Beth Newman

Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis

BACKGROUND The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors. METHODS We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between Jan 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings. FINDINGS 72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16.6% (95% CI 13.6-20.2). Our estimate was 21.4% (14.9-29.8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to <24 months; 18.9%, 14.2-24.7), was highest when assessed by more than one diagnostic method (nine studies; 28.2%, 11.8-53.5), and was about four times higher in women who had an axillary-lymph-node dissection (18 studies; 19.9%, 13.5-28.2) than it was in those who had sentinel-node biopsy (18 studies; 5.6%, 6.1-7.9). 29 studies met the inclusion criteria for the assessment of risk factors. Risk factors that had a strong level of evidence were extensive surgery (ie, axillary-lymph-node dissection, greater number of lymph nodes dissected, mastectomy) and being overweight or obese. INTERPRETATION Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder. FUNDING The National Breast Cancer Foundation, Australia.

Lymphedema After Breast Cancer: Incidence, Risk Factors, and Effect on Upper Body Function

PURPOSE Secondary lymphedema is associated with adverse physical and psychosocial consequences among women with breast cancer (BC). This article describes the prevalence and incidence of lymphedema between 6 and 18 months after BC treatment; personal, treatment, and behavioral correlates of lymphedema status; and the presence of other upper-body symptoms (UBS) and function (UBF). PATIENTS AND METHODS A population-based sample of Australian women (n = 287) with recently diagnosed, invasive BC were evaluated on five occasions using bioimpedance spectroscopy. Lymphedema was diagnosed when the ratio of impedance values, comparing treated and untreated sides, was three standard deviations more than normative data. UBF was assessed using the validated Disability of the Arm, Shoulder, and Hand questionnaire. RESULTS From 6 to 18 months after surgery, 33% (n = 62) of the sample were classified as having lymphedema; of these, 40% had long-term lymphedema. Although older age, more extensive surgery or axillary node dissection, and experiencing one or more treatment-related complication(s) or symptom(s) at baseline were associated with increased odds, lower socioeconomic status, having a partner, greater child care responsibilities, being treated on the dominant side, participation in regular activity, and having good UBF were associated with decreased odds of lymphedema. Not surprisingly, lymphedema leads to reduced UBF; however, BC survivors report high prevalences of other UBS (34% to 62%), irrespective of their lymphedema status. CONCLUSION Lymphedema is a public health issue deserving greater attention. More systematic surveillance for earlier detection and the potential benefits of physical activity to prevent lymphedema and mitigate symptoms warrant further clinical integration and research.

Participation rates in a case-control study: the impact of age, race, and race of interviewer.

PURPOSE Despite concerns about declining participation rates in epidemiologic studies in recent years, relatively few papers have discussed obstacles to recruiting study participants or strategies for optimizing response rates. This report describes factors associated with nonparticipation in a population-based, case-control study of breast cancer and discusses ways to overcome barriers to participation. METHODS Contact and cooperation rates were calculated for participants in the Carolina Breast Cancer Study (CBCS), stratified by case status, age, race, and race of interviewer. Demographic and breast cancer risk factor characteristics of partial and full responders also were compared. RESULTS Contact rates and cooperation rates varied by case/control status and demographic characteristics. Contact rates were lower among controls, younger women, and black women. Cooperation rates were lower among controls, older women, and black cases. Cooperation rates were higher among both black and nonblack women when participants and interviewers were concordant on race. CONCLUSIONS Obstacles to recruitment seem to differ among race and age subgroups, suggesting that recruitment strategies may need to be tailored to potential participants based upon demographic characteristics. Strategies have been implemented to improve response rates in this and other epidemiologic studies; however, additional research and innovation in this area are needed.

The Carolina Breast Cancer Study: integrating population-based epidemiology and molecular biology

SummaryThe integration of epidemiology and molecular biology provides a new strategy to identify additional risk factors for breast cancer and to better understand the role played by traditionally recognized risk factors. The Carolina Breast Cancer Study (CBCS) is a population-based, case-control study designed to identify causes of breast cancer among Caucasian and African-American women who are residents of a 24-county area of central and eastern North Carolina. Information on established and potential breast cancer risk factors is obtained by personal interviews. Blood samples are collected from all consenting participants. Medical record documentation and paraffin-embedded tumor specimens are obtained for all breast cancer patients. DNA from tumor tissue is tested for a variety of molecular alterations characteristic of breast cancer. Germline DNA from blood lymphocytes is evaluated for presence of alleles increasing susceptibility to breast cancer. Statistical analyses evaluate gene-environment interaction by exploring the associations between environmental/behavioral factors and breast cancer in relation to specific molecular alterations (germline and tumor). Results will help identify high-risk women, clarify causal pathways, and hopefully contribute to the prevention of breast cancer.

