Real-Time Assessment Of Breast Cancer Lumpectomy Specimen Margins With Nonlinear Microscopy

Overview

This research is studying a new investigative imaging instrument called a nonlinear microscope (NLM). A nonlinear microscope can produce images similar to an ordinary pathologist's microscope, but without first processing tissue to make slides. This study will determine if a NLM can be used to evaluate tissue during lumpectomy surgery for breast cancer in order to reduce the probability that standard pathologic examination of the specimen after the end of the operation will find close or positive margins, thus possibly requiring the patient to have additional breast surgery.

Detailed description

The purpose of this research study is to improve the treatment of breast cancer and reduce the number of patients who require repeat surgical procedures to completely remove breast malignancy.

In standard procedures, pathologists evaluate tissue samples on a microscope after the surgery is over. The new investigative imaging instrument is an advanced type of microscope that enables evaluation during surgery.

The microscope will not be used directly on the participant or in the operating room, but instead will be used to image tissue immediately after excision but prior to the conclusion of surgery. If pathologic examination using NLM concludes that there is invasive cancer or ductal carcinoma in situ (DCIS) at or close to the margin of the specimen, the surgeon will be notified and may decide to do additional surgical shavings before the patient leaves the operating room, in order to improve the likelihood of achieving clean margins and reduce the probability that the patient will be advised to have another operation to achieve clean margins. For both patients on the experimental arm (NLM) and the control arm (without NLM), standard pathologic evaluation of the specimen will be done some days after the lumpectomy is completed. That pathologic evaluation will decide whether or not to recommend that the patient has additional surgery in order to achieve clean margins. The primary outcome measure is the percentage of patients in each group who are advised to have additional surgery for this reason.

Interventions

• Device nonlinear microscopy imaging of excised surgical margins
  Following standard lumpectomy excision, excised tissue will be imaged with NLM. If invasive cancer or ductal carcinoma in situ (DCIS) is detected on or close to the margin, additional excision may be performed. Following surgery, final margins will be evaluated using paraffin embedded histopathology as per standard procedure. Paraffin embedded histopathology will be used to make a final margin determination.
• Procedure standard lumpectomy without nonlinear microscopy imaging
  Lumpectomy with postoperative paraffin embedded histopathology to make a final margin determination.

Primary outcome measures

• Rate of recommendation for repeat surgery on postoperative histopathology [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Patient scheduled to undergo lumpectomy for breast cancer at BIDMC.
• Core needle biopsy revealing invasive breast cancer or DCIS.
• Female.
• Minimum age of 21 years.
• Eligible for breast conserving surgery, lumpectomy and radiation.
• Estrogen receptor positive (ER+) on core needle biopsy, or if estrogen receptor negative (ER-), have evaluable estrogen receptor status with positive internal control on core biopsy.
• Progesterone receptor positive (PR+) on core needle biopsy if biopsy indicates invasive cancer, or if progesterone receptor negative (PR-) on biopsy indicating invasive cancer, have evaluable progesterone receptor status with positive internal control on core biopsy.
• HER2 IHC and/or FISH ordered on core biopsy, if biopsy indicates invasive cancer.
• Oncotype DX or other genetic assay performed on core biopsy or not requested.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

• Contraindicated for radiation therapy.
• Pregnancy. (Pregnant women will be excluded from this study because radiation therapy is contraindicated during pregnancy.)
• Current invasive cancer or DCIS at the site of a previous surgery.
• Any systemic neoadjuvant (or preoperative) therapy between the core biopsy and lumpectomy.
• Involvement in another therapeutic trial for breast cancer at Dana Farber or elsewhere.
• Risk of poor cosmetic outcome after initial lumpectomy and possible additional excision, as assessed by a study surgeon.
• Recommendation for mastectomy based on radiology.
• Patients that have complex DCIS as indicated on radiology, which would require excising a large tissue volume.
• No or equivocal ER, PR or HER2 testing performed prior to surgery if biopsy indicates invasive cancer.
• No or equivocal ER testing performed prior to surgery if biopsy indicates ductal carcinoma in situ.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Beth Israel Deaconess Medical Center — Boston

Identifiers

NCT: NCT02926729 · 16-145

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