Gayfield S, Ma J, Waleski M
… +7 more, Kim J, Stover D, Gatti-Mays M, Jhawar SR, Johnson K, Boghdadly ZE, Ho K
Breast Cancer Res Treat
· 2026 Mar · PMID 41793532
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PURPOSE: Trastuzumab-deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that revolutionized the treatment approach for breast cancer. However, the infectious risk associated with T-DXd is unknown. Here, we evaluate t...PURPOSE: Trastuzumab-deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that revolutionized the treatment approach for breast cancer. However, the infectious risk associated with T-DXd is unknown. Here, we evaluate the infectious risk of T-DXd against trastuzumab-emtansine (T-DM1), an ADC with an identical monoclonal antibody. METHODS: We conducted a retrospective study of consecutive breast cancer patients who received T-DXd or T-DM1. Demographic data, infection risk factors, infection sites, and opportunistic infections were recorded and compared across treatment groups. Multivariable logistic regression was used to evaluate the association between treatment group and infection, adjusting for clinical risk factors. RESULTS: 374 patients received T-DXd or T-DM1, with 126 receiving T-DXd alone, 196 receiving T-DM1 alone, and 52 patients receiving both treatments. Patients who received T-DXd did so as higher line of therapy (p < 0.001), was given more in the palliative setting (100% vs 33.7%, p < 0.001), had more prior immunosuppressive systemic treatment (78.6% vs 16.9%, p < 0.001), were exposed to more significant corticosteroid courses (17.2% vs 4.5%, p < 0.001), and had more hospitalizations during treatment (57.3% vs 27.7%, p < 0.001). Patients treated with T-DXd had a higher incidence of total infections (24.4% vs 14.0%, p = 0.01); in the infected population, unadjusted analysis reveals that those treated with T-DXd had more bloodstream infections (33.3% vs 5.9%, p = 0.004) and more infection-related mortality (18.2% vs 0%, p = 0.01). Three patients developed opportunistic infections on T-DXd, and 2 of the 3 were treated concurrently with high-dose corticosteroids. For multivariate analysis, after adjustment for clinically relevant variables and those associated with the outcome in univariate analyses, T-DXd was not associated with an increased risk of infection (OR = 1.89, 95% CI: 0.85-4.32, p = 0.12). CONCLUSION: Although patients receiving T-DXd had a higher incidence of infection, no significant difference in infectious risk was found after adjusting for several confounding variables. Infection-related mortality and opportunistic infections were rare and only occurred in the T-DXd cohort. Future prospective studies are warranted to more reliably evaluate the infectious risk of T-DXd compared to T-DM1, particularly as T-DXd is increasingly utilized earlier in the treatment course for breast cancer patients.
Giordano A, Graham N, Aizer AA
… +11 more, Tayob N, Pereslete AM, Schoenfeld JD, Leone JP, Davis R, Erick TK, Mayer EL, Winer EP, Krop I, Tolaney SM, Lin NU
Breast Cancer Res Treat
· 2026 Mar · PMID 41793510
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PURPOSE: Triple-negative breast cancer (TNBC) patients with brain metastases have a poor prognosis and limited treatment options. Preclinical and clinical evidence suggests that radiotherapy may act synergistically with...PURPOSE: Triple-negative breast cancer (TNBC) patients with brain metastases have a poor prognosis and limited treatment options. Preclinical and clinical evidence suggests that radiotherapy may act synergistically with immune checkpoint inhibitors. METHODS: We conducted an open-label, single-arm, phase II study of atezolizumab plus stereotactic radiosurgery (SRS) in metastatic TNBC patients with brain metastases. The primary endpoint was progression-free survival (PFS) according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) bi-compartmental model. Secondary endpoints included extracranial objective response rate, overall survival (OS), and safety and tolerability. A safety run-in analysis for dose-limiting toxicity (DLT) was performed after the first 6 patients were enrolled and completed the assessment period. RESULTS: Six patients were enrolled into the safety run-in phase between May 11, 2018 and October 24, 2019. No DLTs were observed, but the study was closed early due to slow accrual. Patients received a median of 2 atezolizumab cycles (range: 2-16), and SRS was administered to all 6 patients. Treatment-related adverse events (TRAEs) occurred in 4 participants (66.7%); all events were grade 2. The median bi-compartmental PFS was 1.3 months (95% confidence interval (CI): 0.95 - NA) and the median OS was 9.7 months (95% CI: 3.6 - NA). The best observed response by RECIST 1.1 criteria was stable disease ≥ 24 weeks in one participant (16.7%). CONCLUSIONS: Concurrent SRS with atezolizumab was feasible in TNBC patients with brain metastases. However, disease outcomes were poor, and the development of effective therapies for these patients remains a significant unmet medical need. CLINICAL TRIAL REGISTRY NUMBER: https://www. CLINICALTRIALS: gov NCT03483012. Trial Open to Accrual: 05/01/2018.
