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Estrogen receptor expression in residual breast cancer following neoadjuvant chemotherapy.
Premji, Sarah , Keeney, Michael, Choong, Grace M. , Leon‐Ferre, Roberto A. , Haddad, Tufia C. , O’Sullivan, Ciara C. , Hobday, Timothy J. , Ruddy, Kathryn J. , Peethambaram, Prema P. , Hoskin, Tanya L. , Tevaarwerk, Amyé , Giridhar, Karthik V. , Cathcart-Rake, Elizabeth , Yadav, Siddhartha , Ingle, James N. , Boughey, Judy C. , Goetz, Matthew P.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 529-529

10.1200/jco.2025.43.16_suppl.529 Get It

529 Background: Neoadjuvant chemotherapy (NAC) is commonly administered to patients (pts) with estrogen receptor alpha (ER) negative (immunohistochemistry [IHC] 0%) and ER-low (IHC 1-10%) breast cancer (BC). For pts without pathological complete response (pCR), ER expression may differ between baseline and residual BC following NAC. We previously demonstrated adjuvant endocrine therapy (ET) omission in ER-low early-stage BC was associated with significantly worse overall survival (OS); however, this effect was restricted to pts with residual BC following NAC and those with higher baseline ER levels (IHC 6-10%) (Choong et al., ASCO 2024). Here, we assessed how often ER was expressed in residual invasive BC for pts treated with NAC for ER-negative and ER-low BC. Methods: Weidentified pts with pre-treatment (tx) ER-negative and ER-low (regardless of HER2 expression) stage I-III BC treated with NAC who underwent BC surgery at Mayo Clinic Rochester between 2009 and 2023. ER IHC was performed in a CAP/CLIA laboratory. We evaluated ER expression in residual invasive BC for pts without pCR. The percent of pts with a post-tx change in ER status was estimated and reported with 95% Wilson confidence intervals. Results: 955 pts (838 [88%] pre-tx ER-negative; 117 [12%] pre-tx ER-low) met inclusion criteria, of whom 69% had HER2-negative and 31% HER2-positive BC. The median age at diagnosis was 52 (range: 24-86). 496 (52%) had residual BC. Residual BC was more common in HER2-negative versus (vs) positive tumors (56% vs 42%, p < 0.001) but did not differ significantly by ER status (ER-negative 51% vs ER-low 57%, p = 0.22). Of those with residual BC, 277/496 (56%) had ER re-testing. Rates of ER re-testing did not vary for pre-tx ER-negative vs -low (57% vs 51%, p = 0.37) but were significantly lower for HER2-positive vs HER2-negative tumors (39% vs 62%, p < 0.001). Among those with post-tx testing, 31/277 (11%, 95% CI: 8-15%) had an increase in ER expression from pretreatment levels (defined as ER IHC < 1% to either 1-10% or > 10%; or ER IHC 1-10% to > 10%). In these 31 pts, the original NAC was for either TNBC (21/31; 68%) or HER2+ BC (10/31; 32%). In pts with pre-tx ER-negative BC, 27/243 (11%, 95% CI: 8-16%) had ER expression in the residual BC including 14/243 (6%, 95% CI: 3-9%) with ER > 10% and 13/243 (5%, 95% CI: 3-9%) with ER 1-10%. For pts with baseline ER-low BC, 4/34 (12%, 95% CI: 5-27%) had ER > 10% in the residual BC. Among the 31 pts where ER increased following NAC, 21/31 (68%) received adjuvant ET, including 17/18 if ER was > 10% in the residual disease and 4/13 in those with ER 1-10%. Conclusions: In pts treated with NAC for ER-negative or ER-low BC not achieving pCR, we identified higher ER expression in the residual breast cancer in > 10% of pts. Given that omission of ET in ER-low BC with residual cancer following NAC is associated with worse survival, repeat biomarker testing should be considered in those without pCR, and ET individualized according to ER expression.
Treatment-related neutropenia as a predictor of response to adjuvant palbociclib in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109).
Martín, Miguel , Haddad, Tufia C. , Steger, Guenther G. , Suga, Jennifer M. , Loibl, S., Machacek‐Link, Jana, Gauthier, Eric , Scovil, Sara, Fanucci, Kristina A. , Dueck, Amylou C. , Mayer, Erica L. , Zdenkowski, Nicholas , Novik, Yelena , Lemieux, Julie , Traina, Tiffany A , Bellet, Meritxell , Wolff, Antonio C. , Hlauschek, Dominik , Gnant, Michael , DeMichele, Angela

