Early Stage Breast Cancer Pts Research Articles

Elucidating the immune active state of HR+HER2- MammaPrint High 2 early breast cancer.

506 Background: The 70-gene signature, MammaPrint (MP), classifies patients (pts) with early-stage breast cancer (EBC) as having an UltraLow, Low, High 1 (H1), or High 2 (H2) risk of distant recurrence. I-SPY 2 showed that pts with MP H2, HR+HER2- tumors have significantly higher response rates to neoadjuvant chemotherapy + immunotherapy relative to pts with MP H1 tumors. Expression-based immune deconvolution provides more detailed information about immune cell function beyond conventional methods enumerating tumor infiltrating lymphocytes. To elucidate the underlying biology that mediates immune therapy response, we performed in silico analysis of full transcriptome data to characterize immune cell frequencies and antigen presentation in HR+HER2-, MP High Risk EBC from pts enrolled in FLEX. Methods: The prospective, observational FLEX Study (NCT03053193) includes stage I-III pts with EBC who received MP testing and consented to full transcriptome and clinical data collection. Women with HR+HER2-, and MP High Risk invasive ductal EBC were included (n = 2916). Tumors were stratified into MP H1 or MP H2. The R-package Limma was used to preprocess gene expression data. The gene signature-based method xCell was used to determine immune cell abundances for each group based on enrichment score. Expression of genes involved in “antigen processing and presentation KEGG pathway”, and immune regulation, were evaluated between groups. Differences in immune cell frequency and gene expression were determined by a t-test with an adjusted p-value < 0.05. Results: MP classified 79% (n=2292) of HR+HER2- EBC as H1 and 21% (n=624) as H2. Pts with H2 EBC were more likely to be ≤ 50 years (32%) compared to pts with H1 tumors (23%). Although low ER staining (1-10%) tumors were more frequent in H2 vs H1 (15% vs 1%), a majority of H2 tumors (75%) had ER staining > 10%. Nearly 30% of H2 tumors were Grade 1 or 2, whereas 22% of H1 tumors were Grade 3. H2 tumors had significantly higher frequency of antigen presenting cells (APCs) including activated dendritic cells and macrophages, CD4+ memory T cells, CD8+ T cells, memory B cells and plasma cells relative to H1 tumors. The genes expressing PD-1 and PDL-1 and genes involved in antigen processing, including B2Mand TAP1/2, and presentation, i.e., major histocompatibility (MHC) class I ( HLA-A, -B, -F) and class II molecules ( HLA-DM, -DQ), were significantly upregulated in H2 vs H1. Conclusions: H2 tumors exhibited a heighted immune active state compared to H1 tumors among HR+HER2- EBC pts. The presence of APCs and increased antigen presentation, which are critical in eliciting T- and B-cell activation may explain the improved response rates to immunotherapy observed in H2 tumors. Selecting pts based on grade or ER% alone may exclude pts likely to benefit from immune therapy. These data support ongoing trials evaluating the response and benefit of adding immunotherapy to standard of care treatment regimens in MP H2 tumors. Clinical trial information: NCT03053193 .

Association of MammaPrint index and 3-year outcome of patients with HR+HER2- early-stage breast cancer treated with chemotherapy with or without anthracycline.

511 Background: The MammaPrint (MP) risk of distant recurrence signature identifies hormone receptor-positive (HR+), HER2-negative early-stage breast cancer (EBC) patients (pts) with increased or decreased chemosensitivity and chemotherapy (CT) benefit. The MINDACT trial demonstrated excellent outcomes for MP Low Risk tumors without CT, and previous studies show MP High Risk tumors exhibit higher sensitivity and benefit with CT. There remains an unmet clinical need for identifying biomarkers to inform specific regimen planning for pts who qualify for CT. Here, the association of MP index and 3-year (yr) Recurrence-Free Interval (RFI) was evaluated in pts with HR+HER2-, genomically High Risk Luminal B-Type EBC treated with taxane and cyclophosphamide (TC) vs anthracycline + TC (AC-T). Methods: The prospective, observational FLEX Study (NCT03053193) includes stage I-III breast cancer pts who received MP testing, with or without BluePrint (BP) molecular subtyping, and consented to full transcriptome and clinical data collection. Pts with HR+HER2- MP High Risk and BP Luminal B-Type tumors who received chemotherapy with 3-yr follow-up data (N = 614) were included. High Risk tumors were further classified into High 1 (H1; 0.000 to -0.569) or High 2 (H2; -0.570 to -1.000). Differences in 3-year RFI, defined as time from diagnosis to a local-regional recurrence, distant recurrence, or breast cancer specific death per STEEP 2.0 criteria, between H1 and H2 tumors were evaluated by Kaplan-Meier analysis and log-rank test, stratified by CT regimen. Results: Patients had similar age, menopausal status, race, and lymph node status between H2 vs H1 tumors. H2 tumors were more likely Grade 3, compared to H1 tumors. 86% of tumors were classified as H1 Luminal B-Type (N = 530) and 14% were classified as H2 Luminal B-Type (N = 84). AC-T treated tumors had non-significant differences in 3-yr RFI between H1 Luminal B-Type (95.3% [95% CI, 91.8-98.8]; N = 184) and H2 Luminal B-Type (97.7% [95% CI, 93.4-100.0]; N = 44). In contrast, pts with H2 Luminal B-Type (N = 40) tumors treated with TC demonstrated a significantly worse RFI of 86.4% (95% CI, 74.2-100.0) compared with 97.1% (95% CI, 95.1-99.2) in pts with H1 Luminal B-Type (N = 346) tumors, with an absolute difference of 10.7% (p = 0.0076). Conclusions: These data show that among pts with Luminal B-Type tumors, MP H2 have significantly worse 3-yr RFI than pts with MP H1 tumors when treated with TC. This further supports ongoing research demonstrating the significant benefits of anthracycline-based CT for treating H2 Luminal B-Type tumors. Conversely, MP H1 tumors do not appear to benefit from the addition of anthracycline to CT regimen. These FLEX data add to the growing evidence identifying MammaPrint as a comprehensive genomic signature regarding both prognosis as well as selection of systemic therapy for HR+HER2- EBC pts. Clinical trial information: NCT03053193 .

A phase III trial evaluating addition of adjuvant chemotherapy to ovarian function suppression + endocrine therapy in premenopausal women with pN0-1, HR+/HER2- breast cancer (BC) and oncotype recurrence score (RS) ≤25 (OFSET): NRG-BR009.