Tolosa P, García-Fructuoso I, Pascual T
… +23 more, Martínez-Sáez O, Cejalvo JM, Servitja S, Fernández Abad M, Benitez Fuentes JD, Brasó-Maristany F, Sanfeliu E, Lema L, Ruano Y, Parrilla L, Roncero AM, Cobos MÁ, Díaz I, Centelles López KA, Sánchez-Bayona R, Alva M, Madariaga A, Villacampa G, Salvador F, Sánchez-Belmonte A, Malumbres M, Prat A, Ciruelos E
Breast Cancer Res Treat
· 2026 Feb · PMID 41762297
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PURPOSE: Estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (MBC) shows variable outcomes after first-line CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET). The prognostic role of PAM...PURPOSE: Estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (MBC) shows variable outcomes after first-line CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET). The prognostic role of PAM50 intrinsic subtypes (IS) in this setting remains unestablished. We evaluated IS and biomarker profiles in the SOLTI-1801 CDK-PREDICT cohort, focusing on real-world second- and third-line progression-free survival (rwPFS-2L and rwPFS-3L). METHODS: This multicenter observational study reports a post hoc secondary analysis of ER+ /HER2- MBC patients previously treated with first-line CDK4/6i plus ET. Baseline metastatic biopsies were molecularly profiled (PAM50, CCNE1, PDCD1) using the nCounter platform. rwPFS-2L and rwPFS-3L were defined from initiation of second- or third-line therapy to progression or death. Kaplan-Meier and Cox models assessed associations with clinical, molecular, and treatment variables. RESULTS: Among evaluable patients (n = 125 for rwPFS-2L; n = 95 for rwPFS-3L), Luminal A/B subtypes represented most cases, while advanced lines showed more aggressive profiles. Median rwPFS-2L was 7.2 months in luminal IS vs. 6.1 in non-luminal (HR 1.40; 95% CI 0.86-2.30); the Basal-like (BL) subtype correlated with significantly shorter rwPFS-2L (HR 3.82; 95% CI 1.07-13.63). In rwPFS-3L, similar trends were seen (6.4 vs. 3.3 months; HR 1.74; 95% CI 0.98-3.08), with BL showing the poorest outcomes (HR 5.63; 95% CI 1.17-27.02). High CCNE1 expression was linked to shorter rwPFS-2L (HR 1.22; 95% CI 1.02-1.47). Targeted agents were frequent in 2L (51%) and capecitabine in 3L (36%), while endocrine monotherapy yielded poorest rwPFS. CONCLUSIONS: Outcomes after CDK4/6i progression differ by PAM50 IS, supporting its role in guiding post-progression treatment.
Drozd C, Curtit E, Jacquinot Q
… +5 more, Roux P, Paget-Bailly S, Gillet V, Meneveau N, Mougin F
Breast Cancer Res Treat
· 2026 Feb · PMID 41746533
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BACKGROUND: Patients with localized breast cancer receiving adjuvant chemotherapy often experience sleep disturbances, especially insomnia, which significantly impacts quality of life. This study primarily aimed to evalu...BACKGROUND: Patients with localized breast cancer receiving adjuvant chemotherapy often experience sleep disturbances, especially insomnia, which significantly impacts quality of life. This study primarily aimed to evaluate the effects of a 12-week exercise program on insomnia, with secondary outcomes on sleep quality, anxiety/depression, fatigue, pain, and exercise adaptation. METHODS: In this randomized controlled multicenter trial, 20 women with non-metastatic breast cancer and clinically diagnosed insomnia were assigned to a control or training group. The training group underwent a 12-week supervised intermittent aerobic exercise program during chemotherapy. The primary outcome was objective total sleep time; secondary outcomes included insomnia severity, sleep architecture, sleep quality, anxiety/depression, fatigue, pain, and cardiorespiratory capacity. Assessments were performed before chemotherapy (T-1), at baseline (T0), and post-intervention (T3) using polysomnography, actigraphy, validated questionnaires, and a maximal graded exercise test. RESULTS: The prevalence of clinical insomnia increased from 47% before diagnosis to 71% at T-1, reaching 100% at T0. Total sleep time did not increase after training (p = 0.97), although sleep fragmentation decreased. Clinical improvement was observed in physical and activity-related fatigue. Finally, both submaximal exercise adaptation parameters (power and VO/HR) and maximal parameters (power, VO peak, VO/HR) significantly improved. CONCLUSIONS: The training did not increase total sleep time, likely due to insomnia's multifactorial origin. However, training yielded beneficial effects on objective sleep quality and exercise-induced adaptation. Future research is needed to investigate the various etiologies of insomnia to develop tailored and personalized management approaches. CLINICAL TRIALS NUMBER: NCT04867096.