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 526-526

10.1200/jco.2025.43.16_suppl.526 Get It

526 Background: The PALLAS trial (NCT02513394) investigated the efficacy of the addition of palbociclib (palbo) to standard adjuvant endocrine therapy (ET) to reduce breast cancer recurrence. Previous analyses of this trial have not shown significant benefit of combination palbo+ET over ET alone. Given prior data showing that extent of neutropenia is associated with response to palbo and other cell cycle-specific therapies, we evaluated whether extent of neutropenia could identify responders to palbo in the adjuvant setting. Methods: PALLAS is a global, open-label, phase III trial that randomized patients (pts) with stage II-III hormone-receptor positive, HER2-negative breast cancer to receive ET for ≥5 years with or without standard-dose palbo for 2 years in 28-day cycles. The primary endpoint is invasive disease-free survival (iDFS). For this exploratory analysis, the palbo population was classified into pts with treatment-emergent high-grade neutropenia (HGN) with maximum grade ≥3 (absolute neutrophil count <1000), or low-grade/no neutropenia (LGN) with maximum grade <2; these groups were compared to each other and to the ET alone group for 5-year iDFS outcomes. Logistic regression examined individual baseline characteristics associated with HGN during the first 3 cycles within the palbo group. Impact of HGN during the first 3, 6, and 12 cycles on iDFS was tested using univariate and multivariable landmark Cox regression. Results: The safety population included 5736 pts, 2840 allocated to palbo+ET, 2896 to ET alone. Prior publications reported no new safety signals, low rates of serious infection, and no grade 5 treatment-related events. The palbo+ET group consisted of 1006 (35.4%) LGN and 1834 (64.6%) HGN. 5-year iDFS results are shown in the table. Pts who received palbo+ET and developed HGN by the end of cycle 6 had significantly improved 5-year iDFS compared to those who received ET alone (p=0.04), which remained statistically significant when adjusting for body mass index (BMI), prior chemotherapy, and race. Multivariable logistic regression showed lower BMI, prior chemotherapy, Asian race, and prior mastectomy were significantly associated with HGN (all p<0.05). Conclusions: In this exploratory analysis of the phase III PALLAS adjuvant trial, addition of palbo to ET appeared to be superior to ET alone in pts who developed HGN in the first 6 cycles of treatment but not in those who had LGN. These findings are consistent with observations in the metastatic setting suggesting that neutropenia could be a useful biomarker for palbo concentration and efficacy. Clinical trial information: NCT02513394 . Maximum grade neutropenia measured at end of cycle: 5-year iDFS Palbo+ET HGN (%) Palbo+ET LGN (%) ET alone (%) Hazard Ratio p-value 3 84.9 84.4 1.06 0.54 84.9 82.9 1.17 0.06 6 85.6 84.9 1.08 0.44 85.6 83.4 1.19 0.04 12 86.3 85.9 1.06 0.57 86.3 85.0 1.12 0.20
Impact of a collaborative care-based symptom intervention model on chemotherapy adherence in patients with breast cancer.
Ruddy, Kathryn J. , Grzegorczyk, Veronica , Hassett, Michael J. , Greenmyer, Jacob R. , Pachman, Deirdre R. , Storandt, Michael H. , Kroenke, Kurt , Mitchell, Sandra A , Smith, Ashley Wilder , Cheville, Andrea

