Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events

Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from questionnaires, pathology reports, and patients’ charts from 592 patients without preoperative treatment. Breast-feeding duration ≤12 months of the first child was associated with higher frequency of ER+/PgR+ tumors (P=0.02). Median follow-up time was 4.9 years. Higher risk for early events was observed for breast-feeding duration of first child >12 months (LogRank P=0.001), total breast-feeding duration >12 months (LogRank P=0.008), as well as ‘excessive milk production’ during breast-feeding of the first child (LogRank P=0.001). Patients with ‘almost no milk production’ had no events. In a multivariable model including both ‘excessive milk production’ and breast-feeding duration of the first child >12 months, both were associated with a two-fold risk for early events, adjusted HRs 2.33 (95% CI: 1.25-4.36) and 2.39 (0.97-5.85), respectively, while total breast-feeding duration was not. ‘Excessive milk production’ was associated with a two-fold risk of early distant metastases, adjusted HR 2.59 (1.13-5.94), but not duration. In conclusion, ‘excessive milk production’ during breast-feeding was associated with higher risk for early events independent of tumor characteristics, stressing the need to consider host factors in the evaluation of prognostic markers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-298) contains supplementary material, which is available to authorized users

Tumor-specific expression of HMG-CoA reductase in a population-based cohort of breast cancer patients

The mevalonate pathway synthetizes cholesterol, steroid hormones, and non-steriod isoprenoids necessary for cell survival. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme of the mevalonate pathway and the target for statin treatment. HMGCR expression in breast tumors has recently been proposed to hold prognostic and treatment-predictive information. This study aimed to investigate whether HMGCR expression in breast cancer patients was associated with patient and tumor characteristics and disease-free survival (DFS)

No association found between CYP2D6 genotype and early breast cancer events in tamoxifen-treated patients.

Background. CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy may account for some of the discrepancies. We examined the association between CYP2D6 genotype and early breast cancer events in tamoxifen-treated breast cancer patients, in relation to CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy. Material and methods. Pre- and postoperative questionnaires on lifestyle and concomitant medications were completed by 634 primary breast cancer patients between 2002 and 2008, among whom 333 patients had ER-positive tumors and received tamoxifen. CYP2D6*3, *4, *6, *10 and *41 were genotyped. Information on clinical data, breast cancer events, and tumor characteristics was obtained from patients' charts, population registries, the Regional Tumor Registry, and pathology reports. Results. Median follow-up was 4.9 years. Neither poor metabolizers (adjusted HR 0.50; 95% CI 0.07-3.82) nor intermediate metabolizers (adjusted HR 1.00; 95% CI 0.47-2.11) had an increased risk of early breast cancer events when compared with extensive metabolizers. CYP2D6 activity score (taking into account genotype and CYP2D6 inhibitor use) was not associated with early breast cancer events (LogRank, Ptrend = 0.44). Conclusions. CYP2D6 genotype was not associated with tamoxifen treatment outcome, even when CYP2D6 inhibitor use, aromatase inhibitor use, or chemotherapy was taken into account. CYP2D6 genotype may be of minor importance for tamoxifen-treated patients in Scandinavia

Given breast cancer, does breast size matter? Data from a prospective breast cancer cohort.

PURPOSE: Body mass index (BMI), waist-to-hip ratio (WHR), and tumor characteristics affect disease-free survival. Larger breast size may increase breast cancer risk, but its influence on disease-free survival is unclear. The purpose of this study was to elucidate whether breast size independently influenced disease-free survival in breast cancer patients. METHODS: Body measurements were obtained preoperatively from 772 breast cancer patients in a population-based ongoing cohort from southern Sweden. The research nurse measured breast volumes with plastic cups used by plastic surgeons doing breast reductions. Clinical data were obtained from patient charts and pathology reports. RESULTS: Patients with a BMI ≥ 25 kg/m(2) had larger tumors (p 0.85 had larger tumors (p = 0.013), more advanced histological grade (p = 0.0016), and more axillary nodal involvement (p = 0.012). Patients with right + left breast volume ≥ 850 mL were more likely to have larger tumor sizes (p = 0.018), more advanced histological grade (p = 0.031), and more axillary nodal involvement (p = 0.025). There were 62 breast cancer events during the 7-year follow-up. Breast volume ≥ 850 mL was associated with shorter disease-free survival (p = 0.004) and distant metastasis-free survival (p = 0.001) in patients with estrogen receptor (ER)-positive tumors independent of other anthropometric measurements and age. In patients with ER-positive tumors, breast size was an independent predictor of shorter disease-free (HR 3.64; 95 % CI 1.42-9.35) and distant metastasis-free survival (HR 6.33; 95 %CI 1.36-29.43), adjusted for tumor characteristics, BMI, age, and treatment. CONCLUSION: A simple and cheap anthropometric measurement with standardized tools may help identify a subgroup of patients in need of tailored breast cancer therapy