Taghian AJ, Aggarwal M, Shui AM
… +3 more, O'Donnell K, Naoum GE, Brunelle CL
Breast Cancer Res Treat
· 2026 Feb · PMID 41733732
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PURPOSE: To describe bioimpedance spectroscopy (BIS) L-Dex values at breast cancer (BC) diagnosis and within the first year post-surgery in a cohort prospectively screened for breast cancer-related lymphedema (BCRL). We...PURPOSE: To describe bioimpedance spectroscopy (BIS) L-Dex values at breast cancer (BC) diagnosis and within the first year post-surgery in a cohort prospectively screened for breast cancer-related lymphedema (BCRL). We also aim to explore BCRL diagnostic overlap utilizing perometry and BIS thresholds. METHODS: Patients undergoing treatment for unilateral BC were prospectively assessed for subclinical BCRL using BIS and perometry at preoperative baseline and during follow-up. Normal baseline scores were considered an absolute arm volume difference < 5% and an L-Dex score between -10 and + 10. BCRL was defined as relative volume change (RVC) ≥ 5% via perometry or L-Dex > 6.5 increase from preoperative baseline during follow-up. RESULTS: The study cohort included 490 patients who underwent same-day perometry and BIS measurements at preoperative baseline, 306 of whom had same-day measurements postoperatively. At baseline, 99 patients (20.2%) had an absolute arm-volume difference ≥ 5%, and 39 patients (8.0%) had an L-Dex value > 6.5. Among patients with follow-up data (N = 306), 36 (11.8%) were diagnosed with BCRL using one or both tools. Of these, 16 patients (44.4%) were diagnosed by RVC-only, 17 (47.2%) by BIS-only, and 3 (8.3%) by both methods. Kaplan-Meier estimates for BCRL at 1, 2, and 3 years were 7.6%, 8.5% and 8.5% for RVC-only; 5.7%, 8.0%, and 15% for BIS-only; and 15%, 18%, and 25% via any method. CONCLUSION: Although BIS and perometry detected a comparable percentage of subclinical BCRL cases, they identified different individuals, indicating that combining both methods may increase case detection. Preoperative baseline measurements are imperative.
Sisca L, Polito MG, Silletta M
… +17 more, La Cesa A, Scafetta R, Donato M, Gullotta CM, Guarino A, Barnini G, Speziale E, Troiano R, Foderaro S, Iuliani M, Simonetti S, Cavalieri S, Calagna S, Cortellini A, Vincenzi B, Tonini G, Pantano F
Breast Cancer Res Treat
· 2026 Feb · PMID 41729350
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BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring minimal residual disease (MRD) and predicting recurrence in early-stage breast cancer (EBC). Despite growing inter...BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring minimal residual disease (MRD) and predicting recurrence in early-stage breast cancer (EBC). Despite growing interest, the prognostic impact of ctDNA detection in this setting remains to be fully elucidated. METHODS: A systematic review and meta-analysis were conducted on prospective studies assessing the association between ctDNA positivity and outcomes in early or locally advanced non-metastatic breast cancer. Databases including PubMed and the Cochrane Library were systematically searched. Studies were included if they reported hazard ratios (HRs) for disease-free survival (DFS) and/or overall survival (OS) according to ctDNA status. Pooled HRs were calculated using random-effects models; heterogeneity was evaluated with the I statistic. RESULTS: Eighteen studies comprising 1670 patients were included. ctDNA positivity was significantly associated with shorter DFS (pooled HR 6.92, 95% CI 3.64-13.13; p < 0.0001; I = 79.7%). This association held across subtypes and timepoints, including post-surgical and longitudinal assessments. In the neoadjuvant setting, ctDNA positivity was associated with increased recurrence risk (HR 6.06, 95% CI 2.85-12.87; p < 0.0001), while in the adjuvant setting, it was an even stronger predictor of relapse (HR 14.76, 95% CI 1.11-197.02; p = 0.042). In a combined early-stage setting, ctDNA positivity correlated with significantly worse DFS (HR 6.55, 95% CI 1.41-30.39; p = 0.017). A non-significant trend was observed for worse OS (HR 3.91, 95% CI 0.78-19.72; p = 0.098). CONCLUSIONS: ctDNA positivity is a robust prognostic biomarker for recurrence in early breast cancer. Its integration into post-treatment surveillance and interventional trials may enable risk-adapted strategies and early therapeutic intervention.
