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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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Abstract
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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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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[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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Abstract
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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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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Carbohydrate antigen 125, carbohydrate antigen 15-3 and low-density lipoprotein as risk factors for intraocular metastases in postmenopausal breast cancer.
Tang, J, Yan, B, Li, GF, Li, QY, Liu, WF, Liang, RB, Ge, QM, Shao, Y
Medicine. 2021;(43):e27693
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Abstract
The prognosis of patients with postmenopausal breast cancer (PBC) could be improved by the early detection of intraocular metastases (IOMs). However, serum biomarkers for IOMs in PBC remain elusive. In the current study, we investigated patients with PBC, and compared serum parameters in an IOM and a non-IOM group, and then differentiated the risk factors related to IOMs. A comparison between an IOM and a non-IOM (NIOM) group was performed using Student t-test and a Chi-Squared test. After constructing a Poisson regression model to identify risk factors, we plotted receiver operating characteristic curves to evaluate the predictive value of significant risk factors in detecting IOMs. The incidence of IOMs in PBC was 1.16%. The histopathology results were not significantly different between the 2 groups. The levels of serum carbohydrate antigen 125 (CA-125), carbohydrate antigen 15-3 (CA15-3) and alkaline phosphatase were significantly elevated in IOMs compared with NIOMs (P = .082, P < .001, and P < .001, respectively). Compared with NIOMs, age, carbohydrate antigen 19 to 9, hemoglobin, calcium, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A1 were remarkably lower in IOMs (P = .038, P < .001, P < .001, P = .032, P = .041, P < .001, and P = .001, respectively). Poisson regression suggested that CA-125, CA15-3 and LDL were contributing to IOMs in PBC as risk factors (OR = 1.003, 95% CI: 1.001-1.005; OR = 1.025, 95% CI: 1.019-1.033; OR = 0.238, 95% CI: 0.112-0.505, respectively). A receiver operating characteristic curve revealed that the cut-off values for CA-125, CA15-3 and LDL were 16.78 0 U/mL, 63.175 U/mL, and 2.415 mmol/L, respectively. The combination of CA-125 and CA15-3 showed significant diagnostic value (area under the curve [AUC] = 0.982, P < .001). Our investigation suggests that CA-125, CA15-3 and LDL remarkably predict IOMs in PBC as risk factors, and the combination of CA-125 and CA15-3 shows considerable diagnostic value.
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Omega 6 polyunsaturated fatty acids in red blood cell membrane are associated with xerostomia and taste loss in patients with breast cancer.
Amézaga, J, Ugartemendia, G, Larraioz, A, Bretaña, N, Iruretagoyena, A, Camba, J, Urruticoechea, A, Ferreri, C, Tueros, I
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102336
Abstract
Chemosensory and physical complaints are common disorders in cancer patients under chemotherapy treatments that may affect the food intake, leading to a decreased quality of life. Lipid metabolism is a major pathway of cancer proliferation, where erythrocyte membrane phospholipids and their fatty acid composition are promising tools for monitoring metabolic pathways. Relationship between lipid profile in erythrocyte membrane phospholipids and chemosensory alterations in 44 newly diagnosed patients with breast cancer was here investigated. Smell changes and xerostomia were the most common complaints, with xerostomia as the main influencing factor on the development of other taste disorders. Lipid profiles revealed significant negative correlation between diminution of linoleic acid levels and xerostomia as well as positive correlation between increased arachidonic acid and salty taste. The involvement of these polyunsaturated lipids suggests the importance of oxidative and nutritional conditions of cancer patients, which can affect the molecular status for taste signals.
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Breast Cancer Risk From Modifiable and Non-Modifiable Risk Factors among Palestinian Women: A Systematic Review and Meta-Analysis.
Arafat, HM, Omar, J, Muhamad, R, Al-Astani, TAD, Shafii, N, Al Laham, NA, Naser, I, Shamallakh, OM, Shamallakh, KM, Jebril, MAAR
Asian Pacific journal of cancer prevention : APJCP. 2021;(7):1987-1995
Abstract
OBJECTIVE Breast cancer (BC) is known as one of the deadliest forms of cancer, and it is increasing globally. Identifying risk factors for BC is a key point in developing preventive strategies to reduce its occurrence. Herein, we aimed to conduct a systematic review and meta-analysis focus on the risk factors for BC in Palestine. MATERIAL AND METHODS We performed a systematic search via PubMed, MEDLINE, SCOPUS, Science Direct, Cochrane library, Emerald Insight, and Google scholar for identifying studies published on BC risk factors up to March 2021. Pooled odds ratios (OR) are calculated using fixed and random-effect models. Data were processed using Review Manager 5.4 (RevMan 5.4). RESULTS From a total of 73 articles, seven case-control studies met the criteria for systematic review. Meta-analysis results showed that of the known modifiable risk factors for BC, diabetes mellitus (DM) had the highest odds ratio (OR = 4.97, 95% CI 3.00- 8.25) followed by hypertension (OR = 3.21, 95% CI 1.96-5.23), obesity (BMI >30 Kg/m2) (OR = 2.90, 95% CI 2.00- 4.21), and passive smoking (OR = 1.50, 95% CI 1.12- 2.02). Controversially, breastfeeding (OR = 0.37, 95% CI 0.23- 0.61) was protective factor in BC. Of non-modifiable risk factors for BC has reached menopause had the highest odds ratio (OR = 3.74, 95% CI 2.64- 5.29), followed by family history of BC (OR = 2.63, 95% CI 1.07-6.44) and age (≥ 40 years) (OR = 2.49, 95% CI 1.43-4.34). CONCLUSIONS The most significant predictors of BC in Palestine were DM, hypertension, passive smokers, age (>40), reached menopause, and family history of BC. Almost all these risk factors are consistent with known risk factors for breast cancer in other parts of the world.
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Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer-associated fibroblasts.
Cirillo, F, Pellegrino, M, Talia, M, Perrotta, ID, Rigiracciolo, DC, Spinelli, A, Scordamaglia, D, Muglia, L, Guzzi, R, Miglietta, AM, et al
Clinical and translational medicine. 2021;(11):e516
Abstract
Among the prognostic and predictive biomarkers of breast cancer (BC), the role of estrogen receptor (ER)α wild-type has been acknowledged, although the action of certain ERα splice variants has not been elucidated. Insulin/insulin receptor (IR) axis has also been involved in the progression and metastasis of BC. For instance, hyperinsulinemia, which is often associated with obesity and type 2 diabetes, may be a risk factor for BC. Similarly, an aberrant expression of IR or its hyperactivation may correlate with aggressive BC phenotypes. In the present study, we have shown that a novel naturally immortalized BC cell line (named BCAHC-1) is characterized by a unique expression of 46 kDa ERα splice variant (ERα46) along with IR. Moreover, we have shown that a multifaceted crosstalk between ERα46 and IR occurs in BCAHC-1 cells upon estrogen and insulin exposure for growth and pulmonary metastasis. Through high-throughput RNA sequencing analysis, we have also found that the cytokine interleukin-11 (IL11) is the main factor linking BCAHC-1 cells to breast cancer-associated fibroblasts (CAFs). In particular, we have found that IL11 induced by estrogens and insulin in BCAHC-1 cells regulates pro-tumorigenic genes of the "extracellular matrix organization" signaling pathway, such as ICAM-1 and ITGA5, and promotes both migratory and invasive features in breast CAFs. Overall, our results may open a new scientific avenue to identify additional prognostic and therapeutic targets in BC.