Breast Cancer Pooling Project Research Articles

A novel approach to increasing community capacity for weight management a volunteer-delivered programme (ActWELL) initiated within breast screening clinics: a randomised controlled trial

BackgroundIt is estimated that around 30% of breast cancers in post-menopausal women are related to lifestyle. The breast cancer-pooling project demonstrated that sustained weight loss of 2 to 4.5 kg is associated with an 18% lower risk of breast cancer, highlighting the importance of small changes in body weight. Our study aimed to assess the effectiveness a volunteer-delivered, community based, weight management programme (ActWELL) for women with a BMI > 25 kg/m2 attending NHS Scotland Breast Screening clinics.MethodsA multicentre, 1:1 parallel group, randomised controlled trial was undertaken in 560 women aged 50 to 70 years with BMI > 25 kg/m2. On completion of baseline measures, all participants received a breast cancer prevention leaflet. Intervention group participants received the ActWELL intervention which focussed on personalised diet advice and pedometer walking plans. The programme was delivered in leisure centres by (the charity) Breast Cancer Now volunteer coaches.Primary outcomes were changes between groups at 12 months in body weight (kg) and physical activity (accelerometer measured step count).ResultsTwo hundred seventy-nine women were allocated to the intervention group and 281 to the comparison group. Twelve-month data were available from 240 (81%) intervention and 227 (85%) comparison group participants. Coaches delivered 523 coaching sessions and 1915 support calls to 279 intervention participants. Mean weight change was − 2.5 kg (95% CI − 3.1 to − 1.9) in the intervention group and − 1.2 kg (− 1.8 to 0.6) in the comparison group. The adjusted mean difference was − 1.3 kg (95% CI − 2.2 to − 0.4, P = 0.003). The odds ratio for losing 5% weight was 2.20 (95% CI 1.4 to 3.4, p = 0.0005) in favour of the intervention. The adjusted mean difference in step counts between groups was 483 steps/day (95% CI − 635 to 1602) (NS).ConclusionsA community weight management intervention initiated at breast screening clinics and delivered by volunteer coaches doubled the likelihood of clinically significant weight loss at 12 months (compared with usual care) offering significant potential to decrease breast cancer risk.Trial registrationDatabase of registration: ISCRTN.Registration number:11057518.Date trial registered:21.07.2017.Date of enrolment of first participant: 01.09.2017.

Postdiagnosis social networks and breast cancer mortality in the After Breast Cancer Pooling Project.

Large social networks have been associated with better overall survival, though not consistently with breast cancer (BC)-specific outcomes. This study evaluated associations of postdiagnosis social networks and BC outcomes in a large cohort. Women from the After Breast Cancer Pooling Project (n = 9267) provided data on social networks within approximately 2 years of their diagnosis. A social network index was derived from information about the presence of a spouse/partner, religious ties, community ties, friendship ties, and numbers of living first-degree relatives. Cox models were used to evaluate associations, and a meta-analysis was used to determine whether effect estimates differed by cohort. Stratification by demographic, social, tumor, and treatment factors was performed. There were 1448 recurrences and 1521 deaths (990 due to BC). Associations were similar in 3 of 4 cohorts. After covariate adjustments, socially isolated women (small networks) had higher risks of recurrence (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.15-1.77), BC-specific mortality (HR, 1.64; 95% CI, 1.33-2.03), and total mortality (HR, 1.69; 95% CI, 1.43-1.99) than socially integrated women; associations were stronger in those with stage I/II cancer. In the fourth cohort, there were no significant associations with BC-specific outcomes. A lack of a spouse/partner (P = .02) and community ties (P = .04) predicted higher BC-specific mortality in older white women but not in other women. However, a lack of relatives (P = .02) and friendship ties (P = .01) predicted higher BC-specific mortality in nonwhite women only. In a large pooled cohort, larger social networks were associated with better BC-specific and overall survival. Clinicians should assess social network information as a marker of prognosis because critical supports may differ with sociodemographic factors. Cancer 2017;123:1228-1237. © 2016 American Cancer Society.

