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

Loop corrections for Kaluza-Klein AdS amplitudes

Recently we conjectured the four-point amplitude of graviton multiplets in ${\rm AdS}_5 \times {\rm S}^5$ at one loop by exploiting the operator product expansion of $\mathcal{N}=4$ super Yang-Mills theory. Here we give the first extension of those results to include Kaluza-Klein modes, obtaining the amplitude for two graviton multiplets and two states of the first KK mode. Our method again relies on resolving the large N degeneracy among a family of long double-trace operators, for which we obtain explicit formulas for the leading anomalous dimensions. Having constructed the one-loop amplitude we are able to obtain a formula for the one-loop corrections to the anomalous dimensions of all twist five double-trace operators.Comment: 37 pages. One ancillary file containing data on the correlator

Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women

Abstract Introduction The association of breast cancer patients’ mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality. Methods We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of ER examined here included the percentage of tumor cell nuclei positively stained for ER, ER Histo (H)-score, and a score based on an adaptation of an equation presented by Cuzick and colleagues, which combines weighted values of ER H-score, percentage of tumor cell nuclei positively stained for the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) results. This is referred to as the ER/PR/HER2 score. Results After controlling for age at diagnosis, race, study site, tumor stage, and histologic grade in multivariable Cox proportional hazards regression models, both percentage of tumor cell nuclei positively stained for ER (P trend = 0.0003) and the ER H-score (P trend = 0.0004) were inversely associated with breast cancer-specific mortality risk. The ER/PR/HER2 score was positively associated with breast cancer-specific mortality risk in women with ER + tumor (P trend = 0.001). Analyses by race revealed that ER positivity was associated with reduced risk of breast cancer-specific mortality in white women and black women. The two quantitative measures for ER alone provided additional discrimination in breast cancer-specific mortality risk only among white women with ER + tumors (both P trend ≤ 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (P trend = 0.01) and black women (P trend = 0.03) with ER + tumors. Conclusions Our data support quantitative immunohistochemical measures of ER, especially the ER/PR/HER2 score, as a more precise predictor for breast cancer-specific mortality risk than a simple determination of ER positivity

The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors - results of a prospective study

<p>Abstract</p> <p>Background</p> <p>Few data exist on survival or health-related quality of life (QOL) related to herbal remedy use among long-term breast cancer survivors. The objective of this report is to examine whether herbal remedy use is associated with survival or the health-related QOL of these long-term breast cancer survivors.</p> <p>Methods</p> <p>In 1999-2000, we collected the information of herbal remedy use and QOL during a telephone interview with 371 Los Angeles Non-Hispanic/Hispanic white women who had survived more than 10 years after breast cancer diagnosis. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. Patients were followed for mortality from the baseline interview through 2007. 299 surviving patients completed a second telephone interview on QOL in 2002-2004. We used multivariable Cox proportional hazards methods to estimate relative risks (RR) and 95% confidence intervals (CI) for mortality and applied multivariable linear regression models to compare average SF-36 change scores (follow-up - baseline) between herbal remedy users and non-users.</p> <p>Results</p> <p>Fifty-nine percent of participants were herbal remedy users at baseline. The most commonly used herbal remedies were echinacea, herbal teas, and ginko biloba. Herbal remedy use was associated with non-statistically significant increases in the risks for all-cause (44 deaths, RR = 1.28, 95% CI = 0.62-2.64) and breast cancer (33 deaths, RR = 1.78, 95% CI = 0.72-4.40) mortality. Both herbal remedy users' and non-users' mental component summary scores on the SF-36 increased similarly from the first survey to the second survey (<it>P </it>= 0.16), but herbal remedy users' physical component summary scores decreased more than those of non-users (-5.7 vs. -3.2, <it>P </it>= 0.02).</p> <p>Conclusions</p> <p>Our data provide some evidence that herbal remedy use is associated with poorer survival and a poorer physical component score for health-related QOL among women who have survived breast cancer for at least 10 years. These conclusions are based on exploratory analyses of data from a prospective study using two-sided statistical tests with no correction for multiple testing and are limited by few deaths for mortality analysis and lack of information on when herbal remedy use was initiated or duration of or reasons for use.</p

Pregnancy-related factors and the risk of breast carcinoma in situ and invasive breast cancer among postmenopausal women in the California Teachers Study cohort

