Incident Breast Cancer Diagnosis Research Articles

Abstract 2202: Association of multi-morbidity with incident cancer diagnoses

Abstract Background: Multi-morbidity (MM), which is usually defined as a simple count of the number of different diseases an individual has, has previously been identified as a risk factor for some incident cancer diagnoses. This study aimed to use more sophisticated machine learning techniques to classify MM into disease clusters and to investigate their association with incident colorectal (CRC), breast (BC), lung (LC) and prostate (PrC) cancer diagnoses. Methods: Participants in UK Biobank with a hospital (HES) record and no prevalent cancer were included in the study. Self-reported (SR), HES and primary-care (GP) recorded diseases were converted to phecodes. Sex-stratified latent class analyses (LCA) was used to identify disease clusters in the SR data. Associations between clusters and selected cancer diagnoses was undertaken using Cox proportional hazards modelling, adjusting for age, ethnicity, socio-economic status, year and region of recruitment, body mass index, smoking history, alcohol consumption and menopausal hormone therapy use (women only). The analyses were validated using HES and GP data. Results: The analysis included 158,951 women and 127,406 men. Just over 30% (49,061) of women and 37% (48,110) of men had MM (≥2 diseases) at recruitment. LCA identified 10 disease clusters in women, the most common of which was related to respiratory disease, largely comprising asthma (9344; 19.1%). Nine disease clusters were identified in men, the most common of which was related to heart disease (9358; 19.5%), and largely comprising ischemic heart disease and hypertension. No association between disease cluster and incident CRC or BC was identified. In women, LC risk was associated with several disease clusters: respiratory (Hazard Ratio 1.57 (95% confidence interval 1.28 - 1.91) p<0.001), arthritis/gut (1.46 (1.15 - 1.85) p=0.002), hyperlipidemia (1.51 (1.19 - 1.92) p=0.001, cardiac (1.74 (1.40 - 2.17) p<0.001) and type 2 diabetes (T2DM) (1.56 (1.16 - 2.09) p=0.003). In men, LC was associated with disease clusters of hyperlipidemia/hypertension (1.23 (1.02 - 1.48) p=0.03), cardiac (1.40 (1.18 - 1.66) p<0.001), T2DM (1.26 (1.02 - 1.56) p=0.03), respiratory (2.74 (2.21 - 3.39) p<0.001) and cardiometabolic/arthritis (1.81 (1.08 - 3.03) p=0.02). T2DM (0.80 (0.68 - 0.87) p<0.001) was associated with an inverse risk of PrC. Cluster distribution was similar in HES and GP data, with the association between the cardiac and the arthritis clusters replicated for LC in women, and the respiratory cluster for LC and T2DM cluster for PrC in men. Conclusion: Clusters of MM were identified in a large cancer-free population, which were replicated using different sources of healthcare data. Several disease clusters were associated with incident LC and, to a lesser extent, PrC. Further work to understand the potential causal nature of these associations is needed. Citation Format: Megan C. Conroy, Gillian K. Reeves, Naomi E. Allen. Association of multi-morbidity with incident cancer diagnoses [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 2202.

RECEIPT OF CHEMOTHERAPY AND COGNITIVE DECLINE AMONG MEDICARE BENEFICIARIES IN THE US HEALTH AND RETIREMENT STUDY

Abstract Research on cancer and cognitive aging outcomes has been inconsistent, with clinic-based studies showing short-term cognitive declines after chemotherapy, and population-based epidemiological studies observing inverse associations between most cancers and subsequent cognitive aging. We aimed to determine the effect of chemotherapy on cognitive decline and mortality among Medicare beneficiaries in the population-based US Health and Retirement Study (HRS). Using data from HRS-Medicare linked participants ≥65, we identified 858 incident breast, prostate, and kidney cancer diagnoses from 2000 to 2016. Cognitive function was measured using the modified telephone interview for cognitive status (range 0 to 27). Cancer treatment (chemotherapy only, other treatments, and no treatment) was obtained from Medicare claims. We used joint modeling to simultaneously model the association between cancer treatment with cognition decline and mortality. Of 858 participants, 38.7% had breast cancer, 52% had prostate cancer, and 11% had kidney cancer. The mean age at diagnosis was 72.8 years (SD=7.62). 31.7% (n=272) received chemotherapy only, 39.5% (n=339) received other treatment, and 28.8% (n=247) received no treatment. In pooled analyses, receipt of chemotherapy (vs. no treatment) was not significantly associated with cognitive decline (β: 0.08; 95% CI: -0.59, 0.76) but was significantly associated with mortality (HR: 1.39; 95% CI: 1.04, 1.88). In joint modeling, the overall hazard ratio for the receipt of chemotherapy (vs. no treatment) was 1.38 (95% CI: 1.02, 1.88). We found that receipt of chemotherapy was associated with an increased hazard of mortality, but not cognitive decline, compared to those who received no treatment.

