The influence of metabolic factors and ethnicity on breast cancer risk, treatment and survival: The Oslo ethnic breast cancer study

Background - Breast cancer risk remains higher in high-income compared with low-income countries. However, it is unclear to what degree metabolic factors influence breast cancer development in women 30 years after immigration from low- to a high-incidence country. Methods - Using Cox regression models, we studied the association between pre-diagnostic metabolic factors and breast cancer development, and whether this association varied by ethnicity among 13,802 women participating in the population-based Oslo Ethnic Breast Cancer Study. Ethnic background was assessed and pre-diagnostic metabolic factors (body mass index, waist:hip ratio, serum lipids and blood pressure) were measured. A total of 557 women developed invasive breast cancer, and these women were followed for an additional 7.7 years. Results - Among women with an unfavorable metabolic profile, women from south Asia, compared with western European women, had a 2.3 times higher breast cancer risk (HR 2.30, 95% CI 1.18–4.49). Compared with the western European women, the ethnic minority women were more likely to present with triple-negative breast cancer (TNBC) (OR 2.11, 95% CI 0.97–4.61), and less likely to complete all courses of planned taxane treatment (OR 0.26, 95% CI 0.08–0.82). Among TNBC women, above-median triglycerides:HDL-cholesterol (>0.73) levels, compared with below-median triglycerides:HDL-cholesterol (≤0.73) levels, was associated with 2.9 times higher overall mortality (HR 2.88, 95% CI 1.02–8.11). Conclusions - Our results support the importance of metabolic factors when balancing breast cancer prevention and disease management among all women, and in particular among non-western women migrating from a breast cancer low-incidence to a high-incidence country

Adult Height, Insulin Levels and 17β-Estradiol in Young Women

Background: Adult height and insulin levels have independently been associated with breast cancer risk. However, little is known about whether these factors influence estradiol levels. Thus, we hypothesize that adult height in combination with insulin levels may influence premenopausal 17β-estradiol throughout the entire menstrual cycle of possible importance of breast cancer risk. Methods: Among 204 healthy women, aged 25-35 years who participated in the Norwegian EBBA I study, birth weight and age at menarche were assessed by questionnaire, personal health record and interview. 17β-estradiol concentrations were estimated by daily saliva samples throughout one entire menstrual cycle using radioimmunoassay (RIA). Measures of height (cm) were taken as well as waist circumference (cm), body mass index (BMI kg/m2) and total fat percentage (DEXA % fat). Fasting blood samples were drawn, and serum concentrations of insulin were determined. Results: The women reported a mean height of 166.5 cm, birth weight of 3389 g and age at menarche 13.1 years. Mean BMI was 24.4 kg/m2, mean waist circumference 79.5 cm and mean total fat percentage 34.1%. Women with an adult height of more than 170 cm and insulin levels higher than 90 pmol/L experienced on average an 37.2 % increase in 17β- estradiol during an entire menstrual cycle compared to those with the same height, and insulin levels below 90 pmol/L. Moreover, this was also observed throughout the entire menstrual cycle. Conclusion: Our findings support that premenopausal levels of 17β-estradiol vary in response to adult height and insulin levels, suggesting that women who become taller are put at risk for higher estradiol levels when their insulin levels rise of possible importance for breast cancer risk.Anthropolog

17β-Estradiol Levels During An Entire Menstrual Cycle In Response To Adult Stature and Insulin, Of Possible Importance For Breast Cancer Risk: The EBBA-I study.

