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Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal-Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer toward practice changes. This review summarizes key topics discussed to advance research on the role of energy balance, including physical activity, body composition, and dietary intake, on cancer development, cancer outcomes, and healthy survivorship.
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Neoplasias , Animais , Humanos , Exercício FísicoRESUMO
BACKGROUND: Our randomized controlled clinical trial will explore the potential of bazedoxifene plus conjugated estrogen to modulate breast tissue-based risk biomarkers as a surrogate for breast cancer risk reduction. This paper investigates the statistical design features of the trial and the rationale for the final choice of its design. Group sequential designs are a popular design approach to allow a trial to stop early for success or futility, potentially saving time and money over a fixed trial design. While Bayesian adaptive designs enjoy the same properties as group sequential designs, they have the added benefit of using prior information as well as inferential interpretation conditional on the data. Whether a frequentist or Bayesian trial, most adaptive designs have interim analyses that allow for early stopping, typically utilizing only the primary endpoint. A drawback to this approach is that the study may not have enough data for adequate comparisons of a single, key secondary endpoint. This can happen, for example, if the secondary endpoint has a smaller effect than the primary endpoint. METHODS: In this paper, we investigate a trial design called two-endpoint adaptive, which stops early only if a criterion is met for primary and secondary endpoints. The approach focuses the final analysis on the primary endpoint but ensures adequate data for the secondary analysis. Our study has two arms with a primary (change in mammographic fibroglandular volume) and secondary endpoint (change in mammary tissue Ki-67). RESULTS: We present operating characteristics including power, trial duration, and type I error rate and discuss the value and risks of modeling Bayesian group sequential designs with primary and secondary endpoints, comparing against alternative designs. The results indicate that the two-endpoint adaptive design has better operating characteristics than competing designs if one is concerned about having adequate information for a key secondary endpoint. DISCUSSION: Our approach balances trial speed and the need for information on the single, key secondary endpoint.
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Neoplasias da Mama , Humanos , Feminino , Teorema de Bayes , Neoplasias da Mama/prevenção & controle , Projetos de Pesquisa , Futilidade Médica , QuimioprevençãoRESUMO
Aerobic exercise reduces risk for breast cancer and recurrence and promotes visceral adipose tissue (VAT) loss in obesity. However, few breast cancer survivors achieve recommended levels of moderate to vigorous physical activity (MVPA) without supervision. In a two-cohort study, feasibility of 12 weeks of partially supervised exercise was started concomitantly with caloric restriction and effects on body composition and systemic risk biomarkers were explored. In total, 22 obese postmenopausal sedentary women (including 18 breast cancer survivors) with median age of 60 and BMI of 37 kg/m2 were enrolled. Using personal trainers twice weekly at area YMCAs, MVPA was escalated to ≥200 min/week over 9 weeks. For cohort 2, maintenance of effect was assessed when study provided trainer services were stopped but monitoring, group counseling sessions, and access to the exercise facility were continued. Median post-escalation MVPA was 219 min/week with median 12-week mass and VAT loss of 8 and 19%. MVPA was associated with VAT loss which was associated with improved adiponectin:leptin ratio. In total, 9/11 of cohort-2 women continued the behavioral intervention for another 12 weeks without trainers. High MVPA continued with median 24-week mass and VAT loss of 12 and 29%. This intervention should be further studied in obese sedentary women.