TPS612 Background: The TAILORx and RxPONDER trials demonstrated that RS identifies many postmenopausal pts with node-neg and node-pos BC and RS ≤25, who do not benefit from addition of ACT to endocrine therapy (ET). Both trials also showed that certain subsets of premenopausal pts (node-neg/high clinical risk/RS 16-20, node-neg/RS 21-25, and node-pos/RS ≤25) benefited from adding ACT to ET. Most premenopausal pts in these trials did not receive ovarian function suppression (OFS) as part of their ET regimen. Given the observed benefit from OFS in high-risk premenopausal pts with HR+/HER2- BC in the SOFT/TEXT trials, many questioned whether all or part of the observed ACT benefit in the TAILORx/RxPONDER trials may have been the result of chemotherapy-induced OFS. To address this question, we developed OFSET, a phase III, multicenter clinical trial comparing OFS+ET v ACT+OFS+ET. Methods: We hypothesize that addition of ACT to OFS+ET is superior to OFS+ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early-stage BC pts with HR+/HER2- tumors, and a 21-gene RS between 16-25 (for pN0 pts) and 0-25 (for pN1 pts). Secondary objectives include invasive disease-free survival, overall survival, distant recurrence-free interval, breast cancer-free interval, and health-related quality of life (HRQOL). Pts must be node-neg with RS 16-20 (plus high clinical risk), or RS 21-25, or have 1-3 positive nodes with RS ≤25. Stratification is by nodal status/RS status (pN0 RS 16-25 v pN1 RS 0-15 and pN1 RS 16-25), intent to receive CDK4/6 inhibitor (yes; no), and age (18-39 v ≥40). Pts are randomized after surgery to either OFS+ET or ACT+OFS+ET. ET is an aromatase inhibitor (AI). Choice is per investigator discretion; tamoxifen is allowed if AI is not tolerated or if OFS is incomplete. Radiotherapy will be administered per investigator discretion per protocol guidelines. The HRQOL substudy will assess differences in severe menopausal symptoms, measured by the FACT ESS-19 score between arms, as well as increased pain severity (PROMIS). Blood and tumor specimens will be collected for future research. Accrual of 3,960 pts is anticipated to be completed in 7 yrs, 7 mos. Per NSABP B-28 and RxPONDER data, 5yr IBCFS of pN1 pts on the ACT+OFS+ET arm is estimated at 92.3%. Based on TAILORx data, 5yr IBCFS of pN0 pts on the ACT arm is ~95%. Assuming 56% of pts to be pN0 and 44% pN1, and a 0.5% annual loss-to-follow-up rate, the definitive analyses to detect a hazard ratio: 0.75 with ACT+OFS+ET v OFS+ET, with one-sided α of 0.025 and 80% power, will require 380 IBCFS events, expected to occur~11 yrs after study initiation. OFSET was activated Aug 2023. Clinical trial information: NCT05879926 .

Abstract PO2-09-09: Racial/Ethnic Differences in Survival of Male Patients with Stage I-III Breast Cancer by Hormone Receptor Status Using Real-World Data

Abstract Background: Male breast cancer (BC) is rare and accounts for < 1.0% of all BCs in the US. Given its rarity and limited data, racial/ethnic differences in survival outcomes among men with early-stage BC (EBC) at the national level have not been well studied. In this study, we sought to estimate 5-year survival rates and assess how overall survival (OS) in male patients (pts) with EBC differed by race/ethnicity and by hormone receptor (HR) status. Methods: Data were obtained from male pts with stage I-III BC in the 2004-2019 National Cancer Database (NCDB). Racial/ethnic groups included Asian or Pacific Islander (API), Black, Hispanic, and White. HR status was dichotomized as “negative/positive.” The Kaplan-Meier method was used to estimate 5-year OS by race/ethnicity and comparisons were made using log-rank tests. OS, defined as death or censored from the date of diagnosis to the date of death or last contact, was modeled using a multivariable Cox regression, as well as stratified by HR status. Cox models were adjusted for sociodemographic and clinicopathologic factors. Results: Of 22,340 pts, 56.4% were aged ≥65 years; 81.7% were White, 12.4% Black, 3.7% Hispanic, and 2.3% API; 94.3% had HR-positive tumors. 5-year OS rates were greater in API (84.5%) and Hispanic (84.2%) pts as compared with 5-year OS of White pts (77.2%); however, Black pts had a lower rate of 5-year OS (73.4%) (p< .001). Similar findings of estimated 5-year OS rates were observed across racial/ethnic groups stratified by HR status (Table). After adjusting for clinicopathologic factors, Black pts had a higher mortality risk than White pts (adjusted hazard ratio [aHR]=1.13, 95% CI: 1.01-1.25), while Hispanic (aHR=0.65, 95% CI: 0.51-0.85) and API (aHR=0.62, 95% CI: 0.45-0.86) pts had a lower risk of death than white pts. After further adjusting for sociodemographics, there was no significant OS difference between Black and White pts (aHR=0.98, 95% CI: 0.87-1.11); OS rates remained significantly higher in API (aHR=0.69, 95% CI: 0.50-0.96) and Hispanic (aHR=0.60, 95% CI: 0.46-0.79) pts than in White pts. Additionally, pts with a median household income of $50,354-63,332 (aHR=0.86, 95% CI: 0.75-0.99) or of ≥$63,333 (aHR=0.74, 95% CI: 0.64-0.86) had a lower risk of dying than those of < $40,227. Uninsured pts (aHR=1.54, 95% CI: 1.12-2.12) or pts with public insurance (Medicare: aHR=1.54, 95% CI: 1.36-1.75; Medicaid: aHR=1.41, 95% CI: 1.13-1.77) had a higher risk of dying than privately insured pts. In the HR-positive cohort, similar mortality risks between racial/ethnic minoritized and White pts were observed (Table). However, in the HR-negative cohort, after adjusting for sociodemographic and clinicopathologic factors, API pts had a greater risk of death than White pts (aHR=2.75, 95% CI: 1.25-6.03); Black pts also had a higher mortality risk than White pts, though it was not statistically significant (aHR=1.37, 95% CI: 0.87-2.14). Conclusions: In this large retrospective cohort of male EBC pts, API and Hispanic pts had higher OS than White pts. Higher income and private health insurance were associated with greater OS. Black pts had lower OS than their White counterparts when controlling for clinicopathologic factors; however, the difference was not significant after further controlling for sociodemographics. Addressing socioeconomic disparities and inequities that impact access to health care and services may help improve survival outcomes across racial/ethnic groups of male EBC pts. Table. Racial and ethnic differences in overall survival of male patients with stage I-III breast cancer Citation Format: Jincong Freeman, Jared Hara, Olasubomi Omoleye, James Li, Wenji Guo. Racial/Ethnic Differences in Survival of Male Patients with Stage I-III Breast Cancer by Hormone Receptor Status Using Real-World Data [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-09.

Abstract PO3-03-01: Impact of Environmental Temperature on Clinical Outcomes and Tumor Microenvironment of Early-Stage Breast Cancer

Abstract Background Preclinical evidence using mouse model suggests that thermal/cold stress increases tumor growth by modulating the tumor microenvironment (TME); however, the clinical relevance of temperature on breast cancer (BC) outcomes is unknown. Studies show that residing in cold regions is associated with higher incidence of BC. We aim to study the impact of environmental temperature on the pathological complete response (pCR) and survival of early-stage BC patients (pts). Methodology A multi-institutional study was conducted within the Oncology Research Information Exchange Network (ORIEN). We analyzed the clinical and genomic data for early-stage BC pts from 12 centers in different environment zones (5 warm and 7 cold) (based on average annual regional temperature obtained from National Centers for Environmental Information). Cox regression was used to measure the association of climate and overall/relapse-free survival (OS/RFS) after adjusting for age, race, body mass index, grade, stage, treatments, comorbidities, and subtype. Raw feature counts were normalized, and differential expression analysis was carried out using DESeq2, while adjusting for all of the covariates. Differential expression rank order was used for subsequent gene set enrichment analysis (GSEA), performed using the cluster profile package in R. Gene sets queried included the Hallmark, Canonical pathways, and GO Biological Processes Ontology collections available through the Molecular Signatures Database (MSigDB). Results Out of the 1,304 early-stage BC pts, 271 pts received neoadjuvant chemotherapy (NAC) (186 warm, 85 cold). Higher clinical T- and N-stages were observed in pts from warm compared to cold regions (p< 0.001). Pts residing in cold regions had more comorbidities (57.6% vs 4.8%, p< 0.001). Pts in warm regions had higher pCR, though not statistically significant (8% vs 2.5%, p= 0.1). In the overall population, the OS (univariate (UV) HR= 0.48, 95% CI 0.27-0.64, p < 0.001; adjusted HR (aHR)= 0.56, 95% CI 0.32 - 0.96, p= 0.03) and RFS (UV HR= 0.51, 95% CI 0.38 - 0.68, p< 0.001; aHR= 0.52, 95% CI 0.36 - 0.75, p= 0.0005) were higher in pts from warm compared to cold regions (Table 1). Among the patient subgroup treated with NAC, the OS (aHR= 0.35, p= 0.02) and RFS (aHR= 0.49, p= 0.02) of pts from warmer regions was also higher than cold regions. RNA sequencing was performed on 826 tumors (443 warm, 383 cold) using pre-treatment samples. Naïve B-cells (mean: 0.09 vs 0.08, p=0.004), CD4 naïve T cells (0.03 vs 0.02, p= 0.0008), CD4+ memory T cells (0.03 vs 0.02, p= 0.04), gamma-delta T-cells (0.007 vs 0.004, p= 0.006) were higher in pts residing in cold compared to warm regions while CD8 T cells, T regulatory cells, macrophages, dendritic cells, natural killer cells were similar in both regions. Macrophage signaling, cholesterol metabolism and the pathway for negative regulation of cell migration in angiogenesis were upregulated in pts living in warm compared to cold regions. Conclusion Early-stage BC pts living in cold have worse OS and RFS compared to warm regions. Our study is the first to report significant differences in the TME among these pts. However, it is important to acknowledge that the limited availability of comprehensive data regarding patients' relocation to different environmental temperature zones during treatments, and individual temperature preferences may be considered a potential limitation of our study. To ensure the validity and robustness of these intriguing findings, larger multi-center studies should be conducted, encompassing detailed information on the duration of exposure to both warm and cold weather conditions. Table 1: OS and RFS of patients living in warm vs cold environments Citation Format: Arya Mariam Roy, Spencer Rosario, Anthony George, Qiang Hu, Brian Czerniecki, John Carpten, Virginia Borges, Bryan Schneider, Jill Kolesar, Christopher Moskaluk, Craig Shriver, Cindy Matsen, Shridar Ganesan, Sneha Phadke, Wajeeha Razaq, Kristopher Attwood, Shipra Gandhi. Impact of Environmental Temperature on Clinical Outcomes and Tumor Microenvironment of Early-Stage Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-01.

Abstract PO2-19-02: NRG-BR009: Phase III Trial Evaluating Addition of Adjuvant Chemotherapy to Ovarian Function Suppression + Endocrine Therapy in Premenopausal Women with pN0-1, HR+/HER2- Breast Cancer and Oncotype Recurrence Score ≤25 (OFSET)

Abstract Background: Identifying pts with HR-positive/HER2-negative breast cancer (BC) who benefit from adjuvant chemotherapy (ACT) has been a major research focus over the past 20 years. Development and clinical application of genomic classifiers such as the 21-gene recurrence score (RS) has contributed to the biologic understanding of BC and has refined pt selection for ACT. The TAILORx and RxPONDER clinical trials demonstrated that RS identifies many postmenopausal pts with node-negative and node-positive BC and RS < 25, who do not benefit from the addition of ACT to endocrine therapy (ET). However, both trials also showed that certain subsets of premenopausal pts (node-negative/high clinical risk/RS 16-20, node-negative/RS 21-25, and node-positive/RS < 25) benefited from the addition of ACT to ET. Most premenopausal pts in these two trials did not receive ovarian function suppression (OFS) as part of their ET regimen. Given the observed benefit from OFS in high-risk premenopausal pts with HR-positive/HER2-negative BC in the SOFT and TEXT trials, many questioned whether all or part of the observed ACT benefit in the TAILORx/RxPONDER trials may have been the result of chemotherapy-induced OFS. To address this question, OFSET is a Phase III, multicenter clinical trial evaluating the addition of ACT to OFS+ET vs. OFS+ET alone. Methods: We hypothesize that the addition of ACT to OFS+ET is superior to OFS+ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early-stage BC pts with HR-positive/HER2-negative tumors, and a 21-gene RS between 16-25 (for pN0 pts) and 0-25 (for pN1 pts). Secondary objectives include invasive disease-free survival (IDFS), overall survival (OS), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and health-related quality of life (HRQOL). Eligible pts must be node-negative with RS 16-20 (plus high clinical risk), or RS 21-25, or have 1-3 positive nodes with RS < 25. Stratification is by nodal status/RS status (pN0 RS 16-25 vs pN1 RS 0-15 and pN1 RS 16-25), intent to receive CDK4/6 inhibitor (yes; no), and age (18-39 vs ≥40). Pts are randomized after surgery to either OFS+ET or ACT followed by OFS+ET. ET is an aromatase inhibitor per investigator discretion, but tamoxifen is allowed if pts do not tolerate the AI or if OFS is incomplete. Radiation therapy will be administered per investigator discretion according to protocol guidelines. The HRQOL sub-study will assess differences in severe menopausal symptoms, measured by the FACT ESS-19 score, between the arms, as well as increased pain severity (PROMIS) during ACT+OFS+ET compared to OFS+ET. Blood and tumor specimens will be collected for future research. The accrual of 3,960 pts is anticipated to be completed in seven years and seven mos. Based on data from NSABP B-28 and RxPONDER, the 5-year IBCFS of pN1 pts on the ACT+OFS+ET arm is estimated at 92.3%. Based on data from TAILORx, the 5-year IBCFS of pN0 pts on the ACT arm is ~95%. Assuming 56% of the pts to be pN0 and 44% pN1, a 0.5% annual loss-to-follow-up rate, the definitive analyses to detect a hazard ratio: 0.75 with ACT+OFS+ET vs. OFS+ET, with one-sided alpha of 0.025 and 80% power will require 380 IBCFS events, which are expected to occur ~11 years after study initiation. The OFSET study is expected to be activated in the third quarter of 2023. Current accrual (06-19-2023) is 0/3,960 Support: U10CA180868, U10CA180822, UG1CA189867, U24CA196067. NCT05879926. Citation Format: Eleftherios Mamounas, Gong Tang, Shannon Puhalla, Sandra Swain, Patricia Ganz, N. Lynn Henry, Reena Cecchini, Sonya Reid, Priya Rastogi, Charles Geyer, Julia White, Amy Clark, Tufia Haddad, Gregory Vidal, Norman Wolmark. NRG-BR009: Phase III Trial Evaluating Addition of Adjuvant Chemotherapy to Ovarian Function Suppression + Endocrine Therapy in Premenopausal Women with pN0-1, HR+/HER2- Breast Cancer and Oncotype Recurrence Score ≤25 (OFSET) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-02.