Correctness and Completeness of Breast Cancer Diagnoses Recorded in UK CPRD Aurum and CPRD GOLD Databases: Comparison to Hospital Episode Statistics and Cancer Registry (Companion Paper 2).

To evaluate the new Clinical Practice Research Datalink (CPRD) Aurum database, we estimated 'correctness' (ie accuracy, validity) and 'completeness' (ie presence, missingness) of malignant breast cancer diagnoses recorded in CPRD Aurum compared to external linked data sources: Hospital Episode Statistics (HES) Admitted Patient Care (APC), HES Outpatient (OP), and Cancer Registry (CR), and to the previously validated CPRD GOLD. Linkage-eligible, female patients with incident malignant breast cancer diagnosis recorded in at least one study data source were selected. Correctness was the proportion of malignant breast cancer cases recorded in CPRD Aurum or GOLD who also had a diagnosis recorded in HES APC/OP (2004-2019) or CR (2004-2016). Completeness was estimated by identifying all malignant breast cancer diagnoses in HES APC/OP or CR and calculating the proportion with a concordant diagnosis in CPRD Aurum or GOLD. Compared to HES APC/OP, there were 85,659 and 31,452 eligible patients in CPRD Aurum and GOLD, respectively. Correctness estimates were high (CPRD Aurum 83.5%, GOLD 81.7%). Compared to CR, there were 70,190 and 29,597 eligible patients in CPRD Aurum and GOLD, respectively: correctness was 89.1% for CPRD Aurum and 88.2% for GOLD. Completeness estimates for CPRD Aurum and GOLD were high (>90%). Diagnoses were recorded in CPRD Aurum within -7 to 74 days of those in the linked sources. Reasons for discordant diagnostic coding included presence of treatment or other clinical codes only, diagnosis coded after end of follow-up, non-malignant breast cancer in linked data, and administrative codes in lieu of diagnostic codes. These results indicate that correctness and completeness of malignant breast cancer diagnoses in CPRD Aurum were high and similar to CPRD GOLD. This provides confidence in use of CPRD Aurum for research purposes. Where complete case capture is important, researchers should consider linkage to HES APC or CR.

The association between cardiovascular disease and breast and gynecologic cancers among black female patients

IntroductionLittle is known about whether a breast or gynecologic cancer diagnosis increases long-term cardiovascular disease (CVD) risk among Black females. The purpose of this study was to determine whether a breast or gynecologic cancer diagnosis is associated with CVD risk and identify determinants of subsequent CVD risk among Black females with an incident breast or gynecologic cancer diagnosis. MethodsUsing the Southern Community Cohort Study data from 2002–2016, this study was designed to analyze CVD incidence among Black females without cancer or CVD at enrollment. Cox proportional hazards regression models with or without covariates were used to explore the relationship between a breast or gynecologic cancer diagnosis and CVD risk among women without cancer as well as without CVD at enrollment (N=11,486). In addition, Cox proportional hazards regression models, excluding those who developed CVD before breast and gynecologic cancer diagnosis and those with other types of cancers, were used to assess determinants of CVD risk among breast and gynecologic cancer survivors. ResultsOf 11,486 Black females, 531 developed a breast or gynecological cancer (4.6%) over a median follow-up of 140 months (interquartile range: 123-159 months). Compared to women without cancer, women with a breast or gynecological cancers had greater than 20% higher risk of incident CVD during the follow-up period. Without adjusting for covariates, positive association between CVD risk and breast cancer was observed (hazard ratio (HR) = 1.24; 95% confidence interval (CI) = 1.11 - 1.39; p < 0.001); as well as between CVD risk and a gynecological cancer (HR = 1.23; 95% CI = 1.03 - 1.46; p = 0.021). Yet, after adjusting for covariates, CVD risk was only significantly associated with breast cancer (p = 0.001) but not gynecologic cancer. In cancer case-only analyses, CVD risk was significantly increasing with age (p < 0.05). ConclusionsLike study populations of predominantly White females, our results suggest that, adjusting for covariates, Black females possess a higher risk of CVD following a breast cancer diagnosis compared to women who did not develop breast cancer. Our results suggest a need for active CVD surveillance in the cancer survivorship phase.

Early Ascertainment of Breast Cancer Diagnoses Comparing Self-Reported Questionnaires and Electronic Health Record Data Warehouse: The WISDOM Study.

