Stage I-IIIA Breast Cancer Research Articles

Associations between age at diagnosis and chemotherapy dose reductions in women treated for stage I-IIIA breast cancer.

99 Background: Several studies have shown that older women diagnosed with breast cancer and eligible for chemotherapy treatment are more likely to be dose-reduced than younger women; however, most prior studies were limited by small sample sizes and examined relative dose intensity of a single drug. We assessed the association between age at diagnosis with first cycle dose proportion (FCDP) and average relative dose intensity (ARDI) across multiple regimens in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. Methods: This retrospective cohort study included 10,386 women ages 18+ years treated with adjuvant chemotherapy for stage I-IIIA breast cancer at Kaiser Permanente Northern California (KPNC) and Washington (KPWA) between 2004-2019. We examined associations between age at diagnosis with first cycle dose proportion (FCDP, defined as <90% of the guideline-recommended dose, reflecting clinician intent at treatment outset) and average relative dose intensity (ARDI, defined as dose proportion <90% across the course of chemotherapy). We used multivariable-adjusted generalized linear models of the Poisson family with a log link-function and robust standard errors to calculate prevalence ratios (PR) and corresponding 95% confidence intervals (CI). We adjusted for patient and tumor characteristics, with and without adjusting for pre-existing comorbidities. Results: The proportion of women with a FCDP <90% ranged from 3% among women ages 18-39 years to 19% among women ages 75+ years. Women ages 75+ years were statistically significantly more likely to have a FCDP <90% and ARDI <90% vs women ages 40-49 years regardless of adjustment for comorbidities (Table). Conclusions: Older age at diagnosis is strongly associated with chemotherapy dose reductions relative to guideline recommendations, both at the outset of chemotherapy initiation and across the course of treatment. Understanding implications of dose reductions on chemotoxicities and survival will be particularly important for improving the quality of care and long-term outcomes for older women. Age at Diagnosis (years) FCDP <90% Multivariable Adjusted*PR (95% CI) FCDP <90% Additionally Adjusted* for ComorbiditiesPR (95% CI) ARDI <90% Multivariable Adjusted*PR (95% CI) ARDI <90% Additionally Adjusted* for ComorbiditiesPR (95% CI) 18-39 0.81 (0.53-1.23) 0.84 (0.55-1.29) 0.84 (0.68-1.03) 0.85 (0.69-1.04) 40-49 REF REF REF REF 50-64 1.32 (1.08-1.61) 1.29 (1.06-1.59) 1.16 (1.04-1.29) 1.14 (1.02-1.26) 65-74 1.72 (1.36-2.17) 1.65 (1.29-2.10) 1.34 (1.18-1.52) 1.26 (1.11-1.43) 75+ 4.90 (3.61-6.65) 4.39 (3.16-6.09) 1.94 (1.61-2.35) 1.75 (1.44-2.13) p-trend <0.001 <0.001 <0.001 <0.001 *Adjusted for BMI, stage at diagnosis, year of diagnosis, study site, race/ethnicity, income, body mass index, human epidermal growth factor receptor status, grade, nodal number, estrogen and progesterone receptor status.

The landscape of use of NCCN-guideline chemotherapy regimens in stage I-IIIA breast cancer in an integrated healthcare delivery system.

The National Comprehensive Cancer Network (NCCN) guidelines recommend a variety of drug combinations with specific administration schedulesfor the treatment ofearly-stagebreast cancer, allowing physicians to deliver treatments recognizing individual patient complexities, including comorbidities, and patient-physician preference. While use of guideline regimens has shifted over time, there is little data to describe changes in how treatment for early-stage breast cancer has evolved over time. In a cohort of 34,109 women treated for stage I-IIIA breast cancer between 2006-2019 at Kaiser Permanente Northern California and Kaiser Permanente Washington, we present the changes in chemotherapy regimens over time, and explore use of NCCN-guideline regimens (GR), guideline regimens used when said regimens were not included in guidelines, referred to as time-discordant regimens (TDR), and non-guideline regimens (NGR). Results are presented by drug combination and over time. Among 12,506 women receiving chemotherapy, 77.4% (n = 9681) received GRs, 9.1% (n = 1140) received TDRs, and 13.5% (n = 1685) received NGRs. In 2006, AC-T (cyclophosphamide-doxorubicin, paclitaxel) was the most common regimen, with TC (cyclophosphamide-docetaxel) becoming the most prevalent by 2019. NGRs were more common in cyclophosphamide-methotrexate-5-fluorouracil (CMF); cyclophosphamide-doxorubicin-paclitaxel-trastuzumab (ACTH); and paclitaxel-trastuzumab (TH). The use of GR has increased over time (p-trend < 0.001), while use of NGR(both in terms of administration schedule and drug combination)and TDRhave decreased, although patterns vary by drug combination. Chemotherapy delivery has changed markedly over time, with a move toward more use of GR. These data are important for understanding the landscape of chemotherapy delivery in community healthcare settings.

Patient characteristics associated with delayed time to adjuvant chemotherapy among women treated for stage I-IIIA breast cancer.

For patients with breast cancer, delays in chemotherapy initiation have been adversely associated with recurrence and survival. We evaluated patient-level factors associated with delayed chemotherapy initiation, from both diagnosis and surgery, in a community-based cohort of women with early-stage breast cancer. For the Optimal Breast Cancer Chemotherapy Dosing study, we identified a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare delivery systems between 2004 and 2019. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) to identify patient factors associated with delays in chemotherapy initiation after diagnosis (≥90 days) and surgery (≥60 days). Among 10,968 women receiving adjuvant chemotherapy, 21.1% experienced delays in chemotherapy initiation after diagnosis and 21.3% after surgery. Older age, non-Hispanic Black and Hispanic race and ethnicity, and ER+ and/or PR+ disease were associated with increased likelihood of delays to chemotherapy initiation after diagnosis and surgery. People diagnosed in 2012-2019 (vs. 2005-2011), with a higher grade and larger tumor size were less likely to experience delays. Other factors were associated with a higher likelihood of delays specifically from diagnosis (earlier stage, mastectomy vs. breast-conserving surgery), or surgery (higher comorbidity, increased nodal number). Women diagnosed with breast cancer who were at highest risk of progression and recurrence were less likely to experience delays in chemotherapy initiation after diagnosis and surgery. Understanding reasons for chemotherapy delays beyond patient factors may be potentially important to reduce risk of breast cancer recurrence and progression.