Henry NL, Monkman LK, Griffith K
… +7 more, Scheu K, Ghormley T, Armstrong J, Secor M, Jasthi D, Hawley ST, Guetterman T
Breast Cancer Res Treat
· 2026 Feb · PMID 41729321
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PURPOSE: Ovarian function suppression (OFS) reduces the risk of recurrence of hormone receptor-positive breast cancer but increases the likelihood of toxicity and nonpersistence with endocrine therapy. In addition, rates...PURPOSE: Ovarian function suppression (OFS) reduces the risk of recurrence of hormone receptor-positive breast cancer but increases the likelihood of toxicity and nonpersistence with endocrine therapy. In addition, rates of OFS utilization are lower than expected. To increase understanding of these issues, we sought to identify patient factors associated with the use of OFS injections, as well as treatment decision-making and education needs. METHODS: In this convergent mixed methods designed study, patients receiving OFS, who started then discontinued OFS injections, and who never initiated OFS injections underwent 1:1 semi-structured interviews and completed questionnaires on shared decision-making and medication beliefs. RESULTS: Of 33 enrolled participants, 30 completed both the questionnaires and the interview. Median age was 43 (range 32-55), 24 were white (80%), and 20 (66.7%) had received chemotherapy. Four key themes emerged. (1) There was concern about need for more education, especially about short- and long-term side effects of OFS. (2) For those receiving OFS injections, the decision to take OFS was mainly due to a desire to reduce cancer recurrence risk. (3) For those who stopped OFS, injections were often used as a stop-gap measure, with a preference for permanence of oophorectomy. (4) For those who never took OFS, there was often perceived lack of strong physician recommendation. CONCLUSION: Tailored support for patients is needed to optimize decision-making regarding OFS, related to both potential benefits and risks of OFS in addition to adjuvant endocrine therapy. Educational strategies such as peer mentors or decision aids should be explored in this clinical setting.
Sterpi M, Dreyfus N, Lo Y
… +3 more, Fineberg S, Gill H, Makower D
Breast Cancer Res Treat
· 2026 Feb · PMID 41729316
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PURPOSE: Immune-related adverse events (irAEs) have emerged as a potential surrogate marker for immunotherapy response across tumor types. We evaluated the association between irAEs and pathologic complete response (pCR)...PURPOSE: Immune-related adverse events (irAEs) have emerged as a potential surrogate marker for immunotherapy response across tumor types. We evaluated the association between irAEs and pathologic complete response (pCR) in a racially diverse cohort of patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemoimmunotherapy. METHODS: We conducted a retrospective analysis of 46 patients with early-stage TNBC treated with neoadjuvant chemoimmunotherapy between January 2021 and March 2023 at a single NCI-designated Comprehensive Cancer Center. irAEs, tumor-infiltrating lymphocytes (TILs), and clinicopathologic characteristics were abstracted from the medical record. Associations with pCR were analyzed using Fisher's exact and Wilcoxon rank-sum tests. RESULTS: Among 46 patients, the median age was 60.5 years. Most identified as Black (n = 27, 58.7%) or Hispanic (n = 14, 30.4%). irAEs occurred in 13 patients (28.2%), most commonly hypothyroidism, rash, and arthritis. The pCR rate was 55.8% (24/43 evaluable patients). Patients who developed irAEs were more likely to achieve pCR (84.6% vs. 45.2%, p = 0.039). Higher TILs (median 29%) were associated with pCR both as a continuous variable (p = 0.004) and categorically (p = 0.002), but not with irAE development (p = 0.341). pCR was more common among Hispanic patients (p = 0.005), and inversely associated with Black race (p = 0.003) and older age (p = 0.028). CONCLUSION: IrAEs may serve as a surrogate for treatment response to neoadjuvant chemoimmunotherapy in early TNBC. Additionally, racial and age-based differences in treatment response suggest underlying immunologic or biologic variation. These findings highlight the importance of diverse cohort representation in immunotherapy studies and warrant validation in prospective trials.