The goal of this study was to use real-world data sources that may be faster and more complete than self-reported data alone, and timelier than cancer registries, to ascertain breast cancer cases in the ongoing screening trial, the WISDOM Study. We developed a data warehouse procedural process (DWPP) to identify breast cancer cases from a subgroup of WISDOM participants (n = 11,314) who received breast-related care from a University of California Health Center in the period 2012-2021 by searching electronic health records (EHRs) in the University of California Data Warehouse (UCDW). Incident breast cancer diagnoses identified by the DWPP were compared with those identified by self-report via annual follow-up online questionnaires. Our study identified 172 participants with confirmed breast cancer diagnoses in the period 2016-2021 by the following sources: 129 (75%) by both self-report and DWPP, 23 (13%) by DWPP alone, and 20 (12%) by self-report only. Among those with International Classification of Diseases 10th revision cancer diagnostic codes, no diagnosis was confirmed in 18% of participants. For diagnoses that occurred ≥20 months before the January 1, 2022, UCDW data pull, WISDOM self-reported data via annual questionnaire achieved high accuracy (96%), as confirmed by the cancer registry. More rapid cancer ascertainment can be achieved by combining self-reported data with EHR data from a health system data warehouse registry, particularly to address self-reported questionnaire issues such as timing delays (ie, time lag between participant diagnoses and the submission of their self-reported questionnaire typically ranges from a month to a year) and lack of response. Although cancer registry reporting often is not as timely, it does not require verification as does the DWPP or self-report from annual questionnaires.

Routine practice data of three cancer entities: Comparison among cancer registry and health insurance data

IntroductionClaims data and cancer registry data are valuable secondary data sources for addressing health service research questions. This study provides a thorough insight into the comparability of data from health insurance companies and cancer registries in Germany regarding breast, prostate, and lung cancer patients and their treatment. MethodsFor this study claims data of the InGef database and data of the Cancer Registry of Rhineland-Palatinate were used to identify patients living in Rhineland-Palatinate with an incident breast, prostate, or lung cancer diagnosis between Jan. 1, 2018 and Dec. 31, 2019. Both datasets were compared for patient and tumour characteristics as well as treatment strategy. For the descriptive analysis of tumour localisation and treatment all patients were followed up for a maximum of two years. ResultsA total of 1,470 incident cancer cases were identified in the InGef database and 1,694 in the Cancer Registry. Data on sex, age, and tumour localisation matched well for all cancer entities in the cohorts. Data for early UICC stages I+II varied between the cohorts for prostate cancer (84% InGef, 66% Cancer Registry) and lung cancer (29% InGef, 20% Cancer Registry). Larger deviations were found for antihormonal treatment (breast 54% vs. 44%, prostate 32% vs. 18%). Significant differences were found for surgery (breast and lung) and radiation (breast and prostate), respectively. DiscussionAge at diagnosis, tumour localisation, and treatment for breast cancer was well documented in both databases. Tumour-specific deviations were observed for tumour localisations (lung cancer), UICC stage (prostate and lung cancer) and treatment options. ConclusionBoth databases show very good completeness across cancer entities, but at the same time have minor limitations where they could readily complement each other. Individual linkage of claims and registry data could be an important step to improve oncological studies with routine practice data and to overcome the limitations identified.

The Association Between Mammography Screening Frequency and Breast Cancer Treatment and Outcomes: A Retrospective Cohort Study.

Guidelines for optimal frequency of screening mammography vary by professional society. Sparse evidence exists on the association between screening frequency and breast cancer treatment options. The main objective was to examine differences in cancer treatment rendered for U.S. women with different numbers of screenings prior to breast cancer diagnosis. Cancer stage at diagnosis and health care cost were assessed in secondary analyses. This IRB-exempt retrospective study used administrative claims data to identify women aged 44 or older with various numbers of mammographic screenings ≥11 months apart, during the four years prior to incident breast cancer diagnosis from January 2010 to December 2018. Outcomes were assessed over the six months following diagnosis. Generalized linear regression models were used to compare women with differing numbers of mammograms, adjusting for patient characteristics. Claims data review identified 25 492 women who met inclusion criteria. There was a stepwise improvement in each of these screening categories such that women with four screenings, compared to women with only one screening, experienced higher rates of lumpectomy (70% vs 55%) and radiation therapy (48% vs 36%), lower rates of mastectomy (27% vs 34%) and chemotherapy (28% vs 36%), less stage 3 or 4 cancer at diagnosis (15% vs 29%), and lower health care costs within six months postdiagnosis (P < 0.001). Results were similar in a subgroup limited to women aged 44 to 49 at diagnosis. Potential benefits of more frequent screening include less aggressive treatment and lower health care costs among women who develop breast cancer.

Use of a Novel Network-Based Linchpin Score to Characterize Accessibility to the Oncology Physician Workforce in the United States

Physician headcounts provide useful information about the cancer care delivery workforce; however, efforts to track the oncology workforce would benefit from new measures that capture how essential a physician is for meeting the multidisciplinary cancer care needs of the region. Physicians are considered linchpins when fewer of their peers are connected to other physicians of the same specialty as the focal physician. Because they are locally unique for their specialty, these physicians' networks may be particularly vulnerable to their removal from the network (eg, through relocation or retirement). To examine a novel network-based physician linchpin score within nationwide cancer patient-sharing networks and explore variation in network vulnerability across hospital referral regions (HRRs). This cross-sectional study analyzed fee-for-service Medicare claims and included Medicare beneficiaries with an incident diagnosis of breast, colorectal, or lung cancer from 2016 to 2018 and their treating physicians. Data were analyzed from March 2022 to October 2022. Physician characteristics assessed were specialty, rurality, and Census region. HRR variables assessed include sociodemographic and socioeconomic characteristics and use of cancer services. Oncologist linchpin score, which examined the extent to which a physician's peers were connected to other physicians of the same specialty as the focal physician. Network vulnerability, which distinguished HRRs with more linchpin oncologists than expected based on oncologist density. χ2 and Fisher exact tests were used to examine relationships between oncologist characteristics and linchpin score. Spearman rank correlation coefficient (ρ) was used to measure the strength and direction of relationships between HRR network vulnerability, oncologist density, population sociodemographic and socioeconomic characteristics, and cancer service use. The study cohort comprised 308 714 patients with breast, colorectal, or lung cancer. The study cohort of 308 714 patients included 161 206 (52.2%) patients with breast cancer, 76 604 (24.8%) patients with colorectal cancer, and 70 904 (23.0%) patients with lung cancer. In our sample, 272 425 patients (88%) were White, and 238 603 patients (77%) lived in metropolitan areas. The cancer patient-sharing network included 7221 medical oncologists and 3573 radiation oncologists. HRRs with more vulnerable networks for medical oncology had a higher percentage of beneficiaries eligible for Medicaid (ρ, 0.19; 95% CI, 0.08 to 0.29). HRRs with more vulnerable networks for radiation oncology had a higher percentage of beneficiaries living in poverty (ρ, 0.17; 95% CI, 0.06 to 0.27), and a higher percentage of beneficiaries eligible for Medicaid (ρ, 0.21; 95% CI, 0.09 to 0.31), and lower rates of cohort patients receiving radiation therapy (ρ, -0.18; 95% CI, -0.28 to -0.06; P = .003). The was no association between network vulnerability for medical oncology and percent of cohort patients receiving chemotherapy (ρ, -0.03; 95% CI, -0.15 to 0.08). This study found that patient-sharing network vulnerability was associated with poverty and lower rates of radiation therapy. Health policy strategies for addressing network vulnerability may improve access to interdisciplinary care and reduce treatment disparities.

Clinical Impact of ASCO Choosing Wisely Guidelines on Staging Imaging for Early-Stage Breast Cancers: A Time Series Analysis Using SEER-Medicare Data.

American Society for Clinical Oncology released the Choosing Wisely list in 2012, highlighting low-value procedures that lack evidence, advising against the use of positron emission tomography, computerized tomography, and radionuclide bone scans for the staging of early-stage breast cancer at low risk for metastasis. The objective of the study was to assess the impact of the American Society of Clinical Oncology Choosing Wisely guidelines on inappropriate staging imaging among early-stage breast cancers. The Surveillance, Epidemiology, and End Results Program-Medicare data set was used to identify 50,004 women age 66 years and older with new incident diagnosis of early-stage breast cancer (stage 0 through stage 2a; T < 4, N = 0, and M = 0). The primary outcome was the incidence of patients with inappropriate imaging following an early-stage breast cancer diagnosis. The primary outcome was identified within 6 months of the first diagnosis. An interrupted time series analysis using negative binomial regression was performed for outpatient claims for these diagnostic studies versus the two interruptions of guidelines release and guidelines reinforcement. Mean images per patient, percent change for the study period, and rate of change per year were calculated. Imaging rates fell by a modest 2.32% following guidelines release in April 2012 (point estimate = -2.32%; 95% CI, -6.34% to 1.88%). By contrast, imaging rates fell by a four-fold larger amount (point estimate = -9.36%; 95% CI, -13.20% to -5.35%) following guidelines published reminders in journals (or reinforcement) in October 2013. Mean imaging studies per patient (95% CI) declined from 1.80 (1.76 to 1.84) in January 2012 to 1.50 (1.48 to 1.53) by January 2015, representing a 16% decline in imaging overuse in 2015 compared with 3 years earlier. The rate of change (95% CI) in images per patient was initially small at -0.47% (-4.27% to 3.33%) per year between April 2012 and October 2013, but almost eight times faster at -3.70% (-5.81% to -1.60%) per year after October 2013. This analysis demonstrates a substantial decrease in the prevalence of imaging overuse in early-stage breast cancers correlating with the 2013 reinforcement of American Society of Clinical Oncology's 2012 Choosing Wisely guidelines. The creation and dissemination of such resources serves as a powerful tool to improve clinical practice, cost-effectiveness, and patient safety from secondary malignancies, anxiety, and overdiagnosis.

