Improving Response to Chemotherapy by Adding Physical Exercise in the Neoadjuvant Setting of Breast Cancer Patients

University Institute of Maia86 enrolled

Overview

One of the recommended treatments for breast cancer is neoadjuvant chemotherapy (NCT), however, only 20% of the patients subject to this therapy present pathologic complete response (pCR). If exercise-induced tumour size reductions observed in preclinical studies translates to humans, physical training could emerge as a way of increasing rates of pCR to NCT, which would be a valuable clinical achievement. The present randomized controlled trial primary aim is to assess the impact of a physical exercise intervention the NCT efficacy. Following a parallel-arm design, 86 women with primary BC will be allocated 1:1 to a NCT + exercise (experimental) or NCT alone (control) group. The primary outcome is the rate of pCR in each group. Secondary outcomes include treatment tolerability and compliance, tumour infiltrating lymphocytes, ki67, immune, inflammatory, matricellular and myogenic markers, physical fitness, accelerometry, quality of life and body composition.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Breast Cancer

Interventions

Apart from the neoadjuvant chemotherapy treatment (standard of care), participants allocated to the experimental group will additionally participate in a supervised physical exercise program that comprises 3 weekly sessions during the months that the patient is undergoing chemotherapy treatment. Each 75-minute session will comprise a 10-minute warm up, 30 minutes of strength training involving exercise for the major muscle groups, 30 minutes of aerobic training at 40-89% of heart rate reserve and a 5-minute cool down.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. being female gender; 2. age equals or greater than 18 years old; 3. having a newly diagnosed histologically confirmed breast carcinoma IA-IIIC; 4. planned to receive neoadjuvant chemotherapy with anthracyclines or taxanes, that might be associated to anti-HER2 drugs; 5. being followed by the oncology department of the CHVNG/E; 6. medical oncologists consents the practice of physical exercise; 7. the patient is capable of providing written informed consent; 8. the participant accepts to be allocated to the control or experimental group, according to the randomization. Exclusion Criteria: 1. previous cancer diagnostic; 2. evidence of synchronous oncologic disease; 3. physical or psychiatric contraindication to the practice of physical exercise.

Outcomes

Primary Outcomes

Pathologic Complete Response

Pathological response as the primary outcome will be assessed by a blinded pathologist from the tumour surgical specimens after the breast surgery (post-intervention) and will be defined as complete, partial or no response. Besides pathological complete response (defined as ypT0/ypN0), groups will be compared as those with response (complete or partial) versus those with no response. The residual cancer burden which quantifies residual disease after NAC (post-intervention) will also be assessed.

Time frame: Post-intervention / Post-treatment. After neoadjuvant chemotherapy, and after surgery. Up to 33 weeks post-baseline.

Secondary Outcomes

Treatment Tolerance - clinically assessed.

Number of participants with clinically assessed treatment-related adverse events. Will be assessed according to the Common Terminology Criteria for Adverse Events v5.0. The scale uses a minimal value of 1 and a maximal value of 5 to grade each adverse event, with higher scores representing worse outcomes.

Time frame: From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.

Treatment Tolerance - patient reported.

Number of participants with patient-reported adverse events. Will be assessed using the Patient reported outcomes version of the Common Terminology Criteria for Adverse Events v1.0 questionnaire. The scale uses a minimal rating 0 and a maximal rating of 4 to grade each adverse event, with higher scores representing worse outcomes.

Time frame: From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.

Chemotherapy Relative Dose Intensity

Chemotherapy relative dose intensity will be calculated by the following formula: (Delivered dose intensity / Standard dose intensity) x 100%, where Delivered dose intensity = (Delivered total dose, in mg/m2)/(actual time to complete chemotherapy with imputation for missed cycles, in days) and Standard Dose Intensity = (Standard total dose, in mg/m2)/(standard time to complete chemotherapy, in days).

Time frame: From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.

Number of Chemotherapy Dose Reductions

Number of patients that had to reduce the dose of chemotherapy from the dose of chemotherapy initially prescribed (standard dose intensity).

Time frame: From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.

Number of Chemotherapy Delays

Number of patients that had to delay a cycle of chemotherapy, in comparison to what had initially been prescribed (standard dose intensity).

Time frame: From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.

Number of Chemotherapy Early Discontinuations

Number of patients that had to interrupt chemotherapy before the standard dose had been administrated.

Time frame: From baseline (week 0) until the end of chemotherapy, an average of 26 weeks.

Percentage of Tumor Infiltrating Lymphocytes

Assessed at Histology Slides. Intratumoral and stromal infiltrating lymphocyte (TIL) population will be assessed in tumour biopsies (at baseline) and surgical resection specimens collected from the post-neoadjuvant chemotherapy surgery (post-intervention). This will be used to compute intratumoral and stromal TIL's score, recorded as the percentage of TIL's on the analysed area. Only stromal TIL ́s will be quantified in patients with complete pathological response.

Time frame: At baseline (week 0) and post-intervention (after an average of 30 weeks from study enrolment).

Percentage of Tumor Ki67

Assessed at Histology Slides. Ki67 will be assessed in tumour biopsies (at baseline) and surgical resection specimens collected from the post-neoadjuvant chemotherapy surgery (post-intervention).