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 1543-1543

10.1200/jco.2025.43.16_suppl.1543 Get It

1543 Background: Treatment toxicity may limit the ability of cancer patients to receive all recommended cycles of therapy. Four to six cycles of docetaxel plus cyclophosphamide (TC) is a common adjuvant chemotherapy regimen for early-stage breast cancer. We assessed the impact of routine collection of patient-reported outcomes (PROs), coupled with a collaborative care model-based symptom management intervention, on the number of cycles of TC received by patients with breast cancer. Methods: The Enhanced, EHR-facilitated Cancer Symptom Control (E2C2) trial was a cluster-randomized, pragmatic clinical trial, conducted between March 2019 and January 2023 at Mayo Clinic Rochester and within the Mayo Clinic Health System in Minnesota and Wisconsin. Patients regularly reported the severity of 6 SPPADE symptoms (Sleep deficit, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue) on 11-point numerical rating scales. Each symptom score was interpreted as none to mild (0-3), moderate (4-6), or severe (7-10). The E2C2 intervention included symptom management education modules, clinician decision support aids, and the option to discuss severe symptoms with a nurse, physical therapist, or social worker. Patients with breast cancer who received at least one cycle of TC were included in this analysis. We compared the number of cycles of docetaxel and cyclophosphamide completed by patients in the control condition versus those in the intervention condition. Results: We identified 198 patients with breast cancer who received TC during the control condition and 128 who received TC during the intervention condition. Median age was 61.3 years in the control group and 60.3 years in the intervention group, and 94% and 95% were white, respectively. Those receiving treatment during the control condition, on average, completed 3.53 cycles of docetaxel, while those receiving TC during the intervention condition completed 3.77 cycles ( p = 0.014). Seventy-eight percent in the control group completed at least 4 cycles of docetaxel, compared to 84% in the intervention group. Those receiving TC during the control condition completed an average of 3.71 cycles of cyclophosphamide, compared to 3.78 cycles in the intervention condition (p = 0.231). Eighty-four percent of patients in the control group and 86% in the intervention group completed at least 4 cycles of cyclophosphamide. Conclusions: Routine PRO surveillance, coupled with guideline-based collaborative care interventions, was associated with completion of a greater number of cycles of docetaxel. These findings suggest that routine symptom surveillance and management may enhance the docetaxel tolerance profile and improve treatment adherence in patients with early-stage breast cancer, allowing for delivery of an optimized treatment course.
DISCO App: A patient intervention to reduce the financial burden of cancer in a diverse patient population.
Hamel, Lauren M. , Dougherty, David W. , Heath, Elisabeth I. , Mabunda, Lorna, Austin, Teneisha , Assad, Hadeel , Tadesse, Eyouab, Grossi, Roman , Jarbo, Nouran, Eggly, Susan , Kim, Seongho , Mamdani, Hirva Mansurali

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.tps1659 Get It

TPS1659 Background: Financial toxicity, the material and psychological burden of treatment cost, affects up to half of people with cancer and can affect adherence and survival. Financial toxicity is a health equity issue, disproportionately affecting Black patients. Patient education about cost and patient-provider cost discussions are recommended to mitigate financial toxicity but occur infrequently. Our goal is to mitigate financial toxicity through a tailorable education and communication intervention, the DISCO App. The DISCO App was shown to be feasible, acceptable, and preliminarily effective at prompting cost discussions and improving related outcomes in a pilot trial. The aim of the ongoing trial is to test the effectiveness of the DISCO App on short- and longer-term outcomes for Black and White patients with cancer. Methods: This study is a longitudinal RCT. Oncologists are eligible if they treat patients with solid tumors at the trial site. Patients of participating oncologists are eligible if they are ≥ 18 years of age; identify as Black or White; can read and write in English; have an email address; and were diagnosed with a solid tumor for which systemic therapy is a likely recommended treatment. Strata were created to balance arms by patient race, income, age, and sex. Upon consent, patients are randomized to one usual care arm (1) or one of two intervention arms (2 and 3). All patients are asked to allow one treatment discussion with their oncologist to be video recorded for analysis. Prior to the recording, intervention patients utilize the DISCO App on an iPad. The DISCO App includes a video about treatment costs, ways to manage costs, and the importance of discussing costs with oncologists. Once patients enter their socio-demographic information (e.g., employment, insurance) and any financial concerns, they receive a tailored list of questions to ask their oncologist. Arm 3 patients receive an intervention booster via email two months after the recording. Patients complete measures at baseline, right after the recording, and at 1, 3, 6 and 12 months after the recording. Measures assess outcomes including cost discussions, communication quality, cost knowledge, self-efficacy for cost management, referrals for support, short- and longer-term financial toxicity, and treatment adherence. The patient-oncologist interaction is the unit of analysis and we will use multi-linear models to compare outcomes by arm. We anticipate recruiting up to 15 oncologists and 240 patients. Data collection began in March 2021 and will continue until July 2025. Participants to date include 13 oncologists and 192 patients (116 Black, 76 White). Most patients completed the baseline assessment (n=164), the post-interaction assessment (n=137), and at least 1 follow-up assessment (n=132); 125 treatment discussions have been recorded. The IRB reviewed the trial in December 2024 and approved continuation. Clinical trial information: NCT04766190 .
A pilot single-arm, pragmatic trial in progress of in-home versus in-clinic subcutaneous nivolumab administration through Cancer Care (connected access and remote expertise) Beyond Walls (CCBW) program.
Lou, Yanyan , Mazza, Gina L. , Howard, Chanice, Confiado, Sunnie, Baskin, Amber, Jackson, Alexis, Fritsche, Angela Hazel, Lopez, Kai Castrezana , Brown, Jade, Nolan, Luci, Chapin, Dustin, Beliles, Gregory, Tan, Winston, Kharfan‐Dabaja, Mohamed A. , Nowakowski, Grzegorz S. , Dronca, Roxana , Mazza, Gina L , Elantably, Dina , Jones, Jeremy C , Jackson, Alexis, Lopez, Kaila, Nolan, Luci, Smith, Nathan , Willman, Cheryl L.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.tps1657 Get It

