Targeting Stress-Driven Inflammatory and Angiogenic Pathways With Brief ACT to Enhance Neoadjuvant Chemotherapy Response in Locally Advanced Breast Cancer

Официальное название

Effect of Brief Acceptance and Commitment Therapy on Neoadjuvant Chemotherapy Response in Locally Advanced Breast Cancer Through Modulation of Inflammatory and Angiogenic Biomarkers.

Обзор

This clinical trial aims to learn whether a brief psychological therapy called Brief Acceptance and Commitment Therapy (Brief-ACT) can improve the effectiveness of neoadjuvant chemotherapy in patients with locally advanced breast cancer. It will also examine how this therapy affects stress levels and certain blood markers related to inflammation and tumor growth. The main questions this study aims to answer are: Does Brief-ACT improve the rate of pathological complete response (pCR) after chemotherapy? Does Brief-ACT reduce levels of inflammatory and angiogenic biomarkers such as C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), and vascular endothelial growth factor (VEGF)? Does Brief-ACT reduce psychological stress in patients undergoing chemotherapy? Researchers will compare patients who receive Brief-ACT in addition to standard chemotherapy with those who receive standard chemotherapy alone to see if there are differences in treatment response, stress levels, and biomarker levels. Participants will: Receive neoadjuvant chemotherapy according to standard treatment protocols Be assigned to receive Brief-ACT sessions or no additional psychological intervention Attend regular clinic visits for treatment and monitoring Provide blood samples at specific time points for laboratory analysis Complete questionnaires to assess psychological stress

Подробное описание

Breast cancer patients with locally advanced disease frequently experience substantial psychological distress during treatment, which has been associated with adverse biological effects. Chronic psychological stress may activate neuroendocrine pathways, particularly the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased production of pro-inflammatory cytokines and angiogenic factors. These biological alterations, including elevated levels of interleukin-6 (IL-6), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and vascular endothelial growth factor (VEGF), are thought to contribute to tumor progression and resistance to chemotherapy.

Emerging evidence suggests that psychological interventions may influence these biological pathways. Acceptance and Commitment Therapy (ACT), particularly in its brief format (Brief-ACT), has been shown to improve psychological flexibility and reduce stress. However, its potential role in modulating inflammatory and angiogenic biomarkers and improving chemotherapy response in breast cancer patients remains insufficiently explored.

This study is designed as a randomized controlled trial to evaluate the effect of Brief-ACT on treatment response in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy. The intervention is delivered alongside standard chemotherapy and focuses on enhancing psychological flexibility through core ACT processes, including acceptance, cognitive defusion, present-moment awareness, and value-based action.

In addition to evaluating clinical response, this study investigates the potential biological mechanisms underlying the effect of psychological intervention. Serial measurements of inflammatory and angiogenic biomarkers are performed to assess whether changes in psychological stress are associated with modulation of these pathways. This integrative approach aims to bridge psychological and biological domains in cancer treatment.

The findings of this study are expected to provide evidence on whether a structured psychological intervention can serve as an adjunctive strategy to improve chemotherapy outcomes through modulation of stress-related biological processes. If effective, this approach may support the integration of psychosocial care into standard oncological treatment to enhance both clinical and biological outcomes.

Вмешательства

• Поведенческое Brief Acceptance and Commitment Therapy
  Brief Acceptance and Commitment Therapy (Brief-ACT) is a structured psychological intervention delivered during the course of neoadjuvant chemotherapy. The intervention focuses on enhancing psychological flexibility through core ACT processes, including acceptance, cognitive defusion, present-moment awareness, self-as-context, values clarification, and committed action. Sessions are delivered in a brief format tailored to the clinical setting and are integrated into routine oncology care during
• Поведенческое Standard Counseling
  Standard counseling consists of routine supportive communication provided as part of standard clinical care during neoadjuvant chemotherapy. This includes general emotional support, basic health education, and non-directive discussion without the use of structured psychotherapeutic techniques such as Acceptance and Commitment Therapy. This intervention serves as an attention-control condition.
• Препарат Neoadjuvant Chemotherapy
  Standard neoadjuvant chemotherapy regimen administered according to institutional protocols for locally advanced breast cancer.

Первичные конечные точки

• Clinical response according to RECIST version 1.1 [Срок оценки: At the end of cycle 3 (each cycle is 21 days), prior to surgery]

Вторичные конечные точки (5)

• Change in serum interleukin-6 (IL-6) level [Срок оценки: Baseline (prior to initiation of chemotherapy) and after completion of cycle 3 chemotherapy (approximately 9 weeks, each cycle is 21 days)]
• Change in neutrophil-to-lymphocyte ratio (NLR) [Срок оценки: Baseline (prior to initiation of chemotherapy) and after completion of cycle 3 chemotherapy (approximately 9 weeks, each cycle is 21 days)]
• Change in serum vascular endothelial growth factor A (VEGF-A) level [Срок оценки: Baseline (prior to initiation of chemotherapy) and after completion of cycle 3 chemotherapy (approximately 9 weeks, each cycle is 21 days)]
• Change in perceived stress level [Срок оценки: Baseline (prior to intervention), and after completion of intervention, approximately 9 weeks after baseline measurement]
• Change in psychological flexibility measured by Acceptance and Action Questionnaire-II (AAQ-II) [Срок оценки: Baseline (prior to initiation of study intervention) and after completion of intervention (approximately 6-9 weeks after baseline)]

Критерии участия

Критерии включения

• Female patients aged 40-65 years
• Histologically confirmed locally advanced breast cancer
• Planned to undergo neoadjuvant chemotherapy
• ECOG performance status 0-2
• Able to provide informed consent
• Willing to participate in psychological intervention sessions

Критерии исключения

• Severe psychological distress defined as Perceived Stress Scale (PSS-10) score ≥27
• Active infection or inflammatory disease
• Known autoimmune disease
• Cognitive impairment or psychiatric condition interfering with participation
• Concurrent participation in another interventional study

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07570368 · 400.14.5.4/11991/102.9/2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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