mBC Treatment Research Articles

Treatment patterns and clinical outcomes in HER2-low metastatic breast cancer, 2018–2023: A retrospective observational study.

398 Background: Current treatment options for patients (pts) with hormone receptor–positive (HR+) human epidermal growth factor receptor 2–low (HER2-low) (immunohistochemistry [IHC] 1+, IHC 2+/in situ hybridization–negative) metastatic breast cancer (mBC) who progress after endocrine therapy (ET) with or without targeted therapy, including CDK4/6 inhibitors (CDK4/6i) or inhibitors of the PIK3CA/AKT/mTOR pathway, have been limited to chemotherapy (CT).In this study, we assessed recent treatment patterns and clinical outcomes in US pts with HR+/HER2-low mBC. Methods: This was a retrospective observational study using the nationwide Flatiron Health electronic health record-derived de-identified database. Pts aged ≥18 years with no prior cancer (excluding non-melanoma skin cancer), de-novo or recurrent HR+/HER2-low mBC diagnosed between January 2018 and December 2022, and who received any line of treatment (LOT) for mBC (excluding clinical trials) were included. Demographic and clinical characteristics were captured prior to and at the index date (date of mBC diagnosis). Pts were followed up from index date to death, last activity date, or end of the study (September 30, 2023). Real-world overall survival (rwOS) from mBC diagnosis and real-world progression-free survival (rwPFS) from the start of each LOT was calculated using the Kaplan-Meier method. Results: A total of 2692 pts were eligible. Median follow up from mBC diagnosis was 38.3 months (interquartile range [IQR] 24.4, 53.4) and median age at mBC diagnosis was 65.0 years (IQR 56.0, 73.0); 45.3% of pts had de-novo mBC. Median LOT was 2.0 (IQR 1.0, 3.0) up to the end of the study (55.1% of pts received second-line [2L], 28.9% third-line [3L], 15.2% fourth-line [4L], and 7.2% fifth-line [5L] therapy). Serial ET cycles accounted for 65.7% of 2L, 45.2% of 3L, 27.9% of 4L, and 18.5% of 5L therapy. The most common drug categories by LOT are shown in the Table. Median rwOS was 43.0 months (95% confidence interval [CI] 40.0, 46.0). rwPFS was 20.5 months (95% CI 19.0, 22.3) in first-line [1L] therapy, 15.6 months (95% CI 14.0, 18.9) in 2L, 17.1 months (95% CI 13.5, 22.8) in 3L, and 13.4 months (95% CI 9.9, not estimable) in 4L. Conclusions: Treatment of HR+/HER2-low mBC has been heterogenous by LOT and mainly characterized by initial use of ET-based therapy followed by higher CT use in later lines. This is associated with diminishing effectiveness, highlighting a need for new treatments. Top five drug categories by LOT, n (%). 1L (n=2692) 2L (n=1484) 3L (n=778) 4L (n=408) 5L (n=195) ET + CDK4/6i 1537 (57.1) 694 (46.8) 217 (27.9) 76 (18.6) 25 (12.8) Endocrine monotherapy 684 (25.4) 202 (13.6) 126 (16.2) 52 (12.8) 21 (10.8) ET + mTORi 9* 61 (4.1) 55 (7.1) 25 (6.1) 17 (8.7) ET + CT 50 (1.9) 74 (5.0) 45 (5.8) 29 (7.1) 22 (11.3) CT alone 269 (10.0) 270 (18.2) 210 (27.0) 161 (39.5) 82 (42.1) CDK4/6i alone 69 (2.6) 29* 8* 3* 3* *Not a top five drug category in the specified LOT.

Eribulin plus carboplatin combination for HER2-negative metastatic breast cancer: a multicenter, real-world cohort study

BackgroundPre-clinical data suggests a potential synergistic effect of eribulin and platinum. However, clinical data on the combination for metastatic breast cancer (mBC) is lacking. We evaluated the efficacy and safety of eribulin plus carboplatin (ErCb) in patients with mBC.Patients and methodsThis multicenter, real-world cohort study included patients with pre-treated metastatic triple negative breast cancer (TNBC) or endocrine-refractory hormone receptor (HR) positive, HER2-negative mBC who received ErCb. Eribulin (1.4 mg/m2) and carboplatin (target AUC = 2) were administered intravenously on day 1 and 8 of 21-day cycle. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.ResultsFrom March 2022 to December 2023, a cohort of 37 patients were recruited to the study. Among them, 22 patients have TNBC and 15 have HR + HER2 − mBC. Of the 22 patients with TNBC, 8 had an initial diagnosis of the HR + HER2 − subtype. The median treatment was 6 cycles (range, 2 − 8 cycles). In the full cohort, TNBC, and HR + HER2 − subgroup, the ORR were 51.4%, 54.5% and 46.7%, the DCR were 81.1%, 81.8% and 80%, and the median PFS were 5 months, 5 months, and 5.2 months, respectively. The median OS was 12.7 months in the entire cohort and 12.8 months in TNBC subgroup. The most common grade 3/4 hematological AEs were neutropenia (37.8%), leukopenia (35.1%), febrile neutropenia (10.8%), thrombocytopenia (5.4%), and anemia (2.7%). No grade 3/4 non-hematological AEs were observed.ConclusionErCb demonstrated favorable efficacy and tolerability in patients with heavily pre-treated mBC, especially TNBC. The findings of the current study warrant further investigation of the application of this combination in earlier lines of mBC treatment.

Investigating the Salience of Clinical Meaningfulness and Clinically Meaningful Outcomes in Metastatic Breast Cancer Care Delivery

PURPOSE As metastatic breast cancer (mBC) treatment evolves, there is a need to understand how clinical meaningfulness, or a meaningful change in a patient's daily life, and clinically meaningful outcomes inform patient-centered care. Partnering with key stakeholders ensures patient-centered research incorporates the knowledge and expertise of advisors with lived experience. We describe a multistakeholder engagement approach to examine how people living with mBC (PLWmBC), caregivers, and health care providers interpret clinical meaningfulness and clinically meaningful outcomes and their influence on mBC treatment decision making and care. METHODS Qualitative focus groups with PLWmBC, caregivers, and health care providers were conducted and analyzed along three overarching themes: interpretations of clinical meaningfulness and clinically meaningful outcomes; treatment recommendations, preferences, and decisions; and implications for clinical practice. Patient-led and professional organizations served as research partners in study design, implementation, and interpretation of findings. RESULTS Partnerships were established with four patient-led and three professional organizations representing diverse constituencies throughout the United States. Twenty-two focus groups were conducted with 50 PLWmBC, 24 caregivers, and 41 health care providers (oncologists, n = 11; advanced practice providers, n = 13; oncology nurses, n = 17) between March and June 2023. PLWmBC and caregivers were unfamiliar with the concepts of clinical meaningfulness and clinically meaningful outcomes. Although health care providers were familiar, they did not use the terms when discussing treatment with PLWmBC. Across groups, participants emphasized the importance of meaningful outcomes beyond overall survival, including quality of life and improvement in symptoms and functioning. Participants noted that outcomes considered meaningful are individualized and dynamic. CONCLUSION This study offers insight into how partnering with patient advocacy and professional organizations can enhance research quality and aid translation of findings to clinical practice, thereby supporting patient-centered care.