TPS1657 Background: Cancer treatments are traditionally administered in clinical settings, which can isolate patients from their familiar environments and exacerbate physical, psychosocial, and financial burdens. Travel requirements further amplify these challenges, particularly for underserved populations. Studies indicate that patients prefer receiving care at home, and international models have demonstrated the safety of home-delivered chemotherapy since the 1990s; however, no U.S. clinical trial data exists. In response, Mayo Clinic has developed the Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) program, a distributed cancer care delivery model that expands access to quality cancer care by bringing it to the home environment, providing in-home cancer treatment, lab testing, telemedicine, and community paramedic support. This trial evaluates the safety, acceptability, and impact of home-based subcutaneous (SC) nivolumab (Nivo) administration compared to in-clinic treatment within the CCBW initiative. Methods: This open-label, single-arm trial evaluates the impact of SC Nivo administration location—home versus infusion center—on patient reported cancer care experience, patient-preferred treatment location, acceptability, safety, and patient-reported outcomes. Eligible adult patients (ECOG 0-1) receiving IV Nivo for an FDA-approved indication and residing within 75 miles of Mayo Clinic Florida will transition to SC Nivo, receiving two initial in-clinic cycles. If tolerated without injection reactions, four cycles will be administered at home before resuming in-clinic treatment. Exclusion criteria include concurrent investigational/standard treatments or contraindications to immunotherapy. Fifty patients will be enrolled, with an estimated 75% (n=38) providing cancer care ratings after 8 weeks in-clinic and 8 weeks at-home, offering 85% power to detect a mean difference in ratings of 0.50 standard deviations. The primary endpoint is within-patient change in cancer care rating (0–10 scale, CAHPS Cancer Care Survey) comparing 8 weeks of in-clinic vs. at-home care. Secondary endpoints include patient-preferred treatment location, comfort with home injections, safety (grade 3+ adverse events), function (EORTC QLQ-F17), symptoms (PRO-CTCAE), side effect impact (GP5), and healthcare utilization (ER visits, hospitalizations). Cost will be assessed as a tertiary endpoint. The trial has FDA approval (IND #170079), Mayo Clinic IRB approval (#23009663), and ClinicalTrials.gov registration (NCT06265285). Enrollment began in April 2024, with an expected accrual period of 24 months. To date, 10 patients have been enrolled, and final analysis is expected 2.5 years after trial activation. Clinical trial information: NCT06265285 .
Reduced length of stay as an alternative to full outpatient CAR-T services.
Benson, Hollie, Torabi, Yeganeh, Foreman, John W., John, Sunny St, Yennie, Julia, Wilson, CiCi N, Rosenthal, Allison , Foreman, John, John, Sunny St, Wilson, CiCi N

