Skipping Surgery for HER2+ Breast Cancer: Which Patients?

Roxanne Nelson, RN, BSN

May 08, 2019

Surgery is an integral part of a breast cancer treatment regimen, but with recent advances in neoadjuvant systemic therapy (NST), there may be patients who could skip the op.  

Specifically, women with HER2+ breast cancer who achieve a pathologic complete response (pCR) after NST may be candidates for clinical trials that will evaluate non-operative management, say researchers.

However, to be eligible, patients "must have a pCR for both invasive and DCIS components in order to make sure that there was no nidus for recurrence," the researchers explain, and hence they set out to study factors associated with achieving a pCR.

The results were presented May 2 at the 20th Annual Meeting of the American Society of Breast Surgeons (ASBrS).

Commenting for Medscape Medical News, Sarah P. Cate, MD, assistant professor of breast surgery at the Icahn School of Medicine at Mount Sinai, New York City, said the idea of skipping surgery is an important issue and something patients ask about all the time. "They want to know why they still need surgery if there isn't any evidence of cancer after chemo," she said. "These trials will help provide answers for that."

Cate commented that HER2-targeted therapies such as trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech) have changed the treatment landscape in this population.

"We have been seeing really good responses, so there is the question if some of these patients really need surgery," she told Medscape Medical News. "In this study they have identified that certain tumor types are more likely to have a response after chemotherapy and which are less likely to have a complete pathologic response."

However, she cautioned that these data are not saying that surgery is unnecessary for these patients. "The next step is follow-up — after imagining and biopsy are done. Then the next step is how to move forward," she said.

"It's not ready for primetime, but it will be interesting to see what the next steps are with these patients," Cate said.

Study Identifies Features for pCR

"HER2+ tumors have been shown to be very responsive to chemotherapy, especially with the addition of targeted therapies," said lead author Susie Sun, MD, University of Texas MD Anderson Cancer Center, Houston, who discussed the new study at a press briefing.

"The high rate of pCR seen in HER2+ breast cancer highlights the potential for the omission of surgery in this patient cohort," she commented.

However, the problem is how to actively identify patients who achieve pCR, she noted.

The goal of the study was to help identify unique clinicopathologic characteristics associated with finding residual disease following systemic neoadjuvant treatment.

A secondary endpoint was to evaluate the effect of NST on the invasive and DCIS components in patients with HER2+ breast cancer.

The study cohort included 280 women with clinical T1-2, N0-1 HER2+ breast cancer who received NST that was followed by surgical resection. The clinicopathologic characteristics of patients who achieved pCR in the breast and lymph nodes were then compared with those who had residual disease.

Within the cohort, 102 (36.4%) women achieved pCR in both the breast and lymph nodes following NST, while 50 (17.9%) had residual DCIS in the breast only. DCIS was a component found on the initial biopsy of 129 (46.1%) women.

Those with residual disease in their breast and nodes were more likely to have hormone receptor-positive tumors compared with patients who had negative tumors (73.4% vs 50.8%, respectively; P < .0001).

Certain variables were identified that were predictive of residual disease in the breast and nodes, and these included incomplete radiologic response (OR, 5.62; P = .002) and hormone-positive status (OR, 2.56; P < .0001).

The authors found that combined imaging modalities including MRI, mammogram, and ultrasound following NST had a sensitivity of 97.1% and negative predictive value of 70.6% for detecting residual disease in the breast and lymph nodes.

For nearly two thirds of patients (64.3%) with in situ disease on initial biopsy, NST failed to eradicate the DCIS component. In addition, patients with invasive disease with DCIS on initial core biopsy were less likely than those without DCIS to achieve pCR in the breast (31% vs 43%; P = .038).

For the clinical trials to explore the option of skipping surgery, "we need to eradicate invasive and DCIS components of disease to avoid nidus for carcinoma in the future," said Sun.

"Multimodality imaging alone is not reliable in identifying pCR," Sun commented, adding that "image-guided percutaneous biopsy is required to safely select patients for inclusion in ongoing and future elimination of surgery clinical trials."

"Early Stages of Discovery"

"As we look to the future of treatment for patients with breast cancer, it is clear that a better understanding of tumor biology will guide us in omitting unnecessary treatments for some tumor types while remaining appropriately aggressive for others," commented Carla Fisher, MD, FACS, Indiana University School of Medicine, Indianapolis, in a statement.

She noted that the current study highlights clinical and radiologic characteristics of the aggressive HER2+ breast cancers that help predict a complete response to chemotherapy, thereby setting up opportunities to avoid surgery for these patients in the future.

"While still in the early stages of discovery, we look forward to additional research in this area to improve outcomes for our patients with breast cancer," she said.

Cate has reported no relevant financial relationships.

ASBrS Annual Meeting. Patient Selection for Non-Operative Management of HER2+ Invasive Breast Cancer after Neoadjuvant Systemic Therapy. Presented May 2, 2019.

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