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Background Breast cancer remains the number 1 lethal malignancy in women. With rising incidence and decreased mortality, the number of breast cancer survivors has increased. Consequently, sequelae, such as pain, are becoming more important. Purpose The purpose of this study was to identify risk factors for the development of pain in breast cancer survivors. Methods PubMed and Web of Science were systematically screened for studies encompassing risk factors for the development of pain in breast cancer survivors. Meta-analyses were carried out for risk factors described in more than one article. Moderator analysis was performed in case of high heterogeneity ( I 2  > 50%) across studies. Results Seventeen studies were found eligible. Meta-analyses were performed for 17 factors. Significant differences for the odds of developing chronic pain were found for BMI (overall OR: 1.34, 95%CI 1.08–1.67, p  = 0.008), education (overall OR: 1.23, 95%CI 1.07–1.42, p  = 0.005), lymphedema (overall OR: 2.58, 95%CI 1.93–3.46, p  < 0.00001), smoking status (overall OR: 0.75, 95%CI 0.62–0.92, p  = 0.005), axillary lymph node dissection (overall OR: 1.25, 95%CI 1.04–1.52, p  = 0.02), chemotherapy (overall OR: 1.44, 95%CI 1.24–1.68, p  < 0.00001), and radiotherapy (overall OR: 1.32, 95%CI 1.17–1.48, p  < 0.00001). After performing moderator analyses for age, comorbidities, hormone therapy, and breast surgery, hormone therapy became a significant risk factor as well (overall OR: 1.33, 95%CI 1.15–1.54, p  = 0.0001). Conclusion BMI > 30, education < 12–13 years, lymphedema, not smoking, axillary lymph node dissection, chemotherapy, hormone therapy, and radiotherapy were significantly associated with higher odds for the development of chronic pain, with lymphedema being the biggest risk factor. Lack of uniformity across the studies in defining pain, follow-up, measurement tools, and cut-off values for the diagnosis of pain was noted, resulting in greater inter-study variability.

BackgroundThe importance of cognitive appraisals in the effectiveness of pain coping is well established. Two key variables in these appraisal processes are pain catastrophizing (PC) and perceived injustice (PI), which are known to increase the risk of long-term disability and aggravate the pain-related distress through maladaptive behavioral responses. However, to date, the mediating effects of these appraisals have not been examined concurrently in the breast cancer survivor (BCS) population, nor have they been related to health-related quality of life (HRQoL).MethodsUsing cross-sectional data from 110 BCS, structural path analyses were used to examine the mediating effects of PC and PI in the relationship of pain on the HRQoL in BCS.ResultsResults demonstrated a significant direct effect of pain and PI on HRQoL combined with a significant indirect effect through PI, but not through PC. An increase in pain is suggested to result in a decrease in quality of life. On the other hand, an increase in pain also is suggested to increase the PI. A similar relation with PC was not retained as significant.ConclusionThe relative salience of PI as a mediator of HRQoL underscores the fact that PI is not only understudied but also underappreciated and undertreated in the BCS population. The results of our study warrant replication across longitudinal studies but continue to expand upon the evidence of the multifactorial nature of pain coping in BCS.

Background Long-term prospective patient-reported outcomes (PRO) after breast cancer adjuvant radiotherapy is scarce. TomoBreast compared conventional radiotherapy (CR) with tomotherapy (TT), on the hypothesis that TT might reduce lung-heart toxicity. Methods Among 123 women consenting to participate, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to breast/chest wall and regional nodes if node-positive, with a sequential boost (16 Gy/8 fractions/1.6 weeks) after lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to breast/chest wall and regional nodes if node-positive, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. PRO were assessed using the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30. PRO scores were converted into a symptom-free scale, 100 indicating a fully symptom-free score, 0 indicating total loss of freedom from symptom. Changes of PRO over time were analyzed using the linear mixed-effect model. Survival analysis computed time to > 10% PRO-deterioration. A post-hoc cardiorespiratory outcome was defined as deterioration in any of dyspnea, fatigue, physical functioning, or pain. Results At 10.4 years median follow-up, patients returned on average 9 questionnaires/patient, providing a total of 1139 PRO records. Item completeness was 96.6%. Missingness did not differ between the randomization arms. The PRO at baseline were below the nominal 100% symptom-free score, notably the mean fatigue-free score was 64.8% vs. 69.6%, pain-free was 75.4% vs. 75.3%, and dyspnea-free was 84.8% vs. 88.5%, in the TT vs. CR arm, respectively, although the differences were not significant. By mixed-effect modeling on early ≤2 years assessment, all three scores deteriorated, significantly for fatigue, P  ≤ 0.01, without effect of randomization arm. By modeling on late assessment beyond 2 years, TT versus CR was not significantly associated with changes of fatigue-free or pain-free scores but was associated with a significant 8.9% improvement of freedom from dyspnea, P  = 0.035. By survival analysis of the time to PRO deterioration, TT improved 10-year survival free of cardiorespiratory deterioration from 66.9% with CR to 84.5% with TT, P  = 0.029. Conclusion Modern radiation therapy can significantly improve long-term PRO. Trial registration Trial registration number ClinicalTrials.gov NCT00459628 , April 12, 2007 prospectively.

