Breast Cancer Research and Treatment最新文献

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.

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.

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.

Purpose: The objective of this study was to determine whether pre-existing type 2 diabetes is associated with an increased risk of breast cancer-related and all-cause mortality, compared with non-diabetes, and if the risk varies across glycated hemoglobin A1c (HbA1c) categories.

Methods: Using the Clinical Practice Research Datalink, we assembled a cohort of patients at least 18 years old, newly diagnosed with invasive breast cancer between 1998 and 2020, with follow-up until March 2021. Patients were followed from 3 months after breast cancer diagnosis until one of the study outcomes, end of registration with the general practice, or end of study. Multivariable Cox proportional hazards models, adjusted for 33 confounders, were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-related and all-cause mortality, comparing patients with and without type 2 diabetes among patients with and without metastatic breast cancer. In a secondary analysis, HRs for the outcomes were estimated across glycated HbA1c categories.

Results: The cohort included 157,298 patients with incident breast cancer. Among patients with non-metastatic breast cancer (n = 125,268), type 2 diabetes was associated with a 12% increased risk of breast cancer mortality and 21% increased risk of all-cause mortality. Among patients with metastatic breast cancer (n = 32,030), type 2 diabetes was associated with a 22% increased risk of breast cancer mortality and a 24% increased risk of all-cause mortality. The secondary analysis showed that higher glycated HbA1c was associated with an increased risk, in both the non-metastatic and metastatic cohorts.

Conclusion: In this large population-based cohort study, type 2 diabetes was associated with a greater risk of breast cancer-related and all-cause mortality, with an increased risk among patients with type 2 diabetes in the highest glycated HbA1c categories, compared to non-diabetes.

Purpose: The microbiome of the saliva can be influenced by various factors, including systemic diseases and chemotherapy. Oral dysbiosis manifests as altered bacterial composition and abundance, which often correlates with increased local and systemic inflammation. The aim of the study was to investigate the dysbiosis in the saliva of breast cancer (BC) patients before and during neoadjuvant chemotherapy (NAC).

Methods: Saliva samples were collected from 50 breast cancer patients at three timepoints (before, during, and after NAC). Saliva from 10 healthy women was used as control samples. Full-length gene 16S rRNA sequencing and analysis were performed using the Microbiome Analyst platform, R and JADBIO AutomatedML platform to compare the abundances of bacterial taxa.

Results: Alpha and beta diversity measures differed between breast cancer patients and healthy controls. In addition, eight bacterial genera differed significantly between breast cancer patients and controls, including Porphyromonas, Campylobacter, Oribacterium, Veillonella, and Alloprevotella. Longitudinal analysis revealed significant decrease of bacterial diversity in the course of neoadjuvant chemotherapy as well as significant change in the prevalence of a few low-abundant genera.

Conclusions: The obtained results confirm BC-related and NAC-related dysbiosis in saliva, which emphasizes the potential of saliva as a diagnostic and prognostic tool in patients with breast cancer.

Introduction: Triple-negative breast cancer (TNBC) is a highly aggressive subtype and lacks effective targeted therapies. Transmembrane protein 205 (TMEM205) has been implicated in tumor progression and immune resistance, but its precise role and mechanism in TNBC remain unclear. This study aims to explore the function and mechanism of TMEM205 in TNBC progression, as well as its impact on the tumor immune microenvironment.

Methods: The expression and prognostic significance of TMEM205 in breast cancer were analyzed using datasets, such as TCGA and UALCAN. TMEM205 was overexpressed and knocked down in TNBC cell lines (MDA-MB-231 and BT-549), and the effects on cell biological activity were verified by functional assays, including CCK-8, colony formation, wound healing, and Transwell assays. A coculture system of tumor cells and THP-1-derived macrophages was established. Key signaling molecules of TNBC cells were detected by Western blot, and cytokine levels by ELISA, so as to study tumor cell-macrophage interactions. The role of TMEM205 in tumor growth and angiogenesis was further validated through xenograft mouse models and endothelial tube formation assays.

Results: TMEM205 was significantly upregulated in breast cancer tissues and associated with a poor prognosis. TMEM205 overexpression promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells, while TMEM205 knockdown inhibited their biological functions. Furthermore, TMEM205 overexpression not only increased the secretion of IL-6 but also activated the JAK2/STAT3 signaling axis, showing a positive correlation with M2 macrophage infiltration. The TNBC cell-conditioned medium with TMEM205 overexpression significantly promoted endothelial cell angiogenesis.

Conclusion: TMEM205, as a multifunctional oncoprotein in TNBC, jointly drives tumor progression by promoting cell proliferation, metastasis, angiogenesis, and fostering an immunosuppressive microenvironment via M2 macrophage polarization. TMEM205 may be a promising therapeutic target for TNBC.

Background: Despite widespread use of clinico-pathologic and genomic risk scores in early breast cancer (EBC), questions remain as to whether they are predictive, prognostic, or both. We evaluated risk score performance with actual patient outcomes in a trial dataset.

Methods: Discrimination and calibration of PREDICT 2.1 and PREDICT v3 for overall survival (OS) and RSClin for distant metastasis-free survival (DMFS) were compared with actual patient outcomes in 645 postmenopausal, node-negative, hormone-positive patients with EBC from the TEAM pathology substudy. Estimated chemotherapy benefit (low < 3%, moderate 3-5%, high > 5%) was also compared.