Abstract PD4-08: Post-diagnosis physical activity and comorbidities, not BMI, explain mortality risk in the after breast cancer pooling project

Abstract Background: In its 2014 position statement, ASCO concluded that obesity is associated with worse prognosis after cancer diagnosis. However in the same year, a comprehensive review by the World Cancer Research Fund concluded that there was limited evidence that greater body fatness increases risk of overall or breast cancer mortality, indicating that further investigation into lifestyle factors are needed. The After Breast Cancer (ABC) Pooling Project has reported, separately, significant mortality effects of pre-diagnosis BMI and of post-diagnosis physical activity (PA). We investigate whether the effect of BMI can be limited to subgroups characterized by comorbidities and physical activity. Methods: Data are from the three US cohorts that were harmonized in the ABCPP (n=9513) including: the Women's Healthy Eating and Living (WHEL), Life After Cancer Epidemiology (LACE), and Nurses' Health (NHS) studies. Stepwise delayed entry Cox proportional hazards models examined each lifestyle predictor (BMI, PA, and comorbidities assessed after diagnosis) sequentially and together in multivariate models for breast cancer and all-cause mortality. Results: In multivariate models without the other two target variables, PA was significantly associated with a 17% decrease in the risk of breast cancer mortality among women in the highest quartile of PA (MET hr/wk > 21.4), compared to the lowest quartile (MET hr/wk < 2.7) (HR=0.81,95% CI= 0.67,0.97). In the model with major comorbidities, there was a significant 40% increase in the risk of breast cancer mortality among women diagnosed with both diabetes and hypertension (HR=1.40, 95% CI= 1.01,1.93). In the model with BMI, there was no significant association with risk of breast cancer mortality. These results were essentially unchanged with all variables in a single model. For all-cause mortality, the PA-only model showed a significant PA effect with the hazard decreasing from 20% to 40% across quartiles (Q2 HR=0.80, 95% CI=0.71,0.90, Q4 HR=0.62, 95% CI=0.54,0.71). In the comorbidity-only model, both diabetes and hypertension significantly increased hazard of all-cause mortality 80% and 33%, respectively. Having both diagnoses was associated with a significant, 2.3 fold increase in all-cause mortality (HR=2.34, 95% CI= 1.95,2.81). In the BMI-only model, being underweight was associated with a significant 2.4 fold increase in risk of all-cause mortality, and there was a 20 and 37% increase in risk associated with being categorized as obese I or II (Obese I HR=1.23, 95% CI=1.07,1.40, Obese II HR=1.37, 95% CI=1.16,1.61). With all three variables in the model, the risk associated with being obese decreased and became non-significant (Obese I HR=1.06, Obese II HR=1.05), while the significance, strength, and direction of the association of comorbidities and PA with all-cause mortality remained constant. Conclusion: These data suggest that post-diagnosis comorbidities and lack of physical activity, rather than high BMI , are the important risk factors for all-cause and breast cancer specific mortality. While needing further validation, these suggest that physical activity interventions and monitoring treatment for comorbidities should become standard of care for breast cancer survivors. Citation Format: Nelson SH, Marinac CR, Patterson RE, Nachuta SJ, Caan BJ, Chen WY, Shu X-O, Pierce JP. Post-diagnosis physical activity and comorbidities, not BMI, explain mortality risk in the after breast cancer pooling project. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD4-08.

Impact of very low physical activity, BMI, and comorbidities on mortality among breast cancer survivors.

The purpose of this study was to examine post-diagnosis BMI, very low physical activity, and comorbidities, as predictors of breast cancer-specific and all-cause mortality. Data from three female US breast cancer survivor cohorts were harmonized in the After Breast Cancer Pooling Project (n=9513). Delayed entry Cox proportional hazards models were used to examine the impact of three post-diagnosis lifestyle factors: body mass index (BMI), select comorbidities (diabetes only, hypertension only, or both), and very low physical activity (defined as physical activity <1.5 METh/week) in individual models and together in multivariate models for breast cancer and all-cause mortality. For breast cancer mortality, the individual lifestyle models demonstrated a significant association with very low physical activity but not with the selected comorbidities or BMI. In the model that included all three lifestyle variables, very low physical activity was associated with a 22% increased risk of breast cancer mortality (HR 1.22, 95% CI 1.05, 1.42). For all-cause mortality, the three individual models demonstrated significant associations for all three lifestyle predictors. In the combined model, the strength and significance of the association of comorbidities (both hypertension and diabetes versus neither: HR 2.16, 95% CI 1.79, 2.60) and very low physical activity (HR 1.35, 95% CI 1.22, 1.51) remained unchanged, but the association with obesity was completely attenuated. These data indicate that after active treatment, very low physical activity, consistent with a sedentary lifestyle (and comorbidities for all-cause mortality), may account for the increased risk of mortality, with higher BMI, that is seen in other studies.

Post-diagnosis social networks, and lifestyle and treatment factors in the After Breast Cancer Pooling Project.

Larger social networks have been associated with better breast cancer survival. To investigate potential mediators, we evaluated associations of social network size and diversity with lifestyle and treatment factors associated with prognosis. We included 9331 women from the After Breast Cancer Pooling Project who provided data on social networks within approximately two years following diagnosis. A social network index was derived from information about the presence of a spouse or intimate partner, religious ties, community participation, friendship ties, and numbers of living relatives. Diversity was assessed as variety of ties, independent of size. We used logistic regression to evaluate associations with outcomes and evaluated whether effect estimates differed using meta-analytic techniques. Associations were similar across cohorts though analyses of smoking and alcohol included US cohorts only because of low prevalence of these behaviors in the Shanghai cohort. Socially isolated women were more likely to be obese (OR = 1.21, 95% CI:1.03-1.42), have low physical activity (<10 MET-hours/week, OR = 1.55, 95% CI:1.36-1.78), be current smokers (OR = 2.77, 95% CI:2.09-3.68), and have high alcohol intake (≥15 g/d, OR = 1.23, 95% CI:1.00-1.51), compared with socially integrated women. Among node positive cases from three cohorts, socially isolated women were more likely not to receive chemotherapy (OR = 2.10, 95% CI:1.30-3.39); associations differed in a fourth cohort. Other associations (nonsignificant) were consistent with less intensive treatment in socially isolated women. Low social network diversity was independently associated with more adverse lifestyle, but not clinical, factors. Small, less diverse social networks measured post-diagnosis were associated with more adverse lifestyle factors and less intensive cancer treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Physical Activity and Risk of Male Breast Cancer.

The association between leisure-time physical activity (LTPA) and male breast cancer risk is unclear. In the Male Breast Cancer Pooling Project, with 449 cases and 13,855 matched controls, we used logistic regression with study stratification to generate adjusted ORs and 95% confidence intervals (CI) for LTPA tertiles and male breast cancer risk. Compared with low LTPA, medium and high LTPA were not associated with male breast cancer risk (OR, 1.01; 95% CI, 0.79-1.29; 0.90, 0.69-1.18, respectively). In joint-effects analyses, compared with the referent of high body mass index (BMI; ≥25 kg/m(2))/low LTPA, neither medium nor high PA was associated with risk among high BMI men, but normal BMI men (<25 kg/m(2)) with low or medium LTPA were at a nonsignificant ∼16% reduced risk and those with high LTPA were at a 27% reduced risk (OR, 0.73; 95% CI, 0.50-1.07). Physical activity alone may not confer protection against male breast cancer risk.

Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk.

Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers.

Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium.

The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) ORs and 95% confidence intervals (CI), which were then combined using fixed-effects meta-analysis. Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one subanalysis of very high recent alcohol consumption (>60 g/day) was tentatively associated with male breast cancer (ORunexposed referent = 1.29; 95% CI, 0.97-1.71; OR>0-<7 g/day referent = 1.36; 95% CI, 1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. In this analysis of the Male Breast Cancer Pooling Project, we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.