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e13575 Get It

e13575 Background: Cellular therapies continue to expand in diversity, complexity, and financial impact leading clinicians and administrators to seek innovative care options. The paradigm of late has been to move to an outpatient treatment model. However, centers may not find this model to be the safest option for their patients. This pilot project aims to use established outpatient resources to reduce hospital length of stay (LOS) for patients receiving ciltacabtagene autoleucel in an inpatient setting. Methods: Chart review was conducted for 42 patients treated for incidence of CRS, days to onset, LOS, readmissions, and hospital expenses and charges. The cohort showed an 83% incidence of CRS with a mean onset of 7 days. 71% of CRS was limited to Grade 1. The mean LOS was 10.8 days and the readmission rate was 21%. Financial modeling estimated overall cost reduction to range from $13,000 to $20,000 per patient for a LOS of 3 days. A pilot project to reduce LOS was developed with inclusion/exclusion criteria prioritizing patient safety and likelihood of remaining in the outpatient setting. A workflow for administering one dose of tocilizumab for Grade 1 CRS in the outpatient setting was also established to counterbalance readmissions. The goal of the pilot is to reduce the overall LOS from 10 days to 3 days while maintaining readmission rates and comparable charge to reimbursement ratios on net operating income. Results: In the first five months, 25 patients were screened for eligibility. 60% were deemed eligible and 66% of those were discharged after three days. No patients discharged after a minimum admission were readmitted within three days. Current data suggests the readmission rate within 30 days is higher than baseline at 40%. The overall LOS of patients enrolled in the pilot upon infusion was six days. Patients successfully remaining on the pilot have a 60% reduction in LOS. There have been no major safety events. Conclusions: We identified that select patients could be managed in the outpatient setting after a minimum three-midnight hospital admission. A pilot project was developed using our comprehensive care model coupled with a minimum LOS of 3 days. After discharge, patients are followed daily in our outpatient clinic using in-person visits and remote patient monitoring. To counterbalance readmissions, Grade 1 CRS has been treated in the outpatient clinic including administration of tocilizumab. Early data indicates that the workflow is reducing LOS by 60% under patient selection criteria capturing approximately 60% of patients. While readmissions in the first three days post discharge have been parried, there is opportunity to further reduce readmissions in the first 30 days following CAR-T infusion. We anticipate the pilot will reduce costs without negatively impacting reimbursement or readmissions.
Best practices and key barriers for light chain (AL) amyloidosis patient care at US specialized amyloidosis centers: An analysis of ARC-ASPIRE.
Nativi-Nicolau, José , Fajardo, Johana, Galloway, Alyssa, Khella, Sami, Kumar, Nisith, Liedtke, Michaela , Lousada, Isabelle , Patrick, Tiffany, Moffitt, Colleen , Klein, Lori , Tamariz, Gabriela, Veeraraghavalu, Karthikeyan, Haddad-Angulo, Alexandra, Kumar, Nisith