Abstract B095: Association of race and neighborhood deprivation with early-stage breast cancer survival in the United States

Abstract Introduction: Socioeconomic status (SES) of individuals and their neighborhoods holds significant influence over their access to the healthcare system and consequently, the outcomes of their diseases. Inequities in opportunities, education, income, and developmental infrastructure can contribute to poor prognosis and unfavorable outcomes for breast cancer (BC) in areas with lower SES. We studied the association of race and ethnicity with the neighborhood deprivation index (NDI) and the survival of early-stage BC. Methodology We utilized the NDI quintile (qn) developed by the National Cancer Institute, which incorporates variables from dimensions such as wealth and income, education, occupation, and housing conditions. By querying the SEER database from 2010 to 2016, we identified early-stage BC patients (pts) and examined the association between NDI, race/ethnicity and overall survival (OS) and disease-specific survival (DSS). Cox multivariate regression was employed to assess the association between NDI and OS/DSS. Kruskal-Wallis test, and chi-square tests were used for comparisons of continuous, categorical variables respectively. All analyses were adjusted for age, race, grade, insurance, and treatments. Statistical analyses were performed using SAS. Results Out of the 88,572 early-stage BC pts, 27.4 % (n= 24,307) were in the most deprivation (MD) qn, 26.5% (n= 23,447) were in the average deprivation (AD) qn, 17% (n= 15,035) were in the above average deprivation (AA) qn, 15.6% (n= 13,838) were in the least deprivation (LD) qn and 13.5% (n= 11,945) were in the below average deprivation (BA) qn. There was a predominance of racial minorities in the MD and AA qn with Blacks being 13-15% and Hispanics being 15% compared to only 8% Blacks and 6% Hispanics in the LD qn (p<0.001). There was a higher percentage of uninsured pts in the MD qn compared to LD qn (2.2% vs 1.7%, p<0.001). The interaction between NDI and race for OS and DSS was significant (p-interaction 0.0030 and 0.02 respectively). In the multivariate analysis, Whites residing in the MD and AA qn had higher overall and disease-specific mortality compared to those residing in the LD qn (OS- MD: HR= 1.23, 95% CI= 1.14-1.34, p<0.001, AA: HR= 1.32, 95% CI= 1.21-1.44, p<0.001; DSS- MD: HR= 1.29, 95% CI= 1.15-1.45, p<0.001, AA: HR= 1.37, 95% CI= 1.21-1.56, p<0.001). However, this disparity in mortality based on the NDI was not observed for Blacks with early-stage BC (OS- MD: HR= 1.2, 95% CI= 0.98-1.46, p=0.06, AA: HR= 1.17, 95% CI= 0.95-1.44, p= 0.01, DSS- MD: HR= 1.2, 95% CI= 0.94-1.55, p= 0.12, AA: HR= 1.22, 95% CI= 0.94-1.6, p=0.11). Conclusion Blacks with early-stage BC have poor OS and DSS regardless of the SES of the neighborhoods. Personalized treatments are needed for Blacks with early-stage BC to improve their clinical outcomes. Whites living in areas with early-stage BC have poor OS and DSS. To reduce healthcare disparities and enhance breast cancer outcomes, targeted investments and policies should prioritize improving the SES of underprivileged areas with high deprivation. Citation Format: Arya Mariam Roy, Anthony George, Archit Patel, Kristopher Attwood, Shipra Gandhi. Association of race and neighborhood deprivation with early-stage breast cancer survival in the United States [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 B095.

Neighborhood deprivation and race as predictors for cancer-related mortality in breast cancer.

174 Background: The socioeconomic status (SES) of individuals and their neighborhoods significantly influences their access to healthcare and the outcomes of their diseases. Inequities in opportunities, education, income, and infrastructure can contribute to worse prognosis and unfavorable outcomes for certain malignancies in areas with lower SES. We studied the association of race and neighborhood deprivation with the survival of breast cancer (BC). Methods: We linked the neighborhood deprivation index (NDI) data by the National Cancer Institute with the BC cohort from the SEER database diagnosed from 2010 to 2016. NDI score of each county is created using factor analysis to identify variables from 13 SES attributes from the dimensions: wealth/income, education, occupation, housing conditions. NDI was classified into quintiles (qn) (Q1 least deprived - Q5 most deprived). The association between NDI, race/ethnicity and overall survival (OS) and disease-specific survival (DSS) was analyzed using Cox multivariate regression model. All analyses were adjusted for age, race, grade, insurance, and treatments. Results: Most of the early-stage (ES) (N= 88, 572) and advanced-stage (AS) BC (N= 12336) patients (pts) were in the Q5 (ES- 27.4%, AS- 30%) qn. There was a predominance of racial minorities in Q5 and Q4 compared to Q1 qn (ES: Blacks 13-15% vs 8%, Hispanics 15% vs 6%; AS: Blacks 19-23% vs 14%, Hispanics 13% vs 7%, p<0.001). Uninsured ES pts were higher in Q5 compared to Q1 qn (2.2% vs 1.7%, p<0.001). Triple-negative BC was higher in Q5 compared to Q1 qn (ES: 14.5% vs 11.7%; AS: 16.5% vs 8.8%, p<0.001). ES BC pts who live in Q5 qn have inferior OS and DSS compared to Q1 qn, but this trend was not observed in advanced BC (Table 1). The interaction between NDI and race for OS and DSS was significant (p-interaction 0.0030 and 0.02 respectively) for the ES BC, but not for advanced BC (p-interaction 0.67 and 0.72 respectively). In ES BC, Whites residing in Q5 qn had higher overall (OS: HR= 1.23, 95% CI= 1.14-1.34, p<0.001) and disease-specific mortality (DSS: HR= 1.29, 95% CI= 1.15-1.45, p<0.001) compared to Whites from Q1 qn. However, this disparity in mortality based on the NDI was not observed for Blacks with ES BC (OS: HR= 1.2, 95% CI= 0.98-1.46, p=0.06, DSS: HR= 1.2, 95% CI= 0.94-1.55, p= 0.12). Conclusions: Early-stage BC pts from areas with worse NDI have poor OS and DSS. Blacks with early-stage BC have poor OS and DSS regardless of the SES of the neighborhoods. To improve their clinical outcomes, personalized treatments are needed for Black pts with early-stage BC. Targeted investments and policies should prioritize improving the SES of neighborhoods with high deprivation to reduce healthcare disparities and enhance BC outcomes.[Table: see text]

Managing RT Schedules of Early-Stage Breast Cancer Patients with a Genetic-Dosimetric Validated Model for Late Fibrosis

