Omission of Breast Surgery for Breast Cancer Patients With pCR on MRI and Vacuum-assisted Biopsy After NAC (OPTIMIST)

Study Overview
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Brief Summary
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A prospective, multicenter, single-arm non-inferiority trial to demonstrate that breast cancer patients who are predicted to have a pathologic complete response on MRI and vacuum-assisted biopsy after neoadjuvant chemotherapy, and are omitted breast surgery have a non-inferior 5-year disease-free survival compared to those who had received breast surgery.

Detailed Description
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[Background & Rationale for Study] Optimization (rather than de-escalation) of surgery for breast cancer is essential for our patients, and thus it is an important topic discussed actively in all major conferences regarding breast cancer and oncology. A previous study showed that lesion-to-background parenchymal signal enhancement ratio (L-to-B SER) ≤1.6 and/or size ≤ 0.2cm on breast MRI can distinguish pathological complete response (pCR) from minimal residual cancer following neoadjuvant chemotherapy (NAT). In a separate prospective study, 40 patients with near pCR (either tumor size ≤ 0.5 cm or L-to-B SER ≤ 1.6 on MRI) were enrolled and evaluated for the accuracy of US-guided biopsy aided by MRI in predicting pCR in the breast after NAC. US-guided multiple core needle biopsy (CNB) or VAB of the tumor bed, followed by standard surgical excision, was performed. Matched biopsy and surgical specimens were compared to assess pCR. In result, obtaining at least 5 biopsy cores based on tumor size ≤ 0.5 cm and an L-to-B SER of ≤ 1.6 on MRI resulted in 100% NPV and accuracy. No differences in accuracy were noted between CNB and VAB (90% vs. 90%). It was demonstrated that patients who meet these stringent criteria on MRI may forego surgery for breast cancer. Also, a pooled analysis of data from The Royal Marsden, MD Anderson Cancer Center, and Seoul National University Hospital showed that a VAB obtaining at least 6 cores for a lesion ≤2cm on imaging after neoadjuvant chemotherapy can accurately predict pCR at a FNR of 3.2%. For patients who would not benefit from surgery, it is unnecessary in terms of both personal and national medical expenses. Therefore, in order to establish the rationale for whether surgery could be omitted for patients with predicted pCR, it is necessary to demonstrate that the survival rate of patients who skipped breast surgery after confirming no residual cancer on VAB is non-inferior than that of patients who underwent breast surgery. [Study Objectives] To show non-inferiority in terms of disease-free survival (DFS) of omission of breast surgery for breast cancer patients who show no residual tumor on VAB after neoadjuvant chemotherapy. [Study design] Prospective, multicenter, single-arm, non-inferiority trial

Official Title
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Omission of Breast Surgery for Predicted Pathologic Complete Response Patients With MRI and Vacuum-assisted bIopsy in Breast Cancer After Neoadjuvant Chemotherapy a Multicenter, Single-arm, Non-inferiority Trial

Conditions
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Breast Cancer Invasive

Intervention / Treatment
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* Procedure: Breast surgery omission


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sex: female Age: 20 years and older Patients with no clinical/radiologic distant metastasis Tumor type: Invasive ductal carcinoma Tumor subtype: HER2 positive(including luminal B type, triple negative Extent of disease: initial tumor size ≤ 5cm, cN0-2 Patients with measurable tumor size Patients who are expected to achieve pCR after neoadjuvant chemotherapy (MRI size ≤ 1.0 cm AND L-to-B SER ≤ 1.6) Patients with clip inserted to the primary tumor site before or during neoadjuvant chemotherapy Patients with informed consent who are competent to make a voluntary decision Exclusion Criteria: Multifocal lesion (≥2) Extent of residual microcalcification after neoadjuvant chemotherapy > 2cm Bilateral breast cancer or inflammatory breast cancer Contraindication to radiotherapy History of previous contralateral breast cancer Breast cancer patients with distant metastasis Allergic history to MRI contrast Male breast cancer Patients incapable of giving informed consent owing to poor general conditions Patients with BRCA mutation Patients willing to receive breast surgery Patients with a history of cancer diagnosis within 5 years (However, skin cancer other than melanoma and breast carcinoma in situ other than ductal carcinoma in situ can be registered even if 5 years have not passed since the diagnosis)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with pCR predicted by MRI and vacuum-assisted biopsy (VAB) after neoadjuvant chemotherapy<br>When there is no residual tumor cells on the vacuum-assisted biopsy specimen, breast surgery will be omitted. In the case of clinical N0 AND MRI size ≤ 0.5cm AND lesion-to-background signal enhancement ratio ≤1.6, sentinel lymph node biopsy will be omitted. Otherwise, sentinel lymph node biopsy will be performed. If necessary, axillary lymph node dissection will be performed. | Procedure: Breast surgery omission<br>* For patients who are expected to achieve pathologic complete response after neoadjuvant chemotherapy based on MRI findings, vacuum-assisted biopsy will be performed on the main primary lesion marked with a clip. In case of pCR on vacuum-assisted biopsy specimen, breast surgery will be omitted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival | Proportion of patients with no disease recurrence (including loco-regional recurrence, distant metastasis, and contralateral breast cancer) or death. | 5 years after axillary surgery or VAB (in case of axillary surgery omission) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ipsilateral Breast Tumor Recurrence-Free Survival Ipsilateral Breast Tumor Recurrence-Free Survival | Proportion of patients with no disease recurrence in the ipsilateral breast or death | 5 years after axillary surgery or VAB (in case of axillary surgery omission) | 
| Overall Survival | Proportion of patients with no death. | 5 years after axillary surgery or VAB (in case of axillary surgery omission) | 
| Invasive Disease-Free Survival Invasive Disease-Free Survival | Proportion of patients with no invasive disease recurrence (including loco-regional recurrence, distant metastasis, and contralateral breast cancer) or death. | 5 years after axillary surgery or VAB (in case of axillary surgery omission) | 
| QoL, symptoms, and medical cost | Analysis of QoL survey (BREAST-Q), procedure-related symptoms, and medical cost | 1 year after axillary surgery or VAB (in case of axillary surgery omission) | 
| Rate of residual axillary lymph node metastasis on axillary surgery | Proportion of patients with metastatic lymph nodes among those with pCR on VAB | Upon axillary surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant chemotherapy, pathological complete response, vacuum-assisted bIopsy, omission of breast surgery