Abstract Introduction Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear. Methods Among 52,464 postmenopausal women participating in the California Teachers Study (CTS), 624 were diagnosed with breast carcinoma in situ (CIS) and 2,828 with invasive breast cancer between 1995 and 2007. Multivariable Cox proportional hazards regression methods were used to estimate relative risks associated with parity, age at first full-term pregnancy, breastfeeding, nausea or vomiting during pregnancy, and preeclampsia. Results Compared with never-pregnant women, an increasing number of full-term pregnancies was associated with greater risk reduction for both breast CIS and invasive breast cancer (both P trend &lt; 0.01). Women having four or more full-term pregnancies had a 31% lower breast CIS risk (RR = 0.69, 95% CI = 0.51 to 0.93) and 18% lower invasive breast cancer risk (RR = 0.82, 95% CI = 0.72 to 0.94). Parous women whose first full-term pregnancy occurred at age 35 years or later had a 118% greater risk for breast CIS (RR = 2.18, 95% CI = 1.36 to 3.49) and 27% greater risk for invasive breast cancer (RR = 1.27, 95% CI = 0.99 to 1.65) than those whose first full-term pregnancy occurred before age 21 years. Furthermore, parity was negatively associated with the risk of estrogen receptor-positive (ER+) or ER+/progesterone receptor-positive (PR+) while age at first full-term pregnancy was positively associated with the risk of ER+ or ER+/PR+ invasive breast cancer. Neither of these factors was statistically significantly associated with the risk of ER-negative (ER-) or ER-/PR- invasive breast cancer, tests for heterogeneity between subtypes did not reach statistical significance. No clear associations were detected for other pregnancy-related factors. Conclusions These results provide some epidemiologic evidence that parity and age at first full-term pregnancy are involved in the development of breast cancer among postmenopausal women. The role of these factors in risk of in situ versus invasive, and hormone receptor-positive versus -negative breast cancer merits further exploration

Estrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study report

<p>Abstract</p> <p>Background</p> <p>It remains unclear whether estrogenic botanical supplement (EBS) use influences breast cancer survivors' health-related outcomes.</p> <p>Methods</p> <p>We examined the associations of EBS use with health-related quality of life (HRQOL), with fatigue, and with 15 hormone-related symptoms such as hot flashes and night sweats among 767 breast cancer survivors participating in the Health, Eating, Activity, and Lifestyle (HEAL) Study. HRQOL was measured by the Medical Outcomes Study short form-36 physical and mental component scale summary score. Fatigue was measured by the Revised-Piper Fatigue Scale score.</p> <p>Results</p> <p>Neither overall EBS use nor the number of EBS types used was associated with HRQOL, fatigue, or hormone-related symptoms. However, comparisons of those using each specific type of EBS with non-EBS users revealed the following associations. Soy supplements users were more likely to have a better physical health summary score (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.02-2.70). Flaxseed oil users were more likely to have a better mental health summary score (OR = 1.76, 95% CI = 1.05-2.94). Ginseng users were more likely to report severe fatigue and several hormone-related symptoms (all ORs ≥ 1.7 and all 95% CIs exclude 1). Red clover users were less likely to report weight gain, night sweats, and difficulty concentrating (all OR approximately 0.4 and all 95% CIs exclude 1). Alfalfa users were less likely to experience sleep interruption (OR = 0.28, 95% CI = 0.12-0.68). Dehydroepiandrosterone users were less likely to have hot flashes (OR = 0.33, 95% CI = 0.14-0.82).</p> <p>Conclusions</p> <p>Our findings indicate that several specific types of EBS might have important influences on a woman's various aspects of quality of life, but further verification is necessary.</p

Recreational physical activity and risk of triple negative breast cancer in the California Teachers Study

BACKGROUND: Evidence has accumulated showing that recreational physical activity reduces breast cancer risk. However, it is unclear whether risk reduction pertains to specific receptor-defined subtypes. Moreover, few studies have examined whether changes in the amount of recreational physical activity during adulthood influence breast cancer risk. METHODS: A total of 108,907 women, ages 22 to 79 years with no history of breast cancer when joining the California Teachers Study in 1995–1996, completed a baseline questionnaire and were eligible for the study. Through 2012, 5882 women were diagnosed with invasive breast cancer. Breast cancer subtypes were defined by the expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Multivariable Cox proportional hazards models provided adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) for breast cancer overall and ER/PR/HER2-defined subtypes associated with long-term (from high school through age 54 or age at cohort entry, whichever was younger) and baseline (during 3 years prior to baseline) recreational physical activity. Among women who also completed a follow-up questionnaire at 10 years after baseline in 2005–2008 (54,686 women, 1406 with invasive breast cancer), risk associated with changes in the amount of recreational physical activity from baseline to the 10-year follow-up (during 3 years prior to the 10-year follow-up) was determined. RESULTS: Both long-term and baseline strenuous recreational physical activity were inversely associated with risk of invasive breast cancer (P(trend) ≤0.03). The observed associations were mainly confined to women with triple negative breast cancer (TNBC, ER–/PR–/HER2–, P(trend) ≤0.02) or luminal A-like subtype (ER+ or PR+ plus HER2–) who were former users of menopausal hormone therapy at baseline (P(trend) = 0.02, P(homogeneity of trends) ≤0.03). Moreover, women who consistently engaged in the highest level (≥3.51 h/wk/y) of strenuous recreational physical activity between baseline and 10-year follow-up had the lowest risk of breast cancer (HR = 0.71, 95 % CI = 0.52–0.98) when compared to those who were consistently low (≤0.50 h/wk/y). CONCLUSIONS: Strenuous recreational physical activity is associated with lower breast cancer risk, especially TNBC. The benefit may be maximized by consistently engaging in high-intensity recreational physical activity during adulthood. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0723-3) contains supplementary material, which is available to authorized users