Patients with HER2-positive breast cancer and triple-negative breast cancer may not require breast surgery if a pathological complete response can be identified using image-guided vacuum core biopsy following neoadjuvant systemic therapy.
The use of image-guided vacuum-assisted core biopsy (VACB) to identify pathological complete response (pCR) following neoadjuvant systemic therapy in patients with HER2-positive breast cancer and triple-negative breast cancer demonstrated feasibility and allowed for omition of surgery in select patients, according to findings from a phase 2 trial (NCT02945579) published in Lancet Oncology.
With a median follow-up of 26.4 months (interquartile range [IQR], 15.2-39.6), study investigators observed no ipsilateral breast tumor recurrence in 31 patients who had a pCR identified by VACB following neoadjuvant therapy. VACB examinations indicated that 38% of patients had residual disease, and 62% (n = 31/50; 95% CI, 47.2%-75.4%) achieved pCR in the breast.
“As surgeons, we had a responsibility to figure out a way forward to eliminate surgery for patients where it would provide no conceivable benefit,” study author Henry M. Kuerer, MD, PhD, FACS, executive director of Breast Programs at the University of Texas, MD Anderson Cancer Center, said in a comment to CancerNetwork®. “This approach will need to be tested in several larger studies before it becomes a standard treatment option, and we are committed to studying this further.
Authors of the prospective, single-arm phase 2 trial enrolled patients with TNBC or HER2-positive breast cancer across 7 treatment centers in the United States. All patients received external-beam whole-breast irradiation at 40 Gy in 15 fractions or 50 Gy in 25 fractions along with a mandatory boost of 14 Gy in 7 fractions.
The primary end point of the study was biopsy-confirmed ipsilateral breast tumor recurrence rate determined using the Kaplan-Meier method. Planned secondary end points included residual disease rate and number of patients for whom image-guided biopsy of the ipsilateral breast or axillary nodes was recommended during follow-up.
Patients 40 years or older who were not pregnant and had pathologically confirmed, non-recurrent, unicentric, invasive breast cancer were eligible to enroll on the study. Additional inclusion criteria included having a residual breast lesion less than 2 cm and no clinical or pathological evidence of distant disease.
A total of 50 patients enrolled on the study and underwent VACB after receiving neoadjuvant systemic therapy. The median patient age was 62 years (IQR, 55-77), and most were White (76%) and non-Hispanic (82%). Most patients had stage T2N0M0 disease (44%), ductal histology (96%), and TNBC (42%).
In a prespecified analysis, 37% (n = 7/19) of patients with residual disease identified via image-guided VACB had no residual disease at the time of breast surgery, whereas 63% (n = 12/19) had residual disease. Among the latter, the mean size of residual breast disease was 9.00 mm (standard deviation [SD], 5.03) for invasive cancer and 2.33 mm (SD, 2.09) for ductal carcinoma in situ.
According to the study authors, post-hoc outcome analyses identified no difference in rates of breast pCR by tumor hormone receptor status. Investigators reported a pCR rate of 71% (n = 15/21) in patients with TNBC and 55% (n = 16/29) in patients with HER2-positive breast cancer. Among patients with HER2-positive breast cancer, 39% (n = 7/18) of those with hormone receptor (HR)–positive disease and 81% (n = 9/11) of those with HR-negative disease achieved pCR.
There were no notable difference in pCR based on either radiological CRs (82%) compared wirh radiological incomplete responses (52%; P = .06).
Grade 1 complications were observed in 4% (n = 2/50) of patients who underwent VACB. One patient experienced nausea while undergoing the procedure that resolved without intervention. Additionally, another patient experienced malfunctions related to the VACB device that were later rectified. No serious adverse effects or patient deaths occurred.
Kuerer also spoke about how future research could work to answer the question whether radiotherapy could be used as a de-escalation strategy in select patients with breast cancer.
“At MD Anderson, my colleagues are also testing whether radiotherapy alone for certain small hormonally responsive breast cancers can eradicate the cancers without the need for surgery and another de-escalation cohort that is testing the hypothesis that radiotherapy can be eliminated among cases receiving standard preoperative systemic therapies and surgery if no cancer is identified in the specimen,” he said. “Our goal is to allow for maximal control of disease and survival with the minimum of multimodal therapies for breast cancer and other malignancies.”
Kuerer HM, Smith BD, Krishnamurthy S, et al. Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2022;23(12):P1517-1524. doi:10.1016/S1470-2045(22)00613-1