Results: Harrell's C-statistic for OS was 0.6893 and 0.6986 for PREDICT 2.1 and v3, and 0.6603 for DMFS using RSClin. PREDICT 2.1 underestimated and PREDICT v3 overestimated the 10-year OS. RSClin underestimated the 10-year DMFS. Of patients predicted by RSClin to derive a large benefit from chemotherapy, 44% and 99% were estimated to have a small (< 3%) benefit by PREDICT 2.1 and v3, respectively.

Conclusion: All three scores demonstrated moderate discriminatory ability while PREDICT v3 and RSClin had better calibration. However, scores varied widely on expected benefit from chemotherapy, suggesting that RSClin is prognostic but not predictive of chemotherapy benefit. Given the cost of RSClin, further studies are required.

Trial registration: The trials are registered with ClinicalTrials.gov , NCT00279448, NCT00032136, and NCT00036270; NTR 267; Ethics Commission Trial 27/2001; and UMIN, C000000057.

Purpose: This study aimed to identify prognostic factors and to stratify recurrence risk using a prognostic model incorporating the identified factors in patients with residual triple-negative breast cancer (TNBC) following neoadjuvant systemic therapy (NST).

Methods: A retrospective analysis was conducted using data from a prospectively collected single-institution database. Eligible patients had residual TNBC after NST and curative surgery between 2007 and 2020 and completed planned postoperative radiotherapy. Prognostic factors for disease-free survival (DFS) were identified using multivariable Cox proportional hazards regression. Risk groups were stratified according to the number of these factors.

Results: A total of 347 patients were included. With a median follow-up of 61.6 months, the 5-year DFS and overall survival rates were 62.5% and 73.9%, respectively. Lymphovascular invasion (LVI) positivity and residual cancer burden (RCB) class 3 were significant risk factors for worse DFS. The 5-year DFS rates were 82.9% (0 factor), 55.7% (1 factor), and 20.0% (2 factors) (p < 0.001). The new three-tiered stratification using LVI positivity and RCB class 3 demonstrated a higher concordance index compared to RCB class (bootstrap-estimated difference 0.038, 95% CI 0.006-0.070, p = 0.026). Adjuvant capecitabine was associated with improved 5-year DFS in patients with 1 risk factor (71.9% vs. 44.2%, p = 0.027), but not in those with 0 (83.1% vs. 81.7%, p = 0.548) or 2 factors (29.2% vs. 14.6%, p = 0.066).

Conclusion: Patients with residual TNBC can be stratified into risk groups based on LVI and RCB class. The effect of adjuvant treatment varied across these groups. This model may support more tailored adjuvant treatment decisions after NST.

Purpose: With growing interest in surgical de-escalation for breast cancer, tumor bed biopsy (TBB) after neoadjuvant chemotherapy (NACT) has been proposed as a tool to predict pathological complete response (pCR). This meta-analysis assessed the diagnostic accuracy and clinical applicability of TBB in breast cancer patients achieving complete clinical response (cCR) post-NACT.

Methods: PubMed, Embase, and online clinical trial registries were systematically searched up to April 2025 for studies evaluating TBB in cCR patients after NACT. Pooled sensitivity, specificity and false-negative rate (FNR) were calculated using a random-effects model. Heterogeneity was quantified using the I² statistic.

Results: Eight studies met inclusion criteria. Pooled sensitivity was 0.58 (95% CI 0.51-0.65), specificity was 1.00 (95% CI 0.99-1.00) and the pooled false-negative rate was (42%, 95% CI 35-49%) with I² values (65.8% for sensitivity; 0% for specificity).

Conclusion: In this meta-analysis limited to patients achieving clinical complete response after neoadjuvant chemotherapy, tumor bed biopsy demonstrated excellent specificity but suboptimal sensitivity with an unacceptably high false-negative rate. These findings indicate that a negative tumor bed biopsy cannot reliably confirm pathological complete response and therefore cannot replace standard surgical excision at present. While tumor bed biopsy may help identify residual disease, its current diagnostic performance does not support its use as a standalone tool for surgical de-escalation, underscoring the need for further refinement and prospective validation before clinical adoption.

Purpose: To describe upper-body function in women after breast cancer treatment; and to explore the relationship between upper-body function, quality of life and breast cancer- related lymphoedema up to 7-years post-diagnosis.

Methods: This study uses data collected in a prospective, longitudinal, population-based, breast cancer cohort study. The Disability of Arm, Shoulder and Hand questionnaire (short version -QuickDASH), the Functional Assessment of Cancer Therapy-Breast questionnaire (FACT-B) and self-report of a clinical diagnosis were used to assess upper-body function, quality of life and breast cancer-related lymphoedema, respectively, in 2,876 women with invasive breast cancer at three time points: baseline (up to 9 months post-diagnosis), and at 2- and 7-years post-diagnosis. Unadjusted cross-sectional relationships between outcomes of interest were tested at each time point. Unadjusted and adjusted regression analyses were used to explore the potential predictive relationship between upper-body function and lymphoedema.

Results: Upper-body impairment was common up to 7-years post-diagnosis with > 60% of women reporting at least mild impairment and 23.8-25.6% reporting moderate to very severe impairment. Impaired upper-body function at baseline assessment was associated with poorer overall quality of life (mean (standard deviation) FACT-B for no versus mild impairment: 77.5 (11.8) versus 70.9 (12.1), p < 0.05) and increased odds of breast cancer-related lymphoedema at 2 and 7 years follow-up (moderate to severe upper-body function impairment at 2- and 7- years post-diagnosis: Odds Ratio (95% Confidence interval) 2.49 (1.57, 3.93) and 2.54 (1.51, 4.26), respectively).

Conclusion: Future research evaluating whether prospective monitoring of upper-body function and interventions that can address impairment can reduce the risk of breast cancer-related lymphoedema are warranted.