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1.

Introduction  

The use of androgen deprivation therapy (ADT) for prostate cancer is on the rise, but its adverse side effects may include increased fat mass and decreased lean muscle mass. The net effect of ADT on BMI is unknown.  相似文献   

2.

Background

Obesity has been recognized as a risk factor in the development and recurrence of breast cancer and is also associated with poor prognostic outcomes. This systematic review and network meta-analysis aimed to identify the most effective exercise, physical activity, and dietary interventions to reduce fat mass, body fat percentage and body weight as well as potentially increase lean mass in women diagnosed with or at high risk of breast cancer.

Methods

A systematic search of databases was performed up to May 2022. Eligible randomized controlled trials examined the effects of exercise, physical activity and/or dietary interventions on fat mass and lean mass in women diagnosed with or at high risk of breast cancer. A random-effects network meta-analysis was conducted to determine the effects of different interventions across outcomes when sufficient studies were available.

Results

Eighty-four studies (n = 6428) were included in this review. Caloric restriction and combined exercise + caloric restriction significantly reduced fat mass (range, –3.9 to –3.7 kg) and body weight (range, –5.3 to –4.7 kg), whereas physical activity + caloric restriction significantly reduced body fat percentage (–2.4%; 95% confidence interval [CI], –3.4% to –13%) and body mass index (–2.2 kg × m–2; 95% CI, –3.0 to –1.4 kg × m–2) in breast cancer patients. Resistance exercise was the most effective intervention to increase lean mass (0.7 kg; 95% CI, 0.5–1.0 kg) in breast cancer patients.

Conclusion

Multimodal exercise and diet programs were the most effective interventions to reduce fat mass, body fat percentage, and body weight and increase and/or preserve lean mass.  相似文献   

3.

Background  

Androgen deprivation therapy leads to a number of adverse effects including deterioration of the musculoskeletal system and increased risk factors for cardiovascular and metabolic complications. The purpose of this study is to determine the effects, efficacy, retention and compliance of a physical exercise intervention in a large established cohort of prostate cancer patients from the Randomised Androgen Deprivation and Radiotherapy (RADAR) study. Specifically, we aim to compare short- and long-term effects of a prostate cancer-specific supervised exercise program to a standard public health physical activity strategy utilizing printed resources on cardiovascular and metabolic risk factors. Our primary outcomes are cardiorespiratory capacity, abdominal obesity, and lipid and glycemic control, while secondary outcomes include self-reported physical activity, quality of life and psychological distress.  相似文献   

4.

Introduction  

The use of androgen deprivation therapy (ADT) in the treatment of prostate cancer is associated with changes in body composition including increased fat and decreased lean mass. Limited information exists regarding the rate and extent of these changes. This systematic review was conducted to determine the effects of ADT on body composition in prostate cancer patients.  相似文献   

5.
PURPOSE: Androgen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue, functional decline, increased body fatness, and loss of lean body tissue. These physical changes can negatively affect health-related quality of life. Resistance exercise may help to counter some of these side effects by reducing fatigue, elevating mood, building muscle mass, and reducing body fat. METHODS: In a two-site study, 155 men with prostate cancer who were scheduled to receive androgen deprivation therapy for at least 3 months after recruitment were randomly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks (82 men) or to a waiting list control group (73 men). The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported questionnaires after 12 weeks. Secondary outcomes were muscular fitness and body composition. RESULTS: Men assigned to resistance exercise had less interference from fatigue on activities of daily living (P =.002) and higher quality of life (P =.001) than men in the control group. Men in the intervention group demonstrated higher levels of upper body (P =.009) and lower body (P <.001) muscular fitness than men in the control group. The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight, body mass index, waist circumference, or subcutaneous skinfolds. CONCLUSION: Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving androgen deprivation therapy. This form of exercise can be an important component of supportive care for these patients.  相似文献   

6.

Background

Androgen deprivation therapy (ADT) is the mainstay therapy for men with prostate cancer. However, there are musculoskeletal side effects from ADT that increase the risk for osteoporosis and fracture, and can compromise the quality of life of these individuals. The objectives of this study are to determine the efficacy of a home-based walking exercise program in promoting bone health, physical function and quality of life in men with prostate cancer receiving ADT.