Trends in chemotherapy use for early-stage breast cancer from 2006 to 2019

BackgroundLittle is known about how use of chemotherapy has evolved in breast cancer patients. We therefore describe chemotherapy patterns for women with stage I-IIIA breast cancer in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study using data from KPNC (Kaiser Permanente Northern California) and KPWA (Kaiser Permanente Washington).FindingsAmong 33,670 women, aged 18 + y, diagnosed with primary stage I-IIIA breast cancer at KPNC and KPWA from 2006 to 2019, we explored patterns of intravenous chemotherapy use, defined here as receipt of intravenous cytotoxic drugs and/or anti-HER2 therapies. We evaluated trends in chemotherapy receipt, duration over which chemotherapy was received, and number of associated infusion visits. In secondary analyses, we stratified by receipt of anti-HER2 therapies (trastuzumab and/or pertuzumab), given their longer duration. 38.9% received chemotherapy intravenously, declining from 40.2% in 2006 to 35.6% in 2019 (p-trend < 0.001). Among 13,089 women receiving chemotherapy, neoadjuvant treatment increased (4.1–14.7%; p-trend < 0.001), as did receipt of anti-HER2 therapies (20.8–30.9%) (p-trend < 0.001). The average treatment duration increased (5.3 to 6.0 months; p-trend < 0.001), as did the number of infusion visits (10.8 to 12.5; p-trend < 0.001). For those receiving anti-HER2 therapies, treatment duration and average number of visits decreased; among those not receiving anti-HER2 therapies, number of visits increased, with no change in duration.ConclusionsWhile the prevalence of chemotherapy receipt has decreased over time, the use of neoadjuvant chemotherapy has increased, as has use of anti-HER2 therapies; duration and number of administration visits have also increased. Understanding these trends is useful to inform clinical and administrative planning.

Facilitating adaptive coping with fear of recurrence among breast cancer survivors: Feasibility and acceptability outcomes from a three-arm randomized controlled trial.

1630 Background: Fear of cancer recurrence (FCR) is one of the most prevalent and disruptive problems for breast cancer survivors (BCS). Acceptance and commitment therapy (ACT) and cognitive behavioral therapy (CBT) have shown promising effects for FCR in a recent meta-analysis, yet head-to-head comparisons of these interventions are rare. We present feasibility and acceptability outcomes from a randomized controlled trial comparing ACT to CBT and enhanced usual care (EUC) for BCS with clinically significant FCR. Methods: Eligible women were ≥18 years old, diagnosed with stage I-IIIA breast cancer, within 5 years of completing cancer treatment (ongoing endocrine therapy was allowed), and reported clinical FCR at enrollment. Participants were randomly assigned to group-based ACT, CBT, or EUC, all delivered via videoconference. ACT and CBT consisted of 6 weekly 1.5-hour sessions; EUC was a single 1.5-hour survivorship coaching session. Outcomes included accrual, session attendance and engagement, intervention helpfulness, and retention. Variables were summarized by mean (SD) if numerical or relative frequency if categorical. At significance level α = 0.05, the Kruskal-Wallis test was used to compare overall differences between the three groups, and two-sample T-tests with unequal variances were used for pairwise comparisons between the groups with Bonferroni multiple-comparison adjustment. Results: Of 446 BCS who screened eligible, 390 (87.4%) enrolled. Most participants were white (81.8%), not Hispanic (98.4%), partnered (68.4%), and college-educated (71.3%). Most were within 2 years of completing cancer treatment (55.7%), and mean age was 55.8 (SD = 12.0) years. Among those assigned to a 6-session intervention, participants attended a mean of 5.0 (ACT) and 5.2 (CBT) sessions; 96.1% of EUC participants attended the single session. Mean session engagement (rated per participant per session by interventionists on a 0-10 scale) was significantly different across the three groups (p &lt; .0001), with mean (SD) of 9.3 (0.8) for ACT, 9.5 (1.0) for CBT, and 7.9 (1.3) for EUC. Pairwise comparisons showed higher engagement ratings in ACT (p &lt; .0001) and CBT (p &lt; .0001) over EUC, with no significant difference between ACT and CBT (p = .14). At post-intervention, participants rated mean (SD) helpfulness on a 0-10 scale as 7.2 (2.6) for ACT, 7.9 (2.0) for CBT, and 5.5 (2.7) for EUC. Overall, mean helpfulness was significantly different across the groups (p &lt; .0001) and favored CBT over ACT (p = .0109) and EUC (p &lt; .001) and favored ACT over EUC (p &lt; 0.001). Outcome data retention was 93.8% through the 6-month follow-up. Conclusions: High accrual and attendance rates suggest that BCS are receptive to FCR interventions and may find ACT or CBT more engaging and helpful than a single session of survivorship coaching. Clinical trial information: NCT05364450 .