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The inflammation-resolving and insulin-sensitizing properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have potential to augment effects of weight loss on breast cancer risk. In a feasibility study, 46 peri/postmenopausal women at increased risk for breast cancer with a body mass index (BMI) of 28 kg/m2 or greater were randomized to 3.25 g/day combined EPA and DHA (ω-3-FA) or placebo concomitantly with initiation of a weight-loss intervention. Forty-five women started the intervention. Study discontinuation for women randomized to ω-3-FA and initiating the weight-loss intervention was 9% at 6 months and thus satisfied our main endpoint, which was feasibility. Between baseline and 6 months significant change (P < 0.05) was observed in 12 of 25 serum metabolic markers associated with breast cancer risk for women randomized to ω-3-FA, but only four for those randomized to placebo. Weight loss (median of 10% for trial initiators and 12% for the 42 completing 6 months) had a significant impact on biomarker modulation. Median loss was similar for placebo (-11%) and ω-3-FA (-13%). No significant change between ω-3-FA and placebo was observed for individual biomarkers, likely due to sample size and effect of weight loss. Women randomized to ω-3-FA exhibiting more than 10% weight loss at 6 months showed greatest biomarker improvement including 6- and 12-month serum adiponectin, insulin, omentin, and C-reactive protein (CRP), and 12-month tissue adiponectin. Given the importance of a favorable adipokine profile in countering the prooncogenic effects of obesity, further evaluation of high-dose ω-3-FA during a weight-loss intervention in obese high-risk women should be considered. PREVENTION RELEVANCE: This study examines biomarkers of response that may be modulated by omega-3 fatty acids when combined with a weight-loss intervention. While focused on obese, postmenopausal women at high risk for development of breast cancer, the findings are applicable to other cancers studied in clinical prevention trials.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/prevenção & controle , Ácidos Graxos Ômega-3/administração & dosagem , Redução de Peso/fisiologia , Programas de Redução de Peso , Adulto , Idoso , Terapia Comportamental , Biomarcadores Tumorais/sangue , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Restrição Calórica , Citodiagnóstico , Suplementos Nutricionais , Exercício Físico/fisiologia , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Obesidade/dietoterapia , Obesidade/metabolismo , Obesidade/terapia , Placebos , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Programas de Redução de Peso/métodosRESUMO
Similar risk reduction but fewer side effects would predict more uptake and compliance with low (5 mg) versus full (20 mg) dose tamoxifen. Benefit with low dose is demonstrated for perimenopausal/postmenopausal women with intraepithelial neoplasia and high lesion Ki-67. Longer follow-up needed to determine benefit with low lesion Ki-67.See related article by DeCensi et al., p. 3576.
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Doenças Mamárias , Carcinoma in Situ , Lesões Pré-Cancerosas , Mama , Feminino , Humanos , Lesões Pré-Cancerosas/tratamento farmacológico , Tamoxifeno/uso terapêuticoRESUMO
We conducted a multiinstitutional, placebo-controlled phase IIB trial of the lignan secoisolariciresinol diglucoside (SDG) found in flaxseed. Benign breast tissue was acquired by random periareolar fine needle aspiration (RPFNA) from premenopausal women at increased risk for breast cancer. Those with hyperplasia and ≥2% Ki-67 positive cells were eligible for randomization 2:1 to 50 mg SDG/day (Brevail) versus placebo for 12 months with repeat bio-specimen acquisition. The primary endpoint was difference in change in Ki-67 between randomization groups. A total of 180 women were randomized, with 152 ultimately evaluable for the primary endpoint. Median baseline Ki-67 was 4.1% with no difference between arms. Median Ki-67 change was -1.8% in the SDG arm (P = 0.001) and -1.2% for placebo (P = 0.034); with no significant difference between arms. As menstrual cycle phase affects proliferation, secondary analysis was performed for 117 women who by progesterone levels were in the same phase of the menstrual cycle at baseline and off-study tissue sampling. The significant Ki-67 decrease persisted for SDG (median = -2.2%; P = 0.002) but not placebo (median = -1.0%). qRT-PCR was performed on 77 pairs of tissue specimens. Twenty-two had significant ERα gene expression changes (<0.5 or >2.0) with 7 of 10 increases in placebo and 10 of 12 decreases for SDG (P = 0.028), and a difference between arms (P = 0.017). Adverse event incidence was similar in both groups, with no evidence that 50 mg/day SDG is harmful. Although the proliferation biomarker analysis showed no difference between the treatment group and the placebo, the trial demonstrated use of SDG is tolerable and safe.
