Sandoval-Leon, Ana Cristina

Abstract Background Breast cancer chemoprevention is underutilized among high-risk women. We examined whether decision support could increase informed decision making. Methods We conducted a cluster randomized controlled trial to evaluate the effect of a patient-facing decision aid (RealRisks) and provider tool (BNAV) compared with standard education on the number of women with high-risk breast lesions making informed choices. Questionnaires were administered at baseline and 6 and 12 months. The primary outcome was chemoprevention informed choice (defined as adequate knowledge and attitudes congruent with decision) at 6 months. Secondary endpoints included breast cancer risk perceptions, worry, chemoprevention knowledge, decision conflict, and chemoprevention decision. Results Across 31 randomized sites, we enrolled 210 providers, who were primarily breast health specialists. Of these, 24 sites (14 intervention, 10 control) enrolled 412 patients. Among 287 patients evaluable for the primary outcome, there were no statistically significant differences in informed choice between the intervention and control arms at 6 months (35% vs 27%, respectively; P = .20) and 12 months (37% vs 25%, respectively; P = .05). At 6 months, women in the intervention compared with control arm were more likely to have accurate breast cancer risk perceptions (31% vs 21%, respectively; P = .03) and adequate chemoprevention knowledge (33% vs 23%, respectively; P = .04). At 12 months, 52% of women in the control and 50% in the intervention arm self-reported initiating chemoprevention. Conclusion Decision support led to modest improvements in accurate risk perceptions and chemoprevention knowledge but not informed choice. Relatively high chemoprevention uptake was achieved among women with high-risk breast lesions managed mainly by breast health specialists. Trial Registration NCT04496739, https://clinicaltrials.gov/study/NCT04496739?cond=NCT04496739&viewType=Card&rank=1

Abstract Background: Breast cancer (BC) chemoprevention with selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) remains underutilized among high-risk women. Improving knowledge about BC risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this BC risk reduction strategy. Methods: We conducted a cluster randomized controlled trial to evaluate the effectiveness of web-based patient and provider decision support, RealRisks and BNAV, to improve chemoprevention informed choice among women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS). Thirty-one sites, including academic and community practices across the U.S., were randomized to standard patient educational materials alone or combined with RealRisks and BNAV. A total of 412 patients and 210 healthcare providers were enrolled. Patient surveys were administered at baseline, 6 and 12 months. The primary outcome at 6 months was chemoprevention informed choice, defined as adequate chemoprevention knowledge and attitudes congruent with decision. Secondary endpoints included BC risk perceptions, worry, chemoprevention knowledge, decision conflict and chemoprevention decision. Assuming 10% loss to follow up (LTFU), roughly equal accrual across sites, and an intraclass coefficient (ICC) of 0.02, we had 90% power to detect a 15% absolute difference in informed choice if the event rate in the control arm was 10%. Results: Among 24 evaluable sites, 14 were randomized to the intervention arm and 10 to the control arm. Among 210 enrolled providers, median age was 46 (range, 28-83) and 78% were female; 75% physicians and 25% advanced practice providers/nurses; 53% medical oncologists, 29% surgeons, and 10% gynecologists/family practitioners/internists; and 83% had previously prescribed chemoprevention. Among 412 enrolled patients, median age was 53 (range, 35-74), including 77% White, 8% Black, and 10% Asian race, and 14% Hispanic ethnicity. In terms of BC risk factors, 77% had AH and 23% LCIS, 34% had a first-degree family history of BC, and 65% had heterogeneously or extremely dense breasts on mammography. Thirty percent were unevaluable for the primary endpoint (1% ineligible, 26% LTFU, 3% missing data). Among 288 evaluable patients (148 at intervention sites, 140 at control sites), the proportion of patients exercising informed choice at 6 months in the intervention and control arms was 35% vs. 27%, respectively (odds ratio [OR]=1.44, 95% confidence interval [CI]=0.84-2.46, p=0.19; observed ICC=0.006). Compared to patients in the control arm at 6 months, those in the intervention arm were more likely to have accurate BC risk perceptions (OR=1.80, 95% CI=1.11-2.91) and adequate chemoprevention knowledge (OR=1.62, 95% CI=1.00-2.61). We observed no significant differences in BC worry, decision conflict, or chemoprevention decision between study arms. At 6 months, 49% of women in the control arm and 51% in the intervention arm decided to take a SERM or AI for BC chemoprevention (p=0.58), a rate higher than anticipated. Conclusions: We did not observe a significant increase in informed choice among patients and providers assigned to chemoprevention decision support compared to standard educational materials alone. Among women with AH or LCIS seen mainly by breast specialists who prescribed chemoprevention, about