Patient characteristics associated with primary prophylactic granulocyte colony-stimulating factor (G-CSF) use among women treated for early-stage breast cancer.

e12605 Background: The National Comprehensive Cancer Network (NCCN) recommends several chemotherapy regimens for early-stage breast cancer that have elevated risk of neutropenia (&gt;20%). In these regimens, primary prophylactic use of granulocyte colony-stimulating factor (G-CSF) is recommended. Little is known about how patient-level factors relate to receipt of prophylactic G-CSF among women receiving these regimens. Methods: In the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study, we examined use of G-CSF among women with stage I-IIIA breast cancer between 2005-2019 in Kaiser Permanente Northern California (KPNC) and Kaiser Permanente Washington (KPWA). We evaluated the patient-level factors associated with primary prophylactic G-CSF use (≤7 days before to ≤3 days after first day of chemotherapy) among women receiving chemotherapy regimens with high risk of neutropenia, for which the NCCN guidelines recommend prophylactic G-CSF use. Multivariable-adjusted prevalence ratios (PR) and their corresponding 95% Confidence Intervals (95% CI) were calculated using generalized linear models of the Poisson family with a log link-function and robust standard errors. Results: Overall, while all 3,083 women receiving these regimens ultimately received G-CSF, 2412 (79%) received primary prophylactic G-CSF within the period 7 days prior to 3 days post first cycle. Younger women had higher prevalence of prophylactic G-CSF receipt (82.7% in ages 18-39 years vs. 58.1% in 70+ years). Black women had higher prevalence of receipt compared to white women (82.7% in non-Hispanic Black women vs 76.1% in White women). Women with a higher body mass index (BMI) had lower prevalence of receipt compared to normal weight women (73.3% in 35+ kg/m2 group vs 81.5% in 18.5-&lt;25 kg/m2 group). In multivariable models, older women were less likely to receive prophylactic G-CSF (PR70+ vs 18-39: 0.69; 95% CI: 0.57-0.84; p-trend&lt;0.001), as were those with a higher BMI (PRBMI 35+ vs 18.5-&lt;25: 0.92; 95% CI: 0.85, 0.97; p-trend=0.006), and a later year of diagnosis (PR2016-19 vs 2005-07: 0.81; 95% CI: 0.77, 0.85; p-trend&lt;0.001). Although race/ethnicity was not significantly associated with receipt of prophylactic G-CSF use overall in multivariable models, we observed Non-Hispanic Black women to experience slightly higher likelihood of G-CSF receipt than Non-Hispanic White women (PR: 1.08; 95% CI: 1.02, 1.15). Conclusions: Women of older age and those with higher BMI were less likely to receive primary prophylactic G-CSF, as were women treated in later years. Further research looking at timing of G-CSF use is warranted, as are studies examining provider/facility-level factors in relation to patterns of G-CSF use, G-CSF’s impact on survival outcomes, and the real-world impact of decisions around G-CSF use across age, BMI, and racial/ethnic groups.

Prescription drug, healthcare utilization, and lost earnings cost of behavioral interventions for fear of cancer recurrence in breast cancer survivors.

e24095 Background: Breast cancer survivors experience distress due to the fear of cancer recurrence. Acceptance and commitment therapy (ACT) and cognitive behavioral therapy (CBT) can treat the fear of cancer recurrence. However, no study has applied economic evaluation methods to estimate ACT and CBT behavioral intervention costs for breast cancer survivors. Methods: 384 adult stage I-IIIA breast cancer survivors with fear of cancer recurrence were randomly assigned to either the ACT (n = 128), CBT (n = 128), or enhanced usual care (EUC, n = 128) groups. Through micro-costing, we assessed the societal perspective cost of behavioral interventions using 2022 dollars. Per-capita drug costs, healthcare utilization, and lost productivity were calculated using participant survey data. Drug costs were estimated using Micromedex’s Red Book wholesale unit price. The 2022 Medicare Physician Fee Schedule for Indiana estimated healthcare utilization costs from outpatient, inpatient, and emergency visits. Lost productivity costs included work loss, productivity loss, and unpaid work loss, valued by Indiana's mean hourly wage. We assessed the cost differences between baseline (T1) and after the 6-week intervention period (T2). We evaluated between-group differences with Bonferroni's tests for each pairwise group comparison and within-group differences with a paired t-test at a p-value of &lt; 0.05. Results: The mean total per-capita cost change from T1 to T2 in the ACT, CBT, and EUC groups was -$563, -$1622, and -$981, respectively (Table 1). This cost reduction stemmed from drug and healthcare utilization. There was no significant between-group difference in total cost at T1 or T2 and no significant between-group or within-group cost change from T1 to T2. Conclusions: Our cost estimates will be updated at 6 and 12 months of intervention and combined with changes in quality of life and mental health metrics to assess the cost-effectiveness of ACT and CBT for fear of breast cancer recurrence. Clinical trial information: NCT05364450 . [Table: see text]

Methodology for Using Real-World Data From Electronic Health Records to Assess Chemotherapy Administration in Women With Breast Cancer.

Identification of patients' intended chemotherapy regimens is critical to most research questions conducted in the real-world setting of cancer care. Yet, these data are not routinely available in electronic health records (EHRs) at the specificity required to address these questions. We developed a methodology to identify patients' intended regimens from EHR data in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. In women older than 18 years, diagnosed with primary stage I-IIIA breast cancer at Kaiser Permanente Northern California (2006-2019), we categorized participants into 24 drug combinations described in National Comprehensive Cancer Network guidelines for breast cancer treatment. Participants were categorized into 50 guideline chemotherapy administration schedules within these combinations using an iterative algorithm process, followed by chart abstraction where necessary. We also identified patients intended to receive nonguideline administration schedules within guideline drug combinations and nonguideline drug combinations. This process was adapted at Kaiser Permanente Washington using abstracted data (2004-2015). In the OBCD cohort, 13,231 women received adjuvant or neoadjuvant chemotherapy, of whom 10,213 (77%) had their intended regimen identified via the algorithm, 2,416 (18%) had their intended regimen identified via abstraction, and 602 (4.5%) could not be identified. Across guideline drug combinations, 111 nonguideline dosing schedules were used, alongside 61 nonguideline drug combinations. A number of factors were associated with requiring abstraction for regimen determination, including: decreasing neighborhood household income, earlier diagnosis year, later stage, nodal status, and human epidermal growth factor receptor 2 (HER2)+ status. We describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens in large, observational studies. This methodology can improve efficiency of use of large-scale clinical data in real-world populations, helping answer critical questions to improve care delivery and patient outcomes.

