Although having a family history of breast cancer is a well established breast cancer risk factor, it is not known whether it influences mortality after breast cancer diagnosis.
Subjects were 4,153 women with first primary incident invasive breast cancer diagnosed between 1991 and 2000, and enrolled in the Breast Cancer Family Registry through population-based sampling in Northern California, USA; Ontario, Canada; and Melbourne and Sydney, Australia. Cases were oversampled for younger age at diagnosis and/or family history of breast cancer. Carriers of germline mutations in BRCA1 or BRCA2 were excluded. Cases and their relatives completed structured questionnaires assessing breast cancer risk factors and family history of cancer. Cases were followed for a median of 6.5 years, during which 725 deaths occurred. Cox proportional hazards regression was used to evaluate associations between family history of breast cancer at the time of diagnosis and risk of all-cause mortality after breast cancer diagnosis, adjusting for established prognostic factors.
The hazard ratios for all-cause mortality were 0.98 (95% confidence interval [CI]=0.84-1.15) for having at least one first- or second-degree relative with breast cancer, and 0.85 (95% CI=0.70-1.02) for having at least one first-degree relative with breast cancer, compared with having no such family history. Estimates did not vary appreciably when stratified by case or tumor characteristics.
Family history of breast cancer is not associated with all-cause mortality after breast cancer diagnosis for women without a known germline mutation in BRCA1 or BRCA2. Therefore, clinical management should not depend on family history of breast cancer.
breast cancer; survival; mortality; family history
Studies have examined the prognostic relevance of reproductive factors prior to breast cancer (BC) diagnosis, but most have been small and overall their findings inconclusive. Associations between reproductive risk factors and all-cause mortality after BC diagnosis were assessed using a population-based cohort of 3,107 women of white European ancestry with invasive BC (1,130 from Melbourne and Sydney, Australia; 1,441 from Ontario, Canada; and 536 from Northern California, USA). During follow-up with a median of 8.5 years, 567 deaths occurred. At recruitment, questionnaire data were collected on oral contraceptive use, number of full-term pregnancies, age at first full-term pregnancy, time from last full-term pregnancy to BC diagnosis, breastfeeding, age at menarche and menopause and menopausal status at BC diagnosis. Hazard ratios (HR) for all-cause mortality were estimated using Cox proportional hazards models with and without adjustment for age at diagnosis, study center, education and body mass index. Compared with nulliparous women, those who had a child up to 2 years, or between 2 to 5 years, prior to their BC diagnosis were more likely to die. The unadjusted HR estimates were 2.75 (95%CI=1.98–3.83, p<0.001) and 2.20 (95%CI=1.65–2.94, p<0.001), respectively, and the adjusted estimates were 2.25 (95%CI=1.59–3.18, p<0.001) and 1.82 (95%CI=1.35–2.46, p<0.001), respectively). When evaluating the prognosis of women recently diagnosed with BC, the time since last full-term pregnancy should be routinely considered along with other established host and tumor prognostic factors, but consideration of other reproductive factors may not be warranted.
Breast cancer; survival; reproductive; outcome; pregnancy
Although studies have shown that physically active breast cancer survivors have lower all-cause mortality, the association between change in physical activity from before to after diagnosis and mortality is not clear. We examined associations among pre- and postdiagnosis physical activity, change in pre- to postdiagnosis physical activity, and all-cause and breast cancer–specific mortality in post-menopausal women. A longitudinal study of 4,643 women diagnosed with invasive breast cancer after entry into the Women’s Health Initiative study of postmenopausal women. Physical activity from recreation and walking was determined at baseline (prediagnosis) and after diagnosis (assessed at the 3 or 6 years post-baseline visit). Women participating in 9 MET-h/wk or more (~3 h/wk of fast walking) of physical activity before diagnosis had a lower all-cause mortality (HR = 0.61; 95% CI, 0.44–0.87; P = 0.01) compared with inactive women in multivariable adjusted analyses. Women participating in ≥9 or more MET-h/wk of physical activity after diagnosis had lower breast cancer mortality (HR = 0.61; 95% CI, 0.35–0.99; P = 0.049) and lower all-cause mortality (HR = 0.54; 95% CI, 0.38–0.79; P < 0.01). Women who increased or maintained physical activity of 9 or more MET-h/wk after diagnosis had lower all-cause mortality (HR = 0.67; 95% CI, 0.46–0.96) even if they were inactive before diagnosis. High levels of physical activity may improve survival in postmenopausal women with breast cancer, even among those reporting low physical activity prior to diagnosis. Women diagnosed with breast cancer should be encouraged to initiate and maintain a program of physical activity.