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Neoplasias da Mama/tratamento farmacológico , Butileno Glicóis/uso terapêutico , Glucosídeos/uso terapêutico , Hiperplasia/tratamento farmacológico , Lignanas/uso terapêutico , Pré-Menopausa , Adulto , Neoplasias da Mama/patologia , Feminino , Linho/química , Seguimentos , Humanos , Hiperplasia/patologia , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Obesity is associated with worse breast cancer prognosis, however little is known about the level of weight loss required to improve pathway biomarkers. The effects of weight regain on biomarkers are also largely unknown. METHODS: Overweight/obese breast cancer survivors enrolled in an 18-month behavioral weight loss trial provided weight and serum biomarkers [leptin, adiponectin, insulin, plasminogen activator inhibitor-1 (PAI-1), IL-6, TNFα, and hepatocyte growth factor HGF] at baseline, 6, and 18 months (n = 138). Change in biomarkers over time and by weight loss thresholds were examined. RESULTS: Mean weight loss at 6 months was 13.3 ± 5.0 kg; from 6 to 18 months, mean regain was 4.0 ± 5.2 kg. Favorable biomarker modulations were observed at 6 months for leptin, adiponectin, insulin, PAI-1, IL-6, and HGF (P < 0.006 to P < 0.0001). These changes remained significant overall at 18 months despite attenuation in some. Women who lost <10% of baseline weight showed significantly smaller modulation effects for leptin (P < 0.0001), adiponectin:leptin (A/L) ratio (P < 0.0001), PAI-1 (P < 0.001), and insulin (P = 0.003) compared with women who lost >10%. Women who lost >10% observed a significant increase in adiponectin (P < 0.0001), and these women continued to show improved adiponectin from 6 to 18 months despite weight regain. Physical activity contributed additional effects on biomarker change for leptin, A/L ratio, and PAI-1. CONCLUSIONS: These findings are consistent with a clinical target of 10% weight. IMPACT: Sustained increases in adiponectin likely confer benefits for breast cancer prognosis even with weight regain.
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Biomarcadores/metabolismo , Neoplasias da Mama/complicações , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Aumento de Peso/fisiologia , Redução de Peso/fisiologia , Idoso , Neoplasias da Mama/mortalidade , Sobreviventes de Câncer , Feminino , Humanos , População Rural , Análise de SobrevidaRESUMO
PURPOSE: To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction. METHODS: An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS: A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor-positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update. UPDATED RECOMMENDATIONS: In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines.
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Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Interventions that relieve vasomotor symptoms while reducing risk for breast cancer would likely improve uptake of chemoprevention for perimenopausal and postmenopausal women. We conducted a pilot study with 6 months of the tissue selective estrogen complex bazedoxifene (20 mg) and conjugated estrogen (0.45 mg; Duavee) to assess feasibility and effects on risk biomarkers for postmenopausal breast cancer. Risk biomarkers included fully automated mammographic volumetric density (Volpara), benign breast tissue Ki-67 (MIB-1 immunochemistry), and serum levels of progesterone, IGF-1, and IGFBP3, bioavailable estradiol and testosterone. Twenty-eight perimenopausal and postmenopausal women at increased risk for breast cancer were enrolled: 13 in cohort A with baseline Ki-67 < 1% and 15 in cohort B with baseline Ki-67 of 1% to 4%. All completed the study with > 85% drug adherence. Significant changes in biomarkers, uncorrected for multiple comparisons, were a decrease in mammographic fibroglandular volume (P = 0.043); decreases in serum progesterone, bioavailable testosterone, and IGF-1 (P < 0.01), an increase in serum bioavailable estradiol (P < 0.001), and for women from cohort B a reduction in Ki-67 (P = 0.017). An improvement in median hot flash score from 15 at baseline to 0 at 6 months, and menopause-specific quality-of-life total, vasomotor, and sexual domain scores were also observed (P < 0.001). Given the favorable effects on risk biomarkers and patient reported outcomes, a placebo-controlled phase IIB trial is warranted.