Alcohol consumption and insulin concentrations. Role of insulin in associations of alcohol intake with high-density lipoprotein cholesterol and triglycerides.

BackgroundThe relation between alcohol intake and insulin levels may explain, in part, the reported associations of alcohol with cardiovascular disease risk factors, including high-density lipoprotein (HDL) cholesterol, triglycerides, blood pressure, and glucose levels, each of which has been recognized as a component of the insulin resistance syndrome. Methods and ResultsSubjects included nondiabetic participants of the Kaiser Permanente Women Twins Study (1989 through 1990). Usual alcohol intake was assessed as part of a food frequency questionnaire. For women from twin pairs in which both twins drank (n=338), an increment of 12 g of alcohol per day (about one drink) was associated with an 8% lower 2-hour post-glucose-load insulin (P<.01) in a multiple regression analysis for twin data, adjusted for age, body mass index, waist-to-hip ratio, total caloric intake, and family history of diabetes. With genetic influences removed by matched analysis of the subset of 98 monozygotic twin pairs, an intrapair difference of 12 g of alcohol per day was associated with a 12.4% intrapair decrement in postload insulin (P<.01). Inverse associations were also seen for fasting insulin. Alcohol consumption was inversely associated with postload glucose but not with fasting glucose in unmatched (P=.05) and matched (P=.005) analyses. A significant positive association of alcohol intake with high-density lipoprotein cholesterol and an inverse relation of alcohol intake with triglycerides were each independent of insulin levels (Ps.02 in the matched models). Neither systolic nor diastolic blood pressures were related to alcohol consumption in this sample, perhaps because of the rather low level of alcohol intake in the study population (median, 4 g/d). ConclusionsWithin the range of light to moderate drinking habits, alcohol consumption was inversely related to fasting and postload insulin levels. This relation did not explain associations of alcohol intake with lipid levels and may instead reflect an additional mechanism by which moderate alcohol consumption impacts cardiovascular disease risk.

Protective role of appendicectomy on onset and severity of ulcerative colitis and Crohn’s disease

Background and aims: Recent studies on appendicectomy rates in ulcerative colitis and Crohn’s disease have generally not addressed the effect of appendicectomy on disease characteristics. The aims of this study were to compare appendicectomy rates in Australian inflammatory bowel disease patients and matched controls, and to evaluate the effect of prior appendicectomy on disease characteristics. Methods: Patients were ascertained from the Brisbane Inflammatory Bowel Disease database. Controls matched for age and sex were randomly selected from the Australian Twin Registry. Disease characteristics included age at diagnosis, disease site, need for immunosuppression, and intestinal resection. Results: The study confirmed the significant negative association between appendicectomy and ulcerative colitis (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.14–0.38; p<0.0001) and found a similar result for Crohn’s disease once the bias of appendicectomy at diagnosis was addressed (OR 0.34, 95% CI 0.23–0.51; p<0.0001). Prior appendicectomy delayed age of presentation for both diseases and was statistically significant for Crohn’s disease (p=0.02). In ulcerative colitis, patients with prior appendicectomy had clinically milder disease with reduced requirement for immunosuppression (OR 0.15, 95% CI 0.02–1.15; p=0.04) and proctocolectomy (p=0.02). Conclusions: Compared with patients without prior appendicectomy, appendicectomy before diagnosis delays disease onset in ulcerative colitis and Crohn’s disease and gives rise to a milder disease phenotype in ulcerative colitis.

