Breast Cancer Research and Treatment最新文献

Purpose: Breast cancer is the most commonly diagnosed cancer worldwide. To evaluate the safety and efficacy of abemaciclib in combination with endocrine therapy (ET) for the treatment of Hormone Receptor/ Human Epidermal Growth Factor Receptor 2 (HR + /HER2-) advanced or metastatic breast cancer, this systematic review and meta-analysis compared several treatment regimens and patient groups.

Methods: In this systematic review and meta-analysis, we searched (PubMed, Scopus, and the Cochrane from inception to 5 April 2025) to identify the studies that compared abemaciclib plus ET to ET alone. The measure effects used were hazard ratios (HR) for overall survival (OS), progression-free survival (PFS), and invasive disease-free survival (IDFS), while risk ratios (RR) for objective response rate (ORR), clinical benefit rate (CBR), and adverse effects· Forest plots were created using a random effects model, with a p-value < 0·05 was considered statistically significant. This study is registered on PROSPERO (CRD420251009464).

Results: We included fourteen studies comprising 16,116 patients (8592 with abemaciclib plus ET and 7524 with ET alone), abemaciclib plus ET significantly improved PFS (HR 0·54; 95% CI 0·49-0·59, p = 0·00001), IDFS (HR 0·68; 95% CI 0·59-0·78, p = 0·00001), ORR (RR 2·87; 95% CI 1·85-4·44, p = 0·0001), and CBR (RR 1·32; 95% CI 1·14-1·52, p = 0·0002), and a non-statistically significant OS (HR of 0·86; 95% CI 0·74-1·01, p = 0·06). Abemaciclib increased the risk of adverse events; cardiovascular events (4·82 times), increased blood creatinine (8·51 times), nausea (1·95 times), vomiting (2·51 times), abdominal pain (2·64 times), decreased appetite (2·59 times), diarrhea (4·20 times), aspartate aminotransferase (AST) (2·15 times), alanine aminotransferase (ALT) (2·28 times), anemia (3·79 times), thrombocytopenia (5·73 times), leukopenia (5·48 times), neutropenia (8·74 times)· However, it showed a reduced risk of arthralgia (0·73 times).

Conclusion: The combination therapy provides a clinically significant improvement in survival and treatment responses, even though the toxicity is increased but manageable, and requires careful prescription.

Purpose: To improve clinical decision-making in patients with breast cancer receiving CDK 4/6 inhibitors, we examined Duffy status and relative medication modification at Boston Medical Center.

Methods: We performed a retrospective chart review of patients with breast cancer receiving CDK 4/6 inhibitors at Boston Medical Center between January 1, 2021 and June 1, 2024. We included Duffy status as a covariate, where those with unknown Duffy status were assumed to be Duffy non-null.

Results: Of the 71 patients included, race was White in 21% and Black in 54%, where 90% of patients with Duffy-null associated neutrophil count (DANC) were Black. When stratifying by Duffy status, Duffy non-null (38/71) and null patients (21/71) had median pre-treatment nadir absolute neutrophil count (ANC) 2.6 (IQR 1.8) and 1.7 (IQR 1.0) and post-treatment nadir ANC 1.6 (IQR 1.2) and 1.0 (IQR 0.6). Overall, no patients meeting criteria for grades 3-4 neutropenia were hospitalized for neutropenic fever. Older patients had higher odds of dose reduction or treatment delay (adjusted odds ratio [aOR] 3.04, 95% confidence interval [CI] 1.06-9.07). However, patients with DANC had no significant differences in rates of dose reduction or treatment delay [aOR 1.31, 95% confidence interval (CI) 0.37-4.73].

Conclusion: Despite having lower ANC than their non-null counterparts, Duffy null patients on CDK 4/6 inhibitors received standard starting doses without significant differences in dose reduction or treatment delay.

Background: Metastatic metaplastic triple-negative breast cancer (mMpTNBC) is a rare, aggressive subtype with poor responsiveness to standard therapies. Sacituzumab govitecan (SG) is effective in metastatic TNBC (mTNBC), but data in mMpTNBC are limited to case reports.

Patients and methods: This multinational, multicenter, retrospective case series was conducted within the CEBCC-102 real-world evidence project across 18 cancer centers. Female patients with histologically confirmed mMpTNBC treated with ≥ 2L SG outside of clinical trials in Poland, the Czech Republic and Slovakia between August 2021 and June 2025 were included. Clinical data, treatment outcomes, and adverse events (AEs) were collected from medical records and analysed.

Results: Among 303 patients with mTNBC treated with SG in second and later lines within the CEBCC-102 project, 13 women (4.3%) had mMpTNBC and were included in this analysis. Median age was 58 years. PD-L1 CPS ≥ 10 was found in 83% of tested cases. Overall response rate was 36.4%, clinical benefit rate 45.5%, median progression-free survival 3.2 months and median overall survival 8.9 months. Neutropenia (N = 9, 69%) was the most common AE; no febrile neutropenia or treatment discontinuations due to toxicity occurred.

Conclusions: This first international real-world series of SG in mMpTNBC shows clinically relevant activity and manageable toxicity, addressing a critical evidence gap and supporting further prospective studies, particularly in PD-L1-positive disease.

Purpose: We aimed to investigate the prevalence and spectrum of ESR1 mutations alongside cell-free DNA (cfDNA) dynamics in patients with estrogen receptor-positive metastatic breast cancer recruited to the phase II IRIS study who had progressed on first-line aromatase inhibitor (AI) therapy and then continued their AI in combination with Irusostat (40 mg), an irreversible steroid sulfatase inhibitor.

Methods: cfDNA was isolated from 96 serial plasma samples from 24 patients, alongside primary tumour DNA (n = 16), and analysed by next-generation sequencing using a custom-designed mutation panel on the Illumina NovaSeq platform.

Results: Thirteen of 16 tumour DNA samples harboured at least one somatic mutation across nine genes. Twenty one of the 24 patients (88%) had at least one somatic mutation in cfDNA (248 total mutations across 10 genes). Circulating tumour DNA ESR1 mutations (ctESR1m) were the most prevalent, present in 16 patients (76%) with both stable (SD) and progressive disease (PD), showing no clear association with disease progression. Eleven patients had polyclonal ctESR1m within the ligand-binding domain, six at baseline, while five harboured a single ctESR1m variant. Five other patients acquired polyclonal mutations over treatment.

Conclusions: Analysis of serial plasma samples revealed highly dynamic ctESR1m during AI treatment and frequent detection of polyclonal ctESR1m in patients (both with SD and PD) recruited to the IRIS study. These findings, albeit in a limited sample size, underscore the challenge of targeting a single ESR1 mutation and emphasise the need for careful patient selection, specifically those with wild-type ESR1, in trials investigating sequential estrogen-lowering therapies.

Introduction: Breast cancer remains the most frequently diagnosed malignancy among women worldwide. Advances in treatment with the approval of multiple novel therapeutics have led to significant improvements in long-term survival and reduced mortality. Although clinicians are familiar with the more common toxicities linked to targeted therapies, ocular adverse effects often receive less attention. Increasing provider awareness of these potential eye-related toxicities is essential to ensure prompt recognition and timely referral to ophthalmologists for early intervention.

Methods: We reviewed evidence on the prevalence, characteristics, and management of ocular toxicities associated with novel targeted breast cancer therapies.

Conclusion: This review summarizes the major ocular toxicities linked to targeted therapies used in breast cancer and describes current strategies for their effective clinical management.

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.