Anti-Müllerian hormone levels and breast cancer risk in the study of women's health across the nation.

The relation of premenopausal anti-Müllerian hormone (AMH) levels with breast cancer risk has been evaluated in a few studies, but primarily in non-Hispanic White women. We evaluated the association of AMH levels with breast cancer risk in Study of Women's Health Across the Nation (SWAN), a multi-ethnic cohort of women. At enrollment, participants had an intact uterus and ≥ 1 ovary, and ≥ 1 menstrual period in the last 3months. AMH at first measurement was assessed in 1,529 pre- or perimenopausal women using a high-sensitivity ELISA assay; values were natural log transformed. Breast cancer diagnoses were assessed at enrollment and subsequent follow-up visits through 2018 (median 6.1years). In total, 84 women reported an incident breast cancer diagnosis. In multivariable Cox regression models adjusting for age, race and ethnicity, body mass index, and other factors, higher AMH levels were associated with a non-significant increased breast cancer risk. Compared to women in the 1st quartile, the hazard ratio (95% confidence interval) for women in the4th quartile was 1.77 (0.87-3.60). Our results did not suggest a significant association between AMH and breast cancer risk; however, estimates were consistent with prior studies that reported positive associations.

Residential ultraviolet radiation and breast cancer risk in a large prospective cohort.

Ambient ultraviolet (UV) radiation has been increasing due to climate change. While this may result in adverse health consequences such as an increased incidence of skin cancer, UV radiation is also a source of vitamin D, which has been hypothesized to be protective for breast cancer risk. Using a spatiotemporal kriging model, we estimated residential UV exposure levels for the enrollment addresses (2003-2009) of breast cancer-free women aged 35-74years participating in the Sister Study and living in the contiguous United States (N=48,450). Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk associated with UV exposure levels (mW/m2) categorized in quintiles. We examined the association for breast cancer overall (invasive and ductal carcinoma in situ) and by estrogen receptor (ER) status of the tumor. We considered effect modification by regular (≥4 times/week) vitamin D supplement use. Over a median of 10.5years of follow up, 3,510 incident breast cancer diagnoses were reported. We found no evidence of an association between living in areas with higher levels of UV radiation and overall breast cancer risk (HRQ5 vs. Q1=1.00, 95% CI: 0.90, 1.11). Higher UV levels were inversely associated with the risk of ER- breast cancer (HRQ5 vs. Q1=0.73, 95% CI: 0.55-0.99), but not ER+ (HR Q5 vs. Q1=1.04, 95% CI: 0.92-1.18). For ER- breast cancer, the inverse association was only evident in women who did not regularly take vitamin D supplements (HRQ5 vs. Q1=0.52, 95% CI: 0.33-0.81) compared with those who did regularly take vitamin D supplements (HRQ5 vs. Q1=1.02, 95% CI: 0.68-1.54; p-for-heterogeneity=0.12). The findings from this study support a role for UV exposure and vitamin D in the etiology of ER- breast cancer.

Differences in Cancer Care Expenditures and Utilization for Surgery by Hospital Type Among Patients With Private Insurance

With rising expenditures on cancer care outpacing other sectors of the US health system, national attention has focused on insurer spending, particularly for patients with private insurance, for whom price transparency has historically been lacking. The type of hospital at which cancer care is delivered may be an important factor associated with insurer spending for patients with private insurance. To examine differences in spending and utilization for patients with private insurance undergoing common cancer surgery at National Cancer Institute (NCI) centers vs community hospitals. This retrospective cross-sectional study included adult patients with an incident diagnosis of breast, colon, or lung cancer who underwent cancer-directed surgery from 2011 to 2014. Mean risk-adjusted spending and utilization outcomes were examined for each hospital type using multilevel generalized linear mixed-effects models, adjusting for patient, hospital, and region characteristics. Data were collected from the Health Care Cost Institute's national multipayer commercial claims data set, which encompasses claims paid by 3 of the 5 largest commercial health insurers in the United States (ie, Aetna, Humana, and UnitedHealthcare). Data analyses were conducted from February 2018 to February 2019. Hospital type at which cancer surgery was performed: NCI, non-NCI academic, or community. Spending outcomes were surgery-specific insurer prices paid and 90-day postdischarge payments. Utilization outcomes were length of stay (LOS), emergency department (ED) use, and hospital readmission within 90 days of discharge. The study included 66 878 patients (51 569 [77.1%] women; 31 585 [47.2%] aged ≥65 years) with incident breast (35 788 [53.5%]), colon (21 378 [32.0%]), or lung (9712 [14.5%]) cancer undergoing cancer surgery at 2995 hospitals (5522 [8.3%] at NCI centers; 10 917 [16.3%] at non-NCI academic hospitals; 50 439 [75.4%] at community hospitals). Treatment at NCI centers was associated with higher surgery-specific insurer prices paid compared with community hospitals ($18 526 [95% CI, $16 650-$20 403] vs $14 772 [95% CI, $14 339-$15 204]; difference, $3755 [95% CI, $1661-$5849]; P < .001) and 90-day postdischarge payments ($47 035 [95% CI, $43 289-$50 781] vs $41 291 [95% CI, $40 350-$42 231]; difference, $5744 [95% CI, $1659-9829]; P = .006). There were no significant differences in LOS, ED use, or hospital readmission within 90 days of discharge. In this cross-sectional study, surgery at NCI centers vs community hospitals was associated with higher insurer spending for a surgical episode without differences in care utilization among patients with private insurance undergoing cancer surgery. A better understanding of the factors associated with prices and spending at NCI cancer centers is needed.

