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Objective: Flavored non-cigarette tobacco product (NCTP) use is common among US adult tobacco users. To update the estimates of use patterns of flavored NCTPs, this study assessed current NCTP use among adults by flavor use and flavor categories from 2010 to 2019., Methods: We analyzed data from the 2010-2019 Tobacco Use Supplement to the Current Population Survey to estimate the weighted proportion of adult NCTP users by flavor use across survey waves. Flavor use was defined as past 30-day use of any menthol/mint or fruit/other flavors. We used the 2018-2019 data to examine the differences in demographic characteristics and tobacco use patterns among users of menthol/mint or fruit/other flavors compared to exclusive users of tobacco flavor, by product type., Results: Compared to 2014-2015, electronic nicotine delivery system (ENDS) users were more likely (79.0% vs. 66.6%, p < 0.001) to report flavor use in 2018-2019, whereas cigar (26.9% vs. 31.2%, p = 0.030) and pipe (56.3% vs. 65.5%, p = 0.015) smokers were less likely to report flavor use in 2018-2019. In 2018-2019, the most prevalent flavor categories were exclusive use of tobacco flavor among cigar (73.1%) and smokeless tobacco (48.3%) users, and use of fruit/other flavors among ENDS (64.9%) and pipe (48.4%) users. Flavored users were more likely to be young adults aged 18-24 years (cigars, ENDS, smokeless tobacco) and Non-Hispanic Black or Hispanic persons (cigars, ENDS, pipes) compared to tobacco-flavored users., Conclusions: Flavored product use increased among adult ENDS users but decreased among cigar and pipe smokers. These findings could inform tobacco regulatory efforts concerning flavored NCTPs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Commercial cigarette smoking among U.S. adults has declined during the preceding 5 decades (1,2); however, tobacco product use remains the leading cause of preventable disease and death in the United States, and some populations continue to be disproportionately affected by tobacco use (1,2). To assess recent national estimates of commercial tobacco use among U.S. persons aged ≥18 years, CDC, the Food and Drug Administration (FDA), and the National Cancer Institute analyzed 2021 National Health Interview Survey (NHIS) data. In 2021, an estimated 46 million U.S. adults (18.7%) reported currently using any tobacco product, including cigarettes (11.5%), e-cigarettes (4.5%), cigars (3.5%), smokeless tobacco (2.1%), and pipes (including hookah)* (0.9%). † Among those who used tobacco products, 77.5% reported using combustible products (cigarettes, cigars, or pipes), and 18.1% reported using two or more tobacco products. § The prevalence of current use of any tobacco product use was higher among the following groups: men; persons aged <65 years; persons of non-Hispanic other races; non-Hispanic White (White) persons ¶ ; residents of rural (nonmetropolitan) areas; financially disadvantaged (income-to-poverty ratio = 0-1.99); lesbian, gay, or bisexual (LGB) persons; those uninsured or enrolled in Medicaid; adults whose highest level of education was a general educational development (GED) certificate; who had a disability; and who had serious psychological distress. Continued surveillance of tobacco product use, implementation of evidence-based tobacco control strategies (e.g., hard-hitting media campaigns, smoke-free policies, and tobacco price increases), conducting linguistically and culturally appropriate educational campaigns, and FDA regulation of tobacco products will aid in reducing tobacco-related disease, death, and disparities among U.S. adults (3,4)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Terminal duct lobular units (TDLUs) are the structures in the breast that give rise to most breast cancers. Previous work has shown