Breast Cancer Research and Treatment最新文献

Background: Data on neoadjuvant treatment with trastuzumab biosimilars, particularly CT-P6, in combination with pertuzumab, are limited. This study evaluates the efficacy, tolerability, and immunogenicity of CT-P6 plus pertuzumab and chemotherapy, in routine clinical practice for HER2-positive early breast cancer, including translational biomarker analyses related to pathologic complete response (pCR).

Methods: Prospective, multicenter, observational study in 102 patients with HER2-positive early breast cancer. Patients received hospital-preferred neoadjuvant regimens protocols, with (scheme 1 and 3) or without anthracyclines (scheme 2). The primary endpoint was pCR, defined as the absence of invasive tumor in both the breast and axillary lymph nodes (ypT0/ypTis and ypN0). Translational endpoints included soluble HER2, anti-trastuzumab CT-P6 antibodies, and exploratory response-related modeling approaches supported by machine learning techniques.

Results: Among patients who underwent surgery, pCR (ypT0/ypTis and ypN0) was achieved in 57.43% of cases, with no significant differences between anthracycline-based and non-anthracycline-based regimens. Soluble HER2 and anti-trastuzumab CT-P6 antibodies were not significantly associated with pCR. Treatment was well-tolerated; the most relevant Grade 3-4 treatment-related adverse events were diarrhea (2.25%) and asthenia (0.50%). No immunogenicity or clinically relevant cardiotoxicity was observed.

Conclusions: Trastuzumab CT-P6 combined with pertuzumab and chemotherapy can be used in neoadjuvant treatment for HER2-positive early breast cancer, showing pCR rates comparable to the reference trastuzumab and without evidence of immunogenicity. Exploratory analyses of soluble HER2 and anti-trastuzumab CT-P6 antibodies did not demonstrate a significant association with pCR, although this possibility cannot be excluded. Their assessment contributes to the translational understanding of biosimilar integration into curative regimens.

Trial registration: The study has been registered in Clinicaltrials.gov ( https://clinicaltrials.gov/study/NCT06907082 ).

Purpose: Investigate skeletal morbidity (SM) in metastatic breast cancer (MBC) patients undergoing CDK4/6 inhibitors (CDK4/6is) and endocrine therapy (ET).

Methods: In this retrospective study we evaluated skeletal morbidity - defined as the occurrence of skeletal-related events (SREs) in metastatic bone and fragility fractures in non-metastatic bone - in 214 MBC patients who had received ET and CDK4/6is. As secondary aim, we compared VF progression, defined as a new fracture or worsening of a pre-existing fracture at spine CT scan, between 121 patients receiving ET alone (cohort A) and 121 patients on ET plus CDK4/6is (cohort B), balanced using propensity score.

Results: Among the 147 patients (68.7%) with bone metastases, 59 (40.1%) experienced SREs including non-vertebral pathologic fractures (17 patients, 11.6%), pathologic VF progression (21 patients, 14.3%), spinal cord compression (3 patients, 2.0%), radiation to bone (18 patients, 12.2%). Considering the non-metastatic bone, 3 out of 214 patients (1.4%) experienced new non-vertebral fragility fractures, and 26 patients (12.2%) had fragility VF progression. In the comparative study, pathologic VF progression in metastatic bone was 38.3% in cohort A and 29.1% in cohort B (p = 0.093). The corresponding fragility VF progression rate in non-metastatic bone was 22.3% and 12.4% (p = 0.031).

Conclusions: A considerable proportion of women with MBC treated with CDK4/6is + ET experience SM on both metastatic and non-metastatic bone. Patients treated with CDK4/6is + ET had lower SM than those on ET alone.

Purpose: Postmastectomy radiotherapy (PMRT) reduces locoregional recurrence and improves survival in high-risk breast cancer (BC), yet its real-world use remains variable. Population-based data on PMRT utilization and guideline adherence in Switzerland are lacking. We evaluated PMRT patterns, determinants, and adherence to ASCO-ASTRO-SSO recommendations among women with stage I-III BC over two time periods and interpreted findings in the context of the 2025 guideline.

