Quantification of multiple steroid hormones in serum and human breast cancer tissue by liquid chromatography-tandem mass spectrometry analysis.

Introduction: Systemic and local steroid hormone levels may function as novel prognostic and predictive biomarkers in breast cancer patients. We aimed at developing a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous measurement of multiple, biologically pivotal steroid hormones in human serum and breast cancer tissue. Methods: The quantitative method consisted of liquid-liquid extraction, Sephadex LH-20 chromatography for tissue extracts, and analysis of steroid hormones by liquid-chromatography-tandem mass spectrometry. We analyzed serum and tissue steroid hormone levels in 16 and 40 breast cancer patients, respectively, and assessed their correlations with clinical parameters. Results: The method included quantification of nine steroid hormones in serum [including cortisol, cortisone, corticosterone, estrone (E1), 17ß-estradiol (E2), 17α-hydroxyprogesterone, androstenedione (A4), testosterone and progesterone) and six (including cortisone, corticosterone, E1, E2, A4, and testosterone) in cancer tissue. The lower limits of quantification were between 0.003-10 ng/ml for serum (250 µl) and 0.038-125 pg/mg for tissue (20 mg), respectively. Accuracy was between 98%-126%, intra-assay coefficient of variations (CV) was below 15%, and inter-assay CV were below 11%. The analytical recoveries for tissue were between 76%-110%. Tissue levels of E1 were positively correlated with tissue E2 levels (p<0.001), and with serum levels of E1, E2 and A4 (p<0.01). Tissue E2 levels were positively associated with serum E1 levels (p=0.02), but not with serum E2 levels (p=0.12). The levels of tissue E2 and ratios of E1 to A4 levels (an index for aromatase activity) were significantly higher in patients with larger tumors (p=0.03 and p=0.02, respectively). Conclusions: The method was convenient and suitable for a specific and accurate profiling of clinically important steroid hormones in serum. However, the sensitivity of the profile method in steroid analysis in tissue samples is limited, but it can be used for the analysis of steroids in breast cancer tissues if the size of the sample or its steroid content is sufficient.

Pulmonary Function and Lung Fibrosis up to 12 Years After Breast Cancer Radiotherapy.

PURPOSE: Breast cancer (BC) treatment may affect pulmonary function, but evidence of long-term pulmonary toxicity is scarce. This study aimed to evaluate pulmonary function, radiation fibrosis (RF), and patient-reported dyspnea up to 12 years after different BC treatment modalities. METHODS AND MATERIALS: Two hundred fifty patients with BC referred to postoperative radiotherapy (RT) were included in this study. High-resolution computed tomography, pulmonary function tests (PFTs), clinical examinations, and patient-reported dyspnea were assessed before RT and at 3, 6, and 12 months and up to 12 years after RT. RESULTS: Vital capacity (VC), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusion capacity of the lungs for carbon monoxide (DLCO) declined at 3 months after RT and remained low at long-term follow-up except for DLCO, which increased up to 12 years after RT. VC, FEV1, and FVC changes differed between patients treated with and without chemotherapy, and FEV1 differed between patients treated with locoregional and local RT. An early decline in VC, FEV1, and FVC predicted a late decline in PFT values up to 12 years after RT (P = .020, P = .004, and P = .020, respectively). RF, mainly grade 1, was observed in 91% of patients at long-term follow-up. Few patients reported severe dyspnea at long-term follow-up, and there was no statistically significant association with concurrent RF or decline in PFT values from baseline. CONCLUSIONS: Chemotherapy and locoregional RT affected performance in PFTs up to 12 years after RT. Reduction in VC, FVC, and FEV1 3 months after RT predicted a decline in PFT values at long-term follow-up. However, a late decline in PFT values was not associated with long-term RF or patient-reported dyspnea.

Association of serum cortisol and cortisone levels and risk of recurrence after endocrine treatment in breast cancer.

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7-12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17ß-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography-tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan-Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (

Sexual health in long-term breast cancer survivors: a comparison with female population controls from the HUNT study.