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e13574 Get It

e13574 Background: AL (amyloid light chain) amyloidosis is associated with poor prognosis especially if diagnosis occurs with cardiac involvement. Current AL treatments target the plasma cell clone producing the light chains that misfold, aggregate and deposit in various tissues. The multi-organ manifestations of AL amyloidosis require a multidisciplinary care team of hematologist-oncologists, cardiologists, and other healthcare providers (HCPs) for comprehensive, patient-centric management. Since 2022, Amyloidosis Stakeholder Partnerships for Impact, Reach & Equity (ASPIRE), facilitated by Amyloidosis Research Consortium (ARC) has been bringing together biotech and pharmaceutical companies with the shared goal of optimizing amyloidosis patient care. Through this study, ARC-ASPIRE sought to document and share the current best practices and key barriers to patient-centric amyloidosis care at US specialized amyloidosis centers (SACs). A broad range of stakeholders in amyloidosis care – healthcare providers at SACs, patients, referring physicians, and patient advocacy group representatives – were interviewed for this study. This abstract presents findings relevant to the management of patients with AL amyloidosis. Methods: Structured interviews were conducted between December 2023 and February 2024 with 77 amyloidosis stakeholders (physicians, advanced practice providers, registered nurses from 17 SACs, patients, referring physicians, and patient advocacy group representatives), including 12 hematology-oncologists and 8 AL patients. SACs were selected to be representative of current US amyloidosis care, based on geography, amyloidosis patient volume, years since establishment, and types of amyloidosis treated. Results: Three-quarters of participating SACs treat AL patients under a single multidisciplinary amyloidosis program. Multidisciplinary care is facilitated by regular team meetings, dedicated clinic days, and informal communications across specialties. At diagnosis, collaboration between cardiology and hematology-oncology ensures AL patients are accurately diagnosed and promptly treated. Sixty percent of SACs have a centralized intake system, and patients suspected with AL are prioritized to ensure an appointment within 1 week of referral. Key barriers were delayed or missed diagnosis due to low awareness of AL amyloidosis within community oncologists, travel burden to SACs, lack of seamless medical records sharing and telehealth regulations. Conclusions: The best practices outlined in this study serve to educate AL amyloidosis and non-AL amyloidosis HCPs for better multidisciplinary collaboration and early diagnosis. The key barriers identified should be addressed to improve patient care.
Hydroxyurea vs. hypomethylating vs. other agents in chronic myelomonocytic leukemia: A retrospective inspection of treatment strategies among 457 Mayo Clinic patients.
Yousuf, Muhammad , Tefferi, Ayalew , Gangat, Naseema , Pardanani, Animesh , Mangaonkar, Abhishek A. , Faldu, Priyansh, Abdelmagid, Maymona, Aperna, Fnu, Fathima, Saubia , Alsugair, Ali, Reichard, Kaaren K. , He, Rong, Patnaik, Mrinal M. , Fathima, Saubia , Csizmar, Clifford M. , Lasho, Terra L. , He, Rong

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 6579-6579

10.1200/jco.2025.43.16_suppl.6579 Get It

6579 Background: Treatment strategies in chronic myelomonocytic leukemia (CMML) are not standardized and include hydroxyurea (HU) and hypomethylating agents (HMA). In a phase 3 study comparing HU and decitabine, in proliferative CMML, response rates were higher for decitabine (56% vs 31%; p<0.01) but overall survival was similar (p=0.67) between the two groups (Itzykson, R. JCO, 2023. 41:1888). In the current retrospective study, we examined the survival impact of different treatment strategies among 457 Mayo Clinic patients with CMML. Methods: The current study was conducted under institutional review board approved minimum risk protocols allowing retrospective patient data collection and analysis. Diagnostic criteria were according to the International Consensus Classification (Arber et al. Blood 2022. 140:1200). All statistical analyses were conducted using JMP 17 software. For survival analysis, patients were censored at time of allogeneic stem cell transplant (ASCT). Results: A total of 457 patients were considered (median age 72 years; 68% males). 209 patients received CMML-directed therapy: HU (N=102), HMA (N=78; azacitidine 32 and decitabine 46). Responses were adjudicated separately for leukocytosis and anemia; normalization of leukocyte count was achieved in 21% vs. 16 % (p<0.01) for HU vs. HMA and overall response in anemia in 1% vs. 9% (p=0.02), respectively. Overall survival did not appear to be impacted by different treatment strategies at any stage of CMML; (i) treated vs. untreated (p=0.3), (ii) HU vs. HMA for first-line therapy (p=0.3), and (iii) HU/HMAs vs. other drugs as first-line therapy (p=0.1). Blast transformation-free survival (BTFS) was also similar between HU vs. HMA as well as HU/HMA vs. other drugs. In univariate analysis, BTFS was inferior in patients receiving CMML-directed therapy (p<0.01); the particular association (HR 2; 95% CI 1.2-3.3) retained its significance in multivariable analysis that also included other risk factors for BTFS: bone marrow blast ≥10% (HR 4.3), circulating blast ≥2% (HR 2.7), WBC ≥13 x 10 9 /L (HR 1.8), and ASXL1 mutation (HR 1.7). Conclusions: In the current retrospective study that included a large number of patients with CMML, chemotherapy with HU or HMA did not appear to affect overall survival but might have increased the risk of blast transformation. The study also suggests superiority of HU for the treatment of leukocytosis and HMA for anemia. Predictors of blast transformation-free survival (BTFS) in 457 patients diagnosed with chronic myelomonocytic leukemia (CMML). BTFS Univariable analysis p-value (HR) Multivariable analysis p-value (HR) CMML-directed therapy <0.01 (2.9; 1.8-4.7) <0.01 (2; 1.2-3.3) Bone marrow blasts ≥10% <0.01 (12.4) 0.01 (4.3) Circulating blasts ≥2% <0.01 (5.2) <0.01 (2.7) WBC ≥13 x 10 9 /L <0.01 (2.9) 0.02 (1.8) ASXL1 mut <0.01 (2.1) 0.02 (1.7)
Interferon signaling and outcomes in triple-negative breast cancer (TNBC) in FinXX, CALGB 40603 (Alliance) and real-world clinico-genomic data.
Chumsri, Saranya , Liu, Yi , Deshmukh, Sachin Kumar , Leon‐Ferre, Roberto A. , Zahrieh, David M. , Torres, Evanthia T. Roussos , Sikov, William M. , Knutson, Keith L. , Thompson, E. Aubrey , Carter, Jodi M. , Joensuu, Heikki , Boughey, Judy C. , Ingle, James N. , Couch, Fergus J. , Lustberg, Maryam B. , Stover, Daniel G. , Partridge, Ann H. , Carey, Lisa A. , Sledge, George W. , Goetz, Matthew P. , Knutson, Keith L.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 569-569