Methods: This retrospective, population-based study analyzed data from seven Swiss cancer registries, including Eastern Switzerland (2003-2005; n = 4,246), and from Eastern Switzerland alone (2015-2017; n = 976). Eligible patients were women aged ≥ 18 years with stage I-III invasive BC treated by simple mastectomy. PMRT use was examined across original ASCO-ASTRO-SSO-defined risk groups: low-risk (T1-2N0), intermediate-risk (T1-2N1, T3N0), and high-risk (T4 or N2-3). Multivariable regression identified clinicopathologic determinants of PMRT use. Trends in PMRT guideline adherence and regional nodal irradiation (RNI) were evaluated within the framework of evolving clinicobiologic risk paradigms. Overall survival (OS) was analyzed using Kaplan-Meier and Cox regression methods.

Results: Overall PMRT utilization remained low (25-30%) across both periods. PMRT was independently associated with younger age, higher T-/N-stage, lymphovascular invasion (p < 0.01), positive margins, G3 histology, and ER negativity (p < 0.05). Adherence to guidelines improved in low-risk patients (93% to 96%) but declined in high-risk patients (64% to 54%), with decreasing PMRT use in T4 (53% to 27%), N2 (73% to 57%), and N3 disease (83% to 73%). In contrast, PMRT use increased among intermediate-risk patients (23% to 39%), particularly in T1-2N1 disease (19% to 38%) and in the presence of adverse features: LVI + (21%), HER2 + (23%), TNBC (30%), G3 (38%), and age < 45 years (57%). Supraclavicular/axillary RNI declined overall but increased in node-negative patients, paralleling reduced axillary dissection and increased sentinel biopsy (26% to 70%). PMRT was not associated with a statistically significant OS benefit; supraclavicular RNI showed a non-significant trend toward improved OS in N2-3 disease.

Conclusions: This first national analysis provides real-world evidence that PMRT utilization in Switzerland remains low, with underuse in high-risk patients and selective, biologically informed escalation in intermediate-risk disease. While patterns reflect evolving multidisciplinary care, persistent gaps in ASCO-ASTRO-SSO guideline implementation underscore the need for continued surveillance and individualized, risk-adapted PMRT decision-making.

Purpose: To provide an updated review of the literature on physical activity (PA) intervention studies, their characteristics, and their effect size estimates for PA behavior change among early post-treatment breast cancer survivors (BCS).

Methods: Eligible studies were published between 2014-2025 in English, were quasi- or randomized controlled trials, studied BCS ≤ 5 years post-treatment, tested a PA intervention, and assessed PA behavior. We searched PubMed, APA PsycINFO, Embase, and CINAHL (latest search October 2025; CINAHL June 2020). Extracted data included study, participant, intervention, and outcome descriptors. The ROB 2 assessed risk of bias. A random effects model on post-intervention Cohen's d standardized mean differences (SMD) values meta-analysis was performed.

Results: Twenty-two RCTs with a total sample size of 2,390 (mean = 109, range = 26-692) were included. All included BCS were female, were on average 57 years old, and predominantly (> 60%) non-Hispanic White. Most study populations were mixed in terms of cancer stage and treatment type. Intervention duration ranged from 6-104 weeks. All studies except one were partially or fully home-based. All behavioral counseling interventions were theory-based. The overall SMD was d = 0.36 (95% confidence interval: 0.22, 0.50) in favor of the intervention. Two studies had some concerns for risk of bias; all others were rated as low.

Conclusion: The present updated review found a small-to-moderate positive effect of PA interventions on PA behavior change among early post-treatment BCS. We note some shifts in the participant samples and study design since the originally published review. Practical implications for improving the reporting of future research include following established reporting guidelines to enhance reporting transparency, which would allow for more precise quantification of specific intervention effects and deeper contextual understanding of this body of work.

Purpose: De novo oligometastatic breast cancer (OMBC) is often defined as up to five metastases in two or fewer organs at presentation. Studies have suggested favorable outcomes for patients with OMBC; however, management remains controversial. We analyzed outcomes of patients with de novo OMBC treated with physician-expressed curative intent at a single institution.

Methods: We identified patients by performing a keyword search for terms of interest within institutional electronic medical records. We defined OMBC as four or fewer metastases in one organ. Primary surgery was required for inclusion in the analytic cohort. Recurrence-free survival (RFS) and overall survival (OS) were evaluated using Kaplan-Meier methods.

