Yani Lu

Obesity and Survival Among Black Women and White Women 35 to 64 Years of Age at Diagnosis With Invasive Breast Cancer

PURPOSE To evaluate the effect of obesity on survival among black women and white women with invasive breast cancer and to determine whether obesity explains the poorer survival of black women relative to white women. PATIENTS AND METHODS We observed 4,538 (1,604 black, 2,934 white) women who were 35 to 64 years of age when diagnosed with incident invasive breast cancer between 1994 and 1998. Multivariate Cox regression models were used to examine the effect of body mass index (BMI, in kilograms per square meter) 5 years before diagnosis on risk of death from any cause and from breast cancer. RESULTS During a median of 8.6 years of follow-up, 1,053 women died (519 black, 534 white), 828 as a result of breast cancer (412 black, 416 white). Black women were more likely to die than white women (multivariate-adjusted relative risk [RR], 1.33; 95% CI, 1.16 to 1.53). Compared with women with BMI of 20 to 24.9 kg/m(2), those who were obese (BMI ≥ 30 kg/m(2)) had a greater risk of all-cause mortality (RR, 1.23; 95% CI, 1.04 to 1.47) and breast cancer-specific mortality (RR, 1.20; 95% CI, 0.99 to 1.46). These associations were observed among white women (all-cause RR, 1.54; 95% CI, 1.21 to 1.96; breast cancer RR, 1.46; 95% CI, 1.11 to 1.92), but not among black women (all-cause RR, 1.03; 95% CI, 0.81 to 1.29; breast cancer RR, 1.02; 95% CI, 0.79 to 1.33). CONCLUSION Obesity may play an important role in mortality among white but not black patients with breast cancer. It is unlikely that differences in obesity distributions between black women and white women account for the poorer survival of black women.

Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study

To lend clarity to inconsistent prior findings of an inverse association between ultraviolet radiation (UVR) exposure and risk of lymphoid malignancies, we examined the association of prospectively ascertained residential ambient UVR exposure with risk of non-Hodgkin lymphomas (NHLs), multiple myeloma (MM), and classical Hodgkin lymphoma in the California Teachers Study cohort. Among 121 216 eligible women, 629 were diagnosed with NHL, 119 with MM, and 38 with Hodgkin lymphoma between 1995-1996 and 2007. Cox proportional hazards regression was used to estimate incidence rate ratios (RRs) with 95% confidence intervals (CIs). Residential UVR levels within a 20-km radius were associated with reduced risk of overall NHL (RR for highest vs lowest statewide quartile of minimum UVR [≥ 5100 vs < 4915 W-h/m(2)], 0.58; 95% CI, 0.42-0.80), especially diffuse large B-cell lymphoma (RR, 0.36; 95% CI, 0.17-0.78) and chronic lymphocytic leukemia/small lymphocytic lymphoma (RR, 0.46; 95% CI, 0.21-1.01), and MM (RR for maximum UVR, 0.57; 95% CI, 0.36-0.90). These associations were not modified by skin sensitivity to sunlight, race/ethnicity, body mass index, or neighborhood socioeconomic status. Dietary vitamin D also was not associated with risk of lymphoid malignancies. These results support a protective effect of routine residential UVR exposure against lymphomagenesis through mechanisms possibly independent of vitamin D.

Body Size, Recreational Physical Activity, and B-Cell Non-Hodgkin Lymphoma Risk Among Women in the California Teachers Study

Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22-84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61-1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.