half decided to take a SERM or AI. Therefore, relatively high chemoprevention uptake may be achieved among women with high-risk breast lesions managed by breast specialists. Chemoprevention decision support may improve decision antecedents, such as accurate BC risk perceptions and chemoprevention knowledge, but may have a limited role in changing health behaviors. Citation Format: K. D. Crew, G. L. Anderson, K. B. Arnold, A. Michel, M. T. DeLucie, C. W. Law, S. Pruthi, A. C. Sandoval Leon, R. Shirley, M. T. Grosse Perdekamp, S. V. Colonna, S. L. Krisher, T. King, L. D. Yee, T. J. Ballinger, C. Braun-Inglis, D. A. Mangino, K. B. Wisinski, C. A. DeYoung, M. Ross, J. D. Floyd, A. Kaster, L. VanderWalde, T. Saphner, C. Zarwan, S. Lo, C. Graham, A. K. Conlin, K. J. Yost, D. M. Agnese, C. Jernigan, D. L. Hershman, M. L. Neuhouser, J. A. Zell, B. Arun, R. Kukafka. Making informed choices on incorporating chemoprevention into care (MiCHOICE): Cluster randomized controlled trial of decision support for breast cancer chemoprevention, SWOG 1904 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-15.

Abstract Introduction: Metaplastic breast cancer (MpBC) is a rare and histologically diverse subtype of breast cancer (BC) that is frequently triple negative (TN) and exhibits poor responsiveness to chemotherapy (CT). Our group previously reported a low pathologic complete response (pCR) rate among patients (pts) with MpBC treated with neoadjuvant CT in the pre-immunotherapy (IO) era. The standard neoadjuvant approach for pts with stage 2-3 TNBC has evolved with the results of the KEYNOTE-522 (KN522) trial, which demonstrated improved pCR rates, event-free survival (EFS), and overall survival (OS) with the addition of pembrolizumab to CT. However, pts with MpBC were not well-represented in KN522, and their response to IO remains poorly characterized. In this study, we examine the pCR rate with the addition of IO to neoadjuvant CT in pts with TN MpBC. Methods: Pts diagnosed with MpBC and treated at Miami Cancer Institute between 2017-2024 were retrospectively identified by COTA real-world Analytics® platform following IRB approval. Eligible pts had stage 2-3 ER-negative (defined as ER < 10%), PR-negative, HER2-negative MpBC, received neoadjuvant systemic therapy, and subsequently underwent definitive surgery. Demographic, clinical, treatment and outcome data were extracted from the electronic health record. pCR was defined as the absence of residual invasive cancer in the breast and axillary lymph nodes at the time of surgery. Kaplan-Meier method was used to estimate median disease-free survival (mDFS) and median OS (mOS). Comparison between treatment groups for pCR were performed using Fisher’s exact test. No multivariable or survival modeling was performed due to limited statistical power in this small cohort. All p values were two-sided. Results: A total of 27 pts were included in the analysis; 16 pts received CT (in the pre-IO era) with 19.2 months (m) median follow up and 11 pts received CT + IO with 15.5m median follow up. Spindle cell histology was reported in 18.5% of tumors, non-spindle cell in 59.3% and 22.2% were not further specified. Most patients (81.5%) had clinical stage 2 disease, 18.5% had stage 3; median tumor size was 3.2 cm. Anthracycline-based CT was administered to 81.5% of pts, and the remainder received non-anthracycline regimens. pCR was achieved in none of the 16 pts (0.0%) who received CT alone and in 3 of 11 pts (27.3%) who received CT + IO (p=0.046). Among the 3 pts who achieved pCR, 2 had non-spindle cell histology and 1 unspecified. All 3 pCR pts had stage 2 disease, received IO and anthracycline, and experienced immune-related adverse events. mDFS was 23.9m in the CT group and 14.6 m in the CT + IO group (p = 0.641), though follow-up duration differed between groups. Among all pts, mDFS was 15.3 m in those who did not achieve pCR and was not reached in those that did (p = 0.226). mOS was not reached in the CT group and was 20.7m in the CT + IO group (p = 0.192). Conclusion: In this small, retrospective real-world analysis of pts with early-stage TN MpBC, the addition of IO to neoadjuvant CT was associated with a higher pCR rate compared to CT alone. Although the observed pCR rate of 27.3% with CT+IO is lower than that reported in KN522 for unselected TNBC, this likely reflects the small sample size and the inherently CT-resistant biology of MpBC. None of the pts in the CT alone group achieved pCR, suggesting that IO may help to overcome CT resistance in MpBC. Differences in mDFS and mOS were not statistically significant, possibly due to limited follow up and sample size. Despite these limitations, our findings highlight the importance of incorporating IO into treatment for MpBC. Future multicenter analyses are ongoing to validate these results in a larger, more diverse population and to further explore the role of histologic subtypes and immune biomarkers in predicting response. Citation Format: N. Dempsey, L. Hodgson, A. Sandoval-Leon, L. Carcas, M. Ahluwalia, C. Wang, H. Kim, P. Advani, R. Mahtani. Pathologic complete response rates in early-stage triple negative metaplastic breast cancer in the neoadjuvant immunotherapy era: a retrospective review [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-10-07.

