.06 and p=0.76 respectively), PR (p=0.61 and p=0.43 respectively) and C-erbB2 expression (p=0.58 and p=0.76 respectively) in ILC.
CONCLUSIONS: This study revealed that DDR1 and DVL1 are present in both IDC and ILC regardless of the tumour differentiation. More studies are needed to assess the potential of these two proteins in distinguishing IDC from ILC in breast tumours.
OBJECTIVE: This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor-defined breast cancer risk.
DESIGN: A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors.
RESULTS: After a median follow-up of 11.5 y (IQR: 10.1-12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER-PR-)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5-quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER-PR- breast cancer (ER-PR-: HRquintile 5-quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5-quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor-defined breast cancer risk.
CONCLUSION: This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk.
OBJECTIVE: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.
DESIGN: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.
RESULTS: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).
CONCLUSION: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.
METHODS: Uteri from ovariectomized, female Sprague-Dawley rats receiving seven days estradiol, progesterone or genistein (25, 50 and 100mg/kg/day) were harvested and levels of AQP-1, 2, 5 and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR (qPCR) respectively. Distribution of these proteins in uterus was observed by immunohistochemistry.
RESULTS: Genistein caused a dose-dependent increase in uterine AQP-1, 2, 5 and 7 protein and mRNA expression, however at the levels lower than following estradiol or progesterone stimulations. Effects of genistein were antagonized by estradiol receptor blocker, ICI 182780. Estradiol caused the highest AQP-2 protein and mRNA expression while progesterone caused the highest AQP-1, 5 and 7 protein and mRNA expression in uterus. AQP-1, 2, 5 and 7 protein were found to be distributed in the myometrium as well as in uterine luminal and glandular epithelia and endometrial blood vessels. In conclusion, the observed effects of estradiol, progesterone and genistein on uterine AQP-1, 2, 5 and 7 expression could help to explain the differences in the amount of fluid accumulated in the uterus under these different conditions.
MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.
RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.
CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.
Materials and Methods: Twenty-four: Sprague Dawley rats were equally distributed into the following four groups: G1 (control), G2, G3, and G4 represented the groups treated with EBN at graded concentrations of 0, 30, 60, and 120 mg/kg body weight (BW) per day for 8 weeks, respectively. During the experimental period, the BW of each rat was recorded weekly. At the proestrus stage of estrous cycle, blood samples were collected from the hearts of anesthetized rats that were later sacrificed. The uteri were removed for histological and immunohistochemical analyses.
Results: The EBN-treated groups showed an increase in the weights and lengths of uteri as compared to the control. Results showed that relative to G1 and G2, G3 and G4 exhibited proliferation in their uterine luminal and glandular epithelia and uterine glands, and up-regulated expressions of EGF, REGF, VEGF, PCNA, and progesterone receptor, and estrogen receptor in their uteri. The EBN increased the antioxidant (AO) and total AO capacities and reduced the oxidative stress (OS) levels in non-pregnant rats.
Conclusion: Findings of this study revealed that EBN promotes proliferation of the uterine structures as evidenced by the upregulation of the expressions of steroid receptors, EGF, REGF, VEGF, and PCNA in the uterus and increased in the plasma concentrations of AO and reduced levels of OS.
METHODS: The cytotoxic effect of hydromethanolic extract of A. crispa and its solvents partitions (ethyl acetate and aqueous extracts) against breast cancer cells were evaluated by using MTT assay. The cells were treated with concentration of extracts ranging from 15.63 μg/mL- 1000 μg/mL for 72 h. The quantification of phenolic and flavonoid contents of the extracts were carried out to determine the relationship between of phytochemical compounds responsible for cytotoxic and antioxidative activities. The antioxidant capacity was measured by DPPH and ABTS free radical scavenging assay and expressed as milligram (mg) Trolox equivalent antioxidant capacity per 1 g (g) of tested extract.