Diabetes and other comorbidities in breast cancer survival by race/ethnicity: The California Breast Cancer Survivorship Consortium (CBCSC)

Background: The role of comorbidities in survival of patients with breast cancer has not been well studied, particularly in non-white populations. Methods: We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated HRs and 95% confidence intervals (CI) for overall and breast cancer–specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction. Results: Risk of breast cancer–specific mortality increased among breast cancer cases with a history of diabetes (HR, 1.48; 95% CI, 1.18–1.87) or myocardial infarction (HR, 1.94; 95% CI, 1.27–2.97). Risk patterns were similar across race/ethnicity (non-Latina white, Latina, African American, and Asian American), body size, menopausal status, and stage at diagnosis. In subgroup analyses, risk of breast cancer–specific mortality was significantly elevated among cases with diabetes who received neither radiotherapy nor chemotherapy (HR, 2.11; 95% CI, 1.32–3.36); no increased risk was observed among those who received both treatments (HR, 1.13; 95% CI, 0.70–1.84; Pinteraction = 0.03). A similar pattern was found for myocardial infarction by radiotherapy and chemotherapy (Pinteraction = 0.09). Conclusion: These results may inform future treatment guidelines for patients with breast cancer with a history of diabetes or myocardial infarction. Impact: Given the growing number of breast cancer survivors worldwide, we need to better understand how comorbidities may adversely affect treatment decisions and ultimately outcome. Cancer Epidemiol Biomarkers Prev; 24(2); 361–8. ©2014 AACR.

Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status.

BackgroundBlack women are more likely than white women to have an aggressive subtype of breast cancer that is associated with higher mortality and this may contribute to the observed black-white difference in mortality. However, few studies have investigated the black-white disparity in mortality risk stratified by breast cancer subtype, defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Furthermore, it is not known whether additional consideration of p53 protein status influences black-white differences in mortality risk observed when considering subtypes defined by ER, PR and HER2 status.MethodsFour biomarkers were assessed by immunohistochemistry in paraffin-embedded breast tumor tissue from 1,204 (523 black, 681 white) women with invasive breast cancer, aged 35–64 years at diagnosis, who accrued a median of 10 years’ follow-up. Multivariable Cox proportional hazards regression models were fit to assess subtype-specific black-white differences in mortality risk.ResultsNo black-white differences in mortality risk were observed for women with triple negative (ER-negative [ER-], PR-, and HER2-) subtype. However, older (50–64 years) black women had greater overall mortality risk than older white women if they had been diagnosed with luminal A (ER-positive [ER+] or PR+ plus HER2-) breast cancer (all-cause hazard ratio, HR, 1.88; 95% confidence interval, CI, 1.18 to 2.99; breast cancer-specific HR, 1.51; 95% CI, 0.83 to 2.74). This black-white difference among older women was further confined to those with luminal A/p53- tumors (all-cause HR, 2.22; 95% CI, 1.30 to 3.79; breast cancer-specific HR, 1.89; 95% CI, 0.93 to 3.86). Tests for homogeneity of race-specific HRs comparing luminal A to triple negative subtype and luminal A/p53- to luminal A/p53+ subtype did not achieve statistical significance, although statistical power was limited.ConclusionsOur findings suggest that the subtype-specific black-white difference in mortality risk occurs mainly among older women diagnosed with luminal A/p53- breast cancer, which is most likely treatable. These results further suggest that factors other than subtype may be relatively more important in explaining the increased mortality risk seen in older black women.

Reproductive factors and non-Hodgkin lymphoma risk in the California Teachers Study.

Background Non-Hodgkin lymphoma (NHL) is a malignancy etiologically linked to immunomodulatory exposures and disorders. Endogenous female sex hormones may modify immune function and influence NHL risk. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype. Methodology/Principal Findings Women in the California Teachers Study cohort provided detailed data in 1995–1996 on reproductive history. Follow-up through 2007 identified 574 women with incident B-cell NHL. Hazard rate ratios (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models to assess associations between reproductive factors and all B-cell NHL combined, diffuse large B-cell lymphomas, follicular lymphomas, and B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas. Pregnancy was marginally associated with lower risk of B-cell NHL (RR = 0.84, 95% CI = 0.68–1.04). Much of the reduction in risk was observed after one full-term pregnancy relative to nulligravid women (RR = 0.75, 95% CI = 0.54–1.06; P for trend <0.01), particularly for diffuse large B-cell lymphomas (P for trend = 0.13), but not among women who had only incomplete pregnancies. Age at first full-term pregnancy was marginally inversely associated with B-cell NHL risk overall (P for trend = 0.08) and for diffuse large B-cell lymphomas (P for trend = 0.056). Breast feeding was not associated with B-cell NHL risk overall or by subtype. Conclusions Full-term pregnancy and early age at first full-term pregnancy account for most of the observed reduction in B-cell NHL risk associated with gravidity. Pregnancy-related hormonal exposures, including prolonged and high-level exposure to progesterone during a full-term pregnancy may inhibit development of B-cell NHL.