A multicenter real-world study on the efficacy and safety of anlotinib-based treatment for metastatic breast cancer.

e13120 Background: Anlotinib is a multi-targeted small molecule receptor tyrosine kinase (RTK) inhibitor that inhibits angiogenesis. There is only one phase II study on the use of anlotinib in advanced breast cancer (MBC). Therefore, this study aims to analyze its efficacy and safety in the treatment of BC in the real world. It has been approved for the treatment of advanced non-small cell lung cancer and soft tissue sarcoma. There is limited research on the use of anlotinib in advanced breast cancer (MBC). Methods: This study retrospectively analyzed the clinical data of MBC patients who received anlotinib treatment at four domestic centers from January 2021 to December 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Kaplan-Meier analysis was used to analyze PFS and OS, and Cox regression model was used to analyze the hazard ratios (HRs) of anlotinib-based treatment on PFS and OS in different subgroups of patients. A p-value <0.05 was considered statistically significant. Results: A total of 153 MBC patients receiving anlotinib-based treatment were included from four centers. The median age was 51 years (range: 22-76), and the median number of prior lines of therapy was 3. The median PFS was 7.7 months (range: 5.2-10.1 months), and the median OS was 28.0 months (range: 21.4-34.9 months). The median ORR and DCR were 19.6% and 60.1%, respectively. The ORR for HR+/HER2- and triple-negative breast cancer patients was 11.6% and 28.8%, respectively, DCR for HR+/HER2- and triple-negative breast cancer (TNBC) patients was 55.8% and 59.6%, respectively. The median PFS was 9.0 months (range: 6.0-11.9 months) for HR+/HER2- patients and 5.3 months (range: 3.5-7.0 months) for TNBC patients, while the median OS was 33.0 months (range: 24.4-41.5 months) and 14.0 months (range: 9.5-18.4 months), respectively. In the subgroup analysis, age <60 years, initial stage IV disease, Ki67≤60%, and treatment with PD-L1 monoclonal antibodies-based regimen were associated with PFS benefit. ECOG <2 and treatment with PD-L1 monoclonal antibodies-based regimen were associated with prolonged OS. Among the 31 patients with brain metastases receiving anlotinib treatment, 11 had active brain metastases and 20 had stable brain metastases. The median PFS was 8.0 months. The intracranial ORR was 12.9%, and the intracranial DCR was 61.3%. No serious adverse events or treatment-related deaths occurred. Grade I/II adverse reactions included hand-foot syndrome (22.2%) and fatigue (19.6%), while grade III/IV adverse reactions included fatigue (6.5%) and decreased neutrophil count (5.2%). Three patients required dose reduction due to intolerable adverse reactions, and nine patients discontinued treatment. Conclusions: Anlotinib demonstrates good antitumor activity and safety in the treatment of MBC. When combined with chemotherapy or immunotherapy, it can improve PFS and OS without significantly increasing toxicity. In particular, it shows promising intracranial ORR and PFS in patients with brain metastases. Clinical trial information: NCT04541420 .

Cost-utility analysis of a supervised exercise program for patients with metastatic breast cancer in the PREFERABLE-EFFECT randomized controlled trial (RCT).

11121 Background: Exercise for patients with metastatic breast cancer (mBC) significantly reduced fatigue and improved quality of life (QoL) in the multinational PREFERABLE-EFFECT RCT (NCT04120298). Evidence on the cost-effectiveness of exercise for patients with mBC is lacking, albeit essential for implementation in clinical practice. In this study, we evaluated the cost-utility of an exercise program for patients with mBC in the EFFECT RCT. Methods: We conducted a cost-utility analysis using data from the 357 EFFECT trial participants (mean age 55 ± 11 yrs, 75% on 1st/2nd line treatment). These participants, from centers in NL, DE, SE, PL, ES, AU, were randomized to either a 9-month supervised exercise intervention (n=178) or a usual care control group (n=179). We used a societal perspective with a time-horizon of 9 months. Two different scenario analyses (SA) were used to determine intervention costs using a bottom-up micro-costing method: SA-1) 1-on-1 supervision; SA-2) 4-on-1 supervision. Data on healthcare resource use, productivity loss and QoL (converted to QALYs) were collected with country-adapted, self-report questionnaires, including the iMCQ, iPCQ and EQ-5D-5L, at 3-, 6- and 9-months post-baseline. Multiple imputation was performed, and bootstrapping was used to study uncertainty. Results: Compared to usual care, supervised exercise led to a QALY gain of 0.015 (95% CI: -0.02; 0.05) over a 9-month period, corresponding to an increase of 5.3 days in perfect health. The mean intervention costs were €1,696 in SA-1 and €609 in SA-2. The mean total cost differences (adjusted for center and line of treatment) were -€27 (SA-1), and -€1,112 (SA-2), in favor of the exercise group ( Table). The greatest cost-savings occurred in hospital costs, meaning that the exercise group had lower hospital costs compared to the control group (€4,430 vs €5,211). The probability of supervised exercise being cost effective at a willingness-to-pay threshold of €20.000 or €80.000 per QALY gained was 62% or 76% in SA-1, and 91% or 92% in SA-2, respectively. Conclusions: Exercise for patients with mBC is likely to be cost-effective when individually supervised and even dominant (greater cost-savings and more effective) when group-based. Based on our positive findings for both effectiveness and cost-effectiveness, we recommend supervised exercise to be reimbursed as supportive care during treatment for mBC. Clinical trial information: NCT04120298 . [Table: see text]

Sequential use of PI3K/AKT/mTOR pathway inhibitors alpelisib and everolimus in patients with hormone receptor-positive (HR+) metastatic breast cancer.

1057 Background: Alpelisib (A), a PI3K inhibitor, is FDA-approved with fulvestrant for patients with PIK3CA-mutated HR+/HER2- MBC. Everolimus (E), an mTOR inhibitor, is FDA-approved with endocrine therapy (ET) regardless of PI3K/AKT/mTOR pathway mutation status. The efficacy and safety of sequential treatment with these pathway inhibitors is not well described. Methods: This single-center retrospective cohort study identified patients with HR+/HER2- MBC treated with both A and E sequentially, each in combination with ET, in either order from 2012-2023. We collected information on patient demographics, clinical and pathologic characteristics, treatment history, treatment adverse effects, and dates of disease progression (defined as radiographic or clinical progression leading to treatment change) from medical records. Patients treated first with E then A were categorized as Group 1 and those first with A then E as Group 2. Rates of prior CDK4/6i use were compared between groups with the chi-square test; differences in prior lines of therapy were assessed with the Wilcoxon rank sum test. Median PFS1 (PFS on 1st pathway inhibitor) and PFS2 (PFS on 2nd pathway inhibitor) were computed using the Kaplan-Meier method and the impact of prior treatment on PFS2 between groups was compared using Cox proportional hazards analysis. Results: 115 patients with HR+/HER2- MBC were included in this study. There were 62 (54%) patients in Group 1 and 53 (46%) patients in Group 2. Median prior lines of therapy in the metastatic setting for Group 1 was 4 (range 1-13) and for Group 2 was 3 (range 1-8; p=0.08). Median number of intervening therapies between E and A in Group 1 was 2 (range 0-8) and between A and E in Group 2 was 0 (range 0-4; p<0.001). 34/62 (55%) patients in Group 1 and 45/53 (85%) in Group 2 received prior CDK4/6i ( p<0.001). In Group 1, 49/62 (79%) of patients discontinued E for progression and 13 (21%) discontinued for toxicity. Median PFS1 was 9.2 months (95%CI 5.5-13.0) and PFS2 was 5.0 months (95%CI 4.6-7.9). In Group 2, 34/53 (64%) of patients discontinued A for progression and 19 (36%) discontinued for toxicity. Median PFS1 was 9.3 months (95%CI 7.0-14.0) and PFS2 was 3.5 months (95%CI 3.0-4.1). After adjusting for prior CDK4/6i use and prior lines of therapy (total and intervening), PFS2 was not significantly different between the groups. Genomic information will be included at the time of presentation. Conclusions: This is the largest retrospective study to-date of patients treated sequentially with PI3K/AKT/mTOR pathway inhibitors. PFS was longer with the 1st pathway inhibitor than with the 2nd regardless of sequence. This has implications for optimal integration of capivasertib, an AKT inhibitor, into HR+ MBC treatment. Prospective studies testing optimal sequencing are needed.

Unveiling the cost-effectiveness of CDK4/6 inhibitors in treating patients with HR+/HER2- metastatic breast cancer: A closer look at nonmedication expenses.

1532 Background: Cyclin-dependent kinase (CDK)4/6 inhibitors have significantly enhanced survival outcomes in postmenopausal patients diagnosed with HR+ MBC. Their integration with endocrine therapy (ET) has become the standard of care in MBC treatment lines. There are limited economic evaluations of these innovative, yet costly, therapies. This study assesses the cost-effectiveness of these drugs using EHR derived data and administrative claims to estimate cost. Methods: We used the nationwide EHR-derived Flatiron Health (FH) de-identified database to identify 3,879 patients receiving 1st line (1L) treatment for HR+ MBC (2,137 received CDK4/6i+ET and 1,742 received ET alone) between Feb 2015 and Nov 2021. SEER-Medicare claims data was used to supplement the missing cost info in the FH database to quantify monthly medication costs, drawing data from Medicare patients continuously enrolled in PARTs A, B, and D between 2015 to 2021 for at least 24 months and specific to therapeutic approaches for MBC and overall healthcare costs. The costs were adjusted by the patient characteristic: age, race, specific ET or CDK4/6i drug, and Medicare dual eligibility. The effectiveness was measured as progression-free duration in months. All costs were adjusted for inflation. The Incremental Cost Effectiveness Ratio (ICER) analysis was conducted to examine the cost-effectiveness of CDK4/6i as compared with ET alone. Results: Average estimated monthly medication costs were $12,524 and $322 for CDK4/6i+ET and ET alone, respectively. On average, CDK4/6i+ET increased the estimated medication costs by $235,564 over the time to first progression and was associated with a gain of 3.2 months of progression-free survival as compared to ET alone, resulting in an ICER of $73,098 per month without progression. At a willingness-to-pay of $65,000 per month without progression, both groups have 50% probability of being considered cost-effective. Notably, the average estimated monthly non-medication costs (total costs-medication costs) for the CDK4/6i+ET group were $2,278 compared to $4,265 for the ET alone group (p<0.001). On average, CDK4/6i+ET decreased the estimated non-medication costs by $ 22,427. For non-medication costs, the ICER drops to $7,178 per month without progression making the CDK4/6i+ET the dominant cost-effective choice over ET alone. Conclusions: Cost-effectiveness of treating HR+ MBC patients is primarily driven by the cost of CDK4/6i drug prices. However, findings highlight significantly lower overall non-medication healthcare costs using CDK4/6i+ET compared to ET alone in 1L treatment. These cost savings, however, are offset by the high medication costs of CDK4/6i. Thus, lowering the market cost of CDK4/6i drugs or targeting those who can benefit the most could shift the balance in favor of a cost-effective benefit from Medicare perspective.

Abstract PO1-10-06: Understanding clinical meaningfulness in metastatic breast cancer treatment decision-making: experiences and perspectives of patients, caregivers, and clinicians

Abstract Background: While many clinical and non-clinical factors inform metastatic breast cancer (mBC) treatment recommendations; patient preferences, values, and care goals also influence how treatment options are weighed, deliberated, and decided upon. Additionally, in the mBC care setting, clinical meaningfulness and clinically meaningful outcomes (e.g., survival, quality-of-life) are important factors to consider along the care continuum. However, the extent to which patients and their oncology care team align on the interpretation and use of these concepts during treatment decision-making has not been well elucidated. This study examined perspectives on the concepts of (i) clinical meaningfulness and (ii) clinically meaningful outcomes associated with mBC treatment among five key stakeholder groups: patients, caregivers, oncologists, advanced practice providers (APPs), and oncology nurses. Methods: Qualitative semi-structured in-person and web-based focus groups were conducted between March and June 2023 among: (i) people living with mBC; (ii) unpaid or informal caregivers to people with mBC; and providers involved in the care of patients with mBC, including (iii) oncologists, (iv) APPs (i.e., physician assistants and nurse practitioners), and (v) oncology nurses. Discussion guides were developed to elicit stakeholder perspectives on clinical meaningfulness and clinically meaningful outcomes to help identify areas of convergence and divergence between and within stakeholder groups. All discussions were audio recorded and transcribed. The constant comparative approach was used to identify key themes. Results: Twenty-two focus groups were conducted with 50 patients, 24 caregivers, 8 oncologists, 13 APPs, and 17 oncology nurses. Overall, patients and caregivers were unfamiliar with the concepts of clinical meaningfulness and clinically meaningful outcomes, underscoring the critical need for using accessible and patient-friendly terminology in treatment decision-making discussions. While some providers were familiar with these concepts, they reported not using these terms when discussing treatment recommendations with patients. Although some provider participants thought clinical meaningfulness described quantitative endpoints (e.g., additional months of survival), participants across all stakeholder groups described patients’ abilities to achieve life goals (e.g., participation in milestone events and social activities, ability to travel) as paramount. Recommendations for improving treatment decision-making discussions included taking a patient-centered approach, with inclusive, dynamic patient-provider discussions and continuous evaluation of patient priorities across the care continuum, not just at diagnosis. Meaningful outcomes beyond overall survival need to be considered, including quality of life, progression-free survival, minimal or manageable side effects, and improvement in symptom burden and functioning. Across all stakeholders, participants stressed that outcomes considered meaningful are highly individualized and dynamic, evolving over time as patients move through the treatment journey and life stages. Conclusions: Clinical meaningfulness is poorly understood and not often considered in the clinical setting when making mBC treatment decisions, highlighting a need for accessible and patient-friendly terminology in mBC treatment decision-making conversations. While participants valued overall survival, the importance of meaningful outcomes that support patients’ quality of life was emphasized. Study findings can be used to inform both practice and clinical research to better capture meaningful outcomes for patients. Citation Format: Stephanie Graff, Emily Freeman, Meaghan Roach, Rozanne Wilson, Ricki Fairley, Mary Gullatte, Jeanne Stemland, Becky Chan, Paulina Wochal, Julie Katz, Suepattra May-Slater. Understanding clinical meaningfulness in metastatic breast cancer treatment decision-making: experiences and perspectives of patients, caregivers, and clinicians [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 PO1-10-06.

