Henry Kuerer, MD, PhD
The concept of de-escalating surgical therapy for breast cancer continues to find acceptance. This is an exhilarating and potentially pivotal time in the management of invasive breast cancer, as we begin to test the new paradigm that not all patients need surgery for the management of their malignancy after neoadjuvant systemic therapy.
We have known for a very long time that neoadjuvant therapy can eliminate both invasive and in situ carcinoma in up to 50% of patients, particularly when their subtypes are triple-negative disease or HER2-positive cancers. If systemic therapy will increase a patient’s survival from breast cancer, neoadjuvant systemic therapy, given as the primary therapy before consideration of surgery and radiotherapy, can have a dramatic effect locally.
This allows for not only breast-conserving surgery but also potential elimination of surgery altogether prior to radiotherapy. In the past, following systemic therapy, the difficulty has been to distinguish patients with residual disease from patients without any residual cancer. In general, breast imaging after systemic therapy lacks sufficient sensitivity and specificity to safely determine which patients might be safe to move on to radiotherapy without the surgery. Recently, our group demonstrated that percutaneous biopsy after neoadjuvant therapy can accurately identify patients without residual disease.1
Combined biopsy demonstrated an accuracy of 98%, a false-negative rate of 5%, and a negative predictive value of 95% in predicting residual breast cancer.1
Proceeding With Caution
Patients should not be offered elimination of surgery after neoadjuvant systemic therapy unless they are on a prospective clinical trial, as the safety of this approach has not been proved yet. The key here is the optimal, accurate, and safe selection of patients who have had a pathologic complete response (pCR), which is no residual invasive or in situ carcinoma after neoadjuvant systemic therapy. If there is no detectable residual disease among patients who will be receiving radiotherapy, the benefit of surgery would appear to be very low and potentially unnecessary.
This burgeoning new paradigm requires meticulous and precise image-guided biopsy of the tumor bed, which was performed in The University of Texas MD Anderson Cancer Center feasibility trial.1
Using the MD Anderson approach to optimize selection with extensive image-guided biopsy, the trial found that about 48% of patients had no evidence of disease in the breast after neoadjuvant systemic therapy, and the rest of the cases demonstrated either residual carcinoma, atypia (with the correct area sampled, by clip), and/or therapy changes consistent with representative sampling of the tumor bed. In fact, false-negative cases using vacuum-assisted core biopsy in our study clearly demonstrated therapy-related changes in the biopsy specimens, but these cases were unique in that they had only 4 or 6 core biopsies taken, while the median for the rest of the study was 12. This led us to conclude that to safely test the elimination of surgery in our ongoing trial, there should be a minimum of 12 cores of the residual region of prior carcinoma in and around the area of the marker clip; we have limited the trial to patients who present with less than 5 cm of disease by initial breast imaging prior to neoadjuvant systemic therapy.2