Secular Trends in Breast Cancer Risk Among Women With HIV Initiating ART in North America.

Studies suggest lower risk of breast cancer in women with HIV versus without HIV. These estimates may be biased by lower life expectancy and younger age distribution of women with HIV. Our analysis evaluated this bias and characterized secular trends in breast cancer among women with HIV initiating antiretroviral therapy. We hypothesized breast cancer risk would increase over time as mortality decreased. Women with HIV prescribed antiretroviral therapy in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1997 through 2016. We estimated breast cancer hazard (cause-specific hazard ratios) and cumulative incidence accounting for competing risks (subdistribution hazard ratios) to assess changes in breast cancer risk over time. This was assessed overall (1997-2016) and within/across calendar periods. Analyses were adjusted for race/ethnicity and inverse probability weighted for cohort. Cumulative incidence was graphically assessed by calendar period and race/ethnicity. We observed 11,587 women during 1997-2016, contributing 63 incident breast cancer diagnoses and 1,353 deaths [73,445 person-years (median follow-up = 4.5 years)]. Breast cancer cumulative incidence was 3.2% for 1997-2016. We observed no secular trends in breast cancer hazard or cumulative incidence. There were annual declines in the hazard and cumulative incidence of death (cause-specific hazard ratios and subdistribution hazard ratios: 0.89, 95% confidence interval: 0.87 to 0.91) which remained within and across calendar periods. These findings contradict the hypothesis of increasing breast cancer risk with declining mortality over time among women with HIV, suggesting limited impact of changing mortality on breast cancer risk. Additional inquiry is merited as survival improves among women with HIV.

Racial disparities in diabetes care among incident breast, prostate, and colorectal cancer survivors: a SEER Medicare study.

Many cancer survivors with co-morbid diabetes receive less diabetes management than their non-cancer counterparts. We sought to determine if racial/ethnic disparities exist in recommended diabetes care within 12 months of an incident breast, prostate, or colorectal cancer diagnosis. Because co-morbid diabetes decreases long-term survival, identifying predictors of guideline-concordant diabetes care is important. Using the Surveillance, Epidemiology, and End Results cancer registry linked to Medicare claims, we included beneficiaries aged 67+ years with diabetes and incident, non-metastatic breast, prostate, or colorectal cancer between 2008 and 2013. Primary outcomes were diabetes care services 12 months after diagnosis: (1) HbA1c test, (2) eye exam, and (3) low-density lipoprotein (LDL) test. Using modified Poisson models with robust standard errors, we examined each outcome separately. We included 34,643 Medicare beneficiaries with both diabetes and cancer. Mean age at diagnosis was 76.1 (SD 6.2), 47.2% were women; 35% had breast, 24% colorectal, and 41% prostate cancer. In the 12 months after incident cancer diagnosis, 82.4% received an HbA1c test, 55.3% received an eye exam, 77.8% had an LDL test, and 42.0% received all three tests. Compared to non-Hispanic Whites, Blacks were 3% (95% CI 0.95-0.98) less likely to receive a HbA1c test, 10% (95% CI 0.89-0.92) less likely to receive a LDL test, and 8% (95% 0.89-0.95) less likely to receive an exam eye. Blacks and Hispanics were 16% (95% CI 0.81-0.88) and 7% (0.88-0.98) less likely to receive all three tests, after accounting for confounders. Racial/ethnic differences persisted across cancer types. Blacks and Hispanics with breast, prostate, and colorectal cancer and diabetes received less diabetes care after cancer diagnosis compared to non-Hispanic Whites. Differences were not explained by socio-economic factors or clinical need. Our findings are concerning given the high prevalence of diabetes and poor cancer outcomes among racial/ethnicminorities. The next step in this line of inquiry is to determine why minorities are less likely to receive comprehensive diabetes care in order to developtargeted strategies to increase receipt of appropriate diabetes management for these vulnerable populations.

