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BACKGROUND: Lymphedema is a potential lifelong sequela of breast cancer treatment. We sought to: (1) evaluate the worry and knowledge of patients about lymphedema, (2) quantify patients reporting lymphedema education and screening, and (3) determine willingness to participate in lymphedema screening and prevention programs. PATIENTS AND METHODS: A survey evaluating lymphedema-related knowledge and worry was sent to patients treated for stage 0-III breast cancer. Exclusion criteria included > 10 years since diagnosis, missing clinical staging, and those without axillary surgery. Responses were linked with clinicopathologic information. RESULTS: Of 141 patients meeting inclusion criteria, 89% of those without lymphedema were not at all or slightly worried about lymphedema. Higher levels of worry were associated with clinical stage II-III disease [odds ratio (OR) 2.63, p = 0.03], a history of axillary lymph node dissection (ALND) (OR 4.58, p < 0.01), and employment (OR 2.21, p = 0.05). A total of 102 (72%) patients recalled receiving lymphedema education. Lymphedema knowledge was limited, with < 25% of respondents answering > 50% of the risk factor questions correctly. Worry and knowledge were not significantly associated. Of patients without lymphedema, 36% were interested in learning more about lymphedema and 64% were willing to participate in or learn more about a screening program. Most (66%) felt that lymphedema information should be provided before and after cancer treatment. DISCUSSION: A majority of our breast cancer survivors had limited knowledge about lymphedema risk factors. While most patients were not worried about developing lymphedema, higher worry was seen in patients with a higher clinical stage at diagnosis, ALND, and employment. Our findings suggest potential targets and timing for patient-centered educational interventions.
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Neoplasias da Mama , Linfedema , Axila/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Linfedema/cirurgia , Biópsia de Linfonodo Sentinela/efeitos adversosRESUMO
A high density of tumor-associated macrophages (TAMs) is associated with poorer prognosis and survival in breast cancer patients. Recent studies have shown that lipid accumulation in TAMs can promote tumor growth and metastasis in various models. However, the specific molecular mechanisms that drive lipid accumulation and tumor progression in TAMs remain largely unknown. Herein, we demonstrated that unsaturated fatty acids (FAs), unlike saturated ones, are more likely to form lipid droplets in macrophages. Specifically, unsaturated FAs, including linoleic acids (LA), activate the FABP4/CEBPα pathway, leading to triglyceride synthesis and lipid droplet formation. Furthermore, FABP4 enhances lipolysis and FA utilization by breast cancer cells, which promotes cancer cell migration in vitro and metastasis in vivo . Notably, a deficiency of FABP4 in macrophages significantly reduces LA-induced lipid metabolism. Therefore, our findings suggest FABP4 as a crucial lipid messenger that facilitates unsaturated FA-mediated lipid accumulation and lipolysis in TAMs, thus contributing to the metastasis of breast cancer. Highlights: Unlike saturated fatty acids, unsaturated fatty acids preferentially promote lipid droplet formation in macrophages.Unsaturated fatty acids activate the FABP4/CEBPα axis for neutral lipid biosynthesis in macrophagesDeficiency of FABP4 compromised unsaturated fatty acid-mediated lipid accumulation and utilization in macrophagesFABP4-mediated lipid metabolism in macrophages contributes to breast cancer metastasis.
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As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.