Evaluation of Algorithms Using Automated Health Plan Data to Identify Breast Cancer Recurrences.

We updated algorithms to identify breast cancer recurrences from administrative data, extending previously developed methods. In this validation study, we evaluated pairs of breast cancer recurrence algorithms (vs. individual algorithms) to identify recurrences. We generated algorithm combinations that categorized discordant algorithm results as no recurrence [High Specificity and PPV (positive predictive value) Combination] or recurrence (High Sensitivity Combination). We compared individual and combined algorithm results to manually abstracted recurrence outcomes from a sample of 600 people with incident stage I-IIIA breast cancer diagnosed between 2004 and 2015. We used Cox regression to evaluate risk factors associated with age- and stage-adjusted recurrence rates using different recurrence definitions, weighted by inverse sampling probabilities. Among 600 people, we identified 117 recurrences using the High Specificity and PPV Combination, 505 using the High Sensitivity Combination, and 118 using manual abstraction. The High Specificity and PPV Combination had good specificity [98%, 95% confidence interval (CI): 97-99] and PPV (72%, 95% CI: 63-80) but modest sensitivity (64%, 95% CI: 44-80). The High Sensitivity Combination had good sensitivity (80%, 95% CI: 49-94) and specificity (83%, 95% CI: 80-86) but low PPV (29%, 95% CI: 25-34). Recurrence rates using combined algorithms were similar in magnitude for most risk factors. By combining algorithms, we identified breast cancer recurrences with greater PPV than individual algorithms, without additional review of discordant records. Researchers should consider tradeoffs between accuracy and manual chart abstraction resources when using previously developed algorithms. We provided guidance for future studies that use breast cancer recurrence algorithms with or without supplemental manual chart abstraction.

Abstract B077: Understanding the relationship between neighborhood deprivation and breast cancer mortality among Black and White women

Abstract Background: Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who are more likely to die from the disease. To improve our understanding of the relation, we investigated the joint effects of race and neighborhood racial composition, residential mobility, and rurality on the neighborhood deprivation-breast cancer mortality association among White and Black women. Methods: In 2010-2017, 31,358 non-Hispanic White and Black women diagnosed with invasive stage I-IIIA breast cancer were identified by the Georgia Cancer Registry and were followed through 2019 for breast cancer mortality. The neighborhood deprivation index (NDI) was derived through principal component analysis of 2011-2015 block group-level American Community Survey (ACS) data on poverty, income, housing, unemployment, occupation, and education. Neighborhood racial composition and residential mobility were measured using 2011-2015 ACS data. Rurality was measured using Georgia Department of Public Health data. We used Cox proportional hazards regression to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for the association between NDI, in quintiles, and breast cancer mortality, overall and according to joint effects of race and neighborhood characteristics (neighborhood racial composition, residential mobility, and rurality). Results: During follow-up, 2,353 (1,347 non-Hispanic White, 1,006 non-Hispanic Black) women died from breast cancer. Living in the most deprived neighborhoods was associated with a 30% increased risk of breast cancer mortality (quintile 5 vs. 1: HR=1.30, 95% CI 1.13-1.49). The association was present among non-Hispanic White (quintile 5 vs. 1: HR=1.47, 95% CI 1.20-1.79) but not non-Hispanic Black women. We observed similar race-specific patterns when assessing jointly stratified associations. For example, among non-Hispanic White women, neighborhood deprivation was associated with breast cancer mortality irrespective of the additional neighborhood characteristics considered, with the strongest association observed among non-Hispanic White women living in the most deprived rural neighborhoods compared to those living in the least deprived urban neighborhoods (HR=1.70, 95% CI 1.30-2.22). In contrast, no association was found among non-Hispanic Black women in any strata of neighborhood racial composition, residential mobility, or rurality (non-Hispanic Black women living in the most deprived rural neighborhoods vs. those living in the least deprived urban neighborhoods: HR=1.05, 95% CI 0.78-1.41). Conclusions: Consistent with previous studies, our study found that living in a deprived neighborhood may increase breast cancer mortality among non-Hispanic White but not non-Hispanic Black women. Neighborhood racial composition, residential mobility, and rurality did not explain the lack of association among non-Hispanic Black women. Other factors beyond neighborhood may contribute to the high breast cancer mortality rate among this racial group. Citation Format: Lauren E. Barber, Leah Moubadder, Maret L. Maliniak, Jasmine M. Miller-Kleinhenz, Jeffrey M. Switchenko, Lauren E. McCullough. Understanding the relationship between neighborhood deprivation and breast cancer mortality among Black and White women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B077.

Abstract B087: Racial disparities in breast cancer survival: Examining the potential role of neighborhood deprivation and breast adipose tissue inflammation

