Assessment of salivary cadmium levels and breast density in the Marin Women's Study.

BACKGROUND: We aimed to determine if salivary cadmium (Cd) levels had any association with breast density, hoping to establish a less invasive cost-effective method of stratifying Cd burden as an environmental breast cancer risk factor. METHODS: Salivary Cd levels were quantified from the Marin Women's Study, a Marin County, California population composite. Volumetric compositional breast density (BDsxa ) data were measured by single x-ray absorptiometry techniques. Digital screening mammography was performed by the San Francisco Mammography Registry. Radiologists reviewed mammograms and assigned a Breast Imaging-Reporting and Data System score. Early morning salivary Cd samples were assayed. Association analyses were then performed. RESULTS: Cd was quantifiable in over 90% of saliva samples (mean = 55.7 pg/L, SD = 29). Women with higher saliva Cd levels had a non-significant odds ratio of 1.34 with BI-RAD scores (3 or 4) (95% CI 0.75-2.39, p = 0.329). Cd levels were higher in current smokers (mean = 61.4 pg/L, SD = 34.8) than former smokers or non-smokers. These results were non-significant. Pilot data revealed that higher age and higher BMI were associated with higher BI-RAD scores (p < 0.001). CONCLUSION: Salivary Cd is a viable quantification source in large epidemiologic studies. Association analyses between Cd levels and breast density may provide additional information for breast cancer risk assessment, risk reduction plans, and future research directions. Further work is needed to demonstrate a more robust testing protocol before the extent of its usefulness can be established.

COVID-19 Vaccine Perceptions Survey for Real-Time Vaccine Outreach in Marin County, California.

BACKGROUND: Understanding and addressing coronavirus disease 2019 (COVID-19) vaccine hesitancy is crucial to informing vaccination outreach strategies and achieving high vaccination coverage. Marin County, California, United States, has a history of vaccine hesitancy regarding childhood vaccinations required for school entry. OBJECTIVES: We aimed to describe and address COVID-19 vaccine hesitancy in Marin County to inform outreach and messaging. Our objectives were to identify subgroups with high COVID-19 vaccine hesitancy early in distribution, better understand local concerns and feedback about the COVID-19 vaccine distribution process, and inform tailored vaccine messaging to increase vaccination confidence and coverage. METHODS: The survey, which was administered from January 3 to May 10, 2021, queried demographics, vaccine acceptance, reasons for hesitancy, and reasons for acceptance. Open-ended questions were used for respondents to report additional reasons for hesitancy and for general feedback about the vaccine distribution process. We conducted quantitative and qualitative analyses stratified by COVID-19 vaccine acceptance to identify subgroups with high hesitancy. Results were shared weekly in real-time with leadership and key community partners working on vaccine outreach. RESULTS: Among the 5,618 survey responses, there were differences in vaccine hesitancy by sociodemographic characteristics with the highest hesitancy reported among subgroups identifying as Black/African American and young adult, and within the lowest family income grouping. The most common reason for vaccine hesitancy was "uncertain about the side effects of the vaccine" (67.3% endorsement) and responses varied by race and ethnicity. Qualitative data revealed equity-related, vaccine distribution, and vaccine access themes that were not present in structured responses. Vaccine hesitancy survey results were paired with vaccination coverage and COVID-19 case data to inform tailored outreach strategies and priorities week-to-week. CONCLUSIONS: Marin County had some of the highest COVID-19 vaccination rates in the United States during the pandemic and met equity goals aimed at ensuring vulnerable populations received vaccinations. Presenting real-time survey findings with leadership and key community partners informed a timely and tailored COVID-19 vaccine outreach and delivery strategy.

Phased Return of Students to 77 Transitional Kindergarten-8th Grade Schools With Cohesive Mitigation Strategies Serving as Protective Factors Against the Increase of COVID-19 Cases in Marin County: September 2020-January 2021.