that TDLU involution is inversely associated with TDLU metrics, such as TDLU count/100mm 2 , TDLU span (µm), and number of acini/TDLU, and that these metrics may be elevated in the normal breast tissue of women diagnosed with triple-negative (TN) compared with luminal A breast tumors. It is unknown whether this relationship exists in Black women, who have the highest incidence of TN breast cancer and the highest overall breast cancer mortality rate. We examined relationships between TDLU metrics and breast cancer molecular subtype among breast cancer cases in the Black Women's Health Study (BWHS)., Methods: We assessed quantitative TDLU metrics (TDLU count/100mm 2 , TDLU span (µm), and number of acini/TDLU) in digitized 247 hematoxylin and eosin-stained adjacent normal tissue sections from 223 BWHS breast cancer cases, including 65 triple negative (TN) cancers (estrogen receptor (ER) negative, progesterone receptor (PR) negative, human epidermal growth factor-2 (HER2) negative) and 158 luminal A cancers (ER positive, HER2 negative). We evaluated associations of least square mean TDLU metrics adjusted for age and body mass index (BMI) with patient and clinical characteristics. In logistic regression models, we evaluated associations between TDLU metrics and breast cancer subtype, adjusting for age, BMI, and tumor size., Results: Older age and higher BMI were associated with lower TDLU metrics and larger tumor size and lymph node invasion with higher TDLU metrics. The odds of TN compared with luminal A breast cancer increased with increasing tertiles of TDLU metrics, with odds ratios (95% confidence intervals) for tertile 3 versus tertile 1 of 2.18 (0.99, 4.79), 2.77 (1.07, 7.16), and 1.77 (0.79, 3.98) for TDLU count, TDLU span, and acini count/TDLU, respectively., Conclusion: Associations of TDLU metrics with breast cancer subtypes in the BWHS are consistent with previous studies of White and Asian women, demonstrating reduced TDLU involution in TN compared with luminal A breast cancers. Further investigation is needed to understand the factors that influence TDLU involution and the mechanisms that mediate TDLU involution and breast cancer subtype., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women., Methods: We investigated associations between pathogenic variants (PV) in 34 genes with breast cancer risk in 871 cases [307 estrogen receptor (ER)-positive, 321 ER-negative, and 243 ER-unknown] and 1,563 controls in the Ghana Breast Health Study (GBHS), and estimated lifetime risk for carriers. We compared results with those for European, Asian, and African American ancestry women., Results: The frequency of PV in GBHS for nine breast cancer genes was 8.38% in cases and 1.22% in controls. Relative risk estimates for overall breast cancer were: (OR, 13.70; 95% confidence interval (CI), 4.03-46.51) for BRCA1, (OR, 7.02; 95% CI, 3.17-15.54) for BRCA2, (OR, 17.25; 95% CI, 2.15-138.13) for PALB2, 5 cases and no controls carried TP53 PVs, and 2.10, (0.72-6.14) for moderate-risk genes combined (ATM, BARD1, CHEK2, RAD51C, RAD52D). These estimates were similar to those previously reported in other populations and were modified by ER status. No other genes evaluated had mutations associated at P &lt; 0.05 with overall risk. The estimated lifetime risks for mutation carriers in BRCA1, BRCA2, and PALB2 and moderate-risk genes were 18.4%, 9.8%, 22.4%, and 3.1%, respectively, markedly lower than in Western populations with higher baseline risks., Conclusions: We confirmed associations between PV and breast cancer risk in Ghanaian women and provide absolute risk estimates that could inform counseling in Ghana and other West African countries., Impact: These findings have direct relevance for breast cancer genetic counseling for women in West Africa., (©2022 American Association for Cancer Research.)

