Image-guided biopsies accurately identify breast cancer patients who achieve pathologic complete response following neoadjuvant therapy

Results prompt Phase II trial to avoid surgery in select groups of invasive breast cancer patients    

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 (pCR) after neoadjuvant systemic therapy (NST) 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 in Annals of Surgery. The study was first presented by principal investigator Henry M. Kuerer, M.D., Ph.D., professor, Breast Surgical Oncology, at the 2016 San Antonio Breast Cancer Symposium.

Worldwide, triple negative and HER2 positive breast cancers account for about 370,000 women diagnosed annually, says Kuerer. With recent advances in neoadjuvant systemic therapy for both subsets of cancer, the pCR rates found at the time of surgery in these patients can be as high as 60 percent. This high rate of pCR 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 pathological review,” said 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 NST.

“However, by doing the same image-guided, percutaneous needle biopsies after NST 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 Kuerer. “This study also demonstrated that imaging alone has decreased accuracy, specificity and predictive value compared with image guided biopsy in detecting residual disease.”

The prospective single-center study met its primary endpoint and enrolled 40 women with early-stage (stage I, II, III) triple negative (26 patients) or HER-2 positive (14 patients) breast cancer. As per standard practice, all patients received NST. Prior to standard-of-care surgery, all participants consented to undergo image-guided fine needle aspiration (FNA) biopsy and an ultrasound and/or mammography guided vacuum-assisted core biopsy (VACB). The study measured for accuracy and false negative rate, and negative predictive value was calculated for FNA alone, VACB alone and FNA and VACB in combination. Breast pCR was defined as no residual disease at the time of surgery.

Median initial tumor size was 3 centimeters and 40 percent of patients had nodal metastasis at the time of diagnosis. After NST, the median residual tumor size was 1.1 cm, with 94.1 percent of patients having no palpable abnormality.

Researchers found that following NST, VACB combined with FNA had 98 percent accuracy, 5 percent FNR, and 95 percent predictive value for determination of residual disease. Grade 1 biopsy associated adverse events, including bleeding, hematoma and bruising, occurred in six patients (20.4 percent).

“With this knowledge, there’s an obligation to test whether no surgery, or ‘ultimate breast conserving therapy,’ is safe,” said Kuerer.

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-proved pCR after NST will undergo whole-breast radiation, 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,” says Kuerer. “If these findings prove to be true, it would be groundbreaking for patients – both physically and psychologically.”

In addition to Kuerer, other authors on the all-MD Anderson study include: Wei T. Yang, M.D., Gaiane M. Rauch, M.D., Ph.D., Beatriz E. Adrada, M.D., Lumarie Santiago, M.D., Rosalind Candelaria, M.D., Elsa Arribas, M.D., and Tanya Moseley, M.D., all of Diagnostic Radiology; Savitri Krishnamurthy, M.D., Michael Gilcrease, M.D., Ph.D., both of Pathology; Kelly K. Hunt, M.D., Abigail S. Caudle, M.D., Sarah M. DeSnyder, M.D., Anthony Lucci, Jr., M.D., Rosa Hwang, M.D., Mediget Teshome, M.D., and Makesha V. Miggins, M.D., all of Breast Cancer Surgery; Brian P. Hobbs, Ph.D., Biostatistics; Mariana Chavez Mac Gregor, M.D., Breast Medical Oncology and Health Services Research; Benjamin D. Smith, M.D., Ph.D., Radiation Oncology, and Vincente Valero, M.D., Breast Medical Oncology.

The study was financially supported by the PH and Fay Etta Robinson Distinguished Professorship in Cancer Research, a Cancer Center Support Grant from the National Institutes of Health (NIH), CA16672, a NIH P30 grant, CA016672, and funding from the MD Anderson Clinical Research Funding Award Program.