Background and objective Earlier uncertain implications of the coronavirus disease 2019 (COVID-19) pandemic on the pediatric population prompted the authorities to close schools worldwide under the premise that school settings would serve as drivers of an increase in the cases of COVID-19. Safe and equitable full-in-person school instruction is a critical factor in the continued educational gains of children and for their general well-being. The objective of this study was to report epidemiological trends related to the increasing percentage of students returning to in-person instruction, the suspected in-school transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and countywide COVID-19 case rates during the first 21 weeks of school reopening in Marin County, CA, in the fall of 2020. Materials and methods The institutional review board (IRB) approval was waived for this study as it did not involve any identifiable human subjects data. Retrospective electronic reviews of countywide COVID-19 daily case count and COVID-19-related reports associated with in-person school participants from 77 schools in Marin County, CA, from September 8, 2020, to January 29, 2021, were conducted. The data were made available in collaboration with the Marin County Office of Education (MCOE) and Marin County Department of Health and Human Services (Marin HHS). Descriptive trends analyses were performed to determine whether the phased increase of students attending in-person learning was a significant contributor to countywide COVID-19 incidence rate, crude rate, and in-school COVID-19 viral transmission. This is the first long retrospective study of COVID-19 data among the reopened school population during the second half of the first pandemic year. It was conducted in a 21-week surveillance period involving an immense collaboration between Marin County's public health officials and school administrators. Results Over the 21-week observational period involving 17,639 students, 4,938 school staff, and 899,175 student days, the countywide COVID-19 crude rate decreased (from 89.9 to 35.89 per 10,000) as more students returned to in-person learning. The schools' strict adherence to public health guidance and site-specific safety plans against COVID-19 yielded a significantly reduced incidence rate of 0.84% among in-person learning participants; only nine cases were traced to suspected in-school SARS-CoV-2 transmission by way of rigorous contact tracing. The countywide COVID-19 incidence rate was 2.09%. Conclusions It is possible to minimize COVID-19 transmissions in in-person learning settings with cohesive mitigation strategies, specifically strict adherence to proper masking by students and staff while on school grounds. There is no clear correlation that the increasing phased return of students to in-person school drove an increase in countywide COVID-19 cases in Marin County, CA. Our findings revealed that schools were capable of safely resuming operations by following public health orders and recommendations. The increasing percentage of students returning to in-person school did not drive an increased COVID-19 case rate in the community. On the contrary, this analysis revealed that there was a drop in countywide COVID-19 cases as the phased student return percentage increased.

Emergency Medical Service Utilization and Response Following COVID-19 Emergency and Stay-at-Home Policies: An Interrupted Time-Series Analysis.

Objective Examine changing emergency medical services (EMS) utilization and response patterns associated with coronavirus disease 2019 (COVID-19) emergency declaration and stay-at-home orders during the first year of the COVID-19 pandemic. Methods We conducted an uncontrolled interrupted time series analysis of EMS calls (January 1, 2019 - March 1, 2021) in Marin County, California analyzing call volume (All calls, n=46,055); patient refusal of EMS care or transport and patient care resolved on scene (Calls with opportunity for transport; n=37,401); and call severity (Transported calls; n=27,887). Results Pre-COVID-19 (1/1/2019-3/2/2020), EMS transported patients were predominately female (50.6%), 80+ years old (31.6%), and Marin County residents (68.0%). During COVID-19 (3/3/2020-3/1/2021), EMS transported patients were predominately male (52.7%), 35-64 years old (29.8%), and Marin County residents (70.4%). After the first stay-at-home order on 3/17/2020, call volume immediately decreased by 48% (adjusted incidence rate ratio [aIRR]=0.52; 95% CI=0.35,0.79) for children (0-15 years) and 34% for adults 80+ years (aIRR=0.66;95% CI=0.46,0.95). The odds of a transported call being prioritized as severe doubled (adjusted odds ratio [aOR]=2.26; 95% CI=1.11,4.59). Though transport refusals increased by 69% for children after the first order (aOR, 1.69 [95% CI, 1.13-2.52]), immediately following the second order on 12/8/2020, transport refusals decreased by 30% for children but increased 38-40% for adults 35-79 years (aOR=1.40 [95% CI=1.04-1.89] for 35-64 years; 1.38 [95% CI=1.02-1.87] for 65-79 years). Calls resolved on scene by EMS increased after the first order among all ages and after the second order for adults 16-79 years.  Conclusions Call volume reduced for children and older adults after the first COVID-19 stay-at-home order. Changes in call severity, patient care refusals, and on-scene care provided by EMS indicated a changing role for EMS during the outbreak.

Use of SMS-linked electronic surveys for COVID-19 case investigation and contact tracing - Marin County, CA, USA.