Abstract Background: Hispanic/Latinx (HL) and African American (AA) breast cancer (BC) patients (pts) have increased prevalence of high-risk features such as incidence of BC at age <50 and estrogen receptor negativity. We previously showed that AA and HL had a lower fraction of neutrophils and M2 macrophages (Mɸ) despite higher percentage of PD-L1 positive cases. This study aims to further characterize differences in the tumor immune microenvironment between racial and ethnic groups, with a focus on how these differences vary by site of biopsy. Methods: We analyzed 19,459 BC samples tested by NGS (592, NextSeq; WES, NovaSeq) and WTS (NovaSeq; Caris Life Sciences). Race/ethnicity data were self-reported by pts. Immune cell proportions were estimated using WTS deconvolution (Quantiseq). Gene expression was analyzed for T-cell inflammed score (TIS), MAPK Activation Score (MPAS) and interferon-gamma (IFNy) score. Real-world overall survival (OS) data were derived from insurance claims, calculated from tissue collection or treatment initiation to last contact, and analyzed using Kaplan-Meier. Statistical significance was assessed by chi-square and Mann-Whitney U test with p-values adjusted for multiple comparisons (q<0.05). Results: There were 9674 Non-Hispanic Whites (NHW) (primary BC, defined as biopsy (bx) from breast) pBC: n=3,537, 36.6%; (metastatic BC, defined as biopsy outside of the breast) mBC: n=6,137 63.4%, 1800 AA (pBC: n=750, 42%, mBC: n=1,050, 58%), and 1795 HL (pBC: n=842, 47%; mBC n=953, 53%) samples. There were 2364 TNBC (66% NHW, 19% NHB, 15% HL), 4318 HR+/HER2- (76% NHW, 11.6% NHB, 12.4% HL), and 893 HER2+ (68% NHW, 15% NHB, 17% HL). In pBC overall, AA had lower median cell fraction (%) of B cells (4.8% vs 5.3%), M2 Mɸ (3.4% vs 4.4%), but higher median cell fraction of dendritic cells (DC) (2.8% vs 2.6%) compared to NHW while HL had lower median cell fraction of M2 Mɸ (3.9% vs 4.4%) and higher median cell fraction of CD8+ T cell (0.4% vs 0.2%), all q<0.05. In pBC, HL had higher IFNy score (-0.3 vs -0.34), while AA had lower MPAS (-1.2 vs -0.96), all q<0.05. In lymph node bx, AA had lower median % of M2 Mɸ (3.4% vs 4.4%, q<0.05). No significant differences were seen in the liver bx by race but notably there were lower median cell fractions of CD4+, CD8+, and regulatory T cells (0.0 across NHW, AA, HL) across all race/ethnicities vs. other biopsy sites. By subtype, TNBC primary bx yielded much of the significant changes with AA having lower median cell fraction of M2 Mɸ (2.49% vs 3.04%, q= 0.01) compared to NHW. In primary bx, AA (35.6 m vs 48.5 m, HR 1.4, 95% CI 1.2-1.5, p<0.001) and HL (42.4 m vs 48.5 m, HR 1.2, 95% CI 1.1-1.4, p<0.001) had worse median OS versus NHW. In lymph node bx, AA also had worse OS (29.2 m vs 37.2 m, HR 1.2, 95% CI 1-1.5, p=0.03) compared to NHW. In liver bx, there was worse mOS overall but no difference by race (NHW 18.65m, AA 18.79m, HL 20.6m, p =0.73). In HR+/HER2- liver bx AA had worse OS (14.2 m vs 20.9 m, HR 1.3, 95% CI 1-1.7, p=0.03) versus NHW. In HER2+ primary bx, HL had worse OS (43.2m vs 66.9m, HR 1.7, 95% CI 1.1-2.6, p=0.009). There was a trend towards worse mOS in TNBC AA patients receiving pembrolizumab (18.42m vs HL 23.69m vs NHW 35.30m; p=0.16) and HER2+ AA patients receiving trastuzumab deruxtecan (AA: 16.06m vs HL: 26.81m vs NHW: not reached; p = 0.05). Conclusions: We found race and biopsy site specific differences in the breast cancer immune microenvironment. AA pts had lower M2 Mɸ in primary and lymph node