Abstract 2182: Lifestyle factors are associated with late breast cancer outcomes among 5-year survivors of estrogen-receptor positive breast cancer

Abstract Background: Estrogen-receptor (ER)+ breast cancers have a favorable prognosis in the first several years after diagnosis, with adjuvant endocrine therapies for treatment. However, in later years, ER+ breast cancer is associated with poorer prognosis compared to ER- breast cancer. Predictors of late recurrence in women with ER+ breast cancer, and in particular lifestyle factors, have been little studied. Using data from a pooling project of breast cancer survivor cohorts (After Breast Cancer Pooling Project), we prospectively evaluated the association of post-diagnosis lifestyle factors and comorbidities with late breast cancer outcomes. Methods: Analyses included 6,129 women diagnosed with stage I-III invasive ER+ breast cancer (1990-2004) from three US prospective cohorts, who survived disease-free for five years. Pooled and harmonized data were available for post-diagnosis lifestyle factors, comorbidities, cancer treatment, tumor characteristics, and socio-demographics. Late outcomes (defined as &amp;gt;5 years post-diagnosis) included breast cancer recurrence, breast cancer specific-mortality (BCSM), and all-cause mortality. Lifestyle factors and comorbidities were assessed at a mean of about 2 years post-diagnosis. Study heterogeneity was evaluated by the Q statistic. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models stratified by study. Results: After a median follow-up of 6.9 years (11.9 years post-diagnosis), 645 deaths and 564 recurrences were documented. Five-year recurrence and all-cause mortality rates were 7.2% and 6.1%, respectively. Ten-year recurrence and all-causes mortality rates were 12.1% and 15.4%, respectively. In multivariable models, recreational physical activity (PA) of 10-MET h/wk was associated with reduced all-cause mortality (HR: 0.71, 95% CI: 0.60-0.84) and BCSM (HR: 0.77, 95% CI: 0.61-0.99), and non-significantly reduced recurrence risk (HR: 0.87, 95% CI: 0.73-1.03). Multivitamin and antioxidant vitamin supplement use were inversely associated with recurrence (HRs (95% CIs): 0.74 (0.62-0.87) and 0.75 (0.61-0.91), respectively). Current smoking was associated with increased risk of all-cause and BCSM ((HRs (95% CIs): 2.58 (1.99-3.35)) and 1.87 (1.22-2.88), respectively). Women with diabetes had increased risk of late outcomes (HRs 95% CIs: 1.35 (0.95-1.92) for recurrence, 1.86 (1.45-2.40) for all-cause mortality, and 1.75 (1.12-2.73) for BCSM. Hypertension was significantly associated with all-cause mortality only (HR: 1.42, 95% CI: 1.19-1.70). Obesity (BMI ≥30 kg/m2) was not associated with late outcomes. Conclusion: In this large study, post-diagnosis lifestyle factors were important predictors of late breast cancer outcomes. Our findings suggest PA and multivitamin use may improve long-term prognosis for ER-positive breast cancer. Citation Format: Sarah J. Nechuta, Wendy Y. Chen, Marilyn L. Kwan, Elizabeth M. Poole, Shirley W. Flatt, John P. Pierce, Bette J. Caan, Xiao Ou Shu. Lifestyle factors are associated with late breast cancer outcomes among 5-year survivors of estrogen-receptor positive breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2182. doi:10.1158/1538-7445.AM2014-2182

Postdiagnosis social networks and lifestyle and treatment mechanisms in the Ater Breast Cancer Pooling Project (ABCPP).