Identifying modifiable factors that reduce the risk of recurrence and improve survival in breast cancer survivors is a pressing concern. The purpose of this study was to examine the association of physical activity following diagnosis and treatment with the risk of breast cancer recurrence and mortality and all-cause mortality in women with early-stage breast cancer.
Materials and Methods
The sample consisted of 1,970 women from the Life After Cancer Epidemiology study, a prospective investigation of behavioral risk factors and health outcomes. Self-reported frequency and duration of work-related, household and caregiving, recreational, and transportation-related activities during the six months prior to enrollment were assessed. Outcomes were ascertained from electronic or paper medical charts. Hazard ratios and 95% confidence intervals were estimated from delayed entry Cox proportional hazards models.
Although age-adjusted results suggested that higher levels of physical activity were associated with reduced risk of recurrence and breast cancer mortality (P for trend = 0.05 and 0.07, respectively for highest versus lowest level of hours per week of moderate physical activity), these associations were attenuated after adjustment for prognostic factors and other confounding variables (P for trend = 0.36 and 0.26). In contrast, a statistically significant protective association between physical activity and all-cause mortality remained in multivariable analyses (hazard ratio, 0.66; 95% confidence interval, 0.42–1.03; P for trend = 0.04).
These findings do not support a protective effect of physical activity on breast cancer recurrence or mortality but do suggest that regular physical activity is beneficial for breast cancer survivors in terms of total mortality.
Recreational physical activity (RPA) is associated with a reduced risk of developing breast cancer, but there is limited research on whether prediagnostic RPA influences survival after breast cancer diagnosis.
We evaluated the association between prediagnostic RPA and risk of death in 1,508 women with a first breast cancer diagnosis between 1996 and 1997 in the population-based Long Island Breast Cancer Study Project. Five-year mortality through the end of 2002 was assessed using the National Death Index (N=196). An in-person interview was completed shortly after diagnosis to obtain information on lifetime RPA, which was expressed as metabolic equivalent task hours per week (MET-h/wk).
A lower risk of all-cause death was observed for women who engaged in an average of ≥9 MET-h/wk of RPA from menarche to diagnosis compared with women who did not exercise (age and BMI adjusted hazard ratio [HR]=0.57; 95% confidence interval [CI]=0.39–0.83), an association that was similar when evaluated according to menopausal status. Decreased all-cause mortality was found for women with any moderate intensity lifetime RPA (>0 MET-h/wk) (HR=0.62; 95% CI=0.46-0.84) and breast cancer-specific mortality (HR=0.64; 95% CI=0.43-0.93) risk than women who engaged in no moderate RPA. Among postmenopausal women, RPA that took place after menopause resulted in a decrease in overall mortality, whereas no association was observed for RPA which took place prior to menopause (>0 MET-h/wk of RPA vs. no RPA: HR=0.61; 95% CI=0.39-0.94; and HR=1.00; 95% CI=0.65-1.54, respectively).
This study provides support that RPA prior to breast cancer diagnosis improves survival.
Physical activity; exercise; breast cancer; survival; prevention; epidemiology
Research suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.
A total of 2,361 post-treatment breast cancer survivors (Stage I–III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate–vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality.
Those who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events.
Higher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis.
