Around 25% of women undergoing Axillary Clearance (ANC) develop lymphedema (LE). Intervention with a compression garment is recommended to prevent LE but no randomised evidence exists to support this ...strategy.
Methods
A randomised trial tested standard management versus application of graduated compression garments (20‐24 mmHg) to affected arm, for 1 year. Women with node positive breast cancer (n = 1300) undergoing ANC consented to arm volume measurements and those developing a 4–9% relative arm volume increase (RAVI) (subclinical LE) within 9 months post‐surgery were randomised. Primary outcome was proportion of patients developing LE (RAVI > 10%) by 24‐months in each group. Secondary endpoints included Quality of life in each group.
Results
In total 143 patients were randomised (74 no sleeve: 69 compression sleeve) between October 2010 and November 2015. The lymphoedema rate at 24 months in the ‘no sleeve’ group was at 41%, similar to the ‘sleeve’ group (30%: p = 0.32). Thirtytwo patients randomised to the ‘no sleeve’ group had a sleeve applied within 24 months. Body Mass Index (BMI) at randomisation predicted LE at any time point HR 1.04 (CI 1.01–1.08; p = 0.01). Patients with obesity (BMI > 30) had higher rates of LE in both groups (46%) compared to those with BMI < 30 (24%). No difference between patients was found in either group in changes in QoL. Compression sleeves applied after development of LE improved QoL scores (FACT‐B p = 0.007:TOI p = 0.042).
Conclusion
Early intervention with External Compression garments does not prevent clinical LE, particularly in women with a high BMI > 30. The use of prophylactic garments in subclinical LE (RAVI < 9%) is unwarranted.
A Randomised trial of external arm compression garments after axillary node clearance in women developing early arm swelling failed to find an effect of the intervention in preventing lymphoedema.
The differences between breast cancer risk factors in white British/Irish and Asian women attending screening in the UK are not well documented.
Between 2009-15 ethnicity and traditional breast ...cancer risk factors were self-identified by a screening cohort from Greater Manchester, with follow up to 2016. Risk factors and incidence rates were compared using age-standardised statistics (European standard population).
Eight hundred and seventy-nine Asian women and 51,779 unaffected white British/Irish women aged 46-73 years were recruited. Asian women were at lower predicted breast cancer risk from hormonal and reproductive risk factors than white British/Irish women (mean 10 year risk 2.6% vs 3.1%, difference 0.4%, 95%CI 0.3-0.5%). White British/Irish women were more likely to have had a younger age at menarche, be overweight or obese, taller, used hormone replacement therapy and not to have had children.. However, despite being less overweight Asian women had gained more weight from age 20 years and were less likely to undertake moderate physical activity. Asian women also had a slightly higher mammographic density. Asian age-standardised incidence was 3.2 (95%CI 1.6-5.2, 18 cancers) per thousand women/year vs 4.5 (95%CI 4.2-4.8, 1076 cancers) for white British/Irish women.
Asian women attending screening in Greater Manchester are likely to have a lower risk of breast cancer than white British/Irish women, but they undertake less physical activity and have more adult weight gain.
The Predicting Risk of Cancer at Screening (PROCAS) study estimated 10-year breast cancer risk for 53,596 women attending NHS Breast Screening Programme. The present study, nested within the PROCAS ...study, aimed to assess the psychological impact of receiving breast cancer risk estimates, based on: (a) the Tyrer-Cuzick (T-C) algorithm including breast density or (b) T-C including breast density plus single-nucleotide polymorphisms (SNPs), versus (c) comparison women awaiting results.
A sample of 2138 women from the PROCAS study was stratified by testing groups: T-C only, T-C(+SNPs) and comparison women; and by 10-year risk estimates received: 'moderate' (5-7.99%), 'average' (2-4.99%) or 'below average' (<1.99%) risk. Postal questionnaires were returned by 765 (36%) women.
Overall state anxiety and cancer worry were low, and similar for women in T-C only and T-C(+SNPs) groups. Women in both T-C only and T-C(+SNPs) groups showed lower-state anxiety but slightly higher cancer worry than comparison women awaiting results. Risk information had no consistent effects on intentions to change behaviour. Most women were satisfied with information provided. There was considerable variation in understanding.
No major harms of providing women with 10-year breast cancer risk estimates were detected. Research to establish the feasibility of risk-stratified breast screening is warranted.
There are widespread moves to develop risk-stratified approaches to population-based breast screening. The public needs to favour receiving breast cancer risk information, which ideally should ...produce no detrimental effects. This study investigates risk perception, the proportion wishing to know their 10-year risk and whether subsequent screening attendance is affected.
Fifty thousand women attending the NHS Breast Screening Programme completed a risk assessment questionnaire. Ten-year breast cancer risks were estimated using a validated algorithm (Tyrer-Cuzick) adjusted for visually assessed mammographic density. Women at high risk (⩾8%) and low risk (<1%) were invited for face-to-face or telephone risk feedback and counselling.
Of those invited to receive risk feedback, more high-risk women, 500 out of 673 (74.3%), opted to receive a consultation than low-risk women, 106 out of 193 (54.9%) (P<0.001). Women at high risk were significantly more likely to perceive their risk as high (P<0.001) and to attend their subsequent mammogram (94.4%) compared with low-risk women (84.2%; P=0.04) and all attendees (84.3%; ⩽0.0001).
Population-based assessment of breast cancer risk is feasible. The majority of women wished to receive risk information. Perception of general population breast cancer risk is poor. There were no apparent adverse effects on screening attendance for high-risk women whose subsequent screening attendance was increased.
Breast cancer familial risk clinics offer screening and preventive strategies. While BRCA1/BRCA2 genetic testing provides important risk information for some women, panels of more common breast ...cancer risk genetic variants may have relevance to greater numbers of women with familial risk.
