Is Breast Surgery Needed for Everyone with Early-Stage Breast Cancer?

Friday morning at the San Antonio Breast Cancer Symposium (SABCS) ended with four presentations looking at the possibility of using biopsies to test if all breast cancer has been destroyed by neoadjuvant treatment. If a test can be found that can reliably assess complete response, some people may be able to go without surgery. None of the studies presented Friday found a method accurate enough to change practice, but research on sparing people from surgery is likely to continue.

Background

Neoadjuvant treatment, giving chemotherapy or targeted treatments before surgery, is increasingly used for early-stage breast cancer, especially in triple-negative breast cancer and HER2-postive breast cancer. This may lead to pathologic complete response, a term that means that no signs of cancer remain.

Pathological complete response is associated with very low levels of recurrence. It was recently recognized as a surrogate endpoint by the Food and Drug Administration. This means that if a treatment increases rates of pathological complete response, that is a sign that it will also lower rates of recurrence and lengthen life when being considered for special FDA programs and approval.

While pathologic complete response is a very good outcome, it can only be determined through breast surgery. Presenters described the uncomfortable situation highlighted by patients who ask why surgery was needed if there was no cancer left to remove. The studies presented at SABCS on Friday sought to address this dilemma by testing whether a biopsy showing no sign of cancer was a reliable way to determine pathological complete response without surgery.

Results

The four studies aimed to determine if biopsies could predict pathologic complete response in most cases and limit the number of false negative results. A false negative is a result that shows there is no cancer, when there actually is cancer remaining.

RESPONDER Trial

In this study, 398 patients were tested with image-guided, vacuum-assisted biopsy, followed by standard breast surgery – lumpectomy or mastectomy. The surgery would also serve as a reference test to judge the accuracy of the biopsies. The aim was a false-negative rate of 10 percent or less. The results showed a false-negative rate of 17.8 percent. Looking into the results, researchers noted that half of the false negatives may have been due to avoidable causes, and recommended more strict procedures and more limited selection of participants in future studies.

Accuracy of breast biopsy to predict residual cancer: a pooled analysis

This study involved an analysis of previous trials that had used image-guided biopsies to look for residual breast cancer in women treated with neoadjuvant chemotherapy.

The study found that biopsies produced a false-negative rate of 18.7 percent. In a subgroup analysis, they found a group of HER2-positve breast cancers where the false-negative rate was 4.2 percent, but it was a small group and the terms were defined after the studies. Such a result should be confirmed in a randomized trial.

NRG-BR005

This phase II trial looked at biopsies in addition to clinical examinations and imaging to identify if participants had a pathologic complete response. The endpoint was negative predictive value, a measure that says how likely a negative result is to be accurate. The goal was to have 90 percent or higher negative predictive value.

The study looked at biopsies in 98 people followed by lumpectomy and found a negative predictive value of 77.5 percent, which did not meet the primary endpoint.

MICRA Trial

The MICRA trial required using MRI before and after neoadjuvant therapy to guide biopsies, and also gave more specific biopsy instructions, requiring eight cores taken with a 14-gauge biopsy needle. The 14-gauge needle is among the smallest used in the studies presented, and results from this study and others suggest that a larger needle may be needed for accurate results. The study included 167 patients and resulted in a false negative rate of 37 percent.

What Does This Mean for Me

There is a lot of interest among patients and doctors to better suit treatment to a person’s diagnosis, for people who need more or better treatment and also for those whom some standard treatments are not offering any added benefit. With more people getting neoadjuvant treatment and having no sign of cancer at the end, there is, and will continue to be, interest in finding if there are people who do not need to get surgery. However, early efforts are proving the challenge may be a difficult one.

Despite multiple studies looking at this question, none were able to reliably find a method for biopsy to determine pathologic complete response. Additionally, during the presentation, some doctors questioned whether a 10 percent false negative rate is an acceptable goal to begin with.

Many of the presenters suggested adjustments to the method, such as providing more specific guidance on the biopsy needle gauge and the number of cores taken, as well as more careful selection of study participants. Furthermore, pathologist Kalliopi Siziopikou, MD, PhD, in a discussion of these studies, presented larger challenges that remain in this area. She explained that when cancer “shrinks” it does not appear as a tumor the size of an orange becoming a tumor the size of a grape. Instead, it usually results in small clusters of cancer cells throughout the tumor bed, the area that had been occupied by the tumor. These small clusters are less likely to be detected using a biopsy. Also, eliminating surgery means losing other information pathologists learn from removing the tumor bed tissue.

For now, surgery after neoadjuvant therapy remains standard, but as treatments bring better outcomes, and doctors better understand what these effects mean, there may be progress coming in this area soon.