Exercise; Recurrence; Survival; Behavior; Lifestyle
The 2008 Physical Activity (PA) Guidelines recommend engaging in at least 2.5 hours (10 MET-hours/week) of moderate intensity PA per week (defined as 4 METs) to reduce risk of morbidity and mortality. This analysis was conducted to investigate whether this recommendation can be extended to breast cancer survivors. Data from four studies of breast cancer survivors measuring recreational PA from semi-quantitative questionnaires a median of 23 months post-diagnosis (interquartile range 18 to 32 months) were pooled in the After Breast Cancer Pooling Project (n=13,302). Delayed entry Cox proportional hazards models were applied in data analysis with adjustment for age, post-diagnosis body mass index, race/ethnicity, menopausal status, TNM stage, cancer treatment, and smoking history. Engaging in at least 10 MET-hours/week of PA was associated with a 27% reduction in all-cause mortality (n=1,468 events, Hazard Ratio (HR) = 0.73, 95% CI, 0.66–0.82) and a 25% reduction in breast cancer mortality (n=971 events, HR=0.75, 95% CI 0.65–0.85) compared to women who did not meet the PA Guidelines (< 10 MET-hours/week). Risk of breast cancer recurrence (n=1,421 events) was not associated with meeting the PA Guidelines (HR=0.96, 95% CI, 0.86–1.06). These data suggest that adhering to the PA Guidelines may be an important intervention target for reducing mortality among breast cancer survivors.
physical activity guidelines; breast cancer survival; mortality; epidemiology
The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case–control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% Cl 0.3–12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence. © 1999 Cancer Research Campaign
BRCA1; breast cancer; DNA sequencing; mutations; population prevalence; variants
Triple-negative breast cancer, characterized by a lack of hormone receptor and HER2 expression, is associated with a particularly poor prognosis. Focusing on potentially modifiable breast cancer risk factors, we examined the relationship between body size, physical activity, and triple-negative disease risk.
Using data from 155,723 women enrolled in the Women’s Health Initiative (median follow-up 7.9 years), we assessed associations between baseline body mass index (BMI), BMI in earlier adulthood, waist and hip circumference, waist-hip ratio (WHR), recreational physical activity, and risk of triple-negative (N=307) and estrogen receptor-positive (ER+, N=2,610) breast cancers.
Women in the highest versus lowest BMI quartile had 1.35-fold [95% confidence interval (CI): 0.92–1.99] and 1.39-fold (95% CI: 1.22–1.58) increased risks of triple-negative and ER+ breast cancers, respectively. Waist and hip circumferences were positively associated with risk of ER+ breast cancer (p for trend=0.01 for both measures) but were not associated with triple-negative breast cancer. Compared to women who reported no recreational physical activity, women in the highest activity tertile had similarly lower risks of triple-negative and ER+ breast cancers [hazard ratio (HR)=0.77, 95% CI: 0.51–1.13 and HR=0.85, 95% CI: 0.74–0.98, respectively].
Despite biological and clinical differences, triple-negative and ER+ breast cancers are similarly associated with BMI and recreational physical activity in postmenopausal women. The biological mechanisms underlying these similarities are uncertain and these modest associations require further investigation.
If confirmed, these results suggest potential ways postmenopausal women might modify their risk of both ER+ and triple-negative breast cancers.
triple-negative; breast cancer; physical activity; body mass index
Although modifiable risk factors have been included in previous models that estimate or project breast cancer risk, there remains a need to estimate the effects of changes in modifiable risk factors on the absolute risk of breast cancer.
Using data from a case–control study of women in Italy (2569 case patients and 2588 control subjects studied from June 1, 1991, to April 1, 1994) and incidence and mortality data from the Florence Registries, we developed a model to predict the absolute risk of breast cancer that included five non-modifiable risk factors (reproductive characteristics, education, occupational activity, family history, and biopsy history) and three modifiable risk factors (alcohol consumption, leisure physical activity, and body mass index). The model was validated using independent data, and the percent risk reduction was calculated in high-risk subgroups identified by use of the Lorenz curve.
The model was reasonably well calibrated (ratio of expected to observed cancers = 1.10, 95% confidence interval [CI] = 0.96 to 1.26), but the discriminatory accuracy was modest. The absolute risk reduction from exposure modifications was nearly proportional to the risk before modifying the risk factors and increased with age and risk projection time span. Mean 20-year reductions in absolute risk among women aged 65 years were 1.6% (95% CI = 0.9% to 2.3%) in the entire population, 3.2% (95% CI = 1.8% to 4.8%) among women with a positive family history of breast cancer, and 4.1% (95% CI = 2.5% to 6.8%) among women who accounted for the highest 10% of the total population risk, as determined from the Lorenz curve.
These data give perspective on the potential reductions in absolute breast cancer risk from preventative strategies based on lifestyle changes. Our methods are also useful for calculating sample sizes required for trials to test lifestyle interventions.