Three polygenic risk scores (PRS) based on 18 SNPs were investigated in a case-control study of women attending a familial risk clinic. PRS were derived from published general European population allele ORs and frequencies (18-SNPs (SNP18)). In women with BRCA1/BRCA2 mutations, 3 SNPs/13 SNPs, respectively, generated the PRS estimates. In total, 364 incident breast cancer cases (112 with BRCA1/2 mutations) were matched with 1605 controls (691 BRCA1/2) by age last mammogram and BRCA1/2 genetic test result. 87 women with cancer before attendance were also considered. Logistic regression was used to measure PRS performance through ORs per IQR and calibration of the observed to expected (O/E) logarithm relative risk when unadjusted and adjusted for phenotypic risk factors assessed by the Tyrer-Cuzick (TC) model.
SNP18 was predictive for non-carriers of BRCA1/2 mutations (IQR OR 1.55, 95% CI 1.29 to 1.87, O/E 96%). Findings were unaffected by adjustment from TC (IQR OR 1.56, 95% CI 1.29 to 1.89) or when prior cancers were included (IQR OR 1.55, 95% CI 1.30 to 1.87). There was some evidence to support polygenic scores with weights for individuals with BRCA1/2 mutations (BRCA1 IQR OR 1.44, 95% CI 1.17 to 1.76; BRCA2 IQ OR 1.44, 95% CI 0.90 to 2.31).
PRS may be used to refine risk assessment for women at increased familial risk who test negative/have low likelihood of BRCA1/2 mutations. They may alter the recommended prevention strategy for many women attending family history clinics.
Purpose
Women’s worry about developing breast cancer may influence their decision to use preventive therapy. However, the direction of this relationship has been questioned. We prospectively ...investigated the relationship between breast cancer worry and uptake of preventive therapy. The socio-demographic and clinical factors associated with high breast cancer worry were also investigated.
Methods
Women at increased risk of developing breast cancer were recruited from clinics across England (
n
= 408). Participants completed a survey on their breast cancer worry, socio-demographic and clinical factors. Uptake of tamoxifen was recorded at 3 months (
n
= 258 women, 63.2%). Both primary and sensitivity analyses were conducted using different classifications of low, medium and high worry.
Results
39.5% of respondents reported medium breast cancer worry at baseline and 21.2% reported high worry. Ethnic minority women were more likely to report high worry than white women (OR = 3.02, 95%CI 1.02, 8.91,
p
= 0.046). Women educated below degree level were more likely to report high worry than those with higher education (OR = 2.29, 95%CI 1.28, 4.09,
p
= 0.005). No statistically significant association was observed between worry and uptake. In the primary analysis, fewer respondents with medium worry at baseline initiated tamoxifen (low worry = 15.5%, medium = 13.5%, high = 15.7%). In the sensitivity analysis, participants with medium worry reported the highest uptake of tamoxifen (19.7%).
Conclusions
No association was observed between worry and uptake, although the relationship was affected by the categorisation of worry. Standardised reporting of the classification of worry is warranted to allow transparent comparisons across cohorts.
Uptake of preventive therapies for breast cancer is low. We examined whether women at increased risk of breast cancer can be categorized into groups with similar medication beliefs, and whether ...belief group membership was prospectively associated with uptake of preventive therapy.
Women (n = 732) attending an appointment to discuss breast cancer risk were approached; 408 (55.7%) completed the Beliefs About Medicines and the Perceived Sensitivity to Medicines questionnaires. Uptake of tamoxifen at 3 months was reported in 258 (63.2%). The optimal number of belief groups were identified using latent profile analysis.
Uptake of tamoxifen was 14.7% (38/258). One in 5 women (19.4%; 78/402) reported a strong need for tamoxifen. The model fit statistics supported a 2-group model. Both groups held weak beliefs about their need for tamoxifen for current and future health. Group 2 (38%; 154/406 of the sample) reported stronger concerns about tamoxifen and medicines in general, and stronger perceived sensitivity to the negative effects of medicines compared with group 1 (62%; 252/406). Women with low necessity and lower concerns (group 1) were more likely to initiate tamoxifen (18.3%; 33/180) than those with low necessity and higher concerns (group 2) (6.4%; 5/78). After adjusting for demographic and clinical factors, the odds ratio was 3.37 (95% confidence interval, 1.08-10.51; P = .036).
Uptake of breast cancer preventive therapy was low. A subgroup of women reported low need for preventive therapy and strong medication concerns. These women were less likely to initiate tamoxifen. Medication beliefs are targets for supporting informed decision-making.
Preventive therapies, such as tamoxifen, are a risk reduction option for women at increased risk of breast cancer. Little is known about the psychological factors influencing the decision to use chemoprevention. Using latent profile analysis, women who reported a low need for preventive therapy and strong medication concerns were less likely to initiate tamoxifen treatment. Medication beliefs are targets for supporting informed decision-making.
Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models ...have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that selectively attenuates proinflammatory cytokine production at low doses. MW-151 was tested in an APP/PS1 knock-in mouse model that exhibits increases in AD-relevant pathology progression with age, including increases in proinflammatory cytokine levels. Drug was administered during two distinct but overlapping therapeutic time windows of early stage pathology development. MW-151 treatment attenuated the increase in microglial and astrocyte activation and proinflammatory cytokine production in the cortex and yielded improvement in neurologic outcomes, such as protection against synaptic protein loss and synaptic plasticity impairment. The results also demonstrate that the therapeutic time window is an important consideration in efficacy studies of drugs that modulate glia biological responses involved in pathology progression and suggest that such paradigms should be considered in the development of new therapeutic regimens that seek to delay the onset or slow the progression of AD.
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