Define a multifactorial risk prediction model for RT-induced fibrosis and investigate the benefit of a personalized approach for breast cancer (BC) patients (pts) treated with whole breast RT. In a previous study, we confirmed the predictive role of 30 SNPs from the literature and built an interaction aware Polygenic Risk Score (PRS, following the methods from Franco RO 2021) for Late Fibrosis (FG2+) on a cohort of 1500 pts from the REQUITE EU/USA prospective observational study. The PRS weights the radiosensitive (RS) and radioresistant (RR) genetic components and can be included in NTCP models. In a subgroup from the same cohort (390 pts), we have also confirmed an NTCP model based on biologically Equivalent Uniform Dose (BEUD) from PTV DVHs for pts treated at 40-50 Gy and no RT boost. Here, we combine PRS and BEUD into a sigmoid model allowing PRS to modulate BEUD50 (BEUD leading to 50% FG2+), i.e., we permitted a personalized BEUD50. We can also consider this as translating the PRS into a personalized equivalent BEUD, which is added/subtracted to the treatment BEUD. We evaluated model performances through ROC-AUC, calibration plot and Precision-Recall AUC. A total of 381 pts had complete dosimetric/genetic data, prescribed dose 40-50 Gy, and no fibrotic alteration at RT start. We scored FG2+ in 87 pts (23%). PRS ranged from -13 (more RR pts) to 7 (more RS), and a unit in PRS corresponds to 5.3 Gy BEUD or 3 Gy in EQ EUD2 Gy. Table 1 summarizes model performances, with details for subgroups below/above the quartiles I/III of the BEUD distribution. The PRS-only model correctly describes the toxicity rates in the whole population (calibration slope/offset = 0/1). Still, it overestimates/underestimates the absolute risks in the low/high dose ranges. The integrated model improves AUC-ROC and AUC-PRC by 5% and 10% and guarantees a better calibration in pts receiving low/high BEUD to the PTV. We developed a multifactorial model for FG2+ based on two previously validated models and reported the improvement against single-factor models. The BEUD+PRS model is suitable for assisting clinicians in managing early-stage BC pts. The number of fractions or the daily dose could be reduced for RS pts. The integrated model resulted in a possible quantitative tool for driving the planning decision process. Also, it showed a better performance in the high BEUD region, suggesting the potential value of its extension toward RT including boost or ultra hypofractionation. We are testing this extension in the whole REQUITE cohort.

HRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC).

539 Background: Pathologic mutations in BRCA1, BRCA2 and PALB2 lead to impaired homologous recombination repair (HRR). Cells with defects in HRR are dependent on non-homologous DNA end joining for DNA repair through the poly(ADP-ribose) polymerase (PARP) catalytic activity. PARP inhibitors (olaparib, talazoparib) are FDA-approved therapies that are toxic to tumors with HRR deficiency (HRD) and are recommended as adjuvant therapy in high-risk germline BRCA (g BRCA) positive BC. Despite the clinical implications of HRD, the prevalence of HRR alterations and HRD signature in early-stage primary BC and its association with hormone receptor (HR) status has not been well characterized. Methods: This study used the nationwide (US-based, ~280 US cancer clinics) de-identified Flatiron Health-Foundation Medicine BC clinico-genomic database and included patients (pts) who underwent tissue comprehensive genomic profiling (FoundationOne/FoundationOneCDx) between 2014 and 2022. The analysis included all pts with BC who presented with “early” stage I-III disease), had a primary tissue specimen collected within 3 months of diagnosis, and had a reportable novel scar-based HRD signature (HRDsig). Results: A total of 896 primary BC pts with stage I-III met our inclusion criteria. Of these early BC pts 21% (188/896) were HRDsig+ (stage I: 17% (32/188); stage II: 22% (84/376); and stage III: 22% (72/332)). For early BC pts, high rates of HRDsig+ were seen in g BRCA (87% [34/39]), somatic BRCA (s BRCA, 78% [14/18]), and g PALB2 (71% [5/7]) mutated tumors, with a lower rate seen with other HRR genes [16% (10/63); ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, sPALB2, RAD51B, RAD51C, RAD51D and RAD54L]. HRDsig+ was also detected in 16% (135/832) of BC without g/s BRCA or g PALB2 mutations. BC pts who presented with stage I-III disease has similar prevalence of HRDsig+ when compared to those with stage IV disease (21% [188/896] vs 23% [177/767], p = 0.31), with similar trends in HR+ disease (HR+/HER2+: 7% [4/57] vs 9% [4/45], p = 0.73; and HR+/HER2-: 17% [78/466] vs 18% [82/463], p = 0.73). Conversely, in HR- cohorts, decreased prevalence of HRDsig+ was observed in the stage I-III vs stage IV cohort (HR-/HER2+: 3% [1/38] vs 18% [6/33], p = 0.04; HR-/HER2-: 31% [99/321] vs 38% [83/216], p = 0.08). Conclusions: In this study, HR+/HER2- group was the most common early BC subtype, followed by HR-/HER2-, HR+/HER2+, and HR-/HER2+. This distribution is similar to the SEER study, and closely reflects that of the general population. We observed the expected high rates of HRDsig+ in early-stage BC pts with g/s BRCA or g PALB2 mutations where clinical trial data already support the use of PARP inhibitors for early and advanced disease. Importantly, HRDsig positivity was also seen in 16% of early BC without g/s BRCA or g PALB2, and clinical trials will be needed to determine if these pts could also benefit from HRD directed therapies.

Abstract PD1-04: Neighborhood Deprivation Index and Survival in Breast Cancer in the United States

Abstract Introduction: Socioeconomic status (SES) of the individual and neighborhood plays an important role in patients’ (pts) access to the health system and eventually in the outcomes of their disease. Owing to the inequalities in opportunities, education, income, and developmental infrastructures, the area with deprived individual and neighborhood SES may be associated with a poor prognosis of certain malignancies and worse outcomes. We analyzed the association between Neighborhood Deprivation Index (NDI) and survival of early-stage breast cancer (BC). Methods: The NDI created by the National Cancer Institute includes variables from dimensions, such as, wealth and income, education, occupation, and housing conditions which have been used for our analysis. We analyzed the impact of NDI in quintiles (qn). We queried the SEER database from 2010-2016 for all early-stage BC pts and studied the overall survival (OS) and disease-specific survival (DSS) of BC in association with NDI. Cox multivariate regression modeling was performed to measure the association between NDI and OS/DSS. Kruskal-Wallis test was used for comparison for continuous and Chi-Square test was used for categorical variables. All analyses were adjusted for age, race, grade, insurance, surgery (SX), radiation (RN), and chemotherapy (CT). Statistics were performed using SAS. Results: Out of the 88,572 early-stage BC pts, 27.4 % (n= 24,307) were in the most deprivation (MD) qn, 26.5% (n= 23,447) were in the average deprivation (AD) qn, 17% (n= 15,035) were in the above average deprivation (AA) qn, 15.6% (n= 13,838) were in the least deprivation (LD) qn and 13.5% (n= 11,945) were in the below average deprivation (BA) qn. The median age of pts in the LD qn was 59 and MD qn was 61 yrs, p< 0.001. There was a predominance of racial minorities in the MD and AA qn with Blacks being 13-15% and Hispanics being 15% compared to only 8% Blacks and 6% Hispanics in the LD qn (p< 0.001). There was a higher percentage of uninsured pts in the MD qn compared to LD qn (2.2% vs 1.7%, p< 0.001). There were more rural areas in MD qn compared to LD qn (25.9% vs only 0.7%, p< 0.001). There were more pts with grade III disease in MD qn compared to LD qn (34% vs 31.9%, p< 0.001). 96.1% pts underwent SX in MD qn vs 97.1 % had SX in LD qn, p< 0.001. Similarly, 49.7% underwent RN in MD qn vs 56.5% had RN in the LD qn, p< 0.001. Greater percentage of pts received CT in MD qn compared to LD qn (44.6% vs 42.1%, p< 0.001). There was a higher percentage of more aggressive cancers such as triple-negative breast cancer (TNBC) and HER2 positive (HER2+) in MD qn compared to LD qn (14.5%, 17.7% vs 11.7%, 16.5% respectively, p< 0.001). In multivariate analysis, in the overall cohort, those who live in AA qn and MD qn have inferior OS and DSS when compared to those who live in LD qn (OS in AA: Hazard Ratio (HR) 1.3, 95% CI: 1.2-1.4; OS in MD: HR 1.2, 95% CI: 1.1-1.3; DSS in AA: HR 1.3, 95% CI: 1.2-1.5; DSS in MD: HR 1.2, 95% CI: 1.1-1.4, all p< 0.001). Similar results in OS and DSS were observed in hormone receptor-positive HER2 negative (HR+) and HER2+ subtypes, but not in TNBC (Table 1). The 5-year OS rates and DSS rates were also comparatively low in AA qn and MD qn compared to LD qn (OS: AA- 84%, MD- 85%, LD- 98%; DSS: AA- 91%, MD- 92%, LD- 95%, all p< 0.001). Conclusion: Early-stage BC pts from areas with worse NDI have poor OS and DSS, after accounting for the demographic, clinicopathological, treatment-related factors. Investments in poor-resource neighborhoods and policies focusing on improving the SES of areas with high deprivation need to be implemented to reduce health care disparities and improve breast cancer outcomes. Table: Overall Survival and Disease Specific Survival Citation Format: Arya Mariam Roy, Anthony George, Kristopher Attwood, Shipra Gandhi. Neighborhood Deprivation Index and Survival in Breast Cancer in the United States [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 PD1-04.

Abstract P3-12-20: Outcomes of patients with pathologic complete response following neoadjuvant HER2-targeted therapy in patients with HER2+ early stage breast cancer

Abstract BACKGROUND: Contemporary clinical trials of HER2-targeted therapies have shown benefits regarding recurrence and survival in patients (pts) with HER2+ early stage breast cancer. The outcomes of pts treated in community practice settings who had a pathologic complete response (pCR) to neoadjuvant therapy or who had residual disease at definitive surgery (non-pCR) have not been well characterized. This preliminary study aimed to describe the patient characteristics, disease-free survival (DFS) and overall survival (OS) in patients with and without pCR following neaoadjuvant HER2-targeted therapy in The US Oncology Network. METHODS: This retrospective cohort study identified pts diagnosed with stage I-III HER2+ breast cancer who initiated neoadjuvant HER2-targeted therapy in the community setting between April 1, 2014 - March 31, 2019. Pts were followed through the date of last visit, death, or study end (March 31, 2021), whichever occurred first. Data were collected from the US Oncology Network’s electronic medical record database, iKnowMed. Natural language processing/artificial intelligence was used to identify pts with pCR status and pts with disease recurrence during the study period. Patient profiles, risk of recurrence (RR), and time to recurrence (TTR) were assessed descriptively. Kaplan-Meier methods were used to evaluate DFS and OS from the start of neoadjuvant therapy. Results were stratified by pCR status. RESULTS: The study included 641 pts (median age, 55 years), 71% had non-pCR and 29% had pCR. The majority of pts were Caucasian (79%) or black (8%). At diagnosis, 78% of pts had stage I/II disease, and 21% stage III. Nearly 74% were HR+. With a median follow-up of 33 months, pts who had non-pCR had a higher risk of disease recurrence (10.3% vs 8.1%) and a shorter median TTR (18.6 vs 21.1 months) compared to pts with pCR. Three-year DFS (87.5% vs 92.2%) and OS (96.0% vs 98.8%) were lower in pts with non-pCR than with pCR. CONCLUSIONS:Findings from this real-world study of HER2+ early stage breast cancer pts who received neoadjuvant HER2-targeted therapy in the community setting suggested that pts with non-pCR had shorter DFS and OS outcomes than pts with pCR. Pts with non-pCR had a risk of recurrence of nearly 10% over approximately a 3-year time period . This residual risk of recurrence among non-pCR pts suggested a potential opportunity to improve long-term outcomes in this group. Future analyses, including HR subgroups, are planned as data mature and longer follow-up time is available. Results on additional pts with known pCR/non-pCR data, with longer follow-up, and outcomes by HR+ vs HR- status will be presented. Disclosure DeclarationThis study was funded by Puma Biotechnology, Inc. Outcomes of pts with pCR or non-pCR following neoadjuvant HER2-targeted therapyNon-pCRpCROverall CohortN=429N=185N=641Follow-up time, months, median (range)30.8 (0.0,81.6)38.4 (2.8,83.3)33.0 (0.0,83.3)Patients with recurrence, n (%)44 (10.3%)15 (8.1%)59 (9.6%)Time to recurrence, median (range)18.6 (0.0,42.4)21.1 (0.0,60.3)18.8 (0.0,60.3)Disease-free survival at 36 months87.5% (83.4,90.7)%92.2% (86.8,95.4)%89.0% (85.9,91.5)%Overall survival at 36 months96.0% (92.8,97.8)%98.8% (95.2,99.7)%97.0% (94.9,98.3)% Citation Format: Joyce O'Shaughnessy, Nina Oestreicher, Nicole Fulcher, Wan-Yu Tseng, April Beeks, Julia Moore, Deepa Lalla. Outcomes of patients with pathologic complete response following neoadjuvant HER2-targeted therapy in patients with HER2+ early stage breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-20.

The prognostic performance of PREDICT+ in patients (pts) with HER2-positive (HER2+) early-stage breast cancer (EBC).

524 Background: PREDICT+ is a widely used, free, online tool based on traditional clinico-pathological features, including HER2, developed to predict individual mortality of EBC pts and to aid clinical decision making for adjuvant therapy. However, its prognostic role in HER2+ EBC pts treated with chemotherapy (CT) and anti-HER2 therapies remains unclear. We aimed to investigate the prognostic performance of PREDICT+ in HER2+ EBC pts enrolled in the ALTTO trial. Methods: ALTTO is a phase III study evaluating adjuvant lapatinib (L) +/- trastuzumab (T) vs. T alone in pts with HER2+ EBC. Pts enrolled in the ALTTO trial and receiving T-based therapy started concurrently with CT were eligible for this analysis. We calculated PREDICT+ estimates using variables extracted from ALTTO database, blinded to pts outcomes. The prognostic performance of PREDICT+ was evaluated by assessing its calibration and discriminatory accuracy. For calibration, median predicted 5-year (5-yr) overall survival (OS) was compared to observed 5-yr OS. For discriminatory accuracy, the area under the receiver-operator characteristic (AUC under the ROC) curve and corresponding 95% confidence intervals (CI) for predicted 5-yr OS were calculated. Subgroup analyses were performed according to type of anti-HER2 therapy, type of CT, age, hormone receptor (HR) status, nodal status and tumor size. Results: This analysis included 2,794 pts. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT+ underestimated 5-yr OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups (Table). For discriminatory accuracy, AUC under the ROC curve was 73.7% (95%CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analysed subgroups. Conclusions: In HER2+ EBC pts enrolled in the ALTTO trial, the PREDICT+ score highly underestimated OS. The low performance of this prognostic tool was consistent across all pts subgroups. PREDICT+ should be used with caution to give prognostic estimation in HER2+ EBC pts treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.[Table: see text]

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. 963 pts. Mean age is 56years. Mean tumour size is 1.7cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. Over the 8years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Effect of evidence-based nutrition educational intervention on adherence to dietary guidelines (ADG) and weight management among early-stage breast cancer (EBC) patients (pts): A prospective trial.