Background/Objectives: Paclitaxel is a type of small molecule chemotherapy widely used for breast cancer, but its clinical efficacy is often hindered by dose-limiting toxicities such as chemotherapy-induced peripheral neuropathy and neutropenia. Traditional dosing based on body surface area does not account for variations in body composition, which may influence paclitaxel metabolism, toxicity, and treatment outcomes. This review explores the interplay between body composition, physical activity, and paclitaxel pharmacokinetics, emphasizing the potential for personalized dosing strategies. Methods: A comprehensive narrative review was conducted by analyzing the literature on body composition, small molecule chemotherapy-related toxicities, pharmacokinetics, and exercise oncology. Studies examining the role of skeletal muscle mass, adipose tissue, and physical activity in modulating paclitaxel metabolism and side effects were included. Results: Evidence suggests that patients with low skeletal muscle mass are at a higher risk of paclitaxel-induced toxicities due to altered drug distribution and clearance. Sarcopenic obesity, characterized by low muscle and high-fat levels, further exacerbates these risks. Exercise, particularly resistance and aerobic training, has been shown to improve muscle mass, mitigate toxicities, and enhance chemotherapy tolerance. However, the precise mechanisms by which exercise influences paclitaxel pharmacokinetics remain underexplored. Conclusions: Personalized chemotherapy dosing, considering body composition and physical activity, may optimize paclitaxel treatment outcomes. Future research should focus on integrating exercise interventions into oncology care and refining dosing models that account for interindividual differences in drug metabolism. These advancements could improve treatment efficacy while minimizing toxicities in breast cancer patients.

Background Health-related quality of life (HRQOL) assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR) and hypofractionated tomotherapy (TT) have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy. Methods A total of 121 stage I–II breast cancer patients who had undergone breast conserving surgery (BCS) or mastectomy (MA) were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error) was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle. Results On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms), nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better long-term recovery from fatigue than CR patients. ANOVA with the Bonferroni correction did not show any significant differences between groups in HRQOL scores. Conclusions TT patients had a better improvement in global health status and role- and cognitive-functioning, and a faster recovery from fatigue, than CR patients. These results suggest that a shorter fractionation schedule may reduce the adverse effects of treatment.

Background TomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities. Methods The trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test. Results By May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05). Conclusions There were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need confirmation with longer follow-up of patients. Trail registration ClinicalTrials.gov NCT00459628

Background Although aromatase inhibitors have proven to be an effective treatment of hormone receptor-positive breast cancer in postmenopausal women, aromatase inhibitor-induced arthralgia (AIA) is an adverse event associated with low compliance with treatment. The aim of this literature study is to assess the prevalence of AIA and to provide an overview of significant predictors for the development of AIA. Methods A systematic review was conducted using PubMed, Cochrane Library and Web of Science. A meta-analysis was performed and heterogeneity has been investigated by moderator analyses. The meta-analysis was repeated with studies that were considered as best evidence , i.e. studies with an above-average score on the STROBE checklist. Results Twenty-one studies (13,177 participants) were included. Prevalence rates ranged from 0.200 to 0.737. Meta-analysis resulted in a pooled estimate of 0.459 (95% CI = [0.397–0.520) with a high heterogeneity ( I 2  = 98%). Moderator analysis showed no differences regarding heterogeneity. Predictors for the development of AIA included a body mass index of 25–30 kg/m 2 (OR = 0.33), taxane-based chemotherapy (OR = 4.08), stage III cancer (OR = 0.32) and a duration of menopause of 5–10 years (OR = 1.10) or >10 years (OR = 0.44–3.29) (An OR <1 indicates a predictor of lower risk of AIA). Discussion Despite the established benefits of AI, an important portion of the patients experiences AIA. More research is needed to investigate the efficacy of treatments such as exercise therapy for AIA.