Huber E, Gupta GP, Morse R
… +10 more, Abdou Y, Aldrich J, Carey LA, Dees EC, Ray EM, Reeder-Hayes KE, Jones E, Wright JL, Sud S, Casey DL
Breast Cancer Res Treat
· 2026 Feb · PMID 41721913
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PURPOSE: De novo metastatic breast cancer (dnMBC), defined as stage IV disease at initial diagnosis, comprises 6-10% of all metastatic breast cancer cases. Despite therapeutic advances, the unique clinical course of dnMB...PURPOSE: De novo metastatic breast cancer (dnMBC), defined as stage IV disease at initial diagnosis, comprises 6-10% of all metastatic breast cancer cases. Despite therapeutic advances, the unique clinical course of dnMBC remains underexplored, particularly with regard to patterns of first treatment failure and the potential role of metastasis-directed therapy (MDT). This study investigated patterns of treatment failure in patients with dnMBC treated with first line systemic therapy to understand how to better direct local therapies. METHODS: A prospective single-institution database was used to examine patient and tumor characteristics, treatment response, and outcome among 326 patients with dnMBC diagnosed between 2011 and 2022. Anatomic site of first disease progression was categorized as occurring at a pre-existing site only (in breast and/or pre-existing metastatic sites only) vs other (including any combination involving a new metastatic site). Progression patterns were analyzed overall and stratified by clinical subtype. Cumulative incidence functions were used to evaluate time to first treatment failure by site and subtype. RESULTS: Among the full cohort, progression-free survival at 2 years was 32.7% (95% CI [27.3, 38.0]) and at 5 years, 7.8% (95% CI [4.5, 11.2]). In total, 40.8% experienced first progression at pre-existing sites only, while 46.5% progressed at new sites. The cumulative incidence of first progression at a pre-existing site only at 5 years by clinical subtype was: 45.4% for HR + /HER2-, 43.8% for HR-/HER2 + , 39.3% for HR-/HER2-, and 34.5% for HR + /HER2 +. CONCLUSION: A substantial proportion (approximately 40%) of dnMBC patients experience initial progression at pre-existing sites, highlighting a potential role for locoregional and MDT in delaying progression and extending time on first-line systemic therapy. These findings support further prospective evaluation of MDT in dnMBC, with an emphasis on subtype-specific strategies and quality-of-life outcomes.
Vasigh M, Williams AD, Hasler JS
… +10 more, Aggon A, Cohen R, Shulman R, Hayes SB, Anderson PR, Porpiglia AS, Pronovost MT, Pierotti M, Cruz Pico C, Bleicher RJ
Breast Cancer Res Treat
· 2026 Feb · PMID 41712033
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PURPOSE: The use of neoadjuvant chemotherapy (NAC) in breast cancer management has increased, leading to uncertainties in adjuvant treatment benefits. METHODS: We reviewed (cN +) stage II-III breast cancers that underwen...PURPOSE: The use of neoadjuvant chemotherapy (NAC) in breast cancer management has increased, leading to uncertainties in adjuvant treatment benefits. METHODS: We reviewed (cN +) stage II-III breast cancers that underwent NAC and breast-conserving treatment (BCT) between 2010 and 2020 in the National Cancer Database (NCDB). Overall survival (OS) was compared between those who did and did not receive regional nodal irradiation (RNI). RESULTS: The 7137 cN + patients had a mean age of 54.3 ± 10.9. Breast and nodal pCR rates were 25.9% and 35%. RNI was administered in 57.7% (50.0% of the ypN0 and 61.9% of the ypN +). The mean number of nodes removed was 10.3 ± 7.7 in the RNI + and 9.5 ± 7.6 in the RNI- groups (p < 0.01). The mean number of positive nodes was 2.5 ± 4.0 in the RNI + and 1.8 ± 3.5 in the RNI- groups (p < 0.01). In a median follow-up of 68 months, RNI + patients had a worse OS than RNI- patients (79.9% vs. 84.4%, p < 0.001). In the ypN0 population, there was no OS difference between RNI + and RNI- groups (p = 0.4), however, ypN + patients had worse OS if they were RNI + than RNI- (p = 0.007). CONCLUSION: RNI does not improve OS in cN + patients undergoing a complete response from NAC after BCT. Although recurrence cannot be assessed via this data set, these results support individualized decisions to omit RNI in ypN0 patients following NAC and BCT and emphasize the need for further investigation into the potential benefits or harms of RNI in ypN + patients treated with NAC and BCT.