12056 Background: Excess adiposity is linked to an increased risk of worse outcome among EBC pts. Pts undergoing EBC treatment are susceptible to change in nutrition status. However, implementation and assessment of the adherence to lifestyle interventions have been limited. This prospective trial aimed to evaluate the impact of an evidence-based nutrition intervention, according to the ADG, in terms of body composition changes in EBC pts. Methods: Entry criteria: EBC pts candidate to neoadjuvant/adjuvant therapy. At study entry, pts received a nutrition evidence-based tailored intervention. Dietary and anthropometric assessments were evaluated at baseline and after 12-months nutritional intervention. Waist circumference (WC) was assessed as a surrogate measure of fat distribution. ADG was estimated by Med-Diet 14-item questionnaire. Health-Related Quality of Life was analysed with EORTC QLQ-C30. Descriptive statistics was adopted. Associations between variables and groups according to nutritional variables were analysed (Chi-square test). Results: From February 2016 to December 2019, 243 pts were enrolled (median age 49 years): 27.6%/48.6% neoadjuvant/adjuvant treatment. At baseline, 38.3% of pts were overweight and 23.9% were obese. Notably, tumor size was significantly correlated with WC in the whole population (p = 0.003). Moreover, pts with central obesity were more likely to present HER2-negative tumors (57.4% vs. 42.5%, p = 0.03). Most pts reported relevant nutrition impact symptoms and symptoms affected QoL. Particularly, dyspepsia and constipation were more prevalent in overweight and obese pts (p < 0.0001 and p = 0.009, respectively), as well as in pts who gained ≥5% of weight (p = 0.04 and p = 0.02, respectively). At baseline, there was low ADG. After the 12-months intervention, ADG significantly increased (median Med-Diet score: 6 vs.12, p < 0.0001). A high ADG (defines as a Med-Diet score ≥10) significantly correlated with: 1) loss of weight ≥5% from the baseline weight (p = 0.003); 2) change in terms of BMI; 3) prevalence of central obesity. Conclusions: A tailored evidence-based nutritional intervention for EBC pts represents a tool to improve their ADG, weight management and, thus, to potentially influence the disease outcome. [Table: see text]

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

540 Background: Treatment of hormone receptor positive (HR+) ESBC is evolving. The use of chemotherapy (CT) is declining with use of the 21-gene RS assay. This validated tool predicts the likelihood of adjuvant CT benefit in HR+ ESBC. Results from the TAILOR-x study suggest up to 70% of HR+ node negative ESBC patients (pts) may avoid CT with RS ≤25. Our objectives were to assess the clinical and economic impact of RS testing on treatment decisions using real-world data. Methods: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ node negative ESBC pts who had RS testing in Ireland. A survey of Irish breast medical oncologists provided the assumption for the decision impact analysis that grade (G) 1 pts would not receive CT pre RS testing and G2/3 pts would receive CT. Using TAILOR-x results, pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Data was collected via electronic patient records. Descriptive statistics were used. Cost data was obtained via the National Healthcare Pricing Regulatory Authority. The economic analysis was adjusted for changing treatment and assay costs over the study period. Results: 963pts were identified. Mean age 56 years. Mean tumour size 1.87cm. 114 (11.8%), 636(66%), 211(22%), 2(0.2%) pts had G1, G2, G3 and unknown G respectively (resp). 797pts (82.8%) had low RS, 159 (16.5%) had high RS, and 7pts(0.7%) unknown RS. 251pts(26%) were aged < 51 at diagnosis. Of these, 45(17.9%), 145(57.8%), 58(23%), 3(1.2) had G1, G2, G3 and unknown G resp. 208pts(82.9%) had RS ≤ 25, 39pts(15.5%) had RS > 25 and 4pts(1.6%) unknown RS. In the RS ≤ 25 group, 111pts(44%) had RS 0-15, 59(23.5%) had RS16-20, and 38(15.1%) had RS21-25. Post RS testing 595pts(61.8%) had a change in CT decision; 586 changed to hormone therapy (HT) alone, and 9 from HT to CT. In total, 227pts(23.5%) received CT, and 3pts(0.3%) declined. Of pts treated with CT; 9(4%) had RS 0-15, 89(39.2%) had RS16-25, 129(56.8%) had RS > 25. The most common CT regimen was docetaxel and cyclophosphamide(TC), administered to 121pts(53%). RS assay use achieved a 69% change in treatment decision among G2/3 pts and a net 61% reduction in CT use. This resulted in savings of over €4 million in treatment costs. Deducting the assay cost, net savings of over one million euro was achieved. Conclusions: Ireland was the first public healthcare system to approve reimbursement for RS testing. Over the 8 year period of the study, a net 61% reduction in CT use in Irish pts with HR+ ESBC was achieved with conservative net savings of over €1,000,000.

201P - Final results of scalp cooling for hair preservation: A single- institution prospective study

BackgroundThe cancer treatments bring with it body image challenges, causing low self-esteem and contributing to worsen the quality of life. Chemotherapy (CT)-induced hair loss (HL) is one of the most emotionally distressing side effects of several breast cancer (BC) treatments. The DigniCap system (DCS), using the scalp cooling system, has been shown to reduce CT-induced alopecia (A) in a multicenter prospective trial. The purpose of this prospective observational study was to describe our experience. MethodsTwo DCS device are available at the Brindisi Oncology Dpt. From February 2016 and January 2019, 158 consecutive early stage BC pts who received anthracycline and/or taxane-based treatment were enrolled, post local Ethics Committees approval. A nurse and a psychologist were dedicated for these pts. Success of scalp cooling was defined according to the Dean’s scale: G0=no HL; G1 < 25% HL; G2=25–50% HL; G3=50–75% HL; G4 >75% HL. ResultsA total of 158 women were included in the following treatment cohorts: n=70 (44.30%) received 4 courses of EC (epirubicin at 90mg/m2 and cyclophosphamide (c) at 600mg/m2 intravenously (IV) on day 1, with 21 days between cycles) followed by 12 courses of paclitaxel (P) 80mg/m2 IV once a week (w); n=56 (35.4%) received only 4 courses of EC, n=28 pts (17.7%) P (80mg/m2 IV once a w) and concurrent trastuzumab (2mg/Kg IV; loading dose 4mg/kg) for 12 consecutive doses and n=4 (2.6%) pts received 4 courses of TC (docetaxel at 75 at 90mg/m2 and c at 600mg/m2 IV on day 1, every three w. Median age was 49 years (range 31-74). Overall success was observed in 115 pts (72.8%). Full preservation of the hair (G0) was observed in 37 pts (23.4%), G1 in 47 pts (29.7%) and G2 in 31 pts (19.6%). Most frequent scalp cooling-related symptoms were coldness (n=129, 81.6%), neck pain (n=83, 52.2%) and headache (n=113, 71.5%). Overall, 14.6% (n=23) of pts discontinued DCS because of unsatisfactory hair preservation (n=11, 7.0%) and cold discomfort (n=12; 8.4%). Furthermore we observed a hair growth when DCS was continued for pts with A G3 – G4. ConclusionsOur results confirmed and reinforced previous evidences, showing that DCS is a good chance to prevent A during CT with anthracycline and/or taxane-based regimen and supported the wider use to all women with early stage BC. Legal entity responsible for the studySaverio Cinieri. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Prospective trial in early-stage breast cancer (EBC) patients (pts) submitted to nutrition evidence-based educational intervention: Early results of adherence to dietary guidelines (ADG) and body weight change (BWC).