bx while NHW pts showed higher CD8+ T cell in primary tumors. Liver biopsies exhibited low T cell infiltration across all groups. AA pts had worse mOS in primary and lymph node bx compared to NHW but not in liver bx of which we saw worse mOS in all races. These results highlight the need to consider both race and bx site in treatment decisions. Citation Format: R. Hsu, S. Deshmukh, N. Gyabaah-Kessie, E. Rallos, B. Al-Zubeidy, E. Gonzalez, A. G. Baugh, S. Carrel, M. Li, D. Zavala, A. Martynova, P. Jayachandran, D. Stewart, D. Spicer, S. Wu, J. Xiu, G. W. Sledge Jr., R. L. Mahtani, A. C. Sandoval Leon, S. Gandhi, S. Chumsri, M. Lustberg, M. C. Stern, E. T. Roussos Torres. Immune microenvironment and survival differences among Hispanic and African American breast cancer cases by biopsy site [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-12-06.

1051 Background: Hispanics or Latinos (HL) and African Americans or Black (AA) have a higher prevalence of advanced-stage breast cancer (BC) at diagnosis compared to Non-Hispanic Whites (NHW). To understand the role of immune system, we evaluated the tumor immune microenvironment (TIME) by race/ethnicity among HL, AA, and NHW BC patients. Methods: 15544BC samples were tested by NGS (592, NextSeq; WES, NovaSeq) and WTS (NovaSeq; Caris Life Sciences, Phoenix, AZ). Race/ethnicity data is self-reported. Immune cell were estimated using WTS deconvolution (Quantiseq). Gene expression profiles were analyzed for T-cell inflammation score (TIS) and interferon-gamma (IFN-gamma) score. Real-world overall survival (OS) was obtained from insurance claims and calculated from date of tumor biopsy to last contact using Kaplan-Meier estimates. Statistical significance was determined by chi-square and Mann-Whitney U test with p -values adjusted for multiple comparisons (q < .05). Results: 7170 NHW (35.3%, N = 2528) biopsied (bx) from primary breast cancer (pBC), 64.7% (N = 4642) metastatic bx (mBC), 1,508 AA (pBC 39.3% N = 592, mBC 60.7% N = 916), and 1,754 HL (pBC 44.1% N = 774, mBC 55.9% N = 980) cases were included. By subtype, there were 1,956 (60.4% NHW, 20.7% NHB, 18.9% HL) TNBC, 3425 HR+/HER2- (72.6% NHW, 11.9% NHB, 15.6% HL), and 694 HER2+ (64.6% NHW, 15.7% NHB, 19.7% HL). Across all cases, AA (20.5%) and HL (20.4%) had greater incidence (%) of PD-L1+ cases versus (vs) NHW (17.4%), all q < .05. TMB-High (³10 mut/Mb) was similar in NHW (11.5%), AA (10.8%), and HL (10.9%). AA tumors had lower median % cell infiltration of M2-like macrophages (M2 Mφ), B cells, and neutrophils vs NHW (Table). HL had a lower fraction of M2 Mφ and higher CD8+ T cells (Table). AA had lower TIS (-8 vs 1, p = .02) while HL had lower IFN-gamma (-0.38 vs. -0.35, q < .05) vs NHW. By subtype, AA had lower neutrophils (4% vs 4.3%) and increased DC fractions (3.1% vs 2.8%) in TNBC vs NHW, all q < .05; no significant changes seen in HL vs NHW. AA had worse mOS than NHW overall (31.8 vs 36.8 months (mo)), HR 1.1, 95% CI 1 – 1.2, p = < .01), in pBC (40.3 vs 49.9 mo, HR 1.3, 95% CI 1.1 – 1.5, p = < .01), but not mBC (27.4 vs 29.1 mo, HR 1, p = 0.2). HL had similar mOS vs NHW overall (37.4 vs 36.8 mo, HR 0.9, p = 0.9) and in mBC (29.1 vs 31 mo, HR 0.96, p = 0.4), but worse mOS in pBC (44.7 vs 50.0 mo, HR 1.1, 95% CI 1 – 1.3, p = .01). Conclusions: Our study shows worse mOS in AA and HL pBC cases vs NHW, possibly from a less inflamed TIME in AA and HL and lower fraction of neutrophils and M2 Mφ despite higher % of PD-L1+. Targeting Mφ and CD8+ T cells and converting cold to hot TIME may lessen race/ethnic disparities, especially in early-stage BC. Immune cell fraction of NHW, AA and HL BC. NHW (median %) AA (median %) HL (median %) q-valueNHW vs AA q-value NHW vs HL B cell 5.2 4.8 5.0 <.05 0.7 DC 2.6 2.7 2.6 0.08 0.4 M1 Mφ 2.5 2.4 2.4 0.4 0.9 M2 Mφ 4.6 3.7 4.2 <.05 <.05 Neutrophils 3.7 3.5 3.4 <.05 <.05 NK cell 2.9 2.9 2.9 0.7 0.6 CD8+ T cell 0.1 0.15 0.26 0.8 <.05 Treg 1.5 1.5 1.6 0.6 <.05