Abstract Background: Previous studies have found the Black-White disparity in breast cancer survival is greatest among women living in neighborhoods of high socioeconomic status (i.e., low % poverty). This study aimed to examine the association between race and breast cancer mortality according to neighborhood deprivation, a more comprehensive measure of neighborhood socioeconomic status. We also explored the association between neighborhood deprivation and the presence of breast adipose tissue inflammation as a potential biologic mechanism underlying the association. Methods: We examined Black-White disparities in breast cancer mortality overall and stratified by neighborhood deprivation status among 37,369 Black and White women in the Georgia Cancer Registry who were diagnosed with a first primary Stage I-IIIA breast cancer between 2010 and 2017 and followed until December 31, 2019. Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). In a separate analysis, we examined the presence of crown-like structures in breast adipose tissue (CLS-B), detected by CD68 immunohistochemistry, among 342 women with stage I–III breast cancer who underwent mastectomy at Emory University Hospitals in Atlanta, Georgia (2007–2012). Logistic regression models were used to estimate odds ratios (OR) and 95% CIs. For both cohorts of breast cancer patients, neighborhood deprivation was assessed dichotomously using census tract at diagnosis and the neighborhood deprivation index (NDI), which was computed using American Community Survey 5-year estimates for census tracts in Georgia. Results: In Georgia, we found Black women with breast cancer had ~1.8 times higher rate of breast cancer mortality than their White counterparts (age-adj. HR=1.78, 95% CI: 1.63, 1.94). The disparity was attenuated after adjusting for stage and molecular subtype but was not eliminated (multivariable (MV)-adj. HR=1.32, 95% CI: 1.21, 1.45). When stratified by NDI, the disparity was greater among women living in neighborhoods of low deprivation (MV-adj. HR=1.44, 95% CI: 1.26, 1.64) compared to high deprivation (MV-adj. HR=1.17, 95% CI: 1.03, 1.33). Among Emory breast cancer patients, we found high neighborhood deprivation was inversely associated with CLS-B (age- and race-adj. OR=0.48, 95% CI; 0.26, 0.87). We also found Black patients were more likely than their White counterparts to have CLS-B in low deprivation neighborhoods (age-adj. OR=1.79, 95% CI: 0.98, 3.25) but not in high deprivation neighborhoods (age-adj. OR=0.73, 95% CI: 0.24, 2.20), albeit estimates were imprecise. Conclusion: Our study using a population-based cohort of breast cancer patients in Georgia adds to the evidence that racial disparities in breast cancer survival are worse among women living in higher socioeconomic (i.e., low deprivation) neighborhoods. Additionally, we provide evidence of a potential underlying mechanism, finding the prevalence of CLS-B higher for women in low rather than high deprivation neighborhoods, particularly Black women in this group. Citation Format: Maret L. Maliniak, Lauren E. Barber, Jasmine M. Miller-Kleinhenz, Leah Moubadder, Lauren E. McCullough. Racial disparities in breast cancer survival: Examining the potential role of neighborhood deprivation and breast adipose tissue inflammation [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B087.

Provider- and facility-level factors in relation to patients’ receipt of chemotherapy, time to chemotherapy initiation, and receipt of guideline regimens: Results from the optimal breast cancer chemotherapy dosing study.

540 Background: How provider and facility characteristics relate to delivery and attributes of chemotherapy administration is not well understood. Methods: In a cohort of 31,336 women with stage I-IIIA breast cancer diagnosed and treated at Kaiser Permanente Northern California between 2006-2019, we evaluated the relationships between provider-level factors (gender, age, provider-patient racial/ethnic concordance) and facility-level factors (practice size, defined by number of oncologists in the service area, and rurality, defined by the % rurality of the treatment facility) in relation to chemotherapy receipt (yes/no), time to initiation (&gt;/≤90 days after diagnosis), and planned regimen outside of the National Comprehensive Cancer Network guidelines (yes/no). In secondary analyses, the ‘receipt of a planned non-guideline regimen’ outcome was disaggregated into component pieces: regimens that were planned using non-guideline drug combinations, and regimens that were planned using a non-guideline schedule of administration of a guideline drug combination. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). Results: Results suggest that provider- and facility-level factors are associated with various aspects of chemotherapy administration. For example, patients whose race and ethnicity matched that of their provider were less likely to experience a &gt;90-day gap to initiation of chemotherapy (OR=0.83; 95% CI: 0.75-0.91). People treated by older providers were more likely to receive a non-guideline regimen than those treated by younger providers (≥60y vs &lt;40y, OR=1.67, 95% CI: 1.37-2.04), with the effect estimate stronger for non-guideline drug combinations (OR=1.97). People treated by providers practicing in a larger service area (&gt;10 vs ≤5 oncologists) were also less likely to receive non-guideline regimens; this was largely driven by use of drug combinations outside of the guidelines (OR=0.33, 95% CI: 0.15-0.71). People treated by female providers were less likely to receive a non-guideline regimen, specifically a non-guideline administration schedule (OR=0.79, 95% CI: 0.70-0.89). These results were robust to adjustment for several patient-level factors, including age, stage, race/ethnicity, comorbidity, and hormone receptor status, as well as adjustment for significant provider and facility-level factors. Conclusions: Further work is needed to better understand how these associations have changed over time, reasons for guideline non-concordance, and potential impact on patient outcomes.

The evolving landscape of chemotherapy for the treatment of early-stage breast cancer from 2006-2019: Results of a retrospective cohort study.

6600 Background: Chemotherapy has been a part of the evolving landscape of treatment for women with early-stage breast cancer (EBC). Over the last 20 years, standard treatment has included over 20 different drug combinations recommended by the National Comprehensive Cancer Network (NCCN), with nearly 45 variations on dosing and schedule across drug combinations. Little is known about the real-world landscape of chemotherapy used in EBC and how treatment patterns have changed with the advent of new standards of care. We evaluated chemotherapy patterns for women with EBC in the Optimal Breast Cancer Dosing (OBCD) Study, which uses electronic health record (EHR) data from KPNC (Kaiser Permanente Northern California) and Kaiser Permanente Washington (KPWA). Methods: In a cohort of 34,322 women diagnosed and treated for primary stage I-IIIA breast cancer aged 18+ at KPNC and KPWA, we explored patterns of chemotherapy use over time, from 2006 to 2019. We conducted stratified analyses based on receipt of pertuzumab and/or trastuzumab, due to their longer treatment duration. Results: Overall, 13,383 (39.0%) women received intravenous chemotherapy, with a decline observed in receipt of chemotherapy over time (40.5% in 2006 vs 35.9% in 2019) (p-trend&lt;0.001). Of the women who received chemotherapy, 8.5% received neoadjuvant treatment, increasing from 4.1% in 2006 to 14.5% in 2019 (p-trend&lt;0.0001). The average duration of chemotherapy was 5.4 months in 2006, increasing to 6.3 months in 2019 (p-trend&lt;0.0001), and the number of chemotherapy infusion visits increased from an average of 10.7 visits in 2006 to an average of 12.5 in 2019 (p-trend&lt;0.0001). Of those who received chemotherapy, 26.8% received trastuzumab or pertuzumab, with receipt of trastuzumab/pertuzumab increasing over time (p-trend&lt;0.0001). For those receiving trastuzumab/pertuzumab, there was a decrease in treatment duration and average number of chemotherapy administration visits (p-trend&lt;0.0001 for both). Conversely, for those not receiving trastuzumab/pertuzumab, there was an increase in the treatment duration and average number of visits (p-trend&lt;0.0001 for both). Conclusions: While the prevalence of women receiving chemotherapy in our cohort has decreased since 2006, there has been a marked increase in neoadjuvant chemotherapy among those women receiving chemotherapy, as well as an increase in both the duration of chemotherapy treatment and number of associated chemotherapy administration visits, a pattern specifically observed in non-trastuzumab/pertuzumab containing regimens.The change in average duration and number of visits represents a shift in treatment patterns for patients and providers. Understanding trends in breast cancer chemotherapy is useful to inform clinical care and administrative planning for sites delivering chemotherapy for early-stage breast cancer.

