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1.
[Barriers to breast cancer screening for people with disabilities].
Mazellier, S, Ramanah, R, Guldenfels, C, Mathelin, C
Bulletin du cancer. 2022;(2):185-196
Abstract
A significant increase in breast cancer is expected in the coming decades among people with disabilities. However, their participation rate in screening programs is significantly lower than women without disabilities. Our objective was therefore to analyse the barriers to breast cancer screening in people with disabilities based on a recent review of the international literature. The articles analysed were retrieved from the PUBMED database from 2014 to 2020 using the following keywords "breast cancer", "screening" and "disability". A total of 37 studies were included, including 30 original articles and 7 meta-analyses. The main barriers to performing breast cancer screening for women with disabilities were environmental factors such as lack of adapted transportation means or difficult access to medical facilities and mammography. To a lesser extent, the unsupportive views of family caregivers and health care staff about screening were also barriers to screening acceptance by people with disabilities. In general, breast cancer screening is a useful public health measure that reduces the burden of treatment and breast cancer-related mortality. Screening is useful for women over 50 years of age who have a sufficiently long-life expectancy, generally estimated at more than 10 years. Educational measures are needed to reduce the barriers to screening for PH who meet these criteria, their caregivers, and their providers so that they can actively participate in health care, rather than being marginalized because of their disability.
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Quality of life in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer.
Taira, N, Kashiwabara, K, Tsurutani, J, Kitada, M, Takahashi, M, Kato, H, Kikawa, Y, Sakata, E, Naito, Y, Hasegawa, Y, et al
Breast cancer (Tokyo, Japan). 2022;(1):131-143
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BACKGROUND To report our findings on quality of life (QoL) in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). METHODS Patients with HER2-negative MBC were randomly assigned to three different doses of q3w nab-PTX (SD 260 mg/m2 vs. MD: 220 mg/m2 vs. LD 180 mg/m2). QoL was assessed at baseline and during the second, fourth and sixth courses of treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Cancer Fatigue Scale (CFS) and EuroQol 5-Dimension (EQ-5D). Comparisons were performed with mixed-model repeated measures (MMRM). RESULTS A total of 141 patients were enrolled in the parent study, and 136 (96%) (44, 45 and 47 in the SD, MD, and LD groups) were included in the analysis. MMRM analysis showed that the difference from the baseline FACT-Taxane trial outcome index at MD and LD were significantly higher than that at SD (MD vs. SD P < 0.001, LD vs. SD P < 0.001). Differences from baseline for FACT-Taxane total, physical and emotional well-being, and taxane subscale scores at MD and LD were also higher than at SD. The difference from baseline for the CFS score at LD was lower than at SD (P = 0.013) and those for EQ-5D utility scores at MD and LD were higher than at SD (MD vs. SD P = 0.011, LD vs. SD P < 0.001). CONCLUSION QoL of patients treated with 220 or 180 mg/m2 of q3w nab-PTX was significantly better than that of patients treated with 260 mg/m2. TRIAL REGISTRATION The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID: UMIN000015516), on 01/11/2014. Details are available at the following address: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017916.
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Current Status of Contrast Enhanced Mammography: A Comprehensive Review.
Kornecki, A
Canadian Association of Radiologists journal = Journal l'Association canadienne des radiologistes. 2022;(1):141-156
Abstract
OBJECTIVES The purpose of this article is to provide a detailed and updated review of the physics, techniques, indications, limitations, reporting, implementation and management of contrast enhanced mammography. BACKGROUND Contrast enhanced mammography (CEM), is an emerging iodine-based modified dual energy mammography technique. In addition to having the same advantages as standard full-field digital mammography (FFDM), CEM provides information regarding tumor enhancement, relying on tumor angiogenesis, similar to dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). This article reviews current literature on CEM and highlights considerations that are critical to the successful use of this modality. CONCLUSION Multiple studies point to the advantage of using CEM in the diagnostic setting of breast imaging, which approaches that of DCE-MRI.
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Optimization of G-CSF dosing schedule in patients treated with eribulin: a modeling approach.