OBJECTIVES: We sought to quantify the proportion of contacts reported by persons with COVID-19 through a short message service (SMS)-linked survey in comparison to the proportion of contacts reported during a follow-up phone-interview. We also sought to assess improvement in contact tracing timeliness associated with sending SMS-linked surveys. STUDY DESIGN: During December 4-15, 2020, persons identified as COVID-19 cases whose data was entered into Marin County's contact tracing database on even days received a SMS-linked survey and persons whose data was entered on odd days did not; all were called for case investigation and contact tracing. Chi-square test and Fisher's exact test were used to compare demographic data. Chi-square test was used to contrast categorical outcomes, and Wilcoxon's rank-sum test was used for continuous outcomes. RESULTS: Among 350 SMS-linked survey recipients, 85 (24%) responded and 4 (1%) reported contacts using the survey; an additional 303 contacts were reported during phone interviews. Without phone interviews, 99% of reported contacts would have been missed. There was no meaningful difference between study arms in the proportion of contacts notified within 48 h. CONCLUSIONS: This SMS-linked survey had low participation and was not useful for identifying contacts. Phone interviews remained crucial for COVID-19 contact tracing.

First Pregnancy Characteristics, Postmenopausal Breast Density, and Salivary Sex Hormone Levels in a Population at High Risk for Breast Cancer.

BACKGROUND: It remains unknown if later life breast cancer risk as determined by reproductive history is mediated by postmenopausal breast density and/or sex steroid levels. METHODS: Increased breast density is a strong surrogate for future breast cancer risk. A cross-sectional study with a longitudinal follow up for breast health outcomes evaluated women without breast cancer (n = 1,023; 682 = parous), drawn from a high risk postmenopausal population, with questionnaire reported reproductive histories. The questionnaire was linked to prospective screening mammogram breast density measurements, and saliva biospecimens that were used to assess sex steroid hormone levels. RESULTS: Expected age and postmenopause related declines in salivary estradiol (E), progesterone (P), dehydroepiandrosterone (DHEA) and testosterone (T) levels were observed. This was most pronounced for DHEA and T, which were also the only postmenopausal hormone levels significantly associated with any reproductive characteristics: parity and breast feeding for DHEA, age-at-first birth for T. Postmenopausal breast density was borderline significantly lower with parity and higher body mass index (BMI). After multivariate analysis, T was the only hormone level to retain any association (negative, p<0.05) with breast density. CONCLUSIONS AND GENERAL SIGNIFICANCE: While reproductive characteristics, in particular parity, generally demonstrated independent associations with postmenopausal breast density and E, P and DHEA levels, T levels showed concordant inverse associations with age-at-first birth and breast density. These findings suggest that reproductive effects and later life salivary sex steroid hormone levels may have independent effects on later life breast density and cancer risk.

First pregnancy events and future breast density: modification by age at first pregnancy and specific VEGF and IGF1R gene variants.

PURPOSE: Pregnancy characteristics have been associated with breast cancer risk, but information is limited on their relationship with breast density. Our objective was to examine the relationship between first pregnancy characteristics and later life breast density, and whether the association is modified by genotype. METHODS: The Marin Women's Study was initiated to examine breast cancer in a high-incidence mammography population (Marin County, CA). Reproductive characteristics and pregnancy information including pregnancy-induced hypertension (PIH) were self-reported at the time of mammography. Forty-seven candidate single nucleotide polymorphisms were obtained from saliva samples; seven were assessed in relation to PIH and percent fibroglandular volume (%FGV). Breast density assessed as %FGV was measured on full-field digital mammograms by the San Francisco Mammography Registry. RESULTS: A multivariable regression model including 2,440 parous women showed that PIH during first pregnancy was associated with a statistically significant decrease in %FGV (b = -0.31, 95 % CI -0.52, -0.11), while each month of breast-feeding after first birth was associated with a statistically significant increase in %FGV (b = 0.01, 95% CI 0.003, 0.02). PIH and breast-feeding associations with %FGV were modified by age at first birth. In a subsample of 1,240 women, there was evidence of modification in the association between PIH and %FGV by specific vascular endothelial growth factor (VEGF) (rs3025039) and insulin growth factor receptor-1 (IGFR1) (rs2016347) gene variants. CONCLUSION: These findings suggest that first pregnancy characteristics may exert an influence on extent of breast density later in life and that this influence may vary depending on inherited IGFR1 and VEGF genotypes.

Assessing breast cancer risk models in Marin County, a population with high rates of delayed childbirth.

