In a recent The Lancet Oncology study, researchers evaluate the efficacy of radiotherapy in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer or triple-negative breast cancer (TNBC) after neoadjuvant systemic therapy (NST).
Study: Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. Image Credit: Pradit.Ph / Shutterstock.com
The rates of pathological complete response (pCR) to NST have dramatically increased over the past several decades. For example, the rates of pCR to NST in patients with TNBC or HER2-positive breast cancer are approximately 60% to 80%. These high efficacy rates raise the possibility that some patients receiving NST might not require breast and nodal surgery, especially if they have not received adjuvant local therapy with radiotherapy.
Previously, the authors of the current study reported that image-guided vacuum-assisted core biopsy (VACB) of the primary breast tumor bed after NST could identify patients likely to have had a pCR. Since then, several other studies have confirmed that image-guided biopsies can accurately identify those with pCR. The success of image-guided VACB is contingent upon selecting appropriate patients and practicing meticulous standardized techniques.
About the study
In the present study, the researchers present findings from a prospective outcome analysis of a phase II trial of eliminating breast surgery in patients with localized HER2-positive breast cancer or TNBC who were assumed to have had a pCR. The study was conducted across seven centers in the United States in feasibility and expansion cohort phases.
Eligible participants were non-pregnant females aged 40 or older with confirmed, unicentric, non-recurrent, and invasive breast cancer who sought breast-conserving therapy and received standard NST regimens. Patients had TNBC or HER2-positive breast cancer, T1 or T2 disease, and N0 or N1 disease, with no evidence of metastatic disease.
Patients were excluded if they were part of a clinical trial of NST requiring surgical excision of the tumor and lymph nodes, showed distant metastases, and had a prior diagnosis of invasive breast cancer, among other factors.
Patients underwent sonography and mammography after completion of the NST regimen. A breast biopsy was done under ultrasound or stereotactic guidance based on the clinical evaluation of the radiologist performing the biopsy.
Breast surgery was not performed in patients with no residual disease in the breast. Standard nodal and breast surgery was performed in patients with residual disease.
All patients received whole-breast irradiation and a mandatory boost. Patients had a physical examination every six months post-radiotherapy.
The researchers were interested in determining the rate of ipsilateral breast tumor recurrence in those who did not undergo breast surgery at six months, as well as one, two, three, and five years.
The primary endpoint was the time from confirmed pCR to the time of ipsilateral breast tumor recurrence or death. Secondary endpoints were the number of patients with residual disease in the final biopsy, number of patients recommended for ipsilateral breast/axillary nodes during follow-up, and quantification of residual disease in surgical specimens.
Fifty-eight patients provided consent to participate, eight of whom were excluded due to consent withdrawal or ineligibility. Fifty females, with a median age of 62, were enrolled and underwent image-guided VACB after NST.
Breast biopsy was done under ultrasound guidance in seven patients and under stereotactic guidance in 43 participants. The average largest tumor size was initially 2.28 centimeters (cm).
Twenty-one patients had TNBC and 29 had HER2-positive breast cancer. The average final tumor size after NST was 0.9 cm. Seventeen patients had a complete radiologic response.
The mean number of VACB samples was 15.24. VACB specimen examination showed residual disease in 19 patients and pCR in 31 patients. The authors did not identify ipsilateral breast tumor recurrences at 26.4 months follow-up in 31 patients with a pCR on VACB post-NST.
No deaths or other recurrence events were reported. Of the patients with residual disease, seven had no residual disease at the time of breast surgery, while 12 had residual disease.
The average size of residual breast disease was 9.0 millimeters (mm) for invasive carcinoma and 2.33 mm for ductal carcinoma in situ. Nine of the 31 patients without residual disease were recommended to have image-guided nodal/breast biopsy.
The authors did not observe any local or distant recurrences during the first planned two-year analysis. Despite being early, the study findings are notable, given that patients with HER2-positive breast cancer or TNBC with residual disease after NST showed recurrences in the first few years.
Breast conservation is best achieved through the elimination of breast surgery after NST. These findings support the feasibility of this approach.
Additional clinical trials must be conducted to validate these findings before breast surgery elimination in exceptional responders to NST could be considered standard care.
- Kuerer, H. M., Smith, B. D., Krishnamurthy, S., et al. (2022). Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. The Lancet Oncology. doi:10.1016/S1470-2045(22)00613-1.