Breast Cancer Research and Treatment最新文献

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.

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.

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.

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.

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.

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.