Shinn E, Zahrieh D, DeMichele A
… +40 more, Zdenkowski N, Lemieux J, Mao J, Bjelic-Radisic V, Naughton MJ, Pfeiler G, Gelmon K, Balko JM, Egle D, Zoppoli G, Traina T, Jimenez MM, Novoa SA, Haddad T, Chan A, Ring A, Wolff A, Symmans WF, Lorenzo JP, Sabanathan D, Burstein HJ, Nowecki ZI, Pristauz-Telsnigg G, Brufsky A, Bellet-Ezquerra M, Foukakis T, Novik Y, Rubovszky G, Singer CF, Muehlbacher K, Filho OM, Goulioti T, Law E, Partridge AH, Carey LA, Zoroufy A, Hlauschek D, Fesl C, Mayer EL, Gnant M
Breast Cancer Res Treat
· 2026 Feb · PMID 41706231
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Tse SSW, Wong HCY, Charbonneau F
… +16 more, Cao JQ, Hijal T, Kerba M, Waddle MR, Lee SF, Sonis ST, Wolf JR, van den Hurk C, Corbin K, Marta GN, Wong C, Chan RJ, Herst PM, Hill R, Chow E, Kim H
Breast Cancer Res Treat
· 2026 Feb · PMID 41697485
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INTRODUCTION: While randomized clinical trials (RCT) confirmed superiority of Mepitel Film (MF) in reducing acute radiation dermatitis (ARD) compared to standard-of-care (SoC), the incremental cost difference has limited...INTRODUCTION: While randomized clinical trials (RCT) confirmed superiority of Mepitel Film (MF) in reducing acute radiation dermatitis (ARD) compared to standard-of-care (SoC), the incremental cost difference has limited its use. A cost-effectiveness analysis (CEA) was conducted from a Canadian healthcare payer's perspective to guide policy decisions. METHODS: A decision model was constructed to perform a CEA for MF compared to SoC (moisturizers) for prevention of grade 2 or higher ARD following adjuvant hypo-fractionated whole-breast radiotherapy (RT) based on a Canadian multicentre RCT. Direct and indirect cost data were collected from two oncology centers in Canada. Quality-of-life (QoL) utility values were derived from mapping Dermatology Life Quality Index (DLQI) scores for patients with grade 2 or higher ARD at week 6 of RT to EQ-5D. A willingness-to-pay (WTF) threshold of CAD 50,000 per quality-adjusted life years (QALY) gained was used. Deterministic and probabilistic sensitivity analyses were performed to address uncertainty in decision model assumptions. RESULTS: Base case analysis demonstrated that MF is cost-effective in preventing grade 2 or higher ARD as compared with SoC with an incremental cost-effectiveness ratio (ICER) of CAD 3366 per QALY gained. When indirect costs were included, MF resulted in an ICER of CAD 2823 per QALY gained. One-way sensitivity analysis showed that the results were most sensitive to the QoL utility value for ARD. Probabilistic sensitivity analysis confirmed that MF demonstrates 100% probability of cost-effectiveness at a $50,000 per QALY threshold. CONCLUSIONS: MF is a cost-effective intervention for preventing high-grade ARD and should be recommended for patients with breast cancer undergoing adjuvant RT.
Soyano Muller AE, Goodridge DN, Mo Q
… +14 more, Whiting J, Khakpour N, Lee MC, Laronga C, Armaghani AJ, Han H, Soliman H, Costa R, Loftus L, Hoover SJ, Kiluk JV, Jameel Z, Czerniecki BJ, Khong HT
Breast Cancer Res Treat
· 2026 Feb · PMID 41697438
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PURPOSE: Hormone receptor-positive (HR+), HER2-negative breast cancer represents the most common subtype of breast cancer and is characterized by a risk of late recurrence. Neoadjuvant endocrine therapy with aromatase in...PURPOSE: Hormone receptor-positive (HR+), HER2-negative breast cancer represents the most common subtype of breast cancer and is characterized by a risk of late recurrence. Neoadjuvant endocrine therapy with aromatase inhibitors (AIs) is a well-tolerated option in postmenopausal women; however, strategies to enhance its efficacy are needed. Combination of AI with immunotherapy is a promising approach. We evaluated the efficacy and safety of combining an AI with the anti-program death ligand 1 antibody durvalumab in the neoadjuvant setting. METHODS: This single-arm, phase II study used a Simon two-stage design. Postmenopausal patients with early-stage HR+/HER2-negative breast cancer received durvalumab every 4 weeks plus daily AI for 6 months prior to surgery. The primary endpoint was the achievement of a modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0. RESULTS: Seventeen patients were enrolled and received durvalumab plus daily AI for six months before surgery. Treatment was well tolerated, with most adverse events being grade 1-2. A clinical complete response was seen in 58.8% of patients, although no pathologic complete responses occurred. Among the first 14 patients, one achieved mPEPI 0, which did not meet criteria to proceed to stage two. Overall, three patients (17.6%) achieved mPEPI 0. CONCLUSION: Neoadjuvant durvalumab plus AI was safe but demonstrated limited pathologic efficacy in this unselected HR + HER2-negative population. Favorable long-term outcomes support further investigation of immunoendocrine combinations in HR + HER2-negative breast cancer in biomarker-selected subgroups. TRIAL REGISTRATION: NCT03874325. Date of registration. 12-03-2019.