Observational studies demonstrate an association between physical activity and improved outcomes in breast and colon cancer survivors. To test these observations with a large, randomized clinical trial, an intervention that significantly impacts physical activity in these patients is needed. The Active After Cancer Trial (AACT) was a multicenter pilot study evaluating the feasibility of a telephone-based exercise intervention in a cooperative group setting.
Sedentary (engaging in < 60 minutes of recreational activity/week) breast and colorectal cancer survivors were randomized to a telephone-based exercise intervention or usual care control group. The intervention was delivered through the University of California at San Diego; participants received 10 phone calls over the course of the 16-week intervention. All participants underwent assessment of physical activity, fitness, physical functioning, fatigue and exercise self-efficacy at baseline and after the 16-week intervention.
One hundred and twenty-one patients were enrolled through 10 Cancer and Leukemia Group B (CALGB) institutions; 100 patients had breast cancer and 21 had colorectal cancer. Participants randomized to the exercise group increased physical activity by more than 100%, vs. 22% in controls (54.5 vs. 14.6 minutes, p=0.13), and experienced significant increases in fitness (increased 6-minute walk test distance by 186.9 vs. 81.9 ft, p=0.006) and physical functioning (7.1 vs. 2.6, p=0.04) as compared to the control group.
Breast and colorectal cancer survivors enrolled in a multicenter, telephone-based physical activity intervention increased physical activity and experienced significant improvements in fitness and physical functioning. Lifestyle intervention research is feasible in a cooperative group setting.
Breast cancer; exercise; cooperative group; intervention; physical functioning
To assess the accessibility and suitability of schools as recreational sites and to determine whether they are associated with young adolescent girls’ weekend metabolic equivalent-weighted moderate-to-vigorous (MW-MVPA) physical activity and body mass index (BMI).
We drew a half-mile (0.805 km) radius around the residences of participants in Trial of Activity for Adolescent Girls (n=1556) in Maryland, South Carolina, Minnesota, Louisiana, California, and Arizona. We visited all schools and parks within the defined distance and documented their amenities and accessibility on Saturdays in Spring 2003. Staff gathered data on each girls’ height and weight and used accelerometers to record weekend MW-MVPA.
Schools represented 44% of potential neighborhood sites for physical activity. However, a third of schools were inaccessible on the Saturday we visited. Neighborhoods with locked schools were primarily non-white, older, more densely populated, and of lower socioeconomic status. Though there was no relationship between school accessibility on Saturdays and weekend MW-MVPA, the number of locked schools was associated with significantly higher BMI.
The lack of relationship between MW-MVPA and school accessibility may imply that young adolescent girls do not identify schools as recreational resources. However, due to the association between BMI and locked schools, efforts to stem the obesity epidemic should include making schools more accessible.
bmi; obesity; physical activity; built environment; schools; parks
We examined the impact of metropolitan racial residential segregation on stage at diagnosis and all-cause and breast cancer-specific survival between and within black and white women diagnosed with breast cancer in California between 1996 and 2004.
We merged data from the California Cancer Registry with Census indices of five dimensions of racial residential segregation, quantifying segregation among Blacks relative to Whites; block group (“neighborhood”) measures of the percentage of Blacks and a composite measure of socioeconomic status. We also examined simultaneous segregation on at least two measures (“hypersegregation”). Using logistic regression we examined effects of these measures on stage at diagnosis and Cox proportional hazards regression for survival.
For all-cause and breast-cancer specific mortality, living in neighborhoods with more Blacks was associated with lower mortality among black women, but higher mortality among Whites. However, neighborhood racial composition and metropolitan segregation did not explain differences in stage or survival between Black and White women.
Future research should identify mechanisms by which these measures impact breast cancer diagnosis and outcomes among Black women.
Breast cancer; Survival; Stage at diagnosis; Residential segregation; Race
To investigate, among women with breast cancer, how postdiagnosis diet quality and the combination of diet quality and recreational physical activity are associated with prognosis.
This multiethnic, prospective observational cohort included 670 women diagnosed with local or regional breast cancer. Thirty months after diagnosis, women completed self-report assessments on diet and physical activity and were followed for 6 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for death from any cause and breast cancer death.