10.1200/jco.2025.43.16_suppl.569 Get It

569 Background: Several studies established the prognostic role of both the amount and locations of tumor-infiltrating lymphocytes (TILs) in TNBC. Three distinct immunotypes were described based on the amount and locations of TILs: immune enriched (IN), immune excluded, and immune desert. Using single-cell spatial transcriptomic analysis in the Mayo Clinic TNBC cohort, our previous studies showed the central role of interferon (IFN) signaling in IN phenotype. Herein, we evaluated the association between IFN and outcomes in TNBC in 3 independent datasets. Methods: NanoString IO360 was performed in 114 samples from FinXX (NCT00114816) to generate 22-gene IFNα and 33-gene IFNγ signatures. RNA sequencing was performed in 388 samples from CALGB 40603 (NCT00861705). 3038 TNBC samples were tested by WTS (NovaSeq; Caris Life Sciences, Phoenix, AZ). Median values were used as cut-offs for high vs low IFNγ RNA expression and 18-gene IFNγ signature scores. Caris Life Science CODEai was used to evaluate real-world overall survival (OS) obtained from insurance claims and calculated from tissue collection to last contact using Kaplan-Meier estimates. Chi-square, Mann-Whitney U, ANOVA, and Cox regression were used. Results: A high 22-gene IFNα signature score was associated with significantly improved recurrence-free survival (RFS) in FinXX (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.14-0.74, p 0.007) and OS (HR 0.28, 95%CI 0.12-0.66, p 0.003). Similar findings were observed with 33-gene IFNγ signature with significant improvement in RFS (HR 0.21, 95%CI 0.09-0.51, p < 0.001) and OS (HR 0.18, 95%CI 0.08-0.44, p < 0.001). Furthermore, in CALGB 40603, both IFNα and IFNγ scores were positively associated with pathologic complete response (pCR: IFNα p 0.019 and IFNγ p 0.007) and residual cancer burden (RCB: IFNα p 0.044 and IFNγ p 0.013). Using the Caris data platform to further validate, we identified 2899 TNBC patients (pts) with genomic and clinical outcome data. High IFNγ expression was associated with significant improvement in OS (25.95 vs 17.43 months; HR 0.65, 95% CI 0.59 – 0.72, p < 0.001). Similarly, pts with high IFNγ signature scores had significant improvement in median OS (25.79 vs 16.22 months; HR 0.66, 95% CI 0.6 – 0.73, p < 0.001). Conclusions: This study underscores the pivotal role of IFN signaling in TNBC. High IFNα and IFNγ signatures were consistently associated with improved RFS, OS, higher pCR rates, and lower RCB across clinical trial cohorts and real-world data. These findings signify IFN signaling as a potential key biomarker and therapeutic target in TNBC. Support: U10CA180821, U10CA180882, U24CA196171; Breast Cancer Research Foundation, Mayo Clinic Breast Cancer SPORE (P50CA116201-17), Bankhead Coley, W81XWH-15-1-0292, P50CA015083, R35CA253187; https://acknowledgments.alliancefound.org . Genentech. Clinical trial information: NCT00114816 and NCT00861705 .
Association of lifestyle factors and pathological characteristics in patients with early breast cancer and overweight/obesity: Results from the Breast Cancer Weight Loss (BWEL) trial.
Sposetti, Caterina , McCall, Linda, Weiss, Anna , Thomson, Cynthia A. , Hahn, Olwen, Minasian, Lori M. , Nebeling, Linda , Hopkins, Judith O. , Bernstein, Vanessa , Stearns, Vered, White, Julia , Ligibel, Jennifer A. , Ballman, Karla V. , Goodwin, Pamela J. , Hershman, Dawn L. , Paskett, Electra D. , Mayer, Erica L. , Winer, Eric P. , Partridge, Ann H. , Carey, Lisa A.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 561-561