Comparison of methods to diagnose lymphoedema among breast cancer survivors: 6-month follow-up

SummaryOne of the more problematic and dreaded complications of breast cancer is lymphoedema. Our objective was to determine the prevalence of lymphoedema 6-months following breast cancer treatment and to examine potential risk factors among a population-based sample of women residing in South-East Queensland (n=176). Women were defined as having lymphoedema if the difference between the sum of arm circumferences (SOAC) of the treated and untreated sides was >5 cm (prevalence=11.9%) or >10% (prevalence=0.6%), their multi- frequency bioelectrical impedance (MFBIA) score was ≥3 standard deviations above the reference impedance score (prevalence=11.4%), or they reported ‘yes’ when asked if arm swelling had been present in the previous 6 months (prevalence=27.8%). Of those with lymphoedema defined by MFBIA, only 35% were detected using the SOAC method (difference > 5 cm), while 65% were identified via the self-report method (i.e., respective sensitivities). Specificities for SOAC (difference > 5 cm) and self-report were 88.5% and 76.9%, respectively. When examining associations between presence of lymphoedema and a range of characteristics, findings also varied depending on the method used to assess lymphoedema. Nevertheless, one of the more novel and significant findings was that being treated on the non-dominant, compared to dominant, side was associated with an 80% increased risk of having lymphoedema (MFBIA). Our work raises questions about the use of circumferences as the choice of measurement for lymphoedema in both research and clinical settings, and assesses MFBIA as a potential alternative.

A genome wide linkage search for breast cancer susceptibility genes.

Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome‐wide linkage screens, which included a total of 149 multiple case breast cancer families. All families included at least three cases of breast cancer diagnosed below age 60 years, at least one of whom had been tested and found not to carry a BRCA1 or BRCA2 mutation. Evidence for linkage was assessed using parametric linkage analysis, assuming both a dominant and a recessive mode of inheritance, and using nonparametric methods. The highest LOD score obtained in any analysis of the combined data was 1.80 under the dominant model, in a region on chromosome 4 close to marker D4S392. Three further LOD scores over 1 were identified in the parametric analyses and two in the nonparametric analyses. A maximum LOD score of 2.40 was found on chromosome arm 2p in families with four or more cases of breast cancer diagnosed below age 50 years. The number of linkage peaks did not differ from the number expected by chance. These results suggest regions that may harbor novel breast cancer susceptibility genes. They also indicate that no single gene is likely to account for a large fraction of the familial aggregation of breast cancer that is not due to mutations in BRCA1 or BRCA2.

Comorbidity as a predictor of stage of illness for patients with breast cancer.

Objective:The purpose of this research was to determine whether comorbidity affects the stage at which breast cancer is diagnosed. Methods:Data from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (NCI) was merged with Medicare claims for 17,468 women diagnosed with breast cancer from 1993 to 1995. Results:Women with cardiovascular disease, musculoskeletal disorders, mild-to-moderate gastrointestinal disease, and nonmalignant benign breast disease had a 13%, 7%, 14%, and 24% lower odds, respectively, of being diagnosed with advanced breast cancer. Women with diabetes, other endocrine disorders, psychiatric disorders, or hematologic disorders increased the odds of a late-stage diagnosis by 19%, 11%, 20%, and 19% respectively. Mammography screening and contact with the medical care system decreased the odds of late-stage diagnosis. Discussion:Four hypotheses are suggested to explain this link between comorbid illness and stage at diagnosis: (1) the “surveillance” hypothesis, (2) the “physiological” hypothesis, (3) the “competing demand” hypothesis, and (4) the “death from other causes” hypothesis. Conclusions:Comorbidity may complicate the diagnostic decision-making process for breast cancer. The results suggest that contact with the medical care system improves the odds of early-stage diagnosis. Thus, barriers to access for people with chronic conditions may exacerbate those chronic conditions and increase the odds of late-stage breast cancer.

Older Persons' Perception of Risk of Falling: Implications for Fall-Prevention Campaigns

OBJECTIVES We examined older peoples attitudes about falls and implications for the design of fall-prevention awareness campaigns. METHODS We assessed data from (1) computer-assisted telephone surveys conducted in 2002 with Australians 60 years and older in Northern Rivers, New South Wales (site of a previous fall-prevention program; n=1601), and Wide Bay, Queensland (comparison community; n=1601), and (2) 8 focus groups (n=73). RESULTS Participants from the previous intervention site were less likely than were comparison participants to agree that falls are not preventable (odds ratio [OR]=0.76; 95% confidence interval [CI]=0.65, 0.90) and more likely to rate the prevention of falls a high priority (OR=1.31; 95% CI=1.09, 1.57). There was no difference between the groups for self-perceived risk of falls; more than 60% rated their risk as low. Those with a low perceived risk were more likely to be men, younger, partnered, and privately insured, and to report better health and no history of falls. Focus group data indicated that older people preferred messages that emphasized health and independence rather than falls. CONCLUSIONS Although older people accepted traditional fall-prevention messages, most viewed them as not personally relevant. Messages that promote health and independence may be more effective.