Breast Cancer Research and Treatment最新文献

Purpose: The RxPONDER trial showed improved outcomes in premenopausal hormone positive breast cancer (BC) with 1-3 nodes and OncotypeDx (RS) score ≤ 25 with adjuvant chemotherapy (Chemo) use. This study aims to determine whether adjuvant chemotherapy improves survival outcomes in young women (≤ 50 years) with node positive, hormone receptor-positive breast cancer and oncotypeDx score ≤ 25.

Methods: The 2010-2018 National Cancer Database was used to include M0 BC patients aged ≤ 50 years with N1-N3 lymph nodes stages, any T stage, and RS ≤ 25. Kaplan-Meier (KM) and multivariate (MV) propensity score (PS) weighted Cox model was used to compare survival between patients without and with chemo.

Results: 8628 women were included of which 3519 (40.8%) received chemo. KM curves showed that chemo use had better survival at 10 years (93 vs 91%) compared to hormonal therapy alone. Hazard Ratio (HR) comparison between the 2 groups favored chemo [0.602(0.482,0.751)]. Subgroup analysis for mortality benefits showed favorable results in Caucasian race [0.512(0.348,0.752)], both age groups of 18-40 years [0.429(0.217,0.847) and 41-50 years [0.585(0.394,0.869)], and RS 12-25 [0.549(0.379,0.795)].

Conclusions: Based on our analysis, chemo use was noted in 40.8% of young, lymph node + BC patients with an RS score of 0-25. This group of patients had a relative overall survival advantage of around 40% with chemo use, further supporting the findings of the RxPONDER trial. This benefit is of particular significance in patients with a RS of 12-25. The survival advantage was present in all patients less than 50 years, regardless of the age subgroups.

Introduction: An emerging challenge in early breast cancer (eBC) is improving risk assessment through the use of biomarkers. Clinical guidelines have recommended urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1. This study aimed to validate the prognostic and predictive impact of uPA/PAI-1.

Patients and methods: From a prospective cohort of 1270 patients (PiA-study, Prognostic assessment in routine Application, NCT01592825), concentrations of uPA and PAI-1 were determined in fresh tumor tissue (n = 813) by ELISA (FEMTELLE®; LOXO Diagnostics). The uPA/PAI-1 status was defined as low if both uPA and PAI-1 levels were low and as high if one or both were elevated. Primary objectives were the distribution of the uPA/PAI-1 status and its association with clinical/histopathological parameters. Secondary objectives were the association of the uPA/PAI-1 status with recurrence-free interval (RFI), overall survival (OS), and benefit from adjuvant chemotherapy.

Results: A low uPA/PAI-1 status was observed in 37.6% (306 of 813) of the entire cohort and in 47.9% (181 of 378) of those classified as intermediate-risk patients (≥ 35yrs, ≤ pN1, G2, sHR positive/HER2 negative). A low uPA/PAI-1 status was associated with parameters that predict  a favorable prognosis. Overall, 96.7% (95% CI 94.5-98.9) of patients with a low uPA/PAI-1-status remained recurrence-free at five years and 87.2% (95% CI 84.1-90.3) with a high uPA/PAI-1 status even after adjustment to tumor size, nodal status, grading, steroid hormone receptor (sHR) status and HER2 status (adjusted HR 2.6, 95% CI 1.29-5.23). Among intermediate-risk patients without chemotherapy (n = 197), the prognostic value was even more pronounced (HR 10.10, 95% CI 1.13-16.12). Similar results were observed for OS. Only patients with a high uPA/PAI-1 status appeared to benefit from chemotherapy (adjusted HR 0.28, 95% CI 1.12-0.07, p = 0.07).

Conclusion: This prospective analysis confirms the uPA/PAI-1 status as an independent prognostic factor and suggests a predictive impact considering benefit from chemotherapy.

Purpose: Adjuvant endocrine therapy (AET) lowers breast cancer recurrence risk and improves overall survival. However, some women have suboptimal adherence, mainly due to difficulties coping with side effects. We identified different long-term AET adherence trajectories and investigated associated side effects.

Methods: We used multisource data from the French national VICAN2 study, which interviewed women two years after breast cancer diagnosis. We measured AET adherence using the monthly proportion of days covered (PDC) over 41 months (median) after enrolment in VICAN2. Group-Based Trajectory Modelling (GBTM) helped identify adherence trajectory groups.

Results: The 637 women included were categorized into three trajectories: continuous optimal adherence (70.6%), late non-adherence (19.8%), and near-simultaneous discontinuation (9.6%). The most common side effects were hot flashes (78.2%) and joint pain (74.4%). Living alone, always or regularly feeling sad or blue, not receiving chemotherapy, and switching AET were all associated with increased odds of belonging to the near-simultaneous discontinuation group. Younger age (44-54 years), low household income, no contact with a social worker, not receiving chemotherapy, being first prescribed aromatase inhibitors for AET, always experiencing hot flashes, and occasionally experiencing joint pain were all associated with increased odds of belonging to the late non-adherence group.

Conclusion: This study provides valuable insight into the dynamics of AET adherence patterns and related side effects. Identifying women who experience hot flashes and joint pain two years after diagnosis may strongly predict future non-adherence. Managing these side effects could foster long-term adherence and optimise health outcomes.

Purpose: Due to increased sensitivity for early detection compared to mammography, breast MRI is increasingly used for surveillance screening in women with breast cancer, especially in those diagnosed at a young age or with dense breasts. We investigated factors associated with receipt of breast MRI in women with operable breast cancer.

Methods: Our cohort included women with stage 0-III breast cancer seen at an urban academic medical center from January 2018 to June 2023. We collected demographic and clinical data from the electronic health record. The primary endpoint was receipt of surveillance breast MRI > 1 year after diagnosis. Multivariable logistic regression was used to identify factors associated with breast MRI use.

Results: Among 1989 racially/ethnically diverse women, a total of 355 (17.8%) women received at least one surveillance breast MRI. In multivariable analysis, Hispanic and non-Hispanic Black women were less likely to receive surveillance breast MRI than non-Hispanic White women (odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.31-0.63 and OR = 0.57, 95% CI = 0.38-0.86, respectively). However, compared to women with commercial insurance, women with Medicaid were more likely to receive surveillance breast MRI (OR = 1.57, 95% CI = 1.10-2.25). Results were similar when restricting to women diagnosed under age 50 or with dense breasts. Receipt of breast MRI was associated with smaller breast tumor size at recurrence (p = 0.016). Among women who received breast MRI, 22.5% had a false-positive biopsy compared with 11.5% of women who received mammography alone (p < 0.001).

Conclusion: Receipt of breast MRI among breast cancer survivors differed by race, ethnicity, and insurance payor mix. These disparities in the use of breast MRI highlight the need for more standardized guidelines surrounding the optimal role of surveillance breast MRI among women with breast cancer, which can inform targeted public health interventions aimed at promoting more equitable screening practices in this population.

Objectives: To evaluate the clinical benefit of the vinorelbine-gemcitabine every two weeks (VNR-GEMQ2W) regimen in patients with hormone receptor-positive (HR +)/HER2- advanced breast cancer (ABC) treated at a tertiary care hospital and with previous progression on cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i).

Study design: A retrospective analysis was conducted on women treated for HR + /HER2-ABC, with VNR 25 mg/m² and GEM 1000 mg/m² administered every two weeks between 2019 and 2024 at a single hospital.

Main outcome measures: Progression-free survival (PFS), overall response rate (ORR), overall survival, and treatment-related adverse events (AEs) evaluated according to CTCAE version 5.0 were retrospectively analyzed. A subanalysis of the data was performed based on major prognostic factors.

Results: A total of 53 patients were included, with a median age of 56.70 years. The majority had visceral metastases (81.13%). Patients had received a median of three prior lines of therapy - two lines of endocrine therapy and one line of chemotherapy. The median follow-up time was 28 months [interquartile range 15-34]. The median PFS was 4.27 months (95% confidence interval 3.25-6.34), and ORR was 18.87%. Grade ≥ 3 neutropenia was the most frequent severe AE (10.77%), with no treatment discontinuations due to toxicity. Only one case of grade 2 alopecia was reported (1.88%).

Conclusions: Administering after CDK4/6i and capecitabine, VNR-GEMQ2W regimen shows activity in HR + /HER2- ABC and a manageable safety profile. This regimen should be considered as a potential control arm in the design of future clinical trials targeting HR + /HER2- ABC.

This commentary appraises Pieniążek et al.'s study on hematologic prognostic markers in sacituzumab govitecan-treated mTNBC, emphasizing residual confounding, absent Trop-2 data, limited modeling flexibility, and incomplete handling of missingness. Methodological refinement and integration of biological, longitudinal, and clinical variables are proposed to enhance prognostic accuracy and translational applicability.

Background: Quality of life (QOL) data for the Brazilian population with breast cancer are scarce. This study aimed to evaluate QOL in Brazilian women with early-stage breast cancer treated with adjuvant endocrine therapy (ET) and to explore its relationship with patients' clinical and social characteristics and type of healthcare insurance.

Methods: We performed a cross-sectional study among women with early-stage estrogen receptor-positive (ER +) invasive carcinoma of the breast in Brazil. Eligible patients who had received locoregional care and had undergone adjuvant ET for more than 6 months were contacted in person during clinic visits. The EORTC QLQ-C30-V3 and QLQ-BR23 scales were used as questionnaires to assess the QOL of patients.

Results: From June 2021 to March 2024, 774 women with ER + early-stage breast cancer from 14 Brazilian institutions were contacted. A total of 347 women (44.8%) were treated at private institutions. The mean age was 56.5 years (SD 11.9). The median duration of ET use was 3.2 years (SD, 2.1). Multivariate regression analysis revealed that treatment at a public institution was a significant predictor of higher nausea and vomiting scores (p = 0.042), pain (p = 0.0008), financial difficulty (p < 0.0001), arm symptoms (p < 0.0001), and breast symptoms (p < 0.0001).

Conclusion: In this cohort, patients treated at public institutions had lower QOL. Younger age (< 60 years), presence of comorbidities, and ovarian suppression associated with ET were key predictors of poor QOL. These findings provide insights for guiding the development of tailored interventions for the Brazilian population.

Purpose: To evaluate and compare patient perceptions of artificial intelligence (AI) use in mammogram interpretation across academic and safety-net healthcare settings.

Methods: We offered a 29-item survey to patients visiting our safety-net (SNH) and academic (ACH) hospital breast imaging clinics between 04/2024-06/2024 and 02/2023-08/2023, respectively. Demographic data was compared between populations using Chi-squared tests. We used ORs (95% CI) to estimate response odds by patient factors. Significant group differences were further analyzed via multivariable regression.

Results: A total of 924 [ACH: 518(56.1%), SNH: 406(43.9%)] surveys were collected. Participants from the ACH were older (≥ 70 years: 20%vs3.1%, p < 0.001), mostly identified as Non-Hispanic White (56%vs7.2%, p < 0.001), had higher income (≥ $100,000: 49%vs3.2%, p < 0.001), higher education (≥ college: 71%vs20%, p < 0.001) and higher self-reported knowledge of AI (68%vs56%, p < 0.001) compared to SNH. Use of AI alone or as a second reader was accepted by 74%, with SNH participants being less likely to accept [OR(95%CI): 0.71(0.53-0.96), p = 0.02]. SNH participants were more likely to request a reading by AI following radiologist-interpreted abnormalities [1.83(1.35-2.49), p < 0.001], rate AI as the same or better than a radiologist at detecting cancer [1.54(1.12-2.15), p = 0.01], and have higher concern regarding data privacy [1.87(1.22-2.93), p = 0.01]. Higher education [1.99(1.33-2.99), p < 0.001] and self-reported AI knowledge [1.98(1.38-2.83), p < 0.001] were associated with higher acceptance of AI use, while Non-Hispanic Black race [0.40(0.25-0.65), p < 0.001] was associated with lower acceptance when controlled for other covariates.

Conclusion: Significant differences exist in patients' views of AI between the demographically distinct academic and safety-net populations. Our study revealed lower educational attainment and Non-Hispanic Black race as independent factors associated with lower acceptance of AI.

Purpose: Decision-making for chemotherapy in early breast cancer (EBC) in OA (older adults: age ≥ 65 years) is complex due to frailty, multimorbidity, and competing risks for mortality. Magnuson (2021) developed a chemotherapy toxicity prediction score, CARG-BC; its external validation can improve generalizability.

Objectives: CARG-BC's ability to predict grade 3 + chemotoxicity in OA with EBC (primary), unplanned healthcare use, and changes to chemotherapy protocol (secondary).

Methods: A single center retrospective cohort study comprising OA with EBC who received (neo) adjuvant chemotherapy from 2013-2023. Clinical, demographic, CARG-BC, and healthcare usage variables were extracted from patient records. Risk groups based on CARG-BC score were compared using T-test (continuous variables) & χ2 test (categorical variables). Toxicity risk based on CARG-BC score was assessed using logistic regression. The predictive ability of the CARG-BC score was evaluated by calculating AUC.

Results: Of 243 patients, the median age was 70 years (range 65-86), 99.6% female, 80.2% with comorbidities, 33.7% with polypharmacy, 28.8% living alone, and 8.2% seen in the geriatric oncology clinic. Over half (53.9%) had grade 3 + toxicities. Healthcare utilization included 19.8% of patients with at least one unplanned clinic visit, 29.6% an emergency care visit, and 14.4% a hospitalization. The median CARG-BC score was 7 (IQR 3, 8) and the CARG-BC AUC was 0.76 (95% Confidence interval [CI] 0.70, 0.82). The odds of grade 3 + toxicity is increased by 1.33 times per CARG-BC point increase.

Conclusion: The CARG-BC model retained good discrimination for grade ≥ 3 chemotoxicity and should be used in shared-decision-making with OA.

Purpose: In breast cancer, a low skeletal muscle index (SMI) and prognostic nutritional index (PNI) negatively affect patient outcomes. However, the prognostic implications of changes in these values in patients with metastatic breast cancer (MBC) remain unclear. We evaluated the association between baseline levels and changes in SMI and PNI during eribulin treatment and patient outcomes.

Methods: We retrospectively analyzed 67 patients with MBC treated with eribulin. SMI and PNI were assessed at baseline (pre-SMI, and pre-PNI) and at disease progression; changes from baseline were calculated. Patient outcomes were compared according to baseline status and direction of change.

Results: SMI and PNI were not significantly correlated (p = 0.26, R = 0.02). High pre-SMI and high pre-PNI were associated with significantly improved overall survival (OS) (SMI; hazard ratio [HR] = 0.54, p = 0.04, PNI; HR = 0.33, p < 0.001). Patients with SMI gain during eribulin had longer OS than those with stable SMI or loss (HR = 0.48, p = 0.04), whereas PNI increase was not significantly associated with OS (HR = 0.74, p = 0.32).

Conclusion: Baseline SMI and PNI provide complementary prognostic information in patients with MBC receiving eribulin. Furthermore, on-treatment SMI gain, but not PNI increase, was associated with improved survival. Monitoring and enhancing skeletal muscle mass may improve outcomes, highlighting the importance of integrating supportive care strategies during chemotherapy.