1083 Background: T-DXd and SG are both FDA-approved treatments for patients (pts) with HER2-low MBC, but little data exists on the sequential use of these ADCs. Methods: In this multicenter retrospective cohort study, we identified pts with HER2-low MBC treated sequentially with both T-DXd and SG in either order, with or without intervening therapies (IntTx), at 5 academic centers between 2020-2023. We previously reported real-world progression free survival (rwPFS) and real-world overall survival (rwOS) by HR-status and ADC sequence order. Here we provide updated rwPFS and rwOS data, as well as new subgroup analyses by age, sites of disease, and use of IntTx between ADCs for HR- and HR+ disease. Results: 84 pts with HER2-low MBC treated with both T-DXd and SG were included, including 56 pts with HR+/HER2-low MBC (66.7%) and 28 pts with HR-/HER2-low MBC (33.3%). Prior to the start of ADC1, median age was 58 yrs and 22 pts were >65 yrs (26.2%), 65 pts (77.4%) had visceral disease, and 14 pts (16.7%) had central nervous system (CNS) disease. 36 pts (42.9%) had an IntTx between ADCs. Table 1 shows updated rwPFS and rwOS data by HR-status and ADC sequence order. For pts with HR+ and HR- MBC, there was no difference in ADC1 rwPFS or ADC2 rwPFS by age ≤65 vs. >65 yr or by presence vs. absence of visceral disease. For pts with HR- MBC, ADC1 rwPFS and rwOS was shorter for pts with CNS disease vs. pts without CNS disease (rwPFS 5.4 mo (n=6) vs. 8.5 mo (n=22), p=0.03; rwOS 11.6 mo vs. 21.1 mo, p<0.01 respectively). For pts with HR+ and HR- MBC, there was no difference in ADC2 rwPFS with or without receipt of IntTx. There was no difference in time to treatment failure for first IntTx vs. ADC2 if no InTx was given. Conclusions: This is one of the largest multicenter cohorts of pts treated with sequential ADCs for HER2-low MBC. Median rwPFS was longer for ADC1 than ADC2 in all subgroups, regardless of HR-status, ADC sequence order, age ≤65 or >65 yr, presence of visceral disease, or use of IntTx. Among pts with HR-/HER2-low MBC, pts with CNS disease had shorter ADC1 rwPFS and rwOS than pts without CNS disease. [Table: see text]

Abstract Introduction: Interstitial Lung Disease (ILD) is a known adverse event associated with Antibody Drug Conjugates (ADCs), causing fibrosis of the lung. In the DESTINY-Breast 04, TROPICS-02, and ASCENT trials the rate of ILD/Pneumonitis was 12.1%, 0.4%, and 0% respectively. In these studies, the time to first cross-sectional imaging after initiation of ADC was 6 weeks. However, prior treatment with a topoisomerase-1 inhibitor ADC was not permitted in these studies, so the influence of sequential ADC treatments remains unknown. Here, we aimed to characterize the frequency and management of ILD in sequential use of ADCs in a multi-institution retrospective analysis. Methods: We identified patients (pts) with HR+/HER2-low and HR-/HER2-low MBC who had received both Trastuzumab-deruxtecan (T-DXd) and Sacituzumab govitecan (SG) monotherapy (in either order, with or without intervening therapies) who were treated at five academic centers