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Women who chose not to have surgery after a pathologic complete response (pCR) to neoadjuvant therapy for early HER2-positive or triple-negative breast cancer (TNBC) had no recurrences during the first 2 years of follow-up, a small prospective study showed.

Overall, 31 of 50 (62%) women had no evidence of residual disease by image-guided vacuum-assisted core biopsy (VACB). All 31 had standard whole-breast radiotherapy but did not undergo surgery. After a median follow-up of 26.4 months, none of the patients who skipped surgery had ipsilateral recurrence. No serious VACB-related adverse events or treatment-related adverse events occurred.

The early results suggest eliminating surgery is feasible for carefully selected patients who achieve pCR with neoadjuvant therapy for early triple-negative or HER2-positive breast cancer, reported Henry M. Kuerer, MD, of the University of Texas MD Anderson Cancer Center in Houston, and co-authors in .

"We're committed to studying this further with additional patients," Kuerer told 名媛直播. "I don't want to sound dramatic, but I'm positive there are going to be a lot of other clinical trials in this space. Not just in the U.S., but around the world, because it makes sense. Something like 60-70% of the patients don't have any cancer left. They really don't need the surgery as long as we can show this in very well-designed additional studies that this might be a safe approach."

De-Escalation Pathway

The genesis for the trial goes back more than 20 years when investigators found that pCR was associated with improved prognosis, even though doxorubicin-based chemotherapy regimens in use at the time achieved pCR in only about 10% of cases. More circumstantial support for the concept of skipping surgery came from research that validated targeted axillary lymph node dissection as a safe and reliable technique to allow women to avoid total axillary node dissection.

"During that trial, it became clear in my mind that we could do the same thing in the breast," said Kuerer.

Additionally, advances in systemic therapy for breast cancer have led to neoadjuvant regimens that can achieve pCR in 60% or more of early TNBC and HER2-positive breast cancers.

The third key factor in the study design was the use of VACB. A preliminary study that employed standard biopsy technique obtained six cores, which proved insufficient, leading to an unacceptable rate of false-negative results. With VACB, investigators obtained 12 biopsy cores, which improved the accuracy.

In the current study, Kuerer and colleagues evaluated 58 patients with T1-2 N0-1 M0 disease, 50 of whom subsequently received neoadjuvant systemic therapy and follow-up VACB. The study population consisted of 21 patients with TNBC and 29 with HER2-positive breast cancer.

Patients received standard neoadjuvant regimens recommended by their treating oncologists and standard external-beam whole-breast irradiation. After completing neoadjuvant therapy, the patients had mammography and breast ultrasound assessments, and radiologists determined the best imaging guidance for VACB. Breast biopsy was performed under stereotactic or ultrasound guidance, and a minimum of 12 cores were obtained. A clip was placed in the tumor bed to facilitate surgery, if indicated by presence of residual disease.

The primary endpoint was the rate of biopsy-confirmed ipsilateral breast cancer recurrence at 6 months and 1, 2, 3, and 5 years among women whose post-neoadjuvant therapy VACB showed no residual tumor. The 50 patients were all women, and median age was 62. The mean pretreatment largest tumor size was 2.28 cm. Post-treatment VACB showed that 19 patients had residual disease.

Rates of pCR were 71% (15 of the 21 patients) with TNBC and 55% (16 of 29 patients) with HER2-positive breast cancer. Seven of 18 (39%) patients who were hormone receptor (HR)-positive/HER2-positive had a pCR as compared with nine of 11 (81%) with HR-negative/HER2-positive tumors.

TNBC and HER2-positive breast cancer account for about 35% of all breast cancers. Whether the encouraging preliminary results from the study will apply to the much larger HR-positive patient population remains to be seen, said Kuerer. HR-positive breast cancer is less sensitive to neoadjuvant therapy, including neoadjuvant hormonal therapy, and pCR occurs less often as compared with TNBC and HER2-positive tumors.

'Not Ready for Prime Time'

The authors of an expressed caution about the applicability of the findings to the broader population of patients with TNBC and HER2-positive breast cancer. Differences in neoadjuvant regimens, receipt of adjuvant therapy, and higher rates of false-negative results with wider implementation all could influence outcomes.

Nonetheless, the trial "is a significant step towards more precise treatment to restrict morbidity of intervention without compromising patient outcomes," wrote Philip M. Spanheimer, MD, and Katherine E. Reeder-Hayes, MD, of the University of North Carolina at Chapel Hill.

Despite the small numbers and relatively brief follow-up, the results are "pretty exciting," said Deanna Attai, MD, of the UCLA Jonsson Comprehensive Cancer Center in Los Angeles.

"It just fits with everything that we're trying to do in breast and other cancer care, as far as the de-escalation, when dialing back on care doesn't compromise outcomes," she said.

Acknowledging that a 2-year follow-up is relatively brief, Attai noted that TNBC and HER2-positive tumors tend to recur early, adding a measure of confidence to the early findings. The patients were carefully selected and treated at specialized centers, offering caveats to potential extrapolation of the results to the general population of patients with breast cancer.

"I think this is very promising and very encouraging, but it's definitely not ready for prime time," Attai added.

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