Oral contraceptives, menopausal hormone therapy use and risk of B-cell non-Hodgkin lymphoma in the California Teachers Study†

We examined oral contraceptive (OC) and menopausal hormonal therapy (MHT) use in relation to risk of B‐cell non‐Hodgkin lymphoma (NHL). Women under age 85 years participating in the California Teachers Study with no history of hematopoietic cancer were followed from 1995 through 2007. A total of 516 of 114,131 women eligible for OC use analysis and 402 of 54,758 postmenopausal women eligible for MHT use analysis developed B‐cell NHL. Multivariable adjusted and age stratified Cox proportional hazards models were fit to estimate relative risks (RRs) and 95% confidence intervals (95% CI). Ever versus never OC use was marginally associated with lower B‐cell NHL risk, particularly among women first using OCs before age 25 years (RR = 0.72, 95% CI = 0.51–0.99); yet, no duration‐response effect was observed. No association was observed for ever versus never MHT use among postmenopausal women (RR = 1.05, 95% CI = 0.83–1.33) overall or by formulation (estrogen alone, ET, or estrogen plus progestin, EPT). Among women with no MHT use, having bilateral oophorectomy plus hysterectomy was associated with greater B‐cell NHL risk than having natural menopause (RR = 3.15, 95% CI = 1.62–6.13). Bilateral oophorectomy plus hysterectomy was not associated with risk among women who used ET or EPT. These results indicate that exogenous hormone use does not strongly influence B‐cell NHL risk.

Alcohol Consumption Over Time and Risk of Lymphoid Malignancies in the California Teachers Study Cohort

Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995-1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18-22 years, at ages 30-35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.

Cigarette Smoking, Passive Smoking, and Non-Hodgkin Lymphoma Risk: Evidence From the California Teachers Study

Epidemiologic studies conducted to date have shown evidence of a causal relation between smoking and non-Hodgkin lymphoma (NHL) risk. However, previous studies did not account for passive smoking exposure in the never-smoking reference group. The California Teachers Study collected information about lifetime smoking and household passive smoking exposure in 1995 and about lifetime exposure to passive smoking in 3 settings (household, workplace, and social settings) in 1997-1998. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models with follow-up through 2007. Compared with never smokers, ever smokers had a 1.11-fold (95% confidence interval (CI): 0.94, 1.30) higher NHL risk that increased to a 1.22-fold (95% CI: 0.95, 1.57) higher risk when women with household passive smoking were excluded from the reference category. Statistically significant dose responses were observed for lifetime cumulative smoking exposure (intensity and pack-years; both P s for trend = 0.02) when women with household passive smoking were excluded from the reference category. Among never smokers, NHL risk increased with increasing lifetime exposure to passive smoking (relative risk = 1.51 (95% CI: 1.03, 2.22) for >40 years vs. ≤5 years of passive smoking; P for trend = 0.03), particularly for follicular lymphoma (relative risk = 2.89 (95% CI: 1.23, 6.80); P for trend = 0.01). The present study provides evidence that smoking and passive smoking may influence NHL etiology, particularly for follicular lymphoma.

Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status

Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population‐based Womens Contraceptive and Reproductive Experiences Study. Self‐reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]‐hours per week. Our biomarker‐specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER‐positive (ER+) and of HER2‐negative (HER2−) subtypes (both Ptrend ≤ 0.04), but not with other subtypes (all Ptrend > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2–breast cancer decreased with increasing number of MET‐hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all Ptrend ≤ 0.06). The test for homogeneity of trends (HER2– vs. HER2+ ) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (Phomogeneity = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts.