Population-based Cohort Of Women Research Articles

Prospective risk of Type 2 diabetes in 99892 Nordic women with polycystic ovary syndrome and 446055 controls: national cohort study from Denmark, Finland, and Sweden.

What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls? A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries. The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited. This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin. The study cohort included women originating from Denmark (PCOS Denmark, N = 27016; controls, N = 133994), Finland (PCOS Finland, N = 20467; controls, N = 58051), and Sweden (PCOS Sweden, N = 52409; controls, N = 254010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0-14.8), 9.8 (5.1-15.1), and 6.0 (2.0-10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education. The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98-4.60) in Denmark, 3.40 (3.11-3.74) in Finland, and 5.68 (5.20-6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99892; controls, N = 446055), the crude HR for T2D in PCOS was 4.64 (3.40-5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32-3.51). Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities. The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2. Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest. N/A.

Sex steroid levels in women with hypopituitarism: A case-controlled observational study.

Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped. To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay. Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started growth hormone replacement 1995-2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone and estradiol showed similar patterns. Women with HH and adrenocorticotropic hormone (ACTH) deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency. This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement.

Abstract 2204: Evaluating ovarian cancer risk factors in the Mexican Teachers′ Cohort

Abstract Purpose: Ovarian cancer is the most lethal gynecologic cancer in North America, yet our understanding of ovarian cancer risk factors in Mexican women is limited. The aim of the present study was to prospectively evaluate associations between reproductive and lifestyle factors and incident ovarian cancer risk among Mexican women. Methods: The Mexican Teachers′ Cohort (ESMaestras) is a large, prospective, population-based cohort of women (n=115,306) living in a culturally, geographically, and economically diverse 12-state area in Mexico. Reproductive and lifestyle factors were collected on baseline questionnaires administered between 2006-2008, with additional questionnaires collected from the cohort in 2011, and 2014. During follow-up, 187 incident ovarian cancer cases were identified, including 101 via self-report on 2011 and 2014 questionnaires, as well as an additional 85 through linkage with mortality databases, and 3 via other administrative- and cancer registry-based linkages (2 of 3 were also identified via the mortality database linkage). Of the self-reported incident cases, 5 have been validated via mortality databases and 4 via linkage with an administrative database; validation of the remaining self-reported cases is ongoing. Primary analyses examined associations between established ovarian cancer risk factors and incident ovarian cancer. Age-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results: Women in the Mexican Teachers′ Cohort that used hormonal contraceptives (HC), were parous, or had a tubal ligation experienced reduced ovarian cancer risks during follow-up (ever HC use vs. never HR 0.70 [95% CI 0.51-0.95], parous vs. nulliparous 0.48 [0.35-0.68], ever tubal ligation vs. never 0.87 [0.59-1.28]). Ovarian cancer risk was elevated among women with a positive family history of breast cancer (1.34 [0.76-2.36]). Women with a history of endometriosis were at increased ovarian cancer risk (3.43 [1.41-8.34]). Taller adult height (&amp;gt;159 cm vs &amp;lt;150 cm) was not associated with ovarian cancer risk among women in this cohort. Risk estimates were consistent and, in some instances, more pronounced (i.e., HC use and tubal ligation) when limited to incident ovarian cancer cases confirmed via linkage with mortality databases (n=90). Conclusions: Ovarian cancer risk factors identified in the Mexican Teachers′ Cohort were generally consistent with associations reported in predominantly non-Hispanic white populations. More research is needed to better understand ovarian cancer etiology among populations under-represented in cancer research. Citation Format: Britton Trabert, Liliana Gómez Flores Ramos, Marion Brochier, Elisa V. Bandera, Jennifer A. Doherty, Scarlett L. Gomez, Lawrence H. Kushi, Alejandro Mohar, Martín Lajous. Evaluating ovarian cancer risk factors in the Mexican Teachers′ Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2204.

Ultra-processed foods and incident cardiovascular disease and hypertension in middle-aged women.

Ultra-processed food (UPF) intake has increased in recent decades, yet limited knowledge of long-term effects on cardiovascular health persists and sex-specific data is scant. We determined the association of UPF intake with incident cardiovascular disease (CVD) and/or hypertension in a population-based cohort of women. In the Australian Longitudinal Study on Women's Health, women aged 50-55years were prospectively followed (2001-2016). UPFs were identified using NOVA classification and contribution of these foods to total dietary intake by weight was estimated. Primary endpoint was incident CVD (self-reported heart disease/stroke). Secondary endpoints were self-reported hypertension, all-cause mortality, type 2 diabetes mellitus, and/or obesity. Logistic regression models assessed associations between UPF intake and incident CVD, adjusting for socio-demographic, medical comorbidities, and dietary variables. We included 10,006 women (mean age 52.5 ± 1.5; mean UPF intake 26.6 ± 10.2% of total dietary intake), with 1038 (10.8%) incident CVD, 471 (4.7%) deaths, and 4204 (43.8%) hypertension cases over 15years of follow-up. In multivariable-adjusted models, the highest [mean 42.0% total dietary intake] versus the lowest [mean 14.2% total dietary intake] quintile of UPF intake was associated with higher incident hypertension [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.10-1.74; p = 0.005] with a linear trend (ptrend = 0.02), but not incident CVD [OR 1.22, 95% CI 0.92-1.61; p = 0.16] or all-cause mortality (OR 0.80, 95% CI 0.54-1.20; p = 0.28). Similar results were found after multiple imputations for missing values. In women, higher UPF intake was associated with increased hypertension, but not incident CVD. These findings may support minimising UPFs within a healthy diet for women.

Recurrent urinary tract infection management and prevention techniques among a population-based cohort of women.

Recurrent urinary tract infection (rUTI), defined as three or more UTIs in 12 months, has psychological, physical, and financial burden. Many women with rUTI are not satisfied with care and report only starting preventative measures after several infections. The goal of this study is to elucidate current UTI management trends and the implementation of UTI prevention strategies. A web-based study was sent to a national sample of adult women enrolled in ResearchMatch.org. Women were recruited to participate if they had a self-reported UTI in the past 12 months. Of the 755 subjects, nearly 30% reported rUTI. Among women with rUTI, more than 50% reported being peri- or postmenopausal, and two-thirds reported vaginal symptoms. 15.8% of women with rUTI reported dissatisfaction with care versus 7.9% of women without rUTI. Most women see their primary care physician for UTI management and only 26% of women with rUTI follow with a urologist. More than 65% of women increase their fluid intake, wipe from front to back, and urinate after sexual activity to prevent UTIs. Significantly more women with rUTI use transvaginal estrogen, cranberry extract, and low-dose prophylactic antibiotics. These interventions appear to be driven by urologists. Most women who have had a UTI in the last 12 months implement lifestyle changes to prevent future infections. Most women see their PCP for UTI management and women with rUTI are twice as likely to report dissatisfaction with care. Despite urologists optimizing medical rUTI prevention, they appear to be underutilized.

Epigenome-Wide Analysis of DNA Methylation and Optimism in Women and Men.

Higher optimism is associated with reduced mortality and a lower risk of age-related chronic diseases. DNA methylation (DNAm) may provide insight into mechanisms underlying these relationships. We hypothesized that DNAm would differ among older individuals who are more versus less optimistic. Using cross-sectional data from two population-based cohorts of women with diverse races/ethnicities ( n = 3816) and men (only White, n = 667), we investigated the associations of optimism with epigenome-wide leukocyte DNAm. Random-effects meta-analyses were subsequently used to pool the individual results. Significantly differentially methylated cytosine-phosphate-guanines (CpGs) were identified by the "number of independent degrees of freedom" approach: effective degrees of freedom correction using the number of principal components (PCs), explaining >95% of the variation of the DNAm data (PC-correction). We performed regional analyses using comb-p and pathway analyses using the Ingenuity Pathway Analysis software. We found that essentially all CpGs (total probe N = 359,862) were homogeneous across sex and race/ethnicity in the DNAm-optimism association. In the single CpG site analyses based on homogeneous CpGs, we identified 13 significantly differentially methylated probes using PC-correction. We found four significantly differentially methylated regions and two significantly differentially methylated pathways. The annotated genes from the single CpG site and regional analyses are involved in psychiatric disorders, cardiovascular disease, cognitive impairment, and cancer. Identified pathways were related to cancer, and neurodevelopmental and neurodegenerative disorders. Our findings provide new insights into possible mechanisms underlying optimism and health.

Abstract P3-13-07: A comprehensive germline genetic landscape in young Jewish &amp; Arab women with breast cancer

Abstract Background: After decades of research on Ashkenazi Jewish (AJ) founder mutations in BRCA1 and BRCA2 (BRCA), there is still little known about genetics in non-AJ and Arab breast cancer populations in Israel and non-BRCA pathogenic variants (PV) in the total population. We used multigene panel testing (MGPT) to characterize the spectrum and prevalence of PV in cancer susceptibility genes in various Jewish and Arab demographic subgroups. Methods: A population-based cohort of women diagnosed with breast cancer before the age of 46 in a defined geographical area in Northern Israel was recruited as part of the BCINIS study and underwent MGPT. Probability matrices of proportion of PV by gene, and by ethnic sub-group (AJs, Sephardi Jews of North African origin, Sephardi Jews of other Eastern origins, Arabs), age-sub-group (35 and under, 36-45) and first-degree family history of breast, ovary or pancreatic cancer were calculated. Results: Overall, 1650 women were tested, including 1012 Jewish, 530 Arab and 108 non-Jewish/non-Arab women. We detected 375 PV among 363 women (22.7%): 212 in AJ (33.4% of AJs), 61 in Sephardi Jews (14.2% of Sephardi), and 69 in Arabs (13.0% of Arab). Only 162 of the PV (43.2%) were the BRCA AJ founders, another 39 BRCA PV (10.4%) were reported previously, while 15 BRCA PV (4.0%) are likely private. The remaining non-BRCA PV (42.4%) were distributed across 18 genes, with findings predominantly in CHEK2, MUTYH, ATM, BLM, ERCC3, PALB2, and FANCA. The prevalence of PV varied significantly across the ancestral subsets, from 95.5% probability in AJ women diagnosed before age 36 and with first degree family history to only 9.3% in Arab women diagnosed at age 36-45 and without family history. Conclusions: In this comprehensive, population-based, cohort of women with young onset breast cancer, the presence of PV in more than 15 genes is compelling and informs a necessarily broader approach to genetic testing and counseling. Citation Format: Gad Rennert, Bita Nehoray, Flavio Lejbkowicz, Sara Dishon, Shiri Kalet, Joseph Herzog, Thomas Slavin, Danielle Castillo, Kevin Tsang, Sharon Sand, Hedy S Rennert, Jeffrey Weitzel. A comprehensive germline genetic landscape in young Jewish &amp; Arab women with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-13-07.

Period Analysis of Intraracial Differences in Incidence and Survival Rates in Epithelial Ovarian Cancer.

Background To explain the difference in the incidence and relative survival in a population-based cohort of women with epithelial ovarian cancer (EOC) postdiagnosis in the last forty years. EOC is the most common type of all ovarian cancers, but there is inadequate information about the variations related to long-term EOC survival. Methods We acquired the incidence and relative survival rate data from the Surveillance, Epidemiology, and End Results (SEER) registries to analyze the epidemiological variations from 1974 to 2013 in EOC-affected individuals. The survival disparities in EOC-specific individuals due to age, race, and socioeconomic status (SES) were performed by Kaplan-Meier analysis. The Results. The overall incidence of EOC progressively declined to 9.0 per 100,000 from 11.4 in the last forty years. The median survival rate improved to 48 months in the first decade from a previous of 27 months in the fourth decade. The 5-year relative survival rate (RSR) increased to 44.3% that was previously 32.3% at the same time. However, between whites and blacks, an increase from 11 to 18 months was observed in the median survival differences. Between the low and high poverty groups, it was increased from 7 months to 12 months, respectively. Conclusions The incidence rate of RSR and EOC-specific individuals in the last forty years was improved. However, the survival rates among different races and SES differed over time.

Increasing use of post-mastectomy hypofractionated radiation therapy for breast cancer in Victoria.

The aim of this study was to evaluate the use of post-mastectomy hypofractionationed radiation therapy (HFRT) for breast cancer in Victoria, Australia. This is a population-based cohort of women with breast cancer who received post-mastectomy RT to the chest wall with or without nodal irradiation between 2012 and 2017. HFRT was defined as <25 fractions of RT. Data were captured in the Victorian Radiotherapy Minimum Dataset (VRMDS). The changing pattern of HFRT use was evaluated using the Cochran-Armitage test. Patient-, treatment- and institutional-related factors associated with HFRT use were evaluated using multivariable logistic regression. Two thousand and twenty-one women were included in this study, of which 238 (12%) received HFRT. This increased from 8% in 2012 to 18% in 2017 (P-trend < 0.001). Older women were more likely to have HFRT (26% in women above 70 years vs 6% in women under 50 years; P < 0.001). Women who did not have nodal irradiation were more likely to have HFRT than those who did (18% vs 9% respectively; P < 0.001). In multivariate analyses, the progressive increase in HFRT use over time remained statistically significant - women treated in 2017 were four times more likely to receive HFRT than those treated in 2012 (95% CI = 2.1-7.7; P < 0.001). Other factors independently associated with increased likelihood of HFRT use included increasing age at RT, and lack of nodal irradiation. In this first Australian study evaluating the use of post-mastectomy HFRT, we observed increasing HFRT use in Victoria over time. We anticipate this rising trend will continue in the coming years.

Genotype distribution of cervical HPV among Caribbean women in a population-based study in Martinique: The DEPIPAPUFR study.

The Caribbean ranks seventh among the world regions most affected by cervical cancer. HPV-prevalence and genotype distributions also differ from regions. Knowledge of HPV genotype profiles is important for patients care and HPV vaccination implementation. The objective of this study was to describe HPV genotype distribution and risk factors in a population-based cohort of women in Martinique. In this study, 1312 women were included and underwent cervical cancer screening with successful sample collection between 2009 and 2014. Sociodemographic and clinical variables were recorded. Cytological examination of cervical vaginal smear was performed and classified(Bethesda). Detection of HPV DNA was performed with the PapilloCheck© Kit from Greiner Bio-one. Genotypes were analyzed for18 high-risk HPV (hrHPV) and 6low-risk HPV(lrHPV) types. A total of 1075 women were included with a mean age of 49.1±10.5 years. HPV prevalence was 27.6% (297/1075) with 19.4% (209/1075) women with only hrHPV, 5.3% (57/1075) with only lrHPV. Multiple infections (hrHPV/lrHPV) were detected in 31/240 cases of hrHPV (12.9%). A total of 353 hrHPV genotypes were analyzed; the most common HPV types were HPV51 (11.0%), HPV68 (10.8%), HPV53 (9.1%) and HPV 52 (7.1%). HPV16 and HPV18 represented respectively 4.8% and 4.0% of hrHPV genotypes. Abnormal cytology was observed in 34 cases (3.2%), with 14 ASCUS (1.3%), 10 LSIL (0.9%), 5 HSIL (0.5%), 3 ASC-H (0.3%) and 2 AGC (0.2%). Fifteen (44.1%) were hrHPV and 4 (14.7%) lrHPV; 7 cases of hrPHV were in the age-group 25–34 years. Among 1041cases of normal cytology, 225 had positive hrHPV detection (21.6%). This is the first population-based study of HPV profiles in our country, and we found a high prevalence of hrHPV. The most common genotypes were HPV51, 68, 53. These results could serve for cancer vaccination strategies and HPV surveillance in Martinique.

Abstract 858: In utero exposure to anti-nauseants and risk of young-onset colorectal cancer

Abstract Background: Incidence rates of colorectal cancer (CRC) have increased markedly in Generation X, implicating exposures increasingly prevalent in their early life. Bendectin was a common anti-nauseant prescribed in early pregnancy during the 1960s and parallels increasing rates of young-onset CRC. Initially approved in 1956, Bendectin contained doxylamine (antihistamine), pyridoxine (vitamin B6), and dicyclomine (antispasmodic) but was reformulated in 1976 to contain only doxylamine and pyridoxine. Bendectin was removed from the market in 1983 after a series of lawsuits. In utero exposure to Bendectin has been implicated in birth defects and childhood leukemia, but little is known about its effects on health of adult offspring. Methods: We examined the effect of in utero exposure to Bendectin on risk of CRC in adult offspring in the Child Health and Development Studies, a population-based cohort of women receiving prenatal care between June 1959 and September 1966, with deliveries through June 1967 (n=18,751 live births excluding neonatal deaths among 14,507 mothers). Diagnosed conditions and prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received Bendectin in early pregnancy (day 1 - 140 of gestation). Incident cases of CRC in offspring were ascertained through 2018 by linkage with the California Cancer Registry. We used Cox proportional hazards models to estimate hazard ratios (HR), with follow-up accrued from birth through CRC diagnosis, death, or last contact. To address the possibility of confounding by indication, we also examined the effect of nausea and hyperemesis on risk of CRC in offspring. Results: About 6% of mothers (n=890) received Bendectin in early pregnancy. We identified 68 cases of CRC in offspring, diagnosed at ages 23 - 56 years (median age 50 years). In utero exposure to Bendectin was associated with increased risk of CRC in offspring (HR 2.93, 95% CI 1.45, 5.92). Dicyclomine was also associated with increased risk (HR 34.88, 95% CI 4.31, 282.50) when used alone as an antispasmodic (tradename Bentyl). There was no association with risk of CRC in offspring and other anti-nauseants containing meclizine only (HR 1.05, 95% CI 0.38, 2.89) or pyridoxine only (HR 2.20, 95% CI 0.31, 15.85) or with mothers' nausea (HR 0.62, 95% CI 0.23, 1.70). Conclusions: Our findings suggest in utero exposure to Bendectin, and specifically dicyclomine, increases risk of young-onset CRC. These results provide compelling evidence that events in utero are important risk factors of this disease. Bendectin was commonly prescribed in pregnancy during the 1960s, and there may be other medications prescribed during this time that contribute to increasing incidence rates of young-onset CRC. Citation Format: Caitlin C. Murphy, Piera M. Cirillo, Nickilou Y. Krigbaum, Barbara A. Cohn. In utero exposure to anti-nauseants and risk of young-onset colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 858.

947-P: Racial/Ethnic Differences in Type 2 Diabetes Diagnosis among Women with Gestational Diabetes: Creation of a Diverse Population-Based Eight-Year Postpartum Diabetes Cohort

Background: Women with gestational diabetes (GDM) are at increased risk of developing type 2 diabetes, a leading cause of premature morality. While data suggest racial/ethnic minority women bear the disproportionate burden of gestational diabetes, current postpartum GDM cohorts lack adequate diversity to examine whether racial/ethnic disparities persist in the transition to type 2 diabetes. To address this gap, we make use of two NYC public health surveillance databases to construct a novel population-based cohort of women with gestational diabetes and their progression to diabetes diagnosis. Methods: We used a systematic matching process to identify unique cases of women who gave birth between 2009 and 2011 and diabetes diagnosis (two A1c results6.5%) in the following 8 years using linked NYC vital statistics and HbA1c registry data. Results: Of 16,231 women with gestational diabetes, the cumulative incidence of diabetes in 8 years of follow-up was 14.4% (N=2,333 cases) in the overall cohort, 21.1% among non-Hispanic Black women, 15.9% among Hispanic women, 12.3% among Asian women, and 6.1% among non-Hispanic white women. Using this diverse cohort, future analyses will examine racial/ethnic differences in disease progression (e.g., from diabetes to glycemic control) among women with gestational diabetes, which has not been well studied in prior cohorts. Conclusions: This study makes use of diverse public health surveillance data to construct a population-based postpartum cohort of pregnant women to produce pioneering evidence of diabetes disease progression (using HbA1c levels) following pregnancies complicated by GDM. Future research will leverage this novel cohort to investigate how social determinants influence lifecourse racial-ethnic disparities in diabetes. Disclosure T. Janevic: None. K. J. Mccarthy: None. J. J. Kennedy: None. H. Chan: None. G. Van wye: None. V. L. Mayer: None. S. H. Liu: None. M. Huynh: None. Funding National Institutes of Health (R21DK122266)

Practice patterns of platinum chemotherapy use in a population-based cohort of women with nonmetastatic triple-negative breast cancer.

e18590 Background: The use of platinum agents (PT) in neoadjuvant chemotherapy (CTX) for triple negative breast cancer (TNBC) has been debated in research and practice guidelines. In high risk patients, the addition of PT to standard anthracycline and taxane regimens improves pathological complete response without definitive evidence of survival benefit (Korde JCO 2021). Due to PT’s toxicities and unclear benefit in early stage breast cancer, this study aimed to elucidate the real world practice patterns of PT use and overuse in breast cancer patients. Methods: The cohort was defined as women with stage I-III TNBC (ER, PR, and Her2 negative) who received curative intent surgery between 2011-2018. We utilized the Hutchinson Institute for Cancer Outcomes Research (HICOR) database, which links enrollment and claims records from commercial and public health insurance plans with clinical information from Washington state cancer registries (Manohar JACR 2020). We hypothesized there was overuse of PT CTX in this cohort. Overuse was defined as PT use in stage I, in the adjuvant period (NCCN 2020), and in nonstandard CTX regimens (PT use without taxane and anthracycline (NCCN 2020)). Results: Of the 910 women in the cohort, average age was 63, 90% were white, 682 (75%) received CTX, and 36% had commercial insurance, versus 53% with public insurance (Medicare 45%, Medicaid 8%). Of those receiving CTX, 39% received neoadjuvant and 67% adjuvant. Of those receiving CTX, 85 (13%) received PT, and 28 (4%) received PT without anthracycline. Of those receiving PT, 20% had stage I disease, and of those receiving adjuvant CTX, 43 (9%) received PT in the adjuvant period. Conclusions: We found there was overuse and nonstandard use of PT in this real world data. This overuse was demonstrated by the fact that 20% of women receiving PT had low risk stage I disease, and 9% of women receiving adjuvant CTX received PT in the adjuvant period. Additionally, there was nonstandard use, with 4% of women getting CTX receiving PT without anthracycline. Next steps in this research are to evaluate factors influencing overuse and nonstandard use, as well as complication rates with PT use and overuse.[Table: see text]

Choosing Wisely in radiation therapy for breast cancer: Time lag in adoption of hypofractionated radiation therapy in Victoria.

To evaluate the adoption of hypofractionated radiotherapy (HFRT) for breast cancer (BC) in Victoria, Australia. This is a population-based cohort of women with BC who had breast RT as captured in the Victorian Radiotherapy Minimum Data Set between 2012 and 2017. We defined HFRT as<25 fractions of RT. The pattern of HFRT use over time was evaluated with the Cochrane-Armitage test for trend. Factors associated with HFRT were identified using multivariable logistic regression. 12,717 women were included in the study. Overall, 6,653 (52%) patients had HFRT. HFRT use increased from 35% in 2012 to 66% in 2017 (P-trend<0.001). Older women were more likely to have HFRT (74% for women aged≥70years vs. 27% for women aged<50years; P<0.001). Women who had nodal irradiation were less likely to have HFRT compared with those who did not (13% vs. 57%; P<0.001). HFRT use was more common in public than private institutions (57% vs. 46%, P<0.001), and in metropolitan than regional centres (54% vs. 46%, P<0.001). In multivariable analyses, the progressive increase in HFRT use over time was independent of other covariates - women treated in 2017 were 7.3 times (95% CI=6.3-8.6, P<0.001) more likely to be treated with HFRT than in 2012. Age at RT, nodal irradiation, area of residence and institutional type and locations were all independently associated with HFRT use. This large Australian contemporary population-based study demonstrates increasing use of HFRT for BC. However, large sociodemographic and institutional provider-related variations in practice still exist.

Longitudinal Symptom Burden Trajectories in a Population-Based Cohort of Women with Metastatic Breast Cancer: A Group-Based Trajectory Modeling Analysis.

Understanding the symptom burden trajectory for metastatic breast cancer patients can enable the provision of appropriate supportive care for symptom management. The aim of this study was to describe the longitudinal trajectories of symptom burden for metastatic breast cancer patients at the population-level. A cohort of 995 metastatic breast cancer patients with 16,146 Edmonton Symptom Assessment System (ESAS) assessments was constructed using linked population-level health administrative databases. The patient-reported ESAS total symptom distress score (TSDS) was studied over time using group-based trajectory modeling, and covariate influences on trajectory patterns were examined. Cohort patients experienced symptom burden that could be divided into six distinct trajectories. Patients experiencing a higher baseline TSDS were likely to be classified into trajectory groups with high, uncontrolled TSDS within the study follow-up period (χ2 (1, N = 995) = 136.25, p < 0.001). Compared to patients classified in the group trajectory with the highest relative TSDS (Group 6), patients classified in the lowest relative TSDS trajectory group (Group 1) were more likely to not have comorbidities (97.34% (for Groups 1–3) vs. 91.82% (for Group 6); p < 0.05), more likely to receive chemotherapy (86.52% vs. 80.50%; p < 0.05), and less likely to receive palliative care (52.81% vs. 79.25%; p < 0.0001). Receiving radiotherapy was a significant predictor of how symptom burden was experienced in all identified groups. Overall, metastatic breast cancer patients follow heterogeneous symptom burden trajectories over time, with some experiencing a higher, uncontrolled symptom burden. Understanding trajectories can assist in establishing risk-stratified care pathways for patients.

Mammography features for early markers of aggressive breast cancer subtypes and tumor characteristics: A population-based cohort study.

Current breast cancer risk models identify mostly less aggressive tumors, although only women developing fatal breast cancer will greatly benefit from early identification. Here, we evaluated the use of mammography features (microcalcification clusters, computer‐generated Breast Imaging Reporting and Data System [cBIRADS] density and lack of breast density reduction) as early markers of aggressive subtypes and tumor characteristics. Mammograms were retrieved from a population‐based cohort of women that were diagnosed with breast cancer from 2001 to 2008 in Stockholm‐Gotland County, Sweden. Tumor and patient characteristics were obtained from Stockholm Breast Cancer Quality Register and the Swedish Cancer Registry. Multinomial logistic regression was used to individually model each mammographic feature as a function of molecular subtypes, tumor characteristics and detection mode. A total of 4546 women with invasive breast cancer were included in the study. Women with microcalcification clusters in the affected breast were more likely to have human epidermal growth factor receptor 2 subtype (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.24‐2.54) and potentially less likely to have basal subtype (OR 0.54; 0.30‐0.96) compared to Luminal A subtype. High mammographic cBIRADS showed association with larger tumor size and interval vs screen‐detected cancers. Lack of density reduction was associated with interval vs screen‐detected cancers (OR 1.43; 1.11‐1.83) and potentially of Luminal B subtype vs Luminal A subtype (OR 1.76; 1.04‐2.99). In conclusion, microcalcification clusters, cBIRADS density and lack of breast density reduction could serve as early markers of particular subtypes and tumor characteristics of breast cancer. This information has the potential to be integrated into risk models to identify women at risk for developing aggressive breast cancer in need of supplemental screening.

Asthma-like symptoms in young children increase the risk of COPD

Chronic obstructive pulmonary disease (COPD) may originate in early life and share disease mechanisms with asthma-like symptoms in early childhood. This possibility remains unexplored on account of the lack of long-term prospective studies from infancy to the onset of COPD. We aimed to investigate the relationship between asthma-like symptoms in young children and development of COPD. In a population-based cohort of women who gave birth at the central hospital in Copenhagen during period from 1959 to 1961, we investigated data from 3290 mother-child pairs who attended examinations during pregnancy and when the children were aged 1, 3, and 6 years. COPD was assessed from the Danish national registries on hospitalizations and prescription medication since 1994. Asubgroup of 930 individuals underwent spirometry testing at age 50 years. Of the 3290 children, 1 in 4 had a history of asthma-like symptoms in early childhood. The adjusted hazard ratio for hospitalization for COPD was 1.88 (95% CI= 1.32-2.68), and the odds ratio for prescription of long-acting muscarinic antagonists was 2.27 (95% CI= 1.38-3.70). Asthma-like symptoms in early childhood were also associated with a reduced FEV1 percent predicted and an FEV1-to-forced vital capacity ratio at age 50 years (-3.36% [95% CI= -5.47 to -1.24] and -1.28 [95% CI= -2.17 to -0.38], respectively) and with COPD defined according to Global Initiative for Chronic Obstructive Lung Disease stage higher than 1 (odds ratio= 1.96 [95% CI= 1.13-3.34]). This 60-year prospective follow-up of a mother-child cohort demonstrated a doubled risk for COPD from childhood asthma-like symptoms.

Abstract C099: Variance in mode of detection for breast cancer by breast density and stage at diagnosis: A pilot study

Abstract Introduction and Background: Mammography is thought to have an overall sensitivity of 87% according to the Breast Cancer Screening Consortium (BCSC). However, evidence from more recent studies indicate that a significant proportion of patients come into care with breast cancer symptoms, which trigger diagnosis rather than regular screening mammography. Women with breast cancer symptoms often have advanced cancer at diagnosis. This implies that previous negative mammograms are false negatives, and that screening mammography alone was insufficient for this population. Such populations include women with dense breasts, for whom mammography has a known 10-29% decrease in regardless of stage at diagnosis, and women who do not use screening mammography regularly or at all. Specific Experimental Aims: In a US population-based cohort of women who have developed first time breast cancer, we will 1) determine the variance in mode of detection, and 2) determine if mode of detection varied by breast density or by stage at diagnosis. Methods and Design: We identified a cohort of 386 women with a diagnosis of first time breast cancer (ICD codes) within a 7 county, 98.5% coverage population. We randomly sampled 30 women and performed chart review. The data were collated in REDCap, and reported with descriptive statistics. Results: In our pilot random sample (n=30), 33% (10/30) of women had DCIS, 30% (9/30) had non-advanced cancer, and 37% (11/30) had advanced cancer. For women with DCIS, 90% (9/10) were found with screening mammography, compared to only 44% (4/9) of non-advanced, and 45% (5/11) advanced cancers. Approximately 43% (13/30) of women in this sample had dense breasts. Interestingly, 61.5% (8/13) women with dense breasts, and 62.5% (10/16) of women with non-dense breasts had screening mammography as the mode of detection. Finally, among women with dense breasts, 46.1% (6/13) had DCIS, 30.8% (4/13) had non-advanced cancer, and 23.1% (3/13) had advanced cancer, while for women with non-dense breasts, 25% (4/16) had DCIS, 31.2% (5/16) had non-advanced cancer, and 43.8% (7/16) had advanced cancer. Conclusions and Future Directions: These pilot data suggest that our population reflects both the breast density rate (47%, BCSC) and the rate of advanced cancers (36%, SEER) found in the national population, and that there is a strong likelihood that regardless of breast density, but especially for non-DCIS, screening mammography alone may not be sufficient detect breast cancer (44-45%) compared to the BCSC statistic of 87%. This may be due to misattribution of mode of detection for breast cancer, especially in symptomatic later stages of disease. Once the full study is completed, future research regarding outcomes (mortality and otherwise) and stage at diagnosis for patients who use additional screening methods may be valuable. In addition, for women with lower access to, or who choose not to use screening mammography, future research regarding revisiting the use of SBE and CBE as well as other modalities may also be valuable. Citation Format: Susanna N Basappa, Lila JF Rutten. Variance in mode of detection for breast cancer by breast density and stage at diagnosis: A pilot study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C099.

Abstract A079: Social-pain clusters in diverse women with breast cancer, and associations with sociodemographic factors and mortality

Abstract Background: Social factors and physical pain are related bidirectionally and as a function of temperament and disease processes, but the relevance of this to population research is unknown. We developed social-pain clusters, or groups that were similar with regard to social and pain characteristics, in a large, population-based cohort of women with breast cancer, evaluating associations of resulting clusters with sociodemographic factors and mortality. Methods: The study population included 4,279 women from the Pathways Study, a prospective cohort study of women diagnosed from 2006-2013 with stages I-IV breast cancer in Kaiser Permanente Northern California, who provided data on social (social integration, social well-being, loneliness, social well-being) and bodily pain measures at study baseline. Measures included the Medical Outcomes Study Social Support survey, the Functional Assessment of Cancer Therapy, a single-item measure of loneliness from the Center for Epidemiologic Studies-Depression measure, and a previously derived measure of social integration (Kroenke et al.). We used latent class analysis to develop social-pain clusters and used BIC criteria to select the optimal number of clusters. We further evaluated associations of age, race/ethnicity, education, and income with clusters in multivariate-adjusted logistic regression analyses, with adjustment for depressive symptoms, and also evaluated associations of clusters with mortality using Cox models. Results: Cluster analysis produced three clusters including a “resilient” cluster characterized by low social and pain symptomatology (including 30% of study participants), a “distressed” cluster characterized by high symptomatology (20% of participants), and an intermediate cluster characterized by high pain and compromised social function but otherwise high support (50% of participants). Sociodemographic factors associated with higher odds of categorization in the distressed (vs. resilient) cluster included age (OR=1.04, 95% CI: 1.02-1.05), income &amp;lt;$25K (OR=9.30, 95% CI: 5.72-15.13), API race/ethnicity (OR=2.51, 95% CI: 1.72-3.67), and graduate-level education (OR=1.60, 95% CI: 1.16-2.22). Age, low income, and API race/ethnicity were also related to higher odds of categorization in the intermediate (vs. resilient) cluster. However, those in the distressed (HR=1.38, 95% CI: 1.06-1.80), but not intermediate (HR=1.05, CI: 0.83-1.33), cluster had a higher risk of overall mortality. Conclusions: Age, low income, and API race/ethnicity predicted higher social and pain symptomatology in a population-based breast cancer cohort, independent of depressive symptoms. The clustering of these symptoms was related to higher overall mortality. Reference: Kroenke CH, Kwan ML, Neugut AI, Ergas IJ, Wright JD, Caan BJ, Hershman D, Kushi LH. Social networks, social support mechanisms, and quality of life after breast cancer diagnosis. Breast Cancer Res Treat 2013;139(2):515-27. Citation Format: Candyce H. Kroenke, Stacey Alexeeff, Scarlett Lin Gomez, Marilyn L. Kwan, Lawrence H. Kushi. Social-pain clusters in diverse women with breast cancer, and associations with sociodemographic factors and mortality [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A079.

Diabetes and cardiovascular disease mortality among a population-based cohort of women with and without breast cancer

We investigated whether the relationship between diabetes and all-cause and CVD-related mortality differed between women with and without breast cancer among a cohort drawn from the same source population. We interviewed 1,363 women newly diagnosed with breast cancer in 1996-1997, and 1,358 age-matched women without breast cancer, to assess history of physician-diagnosed diabetes. All-cause (n = 631) and CVD-specific mortality (n = 234) was determined by the National Death Index through 2009. We estimated multivariable-adjusted hazard ratios (HRs) for the rates of all-cause and CVD-specific mortality and, to account for competing causes of death, and subdistribution HRs (sHRs) for risk of CVD-related death. Among women with and without breast cancer, respectively, diabetes was associated with: all-cause mortality [HR (95% CI) 1.52 (1.13, 2.05) and 2.17 (1.46, 3.22)]; CVD-specific deaths [1.74 (1.06, 2.84) and 2.06 (1.11, 3.84)]; and risk of CVD-related death [sHR 1.36 (0.81, 2.27) and 1.79 (0.94, 3.40)]. Differences in effect estimates between women with and without breast cancer did not reach statistical significance (p-interaction > 0.10). We found that the positive association between a history of physician-diagnosed diabetes and risk of all-cause and CVD-related mortality is of similar magnitude among a population-based cohort of women with or without breast cancer.