Methods/Design

A 12-month prospective, single-blinded, randomized controlled trial will be conducted to compare the Exercise Group with the Control Group. Sixty men with prostate cancer who will be starting ADT will be recruited and randomly assigned to one of the two groups: the Exercise Group will receive instructions in setting up an individualized 12-month home-based walking exercise program, while the Control Group will receive standard medical advice from the attending physician. A number of outcome measures will be used to assess bone health, physical function, and health-related quality of life. At baseline and 12 months, bone health will be assessed using dual-energy X-ray absorptiometry. At baseline and every 3 months up to 12 months, physical function will be evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale, Activities-specific Balance Confidence Scale, Short Physical Performance Battery, and Six-Minute Walk Test; and health-related quality of life will be assessed using the Functional Assessment of Cancer Therapy Prostate Module and the Medical Outcomes Study 12-item Short Form Health Survey Version 2. A mixed multiple analysis of variance will be used to analyze the data.

Discussion

Musculoskeletal health management remains a challenge in men with prostate cancer receiving ADT. This study addresses this issue by designing a simple and accessible home-based walking exercise program that will potentially have significant impact on reducing the risk of fracture, promoting physical function, and ultimately improving the health-related quality of life in men with prostate cancer receiving ADT.

Trial registration

ClinicalTrials.gov: NCT00834392.  相似文献   

7.

Background  

A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.  相似文献   

8.
Targeted exercise training could reduce risk factors for fracture and obesity-related diseases that increase from breast cancer treatment, but has not been sufficiently tested. We hypothesized that progressive, moderate-intensity resistance + impact training would increase or maintain hip and spine bone mass, lean mass and fat mass and reduce bone turnover compared to controls who participated in a low-intensity, non-weight bearing stretching program. We conducted a randomized, controlled trial in 106 women with early stage breast cancer who were >1 year post-radiation and/or chemotherapy, ≥50 years of age at diagnosis and postmenopausal, free from osteoporosis and medications for bone loss, resistance and impact exercise na?ve, and cleared to exercise by a physician. Women were randomly assigned to participate in 1 year of thrice-weekly progressive, moderate-intensity resistance + impact (jump) exercise or in a similar frequency and length control program of progressive, low-intensity stretching. Primary endpoints were bone mineral density (BMD; g/cm2) of the hip and spine and whole body bone-free lean and fat mass (kg) determined by DXA and biomarkers of bone turnover—serum osteocalcin (ng/ml) and urinary deoxypyrodiniline cross-links (nmol/mmolCr). Women in the resistance + impact training program preserved BMD at the lumbar spine (0.47 vs. −2.13%; P = 0.001) compared to controls. The resistance + impact group had a smaller increase in osteocalcin (7.0 vs. 27%, P = 0.03) and a larger decrease in deoxypyrodinoline (−49.9 vs. −32.6%, P = 0.06) than controls. Increases in lean mass from resistance + impact training were greatest among women currently taking aromatase inhibitors compared to controls not on this therapy (P = 0.01). Our combined program of resistance + impact exercise reduced risk factors for fracture among postmenopausal breast cancer survivors (BCS) and may be particularly relevant for BCS on aromatase inhibitors (AIs) because of the additional benefit of exercise on muscle mass that could reduce falls.  相似文献   

9.

Purpose

The goal of this RCT was to examine the efficacy and safety of a web-based program to improve cardiovascular and bone health outcomes, among 35 BRCA1/2+ breast cancer survivors who underwent prophylactic oophorectomy and thus experienced premature surgical menopause.

Methods

A 12-month commercially available web-based lifestyle modification program (Precision Nutrition Coaching) was utilized. Cardiovascular fitness, dietary intake, leisure time activity, body composition, bone mineral density, bone structure, and muscle strength were assessed.