Abstract P6-08-04: Geographical variation of social deprivation, cardiovascular and other comorbidities in 226,516 patients with early breast cancer in England: results from a National Registry Dataset Analysis

Abstract Background In England, as for many countries, there are geographical variations in treatment uptake and outcomes for patients with early breast cancer (EBC). It is important such inequalities are addressed. The co-existence of cardiovascular disease (CVD) in patients with early breast cancer (EBC) may complicate treatment choices, lead to deviations from standard of care, and be associated with worse cancer and CVD outcomes. Social deprivation is also associated with increased incidence of co-morbidities, reduced cancer treatment rates, and worse cancer survival. If there are regional differences in rates of CVD/co-morbidities and social deprivation these may explain observed differences in treatment uptake and cancer outcomes in EBC. Therefore, in this analysis we evaluated rates of CVD and social deprivation in a large population of patients with EBC in 20 English Cancer Alliances. Methods Cancer registry data as part of The Virtual Cardio-Oncology Research Initiative (VICORI) were used to identify patients diagnosed with stage I-III breast cancer diagnosed between 2013 - 2018 in England. National data (hospital records and national cardiovascular audit databases) were used to describe CVD prevalence (CVDp), Index of Multiple Deprivation (IMD), and Charlson Comorbidity Index (CCI). Patient, disease, tumour, and treatment characteristics were allocated into Cancer Alliance tertiles according to CVDp (minimum (&amp;lt; 33.3rd percentile); middle (33.3rd – 66.6th percentile); maximum (&amp;gt;66.6th percentile)) with approximately equal patient numbers in each group. The disease burden was depicted in bar charts and regional variation as heat maps of England. The percentage of patients in the most deprived quintile of income domain of the IMD were plotted. Funnel plots were used to investigate variations in regional CVD rates based on a logistic regression model. Results Data from 226,516 patients with stage I-IIIA breast cancer with a mean age of 62.5 (+/- 13.7) were included in the analysis. 78,833 patients were assigned to the minimum (37.0%; 95% CI 36.7 – 37.2), 74,443 to the middle (35.5%; 95% CI 35.3 – 35.7), and 73,240 to the maximum (34.7%; 95% CI 34.5 – 34.9) tertile. Geographical variation between Cancer Alliances was demonstrated for CVDp (6% - 9.5%), IMD (2%- 30%), and CCI  4 (8.2% - 9.5%). Variation of CVDp revealed a South/North gradient between Cancer Alliances towards higher percentage, with centrifugal tendency from London. These findings were consistent with a similar pattern seen for variation in IMD quintiles with higher prevalence of most socioeconomic deprived patients located in cancer alliances in the North compared to the South of England. Regional variation was less obvious for CCI. After adjusting for age, TNM stage, IMD, and CCI, differences in the standardised CVD ratio persisted for some cancer alliances suggesting that other factors than those adjusted for are likely accountable for the higher CVDp seen in some Cancer Alliances. An adjusted ordinal logistic regression model demonstrated that older age (aged &amp;gt;75), white ethnicity, and social deprivation were associated with a higher risk of CVDp (p&amp;lt; 0.001). Conclusions This study highlights significant geographical variation of social deprivation, CVDp, and other comorbidities in early breast cancer patients in England which may contribute to the variability in treatment received and breast cancer survival in different regions within the country. Citation Format: Jasmin V Waterhouse, Catherine A. Welch, Nicolo M.L. Battisti, David Adlam, Michael J. Sweeting, Lizz Paley, Paul Lambert, John E. Deanfield, Mark de Belder, Michael D Peake, Alistair Ring. Geographical variation of social deprivation, cardiovascular and other comorbidities in 226,516 patients with early breast cancer in England: results from a National Registry Dataset Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-08-04.

Abstract P3-03-16: A methodology for using real-world data from electronic health records to assess chemotherapy administration in women with breast cancer

