BRCA 1 Gene Mutation, BRCA 2 Gene Mutation, Breast Cancer (Early Breast Cancer)
Conditions
Keywords
BRCA-associated triple-negative early breast cancer, mitomycin, germline mutation BRCA1, BRCA2
Brief summary
This study was designed to evaluate the safety and efficacy of neoadjuvant therapy with mitomycin and carboplatin in patients with BRCA-associated locally advanced triple-negative breast cancer.
Detailed description
The study includes two groups: one is an experimental group receiving chemotherapy according to the MCarb-T regimen, which is compared to a control group treated with the standard AC-TCarb regimen. To participate in this study, patients must have histologically confirmed triple-negative breast cancer (TNBC) in a locally advanced stage and a germline BRCA1 or BRCA2 mutation. All patients with TNBC undergo BRCA1/BRCA2 mutation testing before starting treatment, using either polymerase chain reaction (PCR) or next-generation sequencing (NGS). Patients in the experimental group receive 4 cycles of neoadjuvant chemotherapy with the MCarb regimen (mitomycin + carboplatin AUC5), followed by 12 weekly doses of paclitaxel. Patients in the control group receive 4 cycles of neoadjuvant chemotherapy with the AC regimen (doxorubicin + cyclophosphamide), followed by 12 weekly administrations of the TCarb regimen (paclitaxel + carboplatin AUC2). Clinical assessment is performed after cycles 2 and 4 of MCarb/AC, as well as after completion of the 12 weekly doses of T/ TCarb, with response evaluation according to RECIST 1.1 criteria. Upon completion of cytotoxic chemotherapy, patients undergo surgical treatment. Resected specimens are evaluated using the Miller-Payne grading system and the Residual Cancer Burden (RCB) classification to determine the efficacy of systemic therapy. To assess the safety of neoadjuvant systemic therapy, the frequency and nature of adverse events are recorded during treatment using the NCI CTCAE version 5.0 criteria. As part of the study protocol, complete blood counts with differential and platelet counts (Fonio method) were performed every 7 days, while blood biochemistry, urinalysis, and coagulation tests were carried out every 14 days. After completion of protocol therapy, patients were followed to assess disease status every 3 months during the first year and every 6 months thereafter. Monitoring included physical examination, ultrasound of the breasts and regional lymph nodes, mammography, contrast-enhanced computed tomography of the chest and abdomen, ultrasound or contrast-enhanced magnetic resonance imaging of the pelvis, and bone scintigraphy.
Interventions
PROCEDURENeoadjuvant Chemotherapy (NACT)
neoadjuvant chemotherapy according to the regimen of mitomycin in combination with carboplatin, followed by paclitaxel
Sponsors
N.N. Petrov National Medical Research Center of Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study includes two groups: one is an experimental group receiving chemotherapy according to the MCarb-T regimen, which is compared to a control group treated with the standard AC-TCarb regimen. To participate in this study, patients must have histologically confirmed triple-negative breast cancer (TNBC) in a locally advanced stage and a germline BRCA1 or BRCA2 mutation. All patients with TNBC undergo BRCA1/BRCA2 mutation testing before starting treatment, using either polymerase chain reaction (PCR) or next-generation sequencing (NGS). Patients in the experimental group receive 4 cycles of neoadjuvant chemotherapy with the MCarb regimen (mitomycin + carboplatin AUC5), followed by 12 weekly doses of paclitaxel. Patients in the control group receive 4 cycles of neoadjuvant chemotherapy with the AC regimen (doxorubicin + cyclophosphamide), followed by 12 weekly administrations of the TCarb regimen (paclitaxel + carboplatin AUC2). Clinical assessment is performed after cycles 2 and 4 o
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent to participate in the study; 2. Histopathological confirmation of triple-negative breast cancer; 3. Stage: clinical T1-T4, N0-3, M0; 4. Positive molecular genetic test for BRCA1\|2 gene mutation (PCR test or NGS result); 5. Age \> 18 years; 6. ECOG status 0-1.
Exclusion criteria
1. Prior administration of any systemic therapy for breast cancer; 2. Stage IV disease; 3. Severe uncontrolled chronic comorbidities or acute illnesses; 4. Renal dysfunction; 5. Age \> 70 years; 6. Presence of a second malignant tumor (except for previously cured malignancies); 7. Pregnancy or breastfeeding; 8. Negative molecular genetic test for BRCA1\|2 gene mutation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathomorphological response | From enrollment to pathological assessment (after surgery) from 6 to 7 months | The pathological response assessment will be performed within 14 days after definitive breast surgery. The Miller-Payne grading system will be used to assess the pathological response in the surgical specimen by comparing residual invasive tumor cellularity with the pretreatment core needle biopsy specimen. The Residual Cancer Burden (RCB) will be assessed using the surgical specimens from the breast and regional lymph nodes and will also be calculated within 14 days after surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events incidence | Until 30 days after last patient treatment visit | Adverse events during chemotherapy are any undesirable symptoms, conditions, or diseases that occur in a patient during or after chemotherapy and may be related to its toxic effects. |
| Response rate | At the end of Cycle 2 (each cycle consists of 28 days). At the end of Cycle 4 (each cycle consists of 28 days). At the end of Cycle 6 (each cycle consists of 7 days). At the end of Cycle 12 (each cycle consists of 7 days). | To assess the objective response rate (OR) by RECIST v1.1 2. |
| overall and disease-free survival | "through study completion, an average of 1 year" | Overall survival (OS) refers to the length of time from either the date of diagnosis or the start of treatment that patients are still alive. It is a key endpoint in clinical trials, measuring the effectiveness of a treatment in extending life. Disease-free survival (DFS) is the length of time after primary treatment during which a patient remains free of any signs or symptoms of the cancer. It is used to measure how well a treatment prevents recurrence. |
Countries
Russia
Outcome results
None listed