Hormone receptor status of a first primary breast cancer predicts contralateral breast cancer risk in the WECARE study population

Abstract Background Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history. Methods The Women’s Environmental Cancer and Radiation Epidemiology Study is a population-based case-control study of 1521 CBC cases and 2212 individually-matched controls with unilateral breast cancer. Detailed information about breast cancer risk factors, treatment for and characteristics of first tumors, including estrogen receptor (ER) and progesterone receptor (PR) status, was obtained by telephone interview and medical record abstraction. Multivariable risk ratios (RRs) and 95% confidence intervals (CIs) were estimated in conditional logistic regression models, adjusting for demographics, treatment, and personal medical and family history. A subset of women was screened for BRCA1/2 mutations. Results Lobular histology of the first tumor was associated with a 30% increase in CBC risk (95% CI 1.0–1.6). Compared to women with ER+/PR+ first tumors, those with ER-/PR- tumors had increased risk of CBC (RR = 1.4, 95% CI 1.1–1.7). Notably, women with ER-/PR- first tumors were more likely to develop CBC with the ER-/PR- phenotype (RR = 5.4, 95% CI 3.0–9.5), and risk remained elevated in multiple subgroups: BRCA1/2 mutation non-carriers, women younger than 45 years of age, women without a breast cancer family history, and women who were not treated with tamoxifen. Conclusions Having a hormone receptor negative first primary breast cancer is associated with increased risk of CBC. Women with ER-/PR- primary tumors were more likely to develop ER-/PR- CBC, even after excluding BRCA1/2 mutation carriers. Hormone receptor status, which is routinely evaluated in breast tumors, may be used clinically to determine treatment protocols and identify patients who may benefit from increased surveillance for CBC

Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women's Environmental Cancer and Radiation Epidemiology Study.

Purpose The Women's Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic regression. Cumulative absolute risks (ARs) were estimated by combining RRs from the WECARE Study and population-based SEER*Stat cancer incidence data. Results Women with any first-degree relative with breast cancer had a 10-year AR of 8.1% for CBC (95% CI, 6.7% to 9.8%). Risks also were increased if the relative was diagnosed at an age younger than 40 years (10-year AR, 13.5%; 95% CI, 8.8% to 20.8%) or with CBC (10-year AR, 14.1%; 95% CI, 9.5% to 20.7%). These risks are comparable with those seen in BRCA1/2 deleterious mutation carriers (10-year AR, 18.4%; 95% CI, 16.0% to 21.3%). In the subset of women who tested negative for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2, estimates were unchanged. Adjustment for known breast cancer single-nucleotide polymorphisms did not affect estimates. Conclusion Breast cancer family history confers a high CBC risk, even after excluding women with deleterious mutations. Clinicians are urged to use detailed family histories to guide treatment and future screening decisions for young women with breast cancer

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Dietary and Reproductive Risk Factors for Breast Cancer in the Nurses' Health Studies

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death among US women. Several hormonal, anthropometric, lifestyle, and genetic factors are known to be associated with breast cancer, though these associations may differ by menopausal status and molecular subtype. Studying risk factors in relation to these subtypes can help enhance our understanding of breast cancer etiology. Here, we aim to further explore the mechanisms through which several established and suspected risk factors may influence risk of breast cancer, with an emphasis on modifiable exposures, which may have direct implications for prevention strategies, particularly for premenopausal and non-luminal breast cancers. In Chapter 1, we evaluated the cross-sectional relationship between intakes of caffeine, coffee, decaffeinated coffee, and tea, and comprehensive profiles of urinary estrogens and estrogen metabolites in premenopausal women. We found significant associations between coffee intake and metabolites in the 2-hydroxylation pathway, suggesting a possible mechanism through which coffee may affect breast cancer risk. In Chapter 2, we examined associations between premenopausal plasma carotenoid levels and markers of oxidative stress and subsequent breast cancer risk. In contrast to previously published analyses, which largely focused on postmenopausal carotenoid exposure, we did not find significant inverse associations between circulating carotenoids and risk; additionally we did not observe positive associations between fluorescent oxidation products and risk. However, we did find some evidence that the effects of carotenoids on risk may be modified by single nucleotide polymorphisms in genes related to carotenoid availability and oxidative/antioxidative processes. In Chapter 3, we explored whether the associations of reproductive risk factors with breast cancer vary by intrinsic molecular subtype. We observed evidence that many risk factors are most strongly associated with the hormone receptor-positive luminal A subtype, which comprises the majority of breast cancers, though tests of heterogeneity did not reach significance in many cases. Consistent with previous studies, we observed that breastfeeding may reduce risk of basal-like tumors, and may represent a potential preventive strategy for this aggressive subtype. In conclusion, these analyses, while varied in scope, help elucidate mechanisms by which risk factors may influence breast cancer risk.Epidemiolog

Sodium content of menu items in New York City chain restaurants following enforcement of the sodium warning icon rule, 2015-2017.

In 2016, New York City (NYC) began enforcing a sodium warning regulation at chain restaurants, requiring placement of an icon next to any menu item containing ≥2,300 mg sodium. As menu labeling may improve menu nutritional composition, we investigated whether sodium content of menu items changed following enforcement of the sodium warning icon. All menu offerings at 10 quick-service (QSR) and 3 full-service (FSR) chain restaurants were photographed in 2015 (baseline) and 2017 (follow-up) and matched to nutritional information from restaurant websites; items were categorized as being available at both baseline and follow-up, or at only one timepoint. Linear and logistic regression models, respectively, assessed changes in calculated mean sodium-per-serving per menu item and the odds of an item containing ≥2,300 mg sodium. At baseline, mean per-serving sodium content was 2,160 mg at FSR and 1,070 mg at QSR, and 40.6% of FSR items and 7.2% of QSR items contained ≥2,300 mg sodium per serving. Sodium content did not differ when comparing all items offered at follow-up to all offered at baseline (21 mg, 95% CI: -60,101), or when comparing new versus discontinued items (17 mg, 95% CI: -154, 187). At follow-up, there was no change in the overall likelihood of items requiring a warning icon (OR = 1.32, 95% CI: 0.97,1.79), or when comparing new versus discontinued items (OR = 2.08, 95% CI: 1.02,4.24) (p = 0.04, not significant following Bonferroni correction for multiple analyses). Our findings that the sodium content of menu items did not change following the sodium warning icon regulation underscore difficulties in reducing sodium levels in restaurants; however, our results may be limited by follow-up data collection occurring less than one year post-enforcement. It may take additional time and similar action from other jurisdictions for restaurants to reduce the sodium content of menu items