PURPOSE: Sexual health is an important aspect of quality of life. Knowledge concerning sexual health in long-term breast cancer survivors (BCSs) is limited. This study compared sexual health in BCSs 8 years after diagnosis with similarly aged controls and examined the impact of menopausal status at diagnosis and systemic breast cancer treatments on sexual health. METHODS: Women aged 20-65 years when diagnosed with stage I-III breast cancer in 2011-2012 were identified by the Cancer Registry of Norway (n = 2803) and invited to participate in a nationwide survey. Controls were women from the Trøndelag Health Study (HUNT4). Sexual functioning and sexual enjoyment were measured by the EORTC QLQ-BR23 subscales scored from 0 to 100, and sexual discomfort by the Sexual Activity Questionnaire scored from 0 to 6. Linear regression analyses with adjustments for sociodemographic and health-related variables were performed to compare groups. Differences of ≥ 10% of range score were considered clinically significant. RESULTS: The study samples consisted of 1241 BCSs and 17,751 controls. Sexual enjoyment was poorer (B - 13.1, 95%CI - 15.0, - 11.2) and discomfort higher (B 0.9, 95%CI 0.8, 1.0) among BCSs compared to controls, and larger differences were evident between premenopausal BCSs and controls (B - 17.3, 95%CI - 19.6, - 14.9 and B 1.2, 95%CI 1.0, 1.3, respectively). BCSs treated with both endocrine- and chemotherapy had lower sexual functioning (B - 11.9, 95%CI - 13.8, - 10.1), poorer sexual enjoyment (B - 18.1, 95%CI - 20.7, - 15.5), and more sexual discomfort (B 1.4, 95% 1.3, 1.6) than controls. CONCLUSION: Sexual health impairments are more common in BCSs 8 years after diagnosis compared to similar aged population controls. During follow-up, attention to such impairments, especially among women diagnosed at premenopausal age and treated with heavy systemic treatment, is warranted.

Longitudinal Changes in Circulating Metabolites and Lipoproteins After Breast Cancer Treatment.

The multimodal treatment of breast cancer may induce long term effects on the metabolic profile and increase the risk of future cardiovascular disease. In this study, we characterized longitudinal changes in serum lipoprotein subfractions and metabolites after breast cancer treatment, aiming to determine the long-term effect of different treatment modalities. Further, we investigated the prognostic value of treatment-induced changes in breast cancer-specific and overall 10-year survival. In this study, serum samples from breast cancer patients (n = 250) were collected repeatedly before and after radiotherapy, and serum metabolites and lipoprotein subfractions were quantified by NMR spectroscopy. Longitudinal changes were assessed by univariate and multivariate data analysis methods applicable for repeated measures. Distinct changes were detectable in levels of lipoprotein subfractions and circulating metabolites during the first year, with similar changes despite large differences in treatment regimens. We detect increased free cholesterol and decreased esterified cholesterol levels of HDL subfractions, a switch towards larger LDL particles and higher total LDL-cholesterol, in addition to a switch in the glutamine-glutamate ratio. Non-survivors had different lipid profiles from survivors already at baseline. To conclude, our results show development towards an atherogenic lipid profile in breast cancer patients with different treatment regimens.

Pneumonitis and fibrosis after breast cancer radiotherapy: occurrence and treatment-related predictors.

BACKGROUND: Radiation pneumonitis (RP) and radiation fibrosis (RF) are common side effects after breast cancer (BC) radiotherapy (RT). However, there is a great variation in the frequency of RP and RF. This study presents the occurrence of- and the treatment-related predictors for RP and RF. Further, physician- and patient-reported pulmonary symptoms during the first year after postoperative RT for BC are demonstrated. MATERIALS AND METHODS: From 2007 to 2008, 250 BC patients referred for postoperative RT were included in a prospective cohort study and followed during the first year after RT. High-resolution computed tomography of the lungs and symptom registration were performed before RT and 3, 6, and 12 months after RT. Patient-reported symptoms were registered by standard quality of life questionnaires. Logistic regression analyses were applied to estimate treatment-related predictors for radiological RP (rRP), clinical RP (cRP), radiological RF (rRF), and clinical RF (cRF). RESULTS: The occurrence of rRP and cRP at three months was 78% and 19%, while 12 months after RT rRF and cRF was 89% and 16%, respectively; all reported as grade 1. In multivariable analyses, mastectomy predicted cRP at three months (OR = 2.48, p = .03) and cRF at six months, ipsilateral lung volume receiving 20 Gray or more (V20), V30, and mean lung dose (MLD) predicted rRP at six months (OR = 1.06, p = .0003; OR = 1.10, p = .001; and OR = 1.03, p = .01, respectively). Endocrine treatment predicted cRF at 12 months (OR = 2.48, p = .02). Physicians reported significant more dyspnea at 3 months (p = .003) and patients reported 'a little dyspnea' more at 3 and 12 months compared to baseline (p = .007). CONCLUSION: RP and RF are prevalent in the first year after BC radiation. Mastectomy predicted cRP at three months. V20, V30, D25, and MLD predicted rRP at 6 months, and endocrine treatment predicted cRF at 12 months. Patients and physicians reported dyspnea differently.

Validation of the WHOQOL-Bref: psychometric properties and normative data for the Norwegian general population.