Background: Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive subtype, is highest in US African American women and in Southern residents but has decreased overall since 1992. We assessed whether ER-negative breast cancer is decreasing in all age groups and cancer registries among non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic White (HW) women., Methods: We analyzed 17 Surveillance, Epidemiology, and End-Results (SEER) Program registries (12 for 1992-2016; 5 for 2000-2016) to assess NHW, NHB, and HW trends by ER status and age group (30-39 years, 40-49 years, 50-69 years, 70-84 years). We used hierarchical age-period-cohort models that account for sparse data, which improve estimates to quantify between-registry heterogeneity in mean incidence rates and age-adjusted trends vs SEER overall., Results: Overall, ER-negative incidence was highest in NHB, then NHW and HW women, and decreased from 1992-2016 in each age group and racial or ethnic group. The greatest decrease was for HW women aged 40-49 years, with an annual percent change of -3.5%/y (95% credible interval = -4.4%, -2.7%) averaged over registries. The trend heterogeneity was statistically significant in every race or ethnic and age group. Furthermore, the incidence relative risks by race or ethnicity compared with the race-specific SEER average were also statistically significantly heterogeneous across the majority of registries and age groups (62 of 68 strata). The greatest heterogeneity was seen in HW women, followed by NHB women, and the least in NHW women., Conclusions: Decreasing ER-negative breast cancer incidence differs meaningfully by US region and age among NHB and HW women. Analytical studies including minority women from higher and lower incidence areas may provide insights into breast cancer racial disparities., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Estimates of contralateral breast cancer (CBC) risk in the modern treatment era by year of diagnosis and characteristics of the first breast cancer are needed to assess the impact of recent advances in breast cancer treatment and inform clinical decision making., Methods: We examined CBC risk among 419,818 women (age 30-84 years) who were diagnosed with a first unilateral invasive breast cancer and survived ≥ 1 year in the US Surveillance, Epidemiology, and End Results program cancer registries from 1992 to 2015 (follow-up through 2016). CBC was defined as a second invasive breast cancer in the contralateral breast ≥ 12 months after the first breast cancer. We estimated standardized incidence ratios (SIRs) of CBC by year of diagnosis, age at diagnosis, and tumor characteristics for the first breast cancer. Cumulative incidence of CBC was calculated for women diagnosed with a first breast cancer in the recent treatment era (2004-2015, follow-up through 2016)., Results: Over a median follow-up of 8 years (range 1-25 years), 12,986 breast cancer patients developed CBC. Overall, breast cancer patients had approximately twice the risk of developing cancer in the contralateral breast when compared to that expected in the general population (SIR = 2.21, 95% CI = 2.17-2.25). SIRs for CBC declined by year of first diagnosis, irrespective of age at diagnosis and estrogen receptor (ER) status (p-trends < 0.001), but the strongest decline was after an ER-positive tumor. The 5-year cumulative incidence of CBC ranged from 1.01% (95% CI = 0.90-1.14%) in younger women (age < 50 years) with a first ER-positive tumor to 1.89% (95% CI = 1.61-2.21%) in younger women with a first ER-negative tumor., Conclusion: Declines in CBC risk are consistent with continued advances in breast cancer treatment. The updated estimates of cumulative incidence inform breast cancer patients and clinicians on the risk of CBC and may help guide treatment decisions.

Higher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity. We analyzed data from 1,126 cases (aged 18-74 years) with invasive breast cancer and 2,106 controls recruited from a population-based case-control study in Ghana. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Among controls, medians for age at menarche, parity, age at first birth, and breastfeeding/pregnancy were 15 years, 4 births, 20 years and 18 months, respectively. For women ≥50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0.40 (95% CI 0.20-0.83) and 0.71 (95% CI 0.51-0.98) for ≥19 vs. <13 breastfeeding months/pregnancy, which did not differ by ER. In contrast, for earlier onset cases (<50 years) parity was associated with increased risk for ER-negative tumors (p-heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth. Reproductive risk factor distributions are different from European populations but exhibited etiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Publicly available tumor gene expression datasets are widely reanalyzed, but it is unclear how representative they are of clinical populations. Estimations of molecular subtype classification and prognostic gene signatures were calculated for 16,130 patients from 70 breast cancer datasets. Collated patient demographics and clinical characteristics were sparse for many studies. Considerable variations were observed in dataset size, patient/tumor characteristics, and molecular composition. Results were compared with Surveillance, Epidemiology, and End Results Program (SEER) figures. The proportion of basal subtype tumors ranged from 4 to 59%. Date of diagnosis ranged from 1977 to 2013, originating from 20 countries across five continents although European ancestry dominated. Publicly available breast cancer gene expression datasets are a great resource, but caution is required as they tend to be enriched for high grade, ER-negative tumors from European-ancestry patients. These results emphasize the need to derive more representative and annotated molecular datasets from diverse populations., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