Abstract Introduction Chemotherapy administration in real-world cancer care can differ extensively from clinical trials. It is important to understand real-world practice to identify dose reductions, delays, regimen changes and early discontinuations that impact cancer outcomes. Such variables require knowledge of intended regimens, which may not be well-documented in structured data in electronic health records (EHRs). We examined EHR data from the Kaiser Permanente Northern California (KPNC) site of the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study to develop a process to identify each patient’s intended regimen. Methods In this study of women diagnosed and treated with primary stage I-IIIA breast cancer at KPNC from 2006-2019, and ages 18+y at diagnosis, we analyzed treatment patterns using structured EHR data on the drugs, dosages, and dates at which they were administered (from which intervals and total length can be derived). Chemotherapy agents were identified using the NCI’s CANMED database augmented with other sources. We used these data to categorize patients into the 22 drug combinations described in the National Cancer Care Network (NCCN) guidelines for breast cancer treatment. Within these 22 drug combinations, women were then subcategorized into 45 distinct chemotherapy administration schedules, defined as NCCN guideline regimens (NGRs). For this step, algorithms were developed that categorized patients into NGRs if they received the exact regimen described in the guidelines. For the second step, we conducted a manual review of the EHR data for patients who were unable to be categorized. This enabled us to gradually loosen the criteria (in terms of cycle intervals or number of cycles) so patients whose chemotherapy administration aligned closely with NGRs were categorized into each of the 45 NGRs. Clear patterns emerged of regimens that were administered to multiple patients, despite being outside of the NCCN guidelines, which we have defined as non-standard NGRs. For example, in the drug combination TC (cyclophosphamide and docetaxel) the NGR was TC every 21 days for 4 cycles. We found approximately 1 in 10 patients received 6 cycles, which we defined as a non-NGR. For the remaining uncategorized patients, medical chart abstraction was undertaken as a third step, at which point patients were categorized into either existing regimens or new non-NGRs if their intended regimen had not been previously described in the guidelines. Results Among 31,418 women with breast cancer, 12,427 (39.6%) received chemotherapy. We determined the intended chemotherapy regimens for 6,559 (52.8%) receiving the 45 NGRs using EHR data. We further expanded the algorithms through a manual review of the EHR data, which enabled us to categorize 2,977 (24.0%) additional women into their intended regimens. Abstracted medical notes were reviewed for the remaining patients for whom we had not been able to identify the intended regimen. Across both the manual review and abstraction processes, we were able to identify additional non-standard NGR regimens. In total, 9,536 (76.7%) of women were categorized into their intended regimen through the algorithm/manual review process, while 2891 (23.3%) of women underwent medical chart abstraction to identify the intended regimen. Conclusion Here, we describe the challenges and approaches to operationalize complex, real-world data to identify intended chemotherapy regimens at a granularity and scale not seen previously. We are adapting this method at a second OBCD study site, Kaiser Permanente Washington, where all women have undergone medical chart abstraction. We hope this methodology leads to increased feasibility and efficiency of use of large-scale clinical data, in turn improving cancer care delivery, patient outcome evaluation, and other real-world questions. Citation Format: Jenna Bhimani, Kelli O’Connell, Rachael P. Burganowski, Isaac J. Ergas, Marilyn J. Foley, Grace B. Gallagher, Jennifer J. Griggs, Narre Heon, Tatjana Kolevska, Yuriy Kotsurovskyy, Candyce H. Kroenke, Kanichi G. Nakata, Sonia Persaud, Donna R. Rivera, Janise M. Roh, Sara Tabatabai, Emily Valice, Erin J. Bowles, Elisa V. Bandera, Lawrence H. Kushi, Elizabeth D. Kantor. A methodology for using real-world data from electronic health records to assess chemotherapy administration in women with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-16.

Cost-Effectiveness Analysis of Two Chemotherapy Regiments FAC vs. Taxane for Operable Breast Cancer Patients in Indonesia.

Background:Breast cancer is the deadliest cancer among women worldwide including Indonesia. Both FAC and Taxane-based chemotherapies are often used for patients with early node-positive breast cancer. However, the study regarding the cost-effectiveness of those regiments is still rare. This study aims to analyze the cost-effectiveness of Taxane versus FAC in the Indonesia setting. Methods:Twenty-four patients with stage I-IIIA breast cancer who had received surgery, FAC or Taxane-based adjuvant chemotherapy, and radiation were included in this study. Health-related quality of life was assessed using INA-BCHRQoL. INA-BCHRQoL was mapped to the EuroQoL 5D (EQ-5D) index calculator to get the utility score. All direct cost was retrieved from electronic medical records and hospital information system. Whereas, a questionnaire was designed to collect information about society cost from patients. ICER was counted to summarize the cost-effectiveness of two chemotherapy regiments (Taxane versus FAC). A sensitivity analysis was done to assess the uncertainty result. Results:The results showed there was no significant difference between the score of quality of life and utility in respondents who received FAC chemotherapy and Taxane-based chemotherapy. However, in terms of cost, Taxane was 6.5 times higher than the FAC group per patient for chemotherapy drugs only. Moreover, the total cost of treatments in Taxane-based chemotherapy was approximately 3.7 times more costly than the counterpart in the FAC arm (p=0.000). Taxane-based chemotherapy dominated with ICER IDR 765.213.092 per QALY gained. Overall, FAC was found more cost-effective compared to the Taxane regiment. Conclusion:FAC represents the value of money compared to Taxane-based for breast cancer patients with stage I-IIIA in Indonesia.

Characterizing Beliefs About Breast Cancer and Comorbid Diabetes After Cancer Treatment.

To investigate how breast cancer survivors with comorbid diabetes mellitus (diabetes) conceptualize their illnesses. 19 community-dwelling, English- or Spanish-speaking women with diabetes in New York, New York, who received chemotherapy or hormone therapy for stage I-IIIA breast cancer in the past five years. Semistructured interviews were administered by trained research staff, and were audio recorded and transcribed. Three coders reviewed transcripts through an iterative coding process. An interpretive descriptive approach was used to identify themes. Major themes included an inverse relationship between illness control and concern, variation in perceived illness permanence, and differences in illness consequences. Women with a greater perceived control over breast cancer viewed their diabetes as a larger concern; others felt that their breast cancer could not be controlled but diabetes could. Understanding how breast cancer survivors view diabetes and cancer may explain the variation in survivors' self-management behaviors, and how it may influence their attitudes and behaviors in the context of cancer treatment.