Results: Thirty-nine patients were identified: 12 hormone receptor-positive (HR+)/HER2+ , 2 HR-negative (HR-)/HER2-, 21 HR+ /HER2-, and 4 HR-/HER2+ . Thirty-three patients (84.6%) had 1 metastasis at diagnosis. Median age was 47 years (28-69). Twenty-nine patients (74.4%) underwent adjuvant radiation to the breast. Two-thirds of patients underwent metastasis-directed therapy. Five-year OS was 77% (95% CI 61-95%). Median RFS was 7.1 years (95% CI 4.62-not reached). Five-year RFS was 58% (95% CI 42-81%).

Conclusions: Survival outcomes were favorable among this select cohort. Optimal treatment for de novo OMBC remains unclear. Curative intent trials are underway for HER2+ de novo OMBC.

Purpose: Targeted therapies have improved survival in human epidermal growth factor receptor 2 positive breast cancer (HER2 + BC). However, patients over 75 years of age are often excluded from clinical trials of anti-HER2 therapies, and it is unclear to what extent they receive these treatments in routine care. To address this, we examined age-related patterns of anti-HER2 therapy use in real-world clinical practice in Norway.

Methods: In a nationwide registry-based cohort, we identified women diagnosed with stage I-III HER2 + BC during 2012-2021. We investigated treatment patterns using descriptive statistics and estimated the direct effect of age on anti-HER2 therapy use by Poisson regression.

Results: Among 3526 women with HER2 + BC, anti-HER2 therapy use was consistently high (83-95%) in those under 75 years, decreased to 60% at ages 75-79, and declined further with advancing age to 8% at ≥ 90 years. Neoadjuvant anti-HER2 therapy also decreased with age (from 24% in patients under 75 to 12% in patients over 75 years). Accounting for cancer characteristics, comorbidities, polypharmacy, and socio-economic factors, older patients had reduced likelihood of receiving any anti-HER2 therapy compared with patients younger than 55 (RR 0.75, 95% CI 0.66-0.85, p < 0.001, at age 75-84 and RR 0.21, 95% CI 0.11-0.41, p < 0.001, at age 85 +).

Conclusions: Anti-HER2 therapy use declined substantially after the age of 75 even when accounting for comorbidities and polypharmacy. Chronological age appears important in planning treatment for patients with HER2 + BC. Specific guidelines pertaining to older patients with HER2 + BC are needed to avoid potential undertreatment.

Purpose: To investigate the prognosis and endocrine therapy (ET) efficacy in patients with estrogen receptor (ER)-low breast cancer.

Methods: This retrospective cohort study included patients diagnosed with early-stage breast cancer at a single institution in China from January 2010 to December 2020. Clinicopathological features, survival outcomes, and the effect of ET were compared among patients with ER-low, ER-high, and ER-negative breast cancer. Analyses were stratified by human epidermal growth factor receptor 2 (HER2) status (positive or negative).

Results: A total of 2951 patients were included, consisting of 131 (4.4%) ER-low, 2040 (69.1%) ER-high, and 780 (26.4%) ER-negative patients. In the HER2-negative subgroup, ER-low patients had significantly worse breast cancer-free survival (BCFS) (P = 0.016) and a higher risk of locoregional recurrence (P < 0.001) compared to ER-high patients, while no significant differences were observed in prognosis between ER-low and ER-negative patients. In the HER2-positive subgroup, there were no significant differences in prognosis among patients with different ER expression levels. ET could significantly reduce the risk of locoregional recurrence and distant metastasis and significantly improve BCFS for ER-low patients, especially in the HER2-negative subgroup. However, in the HER2-positive subgroup, ET did not improve BCFS or overall survival for ER-low patients.

Conclusion: HER2-negative/ER-low breast cancer has a similar clinical behavior to triple-negative breast cancer, and ET could significantly reduce the risk of recurrence and metastasis for this subgroup. However, in HER2-positive patients, ER-low breast cancer lacks a predictive role in prognosis and derives no clear benefit from ET.