Women consuming better-quality diets, as defined by higher Healthy Eating Index-2005 scores, had a 60% reduced risk of death from any cause (HRQ4:Q1: 0.40, 95% CI: 0.17, 0.94) and an 88% reduced risk of death from breast cancer (HRQ4:Q1: 0.12, 95% CI: 0.02, 0.99). Compared with inactive survivors consuming poor-quality diets, survivors engaging in any recreational physical activity and consuming better-quality diets had an 89% reduced risk of death from any cause (HR: 0.11, 95% CI: 0.04, 0.36) and a 91% reduced risk of death from breast cancer (HR: 0.09, 95% CI: 0.01, 0.89). Associations observed were independent of obesity status.
Women diagnosed with localized or regional breast cancer may improve prognosis by adopting better-quality dietary patterns and regular recreational physical activity. Lifestyle interventions emphasizing postdiagnosis behavior changes are advisable in breast cancer survivors.
Diet; Exercise; Breast neoplasm; Prognosis
Increased body weight at breast cancer diagnosis has been associated with an increased risk of recurrence and reduced survival. Weight gain is also common following diagnosis. Increasing physical activity (PA) after diagnosis may minimize these adverse outcomes. This study investigated whether PA levels after diagnosis declined from pre-diagnosis levels, and whether any changes in PA varied by disease stage, treatment, age, and body mass index (BMI) in 812 incident population-based stage 0–3a breast cancer patients.
Types of sports and household activities and their frequency and duration for the year prior to diagnosis and for the month prior to the interview (i.e., 4–12 months post-diagnosis) were assessed during a baseline interview.
Patients decreased their total PA by an estimated 2.0 hrs/week from pre- to post-diagnosis, an 11% decrease (p < .05). Greater decreases in sports PA were observed among women treated with radiation and chemotherapy (50% decrease) than women having surgery only (24% decrease) or treated with radiation only (23%) (p < .05). Greater decreases in sports PA were observed among obese patients (41% decrease) than normal weight (24% decrease) patients (p < .05).
PA levels were significantly reduced following breast cancer diagnosis. Greater decreases in PA observed among heavier patients implies a potential for greater weight gain among already overweight women. Randomized controlled trials are needed to evaluate how PA may improve breast cancer prognosis.
exercise; prognosis; treatment; stage; body weight; obesity
Recent reports have shown that physical activity improves the outcome of patients with colorectal cancer as well as breast and prostate cancer. However, the mechanisms whereby physical activity reduces cancer mortality are not well established.
Incident cases of colorectal cancer were identified among participants of the Melbourne Collaborative Cohort Study, a prospective cohort study of 41 528 Australians recruited from 1990 to 1994. Information on tumour site and stage, treatments given, recurrences, and deaths were obtained from systematic review of the medical records. Baseline assessments of physical activity and body size were made, and cases with available plasma had pre‐diagnosis insulin‐like growth factor 1 (IGF‐1) and insulin‐like growth factor binding protein 3 (IGFBP‐3) levels measured. We assessed associations between these hormones and colorectal cancer specific deaths with respect to physical activity.
A total of 526 cases of colorectal cancer were identified, of which 443 had IGF‐1/IGFBP‐3 levels measured. Median follow up among survivors was 5.6 years. For the physically active, increasing IGFBP‐3 by 26.2 nmol/l was associated with a 48% reduction in colorectal cancer specific deaths (adjusted hazard ratio (HR) 0.52 (0.33–0.83); p = 0.006). No association was seen for IGF‐1 (adjusted HR 0.90 (0.55–1.45); p = 0.65). For the physically inactive, neither IGF‐1 nor IGFBP‐3 was associated with disease specific survival.
This study supports the hypothesis that the beneficial effects of physical activity in reducing colorectal cancer mortality may occur through interactions with the insulin‐like growth factor axis and in particular IGFBP‐3.
colorectal cancer; physical activity; insulin‐like growth factor 1; insulin‐like growth factor binding protein 3
This study tested the hypothesis that physician supply thresholds are associated with breast cancer survival in Ontario.
The 5-year survival of 17,820 female breast cancer patients diagnosed between 1995 and 1997 was surveilled until 2003 for all-cause mortality. Physician supply densities in 1991 and 2001 were computed for 49 Ontario regions.