between 2020-2023. Patients had received treatment with the ADC in either routine clinical treatment or as a prior participant on a clinical trial with ADC monotherapy. Information regarding ILD diagnosis, imaging, timing of onset, peak and resolution along with management information was collected and analyzed. Retrospective assessment of ILD toxicity was graded using CTCAE v5.0, based on available clinical and radiographic reports. Results: 10/60 pts who received ADC therapy in this multi-institutional cohort were diagnosed with ILD (all grades). No differences in age or BMI were observed in those who developed ILD versus those who did not, and 9/10 pts were White, 1 was Asian, with a median age of 59 years (47-79 years). Pertinent history in these pts included 3/10 had a prior smoking history, 8/10 had a prior cardiac or pulmonary comorbidity (including sleep apnea, lung cancer, hypertension, hyperlipidemia, thrombosis, or stroke). Prior to receiving their first ADC, 7/10 patients had metastatic disease to the lung. All 10 patients were diagnosed with ILD during treatment with T-DXd. 4 pts initially received T-DXd, then developed ILD and then upon recovery, subsequently received SG. The remaining 6 pts initially received SG (with no reports of ILD), and then received T-DXd and subsequently developed ILD. In the entire cohort, the median time from ADC initiation to first CT scan was 8 weeks (range 1-22 weeks). Within the cohort that developed ILD, the median time from initiation of T-DXd to first CT scan was also 8 weeks (range 6-13 weeks). The median time to diagnoses of ILD was 3 months after initiation of T-DXd (range 0.4-14.5 months). Dyspnea was the most common presenting symptom in 9/10 pts and at diagnosis of ILD, dyspnea was graded as III in 6/10 pts, II in 3/10 pts, and I in 1/10 pts. Diagnostic evaluation included CT chest (9/10), pulmonary consultation (8/10), pulmonary function testing (2/10), and bronchoscopy (1/10). 4/10 patients presented at their highest-grade toxicity at diagnosis. All patients stopped T-DXd treatment, 7 were hospitalized, 7 required supplemental oxygen, and 8 were prescribed steroids for treatment. Of those receiving steroids, the most common starting dose was prednisone 1 mg/kg and doses ranged from 0.5 mg/kg to 9mg/kg prednisone equivalents. No patient received a secondary immunosuppressive agent. The steroid treatment duration ranged from 1-4 months. None of the 10 pts underwent re-challenge with T-DXd and 3/10 developed grade V ILD (death). Conclusion: We observed a 16.6% incidence of all grade ILD (5% grade V ILD) with T-DXd and 0% with SG. In this small cohort study, we did not observe a clear increased risk for ILD with sequential treatment of ADCs. Practice patterns were consistent with recommended diagnostic evaluation and steroid management. Additional strategies are needed to characterize pts most at risk for developing ILD and to identify situations where re-challenge may be safe. Citation Format: Sarah Premji, Laura Huppert, Reshma Mahtani, Samantha Fisch, Naomi Dempsey, Angelina Raimonde-Taylor, Saya Jacob, Laura Quintal, Jo Chien, Michelle Melisko, Ana Sandoval-Leon, Lauren Carcas, Manmeet Ahluwalia, Natasha Harpalani, Jenna Hoppenworth, Dame Idossa, Ruta Rao, Hope Rugo, Karthik Giridhar. Interstitial Lung Disease (ILD) in Sequential Antibody Drug Conjugate (ADC) use in patients with Metastatic Breast Cancer (MBC): A Multi-Institutional experience [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 PO4-12-06.