Results

Average adherence to all program components was 74.8 %. Women in the intervention group maintained their cardiovascular fitness level over the 12 months (1.1 ± 7.9 %), while the control group significantly decreased fitness capacity (?4.0 ± 7.5 %). There was a significant difference between groups in percent change of whole body bone area (?0.8 ± 2.5 control and 0.5 ± 1.30 intervention). We also observed decreased BMI (?4.7 ± 6.2 %) and fat mass (?8.6 ± 12.7 %) in the intervention group due to significant concomitant decreases in caloric intake and increases in caloric expenditure. The control group demonstrated decreased caloric intake and decreased lean tissue mass.

Conclusions

In this population at high risk for detrimental cardiovascular and bone outcomes, a commercially available lifestyle intervention program mitigated a decline in cardiovascular health, improved bone health, and decreased weight through fat loss.

Implications for cancer survivors

Precision Nutrition Coaching has shown benefit in breast cancer survivors for reduced risk of deleterious cardiovascular and bone outcomes.
  相似文献   

10.

BACKGROUND:

Older cancer survivors are at increased risk for secondary cancers, cardiovascular disease, obesity, and functional decline and, thus, may benefit from health‐related interventions. However, to the authors' knowledge, little is known regarding the health behaviors of older cancer survivors and the associations of those behaviors with quality‐of‐life outcomes, especially during the long‐term post‐treatment period.

METHODS:

In total, 753 older (aged ≥65 years) long‐term survivors (≥5 years postdiagnosis) of breast, prostate, and colorectal cancer completed 2 baseline telephone interviews to assess their eligibility for a diet and exercise intervention trial. The interviews assessed exercise, diet, weight status, and quality of life.

RESULTS:

Older cancer survivors reported a median of 10 minutes of moderate‐to‐vigorous exercise per week, and only 7% had Healthy Eating Index scores >80 (indicative of healthful eating habits relative to national guidelines). Despite their suboptimal health behaviors, survivors reported mental and physical quality of life that exceeded age‐related norms. Greater exercise and better diet quality were associated with better physical quality‐of‐life outcomes (eg, better vitality and physical functioning; P < .05), whereas greater body mass index was associated with reduced physical quality of life (P < .001).

CONCLUSIONS:

The current results indicated a high prevalence of suboptimal health behaviors among older, long‐term survivors of breast, prostate, and colorectal cancer who were interested in lifestyle modification. In addition, the findings pointed to the potential negative impact of obesity and the positive impact of physical activity and a healthy diet on physical quality of life in this population. Cancer 2009. © 2009 American Cancer Society.  相似文献   

11.
Management of complications of prostate cancer treatment.   总被引:1,自引:0,他引:1  
Prostate cancer is the most commonly diagnosed noncutaneous cancer in men in the United States. Treatment of men with prostate cancer commonly involves surgical, radiation, or hormone therapy. Most men with prostate cancer live for many years after diagnosis and may never suffer morbidity or mortality attributable to prostate cancer. The short-term and long-term adverse consequences of therapy are, therefore, of great importance. Adverse effects of radical prostatectomy include immediate postoperative complications and long-term urinary and sexual complications. External beam or interstitial radiation therapy in men with localized prostate cancer may lead to urinary, gastrointestinal, and sexual complications. Improvements in surgical and radiation techniques have reduced the incidence of many of these complications. Hormone treatment typically consists of androgen deprivation therapy, and consequences of such therapy may include vasomotor flushing, anemia, and bone density loss. Numerous clinical trials have studied the role of bone antiresorptive therapy for prevention of bone density loss and fractures. Other long-term consequences of androgen deprivation therapy may include adverse body composition changes and increased risk of insulin resistance, diabetes, and cardiovascular disease. Ongoing and planned clinical trials will continue to address strategies to prevent treatment-related side effects and improve quality of life for men with prostate cancer.  相似文献   

12.
Osteoporosis and other body composition changes are important complications of androgen deprivation therapy (ADT) for prostate cancer. Bilateral orchiectomy and gonadotropin-releasing hormone agonist treatment decrease bone mineral density and increase fracture risk. Other factors including diet and lifestyle may contribute to bone loss in men with prostate cancer. Estrogens play an important role in male bone metabolism. Androgen deprivation therapy with estrogens probably causes less bone loss than bilateral orchiectomy or gonadotropin-releasing hormone agonist treatment. Bicalutamide monotherapy increases serum estrogen levels and may also spare bone. Lifestyle modification including smoking cessation, moderation of alcohol use, and regular weight bearing exercise are recommended to decrease treatment-related bone loss. Supplemental calcium and vitamin D are also recommended. Pamidronate (Aredia®), an intravenous bisphosphonate, prevents bone loss during ADT. Other bisphosphonates are probably effective but have not been studied in hypogonadal men. Androgen deprivation therapy increases fat mass and decreases muscle mass. These body composition changes may contribute to treatment-related decreases in physical capacity and quality of life.  相似文献   

13.

