Elimination of Breast Surgery for Invasive Breast Cancer in Exceptional Responders to Neoadjuvant Systemic Therapy Summary Background Neoadjuvant systemic therapy (NRT) for triple-negative breast cancer and HER2-positive breast cancer produces a complete pathologic response in approximately 60% of patients. A complete pathological response to NRT predicts an excellent prognosis and can be accurately determined by image-guided percutaneous vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery , in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had a pathological complete response determined by image-guided VACB. Methods This phase 2, multicenter, single-arm trial was conducted at seven US centers. Women aged 40 years and older who were not pregnant with single-center cT1-2N0-1M0 triple-negative breast cancer or HER2 breast cancer positive and a residual breast lesion of less than 2 cm on imaging after clinically standard NST were eligible for inclusion. The patients underwent a biopsy (minimum of 12 cores) obtained by VACB guided by 9G image of the tumor bed. If no invasive or in situ disease was identified , breast surgery was omitted and patients underwent standard whole-breast radiation therapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the rate of biopsy-confirmed ipsilateral breast tumor recurrence determined by the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579. Results Between March 6, 2017 and November 9, 2021, 58 patients agreed to participate; however, four (7%) did not meet the final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB after NST. The median age of the included patients was 62 years (IQR 55-77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2–75·4]. At a median follow-up of 26.4 months (IQR 15.2–39.6), no ipsilateral breast tumor recurrences occurred in these 31 patients. There were no biopsy-related serious adverse events or treatment-related deaths. Interpretation Elimination of breast surgery in highly selected patients with a complete pathological response determined by image-guided VACB after NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed. |
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Biopsy protocol developed by MD Anderson identifies patients at low risk of recurrence
Patients with early-stage breast cancer who had a pathologic complete response (pCR) to neoadjuvant chemotherapy can skip surgery and receive standard radiation therapy with a low chance of disease recurrence, according to a new study from researchers at the University of Texas MD Anderson Cancer Center.
Results from the Phase II trial, published in The Lancet Oncology , assessed the likelihood of breast cancer returning in patients who are in complete remission after receiving chemotherapy and radiation without surgery.
Each of the 31 patients followed had a complete response to chemotherapy and none had a breast tumor recurrence after a median follow-up of 26.4 months.
“The latest form of breast conservation therapy is to completely eliminate breast surgery for invasive disease,” said principal investigator Henry Kuerer, M.D., Ph.D., professor of Breast Surgical Oncology. “This research adds to growing evidence showing that newer drugs can completely eradicate cancer in some cases, and early results show we can safely eliminate surgery in this select group of women with breast cancer.” .
This is the first modern prospective trial of omission of surgery in patients with early-stage breast cancer who respond favorably to chemotherapy. High responses are indicated by state-of-the-art breast image-guided vacuum-assisted core biopsy (VACB). These results build on Kuerer’s previous research using a biopsy protocol developed by MD Anderson to accurately identify patients who achieve pCR after chemotherapy. These patients, known as "exceptional responders," have a lower risk of breast cancer recurrence and are candidates for avoiding breast surgery.
Improved chemotherapeutic agents have significantly increased pCR rates, and patients with triple-negative or HER2-positive breast cancer are now achieving pCR in 60% to 80% of cases. Combining these high response rates with image-guided selective VACB and strict histological processing has improved clinicians’ ability to determine which patients may not require surgery.
The multicenter trial enrolled 50 women over the age of 40 with early-stage triple-negative or HER2-positive breast cancer and a residual breast lesion of less than 2 centimeters as determined by imaging after standard chemotherapy treatment. Patients had image-guided VACB. If no disease was identified on biopsy, breast surgery was omitted and patients received standard whole-breast radiation therapy.
The average age of the participants was 60.4 years; 21 patients had triple-negative breast cancer and 29 had HER2-positive breast cancer. Thirty-eight participants were white, 10 were black, and 2 were other ethnicities/races. The VACB identified CRP in 31 patients. There were no biopsy-related serious adverse events or treatment-related deaths.
“At the moment, standard breast cancer surgery is still necessary,” Kuerer said.
“While these results are notable and quite promising, it is important for patients to know that this is the beginning of a new type of treatment for select patients. "Much longer follow-up and more studies will be necessary before this approach can be integrated into routine breast cancer care."
Researchers will continue to follow trial participants for long-term results. As a secondary objective of the study, researchers are also measuring minimal residual disease from liquid biopsies to determine if they correlate with CRP.
Although this was a small, non-randomized study, it shows the feasibility of this approach. A larger randomized study is needed to directly compare treatments before considering any changes to the standard of care.
This study was funded by the National Cancer Institute/National Institutes of Health (P30 CA016672, UL1 RR024148), the PH and Fay Etta Robinson Distinguished Professorship in Cancer Research, and funding from the MD Anderson Clinical Research Funding Awards Program .