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Biomarcadores Tumorais , Densidade da Mama/efeitos dos fármacos , Neoplasias da Mama/etiologia , Estrogênios Conjugados (USP)/farmacologia , Indóis/farmacologia , Sistema Vasomotor/efeitos dos fármacos , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Estradiol/sangue , Terapia de Reposição de Estrogênios/métodos , Estrogênios Conjugados (USP)/uso terapêutico , Estudos de Viabilidade , Feminino , Humanos , Indóis/uso terapêutico , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Antígeno Ki-67/análise , Antígeno Ki-67/sangue , Mamografia , Menopausa/sangue , Menopausa/efeitos dos fármacos , Menopausa/fisiologia , Pessoa de Meia-Idade , Projetos Piloto , Pós-Menopausa , Progesterona/sangue , Qualidade de Vida , Fatores de Risco , Testosterona/sangueRESUMO
PURPOSE: Circulating adipose stromal cells (CASC) are thought to be increased in obesity and facilitate angiogenesis, and tumor metastases. METHODS: CASC were identified from buffy coat peripheral blood mononuclear cells (PBMCs) by flow cytometry as CD34brightCD31- CD45- and CASC frequency was compared to adiposity measures in 33 women at increased risk for breast cancer. Feasibility of CASC as a response biomarker for a diet and exercise intervention in ten breast cancer survivors was then explored. RESULTS: For 33 high-risk women, median CASC frequency was 9.7 per million PBMCs and trended positively with body mass index, fat mass index (FMI), and percent android fat. Correlation was significant when BMI was dichotomized at > versus < 35 kg/m2 (p = 0.02). For ten breast cancer survivors with a median BMI of 37 kg/m2, median CASC frequency was 16.4 per million PBMCs. In univariate analyses, change in BMI, total fat and visceral fat were significantly correlated with change in CASC frequency. On multivariate analysis, change in visceral adipose had the strongest association with change in CASC frequency (p < 0.00078). CONCLUSIONS: The association between the reduction in visceral adipose tissue and the decrease in frequency of circulating adipose stromal cells suggests that the latter might be a useful biomarker in clinical trials of obese breast cancer survivors undergoing a weight loss intervention.
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Tecido Adiposo/imunologia , Biomarcadores/sangue , Neoplasias da Mama/sangue , Obesidade/terapia , Tecido Adiposo/citologia , Idoso , Antígenos CD34/metabolismo , Neoplasias da Mama/imunologia , Sobreviventes de Câncer , Estudos Transversais , Dietoterapia , Terapia por Exercício , Feminino , Humanos , Antígenos Comuns de Leucócito/metabolismo , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/imunologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pós-Menopausa , Pré-Menopausa , Células Estromais/citologia , Células Estromais/imunologiaRESUMO
Cardiovascular (CV) toxicity from cancer therapy is a significant and growing concern. Conventional oncology clinical trial designs focused singularly on cancer treatment efficacy have not provided sufficient information on both CV risk factors and outcomes. Similarly, traditional CV trials evaluating standard interventions typically exclude cancer patients, particularly those actively receiving cancer therapy. Neither trial type simultaneously evaluates the balance between CV toxicity and cancer outcomes. However, there is increasing collaboration among oncologists and cardiologists to design new cardio-oncology trials that address this important need. In this review, we detail five ongoing, oncology-based trials with integrated CV endpoints. Key design features include: 1) a careful assessment of baseline risk factors for CV disease; 2) an introduction of cardioprotective interventions at various timepoints in cancer therapy; 3) a balance of the risk of subclinical CV injury with the need for ongoing cancer treatment; and 4) an understanding of the time profile for development of clinically apparent CV toxicity. Additional critical priorities in cardio-oncology clinical research include harmonization of data collection and definitions for all physician- and patient-reported exposures and outcomes.
