Image-Guided Biopsies Accurately Identify Patients With Breast Cancer Who Achieve Pathologic Complete Response Following Neoadjuvant Therapy
In a clinical feasibility trial conducted at The University of Texas MD Anderson Cancer Center, image-guided biopsies identified select breast cancer patients who achieved pathologic complete response after neoadjuvant systemic therapy consisting of chemotherapy and/or targeted therapy. Should the findings be replicated in future studies, this research would be the first indication that surgery altogether may be eliminated for a large group of patients.
The results of this trial are now updated with new data and published by Kuerer et al in Annals of Surgery. The study was first presented by principal investigator Henry M. Kuerer, MD, PhD, Professor, Breast Surgical Oncology, at the 2016 San Antonio Breast Cancer Symposium (Abstract P5-16-30).
Worldwide, triple-negative and HER2-positive breast cancers account for about 370,000 women diagnosed annually, said Dr. Kuerer. With recent advances in neoadjuvant systemic therapy for both subsets of cancer, the pathologic complete response rates found at the time of surgery in these patients can be as high as 60%. This high rate of pathologic complete response naturally raises the question of whether surgery is required for all patients, particularly those who will receive adjuvant radiation.
“We believe surgery may potentially be redundant—at least for triple-negative and HER2-positive breast cancer—because of such a high chance for no evidence of disease at the time of pathologic review,” said Dr. Kuerer. “If there’s no cancer left after the patient has received chemotherapy and the patient is going to receive local radiation therapy, is surgery actually needed?”
The challenge has been that standard breast imaging methods cannot accurately predict residual disease after neoadjuvant systemic therapy.
“However, by doing the same image-guided, percutaneous needle biopsies after neoadjuvant systemic therapy that we do at time of diagnosis, our research reveals we may be able to accurately predict which women will have cancer or not,” said Dr. Kuerer. “This study also demonstrated that imaging alone has decreased accuracy, specificity, and predictive value compared with image-guided biopsy in detecting residual disease.”
Major Findings
The prospective single-center study met its primary endpoint and enrolled 40 women with early-stage (stage I–III) triple-negative (n = 26) or HER2-positive (n = 14) breast cancer. As per standard practice, all patients received neoadjuvant systemic therapy.
Prior to standard-of-care surgery, all participants consented to undergo image-guided fine-needle aspiration biopsy and an ultrasound and/or mammography guided vacuum-assisted core biopsy. The study measured for accuracy and false-negative rate, and negative predictive value was calculated for fine-needle aspiration alone, vacuum-assisted core biopsy alone, and fine-needle aspiration and vacuum-assisted core biopsy in combination. Breast pathologic complete response was defined as no residual disease at the time of surgery.
Median initial tumor size was 3 centimeters and 40% of patients had nodal metastasis at the time of diagnosis. After neoadjuvant systemic therapy, the median residual tumor size was 1.1 cm, with 94.1% of patients having no palpable abnormality.
Researchers found that following neoadjuvant systemic therapy, vacuum-assisted core biopsy combined with fine-needle aspiration had 98% accuracy, 5% false-negative rate, and 95% predictive value for determination of residual disease. Grade 1 biopsy–associated adverse events, including bleeding, hematoma, and bruising, occurred in six patients (20.4%).
“With this knowledge, there’s an obligation to test whether no surgery, or ‘ultimate breast-conserving therapy,’ is safe,” said Dr. Kuerer.
Continued Trial
The accuracy of the preliminary findings led MD Anderson’s Institutional Review Board to approve and open a new phase II clinical trial at MD Anderson and then across the MD Anderson Cancer Network. The study is enrolling women with stage I and II HER2-positive and triple-negative breast cancer. Participants who achieve image-guided, biopsy-proven pathologic complete response after neoadjuvant systemic therapy will undergo whole-breast radiation therapy, without surgery. The trial is the first to use image-guided biopsies in this setting and not include surgery.
“There is an urgency to test whether surgery is needed. In conversations with my patients, many express concerns about overtreatment. They want the most personalized care with as minimal treatment as possible, and I am honored to be involved with this essential study,” said Dr. Kuerer. “If these findings prove to be true, it would be groundbreaking for patients—both physically and psychologically.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