Abstract CT116: Same-day administration of Eflapegrastim with chemotherapy enhances neutropenic recovery in neutropenic rats and in early-stage breast cancer patients

Abstract Background: Chemotherapy-induced neutropenia increases the likelihood of life-threatening infections. Currently, long-acting G-CSF products are administered 24 hours after chemotherapy (CT). Eflapegrastim's (Efla) greater marrow resident time should provide a pharmacodynamic advantage over pegfilgrastim (Peg), translating into a shorter duration of neutropenia (DN). The therapeutic potential of Efla, a long-acting G-CSF, was evaluated in a neutropenic rat model where neutropenia was induced via intraperitoneal docetaxel/cyclophosphamide. This study compared the DN with that of vehicle control and Peg at 0, 2, 5, and 24 hrs post-CT. We found that at all-time points, there was a marked reduction in the degree of neutropenia and a more rapid rate of absolute neutrophil count (ANC) recovery with Efla compared to Peg. When Efla was administered concomitantly with CT, ANC returned to normal within 12hrs for Efla vs 2.2 days post-nadir for Peg, while the DN in the vehicle group was 7 days. Pharmacokinetics (PK) of Efla for same-day dosing were similar to those reported for next-day dosing. Based on these results, a Phase 1 clinical trial is ongoing; results for the first 9 patients are reported. Material and Methods: Phase 1, open-label study where Efla is administered at a fixed dose of 13.2 mg at 0.5, 3, and 5 hours s.c. after the i.v. infusion of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) CT in patients with confirmed stage I-IIIA breast cancer. Patients &amp;gt;18 years, ECOG &amp;lt;2, adequate hematological, renal, hepatic function &amp; candidates for neoadjuvant or adjuvant CT were randomized 1:1:1 to Efla dose schedules. The primary endpoint was the duration of severe neutropenia (DSN) in Cycle 1. Secondary endpoints include incidence of Grade 3 febrile neutropenia (FN), PK &amp; safety in Cycle 1. Results: Nine patients (3 patients per cohort) were enrolled. Protocol defined dose-limiting toxicity was not met in any cohort. One patient each in the 3 hr and 5 hr cohorts, developed severe neutropenia and FN. The PK of Efla for patients in the same-day dosing cohorts were similar to those observed for next-day dosing, as predicted by neutropenic rat results. Conclusions: Results to date from both nonclinical and clinical studies were similar and support our hypothesis that the higher and more sustained marrow resident time of Efla appears to provide an effective prophylaxis against severe neutropenia when administered on the same day as CT. The 0.5 hour cohort of the study is being expanded to confirm these promising results. Citation Format: John A. Barrett, Shanta Chawla, Prasad S. Kolli, Yu- Yon Kim, Sri Lakshmikanthan, Meera Tugnait, Lyndah K. Dreiling, Francois Lebel. Same-day administration of Eflapegrastim with chemotherapy enhances neutropenic recovery in neutropenic rats and in early-stage breast cancer patients [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 CT116.

Baseline cancer worry and tumor marker testing among earlier-stage breast cancer patients participating in a Choosing Wisely pilot.

153 Background: We developed a patient-facing video aimed at raising early breast cancer survivors’ adherence to ASCO’s Choosing Wisely recommendation against surveillance tumor marker testing. To understand the impact of the video on cancer worry regarding recurrence, we surveyed breast cancer survivors before and after viewing the video. Methods: Women with stage I-IIIA breast cancer (N=246) treated at six regional community clinics were surveyed prior to viewing a video at the start of surveillance, then again at follow-up one year later (N=171). Both surveys included the Cancer Worry Scale (CWS-8 items, 4-point Likert scale). Tumor marker (TM) testing during surveillance was collected for 728 patients and linked to surveys among those who provided consent (N=105). Results: Most women (77%) were white age 50+. Among women who completed both questionnaires (N=153), the average CWS summary score was 17.1 at baseline (range=9-29) and 16.9 at follow-up ( p=0.48, range=8-30). Women who did not view the video (A) and those with high baseline cancer worry (B) who viewed the video had similar rates of TM testing (19%) compared to patients with low baseline cancer worry (C) who viewed the video (3%). Cancer worry is highly correlated with the decision to use of TM testing. Viewing an informational video that provided evidence-based advice on follow-up and testing did not impact cancer worry. Enrollment among eligible patients was impacted by challenges to proactively identify and consent patients during their transition to surveillance. Conclusions: Patients with high baseline cancer worry may need different or additional guidance beyond an educational video during their transition to surveillance for breast cancer. [Table: see text]

A pilot study to increase adherence to ASCO Choosing Wisely recommendations for breast cancer surveillance at community clinics.

18 Background: ASCO 2012 Choosing Wisely recommends against serum tumor marker tests and advanced imaging for breast cancer survivors who are asymptomatic for recurrence. Our pilot aimed to measure and raise adherence to this recommendation through a patient video at regional community clinics. Methods: Eligibility for study included patients with 1+ long-term follow-up visit within 3 months of end of treatment in the pre- or post-intervention period: Clinic tumor registries were queried for stage I-IIIA breast cancer patients treated with curative intent. The intervention included 1) academic detailing for oncologists at a regular meeting and 2) a video about the recommendation shown to patients at end of active treatment. Surveillance data was manually abstracted. We define adherence as no asymptomatic tests in the first 13 months of surveillance. Results: Advanced imaging adherence was high before and after the intervention (99-100%). Tumor marker (TM) adherence is in the table. Six of seven providers with low (&lt;60%) TM adherence before the intervention maintained low TM adherence after. One provider with low TM adherence and all 3 providers with moderate (60-90%) TM adherence increased to high TM adherence (&gt;90%). TM adherence was better among patients who viewed the video (130 of 145, 90%) than those who did not (452 of 556, 81%) in the post-intervention period. The higher TM adherence among patients who viewed the video and the wide range in adherence among providers suggest that tumor marker use may be both patient- and provider-driven. Population characteristics may explain some of the variation in adherence. Conclusions: While adherence to recommendations regarding high-cost imaging was high, wide variation in tumor marker adherence among providers and high baseline adherence for advanced imaging suggests that interventions targeting surveillance testing may wish to focus primarily on tumor markers and provider outreach. [Table: see text]