Researchers Investigate Vacuum-Assisted Excision of Small Breast Cancers

LAS VEGAS—If the ongoing SMALL (Open Surgery versus Minimally invasive vacuum-Assisted excision smaLL screen-detected breast cancer) trial finds vacuum-assisted excision noninferior to standard lumpectomy, breast surgeons may be adding a new tool to their armamentarium in another shift toward de-escalation of treatment for small, early-stage breast cancers.

“It’s reasonable to start off asking, why are we talking about minimally invasive treatment for small cancers?” said Stuart McIntosh, MD, a professor of surgical oncology at Queen’s University Belfast, in Northern Ireland, speaking at the 2025 annual meeting of the American Society of Breast Surgeons.

It’s well known that the introduction of widespread population screening mammography resulted in a significant increase in the detection of small, early-stage breast cancers without a reduction in the incidence of large tumors or metastatic disease, Dr. McIntosh said.

“Coupled with that, we know many of these small breast cancers have biologically favorable characteristics. That has led to these cancers being described as overdiagnoses, cancers that would not have become clinically apparent had a woman not attended for screening mammography. But [it’s] not overdiagnosis, it’s just diagnosis. The problem is overtreatment disproportionate to their level of risk.”

There are a number of minimally invasive options available, such as cryoablation and radiofrequency ablation. Vacuum-assisted excision (VAE) is routinely used in the United Kingdom for excising benign lesions and diagnosing and managing lesions of “indeterminant malignant potential,” Dr. McIntosh said.

“We know that we can assess whether a lesion is excised radiologically, and there are data to support the tolerability and acceptability among patients done under local anesthetic in an outpatient setting.”

Believing that VAE could be useful as a treatment for early-stage breast cancer, Dr. McIntosh and his colleagues are running SMALL, a phase 3, multicenter randomized trial comparing VAE with standard breast-conserving surgery for small cancers.

“We’re asking if this approach is feasible, acceptable to clinicians and to patients, can be done with acceptable re-excision rates, what are long-term recurrence implications, and can we safely avoid sentinel lymph node biopsy in this setting,” Dr. McIntosh said.

The study includes women 47 years of age and older with screen-detected breast cancer tumors less than 15 mm and favorable features: grade 1 and estrogen receptor–positive/HER2-negative. Patients are randomized 2:1 in favor of VAE; those randomized to surgery undergo wide local excision, with or without sentinel lymph node biopsy, followed by radiation therapy (RT) and endocrine therapy (ET) according to local practice; all patients undergoing VAE undergo RT and ET.

Since margins cannot be assessed pathologically in patients undergoing VAE, specimens from the arm will be evaluated radiologically. “Where the radiologists feel the lesions are incompletely excised, or where on the VAE specimen the pathologist feels [there] is an upgrade to grade 3, those patients will cross over to have standard surgery and RT and ET,” Dr. McIntosh said.

The trial has two primary end points, the first being a noninferiority comparison of the need for a second surgery. “Re-excision rates in the U.K. after standard surgery are 15% to 20%. We’ve set a 10% noninferiority margin, so if the re-excision rate is not more than 10% greater than it is for standard surgery, VAE is noninferior,” Dr. McIntosh said.

The second primary end point is local recurrence after VAE. “Because local recurrence in this setting is very low—around 1% to 2% at five years—we have set an unacceptable rate of local recurrence at 3% at five years. If local recurrence after VAE exceeds this, we will declare that not a satisfactory outcome.”

At the time of his presentation, SMALL had enrolled 650 patients with a goal of enrolling 801; as of August 2025, they’d enrolled an additional 14 patients and expect to reach full accrual by May 2026.

“Roughly half of patients approached consent to be randomized into the study, which is a pretty good uptake rate for a surgical RCT [randomized controlled trial],” Dr. McIntosh said.

David R. Brenin, MD, the M.C. Wilhelm Professor in Diseases of the Breast at the University of Virginia Medical Center, in Charlottesville, observed that VAE is a natural extension of the de-escalation of treatment for early-stage breast cancer that has been going on for some time, “removing the tumor in the least invasive way a tumor can be removed at this point. It’s an interesting study and hopefully will be successful in reaching its end points.”

The obvious advantage for patients would be avoiding all that goes along with a typical surgical procedure: insertion of an IV, being wheeled into the OR, and receiving either local anesthetic with sedation or undergoing general anesthesia.

“VAE is like an extended biopsy, using the same equipment in the same physical setting [the radiology suite] but excising quite a bit more tissue than would be excised with a core biopsy,” Dr. Brenin said.

From a surgical point of view, the main difference is removal of the specimen in a piecemeal manner rather than en bloc with margins. “The question is, is that important and how could it be important in terms of local recurrence?” Dr. Brenin said. “Ideally, surgeons performing lumpectomy achieve negative margins; when we don’t, we typically remove more tissue.

“That was touched on in the presentation. Their cutoff for noninferiority is 10% greater than the 15% to 20% re-excision rate in the U.K., so 30%. That seems a bit high to me, but from the patient’s perspective, that would be a first visit to the OR, not a repeat or second curative procedure,” Dr. Brenin said.

He did have a concern, however, about a potential bias in the study: Patients randomized to VAE who do not cross over to surgery must undergo both RT and ET, both of which are known to reduce local recurrence, while adjuvant therapy for patients in the standard arm is left to local practice. “This difference in the treatment arms would introduce a confounder during follow-up,” Dr. Brenin said.

Dr. McIntosh responded to this concern, which he and his colleagues suspected others might—incorrectly, he maintained—share, by clarifying the study’s unique design. “We are not carrying out a direct, randomized comparison of local recurrence between the two groups. We know this should be extremely low after standard surgery, around 1% at five years, therefore doing a randomized comparison would require a very large number of patients.

“Rather, in the VAE arm, after consultation with patients, we agreed that a local recurrence rate of greater than 3% would be unacceptable. We will also monitor the local recurrence rate in the surgery arm to ensure that our estimates are reflective of contemporary practice,” he concluded.