Breast Neoplasm Malignant Female
Conditions
Keywords
Surveillance for breast cancer relapses, Omission of local therapies, Omission of surgery, Omission of radiotherapy
Brief summary
HER2-positive and Triple-negative are subtypes of breast cancer more sensitive to systemic therapies, where the complete pathological response rate may be higher than 50%. This gave rise to doubts about the usefulness of traditional local treatments for such responders. Omission of surgery after vacuum assisted breast biopsy (VABB) as well omission of radiotherapy after conservative surgery would now seem to be reasonable alternatives to standard care for highly selected patients, in whom systemic treatments have provided the maximum response.
Detailed description
This is a prospective phase 2 non-randomized non-inferiority trial with two independent investigational arms. In each arm a 2-stage non-inferiority group-sequential design will be implemented; the overall sample per arm is of 76 patients, 43 of which will be recruited at the first stage. For each arm a futility evaluation is foreseen at the first stage, the results of which will be presented to an independent Data Safety and Monitoring Committee (iDSMC) (see Statistical analyses paragraph). Arm A will evaluate the omission of surgery in unifocal T1-2 clinically N0, M0 patients who will demonstrate maximum response after neoadjuvant systemic treatment (i.e. whole breast irradiation only). Arm B will evaluate the omission of radiotherapy in patients with complete pathological response proved by standard conservative surgical treatment (i.e. conservative surgery only). Patients candidate to arm A, who refuse the omission of surgery and then operated, are eligible for arm B if complete pathological response is confirmed after standard surgical treatment. Moreover, patients who refuse VABB and N1 patients with complete pathological response confirmed by partial mastectomy and surgical staging of axilla (SLNB and or TAD) are also eligible for arm B. Arm B patients must have confirmed complete pathological response by local-regional surgery. Therefore, omission of radiotherapy will be ultimately offered to a cohort of patients with T1-2, N0-1, M0 breast cancer conservatively operated, in whom complete pathological response to a neoadjuvant therapies is confirmed on the entire surgical specimen of the tumor bed and of the sampled nodes. In each study arm non inferiority of 5-year EFS will be tested against historical data. No between arms statistical comparison is foreseen.
Interventions
OTHEROmission of local therapies
Omission of surgery (arm A) or radiotherapy (arm B) in those patients who have had the maximum response by neoadjuvant treatments. Maximum responders are those patients with no evidence of residual disease after neoadjuvant treatment at imaging -including mammography, US evaluation and contrast imaging procedures (MRI and/or CEM)-, confirmed by VABB on marked site of ascertained lesion. This study is open to all patients with T1-2, N0-1, M0 HER2-positive or triple negative breast cancer, treated with neoadjuvant systemic treatment, irrespective of treatments delivered.
Sponsors
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is open to all patients with T1-2, N0-1, M0 HER2-positive or triple negative breast cancer, treated with neoadjuvant systemic treatment, irrespective of treatments delivered. The aim of the study is to evaluate outcome in maximum responders to neoadjuvant systemic therapies, when surgery or whole breast irradiation are alternatively omitted. Arm A will evaluate the omission of surgery in unifocal T1-2 clinically N0, M0 patients who will demonstrate maximum response after neoadjuvant systemic treatment (i.e. whole breast irradiation only). Arm B will evaluate the omission of radiotherapy in patients with complete pathological response proved by standard conservative surgical treatment (i.e. conservative surgery only).
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women ≥ 18y. * Initial diagnosis of unifocal HER2-positive (regardless of HR status) or Triple-negative (HR positivity lower than 10% is allowed) T1-2, N0-1, M0 breast cancer. * Treated with neoadjuvant systemic treatment according to the center recommendations. * Maximum responders and/or complete pathological response proved by surgery. * Scheduled for breast conservation. * Giving specific informed consent.
Exclusion criteria
* One of the inclusion criteria missed. * Residual ductal carcinoma in situ (DCIS) at VABB and/or surgery. * Bilateral synchronous breast cancer. * Previous malignancy within 5 years. * BRCA1-2, PALB2 or p53 proven mutation carrier (VUS are
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Events-free survival (EFS) for each study arm. | 5 years | Events considered are: local recurrence, distant metastases, or death, whichever will occur first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to rescue surgery | 5 years | Delayed of treatment in case of local-regional disease reappearance |
Countries
Italy
Contacts
Primary ContactMassimiliano Gennaro, MD
Backup ContactKiara Muca
Outcome results
None listed