Background: The normal breast cells develop into malignant cells as a result of a complex interplay between genetic, environmental, nutritional and hormonal factors. Attained adult stature and insulin levels, risk factors for breast cancer, may also vary in response to the same factors. Thus, we hypothesize that 17β-estradiol, a key factor in the carcinogenesis of the breast, may vary in response to adult height in combination with insulin levels of possible importance of breast cancer risk. Methods: Among 204 healthy women, aged 25-35 years who participated in the Norwegian EBBA-I study, 17β-estradiol concentrations were measured in daily saliva samples throughout one entire menstrual cycle using radioimmunoassay (RIA). Attained height (cm) was measured, and serum concentrations of insulin were determined in fasting blood samples. The associations between adult height, insulin and 17β-estradiol levels throughout a menstrual cycle were studied using multivariate linear regression analyses and linear mixed models for repeated measures. Adjustments for potential confounding factors were performed. Results: A 37.2 % increase in 17β-estradiol levels was observed during the entire menstrual cycle among women with an adult height ≥170 cm (upper tertile) and insulin levels ≥ 90 pmol/L (upper tertile) compared to women with the same attained adult height, and insulin levels < 90pmol/L. The association was even more pronounced when we looked into those women with attained adult height ≥170 cm (upper tertile) and serum insulin ≥ 101 pmol/L (upper quartile) (Fig. 1). Adjustments for potential confounding factors were performed. Conclusion: Our findings support that premenopausal levels of 17β-estradiol vary in response to adult height and insulin levels, suggesting that women who become taller are put at risk for higher estradiol levels throughout the entire menstrual cycle when their insulin levels rise, of possible importance for breast cancer risk.AnthropologyHuman Evolutionary Biolog

Ny medikamentell behandling av brystkreft Adjuvant behandling med trastuzumab ved tidlig stadium av brystkreft - en helseøkonomisk analyse

Source at https://www.helsebiblioteket.no/Denne rapporten er andre del av et oppdrag fra Sosial- og helsedirektoratet og RHF - fagdirektørene med fokus på virkestoffet trastuzumab ved adjuvant behandling av brystkreft. Adjuvant behandling gis i tillegg til hovedbehandlingen (for eksempel kirurgi) for å påvirke eventuelt gjenværende kreftceller hos pasienten. Denne delen av oppdraget vurderer de helseøkonomiske konsekvensene av adjuvant behandling av brystkreft med dette virkestoffet. Trastuzumab markedsføres i Norge under produktnavnet Herceptin ®

Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer

The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10-6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .)

Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study

Background Presence of disseminated tumor cells (DTCs) in bone marrow (BM) after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response. Methods A total of 1121 patients with pN1-3 or pT1c/T2G2-3pN0-status were enrolled. All had completed primary surgery and received 6 cycles of anthracycline-containing chemotherapy. BM-aspiration was performed 8-12 weeks after chemotherapy (BM1), followed by a second BM-aspiration 6 months later (BM2). DTC-status was determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. If DTCs were present at BM2, docetaxel (100 mg/m2, 3qw, 6 courses) was administered, followed by DTC-analysis 1 month (BM3) and 13 months (BM4) after the last docetaxel infusion. Results Clinical follow-up (FU) is still ongoing. Here, the descriptive data from the study are presented. Of 1085 patients with a reported DTC result at both BM1 and BM2, 94 patients (8.7%) were BM1 positive and 83 (7.6%) were BM2 positive. The concordance between BM1 and BM2 was 86.5%. Both at BM1 and BM2 DTC-status was significantly associated with lobular carcinomas (p = 0.02 and p = 0.03, respectively; chi-square). In addition, DTC-status at BM2 was also associated with pN-status (p = 0.009) and pT-status (p = 0.03). At BM1 28.8% and 12.8% of the DTC-positive patients had ≥2 DTCs and ≥3 DTCs, respectively. At BM2, the corresponding frequencies were 47.0% and 25.3%. Of 72 docetaxel-treated patients analyzed at BM3 and/or BM4, only 15 (20.8%) had persistent DTCs. Of 17 patients with ≥3 DTCs before docetaxel treatment, 12 patients turned negative after treatment (70.6%). The change to DTC-negativity was associated with the presence of ductal carcinoma (p = 0.009). Conclusions After docetaxel treatment, the majority of patients experienced disappearance of DTCs. As this is not a randomized trial, the results can be due to effects of adjuvant (docetaxel/endocrine/trastuzumab) treatment and/or limitations of the methodology. The clinical significance of these results awaits mature FU data, but indicates a possibility for clinical use of DTC-status as a residual disease-monitoring tool and as a surrogate marker of treatment response. Trial registration Clin Trials Gov NCT0024870