Wang J, Bayard S, Assel M
… +8 more, Kim M, Moo TA, Vickers AJ, Carlsson SV, Mehrara B, Morrow M, Nelson JA, Tadros AB
Breast Cancer Res Treat
· 2026 Feb · PMID 41689671
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PURPOSE: Electronic patient-reported outcomes (ePROs) are used postoperatively to detect complications through real-time symptom monitoring. This study examines whether alerts triggered through the "Recovery Tracker" (RT...PURPOSE: Electronic patient-reported outcomes (ePROs) are used postoperatively to detect complications through real-time symptom monitoring. This study examines whether alerts triggered through the "Recovery Tracker" (RT), an ePRO system, predict 30-day re-admission or re-operation after lumpectomy. METHODS: We retrospectively reviewed breast cancer patients who underwent lumpectomy at a single institution between August 2018 and May 2024. Patients who completed RT surveys on postoperative days 1-5 were included. Symptom alerts categorized as red (urgent) and yellow (less urgent) were analyzed using generalized additive and univariable logistic regression models. RESULTS: Among 8723 included patients, 2552 (29%) triggered at least one alert. Yellow alerts were more common than red across all days. Most red alerts were related to pain or vomiting; most yellow alerts were related to pain or wound redness. Overall, symptom severity and interference decreased over time. Triggering an alert was associated with increased risk of 30-day re-admission or re-operation (odds ratio [OR] 2.86, 95% confidence interval [CI] 1.64-5.03; p < 0.001). However, absolute event rates were low (re-admission 0.3%, re-operation 0.2%), and the absolute risk increase associated with any alert was minimal (0.7%, 95% CI 0.2%-1.1%). CONCLUSION: Although triggering at least one ePRO alert is associated with an increased relative risk for re-admission or re-operation, the absolute risk increase of re-admission and re-operation is very small. With enhanced follow-up by the clinical team among patients who trigger an alert, patients can be reassured that most symptoms will resolve on their own or can be treated with outpatient intervention.
Brown NL, Howell SJ, Papantoniou D
… +10 more, Eriksson O, Bergqvist M, Williams A, Kavanagh A, Backlund A, Albu-Kareem A, Elinder E, Larsson K, Uminska M, Ekholm M
Breast Cancer Res Treat
· 2026 Feb · PMID 41670750
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PURPOSE: Thymidine kinase 1 activity (TKa) has previously been demonstrated as a prognostic biomarker for progression-free survival (PFS) in hormone receptor-positive, HER2-negative metastatic breast cancer (MBC), but it...PURPOSE: Thymidine kinase 1 activity (TKa) has previously been demonstrated as a prognostic biomarker for progression-free survival (PFS) in hormone receptor-positive, HER2-negative metastatic breast cancer (MBC), but its optimal use remains undefined. This study evaluated the prognostic performance of TKa across multiple sampling time points and thresholds in patients receiving first-line CDK4/6 inhibitor plus aromatase inhibitor therapy. METHODS: TKa was measured (DiviTum® assay) at baseline (BL), cycle 1 day 15 (C1D15), and cycle 2 day 1 (C2D1) in patients enrolled in the PDM-MBC study (n = 90). Thresholds for PFS discrimination were identified using maximally selected rank statistics, with predefined cut-offs tested for comparison. Prognostic performance was assessed using the corrected Akaike information criterion (AICc) and Harrell's concordance index (C-index). RESULTS: TKa was prognostic at all time points. Data-derived thresholds identified groups with differing PFS and overall survival (OS), and predefined cut-offs (≥ 50, ≥ 100, ≥ 250 DiviTum® units of Activity [DuA]) also discriminated survival outcomes. BL and C2D1 models performed better than C1D15 and comparably to multi-time-point models. Among patients with BL TKa ≥ 250 DuA, suppression to < 100 DuA at C1D15 was associated with longer median PFS (23.9 vs. 10.3 months; p = 0.034). CONCLUSION: Baseline TKa provides prognostic information, with potential added value from repeated testing in those with high baseline levels. TKa behaves as a continuous biomarker of risk, and continuous modelling may offer more clinically informative individual risk estimation, while thresholds may retain value for specific clinical contexts. Validation in larger cohorts is warranted to support integration into routine practice.