Abstract PS11-01: Brain metastases in metastatic breast cancer: prevalence per line of treatment and cumulative incidence in a cohort of 18075 real-world patients

Abstract BACKGROUND Historic data suggest that incidence of brain metastasis (BM) is relatively distributed over time in HER2-positive (HER2+) breast cancer (BC), occurs early in triple negative BC (TNBC), and occurs late in hormone receptor-positive (HR+) metastatic BC (mBC). However, the timing of BM relative to line of therapy has not been well described. We describe the prevalence per line of therapy and cumulative incidence of BM in a large real-world cohort of patients (pts) with mBC, by BC subtype and line of therapy. METHODS This analysis used data from the longitudinal US Flatiron Health de-identified database, which provides unstructured and structured electronic health record-derived data from >2.6 million pts with cancer in ~800 unique sites of care. Eligible pts had initiated a first line of treatment (index data) for mBC up to March 1, 2021, to allow for ≥2 years potential follow-up time. Baseline characteristics were assessed, and pts categorized by HER2 and HR status: 1) HR+, HER2+; 2) HR+, HER2–, 3) HR–, HER2+ and 4) TNBC (i.e., negative for HR and HER2). For the last two categories, HER2-low subsets were defined based on immunohistochemistry results (1+, 2+, or equivocal). Lines of therapy were derived using both treatment regimens and progression data. The primary outcome was the first diagnosis of BM. The prevalence of BM was evaluated by subtype, at the index date, and by the line of therapy. The cumulative incidence function (CIF) of BM was used to estimate the risk of BM in pts free of BM at the index date, and death was treated as a competing event. RESULTS Overall, 18075 pts were included (HR+, HER2+: 3062 pts [16.9%]; HR–, HER2+: 902 pts [5.0%]; HR+, HER2–: 12331 pts [68.2%] [HR+, HER2-low: 7062 (39.1%)]; TNBC: 1780 pts [9.8%] [HR–, HER2-low: 725 pts (4.0%)]). Median age at the index date was 64 years (interquartile range: 54, 73) and 10271pts (56.8%) had visceral metastasis. In total, 5951 pts (32.9%) had de novo disease, 12090 (66.9%) had recurrent disease, and 34 (0.2%) did not have available data for mBC type. The table shows the number of pts by line of therapy, prevalence of BM, and cumulative incidence of BM from the index date. Of the included pts, 1306 (7.2%) had a BM at the index date; the CIF was run on the remaining 16973 pts. Overall, 2248 pts (13.2%) had an incident BM event during follow-up (HR+, HER2+: 578 events; HR–, HER2+: 237 events; HR+, HER2–: 1119 events [HR+, HER2-low: 619 events]; TNBC: 314 events [HR–, HER2-low: 124 events]), 9314 had a competing event, and 5411 were censored. By fourth-line therapy, the prevalence of BM was 26.1% in HR+, HER2+; 37.1% in HR–, HER2+; 24.7% in TNBC (HR–, HER2-low: 27.9%); but remained low at 7.2% in HR+, HER2– (HR+, HER2-low: 9.4%). The cumulative incidence of BM at 60 months was 23% in HR+, HER2+, 34% in HR–, HER2+, 10% in HR+, HER2–, and, 22% in TNBC. Overall, the HER2-low subsets had BM prevalence and cumulative incidence that were very close to those that were HER2–. CONCLUSIONS This large analysis of real-world data demonstrates that the prevalence of BM across pts with mBC differs by tumor subtype and by line of therapy. Conversely, HER2-low status may have limited impact. The cumulative incidence of BM was highest in the HR–, HER2+ and TNBC subgroups, and lowest in the HR+, HER2– subgroup; despite this, due to the high proportion of HER2–, HR+ mBC cases, the HR+, HER2– group represented the largest number of BM events. These data emphasize the need for clinical and biologic predictors of BM and for strategies to prevent their onset, and provide information on the impact of BM inclusion and exclusion criteria in clinical trials for pts with mBC. Number of patients by line of therapy, prevalence of BM, and cumulative incidence of BM from the index date BM, brain metastasis; HR, hormone receptor, pts, patients; TNBC, triple negative breast cancer. Citation Format: Sarah Sammons, Jose Leone, Thibaut Sanglier, Peter Lambert, Filippo Montemurro, Raf Poppe, Eleonora Restuccia, Sara Tolaney, Nancy Lin. Brain metastases in metastatic breast cancer: prevalence per line of treatment and cumulative incidence in a cohort of 18075 real-world patients [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 PS11-01.

Abstract GS02-10: Effects of a structured and individualized exercise program on fatigue and health-related quality of life in patients with metastatic breast cancer: the multinational randomized controlled PREFERABLE-EFFECT study

Abstract INTRODUCTION: Patients with metastatic breast cancer (mBC) often experience cancer- and treatment-related side effects that can impair daily life activities and health-related quality of life (HRQoL). Interventions are needed that improve HRQoL by alleviating fatigue and other side effects during palliative BC cancer treatment. Recent evidence-based international guidelines (ASCO, ACSM) recommend exercise for patients with BC during adjuvant treatment for reducing side effects. However, evidence of the effectiveness of exercise in patients with mBC is scarce. The PREFERABLE-EFFECT study (NCT04120298) was designed to assess the effects of a 9-month supervised exercise program in patients with mBC on fatigue, HRQoL, and other cancer- and treatment-related side effects. METHODS: PREFERABLE-EFFECT is a multinational, randomized controlled trial including patients with mBC from five European countries (Germany, Poland, Spain, Sweden, The Netherlands) and Australia. Participants were randomly assigned to usual care or an individualized, structured exercise program consisting of aerobic, resistance, and balance training. The first six months included twice weekly supervised exercise sessions of one hour. In the last three months, one supervised session was replaced by an unsupervised session, supplemented by an exercise App. All participants received general exercise advice (physical activity ≥ 30 min/day) and an activity tracker. Our primary outcomes, physical fatigue (subscale of the EORTC QLQ-FA12) and HRQoL (summary score of the EORTC QLQ-C30), were assessed at baseline, 3, 6, and 9 months. Among other physical fitness outcomes, maximal short exercise capacity was assessed with the Steep Ramp Test. The intervention effects (intention-to-treat) were determined by comparing the change from baseline to 3, 6 (i.e., primary endpoint) and 9 months between groups using separate mixed models for repeated measures, adjusted for baseline values of the outcome variable and stratification factors (mBC line of treatment (1st/2nd vs. 3rd or higher) and study center). A significant improvement of either or both primary outcomes (applying the Bonferroni-Holm method) was considered as successful. RESULTS: Between 2019-2022, we included 357 patients with mBC, with 178 patients randomized to the exercise intervention and 179 to usual care. Patients were, on average, 55.4 years of age (SD=11.1), most patients received 1st or 2nd line of treatment at study enrollment (74.8%) and had bone metastases (73.9%). At 6 months (primary endpoint), participation in the exercise intervention resulted in statistically significant positive effects on both primary outcomes, compared to usual care: physical fatigue was lower (mean difference: -5.3, 95% CI -10.0; -0.6, p=0.027, effect size (ES)=0.22) and HRQoL was better (+4.8, 95% CI 2.2; 7.4, p=0.0003, ES=0.33). Beneficial effects were also found at 3 months (physical fatigue: -3.4, -7.8; 1.0, ES=0.14 and QoL: 3.9, 1.5; 6.3, ES=0.27) and 9 months (physical fatigue: -5.6, -10.9; -0.4, ES=0.24 and QoL: +4.3, 1.4; 7.3, ES=0.31). Further, at the primary endpoint, we found positive exercise effects on physical fitness (+24.3 Watts, 15.5; 33.1, ES=0.42) and numerous QLQ-C30 scales, including social functioning (+5.5, 0.2; 10.8, ES=0.20), pain (-7.1, -12.1; -1.9, ES=0.28) and dyspnea (-7.6, -12.2; -3.0, ES=0.28). Two SAEs occurred (one wrist fracture and one sacral stress fracture), neither related to bone metastases. CONCLUSION: This large multinational study demonstrated significant beneficial effects of a supervised exercise intervention offered during palliative treatment on mBC patients’ fatigue, HRQoL, and other clinically relevant outcomes. Based on these findings, we recommend supervised resistance and aerobic exercise as part of supportive care regimens during palliative treatment of mBC. Citation Format: Anne May, Anouk Hiensch, Johanna Depenbusch, Martina Schmidt, Evelyn Monninkhof, Mireia Pelaez, Dorothea Clauss, Philipp Zimmer, Jon Belloso, Mark Trevaskis, Helene Rundqvist, Joachim Wiskemann, Jana Muller, Carlo Fremd, Renske Altena, Joanna Kufel-Grabowska, Rhode Bijlsma, Lobke van Leeuwen-Snoeks, Daan ten Bokkel-Huinink, Gabe Sonke, Bruce Mann, Prudence Francis, Gary Richardson, Isabel Álvarez, Wolfram Malter, Elsken Van der Wall, Neil Aaronson, Elżbieta Senkus, Ander Urriticoechea, Eva Zopf, Wilhelm Bloch, Martijn Stuiver, Yvonne Wengström, Karen Steindorf. Effects of a structured and individualized exercise program on fatigue and health-related quality of life in patients with metastatic breast cancer: the multinational randomized controlled PREFERABLE-EFFECT study [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 GS02-10.

Abstract PO1-18-01: Patient Preferences for HR+/HER2- Metastatic Breast Cancer Treatments in Italy: A Qualitative Assessment

Abstract Objectives: Factors that influence treatment preferences of patients with hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) are being investigated using discrete choice experiment (DCE) methodology. Appropriate attributes for the ongoing quantitative online survey phase were identified by this initial qualitative pilot study. Methods: To generate hypotheses and inform variables of the quantitative survey, the pilot phase consisted in online telephone interviews with patients with a diagnosis of Stage IV HR+/HER2- breast cancer at various stages of treatment. Interviews focused on exploring patients' perspectives on their interaction with physicians, preferences, and treatment experiences. Transcripts were coded using NVivo software to identify key themes. The ongoing DCE online survey aims to recruit patients meeting the same selection criteria as in the qualitative phase, also at various stages of treatment. Results: Fifteen mBC patients (median age, 43 years [range, 29-64]), including nine chemotherapy-treated and six without chemotherapy exposure, were enrolled in the pilot qualitative study. Eight and four patients reported receiving little information about their treatment plan and their risk status beyond the risk of relapse, respectively. Most participants did not know what to expect from their therapy but expressed trust in their physician’s decision in terms of treatment goals. Few patients (n=3) looked for a second opinion before starting treatment. Four out of fifteen patients declared that they were actively involved in their treatment plan decision, although all relied on their physician’s knowledge and decision. Reduced symptoms and improved quality of life (QoL) were patients’ main treatment goals, and side-effects and efficacy of treatment were their main concerns. When asked about the degree of acceptability of certain side effects, some participants considered hair loss and vomiting as unacceptable side effects, regardless of severity, while others considered them to be the most acceptable. This discrepancy is to be interpreted in the light of participants’ own treatment journey. Severity and duration of side-effects were mentioned by three patients as acceptability factors. In a choice task, patients were asked to express preferences between two hypothetical treatments. Efficacy (n=9) and administration mode (n=6) were spontaneously deemed important for treatment selection. While assessing the difference in risk between the two hypothetical treatments, ten patients explained that the main choice feature was extended progression-free survival (PFS) rate. Risk of infection and neutropenia (n=12) were concerns expressed by most patients in the post-COVID-19 period. Considering their substantial impact on QoL, alopecia (n=9) and vomiting (n=9) were presented by patients as particularly important, regardless of their degree of severity; whereas almost all patients reported that only severe fatigue (n=12), diarrhea (n=13) or nausea (n=13) would be an issue. These results allowed selection of the following attributes for further quantification of their preference weights in a DCE: PFS, risk of neutropenia, risk of alopecia, risk of vomiting, risk of diarrhea, risk of grade 3/4 side effects and mode of administration. Conclusions: This qualitative pilot study allowed for identification of what matters most to patients when selecting a treatment for mBC, which will be further assessed in the DCE. It also highlighted the need of patients with HR+/HER2- mBC for information about their treatment, potential side-effects, and health management. This research suggests that there is a need for patients to be more involved in treatment plans, and that taking patient preferences into account may help improve the treatment selection experiences. Citation Format: Grazia Arpino, Carmine De Angelis, Lorenzo Gerratana, Matteo Lambertini, Sarah Igidbashian, Martina Bellini, Serena Giuntoli, Xavier Guillaume, Julie Behillil, Claire Graziani-Taugeron. Patient Preferences for HR+/HER2- Metastatic Breast Cancer Treatments in Italy: A Qualitative Assessment [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 PO1-18-01.