RESULTS: The hydromethanolic and ethyl acetate extracts showed moderate cytotoxic effect against MCF-7 with IC50 values of 57.35 ± 19.33 μg/mL, and 54.98 ± 14.10 μg/mL, respectively but aqueous extract was inactive against MCF-7. For MDA-MB-231, hydromethanolic, ethyl acetate and aqueous extracts exhibited weak cytotoxic effects against MDA-MB-231 with IC50 values more than 100 μg/mL. The plant revealed high total phenolic content, total flavonoid and antioxidant capacity.
CONCLUSION: The response of different type of breast cancer cell lines towards A. crispa extract and its partitions varied. Accordingly, hydromethanolic and ethyl acetate extracts appear to be more cytotoxic to oestrogen receptor (ER) positive breast cancer than oestrogen receptor (ER) negative breast cancer. However, aqueous extract appears to have poor activity to both types of breast cancer. Besides that, hydromethanolic and ethyl acetate extracts exhibit higher TPC, TFC and antioxidant capacity compared to aqueous extract. Synergistic effect of anticancer and antioxidant bioactives compounds of A. crispa plausibly contributed to the cytotoxic effects of the extract.
OBJECTIVE: This study aimed to examine the cost-effectiveness of second-line endocrine therapies for the treatment of postmenopausal women with HR + and HER2 - mBC.
METHODS: A Markov model was developed to analyze the cost-effectiveness of the therapies over a 15-year time horizon from a public healthcare payer's perspective. The efficacy and utility parameters were determined via a systematic search of the literature. Direct medical care costs were used. A discount rate of 2% was applied for costs and outcomes. Subgroup analysis was performed for non-visceral metastasis. A series of sensitivity analyses, including probabilistic sensitivity analysis (PSA) and threshold analysis were performed.
RESULTS: Base-case analyses estimated incremental cost-effectiveness ratios (ICERs) of 3 million and 6 million Japanese yen (JPY)/quality-adjusted life year (QALY) gained for TOR and FUL 500 mg relative to EXE, respectively. FUL 250 mg and EXE + EVE were dominated. The overall survival (OS) highly influenced the ICER. With a willingness-to-pay (WTP) threshold of 5 million JPY/QALY, the probability of TOR being cost-effective was the highest. Subgroup analysis in non-visceral metastasis revealed 0.4 and 10% reduction in ICER from the base-case results of FUL5 500 mg versus EXE and TOR versus EXE, respectively, while threshold analysis indicated EVE and FUL prices should be reduced 73 and 30%, respectively.
CONCLUSION: As a second-line therapy for postmenopausal women with HR +/HER2 - mBC, TOR may be cost-effective relative to other alternatives and seems to be the most favorable choice, based on a WTP threshold of 5 million JPY/QALY. FUL 250 mg is expected to be as costly and effective as EXE. The cost-effectiveness of EXE + EVE and FUL 500 mg could be improved by a large price reduction. However, the results are highly sensitive to the hazard ratio of OS. Policy makers should carefully interpret and utilize these findings.
METHODS: In this population-based case series, we evaluated breast cancer risk factors in relation to 10-year all-cause mortality (ACM) and 5-year recurrence by molecular subtype among 3012 women with invasive breast cancer in Sarawak, Malaysia. A total of 579 deaths and 314 recurrence events occurred during a median follow-up period of ~ 24 months. Subtypes (luminal A-like, luminal B-like, HER2-enriched, triple-negative) were defined using immunohistochemical markers for hormone receptors and human epidermal growth factor receptor 2 (HER2) in conjunction with histologic grade. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between risk factors and ACM/recurrence were estimated in subtype-specific Cox regression models.
RESULTS: We observed heterogeneity in the relationships between parity/breastfeeding, age at first full-term pregnancy (FFP), family history, body mass index (BMI), and tumor subtype (p value 30 vs
METHODS: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women's Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention.
RESULTS: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10- 6 for ModelER+ and 3.0 × 10- 6 for ModelGail.
CONCLUSIONS: Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention.