Extracellular Fluid Changes During Neoadjuvant Chemotherapy

Florence Nightingale Hospital, Istanbul

Status: Active, not recruiting

Conditions: Lymphedema Arm

Study type: Observational

Funder types: Other

Identifiers

NCT07315880

FNH2025-2

Details and patient eligibility

About

The purpose of this prospective clinical study is to evaluate whether neoadjuvant chemotherapy (NACT) is associated with an increase in extravascular (extracellular) fluid in the ipsilateral upper extremity, an early indicator of breast cancer-related lymphedema (BCRL), in patients with newly diagnosed breast cancer who have not yet undergone breast surgery or axillary lymph node dissection.

Adult patients with a new diagnosis of breast cancer for whom standard NACT is planned will undergo baseline assessments prior to initiation of chemotherapy and follow-up assessments approximately two weeks after completion of NACT. Extravascular fluid status will be evaluated using bioimpedance spectroscopy (L-Dex) and standardized upper extremity circumference measurements.

The primary objective is to assess within-subject changes in extracellular fluid following NACT. Secondary objectives include evaluating the frequency of extracellular fluid increase and exploring associations between extracellular fluid changes and selected patient- and disease-related characteristics, such as age, clinical nodal status, molecular subtype, body mass index, hormone receptor status, and receipt of targeted therapy.

Full description

Breast cancer-related lymphedema (BCRL) is a chronic condition that can adversely affect upper extremity function and quality of life. Although BCRL is traditionally regarded as a postoperative complication related to axillary surgery or radiotherapy, accumulating evidence suggests that lymphatic dysfunction and extracellular fluid accumulation may begin earlier in the treatment course, including during neoadjuvant chemotherapy (NACT). Identifying such early, subclinical changes may enable timely preventive strategies.

This prospective, single-center clinical study is designed to evaluate whether neoadjuvant chemotherapy (NACT) is associated with an increase in extravascular (extracellular) fluid in the ipsilateral upper extremity among patients with newly diagnosed breast cancer who have not yet undergone breast surgery or axillary lymph node dissection.

The study was initiated on January 1, 2021, with a planned completion date of December 31, 2025. All participants are recruited and followed at the Istanbul Florence Nightingale Hospital Breast Health Center.

Eligible participants are adult women (≥18 years) with histologically confirmed breast cancer who are scheduled to receive standard NACT. Patients with prior breast or axillary surgery, preexisting clinical lymphedema, incomplete chemotherapy, or non-standard treatment regimens are not included.

Each participant undergoes two standardized assessment visits: a baseline evaluation conducted prior to initiation of NACT and a post-treatment evaluation performed approximately two weeks after completion of NACT and before definitive breast surgery.

At both visits, segmental bioimpedance spectroscopy using the L-Dex U400® device and upper extremity circumference measurements are performed following standardized procedures. For bioimpedance spectroscopy, two consecutive measurements are obtained and averaged to generate the L-Dex score. Arm circumferences are measured at 5-cm intervals along the upper limb, with three measurements averaged at each point. All assessments are conducted by the same trained clinician to ensure measurement consistency.

The standard neoadjuvant chemotherapy regimen consists of four cycles of intravenous doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) administered every 21 days, followed by weekly paclitaxel (80 mg/m²) for 12 weeks. Patients with HER2-positive disease receive trastuzumab and pertuzumab according to standard loading and maintenance dosing schedules concurrently with paclitaxel therapy.

The study evaluates changes in extracellular fluid status using bioimpedance spectroscopy and arm circumference measurements, and explores associations between these changes and selected patient- and disease-related characteristics.

Enrollment: 111 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female patients aged 18 years or older.
• Histologically confirmed diagnosis of breast cancer.
• Planned to receive standard neoadjuvant chemotherapy (NACT) prior to surgery.
• Patients who agreed to participate in the study.
• No contraindications to bioimpedance spectroscopy (BIS), including implanted electronic devices, open wounds or infections on the measurement site, pregnancy, severe non-cancer-related edema, or inability to maintain a supine position during measurement.

Exclusion criteria

• Presence of clinically detectable lymphedema at baseline.
• Incomplete or discontinued chemotherapy for any reason.
• Receiving non-standard chemotherapy regimens outside the study protocol.
• Any medical condition or device that prevents accurate BIS measurement.

Trial design

111 participants in 1 patient group

Breast cancer patients receiving standard neoadjuvant chemotherapy prior to surgery

Description:

This group includes female patients diagnosed with breast cancer who are planned to receive standard neoadjuvant chemotherapy (NACT) prior to any surgical intervention. Participants have not yet undergone breast surgery or axillary lymph node dissection at the time of enrollment. The group will be assessed for early changes in extravascular (extracellular) fluid and subclinical lymphedema using bioimpedance spectroscopy (L-Dex) and arm circumference measurements before and after completion of NACT. All participants follow the same chemotherapy protocol, which may include anthracyclines, cyclophosphamide, paclitaxel, and, if HER2-positive, trastuzumab and pertuzumab.