Background  

Established risk factors for prostate cancer have not translated to effective prevention or adjuvant care strategies. Several epidemiologic studies suggest greater body adiposity may be a modifiable risk factor for high-grade (Gleason 7, Gleason 8-10) prostate cancer and prostate cancer mortality. However, BMI only approximates body adiposity, and may be confounded by centralized fat deposition or lean body mass in older men. Our objective was to use bioelectric impedance analysis (BIA) to measure body composition and determine the association between prostate cancer and total body fat mass (FM) fat-free mass (FFM), and percent body fat (%BF), and which body composition measure mediated the association between BMI or waist circumference (WC) with prostate cancer.  相似文献   

14.
IntroductionThe impact of prehabilitation remains controversial due to a short presurgical waiting period and the diminished capacity of the patient population. A strategy to augment and optimize the effectiveness of prehabilitations for abdominal cancer patients may be found in the unlikely field of sport science. We investigated the use of blood flow restriction training and sport nutrition supplementation to augment functional capacity and increase muscle strength in twenty-four abdominal cancer patients awaiting surgery.Materials and methodsThe sport science-based program was comprised of blood flow restriction exercise 5 to 6 times per week and a daily sports nutrition supplement containing l-citrulline, creatine monohydrate, and whey protein. Results: After 4 weeks of prehabilitation, 6-min walk test, timed up and go, short physical performance battery, 5-chair stand test and physical component score of quality of life were significantly improved (all p < 0.05). Total body and appendicular lean mass as assessed by dual energy X-ray absorptiometry increased by 0.73 ± 1.04 kg (p = 0.004) and 0.42 ± 0.64 kg (p = 0.006), respectively. Total body fat mass and trunk fat mass decreased (p = 0.004 and p = 0.021). There were no significant changes in hand grip strength, fear of falling, the mental component summary of quality of life, or fasting serum concentrations of myostatin, follistatin, and growth hormone.ConclusionA multimodal prehabilitation program, which encompasses blood flow restriction training and sports nutrition supplements, is both feasible and effective in improving lean mass and physical function in abdominal cancer patients prior to surgery.  相似文献   

15.

Purpose

Randomized clinical trials are inconclusive regarding the role of physical exercise in anthropometric measurements, quality of life, and survival in breast cancer patients. Our aim was to conduct a systematic review and meta-analysis to assess the effects of physical exercise on these outcomes in women who went through curative treatment of early-stage breast cancer.

Methods

Pubmed, Embase, Cochrane Library were searched for randomized clinical trial comparing physical exercise (counseling or structured programs with supervised/individualized exercise sessions) with usual care in women that went through for breast cancer treatment. Primary outcomes were overall survival and disease-free survival, while secondary outcomes were weight loss, body mass index, waist–hip ratio, percentage of body fat, and quality of life.

Results

We found 60 randomized clinical trials, only one of them showed mortality data; the HR for mortality was 0.45 (95% CI 0.21–0.97) for the intervention group when compared to the control group. Physical exercise was associated with weight reduction (??1.36 kg, 95% CI ??2.51 to ??0.21, p?=?0.02), lower body mass index (??0.89 kg/m2, 95% CI ??1.50 to ??0.28, p?<?0.01), and lower percentage of body fat (??1.60 percentage points, 95% CI ??2.31 to ??0.88, p?<?0.01). There was an increase in the quality of life (standardized mean difference of 0.45, 95% CI 0.20–0.69, p?<?0.01).