Abstract RF02-03: Trastuzumab deruxtecan (T-DXd) in combination with anastrozole or fulvestrant in patients with HER2-low HR+ advanced/metastatic breast cancer: a Phase 1b, open-label, multicenter, dose-expansion study (DESTINY-Breast08)

Abstract Background: Trastuzumab deruxtecan (T-DXd) is approved in over 40 countries for the treatment of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low (a score of 1+ on immunohistochemistry [IHC] analysis or an IHC score of 2+ and negative results on in-situ hybridization) breast cancer who have received prior chemotherapy in the metastatic setting or who developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. DESTINY-Breast08 (DB-08) was designed to establish the safety, tolerability, and preliminary activity of T-DXd in combination with widely used standard of care therapies in HER2-low hormone receptor (HR)+ metastatic breast cancer (mBC). Results reported here are from the dose-expansion stage of the Phase 1b, multicenter, open-label, parallel-assignment DB-08 study arms investigating T-DXd–endocrine therapy (ET) combinations [NCT04556773]. Methods: Eligible patients had centrally confirmed HER2-low advanced/mBC with measurable disease per RECIST 1.1 and were documented as HR+. Among patients with mBC, ≤1 prior line of ET ± a targeted therapy was allowed, and prior chemotherapy in the mBC setting was exclusionary. Patients received T-DXd 5.4 mg/kg intravenously (IV) every three weeks (Q3W) + anastrozole 1 mg orally daily (T-DXd + ANA) or T-DXd 5.4 mg/kg IV Q3W + fulvestrant 500 mg intramuscularly Q4W, with a 500 mg loading dose on Cycle 1 Day 15 (T-DXd + FUL). Primary endpoints were safety and tolerability; secondary endpoints included objective response rate (ORR), progression-free survival, duration of response (all evaluated by investigator per RECIST 1.1), and overall survival (OS). Data cutoff (DCO) was ~24 weeks after the last patient in each arm had received study treatment. Results: As of February 20, 2023, 21 patients in the T-DXd + ANA arm and 20 patients in the T-DXd + FUL arm had received study treatment. Median age was 55 and 66 years, 67% and 75% of patients received a prior line of ET ± a targeted therapy for mBC, 33% and 25% had no prior line of treatment for mBC, and median follow up in censored patients was 12.1 months (range 4.0, 17.3) and 8.5 months (range 1.3, 15.1) in the T-DXd + ANA and T-DXd + FUL arms, respectively. Adverse events (AEs) occurred in 95.2% (20/21) of patients in the T-DXd + ANA arm and 100% (20/20) of patients in the T-DXd + FUL arm, with AEs ≥Grade 3 occurring in 47.6% (10/21) and 55.0% (11/20) of patients in each arm, respectively. The most common any-grade AEs, occurring in ≥30% of patients in either arm, are reported in the Table. Three (15%) adjudicated drug-related interstitial lung disease/pneumonitis events were reported in the T-DXd + FUL arm (all Grade 2; at DCO, one case had resolved, one was resolving, and one was not resolved); none were reported in the T-DXd + ANA arm. AEs were manageable by drug interruption and dose reduction. Confirmed ORR was 71.4% (15/21; 95% confidence interval [CI] 47.8, 88.7) in the T-DXd + ANA arm, and 40.0% (8/20; 95% CI 19.1, 64.0) in the T-DXd + FUL arm (Table). OS data were not mature at this DCO. Conclusions: Safety profiles for T-DXd-ET combinations were generally comparable to T-DXd monotherapy and manageable with dose modification and routine clinical practice. T-DXd in combination with anastrozole or fulvestrant was active in first- or second-line treatment of patients with HER2-low HR+ mBC. Citation Format: Komal Jhaveri, Fabrice André, Erika Hamilton, Peter Schmid, Carey Anders, Laura Testa, Inna Ganshina, Yen-Shen Lu, Seock-Ah Im, Robyn Young, Magdalena Wrona, Caron Lloyd, Yiwen Zhang, Sherene Loi. Trastuzumab deruxtecan (T-DXd) in combination with anastrozole or fulvestrant in patients with HER2-low HR+ advanced/metastatic breast cancer: a Phase 1b, open-label, multicenter, dose-expansion study (DESTINY-Breast08) [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 RF02-03.

Abstract PO2-13-11: High circulating tumor DNA (ctDNA) concentration was associated with shorter progression free survival in patients with metastatic breast cancer

Abstract Background: Metastatic breast cancer can be classified into different subtypes depending on hormone receptor (HR) and HER2 status. The subtype can change during tumor progression, and repeated biopsy is needed to deliver the most appropriate treatment every time a new lesion is found. It is not always possible to get a new biopsy from metastatic sites, and therefore liquid biopsy using circulating tumor DNA (ctDNA) is suggested as an alternative method to replace conventional biopsy. Methods: We performed a prospective serial collection of 65 ctDNA samples from 17 patients with metastatic breast cancer (mBC) at Seoul National University Hospital from October 2020 to March 2022. We used IMBdx AlphaLiquid®100 method to detect the genetic changes and analyzed the correlation with clinical outcomes. Results: Median age was 45 (range 32 – 62). Fifteen patients (88.2%) were relapsed mBC and most of the patients (14/17: 82.4%) were HR-positive and HER2-negative. Most of the patients had their ctDNA examined at baseline and at the time of maximal response and/or at progression. Fifteen patients (88.2%) received systemic therapy including hormone therapy, anti-HER2 therapy, and cytotoxic chemotherapy. Eight patients (47.1%) were on the first-line treatment for mBC, and 7 patients (41.2%) were on the second or later lines for mBC at the time of baseline sampling. The concentration of ctDNA and the sum of mutated allelic frequency was calculated for each sample. The ctDNA concentration ranged from 0.71 to 1386.00 ng/mL, and the median value was 5.37 ng/mL. We dichotomized these samples into two groups, with ctDNA concentration either higher or lower than the median value. Then we analyzed progression free survival (PFS) of each group. Patients with higher ctDNA concentration showed shorter PFS (7 mo. vs. not reached, p< 0.001). The sum of mutated allelic frequency ranged from 0.00% to 223.46% and the median value was 6.36%. Patients with higher mutated allelic frequency showed shorter PFS (6 mo. vs. 22 mo., p< 0.001). In addition, the PFS was significantly worse in patients who had mutated PIK3CA (5 mo vs. 22 mo, p< 0.001). The patients with mutated TP53 also showed shorter PFS (6 mo vs. 17 mo, p< 0.001) in univariate analysis. High estrogen receptor positivity in immunohistochemistry was correlated with lower mutated allelic frequency in ctDNA (p=0.003) but had no impact on the concentration of ctDNA (p=0.165). The concentration of ctDNA differed by metastatic sites. Patients with metastases to bones (p=0.007), liver (p< 0.001), soft tissue or lymph nodes (p=0.002) were more likely to have higher concentrations of ctDNA, while patients with brain metastases had significantly lower ctDNA concentration (p=0.006). When the sum of mutated allelic frequency of ctDNA and metastatic sites was analyzed, bone (p=0.001), liver (p< 0.001), and soft tissue or lymph node (p< 0.001) metastases had a positive correlation, while brain had negative correlation (p=0.017). Lung or pleural metastases had no significant correlation with ctDNA, neither concentration (p=0.271) nor mutated allelic frequency (p=0.965). Conclusion: Patients with mBC with higher concentrations of ctDNA or higher mutated allelic frequency of ctDNA at baseline showed significantly shorter PFS. PIK3CAmt and TP53mt detected by liquid biopsy could be used as a poor prognostic biomarkers for mBC patients. Citation Format: Hanbaek Yi, Tae-Yong Kim, Myung Geun Song, Hwang-Phill Kim, Tae-You Kim, Jinyong Kim, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im. High circulating tumor DNA (ctDNA) concentration was associated with shorter progression free survival in patients with metastatic 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 PO2-13-11.