There were independent threshold effects for general practitioners (GP; 7.25 per 10,000) and obstetrician/gynecologists (OB/GYN; 6 per 100,000) at or above which women with breast cancer were more likely to survive for 5 years. The respective risk of living in areas undersupplied with OB/GYN and GP increased 30% to nearly 5-fold during the 1990s. Five-year survival tended to be lower in provincial areas outside of Toronto, which experienced GP (odds ratio, 0.83; 90% CI, 0.70–0.99) and OB/GYN (odds ratio, 0.76; 95% CI, 0.61–0.96) supply decreases.
As they do in America, primary care physician supplies in Canada seem to matter in the effective provision of cancer care. Community resources such as health care service endowments, including physician supplies, may be particularly critical to the performance of health care systems such as Canada’s, which aim to provide medically necessary care for all.
PMID: 20051549 CAMSID: cams1408
OBJECTIVES: Some studies of white women suggest that exercise reduces the incidence of breast cancer. There are no data on black women. We assessed the relationship between strenuous physical activity and prevalent breast cancer among participants in the Black Women's Health Study. METHODS: Data on strenuous recreational physical activity at various ages and other factors were collected in 1995 by mail questionnaire from 64,524 United States black women aged 21 to 69 years. The 704 women who reported breast cancer (cases) were matched on age and on menopausal status at the time of the breast cancer diagnosis with 1408 women who did not report breast cancer (controls). Odds ratios for levels of physical activity at various ages were derived from conditional logistic regression with control for potential confounding factors. RESULTS: Odds ratios for > or =7 h per week relative to < 1 were significantly reduced for strenuous activity at age 21 for breast cancer overall and premenopausal breast cancer, at age 30 for breast cancer overall, and at age 40 for postmenopausal breast cancer. There was no evidence of a reduction associated with exercise in high school. CONCLUSIONS: The findings of the present study suggest that strenuous physical activity in early adulthood is associated with a reduced risk of breast cancer in African-American women.
Physical activity offers many benefits to breast cancer survivors, yet research on physical activity during the immediate period following a breast cancer diagnosis is limited. In a prospective cohort study of 1,696 women diagnosed with invasive breast cancer in the Kaiser Permanente Northern California Medical Care Program from 2006–2009, we describe change in self-reported physical activity levels from around diagnosis to six months post-diagnosis and determine factors associated with change. Participants completed a comprehensive physical activity questionnaire at baseline (2 months post-diagnosis) and at follow-up (8 months post-diagnosis). Predictors of physical activity change were determined by multivariable linear regression. Reductions in all physical activity levels were observed (P<0.0001); mean (SD) change (hours/week) of moderate-vigorous physical activity (MVPA) was −1.28 (4.48) and sedentary behavior was −0.83 (6.95). In fully-adjusted models, overweight and obesity were associated with greater declines in MVPA of −1.58 hours/week (SD=0.92) and −1.29 hours/week (SD=0.93), respectively (P=0.0079). Receipt of chemotherapy only was also associated with a greater decrease in MVPA (−2.12 hours/week; SD=0.92; P<0.0001), specifically for recreational activities (−1.62 hours/week; SD=0.64; P=0.0001). These data suggest challenges in maintaining physical activity levels during active treatment among women with breast cancer. Interventions to encourage physical activity in breast cancer survivors should be pursued.
Breast Cancer; Chemotherapy; Cohort Studies; Physical Activity; Exercise; Radiation Therapy; Sedentary Lifestyle; Cancer Survivorship
Several, but not all, studies have observed increased risks of testicular germ cell cancer (TGCC) associated with bicycling and other recreational activities. To further examine whether physical activity (PA) in adolescence is associated with TGCC risk, the authors conducted a case-control study in western Washington State.
Cases (n=391) were men diagnosed with TGCC who were identified through a population-based cancer registry. Controls (n=1023) were men identified from the general population in western Washington State by using random digit telephone dialing. Participants were queried about various specific PA in grades 7–12 including bicycling, horseback riding, competitive sports, physical education class, as well as moderate, vigorous, and sedentary activities in general.
In multivariate analyses, bicycling, vigorous-intensity activities, and sedentary activities were not associated with TGCC risk, while horseback riding and wrestling were associated with decreased risks, and moderate-intensity activities, soccer, basketball and intermediate duration of competitive activities were associated with increased risks.