Conclusions

The articles found had heterogeneous types of intervention, but they showed significant effects on anthropometric measures and quality of life. Among them, only one study had mortality as outcome and it showed physical exercise as a protective intervention. Despite these findings, publication bias and poor methodological quality were presented. Physical exercise should be advised for breast cancer survivors since it has no adverse effects and can improve anthropometrics measures and quality of life. PROSPERO registry: CRD42014008743.
  相似文献   

16.
IntroductionOlder men with prostate cancer are commonly affected by reductions in lean mass and physical function following androgen deprivation therapy (ADT). Resistance-based exercise programs are critical to counteract the musculoskeletal toxicities derived from prostate cancer treatment and aging. However, there is significant variability in the effects of exercise interventions. Examining demographic and clinical moderators of exercise effects in this patient group can assist in identifying which subgroups of patients benefit most. Therefore, we examined the effects and moderators of resistance-based exercise programs on sarcopenia-related outcomes that included lean mass, skeletal muscle index, physical function, and muscle strength in older men with prostate cancer.Materials and MethodsData were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. For the present study, we included data from trials that examined the effects of supervised resistance-based exercise interventions on lean mass outcomes, muscle strength, and physical function in patients with prostate cancer previously or currently treated with ADT. Linear mixed models were undertaken to analyse the effects of resistance-based exercise programs considering the clustering of patients within studies. Effects were evaluated by regressing the study group on the post-intervention value of the outcome adjusted for the baseline value, while potential moderators were examined by adding the moderator and its interaction term into the regression model.ResultsA total of 560 patients with prostate cancer (age: 69.5 ± 7.8 yrs.; body mass index: 28.6 ± 4.0 kg.m−2) previously or currently treated with ADT were included. Resistance-based exercise programs resulted in significant effects on whole-body and appendicular lean mass and the skeletal muscle index (P < 0.05), with improvements observed across different characteristics. Improvements were also observed in 400-m walk and 6-m backwards tandem walk (P < 0.05), with patients presenting with lower baseline levels deriving greater exercise effects on 400-m walk (−19.4 s, 95% confidence interval [CI]: −36.6 to −2.3) and 6-m backwards tandem walk tests (−3.0 s, 95% CI: −5.7 to −0.3). For relative muscle strength, significant exercise effects were observed, with greater effects in younger patients (0.35 kg.kg−1, 95% CI: 0.22 to 0.48).DiscussionResistance-based exercise programs effectively improve well-known markers of sarcopenia in men with prostate cancer, with specific subgroups of patients, such as those younger and presenting with lower baseline levels of physical function, deriving greater effects on muscle strength and physical function, respectively.  相似文献   

17.
More than a third of cancers are diagnosed in people over the age of 75. Androgen deprivation for prostate cancer and aromatase inhibitors in breast cancer accelerate age-related bone loss and increase fracture rates. BMD should be checked by dual energy X-ray absorptiometry at baseline and, dependent on risk, every 12–24 months. Sufficient calcium, vitamin D and exercise are part of primary fracture prevention. Resistance exercise in particular may improve functional activity and bone density. In men at increased fracture risk and women with postmenopausal early breast cancer, antiresorptive treatment is warranted to reduce fracture rate and to increase overall survival in breast cancer. Bone metastases (BM) are common in breast and prostate cancer and lytic bone lesions typical of multiple myeloma. They can cause fractures, pain and spinal cord compression, require surgery or radiation for symptom relief, and lead to hypercalcaemia. Multidisciplinary working with patients and carers can improve quality of life for elderly patients with BM and mitigate the adverse consequences of therapy. Bisphosphonates and other osteoclast inhibitors such as denosumab reduce this morbidity, improve quality of life and reduce pain. Especially in the elderly, attention should be paid to renal function and to risk factors for osteonecrosis with bone-modifying agents. Attention should also be paid to hypocalcaemia risk, which can be considerable in elderly men with metastatic prostate cancer and vitamin D deficiency. We urgently need further research specifically directed at assessing risks and benefits of bone targeted treatments in the growing population of elderly cancer patients.  相似文献   

18.

Background

Studies in breast cancer-related lymphedema (BRCL) have exclusively examined total arm volume, but not the specific tissue composition that contributes to total volume. We evaluated baseline differences in arm tissue composition [fat mass, lean mass, bone mineral content (BMC), and bone mineral density (BMD)] between the affected and unaffected arms in women with BRCL. We compared changes in arm tissue composition and self-reported lymphedema symptoms after 1 year of weight-lifting versus control.