Dietary Antioxidant Vitamins and Minerals and Breast Cancer Risk: Prospective Results from the SUN Cohort

There is growing interest in natural antioxidants and their potential effects on breast cancer (BC). Epidemiological evidence, however, is inconsistent. We prospectively evaluated the association between dietary intake of vitamins A, C, and E, selenium, and zinc and BC among 9983 female participants from the SUN Project, a Mediterranean cohort of university graduates. Participants completed a food frequency questionnaire at baseline, and biennial follow-up information about incident BC diagnosis was collected. Cases were ascertained through revision of medical charts and consultation of the National Death Index. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI). During an average follow-up of 11.3 years, 107 incident BC cases were confirmed. The multivariable HRs (95% CI) for BC comparing extreme tertiles of energy-adjusted dietary intakes were 1.07 (0.64–1.77; Ptrend = 0.673) for vitamin A, 1.00 (0.58–1.71; Ptrend = 0.846) for vitamin C, 0.92 (0.55–1.54; Ptrend = 0.728) for vitamin E, 1.37 (0.85–2.20; Ptrend = 0.135) for selenium, and 1.01 (0.61–1.69; Ptrend = 0.939) for zinc. Stratified analyses showed an inverse association between vitamin E intake and postmenopausal BC (HRT3 vs. T1 = 0.35; 95% CI, 0.14–0.86; Ptrend = 0.027). Our results did not suggest significant protective associations between dietary vitamins A, C, and E, selenium, or zinc and BC risk.

PCN335 The Impact Of Guideline Adherence On Survival In Early Breast Cancer Patients

Breast cancer (BC) is the most common malignancy in women. Treatment guidelines recommend specific diagnostic measures and a subsequent treatment. The aim of this study was to investigate adherence to guidelines regarding diagnostics and treatment of early BC patients, and the association of guideline adherence with overall survival during the first year after diagnosis. All patients with an incident BC diagnosis (24 months wash-out period; ICD-10: C50) without metastases (early BC) between 01/01/2012 and 30/03/2018 were included from a German claims dataset (AOK PLUS). Recommendations regarding diagnostics and treatment from relevant German guidelines were extracted; subsequently, guideline adherence was assessed in each patient. Impact of guideline adherence on the risk for early death was ascertained using a multivariable Cox regression model. Of 13,671 patients with early BC, 98.4% were female. Mean age was 69.0 years (SD 15.2) at first observed BC diagnosis, mean Charlson-Comorbidity-Index (CCI) was 3.6 (SD 2.4). Within 1 year before or 90 days after initial diagnosis, 73.0% of the patients underwent mammography, 52.7% sonography, in 57.5% a biopsy was done and 21.0% did not receive any of these. One third of all patients did not receive any treatment in the first year (32.2%), whereas 67.8% received a treatment: 58.2% had a surgery, 43.9% radiotherapy and 59.0% received any pharmacological treatment. The risk to die within the first year after first BC diagnosis was higher for patients without any diagnostics (HR 2.792; p<0.001) and without any treatment (HR 2.085; p<0.001), talking age and CCI of patients into account. These results were checked and confirmed by excluding all patients that died within the first 90 days (no diagnostics: HR 2.354; p<0.001; no treatment: 1.588; p<0.001). A substantial percentage of early BC patients are not treated according to guidelines. Guidline non-adherence is associated with a higher mortality risk.

Measurement of mitochondrial DNA copy number in dried blood spots: A pilot study

BackgroundWe evaluated the feasibility of mitochondrial DNA (mtDNA) copy number measurement in dried blood spots (DBS), its comparability with measurement in whole blood samples, and stability of mtDNA copy number from DBS over time. MethodsWomen in this pilot study were participants in the Sister Study, a large prospective cohort. Sister Study participants provided a whole blood sample and DBS at enrollment. A second DBS sample was collected 5–10 years later from a subcohort of women with and without an incident breast cancer diagnosis between collections. Among 54 women (27 with breast cancer, 27 without) we measured mtDNA copy number from whole blood at enrollment and from DBS at both time points. ResultsThe average age at enrollment was 58.7 years (range:50–69). Values of mtDNA copy number measured in whole blood samples and DBS from enrollment were moderately correlated (Spearman R = 0.45; p = 0.005). Stability of mtDNA copy number in DBS from the two time points was moderate overall (ICC = 0.50) and similar between women with (ICC = 0.50) and without (ICC = 0.51) a breast cancer diagnosis between the two collections. ConclusionsOur results suggest that measurement of mtDNA copy number in DBS is feasible and may be a valid alternative to measurement in whole blood samples.

The clinical impact of ASCO “choosing wisely” recommendations on staging imaging for early stage breast cancers: An interrupted time-series analysis utilizing SEER-Medicare data.