BACKGROUND: The World Health Organization's Quality of Life Questionnaire (WHOQOL-Bref) is a frequently used instrument to assess the quality of life in both healthy and ill populations. Inquiries of the psychometric properties of the WHOQOL-Bref report that the validity and reliability is generally satisfactory. However, some studies fail to support a four-factor dimensionality; others report poor reliability of the social and environmental domain; and there may be some challenges of supporting construct validity across age. This paper evaluates the psychometric properties of the Norwegian WHOQOL-Bref and extends previous research by testing for measurement invariance across age, gender and education level. In addition, we provide updated normative data for the Norwegian population. METHODS: We selected a random sample of the Norwegian population (n = 654) aged 18-75 years. Participants filled out the WHOQOL-Bref, the Utrecht Work Engagement Scale and various sociodemographic variables. RESULTS: We found an acceptable convergent and discriminate validity and internal consistency of the physical, psychological and environmental domains, but a marginal reliability was found for the social domain. The factor loadings were invariant across gender, education and age. Some items had low factor loadings and explained variance, and the model fit for the age group 60-75 years were less satisfactory. CONCLUSIONS: The original four-factor dimensionality of the WHOQOL-Bref displayed a better fit to the data compared to the one-factor solution and is recommended for use in the Norwegian population. The WHOQOL-Bref is suitable to use across gender, education and age, but for assessment in the oldest age group, the WHOQOL-Old module could be a good supplementary, but further studies are needed.

Everyday life in breast cancer survivors experiencing challenges: A qualitative study.

BACKGROUND: Early diagnosis and treatment of breast cancer results in an increasing number of survivors, some of whom face new challenges in their transition to daily life. AIM: Based on these experiences, the aim of this study was to describe the everyday life in breast cancer survivors experiencing challenges. MATERIAL AND METHOD: Eleven women recruited from a follow-up study of breast cancer patients participated in qualitative interviews about their everyday occupations seven years after ending treatment. The inductive analysis revealed ten categories that were organized into five subthemes under the two main themes 'bodily and mental loneliness' and 'new center of gravity in everyday life'. RESULTS: Findings showed how relevant information and guidance; active support to the client and their relatives; and a balance between occupations at home and at work were important matters to handle their everyday life challenges. CONCLUSION AND SIGNIFICANCE: By assisting these women in finding new patterns of meaningful occupations that positively affect their everyday life, the study suggests some central elements to be included in future follow-up practice for breast cancer survivors. Approaching this goal, occupational therapists should contribute to more involvement assisting cancer survivors and their partners in finding new patterns of meaningful occupations that positively affect their everyday life.

A randomized study of the effect of patient positioning on setup reproducibility and dose distribution to organs at risk in radiotherapy of rectal cancer patients.

BACKGROUND: The patient positioning in pelvic radiotherapy (RT) should be decided based on both reproducibility and on which position that yields the lowest radiation dose to the organs at risk (OAR), and thereby less side effects to patients. The present randomized study aimed to evaluate the influence of patient positioning on setup reproducibility and dose distribution to OAR in rectal cancer patients. METHODS: Ninety-one patients were randomized into receiving RT in either supine or prone position. The recruitment period was from 2005 to 2008. Position deviations were derived from electronic portal image registrations, and setup errors were defined as deviations between the expected and the actual position of bony landmarks. Setup deviations were expressed into three table shift values (∆x, ∆y, ∆z) from which the deviation vector [Formula: see text] were calculated. The estimated lengths of [Formula: see text] defined the main outcome and were compared between prone and supine positions using linear mixed model statistics. The mean volume of each 5 Gy increments between 5 and 45 Gy was calculated for the small bowel and the total bowel, and the dose volumes were compared between prone and supine position. RESULTS AND CONCLUSION: Data from 83 patients was evaluable. The mean [Formula: see text] was 5.8 mm in supine position and 7.1 mm in prone position (p = 0.024), hence the reproducibility was significantly superior in supine position. However, the difference was marginal and may have borderline clinical importance. The irradiated volumes of the small bowel and the total bowel were largest in the supine position for all dose levels, but none of those were significantly different. The patient positioning in RT of rectal cancer patients may therefore be decided based on other factors such as the most comfortable position for the patients.

One-year course of fatigue after post-operative radiotherapy in Norwegian breast cancer patients--comparison to general population.