Methods

We utilized data from physical activity and lymphedema trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy X-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities.

Results

At baseline, the affected arm had more fat (? = 89.7 g; P < 0.001) and lean mass (? = 149.1 g; P < 0.001), but less BMC (? = ?3.2 g; P < 0.001) and less BMD (? = ?5.5 mg/cm2; P = 0.04) than the unaffected arm. After 12 months of weight-lifting, composition of the affected arm was improved: lean mass (71.2 g; P = 0.01) and BMD (14.0 mg/cm2; P = 0.02) increased, arm fat percentage decreased (?1.5%; P = 0.003). Composition of the unaffected arm was only improved in lean mass (65.2 g; P = 0·04). Increases in lean mass were associated with less severe BCRL symptoms.

Conclusions

Among women with BRCL, slowly progressive weight-lifting could improve arm tissue composition. Changes in arm tissue composition predict changes in symptom burden. Investigating the combined effects of exercise and weight loss on arm tissue composition and BCRL symptoms may provide additional insight into the benefits of lifestyle modification on lymphedema biology.
  相似文献   

19.
Androgens are important determinants of body composition in men. Androgen-deprivation therapy, the mainstay of treatment for advanced prostate cancer, increases fat mass and decreases lean body mass. These adverse changes in body composition may contribute to treatment-related fatigue, fracture risk, insulin resistance, and increased cardiovascular disease risk. Potential strategies to treat or prevent these adverse body composition changes include exercise training, alternative forms of hormonal therapy, and insulin-sensitizing agents.  相似文献   

20.

Introduction

Physical inactivity and overweight are risk factors for postmenopausal breast cancer. The effect of physical activity may be partially mediated by concordant weight loss. We studied the effect on serum sex hormones, which are known to be associated with postmenopausal breast cancer risk, that is attributable to exercise by comparing randomly obtained equivalent weight loss by following a hypocaloric diet only or mainly by exercise.

Methods

Overweight, insufficiently active women were randomised to a diet (N = 97), mainly exercise (N = 98) or control group (N = 48). The goal of both interventions was to achieve 5–6 kg of weight loss by following a calorie-restricted diet or an intensive exercise programme combined with only a small caloric restriction. Primary outcomes after 16 weeks were serum sex hormones and sex hormone-binding globulin (SHBG). Body fat and lean mass were measured by dual-energy X-ray absorptiometry.

Results

Both the diet (−4.9 kg) and mainly exercise (−5.5 kg) groups achieved the target weight loss. Loss of body fat was significantly greater with exercise versus diet (difference −1.4 kg, P < 0.001). In the mainly exercise arm, the reduction in free testosterone was statistically significantly greater than that of the diet arm (treatment effect ratio [TER] 0.92, P = 0.043), and the results were suggestive of a difference for androstenedione (TER 0.90, P = 0.064) and SHBG (TER 1.05, P = 0.070). Compared with the control arm, beneficial effects were seen with both interventions, diet and mainly exercise, respectively, on oestradiol (TER 0.86, P = 0.025; TER 0.83, P = 0.007), free oestradiol (TER 0.80, P = 0.002; TER 0.77, P < 0.001), SHBG (TER 1.14; TER 1.21, both P < 0.001) and free testosterone (TER 0.91, P = 0.069; TER = 0.84, P = 0.001). After adjustment for changes in body fat, intervention effects attenuated or disappeared.

Conclusions

Weight loss with both interventions resulted in favourable effects on serum sex hormones, which have been shown to be associated with a decrease in postmenopausal breast cancer risk. Weight loss induced mainly by exercise additionally resulted in maintenance of lean mass, greater fitness, greater fat loss and a larger effect on (some) sex hormones. The greater fat loss likely explains the observed larger effects on sex hormones.

Trial registration

ClinicalTrials.gov identifier: NCT01511276. Registered on 12 January 2012.

Electronic supplementary material

The online version of this article (doi:10.1186/s13058-015-0633-9) contains supplementary material, which is available to authorized users.  相似文献   

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