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Neoplasias da Mama , Microbioma Gastrointestinal , Humanos , Estados Unidos/epidemiologia , Feminino , Disbiose/microbiologia , Bactérias/genética , Ácidos Graxos Voláteis , Microbioma Gastrointestinal/genética , Fezes/microbiologia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análiseRESUMO
Background: Sarcomas are a diverse group of neoplasms that vary greatly in clinical presentation and responsiveness to treatment. Given the differences in the sites of involvement, rarity, and treatment modality, a multidisciplinary approach is required. Previous literature suggests patients with sarcoma suffer from poorer quality of life (QoL) especially physical and functional wellbeing. Adolescent and young adult (AYA) patients are an underrepresented population in cancer research and have differing factors influencing QoL. Methods: Retrospective analysis of Young Adult patients (age 18-39) enrolled in the Sarcoma Tissue Repository at University of Iowa. QoL was assessed using the self-report FACT-G questionnaire at enrollment and 12 months post-diagnosis; overall scores and the 4 wellbeing subscales (Physical, Emotional, Social, Functional) were calculated. Linear mixed effects models were used to measure the association between the rate of change in FACT-G subscale scores and baseline clinical, comorbidity, and treatment characteristics. Results: 49 patients were identified. 57.1% of patients had a malignancy involving an extremity. Mean FACT-G scores of overall wellbeing improved from baseline to 12 months (76.4 vs. 85.4, p < 0.01). Social and emotional wellbeing did not differ significantly between baseline and 12 months. Physical wellbeing (18.8 vs. 23.9, p < 0.01) and functional wellbeing (16.8 vs. 20.0, p< 0.01) scores improved from baseline to 12 months. No difference was seen for FACT-G overall scores for age, sex, laterality, marital status, performance status, having children, clinical stage, limb surgery, chemotherapy, or tumor size. A difference was demonstrated in physical wellbeing scores for patients with baseline limitation (ECOG 1-3) compared to those with no baseline limitation (ECOG 0) (p = 0.03). A difference was demonstrated in social wellbeing based on anatomical site (p = 0.02). Conclusion: Young adults with sarcoma treated at a tertiary center had improvements in overall reported QoL at 12 months from diagnosis. Overall baseline QoL scores on FACT-G were lower than the general adult population for YA patients with sarcoma but at 12 months became in line with general population norms. The improvements seen merit further investigation to evaluate how these change over the continuum of care. Quality of life changes may be useful outcomes of interest in sarcoma trials.
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Introduction: Younger age at diagnosis is a risk factor for poor health-related quality of life (HRQOL) in long-term breast cancer survivors. However, few studies have specifically addressed HRQOL in young adults with breast cancer (i.e., diagnosed prior to age 40), nor have early changes in HRQOL been fully characterized. Methods: Eligible female patients with breast cancer were identified through our local cancer center. To establish HRQOL, patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) around diagnosis and 12 months later. Sociodemographic factors, genetic susceptibility to cancer, tumor- and treatment-related factors, and comorbidities (e.g., depression/anxiety) were abstracted from medical records and the local oncology registry. Mixed-effects models were used to identify changes in FACT-B scores during the first year of treatment and to determine whether any demographic/treatment-related factors modulated changes in scores. Results: Health-related quality of life in young patients with breast cancer was within normal limits at baseline, with a FACT-B overall well-being score of 108.5 (95% confidence limits [CI] = 103.7, 113.3). Participants reported slight improvements over a 12-month period: FACT-B overall well-being scores increased 6.6 points (95% CI = 2.1, 11.1, p < 0.01), functional well-being improved 3.0 points (95% CI = 2.0, 4.1, p < 0.01), emotional well-being improved 1.9 points (95% CI = 0.9, 2.8, p < 0.01), and physical well-being improved 1.5 points (95% CI = 0.2, 2.8, p = 0.03), on average. Participants with anxiety/depression at baseline reported greater improvements in FACT-B overall well-being (change: 12.9, 95% CI = 6.4, 9.5) and functional well-being (change: 5.2, 95% CI = 3.5, 6.9) than participants who did not have anxiety/depression at baseline (change in FACT-B overall well-being: 4.9, 95% CI = 0.2, 9.7; change in functional well-being: 2.3, 95% CI = 1.1, 3.4). Marital status, reconstructive surgery, and baseline clinical staging were also significantly associated with changes in aspects of HRQOL, although their impact on change was relatively minimal. Conclusion: Young women with breast cancer do not report HRQOL concerns during the first year of treatment. Improvements in HRQOL during the first year of treatment may be attributable to a sense of relief that the cancer is being treated, which, in the short run, may outweigh the negative late effects of treatment.