Abstract Introduction. T-DXd is FDA-approved for patients (pts) with hormone receptor positive (HR+) or HR- HER2-low (IHC 1+ or 2+, ISH-) MBC and SG is FDA-approved for pts with HR+/HER2- and triple negative MBC. However, several outstanding questions impact the use of these drugs in clinic, including: 1) what is the efficacy and safety of these agents in real-world populations with diverse pt characteristics not well represented in the pivotal phase III trials, and 2) what is the impact of sequential treatment with ADCs on the efficacy and safety of these agents. Methods. In this multicenter retrospective cohort study, we identified pts with HR+/HER2-low and HR-/HER2-low MBC who had received both T-DXd and SG monotherapy (in either order, with or without intervening therapies) treated at 5 academic centers between 2020-2023. Pts received treatment per standard of care or on a clinical trial with ADC monotherapy. We describe pt demographic and clinical characteristics, treatment history, key safety parameters, and response and survival data by HR+ status and ADC sequence order. Results. Sixty pts with MBC treated sequentially with T-DXd and SG were included in this analysis, including 45 pts with HR+/HER2-low MBC (75.0%) and 15 pts with HR-/HER2-low MBC (25.0%). Most pts were female (n=59; 98.3%), non-Hispanic (n=49, 81.7%), and white (n=43, 71.7%). Median age at start of ADC #1 was 56.6 years (range 23-82). Prior to treatment with ADC #1, most pts had visceral disease (n=45, 75.0%) and 16 (26.7%) had central nervous system metastases. Among pts with HR+/HER2-low MBC, median time from MBC diagnosis to treatment with ADC #1 was 49.0 months, with 4 median lines of prior therapy in the metastatic setting (2 endocrine, 2 chemo). Approximately half of the HR+ pts received T-DXd prior to SG (n=22, 48.9%; median 3.0 prior lines of therapy for MBC, range 1-9) while the other half received SG prior to T-DXd (n=23, 51.1%; median 4.5 prior lines of therapy for MBC, range 1-10). 44% (n=20) received an intervening therapy between ADCs. For HR+ pts who received T-DXd prior to SG, response and survival data is as follows for T-DXd and SG respectively: Overall response rate (ORR) [54.5% and 21.1%], time to next treatment (TTNT) [4.3 mo and 1.6 mo], and real-world overall survival (rwOS) [19.8 mo and 4.9 mo]. For HR+ pts who received SG prior to T-DXd, response and survival data is as follows for SG and T-DXd respectively: ORR [78.3% and 42.9%], TTNT [8.6 mo and 2.8 mo], and rwOS [22.3 mo and 7.3 mo]. Among pts with HR-/HER2-low MBC, median time from MBC diagnosis to treatment with ADC #1 was 8.2 months with 2 median lines of prior therapy in the metastatic setting (2 chemotherapy); 66.7% (n=10) received prior immunotherapy. Most HR- pts received SG prior to T-DXD (n=14, 93.3%) and 40.0% (n=6) received an intervening therapy between ADCs. For HR- pts who received SG prior to T-DXd, response and survival data is as follows for SG and T-DXd respectively: ORR [64.3% and 38.5%], TTNT [6.2 mo and 2.7 mo, and rwOS [15.7 mo and 6.5 mo]. In terms of key safety parameters during treatment with T-DXd, 13.3% of pts (8/60) required a dose reduction. 16.7% (10/60) were diagnosed with interstitial lung disease (ILD)/pneumonitis of any grade including 3 pts with grade 3-4 ILD (5.0%) and 3 pts with grade 5 ILD (5.0%). During treatment with SG, 40.0% of pts (24/60) required a dose reduction. 83.3% (50/60) received growth factor support (24 pts primary prophylaxis; 26 pts secondary prophylaxis); 9 pts (15%) required treatment delay due to neutropenia. Conclusion. This study represents the largest multicenter series to date of pts treated with sequential ADCs for HR+/HER2-low or HR-/HER2-low. ORR was higher and TTNT was longer for ADC #1 than ADC #2 in all subgroups, regardless of HR+ status and ADC sequence order. An additional ~30 pts will be reported at time of final analysis. Future prospective studies are planned to further clarify the efficacy and safety of sequential ADC use and to identify biomarkers of response and resistance. Key demographic, clinical and treatment characteristics in pts with HR+ and HR- HER2-low MBC treated sequentially with T-DXd and SG (in either order, with or without intervening therapies) Abbreviations: T-DXd (trastuzumab deruxtecan), SG (sacituzumab govitecan), MBC (metastatic breast cancer), ADC (antibody drug conjugate), HR (hormone receptor), HER2 (human epidermal growth factor receptor 2), CNS (central nervous system), ET (endocrine therapy), ORR (overall response rate), TTNT (time to next treatment), rwOS (real world overall survival), CI (confidence interval) * Several pts on ADC #2 with ongoing treatment and first scan pending, hence smaller denominator for response assessment Citation Format: Laura Huppert, Reshma Mahtani, Samantha Fisch, Naomi Dempsey, Sarah Premji, Angelina Raimonde-Taylor, Saya Jacob, Laura Quintal, Jo Chien, Michelle Melisko, Ana Sandoval-Leon, Lauren Carcas, Manmeet Ahluwalia, Natasha Harpalani, Jenna Hoppenworth, Dame Idossa, Ruta Rao, Karthik Giridhar, Hope Rugo. Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC) [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 PS08-04.