Given breast cancer, does breast size matter? Data from a prospective breast cancer cohort

PURPOSE: Body mass index (BMI), waist-to-hip ratio (WHR), and tumor characteristics affect disease-free survival. Larger breast size may increase breast cancer risk, but its influence on disease-free survival is unclear. The purpose of this study was to elucidate whether breast size independently influenced disease-free survival in breast cancer patients. METHODS: Body measurements were obtained preoperatively from 772 breast cancer patients in a population-based ongoing cohort from southern Sweden. The research nurse measured breast volumes with plastic cups used by plastic surgeons doing breast reductions. Clinical data were obtained from patient charts and pathology reports. RESULTS: Patients with a BMI ≥ 25 kg/m(2) had larger tumors (p 0.85 had larger tumors (p = 0.013), more advanced histological grade (p = 0.0016), and more axillary nodal involvement (p = 0.012). Patients with right + left breast volume ≥ 850 mL were more likely to have larger tumor sizes (p = 0.018), more advanced histological grade (p = 0.031), and more axillary nodal involvement (p = 0.025). There were 62 breast cancer events during the 7-year follow-up. Breast volume ≥ 850 mL was associated with shorter disease-free survival (p = 0.004) and distant metastasis-free survival (p = 0.001) in patients with estrogen receptor (ER)-positive tumors independent of other anthropometric measurements and age. In patients with ER-positive tumors, breast size was an independent predictor of shorter disease-free (HR 3.64; 95 % CI 1.42-9.35) and distant metastasis-free survival (HR 6.33; 95 %CI 1.36-29.43), adjusted for tumor characteristics, BMI, age, and treatment. CONCLUSION: A simple and cheap anthropometric measurement with standardized tools may help identify a subgroup of patients in need of tailored breast cancer therapy

Genetic factors, body constitution, and tumor characteristics in relation to breast cancer prognosis

Prior advancements in research on biomarkers and prognostic host factors have made it increasingly clear that breast cancer is an immensely heterogeneous disease. It remains difficult to predict which patients will benefit from different breast cancer treatments. Hence, interest in personalized medicine is internationally wide-spread and growing. In paper I, we found that tumor detection mode, as well as several tumor- and preoperative patient characteristics were associated with nonadherence to adjuvant endocrine treatment. Furthermore, two clinical profiles were strongly associated with nonadherence to adjuvant endocrine breast cancer therapy at both the 1- and the 2-year follow-up visits. In paper II, we found that waist-to-hip ratio (WHR), waist circumference, as well as breast volume were associated with disease-free survival. Breast cancer patients with ER positive tumors and a breast volume ≥850 mL had a significantly shorter disease-free survival, regardless of age, WHR, waist circumference, and BMI. In paper III, a strong interaction between having any COX2 rs5277 C-allele and ER status on disease-free survival was found. The effect was further modified by breast volume. Two subgroups of patients were identified: GG carriers with a large breast volume who responded poorly to chemotherapy regardless of ER status and C-allele carriers with ER positive tumors and a large breast volume who responded poorly to endocrine treatment but responded well to chemotherapy. In paper IV, the IL6 rs1800795 Any C genotype was strongly associated with early events among patients with ER negative tumors, particularly among radiotherapy-treated patients, and among chemotherapy-treated patients regardless of ER status. In conclusion, taking a more holistic view of the patient may prove beneficial both in and outside the clinic, ultimately paving the way for more personalized breast cancer treatment

Paternal intelligence affects school grades in children with and without ADHD - a register-based study