Background. Lymphoedema of the operated and irradiated breast is a common complication following early breast cancer treatment. There is no consensus on objective diagnostic criteria and standard measurement tools. This study investigates the use of ultrasound elastography as an objective quantitative measurement tool for the diagnosis of parenchymal breast oedema. Patients and methods. The elasticity ratio of the subcutis, measured with ultrasound elastography, was compared with high-frequency ultrasound parameters and subjective symptoms in twenty patients, bilaterally, prior to and following breast conserving surgery and breast irradiation. Results. Elasticity ratio of the subcutis of the operated breast following radiation therapy increased in 88.9% of patients, was significantly higher than prior to surgery, unlike the non operated breast and significantly higher than the non operated breast, unlike preoperative results. These results were significantly correlated with visibility of the echogenic line, measured with high-frequency ultrasound. Big preoperative bra cup size was a significant risk factor for the development of breast oedema. Conclusions. Ultrasound elastography is an objective quantitative measurement tool for the diagnosis of parenchymal breast oedema, in combination with other objective diagnostic criteria. Further research with longer follow-up and more patients is necessary to confirm our findings.

BackgroundBreast cancer remains the most frequently diagnosed malignancy among women worldwide, with rising incidence numbers. In Belgium, one out of eight women will be diagnosed with breast cancer. Fortunately, 80% of those breast cancer patients will still be alive 10 years after diagnosis due to improvements in screening and treatment strategies. However, an important portion of the breast cancer survivors (BCS) will face side effects, such as sleep disturbances, long after treatment ends. It has been demonstrated that untreated insomnia in BCS negatively impacts mood, physical symptoms, pain sensitivity, fatigue, and quality of life. Furthermore, insomnia is increasingly considered an independent risk factor for future depression in BCS. The importance of understanding sleep disturbances in cancer populations has been highlighted and recognized as warranting further research. Therefore, the purpose of this systematic review was to determine the prevalence and the risk factors for the development of sleep disturbances in BCS.MethodsPubMed, Web of Science, and PEDro were systematically screened for studies encompassing data regarding the prevalence or risk factors of sleep disturbances in BCS. If possible, meta-analyses were performed. Subgroup analyses were undertaken based on the methodological quality, study design, type of sleep disturbance, and the use of a measurement tool with strong psychometric properties to investigate significant heterogeneity (I2 > 50%) across studies.ResultsA total of 27 studies were found eligible. The pooled estimate for sleep disturbances prevalence is 0.40 (95% confidence interval (CI) = [0.29–0.52], I2 = 100%, p < 0.00001) and ranged from 0.14 (95% CI = [0.04–0.24]) to 0.93 (95% CI = [0.91–0.95]). Subgroup analyses did not reduce the heterogeneity among studies. Meta-analyses were performed for seven risk factors. Significant differences for the odds of developing sleep disturbances were found for hot flashes (pooled OR (ORp) 2.25, 95% CI = [1.64–3.08], I2 = 0%, p = 0.90), race (ORp 2.31, 95% CI = [1.56–3.42], I2 = 0%, p = 0.47), and menopause (ORp 1.84, 95% CI = [1.11–3.06], I2 = 0%, p = 0.70). After withdrawing the studies that did not rely on the use of a measurement tool with strong psychometric properties, pain (ORp 2.31, 95% CI = [1.36–3.92], I2 = 27%, p = 0.25), depressive symptoms (ORp 3.20, 95% CI [2.32–4.42], I2 = 0%, p = 0.63), and fatigue (ORp 2.82, 95% CI = [1.98–4.02], I2 = 0%, p = 0.60) became significant as well, with a substantial decrease of heterogeneity.ConclusionPrevalence for sleep disturbances ranged from 0.14 to 0.93 with the vast majority of the studies investigating insomnia and sleep-wake disturbances. High heterogeneity makes it difficult to draw firm conclusions. Pain, depressive symptoms, hot flashes, fatigue, non-Caucasian race, and menopausal status were significantly associated with increased odds for developing sleep disturbances.

Background Scapula alata (SA) is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT). Methods The trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements. Results Of 119 evaluable patients, 13 (= 10.9%) had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 ( P = 0.009), 6.1 ( P = 0.016), and 6.1 ( P = 0.005), respectively. Randomization group was not significant. At one to three months’ post-RT, mean arm volume increased by 4.1% ( P = 0.036) and abduction decreased by 8.6% ( P = 0.046) among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient. Conclusion The relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature.