Clinical trial NCT03975179: Omitting vs. Doing Intraoperative Frozen Section Biopsy for Margin Status in Breast Conserving Surgery
Official title: A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy For Resection MArgin Status in Selected Patients Undergoing Breast Conserving Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: frozen section biopsy
resection margin
breast conserving surgery
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Korean Breast Cancer Study Group
First posted: 2019-06-05
Enrollment: 1292
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: * Study phase: 3
* Indication: Breast cancer patients undergoing breast conserving surgery
* Primary objectives: To determine the effect of selective omission of intraoperative margin evaluation via frozen section on margin positive rate Secondary objectives: To determine the effect of selective omission of intraoperative margin evaluation via frozen section on reoperation rate, local recurrence rate, operation time, resection volume, medical cost and patient quality-of life
* Hypothesis: Omitting intraoperative margin evaluation via frozen section biopsy in selected breast cancer patients does not increase margin positive rate
* Study design: Randomized controlled trial
* Sample size: 1292 patients
* Procedures: breast conserving surgery +/- margin frozen section biopsy (+/- additional resection)

Detailed description: 1.1 Preoperative work-up Preoperative breast MRI is recommended to assess multifocal/centric lesions and non-mass enhancement surrounding main mass. Preoperative needle localization or skin marking is done by each hospital's method.

1.2 Surgical procedure Initial wide excision is performed as usual. The recommended target gross margin is one finger breadth. Orientation of the specimen will be done according to each center's principle. Randomization for frozen section biopsy vs. omission is done intraoperatively, after initial wide excision. For the frozen section biopsy omission group, no further procedures will be done. For the frozen section biopsy group, frozen section biopsy is performed on the specimen or cavity by the operating surgeon. The precise method is decided by the surgeon's discretion, but the recommended method is as follows. A minimum 1 x 0.5cm size of breast parenchymal tissue will be excised at minimum four directions of the specimen or cavity with a thickness of approximately 0.1cm (Figure).

Additional resection according to frozen section biopsy result will be decided by the surgeon's discretion. After review of final pathology report, decision of second operation for re-excision will also be done by surgeon's discretion. A recommendation of considering re-excision for only a positive margin (tumor on inked margin) is noted but not mandatory. Data on additional resection or re-excision must all be reported.

1.3 Pathology procedure Evaluation procedure of the frozen section biopsy specimen and wide excision, additional excision specimen is done by each hospital's method. A pathology report of both intraoperative frozen section biopsy result and final pathology result of the frozen section biopsy tissue must be done. Gross specimen measurements (height x length x depth) must be specified on pathology report. Also margin status must be recorded, positive margin defined as "no ink on tumor" for DCIS and invasive cancer. Recording of margin distance from superior, inferior, medial, lateral, margin is recommended. If all margin distance is not feasible for recording, at least margin distance of closest margin must be recorded. The final pathology result of the additional resection specimen after frozen section result must describe whether residual cancer cells were present and the site of them. This is the same for re-operation resection specimens. Thorough microscopic examination for residual cancer cells in additional/re-operation resection specimens is warranted.

1.4 Postoperative care and adjuvant therapy Postoperative care will be performed as usual. Routine adjuvant care will be given, including adjuvant radiation therapy.

1.5 Follow-up The subject's participation of this clinical trial finishes at last fill in of postoperative quality-of-life questionnaire or after last surgery.

Annual clinical examination, mammography and breast sonography is recommended for 5-year local recurrence assessment. Local recurrence is defined as pathologically confirmed ipsilateral breast tumor recurrence.

1.6 Alternatives This is a randomization between two commonly accepted surgical techniques and there is not any oncological increased risk with either. All routine precautions will be taken to minimize overall surgical risk. Alternatives to the trial would be to have standard breast conserving surgery with or without intraoperative frozen section biopsy according to surgeon's discretion and patients will be informed of this. In addition, all patients will be informed of their option for mastectomy as well.

1.7 Compensation Patients will not be paid for participating in this study. Medical expenses occurred during this study will be paid by the patient. This includes costs associated with re-operation for margin re-excision.

Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed breast cancer by core needle biopsy with clinical stage T1-3 by American Joint Committee on Cancer(AJCC) 8th edition
* Candidate of breast-conserving surgery
* Daughter nodule within ≤ 1cm distance of main mass on breast MRI
* Non-mass enhancement extent within ≤ 1cm distance of main mass on breast MRI
* Ability to understand and willing to sign a written informed consent document : Patients who consent about deciding whether frozen biopsy will be performed by randomization

Exclusion Criteria:

* cT4 tumors (AJCC 8th edition)
* Cancer diagnosis confirmed by vacuum-assisted biopsy or surgical biopsy
* Initial operation plan being total mastectomy (conversion to total mastectomy after intraoperative frozen section biopsy is acceptable)
* Personal history of ipsilateral breast cancer
* Ductal carcinoma in situ component on CNB result
* Lobular carcinoma (invasive, in situ)
* Neoadjuvant chemotherapy
* Lesion with microcalcification (microcalcification that is only contained inside the cancer mass is acceptable)
* Multicentric tumor, however a daughter nodule within ≤ 1cm distance on breast MRI is acceptable
* Non-mass enhancement extent wider than 1cm distance of main mass on breast MRI

Primary outcomes:
measure: Resection margin status
timeFrame: 2 weeks after primary surgery
Secondary outcomes:
measure: Reoperation rate
timeFrame: 2 months after primary surgery
measure: Operation time
timeFrame: Immediately after primary surgery
measure: Cost effectiveness
timeFrame: 3 months after primary surgery
measure: Resection volume
timeFrame: 3 months after primary surgery
measure: Number of patients with residual cancer after reoperation
timeFrame: 3 months after primary surgery
measure: Number of patients with residual cancer after re-excision according to frozen section biopsy result
timeFrame: 3 months after primary surgery
measure: Patient quality-of-life assessment: BREAST-Q survey
timeFrame: 1 year after primary surgery
Other outcomes:
measure: Local recurrence
timeFrame: 5 years after primary surgery
Locations:
city: Goyang-si
country: Korea, Republic of
facility: Ilsan Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
Study officials:
affiliation: Samsung Medical Center
name: Byung Joo Chae
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yoo TK, Kang YJ, Jeong J, Song JY, Kang SH, Lee HY, Kim ET, Yi O, Lee HB, Choi S, Park HS, Gwak G, Kim JI, Kim MK, Lee J, Kang HJ, Chae BJ. A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial). J Breast Cancer. 2021 Dec;24(6):569-577. doi: 10.4048/jbc.2021.24.e51.