2078 Background: The “Choosing Wisely” (CW) list, released by the American Society for Clinical Oncology (ASCO), highlights low-value procedures. In 2012, the CW recommendations advised against the use of staging imaging, including Positron Emission Tomography (PET), Computerized Tomography (CT) and radionuclide bone scans, for the staging of early breast cancer at low risk for metastasis. The objective of this study was therefore to assess the impact of the ASCO CW recommendations on staging imaging among early stage breast cancers. Methods: Women above the age of 66 with an early stage incident breast cancer diagnoses between 2010 and 2015 were identified within the linked SEER-Medicare data. The primary outcome of interest was the proportion of patients with a claim for staging imaging in the six months following the breast cancer diagnosis. Negative binomial regression, adjusting for pre-recommendation trends, was performed to estimate the changes in the rate of imaging staging within each year following the release of the recommendation. Results: A total of 50,004 women were identified during the study period. Prior to the release of the recommendations in 2012, the staging imaging rates among women newly diagnosed with early stage breast cancers were 5% greater in 2010 (p&lt;.01) and 4% greater in 2011 (p&lt;.01). Following the release of the recommendations, staging imaging rates did not decrease significantly in 2013 (2%;p=0.18). Imaging rates did, however, significantly decrease by 13% in 2014 (p&lt;0.01) and by 16% in 2015 (p&lt;0.01). Conclusions: The CW recommendation was associated with a significant decrease in unadvised staging imaging among incident early stage breast cancer diagnosis in the second and third year following its release. These findings demonstrate an improvement in the proportion of potentially inappropriate staging imaging in early stage breast cancers. The creation and dissemination of resources, such as the CW recommendations, serves as a powerful tool to improve clinical practice, quality of care, and patient safety from secondary malignancies, anxiety, and overdiagnosis.

Improved outcomes among breast cancer patients with more frequent mammography screening.

e19146 Background: Guidelines for optimal frequency of screening mammography (annual, biennial, never/choice of patient) vary by professional society, due to mixed or insufficient evidence regarding its benefits and harms. Little evidence exists on the impact of screening frequency, rather than any screening, on health outcomes. In this study, we measured differences in cancer stage at diagnosis, treatment rendered, mortality, and cost of treatment for women with different numbers of screenings prior to breast cancer diagnosis. Methods: Utilizing administrative claims, we identified 25,492 women aged 44 or older with various numbers of mammographic screening ≥ 11 months apart during the four years prior to their incident breast cancer diagnosis from 2010 to 2018. Outcomes were assessed during the six months following diagnosis. Regression models were used to compare women with differing numbers of mammograms (0, 1, 2, 3, or 4/5), adjusting for demographic characteristics and baseline comorbidities. Results: More screenings were associated with less advanced cancer at diagnosis, higher rates in lumpectomy and radiation, lower rates in mastectomy and chemotherapy, lower costs and mortality within 6 months post diagnosis (Table). Results were similar in a subgroup with only women aged 44-49 at diagnosis (not shown). Conclusions: Increased frequency of screening mammography is associated with earlier breast cancer stage at diagnosis, less toxic and invasive treatment, lower mortality, and lower cost, including for women under age 50. [Table: see text]

Dioxin exposure and breast cancer risk in a prospective cohort study

BackgroundDioxins are persistent organic pollutants generated from industrial combustion processes such as waste incineration. To date, results from epidemiologic studies of dioxin exposure and breast cancer risk have been mixed. ObjectivesTo prospectively examine the association between ambient dioxin exposure using a nationwide spatial database of industrial dioxin-emitting facilities and invasive breast cancer risk in the Nurses’ Health Study II (NHSII). MethodsNHSII includes female registered nurses in the US who have completed self-administered biennial questionnaires since 1989. Incident invasive breast cancer diagnoses were self-reported and confirmed by medical record review. Dioxin exposure was estimated based on residential proximity, duration of residence, and emissions from facilities located within 3, 5, and 10 km around geocoded residential addresses updated throughout follow-up. Cox regression models adjusted for breast cancer risk factors were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsFrom 1989 to 2013, 3840 invasive breast cancer cases occurred among 112,397 participants. There was no association between residential proximity to any dioxin facilities (all facilities combined) and breast cancer risk overall. However, women who resided within 10 km of any municipal solid waste incinerator (MSWI) compared to none had increased breast cancer risk (adjusted HR = 1.15, 95% CI: 1.03, 1.28), with stronger associations noted for women who lived within 5 km (adjusted HR = 1.25, 95% CI: 1.04, 1.52). Positive associations were also observed for longer duration of residence and higher dioxin emissions from MSWIs within 3, 5, and 10 km. There were no clear differences in patterns of association for ER + vs. ER-breast cancer or by menopausal status. DiscussionResults from this study support positive associations between dioxin exposure from MSWIs and invasive breast cancer risk.