Klugman MF, Aboumrad M, Chen R
… +4 more, Marshall CH, Canzoniero JV, Wolff AC, Visvanathan K
Breast Cancer Res Treat
· 2026 Feb · PMID 41670749
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BACKGROUND: Prognostic factors and treatment outcomes have been identified in estrogen receptor (ER) low-positive early-stage breast cancer. This study evaluates outcomes in ER low-positive de novo metastatic breast canc...BACKGROUND: Prognostic factors and treatment outcomes have been identified in estrogen receptor (ER) low-positive early-stage breast cancer. This study evaluates outcomes in ER low-positive de novo metastatic breast cancer (dnMBC) patients. METHODS: We conducted a retrospective cohort study of adults with human epidermal receptor-2 negative dnMBC diagnosed from 2018 to 2021 in the National Cancer Database. We classified ER status as negative (< 1%), low-positive (1-10%), or positive (11-100%). We compared overall survival by ER status using Cox regression, adjusting for age, metastatic sites, race/ethnicity, comorbidities, insurance, and treatment receipt. We then analyzed the cohort with ER low-positive patients stratified by progesterone receptor (PR) status, defined as negative (< 1%) or positive (1-100%). Among ER low-positive patients, we evaluated survival by first-course treatment. We distinguished cytotoxic chemotherapy from cyclin-dependent kinases 4 and 6 inhibitor (CDK4/6i) therapy based on the timing of endocrine therapy and chemotherapy. RESULTS: Among 27,672 patients, 3% had ER low-positive dnMBC. ER low-positive/PR-positive patients had longer median (95% CI) survival [19.8 (14.8-24.8) months] compared to both ER low-positive/PR-negative [11.8 (10.6-13.5) months] and ER-negative [12.9 (12.5-13.6) months] patients. ER low-positive/PR-positive patients had decreased risk of death compared to ER-negative patients (hazard ratio = 0.84, 95% CI 0.71-1.00), while ER low-positive/PR-negative patients did not. ER low-positive dnMBC patients who received chemotherapy followed by endocrine therapy (± CDK4/6i) or endocrine therapy + CDK4/6i had improved or similar survival compared to patients who received chemotherapy alone. CONCLUSIONS: PR-positivity identifies a subgroup of ER low-positive dnMBC patients with superior survival compared to ER-negative patients. First-line treatment incorporating endocrine therapy may be appropriate to consider for ER low-positive patients.
Martin E, Chichua M, Chiodi CK
… +17 more, Zyumbileva P, Lapidari P, Pagliuca M, Gillanders E, Barbier A, Bertaut A, Boinon D, Martin AL, Everhard S, Golli L, Jouannaud C, Kaderbhai C, Mery B, Rigal O, Franzoi MA, Vaz-Luis I, Di Meglio A
Breast Cancer Res Treat
· 2026 Feb · PMID 41667883
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PURPOSE: Longitudinal studies are essential for investigating outcome evolution among cancer survivors. However, longitudinal designs pose specific challenges, such as attrition and premature dropout. We aimed to assess...PURPOSE: Longitudinal studies are essential for investigating outcome evolution among cancer survivors. However, longitudinal designs pose specific challenges, such as attrition and premature dropout. We aimed to assess experiences and perspectives on participation in longitudinal studies among survivors of early-stage breast cancer, and inform interventions aiming to reduce attrition. METHODS: Motivation, facilitators, challenges, and perspectives regarding participation in a longitudinal study were qualitatively assessed via interviews and focus groups. A thematic content analysis was performed. RESULTS: Between May and August 2023, 30 patients previously enrolled in the longitudinal CANTO cohort study (NCT01993498) were included: 17 participated in individual semi-structured interviews and 13 in two separate focus groups involving distinct participants. We identified four key themes: (1) joining the study as an expression of purpose and personal security, (2) ongoing engagement, as a response to flexible processes, a reassuring study environment, and personal commitment, (3) ongoing engagement, challenged by accumulating (practical and emotional) burdens and a reduced sense of connection to the study, and (4) participant-identified needs for a more supportive study experience. Findings emphasized the importance of enhancing communication with study participants, flexibility enabling decentralized participation, reducing burden of patient-generated data via repetitive questionnaires, supporting navigation of study procedures and minimizing the risk of a digital divide, and routinely disseminating study findings. CONCLUSION: These findings will inform strategies to reduce attrition and enhance the overall participant experience in longitudinal studies.