115 Background: Larger social networks have been associated with better breast cancer survival. To investigate potential mediators, we evaluated associations of social network size and diversity with lifestyle and treatment factors associated with prognosis. Methods: We included 9,331 women from the After Breast Cancer Pooling Project who provided data on social networks within two years following diagnosis. A social network index was derived from information about the presence of a spouse or intimate partner, religious ties, community participation, friendship ties, and numbers of relatives. Diversity was assessed as variety of ties, independent of size. We used logistic regression to evaluate associations with outcomes and evaluated whether effect estimates differed using meta-analytic techniques. Results: Associations of social networks and outcomes generally did not differ by cohort. Because of the low prevalence of smoking and alcohol consumption in the Shanghai cohort, however, analyses of smoking and alcohol included US cohorts only. Women who were socially isolated (small networks) were more likely to be obese (body mass index&gt;30 kg/m2, OR=1.21, 95% CI:1.03-1.42) and have low physical activity (&lt;10 MET-h/wk, OR=1.53, 95% CI:1.34-1.75) compared to socially integrated women. Women with low network diversity were more likely to be current smokers (OR=3.68, 95% CI:2.19-6.19) and have high alcohol consumption (&gt;15 g/d alcohol, OR=2.43, 95% CI:1.60-3.69). Among node positive cases, socially isolated women were more likely not to receive chemotherapy (OR=1.52, 95% CI:1.03-2.25). By contrast, low network diversity, but not social network size, was associated with greater odds of not receiving adjuvant hormonal therapy (OR=1.52, 95% CI:1.03-2.23). Associations with surgery were nonsignificant. Conclusions: In a large pooled cohort, small, less diverse social networks measured post-diagnosis were associated with more adverse lifestyle factors and less intensive cancer treatment, which may help to explain poorer breast cancer prognosis in socially isolated women.

Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results

The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors. In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design-specific (case-control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided. Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86). Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.

Lifetime Cigarette Smoking and Breast Cancer Prognosis in the After Breast Cancer Pooling Project

There is controversy on whether former smokers have increased risk for breast cancer recurrence or all-cause mortality, regardless of how much they smoked. Data were from three US cohorts in the After Breast Cancer Pooling Project, with detailed information on smoking among 9975 breast cancer survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed entry Cox proportional hazards models were used to examine the relationships of smoking status, cigarettes per day, years of smoking, and pack years with breast cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and overall mortality (n = 1803). Compared with never smokers, former smokers with less than 20 pack-years of exposure had no increased risk of any outcome. However, former smokers with 20 to less than 34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26% increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former smokers with 35 or more pack-years of exposure, the probability of recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to 1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to 2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54). Lifetime cigarette smoking was statistically significantly associated with a poor prognosis among women diagnosed with breast cancer, dose-dependent increased risks of recurrence, and breast cancer and all-cause mortality.

Postdiagnosis Cruciferous Vegetable Consumption and Breast Cancer Outcomes: A Report from the After Breast Cancer Pooling Project

Cruciferous vegetables are a major source of glucosinolate-derived bioactive compounds such as isothiocyanates, which have been shown in animal and in vitro studies to inhibit cancer growth and progression. Few studies have investigated cruciferous vegetable intake after diagnosis and breast cancer outcomes. Using data from the After Breast Cancer Pooling Project, which includes prospective data from U.S. and Chinese breast cancer survivors, we evaluated the association of cruciferous vegetables with breast cancer outcomes. Analyses included 11,390 women diagnosed with stage I-III invasive breast cancer (1990-2006) from four cohorts. Cruciferous vegetable intake (g/day) was assessed using food frequency questionnaires (mean of 22 months postdiagnosis). Study heterogeneity was evaluated by the Q statistic; hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using delayed-entry Cox regression models stratified by study. After a median follow-up of 9.0 years, 1,725 deaths and 1,421 recurrences were documented. In pooled analyses using study-specific quartiles, cruciferous vegetable intake was not associated with breast cancer outcomes, adjusting for known clinical prognostic factors and selected lifestyle factors. HRs (95% CIs) by increasing quartiles (reference = lowest quartile) were 1.08 (0.93-1.25), 1.01 (0.87-1.18), and 1.10 (0.95-1.28) for recurrence (P(trend) = 0.34) and 1.01 (0.88-1.15), 0.97 (0.84-1.11), and 0.99 (0.86-1.13) for total mortality (P(trend) = 0.84). No associations were observed for subgroups defined by estrogen receptor status, stage, or tamoxifen therapy. Cruciferous vegetable intake at approximately two years after diagnosis was not associated with recurrence or mortality. Our results do not support an association between postdiagnosis cruciferous vegetable intake and breast cancer outcomes.

Postdiagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project

Vitamin supplement use after breast cancer diagnosis is common, but little is known about long-term effects on recurrence and survival. We examined postdiagnosis supplement use and risk of death or recurrence in the After Breast Cancer Pooling Project, a consortium of four cohorts of 12,019 breast cancer survivors from the United States and China. Post-treatment supplement use (vitamins A, B, C, D, E, and multivitamins) was assessed 1-5 years postdiagnosis. Associations with risk of recurrence, breast cancer-specific mortality, or total mortality were analyzed in Cox proportional hazards models separately by cohort. Individual cohort results were combined using random effects meta-analysis. Interactions with smoking, treatment, and hormonal status were examined. In multivariate models, vitamin E was associated with a decreased risk of recurrence (RR: 0.88; 95 % CI 0.79-0.99), and vitamin C with decreased risk of death (RR: 0.81; 95 % CI 0.72-0.92). However, when supplements were mutually adjusted, all associations were attenuated. There were no statistically significant associations with breast cancer mortality. The use of antioxidant supplements (multivitamins, vitamin C, or E) was not associated with recurrence, but was associated with a 16 % decreased risk of death (95 % CI 0.72-0.99). In addition, vitamin D was associated with decreased risk of recurrence among ER positive, but not ER negative tumors (p-interaction = 0.01). In this large consortium of breast cancer survivors, post-treatment use of vitamin supplements was not associated with increased risk of recurrence or death. Post-treatment use of antioxidant supplements was associated with improved survival, but the associations with individual supplement were difficult to determine. Stratification by ER status and considering antioxidants as a group may be more clinically relevant when evaluating associations with cancer risk and mortality.

Postdiagnosis Alcohol Consumption and Breast Cancer Prognosis in the After Breast Cancer Pooling Project

Alcohol consumption is an established risk factor for incident breast cancer. However, its role in breast cancer prognosis remains unclear. We conducted an investigation of postdiagnosis alcohol consumption with recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. Women were diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors from three prospective US cohorts. Alcohol intake was assessed at cohort entry (mean 2.1 years postdiagnosis) using a food frequency questionnaire. HR and 95% confidence intervals (CI) were estimated using delayed entry Cox proportional hazards models with adjustment for known prognostic factors. After a mean follow-up of 10.3 years, 1,646 recurrences and 1,543 deaths were ascertained. 5,422 women (58%) were considered drinkers (≥0.36 g/day of alcohol, ≥0.25 drinks/week) with a median of 5.3 g/day. Overall, compared with nondrinking, regular alcohol intake (≥6.0 g/day) was not associated with risk of recurrence (HR for 6 to less than 12 g/day, 1.03; 95% CI, 0.86-1.24; HR for 12 to less than 24 g/day, 1.12; 95% CI, 0.93-1.34; HR for ≥24 g/day, 1.04; 95% CI, 0.84-1.31). However, risk varied significantly by menopausal status (P for interaction < 0.05). Postmenopausal women who regularly consumed alcohol (≥6.0 g/day) had increased risk of recurrence (HR, 1.19; 95% CI, 1.01-1.40). Alcohol intake was not associated with mortality. Regular alcohol consumption was not associated with breast cancer recurrence and total mortality overall, yet recurrence risk was only elevated in postmenopausal women. The association between alcohol intake and recurrence may depend on menopausal status at breast cancer diagnosis.