The lack of internal consistency of the findings within the current study and of findings among prior studies, suggests that PA contributes little, if any, to the risk of TGCC.
testicular cancer; physical activity; case-control study; adolescent
Ancestral mutations in BRCA1 and BRCA2 are common in people of Ashkenazi Jewish descent and are associated with a substantially increased risk of breast and ovarian cancer. Women considering mutation testing usually have several personal and family cancer characteristics, so predicting mutation status from one factor alone could be misleading. The aim of this study was to develop a simple algorithm to estimate the probability that an Ashkenazi Jewish woman carries an ancestral mutation, based on multiple predictive factors.
We studied Ashkenazi Jewish women with a personal or family history of breast or ovarian cancer and living in Melbourne or Sydney, Australia, or with a previous diagnosis of breast or ovarian cancer and living in the UK. DNA samples were tested for the germline mutations 185delAG and 5382insC in BRCA1, and 6174delT in BRCA2. Logistic regression was used to identify, and to estimate the predictive strength of, major determinants.
A mutation was detected in 64 of 424 women. An algorithm was developed by combining our findings with those from similar analyses of a large study of unaffected Jewish women in Washington. Starting with a baseline score, a multiple of 0.5 (based on the logistic regression estimates) is added for each predictive feature. The sum is the estimated log odds ratio that a woman is a carrier, and is converted to a probability by using a table. There was good internal consistency.
This simple algorithm might be useful in the clinical and genetic counselling setting. Comparison and validation in other settings should be sought.
Ashkenazi Jews; BRCA1; BRCA2; breast cancer; mutations; ovarian cancer
Physical activity may influence breast cancer risk through multiple mechanisms and at different periods in life. In this study we evaluate breast cancer risk associated with total and vigorous physical activity at ages 15, 30, and 50 years and the referent year prior to diagnosis/selection. Participants were non-Hispanic white (NHW) (1527 cases and 1601 control subjects) and Hispanic/American Indian (HAI) (798 cases and 924 controls) women. Both total and vigorous activity reduced risk of breast cancer in a dose-response manner. Among premenopausal women, only high total metabolic equivalent of the task (MET) hours of activity during the referent year was associated with reduced breast cancer risk in NHW women (odds ratio [OR] 0.62; 95% confidence interval [CI] 0.43, 0.91). Among postmenopausal women, physical activity had the greatest influence among women not recently exposed to hormones. Among these women, high total lifetime activity reduced risk of breast cancer for both NHW (OR 0.60; 95% CI 0.36, 1.02; p trend 0.01) and HAI women (OR 0.52; 95% CI 0.23, 1.16; p trend 0.07). Additionally, high total MET hours of activity at age 30 years (OR 0.56; 95% CI 0.37, 0.85) and at age 15 years (OR 0.57; 95% CI 0.38, 0.88) reduced breast cancer risk among postmenopausal NHW women not recently exposed to hormones. Among HAI women, more recent activity performed during the referent year and at age 50 appeared to have the greatest influence on breast cancer risk. Among postmenopausal NHW women. there was a significant interaction between physical activity and hormone replacement therapy (p value, 0.01), while among postmenopausal HAI women, physical activity interacted with body mass index (p value, 0.04). These data suggest that physical activity is important in reducing risk of breast cancer in both NHW and HAI women.
BMI; Breast Cancer; Physical Activity; Hispanic; Hormones
To examine associations between recreational physical activity and quality of life (QOL) in a multi-ethnic cohort of breast cancer survivors, specifically testing whether associations are consistent across racial/ethnic groups after accounting for relevant medical and demographic factors that might explain disparities in QOL outcomes.
Data were collected from a population-based cohort of non-Hispanic White (n=448), Black (n=197), and Hispanic (n=84) breast cancer survivors (Stage 0-IIIa) in the Health, Eating, Activity, and Lifestyle (HEAL) Study. Physical activity was assessed approximately 2.5 years breast cancer diagnosis, with QOL assessed on average 6–12 months later. We used structural equation modeling to examine relationships between meeting recommended levels of physical activity and QOL, stratifying by race/ethnicity and adjusting for other demographic, comorbidity, and treatment effects.