INTRODUCTION: This study was designed to compare the Breast Cancer Risk Assessment Tool (BCRAT; Gail), International Breast Intervention Study (IBIS; Tyrer-Cuzick), and BRCAPRO breast cancer risk assessment models using data from the Marin Women's Study, a cohort of women within Marin County, California, with high rates of breast cancer, nulliparity, and delayed childbirth. Existing models have not been well-validated in these high-risk populations. METHODS: Discrimination was assessed using the area under the receiver operating characteristic curve (AUC) and calibration by estimating the ratio of expected-to-observed (E/O) cases. The models were assessed using data from 12,843 participants, of whom 203 had developed cancer during a 5-year period. All tests of statistical significance were 2-sided. RESULTS: The IBIS model achieved an AUC of 0.65 (95% confidence interval [CI], 0.61-0.68) compared with 0.62 (95% CI, 0.59-0.66) for BCRAT and 0.60 (95% CI, 0.56-0.63) for BRCAPRO. The corresponding estimated E/O ratios for the models were 1.08 (95% CI, 0.95-1.25), 0.81 (95% CI, 0.71-0.93), and 0.59 (95% CI, 0.52-0.68). In women with age at first birth > 30 years, the AUC for the IBIS, BCRAT, and BRCAPRO models was 0.69 (95% CI, 0.62-0.75), 0.63 (95% CI, 0.56-0.70), and 0.62 (95% CI, 0.56-0.68) and the E/O ratio was 1.15 (95% CI, 0.89-1.47), 0.81 (95% CI, 0.63-1.05), and 0.53 (95% CI, 0.41-0.68), respectively. CONCLUSIONS: The IBIS model was well calibrated for the high-risk Marin mammography population and demonstrated the best calibration of the 3 models in nulliparous women. The IBIS model also achieved the greatest overall discrimination and displayed superior discrimination for women with age at first birth > 30 years.

Recent trends in hormone therapy utilization and breast cancer incidence rates in the high incidence population of Marin County, California.

BACKGROUND: Recent declines in invasive breast cancer have been reported in the US, with many studies linking these declines to reductions in the use of combination estrogen/progestin hormone therapy (EPHT). We evaluated the changing use of postmenopausal hormone therapy, mammography screening rates, and the decline in breast cancer incidence specifically for Marin County, California, a population with historically elevated breast cancer incidence rates. METHODS: The Marin Women's Study (MWS) is a community-based, prospective cohort study launched in 2006 to monitor changes in breast cancer, breast density, and personal and biologic risk factors among women living in Marin County. The MWS enrolled 1,833 women following routine screening mammography between October 2006 and July 2007. Participants completed a self-administered questionnaire that included items regarding historical hormone therapy regimen (estrogen only, progesterone only, EPHT), age of first and last use, total years of use, and reason(s) for stopping, as well as information regarding complementary hormone use. Questionnaire items were analyzed for 1,083 non-Hispanic white participants ages 50 and over. Breast cancer incidence rates were assessed overall and by tumor histology and estrogen receptor (ER) status for the years 1990-2007 using data from the Northern California Surveillance, Epidemiology and End Results (SEER) cancer registry. RESULTS: Prevalence of EPHT use among non-Hispanic white women ages 50 and over declined sharply from 21.2% in 1998 to 6.7% by 2006-07. Estrogen only use declined from 26.9% in 1998 to 22.4% by 2006-07. Invasive breast cancer incidence rates declined 33.4% between 2001 and 2004, with drops most pronounced for ER+ cancers. These rate reductions corresponded to declines of about 50 cases per year, consistent with population attributable fraction estimates for EPHT-related breast cancer. Self-reported screening mammography rates did not change during this period. Use of alternative or complementary agents did not differ significantly between ever and never hormone users. Of women who reported stopping EPHT in the past 5 years, 60% cited "health risks" or "news reports" as their primary reasons for quitting. CONCLUSION: A dramatic reduction in EPHT use was followed temporally by a significant reduction in invasive and ER+ breast cancer rates among women living in Marin County, California.

Differences in reproductive risk factors for breast cancer in middle-aged women in Marin County, California and a sociodemographically similar area of Northern California.