Highlights of This Issue

Although alcohol consumption is an established risk factor for incident breast cancer, its role in breast cancer prognosis is unclear. Kwan and colleagues evaluated postdiagnosis alcohol consumption with both cancer recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. The authors report that regular alcohol intake was not associated with risk of breast cancer recurrence; however, postmenopausal women who regularly consumed alcohol had increased risk of recurrence.There is a positive association between calcium intake and prostate cancer risk. Rowland and colleagues evaluated whether this association was modified by particular vitamin D receptor (VDR) genotypes that influence calcium absorption. Among men with a low calcium absorption VDR genotype, those in the lowest quartile of calcium intake had a 50% reduction in prostate cancer risk compared with those in the upper quartiles of calcium intake. These findings are consistent with the hypothesis that genetic determinants of calcium absorption influence prostate cancer risk and may contribute to racial disparities in prostate cancer incidence and mortality rates.The interpretation of uterine cancer rates is complicated because risk estimates often include women who have already undergone hysterectomies. To address this, Siegel and colleagues used population-based cancer registries, U.S. Census data and data from the Behavioral Risk Factor Surveillance System to estimate hysterectomy-corrected, age-adjusted uterine cancer rates. The authors report that stateby-state hysterectomy-corrected uterine cancer incidence rates were consistently higher than uncorrected rates. Failure to adjust uterine cancer rates for hysterectomy prevalence distorts the true geographic and racial patterns.There is strong association between high viral load (VL) of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS), yet little data is available regarding HPV16 and invasive SCC. Sundström and colleagues evaluated HPV16 VL in women with CIS and invasive SCC and found low VLs were common among both CIS and SCC cases. In SCC cases, high HRV16 VL conferred increased risk, but only from 3 years before diagnosis, which differs considerably from CIS cases. HPV16 VL dynamics are complex in SCC, which may limit its use in screening.

Weight Change and Survival after Breast Cancer in the After Breast Cancer Pooling Project

Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of postdiagnostic weight variation on survival, we examined the relationship by comorbid status and initial body mass index (BMI). The current analysis included 12,915 patients with breast cancer diagnosed between 1990 and 2006 with stage I-III tumors from four prospective cohorts in the United States and China. HRs and 95% confidence intervals (CI) representing the associations of five weight change categories [within <5% (reference); 5%-<10% and ≥10% loss and gain] with mortality were estimated using Cox proportional hazards models. Mean weight change was 1.6 kg. About 14.7% women lost and 34.7% gained weight. Weight stability in the early years postdiagnosis was associated with the lowest overall mortality risk. Weight loss ≥10% was related to a 40% increased risk of death (HR, 1.41; 95% CI, 1.14-1.75) in the United States and over three times the risk of death (HR, 3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by prediagnosis BMI, and in the United States, lower survival was seen for women who lost weight and had comorbid conditions. Weight gain ≥10% was associated with a nonsignificant increased risk of death. Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. Weight control strategies for breast cancer survivors should be personalized to the individual's medical history.

Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women

Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer-specific mortality and a statistically significant reduced risk of recurrence.

Pre-diagnosis body mass index and survival after breast cancer in the After Breast Cancer Pooling Project

Obese and underweight women who develop breast cancer may have poorer survival compared with normal-weight women. However, the optimal weight for best prognosis is still under study. We conducted a prospective investigation of pre-diagnosis body mass index (BMI) and mortality among 14,948 breast cancer patients in the After Breast Cancer Pooling Project. Breast cancer patients diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors were drawn from four prospective cohorts. Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of BMI categories (World Health Organization international classifications) with recurrence and mortality were estimated using delayed entry Cox proportional hazards models. Obese (30 to < 35 kg/m(2)), severely obese (35 to < 40 kg/m(2)), and morbidly obese (≥ 40 kg/m(2)) were examined. After a mean follow-up of 7.8 years, 2,140 deaths and 2,065 recurrences were documented. Both underweight (HR = 1.59; 95% CI: 1.18, 2.13) and morbidly obese women (HR = 1.81; 95% CI: 1.42, 2.32) had the greatest risk of overall mortality compared with normal weight (18.5-24.9 kg/m(2)) women. Severe obesity (HR = 1.09; 95% CI: 0.88, 1.36) and obesity (HR = 1.11; 95% CI: 0.97, 1.27) were related to small non-significant increased risks. Overweight (25.0-29.9 kg/m(2)) was not associated with any excess risk compared with normal weight. Similar associations were found for breast cancer death and non-breast cancer death but not recurrence. Women who were underweight and morbidly obese before breast cancer diagnosis were at the greatest risk of all-cause mortality. Morbidly obese women were also at increased risk of death from breast cancer. These results suggest that degree of obesity confers differential risk on survival.