Abstract Background: Despite evidence of substantial breast cancer risk reduction, few high-risk women adopt chemopreventive medications such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). Women with benign breast disease, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have an increased risk of developing breast cancer and derive a greater benefit from antiestrogens compared to other high-risk women. Reasons for low uptake of chemoprevention include insufficient patient and clinician knowledge about antiestrogens, time constraints during the clinical encounter, and concerns about side effects. To address these barriers, we have developed patient and provider web-based decision support tools to improve informed choice about breast cancer chemoprevention among women with AH or LCIS. Study design: We are conducting a cluster-randomized controlled trial of clinical decision support to improve chemoprevention informed choice among women with AH or LCIS and their treating providers. Twenty-six U.S. sites through the SWOG Cancer Research Network were randomly assigned 1:1 to standard educational materials alone or in combination with the patient-centered decision aid (RealRisks) and provider decision support tool (BNAV). A total of 415 patients and 200 healthcare providers will be recruited from these sites. RealRisks consists of interactive modules to calculate personalized breast cancer risk and elicit preferences on chemoprevention. The modules are available in English and Spanish. BNAV is comprised of self-directed case-based learning modules on breast cancer risk assessment and chemoprevention. Patients complete questionnaires at baseline, 6 and 12 months. Providers complete surveys at baseline and after their enrolled patient’s 6-month clinical encounter. The primary endpoint is chemoprevention informed choice at 6 months, using a measure combining knowledge, attitude, and intention scales. Secondary endpoints include perceived breast cancer risk/worry, chemoprevention knowledge/intention, decision conflict/regret, shared decision-making, and chemoprevention uptake. For patients who begin chemoprevention, adherence and reasons for discontinuation are assessed annually for up to 5 years. Barriers and facilitators to implementing RealRisks and BNAV into clinic workflow will be assessed by conducting patient and provider interviews at baseline and mid-implementation. Eligibility criteria: Eligible patients include women, age 35-74 years, with AH or LCIS, no history of breast cancer, no prior use of SERMs or AIs, no bilateral mastectomies, English or Spanish-speaking, and access to the internet. Eligible providers include breast surgeons, medical oncologists, primary care providers, and physician extenders who see patients with AH or LCIS. Statistical methods: We have 90% power to detect a 15% increase in the frequency of chemoprevention informed choice with a 1-sided 0.025 level test, assuming an intraclass correlation (ICC) of 0.02 to account for clustering, roughly equal accrual at each site, 10% loss to follow-up, and ≤10% event rate in the control arm. Current/target accrual: The trial was activated on 9/1/2020. As of 7/7/2022, all 26 sites have been randomized, 157/200 providers and 184/415 patients have been enrolled. Discussion: Our hybrid effectiveness/implementation study seeks to evaluate the effectiveness of a multi-level intervention in promoting informed decision-making about breast cancer chemoprevention. Study results will provide valuable insights on how the decision support tools are integrated in diverse clinical settings. Citation Format: Katherine D. Crew, Garnet Anderson, Kathryn Arnold, Andrew Stieb, Jacquelyn N. Amenta, Cynthia Law, Ana Sandoval-Leon, Sarah Colonna, Tari King, Debra Mangino, Sandhya Pruthi, Maria Grosse Perdekamp, Christa Braun-Inglis, Stacy Krisher, Lisa Yee, Danielle Bertoni, Samantha Seaward, Kari B. Wisinski, Justin Floyd, Corrine Zarwan, Tarah J. Ballinger, Lindi VanderWalde, Masey M. Ross, Preston Steen, Shelly Lo, Alison Conlin, Kathleen Yost, John Ellerton, Erin Lin, Holly J. Pederson, Sagar Sardesai, Cheryl Jernigan, Dawn Hershman, Marian L. Neuhouser, Banu K. Arun, Rita Kukafka. SWOG 1904: Cluster-randomized controlled trial of patient and provider decision support to increase chemoprevention informed choice among women with atypical hyperplasia or lobular carcinoma in situ (MiCHOICE) [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 OT1-15-01.