Reda, M, Macaire, P, Bellio, H, Uwer, L, Ilie, S, Lorgis, V, Hennequin, A, Ladoire, S, Rederstorff, E, Fumoleau, P, et al
Cancer chemotherapy and pharmacology. 2022;(2):197-208
Abstract
BACKGROUND Granulocyte colony-stimulating factors (G-CSF) are commonly given to limit chemotherapy-induced neutropenia, but, in case of weekly chemotherapy such as eribulin, their administration schedules remain empirical. OBJECTIVES This pharmacokinetic/pharmacodynamic (PK/PD) study was conducted to establish the effect of different G-CSF regimens on neutropenia's incidence for patients treated by eribulin, to propose an optimal G-CSF dosing schedule. METHODS A population PK/PD model was developed to describe absolute neutrophil counts' (ANC) time course in 87 cancer patients receiving eribulin. The structural model considered ANC dynamics, neutropenic effect of eribulin and stimulating effect of G-CSF. Final model estimates were used to calculate neutropenia's incidence following different G-CSF dosing schedules for 1000 virtual subjects. RESULTS The final model successfully described most of the ANC time course for all patients. Simulations showed that a single G-CSF administration 48 h after each eribulin injection reduced the risk of severe neutropenia from 29.7 to 5.2%. Five days of G-CSF only after the second eribulin injection or no G-CSF administration induces similar incidence of neutropenia. CONCLUSION Simulations showed a single G-CSF administration 48 h after the end of each eribulin injection seems to be the optimal schedule to reduce eribulin-induced neutropenia. However, the new administration scheme should be tested in real life to evaluate its pertinence. TRIAL REGISTRATION Eudract 2015-001753-32, 2015/01/26.
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Linking Physical Activity to Breast Cancer via Sex Hormones, Part 1: The Effect of Physical Activity on Sex Steroid Hormones.
Swain, CTV, Drummond, AE, Boing, L, Milne, RL, English, DR, Brown, KA, van Roekel, EH, Dixon-Suen, SC, Lynch, MJ, Moore, MM, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2022;(1):16-27
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The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorticoids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity-sex hormone-breast cancer pathway. The confirmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer.See related reviews by Lynch et al., p. 11 and Drummond et al., p. 28.
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Randomized Controlled Phase II Evaluation of Two Dose Levels of Bupropion Versus Placebo for Sexual Desire in Female Cancer Survivors: NRG-CC004.
Barton, DL, Pugh, SL, Ganz, PA, Plaxe, SC, Koontz, BF, Carter, J, Greyz-Yusupov, N, Page, SJ, Rowland, KM, Balcueva, EP, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022;(4):324-334
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PURPOSE Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities. METHODS Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t-tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t-test. RESULTS Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups. CONCLUSION Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.
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Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity-Breast Cancer Links.
Bustamante-Marin, XM, Merlino, JL, Devericks, E, Carson, MS, Hursting, SD, Stewart, DA
Frontiers in endocrinology. 2021;:632284
Abstract
The worldwide prevalence of overweight and obesity has tripled since 1975. In the United States, the percentage of adults who are obese exceeds 42.5%. Individuals with obesity often display multiple metabolic perturbations, such as insulin resistance and persistent inflammation, which can suppress the immune system. These alterations in homeostatic mechanisms underlie the clinical parameters of metabolic syndrome, an established risk factor for many cancers, including breast cancer. Within the growth-promoting, proinflammatory milieu of the obese state, crosstalk between adipocytes, immune cells and breast epithelial cells occurs via obesity-associated hormones, angiogenic factors, cytokines, and other mediators that can enhance breast cancer risk and/or progression. This review synthesizes evidence on the biological mechanisms underlying obesity-breast cancer links, with emphasis on emerging mechanism-based interventions in the context of nutrition, using modifiable elements of diet alone or paired with physical activity, to reduce the burden of obesity on breast cancer.
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Adherence to Dietary Recommendations after One Year of Intervention in Breast Cancer Women: The DIANA-5 Trial.