P1-08-02: Pre-Diagnosis Body Mass Index and Breast Cancer Prognosis and Survival: Report from the after Breast Cancer Pooling Project.

Abstract Background: A large body of evidence dating back over 30 years suggests that obese women have poorer survival after a breast cancer (BC) diagnosis compared to non-obese women. Despite most studies supporting an association of elevated risk of overall mortality with obesity, the relationship of obesity with risk of BC recurrence, BC mortality and non-BC mortality remains unclear. Furthermore, reports suggest that the association of BMI with BC outcomes may be U or J shaped, prompting the necessity of examining underweight and more severely obese women as independent groups. We conducted a pooled investigation of pre-diagnosis BMI and BC recurrence and survival using data from the After Breast Cancer Pooling Project (ABCPP). Materials and Methods: The ABCPP includes 14,950 BC survivors from four prospective cohorts (three US and one Shanghai, China) diagnosed from 1990–2006 with invasive primary AJCC Stage I-III BC at ages 20–83 years. A random effects meta-analysis was conducted to assess heterogeneity across studies and poolability of data. Delayed entry Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of pre-diagnosis BMI (underweight &amp;lt;18.5 kg/m2, normal 18.5-&amp;lt;25 kg/m2, overweight 25-&amp;lt;30 kg/m2, obese ≥30 kg/m2) with BC recurrence, BC death, non-BC death, and overall death, adjusted for age at diagnosis, stage, race/ethnicity, menopausal status, hormone receptor status, number of positive lymph nodes, treatment, smoking history, and comorbidity (diabetes, hypertension, and/or CVD). Subgroup analyses further divided the obesity group into obese (30-&amp;lt;35 kg/m2), severely obese (35-&amp;lt;40 kg/m2), and morbidly obese (≥40 kg/m2) categories. Results: No heterogeneity in effect estimates by study was found. 2104 deaths (1416 BC-related) and 2320 recurrences were observed after a mean (SD) of 7.66 (3.95) years of follow-up. Both underweight and obese women had a statistically significant increased risk of overall death compared to normal-weight women (underweight HR=1.69; 95% CI: 1.25, 2.28 and obese HR=1.22; 95% CI: 1.08, 1.38; p for nonlinear association&amp;lt;0.01). Similar associations were found for non-BC death. Obese but not underweight was associated with increased risk of BC death (HR=1.17; 95% CI: 1.01, 1.36) and recurrence (HR=1.11; 95% CI: 0.98, 1.26). When examining finer obesity categories, the morbidly obese women had the greatest risk for all outcomes (overall death HR=1.90; 95% CI: 1.48, 2.45; non-BC death HR= 3.27; 95% CI: 2.25, 4.77; BC death HR = 1.47; 95% CI: 1.05, 2.06; recurrence HR = 1.27; 95% CI: 0.95, 1.71). No effect modification was observed by menopausal status, hormone receptor status, chemotherapy, and smoking. In all analyses, overweight women had similar risk of outcomes compared to normal-weight women. Discussion: In this large pooling study of nearly 15,000 BC survivors, we found that the association between BMI and BC outcomes, specifically overall death and non-BC death, was U shaped with both underweight and obese women at greatest risk. Morbidly obese women were at even greater risk compared to other obesity groups. Maintaining a healthy weight throughout adult life may be beneficial for BC prognosis and survival. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-02.