Clinical trial NCT05505357: Omission of Breast Surgery for Breast Cancer Patients With pCR on MRI and Vacuum-assisted Biopsy After NST (OPTIMIST)
Official title: Omission of Breast Surgery for Predicted Pathologic Complete Response Patients With MRI and Vacuum-assisted bIopsy in Breast Cancer After Neoadjuvant Systemic Therapy: a Multicenter, Single-arm, Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer Invasive
Keywords: neoadjuvant systemic therapy
pathological complete response
vacuum-assisted bIopsy
omission of breast surgery
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health & Welfare, Korea
First posted: 2022-08-17
Enrollment: 533
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 systemic therapy, and are omitted breast surgery have a non-inferior 5-year disease-free survival compared to those who had received breast surgery.

Detailed description: \[Background \& Rationale for Study\]

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 systemic therapy (NST). 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 NST. 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 NST 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 NST.

\[Study design\]

Prospective, multicenter, single-arm, non-inferiority trial

Eligibility criteria: 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)

Primary outcomes:
measure: Disease-Free Survival
timeFrame: 5 years after axillary surgery or VAB (in case of axillary surgery omission)
Secondary outcomes:
measure: Ipsilateral Breast Tumor Recurrence-Free Survival Ipsilateral Breast Tumor Recurrence-Free Survival
timeFrame: 5 years after axillary surgery or VAB (in case of axillary surgery omission)
measure: Overall Survival
timeFrame: 5 years after axillary surgery or VAB (in case of axillary surgery omission)
measure: Invasive Disease-Free Survival Invasive Disease-Free Survival
timeFrame: 5 years after axillary surgery or VAB (in case of axillary surgery omission)
measure: QoL, symptoms, and medical cost
timeFrame: 1 year after axillary surgery or VAB (in case of axillary surgery omission)
measure: Rate of residual axillary lymph node metastasis on axillary surgery
timeFrame: Upon axillary surgery
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Han-Byoel Lee
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim SY, Cho N, Shin SU, Lee HB, Han W, Park IA, Kwon BR, Kim SY, Lee SH, Chang JM, Moon WK. Contrast-enhanced MRI after neoadjuvant chemotherapy of breast cancer: lesion-to-background parenchymal signal enhancement ratio for discriminating pathological complete response from minimal residual tumour. Eur Radiol. 2018 Jul;28(7):2986-2995. doi: 10.1007/s00330-017-5251-8. Epub 2018 Jan 29.
citation: Lee HB, Han W, Kim SY, Cho N, Kim KE, Park JH, Ju YW, Lee ES, Lim SJ, Kim JH, Ryu HS, Lee DW, Kim M, Kim TY, Lee KH, Shin SU, Lee SH, Chang JM, Moon HG, Im SA, Moon WK, Park IA, Noh DY. Prediction of pathologic complete response using image-guided biopsy after neoadjuvant chemotherapy in breast cancer patients selected based on MRI findings: a prospective feasibility trial. Breast Cancer Res Treat. 2020 Jul;182(1):97-105. doi: 10.1007/s10549-020-05678-3. Epub 2020 May 16.
citation: Tasoulis MK, Lee HB, Yang W, Pope R, Krishnamurthy S, Kim SY, Cho N, Teoh V, Rauch GM, Smith BD, Valero V, Mohammed K, Han W, MacNeill F, Kuerer HM. Accuracy of Post-Neoadjuvant Chemotherapy Image-Guided Breast Biopsy to Predict Residual Cancer. JAMA Surg. 2020 Dec 1;155(12):e204103. doi: 10.1001/jamasurg.2020.4103. Epub 2020 Dec 16.