1. Samson, Kurt

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DALLAS-Researchers at MD Anderson Cancer Center have developed a clinicopathologic profile in HER2-positive breast cancer patients that they believe could one day help identify women who can safely forego surgery in favor of nonoperative management after systemic adjuvant therapy.


Hormone-positive tumor status, possible ductal carcinoma in situ (DCIS), and inconclusive findings on imaging after completing neoadjuvant chemotherapy (NCT) were identified as possible characteristics that might be used to differentiate patients who may not require surgery, according to findings presented at the American Society of Breast Surgeons Annual Meeting (Abstract 575089).


The findings could also be used to help identify unique characteristics associated with HER2-positive cancers for patients who may become eligible for inclusion in clinical trials investigating non-operative management of exceptional NCT responders, said lead researcher Susie Sun, MD, a breast surgery oncology fellow at MD Anderson.


She and her colleagues reported that, following NCT, 55.4 percent of women with invasive HER2-positive cancer achieved a pathologically complete response (pCR), 37.5 percent of both pCR invasive and DCIS cancer was eliminated, and 17.9 percent had eradication of only residual DCIS.

Susie Sun, MD. Susie... - Click to enlarge in new windowSusie Sun, MD. Susie Sun, MD

Confirmation of NCT response using combined imaging modalities (MRI, mammogram, ultrasound) is often inconclusive and carries a high rate of false negatives in HER2-positive patients. However, HER2-positive tumors are highly responsive to chemotherapy, studies show, especially with the addition of targeted anti-HER2 therapies, Sun explained.


"Although radiological imaging such as mammograms, ultrasounds, and MRIs have been shown to be unreliable in identifying patients with pCR, we have previously determined that patients with clinically significant residual disease can be accurately identified using a combination of multimodality imaging and image-guided, vacuum-assisted biopsy to the tumor bed," she said.


There is increasing evidence that certain HER2-positive breast cancer patients are exceptional NCT responders, she noted, suggesting that when properly identified, such patients might be good candidates for non-operative treatment.


"No one wants to have surgery unnecessarily," Sun said. "This study and the clinical trial may help us delineate which patients may be effectively treated non-operatively, while allowing us to provide more aggressive surgical intervention to the women with HER2-positive breast cancer who need it."


She and her colleagues examined data on 280 T1-T2, N0-N1 HER2-positive breast cancer patients and found that 36.4 percent had a pCR to NCT in breast and lymph nodes.


"Our study shows that hormone receptor-positive disease, the presence of DCIS at diagnosis, and inconclusive imaging results following neoadjuvant chemotherapy correlated with an incomplete response to NCT, suggesting that these women must go on to surgical treatment," she stated.


Trial Subjects

The findings come from the Multicenter Trial for Eliminating Breast Cancer Surgery in Exceptional Responders with Neoadjuvant Systemic Therapy. Henry Kuerer, MD, PhD, Professor in the Department of Breast Surgical Oncology, is principal investigator, and he also serves as Executive Director of Breast Programs at MD Anderson.


Kuerer said the findings could be especially helpful in selecting subjects for HER2-positive clinical trials. "This study is particularly important right now because it may help identify optimal patients for ongoing clinical trials omitting surgery for carefully selected HER2-positive patients," he explained.

Henry Kuerer, MD, Ph... - Click to enlarge in new windowHenry Kuerer, MD, PhD. Henry Kuerer, MD, PhD

"These findings are extremely important because of the inability of medical imaging to reliably confirm the absence of cancer following initial NCT. They help delineate the types of HER2-positive tumors that should not be included in our trials."


Among the other findings, the researchers found that patients with incomplete pathologic response were more likely to have hormone receptor-positive compared with negative tumors (73.4% vs. 50.8%). Also, those with both invasive disease and DCIS on initial biopsy were less likely than those without DCIS to achieve pathologically complete response (31% vs. 43%).



Carla Fisher, MD, Associate Professor of Surgery and Medical Director of Breast Surgical Oncology at Indiana School of Medicine, Indianapolis, commented on the findings.


"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," she said.

Carla Fisher, MD. Ca... - Click to enlarge in new windowCarla Fisher, MD. Carla Fisher, MD

"This study highlights clinical and radiologic characteristics of the aggressive HER2-positive 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."


As with any new advances in health care management, especially those looking at de-escalating treatment, there will be some patients that prefer to stick with standard treatment and not participate in a clinical trial, noted Judy Boughey, MD, Professor of Surgery and Chair of the Surgery Research Division at Mayo Clinic, Rochester, Minn.


"The information from this trial will be critical to safely advance care, but patients and their tumors must first meet the inclusion criteria: excellent response to neoadjuvant chemotherapy, confirmed on imaging, and percutaneous biopsies of the tumor bed to confirm there is no residual breast cancer."


She also said that results from the ongoing trial (which is open at UPMC, Mayo Clinic, and Carolinas Medical Center) will provide important information on outcomes in these patients to help guide future research, as will the ongoing NRG clinical trial BR005 which is looking at the correlation of percutaneous tumor bed biopsies and surgical.


Kurt Samson is a contributing writer.


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