Bruno, E, Krogh, V, Gargano, G, Grioni, S, Bellegotti, M, Venturelli, E, Panico, S, Santucci de Magistris, M, Bonanni, B, Zagallo, E, et al
Nutrients. 2021;(9)
Abstract
The Diet and Androgen-5 (DIANA-5) trial aimed at testing whether a dietary change based on the Mediterranean diet and on macrobiotic principles can reduce the incidence of breast cancer (BC)-related events. We analyzed the adherence to the DIANA-5 dietary recommendations by randomization group after 1 year of intervention. We evaluated the association between dietary adherence and changes in body weight and metabolic syndrome (MS) parameters. BC women aged 35-70 years were eligible. After the baseline examinations, women were randomized into an intervention group (IG) or a control group (CG). A total of 1344 BC women (689 IG and 655 CG) concluded the first year of dietary intervention. IG showed greater anthropometric and metabolic improvements compared to CG. These changes were significantly associated with increased adherence to the dietary recommendations. Women who increased recommended foods consumption or reduced discouraged foods consumption showed an Odds Ratio (OR) of 1.37 (0.70-2.67) and 2.02 (1.03-3.98) to improve three or more MS parameters. Moreover, women in the higher category of dietary change showed a four times higher OR of reducing body weight compared to the lower category (p < 0.001). The DIANA-5 dietary intervention is effective in reducing body weight and MS parameters.
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Feasibility of pharmacometabolomics to identify potential predictors of paclitaxel pharmacokinetic variability.
Chen, L, Chen, CS, Sun, Y, Henry, NL, Stringer, KA, Hertz, DL
Cancer chemotherapy and pharmacology. 2021;(3):475-483
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PURPOSE Paclitaxel is a commonly used chemotherapy drug with substantial variability in pharmacokinetics (PK) that affects treatment efficacy and toxicity. Pharmacometabolomic signatures that explain PK variability could be used to individualize dosing to improve therapeutic outcomes. The objective of this study was to identify pretreatment metabolites or metabolomic signatures that explain variability in paclitaxel PK. METHODS This analysis was conducted using data previously collected on a prospective observational study of 48 patients with breast cancer receiving weekly 80 mg/m2 paclitaxel infusions. Paclitaxel plasma concentrations were measured during the first infusion to estimate paclitaxel time above threshold (Tc>0.05) and maximum concentration (Cmax). Metabolites measured in pretreatment whole blood by nuclear magnetic resonance spectrometry were analyzed for an association with Tc>0.05 and Cmax using Pearson correlation followed by stepwise linear regression. RESULTS Pretreatment creatinine, glucose, and lysine concentrations were positively correlated with Tc>0.05, while pretreatment betaine was negatively correlated and lactate was positively correlated with Cmax (all uncorrected p < 0.05). After stepwise elimination, creatinine was associated with Tc>0.05, while betaine and lactate were associated with Cmax (all p < 0.05). CONCLUSION This study identified pretreatment metabolites that may be associated with paclitaxel PK variability demonstrating feasibility of a pharmacometabolomics approach for understanding paclitaxel PK. However, identification of more robust pharmacometabolomic predictors will be required for broad and routine application for the clinical dosing of paclitaxel.
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DDR1 Affects Metabolic Reprogramming in Breast Cancer Cells by Cross-Talking to the Insulin/IGF System.
Vella, V, Giuliano, M, Nicolosi, ML, Majorana, MG, Marć, MA, Muoio, MG, Morrione, A, Maggiolini, M, Lappano, R, De Francesco, EM, et al
Biomolecules. 2021;(7)
Abstract
The insulin receptor isoform A (IR-A), a dual receptor for insulin and IGF2, plays a role in breast cancer (BC) progression and metabolic reprogramming. Notably, discoidin domain receptor 1 (DDR1), a collagen receptor often dysregulated in cancer, is involved in a functional crosstalk and feed forward loop with both the IR-A and the insulin like growth factor receptor 1 (IGF1R). Here, we aimed at investigating whether DDR1 might affect BC cell metabolism by modulating the IGF1R and/or the IR. To this aim, we generated MCF7 BC cells engineered to stably overexpress either IGF2 (MCF7/IGF2) or the IR-A (MCF7/IR-A). In both cell models, we observed that DDR1 silencing induced a significant decrease of total ATP production, particularly affecting the rate of mitochondrial ATP production. We also observed the downregulation of key molecules implicated in both glycolysis and oxidative phosphorylation. These metabolic changes were not modulated by DDR1 binding to collagen and occurred in part in the absence of IR/IGF1R phosphorylation. DDR1 silencing was ineffective in MCF7 knocked out for DDR1. Taken together, these results indicate that DDR1, acting in part independently of IR/IGF1R stimulation, might work as a novel regulator of BC metabolism and should be considered as putative target for therapy in BC.