Abstract PO5-12-06: Minimization of treatment toxicity/side effects and their impact on quality of life (QoL) in patients (pts) with ER+/HER2- metastatic breast cancer (mBC)

Abstract Introduction: Treatment toxicity and side effects may be underreported (Basu Roy. J Thorac Oncol 2018:13:1815-17) and can negatively impact QoL. As such toxicities can influence pts’ treatment decisions, we surveyed pts with ER+/HER2- mBC to better understand the impact and patient reporting accuracy of treatment toxicities/side effects. Methods: The EQUALS 3 (ESR1 QUAlity of Life Survey 3), 55-question survey was designed by the EQUALS Steering Committee, trialed by pt advocates, emailed to US subjects (Cure Media Group and authors’ contacts), and posted to private BC Facebook and Twitter groups for 2 wks in June 2023. Eligible pts had ER+/HER2- mBC and treatment changes due to disease progression. Pts received a $10 gift card at survey completion. Survey answers were descriptively summarized. Results: 213 pts completed the survey. Most were < 60 yrs of age (77%), White (44%) or Hispanic/Latino (48%), peri-/postmenopausal (54%), and college-educated (71%); had income >$50,000 (66%); lived in urban (51%)/rural areas (22%); and had therapy lines of 1st (8%), 2nd (36%), or 3rd+ (51%). Current mBC treatments were endocrine therapy (ET) ± targeted therapies (70%), antibody drug conjugate (8%), chemotherapy (11%), and other (10%). Most pts had a female oncologist (65%) who worked in an academic hospital (61%); 68% had >1 oncologist. Surveyed pts reported toxicity concerns for side effects ranging from serious to nuisance. Side effects most frequently reported as extremely/moderately concerning were respiratory symptoms (51%), blood clots in lungs (49%) or heart/brain (47%), cognitive dysfunction (47%), infections (46%), nausea/vomiting (44%), cardiac adverse effects (44%), diarrhea (42%), gait instability (41%), fatigue (39%), joint pain (39%), hair loss (33%), or sexual dysfunction (27%). Although 49% of pts felt comfortable speaking to their medical team (MT) about side effects, 62% reported having minimized side effects to their MT due to fears/concerns of being seen as a complainer (70%), dose reduction (66%), being taken off drug (65%), not accessing other drugs with similar toxicities (61%), reduced efficacy with lower dose (59%), or coming off trial (47%). Almost half (47%) did not report treatment side effects, mostly due to fear of being seen as a complainer (63%), being taken off drug (57%), reduced efficacy with lower dose (51%), dose reduction (50%), not accessing other drugs (50%), or coming off trial (41%). QoL was poor/very poor in 20% of pts and QoL was the most common (68%) important/very important factor for making a treatment decision based on risks. Most common side effects that negatively impacted QoL were sexual dysfunction (45%), joint pain (38%), vaginal atrophy/dryness (36%), fatigue (33%), bone pain (31%), and hair loss (26%). Toxicities/side effects also impacted pts’ anxiety (49%), career (46%), marriage (42%), finances (32%), housework (30%), and relationships (19%). Regret after taking a cancer medication due to side effects was reported by 46% of pts. Conclusion: In this survey of pts with ER+/HER2- mBC on ET predominantly, many treatment side effects caused concern, not necessarily related to their seriousness, and most pts had minimized or hid side effects at some point due to fear of negative perceptions from their MT, reduced treatment efficacy, or clinical trial changes. Although QoL was overall good for most, 20% had poor QoL (largely impacted by sexual dysfunction, joint pain, and vaginal issues). Regret about toxicities was also common and should be explored. Provider awareness of pts’ toxicity experience, fears, and impacts on daily lives opens the door for educational tools to improve MT communications for treatment decisions, informed consent, and more accurate toxicity reporting in clinical trials. Citation Format: Sarah Sammons, Jane Meisel, Kelly Shanahan, Timothy Pluard, Fumiko Chino, Dario Trapani, Dominic Carroll, Monica Kozlowski, Elizabeth Attias, Nicole Kuderer. Minimization of treatment toxicity/side effects and their impact on quality of life (QoL) in patients (pts) with ER+/HER2- 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 PO5-12-06.

Abstract PO3-12-05: Patient (pt)-provider communication challenges about side effects/toxicities from metastatic breast cancer (mBC) treatments