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PURPOSE: Exposure to the polyphenolic plant lignan secoisolariciresinol diglucoside (SDG) and its metabolite enterolactone (ENL) has been associated with reduced breast cancer progression, particularly for estrogen receptor alpha (ERα)-negative disease, and decreased preclinical mammary tumor growth. However, while preclinical studies have established that SDG and ENL affect measures of progression in models of triple-negative breast cancer (TNBC, a subset of ERα-negative disease), the molecular mechanisms underlying these effects remain unclear. METHODS: C57BL/6 mice were fed a control diet (control, 10% kcal from fat) or control diet + SDG (SDG, 100 mg/kg diet) for 8 weeks, then orthotopically injected with syngeneic E0771 mammary tumor cells (a model of TNBC); tumor growth was monitored for 3 weeks. The role of reduced NF-κB signaling in SDG's anti-tumor effects was explored in vitro via treatment with the bioactive SDG metabolite ENL. In addition to the murine E0771 cells, the in vitro studies utilized MDA-MB-231 and MCF-7 cells, two human cell lines which model the triple-negative and luminal A breast cancer subtypes, respectively. RESULTS: SDG supplementation in the mice significantly reduced tumor volume and expression of phospho-p65 and NF-κB target genes (P < 0.05). Markers of macrophage infiltration were decreased in the distal-to-tumor mammary fat pad of mice supplemented with SDG relative to control mice (P < 0.05). In vitro, ENL treatment inhibited viability, survival, and NF-κB activity and target gene expression in E0771, MDA-MB-231, and MCF-7 cells (P < 0.05). Overexpression of Rela attenuated ENL's inhibition of E0771 cell viability and survival. CONCLUSIONS: SDG reduces tumor growth in the E0771 model of TNBC, likely via a mechanism involving inhibition of NF-κB activity. SDG could serve as a practical and effective adjuvant treatment to reduce recurrence, but greater understanding of its effects is needed to inform the development of more targeted recommendations for its use.
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Anti-Inflamatórios/farmacologia , Butileno Glicóis/farmacologia , Linho/química , Glucosídeos/farmacologia , Neoplasias Mamárias Animais/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , 4-Butirolactona/análogos & derivados , 4-Butirolactona/sangue , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Biomarcadores , Butileno Glicóis/administração & dosagem , Butileno Glicóis/química , Linhagem Celular Tumoral , Sobrevivência Celular , Citocinas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica , Glucosídeos/administração & dosagem , Glucosídeos/química , Imuno-Histoquímica , Lignanas/sangue , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/patologia , CamundongosRESUMO
Premature menopause is a serious long-term side effect of chemotherapy. We evaluated long-term pregnancy and disease-related outcomes for patients in S0230/POEMS, a study in premenopausal women with stage I-IIIA estrogen receptor-negative, progesterone receptor-negative breast cancer to be treated with cyclophosphamide-containing chemotherapy. Women were randomly assigned to standard chemotherapy with or without goserelin, a gonadotropin-releasing hormone agonist, and were stratified by age and chemotherapy regimen. All statistical tests were two-sided. Of 257 patients, 218 were eligible and evaluable (105 in the chemotherapy + goserelin arm and 113 in the chemotherapy arm). More patients in the chemotherapy + goserelin arm reported at least one pregnancy vs the chemotherapy arm (5-year cumulative incidence = 23.1%, 95% confidence interval [CI] = 15.3% to 31.9%; and 12.2%, 95% CI = 6.8% to 19.2%, respectively; odds ratio = 2.34; 95% CI = 1.07 to 5.11; P = .03). Randomization to goserelin + chemotherapy was associated with a nonstatistically significant improvement in disease-free survival (hazard ratio [HR] = 0.55; 95% CI = 0.27 to 1.10; P = .09) and overall survival (HR = 0.45; 95% CI = 0.19 to 1.04; P = .06). In this long-term analysis of POEMS/S0230, we found continued evidence that patients randomly assigned to receive goserelin + chemotherapy were not only more likely to avoid premature menopause, but were also more likely to become pregnant without adverse effect on disease-related outcomes.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Menopausa Precoce/efeitos dos fármacos , Insuficiência Ovariana Primária/prevenção & controle , Adulto , Antraciclinas/administração & dosagem , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Feminino , Seguimentos , Gosserrelina/administração & dosagem , Humanos , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Receptores de Estrogênio/metabolismo , Taxa de SobrevidaRESUMO