INTRODUCTION: Fatigue after treatment for breast cancer (BC) is common, but poorly understood. We examined the fatigue levels during first year after radiotherapy (RT) according to the extent of RT (local or locoregional), hormonal therapy (HT) and chemotherapy (CT). The impact of comorbidity was also explored. Moreover, we compared fatigue levels in patients with the general population (GenPop) data. MATERIAL AND METHODS: BC patients (n = 250) referred for post-operative RT at St. Olavs Hospital, Trondheim, Norway, were enrolled. Fatigue was measured by the EORTC QLQ-C30-fatigue subscale, ranging from 0 to 100, before RT (baseline), after RT, and at three, six, and 12 months. Clinical and treatment-related factors were recorded at baseline. GenPop data was available from a previous survey (n = 652). Linear mixed models and analysis of covariance were applied. RESULTS: Compliance ranged from 87% to 98%. At baseline, mean value (SD) of fatigue in BC patients was 26.8 (23.4). The level increased during RT (mean change 8.3, 95% CI 5.5-11.1), but declined thereafter and did not differ significantly from pre-treatment levels at subsequent time points. In age-adjusted analyses, locoregional RT accounted for more overall fatigue than local RT (mean difference 6.6, 95% CI 1.2-12.0), but the association was weakened and not statistical significant when adjusting for CT and HT. Similar pattern was seen for CT and HT. The course of fatigue differed significantly by CT (p < 0.001, interaction test). At baseline, fatigue levels were higher in patients with than without CT, but at subsequent time points similar levels were evident, indicating a temporary adverse effect of CT. Comorbidity was significantly associated with increased level of fatigue, independent of other factors (mean difference 8.1, 95% CI 2.2-14.1). BC-patients were not significantly more fatigued than GenPop, except for immediately after ending RT, and then only among those without comorbidity (mean 35.9 vs. 25.8, p < 0.001). CONCLUSION: Comorbidity seems to be a more important determinant for fatigue levels than the cancer treatment.

Early effects of contemporary breast radiation on health-related quality of life - predictors of radiotherapy-related fatigue.

BACKGROUND AND PURPOSE: The aim of this study was to report on early effects of contemporary radiotherapy (RT) on health-related quality of life (HRQOL) and explore treatment-related contributors to the development of fatigue during RT in breast cancer (BC) patients. MATERIAL AND METHODS: Consecutive BC patients (n = 248) referred for postoperative RT at St. Olavs University Hospital in Trondheim, Norway were enrolled from February 2007 to October 2008. Clinical- and treatment data were recorded, and HRQOL were assessed before starting (baseline) and immediately after ending RT using the "EORTC QLQ-C30" and the breast module "EORTC QLQ-BR23". Change scores from baseline were calculated. Predictors of increased fatigue during RT were explored with multiple regression analysis adjusted for relevant confounders. RESULTS: The global QOL- and all functional scales remained stable, except for "future perspective" which improved significantly during RT. Breast symptoms and fatigue increased significantly during RT. Groups with elevated baseline fatigue remained more stable during RT than those with lower levels at baseline. The body volume receiving 40 Gy or more (V40) was a significant predictor of increased fatigue during RT adjusted for chemotherapy, comorbidity and age (p = 0.035). CONCLUSION: Contemporary RT has limited early effects on HRQOL. V40 is a significant predictor of RT-related fatigue.

Validation of the intestinal part of the prostate cancer questionnaire "QUFW94": psychometric properties, responsiveness, and content validity.

PURPOSE: Several treatment options are available for patients with prostate cancer. Applicable and valid self-assessment instruments for assessing health-related quality of life (HRQOL) are of paramount importance. The aim of this study was to explore the validity and responsiveness of the intestinal part of the prostate cancer-specific questionnaire QUFW94. METHODS AND MATERIALS: The content of the intestinal part of QUFW94 was examined by evaluation of experienced clinicians and reviewing the literature. The psychometric properties and responsiveness were assessed by analyzing HRQOL data from the randomized study Scandinavian Prostate Cancer Group 7 (SPCG)/Swedish Association for Urological Oncology 3 (SFUO). Subscales were constructed by means of exploratory factor analyses. Internal consistency was assessed by Cronbach's alpha. Responsiveness was investigated by comparing baseline scores with the 4-year posttreatment follow-up. RESULTS: The content validity was found acceptable, but some amendments were proposed. The factor analyses revealed two symptom scales. The first scale comprised five items regarding general stool problems, frequency, incontinence, need to plan toilet visits, and daily activity. Cronbach's alpha at 0.83 indicated acceptable homogeneity. The second scale was less consistent with a Cronbach's alpha at 0.55. The overall responsiveness was found to be very satisfactory. CONCLUSION: Two scales were identified in the bowel dimension of the QUFW94; the first one had good internal consistency. The responsiveness was excellent, and some modifications are suggested to strengthen the content validity.