11575 Background: Weight gain and overweight have been related to an increased risk of recurrence and mortality in patients affected by EBC. However, the adherence to nutritional intervention is not entirely explored. The aims of this prospective study were to evaluate the ADG and the effectiveness of nutritional intervention in terms of BWC in pts with EBC undergoing treatment. Methods: Entry criteria: EBC pts candidate to neoadjuvant/adjuvant therapy. At study entry, pts received a nutrition evidence-based tailored educational intervention by a skilled dietitian. Anthropometric and dietary assessments were performed. ADG was estimated through the validated Med-Diet 14-item questionnaire. Health-Related Quality of Life was analyzed with the EORTC QLQ-C30. Descriptive statistics was adopted. Associations between variables and groups according to nutritional variables were analysed (Chi-square test). Results: From February 2016 to December 2018, 204 pts were enrolled (median age 49 years): 27.5%/72.5% neoadjuvant/adjuvant treatment. At baseline, 2.5% of pts were underweight, 41.7% were normal weight, 33.3% were overweight and 22.5% were obese. Moreover, 47.5% of pts gained ≥5% of their usual weight and 25.5% performed physical activity. Significant nutritional impact symptoms were reported: dyspepsia (51.5%), constipation (62.3%) and dysgeusia (34.8%). The majority of pts presented dietary patterns high in fat (median fat intake: 35.2% from total energy intake) and low in dietary fiber (median dietary fiber intake: 17.2 g/day). A significant correlation between baseline BMI and tension was observed ( p &lt; 0.0001) as well as BMI and worry, irritability and depression ( p &lt; 0.0001, p &lt; 0.0001 and p = 0.008, respectively). Six months after the intervention, the median ADG was high (median Med-Diet score was 12). A high adherence to nutrition guidelines (defines as a Med-Diet score ≥10, 112 patients) significantly correlated with a weight loss ≥5% from the baseline weight ( p = 0.005). Furthermore, the weight loss ≥5% was correlated with a lower rate of depression ( p = 0.05). Conclusions: A tailored nutritional intervention for EBC pts undergoing adjuvant or neoadjuvant therapy has the potential to improve their ADG, in order to achieve a weight loss.

104P - Final results of scalp cooling for hair preservation: A single-institution prospective study

Abstract Background The cancer treatments bring with it body image challenges, causing low self-esteem and contributing to worsen the quality of life. Chemotherapy (CT)-induced hair loss (HL) is one of the most emotionally distressing side effects of several breast cancer (BC) treatments. The DigniCap system (DCS), using the scalp cooling system, has been shown to reduce CT-induced alopecia (A) in a multicenter prospective trial. The purpose of this prospective observational study was to describe our experience. Methods Two DCS device are available at the Brindisi Oncology Dpt. From February 2016 and January 2019, 158 consecutive early stage BC pts who received anthracycline and/or taxane-based treatment were enrolled, post local Ethics Committees approval. A nurse and a psychologist were dedicated for these pts. Success of scalp cooling was defined according to the Dean’s scale: G0=no HL; G1 75% HL. Results A total of 158 women were included in the following treatment cohorts: n = 70 (44.30%) received 4 courses of EC (epirubicin at 90 mg/m2 and cyclophosphamide (c) at 600 mg/m2 intravenously (IV) on day 1, with 21 days between cycles) followed by 12 courses of paclitaxel (P) 80 mg/m2 IV once a week (w); n = 56 (35.4%) received only 4 courses of EC, n = 28 pts (17.7%) P (80 mg/m2 IV once a w) and concurrent trastuzumab (2 mg/Kg IV; loading dose 4 mg/kg) for 12 consecutive doses and n = 4 (2.6%) pts received 4 courses of TC (docetaxel at 75 at 90 mg/m2 and c at 600 mg/m2 IV on day 1, every three w. Median age was 49 years (range 31-74). Overall success was observed in 115 pts (72.8%). Full preservation of the hair (G0) was observed in 37 pts (23.4%), G1 in 47 pts (29.7%) and G2 in 31 pts (19.6%). Most frequent scalp cooling-related symptoms were coldness (n = 129, 81.6%), neck pain (n = 83, 52.2%) and headache (n = 113, 71.5%). Overall, 14.6% (n = 23) of pts discontinued DCS because of unsatisfactory hair preservation (n = 11, 7.0%) and cold discomfort (n = 12; 8.4%). Furthermore we observed a hair growth when DCS was continued for pts with A G3 – G4. Conclusions Our results confirmed and reinforced previous evidences, showing that DCS is a good chance to prevent A during CT with anthracycline and/or taxane-based regimen and supported the wider use to all women with early stage BC. Legal entity responsible for the study Saverio Cinieri. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Impact of Oncotype-DX testing on choice of chemotherapy.

e12049 Background: The Oncotype DX test has been shown to change treatment plans in ~30% of cases, but it is unclear if it changes the type of chemotherapy offered. We sought to determine if the availability of Oncotype DX testing in BC resulted in a change in the type of chemotherapy regimens used on early stage breast cancer pts. Methods: This was a cohort study in which pts treated in the 2 years prior to the availability of Oncotype Dx testing were compared to pts treated in the 2 years after it became available in BC. Charts were audited and divided into pre- and post- availability of Oncotype DX testing. The groups were compared for differences in length of chemotherapy (12 vs &gt; 12 weeks), type of agents used (anthracycline vs non-anthracycline) and myelosuppressive potential of regimen chosen. Results: A total of 831 pts fulfilled enrollment criteria; 360 were seen in the pre Oncotype era and 471 were seen in the post Oncotype era. A total of 250 (30.1%) pts were treated with chemotherapy in both cohorts with a median age of 59 for both groups (range of 29-80 and 24-80 respectively, p = NS). There was a decrease of 11.5% in pts receiving chemotherapy from 36.6% to 25.1% (p = 0.0003). Of the pts who received chemotherapy, there was a shift away from regimens containing anthracycline (49.2% vs 32.2%, p = 0.0070) and a shift towards more myelosuppressive chemotherapy regimens (p = 0.0344). There was a significant difference in the duration of chemotherapy regimens chosen with post Oncotype era pts receiving short course chemotherapy 69.5% of the time, compared to only 56.8% in the pre Oncotype era (p = 0.0491). Conclusions: The availability of Oncotype DX testing has resulted in a shift towards use of shorter, more myelosuppressive, non-anthracycline containing chemotherapy protocols. Since being publicly available, fewer pts are receiving chemotherapy but our data suggests a 10% change in treatment plan compared to the 30% change seen in other literature. Further study is warranted to ensure long term outcomes are not negatively impacted by the move towards shorter chemotherapy regimens.