Symptoms in long-term breast cancer survivors:A cross-sectional study in primary care

Purpose: Various long-term symptoms can manifest after breast cancer treatment, but we wanted to clarify whether these are more frequent among long-term breast cancer survivors than matched controls and if they are associated with certain diagnoses. Methods: This was a cross-sectional, population-based study of 350 breast cancer survivors treated with chemo- and/or radiotherapy >= 5 years (median 10) after diagnosis and 350 women without cancer matched by age and primary care physician. All women completed a questionnaire enquiring about symptoms, underwent echocardiography to assess the left ventricle ejection fraction, and completed the Hospital Anxiety and Depression Scale. Cardiovascular diseases were diagnosed from primary care records. In a multivariable logistic regression analysis, symptoms were adjusted for the long-term effects and compared between cohorts and within the survivor group. Results: Concentration difficulties, forgetfulness, dizziness, and nocturia were more frequent among breast cancer survivors compared with controls, but differences could not be explained by cardiac dysfunction, cardiovascular diseases, depression, or anxiety. Intermittent claudication and appetite loss were more frequent among breast cancer survivors than controls and associated with cardiac dysfunction, depression, and anxiety. Breast cancer survivors treated with chemotherapy with/without radiotherapy were at significantly higher odds of forgetfulness and nocturia, but significantly lower odds of dizziness, compared with breast cancer survivors treated with radiotherapy alone. Conclusions: Intermittent claudication and appetite loss are common among breast cancer survivors and are associated with cardiac dysfunction and mood disorders. Other symptoms varied by whether the patient underwent chemotherapy with/without radiotherapy (forgetfulness and nocturia) radiotherapy alone (dizziness). (C) 2020 The Author(s). Published by Elsevier Ltd

Xist and Tsix transcription dynamics is regulated by the X-to-autosome ratio and semistable transcriptional states

In female mammals, X chromosome inactivation (XCI) is a key process in the control of gene dosage compensation between Xlinked genes and autosomes. Xist and Tsix, two overlapping antisense-transcribed noncoding genes, are central elements of the X inactivation center (Xic) regulating XCI. Xist upregulation results in the coating of the entire X chromosome by Xist RNA in cis, whereas Tsix transcription acts as a negative regulator of Xist. Here, we generated Xist and Tsix reporter mouse embryonic stem (ES) cell lines to study the genetic and dynamic regulation of these genes upon differentiation. Our results revealed mutually antagonistic roles for Tsix on Xist and vice versa and indicate the presence of semistable transcriptional states of the Xic locus predicting the outcome of XCI. These transcriptional states are instructed by the X-t

Health-related quality of life of early-stage breast cancer patients after different radiotherapy regimens

Purpose To evaluate and compare health-related quality of life (HRQL) of women with early-stage breast cancer (BC) treated with different radiotherapy (RT) regimens. Methods Data were collected from five prospective cohorts of BC patients treated with breast-conserving surgery and different RT regimens: intraoperative RT (IORT, 1 x 23.3 Gy; n = 267), external beam accelerated partial breast irradiation (EB-APBI, 10 x 3.85 Gy; n = 206), hypofractionated whole breast irradiation(hypo-WBI, 16 x 2.67 Gy; n = 375), hypo-WBI + boost(hypo-WBI-B, 21-26 x 2.67 Gy; n = 189), and simultaneous WBI + boost(WBI-B, 28 x 2.3 Gy; n = 475). Women >= 60 years with invasive/in situ carcinoma <= 30 mm, cN0 and pN0-1a were included. Validated EORTC QLQ-C30/BR23 questionnaires were used to asses HRQL. Multivariable linear regression models adjusted for confounding (age, comorbidity, pT, locoregional treatment, systemic therapy) were used to compare the impact of the RT regimens on HRQL at 12 and 24 months. Differences in HRQL over time (3-24 months) were evaluated using linear mixed models. Results There were no significant differences in HRQL at 12 months between groups except for breast symptoms which were better after IORT and EB-APBI compared to hypo-WBI at 12 months (p < 0.001). Over time, breast symptoms, fatigue, global health status and role functioning were significantly better after IORT and EB-APBI than hypo-WBI. At 24 months, HRQL was comparable in all groups. Conclusion In women with early-stage breast cancer, the radiotherapy regimen did not substantially influence long-term HRQL with the exception of breast symptoms. Breast symptoms are more common after WBI than after IORT or EB-APBI and improve slowly until no significant difference remains at 2 years posttreatment.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Clinical characteristics and survival patterns of subsequent sarcoma, breast cancer, and melanoma after childhood cancer in the DCOG-LATER cohort

Purpose Childhood cancer survivors are at increased risk of developing subsequent malignant neoplasms (SMNs). We compared survival and clinical characteristics of survivors with SMNs (sarcoma, breast cancer, or melanoma) an

Fitting the Puzzle Pieces: The Bigger Picture of XCI

X chromosome inactivation (XCI) is a mammalian-specific process initiated in all female cells, leading to one inactivated X chromosome. The robust nature of XCI, and the complex mechanisms involved in directing this process, makes XCI an important model system to study all aspects of gene regulation. XCI is divided into distinct phases: initiation, establishment, and maintenance of the inactive X (Xi). Recent studies shed important new light on the mechanisms directing all three phases of XCI. These findings include new regulatory pathways in XCI initiation, and the identification of a plethora of new factors involved in establishing and maintaining the Xi. In this review, we will highlight and discuss these new findings in the bigger picture of XCI

Simultaneous integrated boost irradiation after breast-conserving surgery: physician-rated toxicity and cosmetic outcome at 30 months' follow-up

PURPOSE: To evaluate toxicity and cosmetic outcome (CO) in breast cancer survivors treated with three-dimensional conformal radiotherapy with a hypofractionated, simultaneous integrated boost (3D-CRT-SIB) and to identify risk factors for toxicity, with special focus on the impact of age. METHODS AND MATERIALS: Included were 940 consecutive disease-free patients treated for breast cancer (Stage 0-III) with 3D-CRT-SIB, after breast-conserving surgery, from 2005 to 2010. Physician-rated toxicity (Common Terminology Criteria for Adverse Events version 3.0) and CO were prospectively assessed during yearly follow- up, up to 5 years after radiotherapy. Multivariate logistic regression analyses using a bootstrapping method were performed. RESULTS: At 3 years, toxicity scores of 436 patients were available. Grade >/= 2 fibrosis in the boost area was observed in 8.5%, non-boost fibrosis in 49.4%, pain to the chest wall in 6.7%, and fair/poor CO in 39.7% of cases. Radiotherapy before chemotherapy was significantly associated with grade >/= 2 boost fibrosis at 3 years (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.3-6.0). Non-boost fibrosis was associated with re-resection (OR 2.2, 95% CI 1.2-4.0) and larger tumors (OR 1.1, 95% CI 1.0-1.1). At 1 year, chest wall pain was significantly associated with high boost dosage (OR 2.1, 95% CI 1.2-3.7) and younger age (OR 0.4, 95% CI 0.2-0.7). A fair/poor CO was observed more often after re-resection (OR 4.5, 95% CI 2.4-8.5), after regional radiotherapy (OR 2.9, 95% CI 1.2-7.1), and in larger tumors (OR 1.1, 95% CI 1.0-1.1). CONCLUSIONS: Toxicity and CO are not impaired after 3D- CRT-SIB. Fibrosis was not significantly associated with radiotherapy parameters. Independent risk factors for fibrosis were chemotherapy after radiotherapy, re-resection, and larger tumor size. Re-resection was most predictive for worse CO. Age had an impact on chest wall pain occurrence