Background: Managing cardiovascular risk is key for breast cancer survivors, many of whom have pre-existing conditions like hypertension and hyperlipidaemia. Research suggests compliance with cardiovascular medication declines after a breast cancer diagnosis. However, these studies rely on population-level averages, which mask patient heterogeneity and longitudinal variations in compliance. This study aimed to identify compliance trajectories with cardiovascular medication around a breast cancer diagnosis and describe associated characteristics.

Methods: Using the French National Health Data System, we constructed a cohort of women diagnosed with incident breast cancer (2016-2020) who received at least 2 cardiovascular drug classes before diagnosis for primary prevention, defined as treatment of cardiovascular risk factors in the absence of established cardiovascular disease. Compliance trajectories were analysed over 3 years using group-based trajectory modelling.

Results: Among 35,399 women, 6 trajectories were identified: stable high compliance (49.9%), moderate stable (21.2%), low stable (12.8%), sharp decline post-diagnosis (9.8%), treatment discontinuation post-diagnosis (3.4%), and very low and declining (2.9%). Declining trajectories were associated with higher rates of metastases and chemotherapy.

Conclusion: This study revealed substantial heterogeneity in compliance responses post-diagnosis. While most women maintained stable compliance, a significant subset experienced sharp declines, likely linked to cancer severity. Early interventions post-diagnosis could reduce cardiovascular risk and improve outcomes.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of tumor protein 53 (TP53) mutation and with limited targeted therapies. Despite being clinically advantageous, direct targeting of mutant TP53 has been challenging. Therefore, we hypothesized that p53-mutant TNBC cells rely upon other potentially targetable survival pathways.

Methods: In vitro and in silico screens were used to identify drugs that induced preferential death in TP53-mutant cells. The effect of the ferroptosis inducer ML-162 was tested both in vitro and in vivo and the mechanism of cell death following ML-162 treatment or GPX4 knockout was determined.

Results: High-throughput drug screening demonstrated that TP53-mutant TNBCs are highly sensitive to peroxidase, cell cycle, cell division, and proteasome inhibitors. We further characterized the effect of the ferroptosis inducer ML-162 and demonstrated that ML-162 induces preferential ferroptosis in TP53-mutant TNBC cells. Treatment of TP53-mutant xenografts with ML-162 suppressed tumor growth and increased lipid peroxidation in vivo. Testing ferroptosis inducers demonstrated TP53-missense mutant, and not TP53-null or wild-type cells, were more sensitive to ferroptosis, and expression of mutant TP53 genes in p53-null cells sensitized cells to ML-162 treatment.

Conclusions: This study demonstrates that TP53-mutant TNBC cells have unique survival pathways that can be effectively targeted. Our results illustrate the intrinsic vulnerability of TP53-mutant TNBCs to ferroptosis and highlight GPX4 as a potential target for the precision treatment of TP53-mutant TNBC.

RISE UP (Revolutionizing Investigations to StEp Up Prevention) for breast cancer brought together leading cancer specialists, women's health providers, basic and population scientists, regulators, politicians, industry leaders, patient advocates, and more from around the world to discuss and chart a radical rethinking of breast cancer prevention and risk reduction through a lens of hormonal management across a woman's life course. The presentations at RISE UP were organized to outline a path forward by leveraging what we know about breast cancer biology, early detection, treatment, and endocrine therapy toward a better and sustainable approach for breast cancer prevention. Important conference considerations were to expand our thinking about prevention by broadly considering how the hormonal environment during different life phases or common benign conditions could be better managed to minimize breast cancer risk. This set the stage for transitioning to advances in risk prediction, promising risk-reducing agents, and biomarker-driven trials to test them. Biomarker-based trials discussed focused on 1) lower or intermittent doses of standard prevention agents, 2) drugs already approved for other health purposes, and 3) maximizing benefits from lifestyle interventions alone or in combination. Throughout RISE UP, there was a strong focus on promoting health equity, including comprehensive reproductive health access, equitable representation in clinical trials, and strategies to educate women, providers, and advocates about disparities in care and how to successfully reduce them. The meeting concluded with a competition for innovative approaches to breast cancer prevention that could be integrated into hormonal and women's health interventions. RISE UP was an innovative conference that provided a forum for cross-cutting topics in women's health that do not currently exist. The insights shared at RISE UP will be paradigm shifting in breast cancer prevention and women's health space in the years to come.