Background: Westernization and etiologic heterogeneity may play a role in the rising breast cancer incidence in Asian American (AA) women. We report breast cancer incidence in Asian-origin populations., Methods: Using a specialized Surveillance, Epidemiology, and End Results-9 Plus API Database (1990-2014), we analyzed breast cancer incidence overall, by estrogen receptor (ER) status, and age group among non-Hispanic white (NHW) and AA women. We used age-period-cohort models to assess time trends and quantify heterogeneity by ER status, race and ethnicity, and age., Results: Overall, breast cancer incidence increased for most AA ethnicities (Filipina: estimated annual percentage change [EAPC] = 0.96%/year, 95% confidence interval [CI] = 0.61% to 1.32%; South Asian: EAPC = 1.68%/year, 95% CI = 0.24% to 3.13%; Chinese: EAPC = 0.65%/year, 95% CI = 0.03% to 1.27%; Korean: EAPC = 2.55%/year, 95% CI = 0.13% to 5.02%; and Vietnamese women: EAPC = 0.88%/year, 95% CI = 0.37% to 1.38%); rates did not change for NHW (EAPC = -0.2%/year, 95% CI = -0.73% to 0.33%) or Japanese women (EAPC = 0.22%/year, 95% CI = -1.26% to 1.72%). For most AA ethnicities, ER-positive rates statistically significantly increased, whereas ER-negative rates statistically significantly decreased. Among older women, ER-positive rates were stable for NHW and Japanese women. ER-negative rates decreased fastest in NHW and Japanese women among both age groups., Conclusions: Increasing ER-positive incidence is driving an increase overall for most AA women despite declining ER-negative incidence. The similar trends in NHW and Japanese women (vs other AA ethnic groups) highlight the need to better understand the influences of westernization and other etiologic factors on breast cancer incidence patterns in AA women. Heterogeneous trends among AA ethnicities underscore the importance of disaggregating AA data and studying how breast cancer differentially affects the growing populations of diverse AA ethnic groups., (Published by Oxford University Press 2020.)

Black women in the United States are disproportionately affected by early-onset, triple-negative breast cancer. DNA methylation has shown differences by race in healthy and tumor breast tissues. We examined associations between genome-wide DNA methylation levels in breast milk and breast cancer risk factors, including race, to explain how this reproductive stage influences a woman's risk for, and potentially contributes to racial disparities in, breast cancer. Breast milk samples and demographic, behavioral, and reproductive data, were obtained from cancer-free, uniparous, and lactating U.S. black ( n = 57) and white ( n = 82) women, ages 19-44. Genome-wide DNA methylation analysis was performed on extracted breast milk DNA using the Infinium HumanMethylation450 BeadChip. Statistically significant associations between breast cancer risk factors and DNA methylation beta values, adjusting for potential confounders, were determined using linear regression followed by Bonferroni Correction ( P < 1.63 × 10 -7 ). Epigenetic analysis in breast milk revealed statistically significant associations with race and lactation duration. Of the 284 CpG sites associated with race, 242 were hypermethylated in black women. All 227 CpG sites associated with lactation duration were hypomethylated in women who lactated longer. Ingenuity Pathway Analysis of differentially methylated promoter region CpGs by race and lactation duration revealed enrichment for networks implicated in carcinogenesis. Associations between DNA methylation and lactation duration may offer insight on its role in lowering breast cancer risk. Epigenetic associations with race may mediate social, behavioral, or other factors related to breast cancer and may provide insight into potential mechanisms underlying racial disparities in breast cancer incidence., (©2019 American Association for Cancer Research.)

Recent reports of converging black and white breast cancer incidence rates have gained much attention, potentially foreshadowing a worsening of the black-white breast cancer mortality disparity. However, these incidence rates also reflect the sum of non-Hispanics and Hispanics that may mask important ethnicity-specific trends. We therefore assessed race- and ethnicity-specific breast cancer trends using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 13 Registries Database (1992-2014). Age-period-cohort models projected rates for 2015-2030. Results confirmed merging of age-standardized incidence rates for blacks and whites circa 2012, but not for non-Hispanic black (NHB) and non-Hispanic white (NHW) women. Incidence rates were highest for NHW women (n = 382 290), followed by NHB women (n = 51 074), and then Hispanic white women (n = 48 651). The sample size for Hispanic blacks was too small for analysis (n = 693). Notably, future incidence rates are expected to slowly increase (2015 through 2030) among NHW women (0.24% per year, 95% confidence interval [CI] = 0.17 to 0.32) and slowly decrease for NHB women (-0.14% per year, 95% CI = -0.15 to -0.13). A putative worsening of the black-white mortality disparity, therefore, seems unlikely. Ethnicity matters when assessing race-specific breast cancer incidence rates.