10.1200/jco.2025.43.16_suppl.561 Get It

561 Background: Obesity and other lifestyle factors are associated with breast cancer (BC) risk and outcomes. These relationships appear to vary in pre- vs postmenopausal women. Here we explore associations between pathological features, diet quality and physical activity (PA) in patients (pts) with BC enrolled in the BWEL (Alliance for Clinical Trials in Oncology A011401) trial, stratifying for menopausal status. Methods: BWEL is a phase III trial evaluating the impact of a weight loss intervention on disease outcomes in 3180 pts with stage II-III HER2– BC and body mass index ≥27 kg/m 2 . The first 542 BWEL pts underwent assessment of PA (7-Day PA Recall) and diet (24-hour Diet Recall) at enrollment. Healthy Eating Index 2020 (HEI) score (0-100, higher value = healthier diet) and minutes/week (min/wk) of moderate/vigorous PA (MVPA) were calculated. Estrogen receptor (ER) and progesterone receptor (PR) expression level (%) were abstracted from pathology reports. Analyses of links between HEI score, MVPA min/wk, % ER/PR, stratified by menopausal status, were conducted using t-tests; differential associations by menopausal status used linear regression models with interaction term. Results: In 523 pts with available pathology data, 76.5% had ER/PR+ BC, 56.2% were postmenopausal. Median HEI score was 50.1 (range 18.1-96.4), median MVPA min/wk was 0 (range 0-630), median time from diagnosis to enrollment was 10.0 months (range 2.4-13.1). In postmenopausal pts, higher diet quality was linked to increased % ER and PR (HEI above vs below median, mean % ER 78.0 vs 66.1, p=0.012; mean % PR 57.7 vs 43.1, p=0.004). The relationship between HEI score and % ER/PR differed significantly by menopausal status (interaction term of menopausal status and % ER: p=0.006; and % PR: p=0.012); there were no significant associations between HEI scores and % ER/PR in premenopausal pts. There were no significant associations between PA and % ER/PR. Conclusions: Healthier diet was associated with higher % ER and PR in postmenopausal pts with BC, but no relationship was seen in premenopausal pts. These data suggest that lifestyle factors may influence BC pathologic features related to outcomes in older women. Support: U10CA180821, U10CA180882, UG1CA189823, U24CA196171, https://acknowledgments.alliancefound.org . Clinical trial information: NCT02750826 . % ER mean (SD) p value % PR mean (SD) p value Post-Menopausal HEI* score≤50.1 [n=134]>50.1 [n=156] 66.1 (43.3)78.0 (36.8) 0.012 43.1 (41.8)57.7 (41.0) 0.004 MVPA † min/wk0 [n=147]≥1 [n=147] 74.5 (39.3)70.3 (41.2) 0.37 50.0 (41.8)53.0 (42.0) 0.41 Pre-Menopausal HEI* score≤50.1 [n=124]>50.1 [n=103] 70.5 (38.5)65.5 (43.0) 0.15 53.5 (41.1)49.1 (43.0) 0.43 MVPA † min/wk0 [n=112]≥1 [n=113] 66.3 (41.0)66.3 (41.2) 0.99 49.5 (41.4)52.6 (42.7) 0.59 *Healthy Eating Index. † Moderate/Vigorous Physical Activity.