OBJECTIVE: This study aimed to test the feasibility of a 12-month weight loss intervention using telephone-based counseling plus community-situated physical activity (PA) in female breast cancer (BC) and colorectal cancer (CRC) survivors. METHODS: This multisite cooperative group study enrolled sedentary, female, postmenopausal BC and CRC survivors with BMI ≥ 25 kg/m2 to receive 12-month fitness center memberships and telephone counseling encouraging 150 min/wk of PA and a 500-kcal/ddecrease in energy intake. Feasibility criteria included accrual, adherence, and retention. Target weight loss was ≥ 5%. RESULTS: Among 25 BC survivors, median baseline BMI was 37.2 (range: 27.7-54.6), accrual occurred in 10 months, 60% and 28% met diet and exercise goals, 80% provided 12-month measures, and average weight loss was 7.6% (95% CI: -3.9%, 19.2%). Among 23 CRC survivors, median BMI was 31.8 (range: 26.4-48.7), accrual occurred in 24 months, 61% and 17% met diet and exercise goals, 87% provided measures, and average weight loss was 2.5% (95% CI: -8.2%, 13.3%). CONCLUSIONS: It is feasible to recruit and retain BC survivors in a cooperative group diet and PA weight loss trial. BC survivors achieved clinically meaningful weight loss but did not meet a priori adherence goals. In CRC survivors, recruitment was more difficult, and the intervention was less effective.
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Neoplasias da Mama/terapia , Sobreviventes de Câncer/psicologia , Neoplasias Colorretais/terapia , Dieta/métodos , Obesidade/terapia , Redução de Peso/fisiologia , Neoplasias Colorretais/psicologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/psicologiaRESUMO
Marine omega-3 fatty acids promote resolution of inflammation and have potential to reduce risk of obesity-related breast cancer. For prevention trials in obese women, inflammatory cytokines, aromatase, and measures of breast immune cell infiltration are logical, as are biomarkers of growth factor, adipokine, and estrogen signaling. Where best to look for marker change: in the circulation (easiest), in benign breast tissue (most relevant), or in visceral adipose (inflammation often most marked)? A null biomarker modulation trial may reflect limitations in design, source and dose of fatty acids, or biomarkers and should not lead to premature abandonment of marine omega-3 fatty acids for cancer prevention. Cancer Prev Res; 11(4); 187-90. ©2018 AACRSee related article by Gucalp et al., p. 203.
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Neoplasias da Mama , Doença da Mama Fibrocística , Biomarcadores , Ácidos Docosa-Hexaenoicos , Ácidos Graxos Ômega-3 , Feminino , HumanosRESUMO
PURPOSE: The purpose of the study was to prospectively examine changes in subjective and objective cognitive functions and quality of life (QOL) for pre- and peri-menopausal women receiving chemotherapy for breast cancer and to explore potential predictors of cognitive changes. METHODS: Participants were assessed as follows: prior to chemotherapy (T1), after cycle 3 (T2), within 2-3 weeks of completing adjuvant chemotherapy (T3) (N = 20), and 8+ years later (T4; n = 18). Objective cognitive function was measured with the High Sensitivity Cognitive Screen (T1, T3, T4). Subjective measures for cognitive function, depressive symptoms, fatigue, and mental and physical QOL were assessed at all time points. Estradiol levels were measured at T1, T2, and T3. The Functional Assessment of Cancer Therapy-Cognition and the MD Anderson Cancer Symptom Inventory item for neuropathy were administered at T4. RESULTS: No significant changes in objective cognitive function were found. However, participants reported decreased cognitive function over the course of treatment accompanied by depressive symptoms and fatigue. Depression and fatigue returned to near-baseline levels at T4, but over half of the participants continued to report mild to moderate depression. Estradiol levels were not associated with cognitive function. Neuropathy and higher body mass index (BMI) were associated with persistent cognitive complaints at T4 (adjusted R 2 = 0.712, p = 0.001). Higher QOL was correlated with better subjective cognitive function (r = 0.705, p = 0.002) and lower body mass index (r = - 0.502, p = 0.017) at T4. CONCLUSIONS: Further investigation of BMI, neuropathy, and depressive symptoms as predictors of persistent cognitive dysfunction following chemotherapy for breast cancer is warranted.