BACKGROUND: The Northern California county of Marin (MC) has historically had high breast cancer incidence rates. Because of MC's high socioeconomic status (SES) and racial homogeneity (non-Hispanic White), it has been difficult to assess whether these elevated rates result from a combination of established risk factors or other behavioral or environmental factors. This survey was designed to compare potential breast cancer risks and incidence rates for a sample of middle-aged MC women with those of a demographically similar population. METHODS: A random sample of 1500 middle-aged female members of a large Northern California health plan, half from Marin County (MC) and half from a comparison area in East/Central Contra Costa County (ECCC), were mailed a survey covering family history, reproductive history, use of oral contraceptives (OC) and hormone replacement therapy (HRT), behavioral health risks, recency of breast screening, and demographic characteristics. Weighted data were used to compare prevalence of individual breast cancer risk factors and Gail scores. Age-adjusted cumulative breast cancer incidence rates (2000-2004) were also calculated for female health plan members aged 40-64 residing in the two geographic areas. RESULTS: Survey response was 57.1% (n = 427) and 47.9% (n = 359) for MC and ECCC samples, respectively. Women in the two areas were similar in SES, race, obesity, exercise frequency, current smoking, ever use of OCs and HRT, age at onset of menarche, high mammography rates, family history of breast cancer, and Gail scores. However, MC women were significantly more likely than ECCC women to be former smokers (43.6% vs. 31.2%), have Ashkenazi Jewish heritage (12.8% vs. 7.1%), have no live births before age 30 (52.7% vs. 40.8%), and be nulliparous (29.2% vs. 15.4%), and less likely to never or rarely consume alcohol (34.4% vs. 41.9%). MC and ECCC women had comparable 2000-2004 invasive breast cancer incidence rates. CONCLUSION: The effects of reproductive risks factors, Ashkenazi Jewish heritage, smoking history, and alcohol consumption with regard to breast cancer risk in Marin County should be further evaluated. When possible, future comparisons of breast cancer incidence rates between regions should adjust for differences in income and education in addition to age and race/ethnicity, preferably by using a sociodemographically similar comparison group.

Impact of intercensal population projections and error of closure on breast cancer surveillance: examples from 10 California counties.

INTRODUCTION: In 2001, data from the California Cancer Registry suggested that breast cancer incidence rates among non-Hispanic white (nHW) women in Marin County, California, had increased almost 60% between 1991 and 1999. This analysis examines the extent to which these and other breast cancer incidence trends could have been impacted by bias in intercensal population projections. METHOD: We obtained population projections for the year 2000 projected from the 1990 census from the California Department of Finance (DOF) and population counts from the 2000 US Census for nHW women living in 10 California counties and quantified age-specific differences in counts. We also computed age-adjusted incidence rates of invasive breast cancer in order to examine and quantify the impact of differences between the population data sources. RESULTS: Differences between year 2000 DOF projections and year 2000 census counts varied by county and age and ranged from underestimates of 60% to overestimates of 64%. For Marin County, the DOF underestimated the number of nHW women aged 45 to 64 years by 32% compared to the 2000 US census. This difference produced a significant 22% discrepancy between breast cancer incidence rates calculated using the two population data sources. In Los Angeles and Santa Clara counties, DOF-based incidence rates were significantly lower than rates based on census data. Rates did not differ significantly by population data source in the remaining seven counties examined. CONCLUSION: Although year 2000 population estimates from the DOF did not differ markedly from census counts at the state or county levels, greater discrepancies were observed for race-stratified, age-specific groups within counties. Because breast cancer incidence rates must be calculated with age-specific data, differences between population data sources at the age-race level may lead to mis-estimation of breast cancer incidence rates in county populations affected by these differences, as was observed in Marin County. Although intercensal rates based on population projections are important for timely breast cancer surveillance, these rates are prone to bias due to the error of closure between population projections and decennial census population counts. Intercensal rates should be interpreted with this potential bias in mind.

Breast cancer incidence and mortality trends in an affluent population: Marin County, California, USA, 1990-1999.

BACKGROUND: Elevated rates of breast cancer in affluent Marin County, California, were first reported in the early 1990s. These rates have since been related to higher regional prevalence of known breast cancer risk factors, including low parity, education, and income. Close surveillance of Marin County breast cancer trends has nevertheless continued, in part because distinctive breast cancer patterns in well-defined populations may inform understanding of breast cancer etiology. METHODS: Using the most recent incidence and mortality data available from the California Cancer Registry, we examined rates and trends for 1990-1999 for invasive breast cancer among non-Hispanic, white women in Marin County, in other San Francisco Bay Area counties, and in other urban California counties. Rates were age adjusted to the 2000 US standard, and temporal changes were evaluated with weighted linear regression. RESULTS: Marin County breast cancer incidence rates between 1990 and 1999 increased 3.6% per year (95% confidence interval, 1.8-5.5), six times more rapidly than in comparison areas. The increase was limited to women aged 45-64 years, in whom rates increased at 6.7% per year (95% confidence interval, 3.8-9.6). Mortality rates did not change significantly in Marin County despite 3-5% yearly declines elsewhere. CONCLUSION: Patterns of breast cancer incidence and mortality in Marin County are unlike those in other California counties, and they are probably explained by Marin County's unique sociodemographic characteristics. Similar trends may have occurred in other affluent populations for which available data do not permit annual monitoring of cancer occurrence.