ADHD profoundly impacts educational attainment, quality of life, and health in young adults. However, certain subgroups of ADHD patients seem to do quite well, potentially due to differences in intelligence and socioeconomic status. Here we used paternal intelligence from the Swedish Defence Conscription and Assessment register, to investigate the role of genetic propensity for intelligence, on school performance in a large cohort of ADHD patients and matched controls. Patients treated for ADHD in Linköping, Sweden between 1995 and 2020 (n = 3262), sex- and age-matched controls (n = 9591) as well as their parents and siblings were identified using regional and national registers. Socioeconomic and demographic data, ADHD diagnosis and treatment and school grades at age 16 for the study population were extracted from Swedish National registers. We explored the associations between paternal intelligence and child school performance using linear mixed models and mediation analyses, taking a wide range of potential covariates into account. Results indicate that paternal intelligence was positively associated with standardized school grades in their offspring (Zadjusted=0.09, 95%CI 0.07, 0.10). This effect was present in both ADHD patients and controls, but ADHD patients had significantly lower standardized grades (Zadjusted=-1.03, 95%CI -1.08, -0.98). Child ADHD did not serve as a mediator for how paternal intelligence affected school grades. Our findings indicate that ADHD prevents children from reaching their academic potential at all levels of paternal intelligence. Increased understanding of the contributions of ADHD, intelligence, and SES to functional outcomes can help clinicians to better personalize interventions to the unique preconditions in each patient.Funding Agencies|Linkoping University</p

IL6 genotype, tumour ER-status, and treatment predicted disease-free survival in a prospective breast cancer cohort.

In breast cancer, high levels of the inflammatory cytokine interleukin-6 (IL-6) have been associated with disease-free survival and treatment resistance. Increased serum levels of IL-6 have been correlated with increased levels of NF-κβ and aromatase expression in adipose tissue. Several IL6 single nucleotide polymorphisms have been associated with breast cancer prognosis, but the impact may differ depending on tumour oestrogen receptor (ER) status. This translational study investigated the association between IL6 genotypes, ER-status, and treatment on the risk of early events among breast cancer patients

Abstract 4218: Combined effect of COX2 genotype, ER status, body constitution, and treatment on risk of early events in breast cancer patients

Abstract Aim: The aim of the present study was to investigate the impact of the COX2 rs5277 polymorphism on early events and treatment response in relation to tumor ER-status and to determine whether any effect is modified by body constitution. Background: The synonymous COX2 rs5277 polymorphism (306G&amp;gt;C, V102V) has been directly linked to several cancers associated with inflammation. Breast cancer patients with tumors expressing COX-2 have a shorter disease-free survival. It is currently unclear whether the rs5277 genotype is correlated with tumor COX-2 expression. Tumor COX-2 expression may have contrasting effects on breast cancer tumors depending on the tumor's estrogen receptor (ER) status. It has been associated with increased estrogen levels in ER-positive tumors and Akt-pathway activation in ER-negative tumors. Methods: The present study is based on data collected from 634 patients initiating treatment between October 2002 and October 2008. Risk of early events was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained at the pre-operative visit. Clinical data, patient-, and tumor-characteristics were obtained from questionnaires, patients' charts, population registries, and pathology reports. Results: Among all patients, 70.1% were GG-carriers, 27.5% were GC-carriers, and 2.4% were CC-carriers. Median follow-up was 5.1 years. Median age was 59.6 years (range 25-99 years). No association was seen between the G/G genotype and risk of early events in patients with ER-positive tumors, but this genotype conferred an over 4-fold increased risk in patients with ER-negative tumors (Pinteraction=0.015). G/G-carriers with a larger breast volume who had received chemotherapy had a 9-fold risk of early events irrespective of ER-status. C-allele carriers with ER-positive tumors who had a larger breast volume and had received endocrine-therapy had a 2-fold increased risk of early events. Conclusion: COX2 genotype, body constitution, and ER-status had a combined effect on the risk of early events and treatment response. The high risk for early events in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may provide a tool for identifying patients in need of more personalized treatment. Citation Format: Andrea Markkula, Maria Simonsson, Christian Ingvar, Carsten Rose, Helena Jernström. Combined effect of COX2 genotype, ER status, body constitution, and treatment on risk of early events in breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4218. doi:10.1158/1538-7445.AM2014-4218</jats:p