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Neoplasias da Mama/psicologia , Quimioterapia Adjuvante/psicologia , Transtornos Cognitivos/psicologia , Qualidade de Vida/psicologia , Adulto , Neoplasias da Mama/patologia , Estudos Transversais , Feminino , Humanos , Estudos LongitudinaisRESUMO
OBJECTIVE: This study examined the effects of a group phone-based weight management intervention on change in physical activity as measured via accelerometer and self-report in rural breast cancer survivors. The study also evaluated the role of physical activity on clinically meaningful cut points for weight loss (baseline to 6 months) and weight loss maintenance (6 to 18 months). METHODS: Participants were breast cancer survivors in a weight management intervention who provided valid weight and accelerometer data (N = 142). Participants were categorized into four groups based on weight loss ≥10% and weight regain ≥5% at 18 months. RESULTS: Accelerometer-measured moderate-to-vigorous physical activity (MVPA) significantly increased from baseline to 6 months (+46.9 minutes). MVPA declined during maintenance but remained significantly greater than baseline. Self-reported MVPA followed a similar pattern as accelerometer MVPA, but estimates were significantly higher. Participants in the high loss, low regain group had significantly higher MVPA at all points. CONCLUSIONS: A distance-based weight management intervention for survivors improved physical activity outcomes over 18 months. Self-reported physical activity was substantially higher than accelerometer measured. Findings highlight the importance of device-based measurement for characterizing the magnitude of physical activity change as well as the role of physical activity in weight management outcomes.
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Neoplasias da Mama/complicações , Sobreviventes de Câncer/psicologia , Exercício Físico , Obesidade/terapia , Telemedicina , Redução de Peso , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , População Rural , Autorrelato , Resultado do TratamentoRESUMO
PURPOSE: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) frequently occur in women being treated for breast cancer. Prior studies suggest high prevalence of vitamin D deficiency in breast cancer patients with musculoskeletal (MS) pain. We conducted a randomized, placebo-controlled trial to determine if 30,000 IU vitamin D3 per week (VitD3) would prevent worsening of AIMSS in women starting adjuvant letrozole for breast cancer. METHODS: Women with stage I-III breast cancer starting adjuvant letrozole and 25(OH)D level ≤40 ng/ml were eligible. All subjects received standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 and were randomized to 30,000 IU oral VitD3/week or placebo. Pain, disability, fatigue, quality of life, 25(OH)D levels, and hand grip strength were assessed at baseline, 12, and 24 weeks. The primary endpoint was incidence of an AIMSS event. RESULTS: Median age of the 160 subjects (80/arm) was 61. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 weeks, and 31 at 24 weeks in the placebo arm and 22, 53, and 57 in the VitD3 arm. There were no serious adverse events. At week 24, 51% of women assigned to placebo had a protocol defined AIMSS event (worsening of joint pain using a categorical pain intensity scale (CPIS), disability from joint pain using HAQ-II, or discontinuation of letrozole due to MS symptoms) vs. 37% of women assigned to VitD3 (p = 0.069). When the brief pain inventory (BPI) was used instead of CPIS, the difference was statistically significant: 56 vs. 39% (p = 0.024). CONCLUSIONS: Although 30,000 IU/week of oral vitamin D3 is safe and effective in achieving adequate vitamin D levels, it was not associated with a decrease in AIMSS events based on the primary endpoint. Post-hoc analysis using a different tool suggests potential benefit of vitamin D3 in reducing AIMSS.