Abstract Introduction: Treatment decisions for ER+/HER2- mBC may be influenced by pt knowledge about treatment side effects, which is shaped by pt-provider communication. We conducted a survey of pts with ER+/HER2- mBC to better understand pt expectations and experiences of treatment toxicities, the extent they were discussed by the pts’ medical team (MT), and the sources/types of side effect information pts prefer. Methods: The 55-question, online ESR1 QUAlity of Life Survey 3 (EQUALS 3) survey was emailed to US pts from the Cure Media Group and authors’ contacts, and posted to private BC Facebook and Twitter pt groups for 2 weeks in June 2023. Eligible pts had ER+/HER2- mBC and reported changing treatments due to progression. Pts received a $10 gift card at survey completion. Survey answers were descriptively summarized. Results: 213 pts completed the survey; they were < 60 yrs of age (77%), White (44%) or Hispanic/Latino (48%), peri-/postmenopausal (54%), and urban-area residents (51%); and had college education (71%) and household income >$50K (66%). Most pts were on 2nd (36%) or 3rd+ (51%) therapy lines. Current mBC treatments were endocrine therapy ± targeted agent (70%), antibody-drug conjugate (8%), chemotherapy (11%), and others (10%). Most pts’ oncologists were female (65%), BC specialists (51%), and from an academic hospital (61%). Only half (49%) of surveyed pts felt extremely/very comfortable discussing side effects with their MT. Although 86% felt well informed about treatment toxicities, MTs did not proactively ask about pts’ greatest concerns on side effects for 15% of pts, nor about what side effects pts would find tolerable or intolerable for 25%. Oncologist/MT inquired about acceptability of side effects most often with treatment change (25%) or when brought up by the pt (20%), and at every single visit for only 19% of pts. Most pts felt extremely prepared for treatment toxicities (78%) and well prepared to manage them (86%), but 19% of pts still felt that their MT did not provide optimal guidance on managing potential side effects. Pt-centered conversations were most often missing: what rare but serious side effects to expect (44%), how to deal with potential side effects (39%), and what common side effects to expect (32%). Pts also reported that the likelihood of experiencing side effects (40%), what rare but serious side effects to expect (39%), and how to deal with potential side effects (28%) were not well presented. To facilitate treatment decisions, pts would like more time discussing treatment options (48%) or side effects (39%); additional written or visual resources on side effects (29%, 23%, respectively) or efficacy (39%, 8%); and the ability to ask questions and receive meaningful answers (39%), talk to other pts (20%), or listen to videos of their stories (11%). Pt testimonials (45%), toxicity descriptions/examples (42%), and toxicity management strategies (36%) were the most common additional forms of information that pts would like to have had on side effects. Conclusion: In this survey of pts with ER+/HER2- mBC, not all pts were comfortable discussing treatment toxicities with their MT, but MTs are mostly addressing side effects. However, there is still room for communication improvement and additional forms of toxicity information are needed for optimal decision-making. Despite generally feeling well prepared for toxicities, a significant proportion of pts report that the range and specifics of side effects and how to manage them were missing or not well presented in MT discussions. This survey highlights the need to improve both provider and pt education with the goal of effectively communicating toxicity specifics of mBC therapies, as well as the need for standardized pt education tools detailing risks and benefits of mBC therapies to assist pts in shared decision-making conversations. Citation Format: Sarah Sammons, Jane Meisel, Timothy Pluard, Kelly Shanahan, Fumiko Chino, Dario Trapani, Dominic Carroll, Monica Kozlowski, Elizabeth Attias, Nicole Kuderer. Patient (pt)-provider communication challenges about side effects/toxicities from metastatic breast cancer (mBC) treatments [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 PO3-12-05.

Male breast cancer differs from female breast cancer in molecular features that affect prognoses and drug responses

BackgroundMale breast cancer (MBC) is a rare malignancy with a worse prognosis than female breast cancer (FBC). Current MBC treatment strategies are based on those for FBC. However, molecular differences between MBC and FBC with respect to prognosis and drug responses remain unclear. MethodsAfter controlling for confounding factors with propensity score matching (PSM), differences between MBC and FBC were comprehensively analyzed using many types of data: survival, immune microenvironments, sex hormone responses, drug sensitivity, transcriptomes, genomes, epigenomes, and proteomes. ResultsOverall survival (OS) and cancer-specific survival (CSS) were both worse for MBC than for FBC. Differentially expressed mRNAs were enriched in numerous cancer-related functions and pathways, with SPAG16 and STOX1 being as the most important prognosis-related mRNAs for MBC. Competing endogenous RNA (ceRNA) and transcription factor (TF)-mRNA regulatory networks contain potential prognostic genes. Nine genes had higher mutation frequencies in MBC than in FBC. MBC shows a comparatively poor response to immunotherapy, with five proteins that promote breast cancer progression being highly expressed in MBC. MBC may be more responsive than FBC to estrogen. We detected six United States Food and Drug Administration (FDA)-approved therapeutic target genes as being differentially expressed between MBC and FBC. ConclusionThe poor prognosis of MBC compared to FBC is due to numerous molecular differences and resulting drug responses.

Study design for DESTINY-Breast Respond HER2-low Europe: T-DXd in patients with HER2-low advanced breast cancer.

Trastuzumab deruxtecan (T-DXd) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). Results on T-DXd treatment in HER2-low mBC have so far been limited to clinical trials. DESTINY-Breast Respond HER2-low Europe (NCT05945732) is a multi-center, multi-country, observational, prospective, non-interventional study planning to enroll 1350 patients from 216 sites receiving T-DXd or conventional chemotherapy as their routine clinical care for advanced stage breast cancer in 12 European countries. This non-interventional study will provide real-world insight into T-DXd treatment for HER2-low mBC with data on effectiveness, safety and tolerability, patient-reported outcomes, treatment patterns, geriatric health status and HER2 testing. This will be beneficial for improving guidance to maximize patient treatment benefit.

The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities

HER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients’ prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantitative systems pharmacology model of the pathophysiology of HER2+ mBC that was extensively calibrated and validated against multiscale data to quantitatively predict and characterize the signal transduction and preclinical tumor growth kinetics under different therapeutic interventions. Focusing on the second-line treatment for HER2+ mBC, e.g., antibody-drug conjugates (ADC), small molecule inhibitors/TKI and chemotherapy, the model accurately predicted the efficacy of various drug combinations and dosing regimens at the in vitro and in vivo levels. Sensitivity analyses and subsequent heterogeneous phenotype simulations revealed important insights into the design of new drug combinations to effectively overcome various resistance scenarios in HER2+ mBC treatments. In addition, the model predicted a better efficacy of the new TKI plus ADC combination which can potentially reduce drug dosage and toxicity, while it also shed light on the optimal treatment ordering of ADC versus TKI plus capecitabine regimens, and these findings were validated by new in vivo experiments. Our model is the first that mechanistically integrates multiple key drug modalities in HER2+ mBC research and it can serve as a high-throughput computational platform to guide future model-informed drug development and clinical translation.

Arsenic Immobilization for Paddy Field and Improvement of Rice (Oryza sativa L.) Growth through Cerium–Manganese Modified Wheat Straw Biochar Application

Arsenic (As) frequently emerges in paddy soils, necessitating measures to combat soil pollution and protect rice crops from As contamination. In this study, a novel functional biochar (MBC) by loading cerium manganese oxide was prepared, and its effects on soil As immobilization and As uptake by rice in two different As-contaminated paddy soils of 68.99 and 158.52 mgAs·kg−1 (marked as soil-L and soil-H, respectively) were detected. The pot experiment manifested that MBC performed better in stabilizing soil As than original biochar. The incorporation of MBC facilitated the conversion of soil active As to the stable state, promoted the growth of rice plants, and reduced As uptake by rice. Specifically, the total plant biomasses for MBC treatment were increased by 16.13–70.07% and 12.36–92.58% in soil-L and soil-H compared with CK (without material input), respectively. MBC treatments resulted in a reduction of As contents by 34.67–60.13% in roots, 43.68–66.90% in stems, and 54.72–64.65% in leaves for soil-L. Furthermore, in soil-H, the As content in rice roots, stems, and leaves showed a decrease by 49.26–79.03%, 87.10–94.63%, and 75.79–85.71% respectively. This study provides important insights for the remediation of As-contaminated paddy soil using MBC.