Structural equation modeling indicated that meeting recommended levels of physical activity had significant positive associations with QOL for Black and for non-Hispanic White women, (p<0.05). Fewer Black women reported meeting recommended physical activity levels (p<0.001); but meeting recommendations was associated with better QOL. Post-hoc tests showed that meeting physical activity recommendations was specifically associated with better vitality, social functioning, emotional roles, and global QOL (all p’s< 0.05).
These results suggest that meeting recommended levels of physical activity is associated with better QOL in non-Hispanic White and Black breast cancer survivors. Findings may help support future interventions among breast cancer survivors and promote supportive care that includes physical activity; although more research is needed to determine these relationships among Hispanic and other ethnic minority women.
Physical Activity; Quality of Life; Ethnicity; Breast Cancer
Mammographic breast density is a highly heritable (h2 > 0.6) and strong risk factor for breast cancer. We conducted a genome-wide linkage study to identify loci influencing mammographic breast density (MD).
Epidemiological data were assembled on 1,415 families from the Australia, Northern California and Ontario sites of the Breast Cancer Family Registry, and additional families recruited in Australia and Ontario. Families consisted of sister pairs with age-matched mammograms and data on factors known to influence MD. Single nucleotide polymorphism (SNP) genotyping was performed on 3,952 individuals using the Illumina Infinium 6K linkage panel.
Using a variance components method, genome-wide linkage analysis was performed using quantitative traits obtained by adjusting MD measurements for known covariates. Our primary trait was formed by fitting a linear model to the square root of the percentage of the breast area that was dense (PMD), adjusting for age at mammogram, number of live births, menopausal status, weight, height, weight squared, and menopausal hormone therapy. The maximum logarithm of odds (LOD) score from the genome-wide scan was on chromosome 7p14.1-p13 (LOD = 2.69; 63.5 cM) for covariate-adjusted PMD, with a 1-LOD interval spanning 8.6 cM. A similar signal was seen for the covariate adjusted area of the breast that was dense (DA) phenotype. Simulations showed that the complete sample had adequate power to detect LOD scores of 3 or 3.5 for a locus accounting for 20% of phenotypic variance. A modest peak initially seen on chromosome 7q32.3-q34 increased in strength when only the 513 families with at least two sisters below 50 years of age were included in the analysis (LOD 3.2; 140.7 cM, 1-LOD interval spanning 9.6 cM). In a subgroup analysis, we also found a LOD score of 3.3 for DA phenotype on chromosome 12.11.22-q13.11 (60.8 cM, 1-LOD interval spanning 9.3 cM), overlapping a region identified in a previous study.
The suggestive peaks and the larger linkage signal seen in the subset of pedigrees with younger participants highlight regions of interest for further study to identify genes that determine MD, with the goal of understanding mammographic density and its involvement in susceptibility to breast cancer.
Long-term physical activity is associated with lower breast cancer risk. Little information exists on its association with subsequent survival.
California Teachers Study cohort members provided information in 1995–1996 on long-term (high school through age 54 years) and recent (past 3 years) participation in moderate and strenuous recreational physical activities. The 3,539 women diagnosed with invasive breast cancer after cohort entry and through December 31, 2004, were followed through December 31, 2005. Of these, 460 women died, 221 from breast cancer. Moderate and strenuous physical activities were combined into low (≤0.50 hr/wk/yr of any activity), intermediate (0.51–3.0 hr/wk/yr of moderate or strenuous activity but no activity >3.0 hr/wk/yr) or high activity (>3.0 hr/wk/yr of either activity type). Multivariable relative risks (RR) and 95% confidence intervals (CI) for mortality were estimated using Cox proportional hazards methods, adjusting for race/ethnicity, estrogen receptor status, disease stage, and baseline information on comorbidities, body mass index, and caloric intake.
Women with high or intermediate levels of long-term physical activity had lower risk of breast cancer death (RR=0.53, 95% CI=0.35–0.80; and RR=0.65, 95% CI=0.45–0.93, respectively) than women with low activity levels. These associations were consistent across estrogen receptor status and disease stage, but confined to overweight women. Deaths due to causes other than breast cancer were related only to recent activity.
Consistent long-term participation in physical activity before breast cancer diagnosis may lower risk of breast cancer death, providing further justification for public health strategies to increase physical activity throughout the lifespan.