Medical experts are questioning whether women who respond fully to neoadjuvant systemic therapy (NST) for breast cancer still need surgery, after a research review found that more than 60% of those with triple-negative breast cancer and human epidermal growth factor receptor 2- (HER2) positive breast cancer had a complete response to NST, given before surgery.
An increasing number of people diagnosed with early-stage breast cancer and treated with systemic therapies like chemotherapy or targeted therapy achieve a “complete response” before breast-removal surgery, reports Medical News Today.
Triple-negative breast cancer represents 10%-20% of breast cancer cases, while HER2-positive breast cancer represents around 30% of breast cancers.
Recently, researchers conducted a phase two trial examining subjects with HER2-positive breast cancer or triple-negative breast cancer who had experienced a complete response to NST.
They found it might be possible to “eliminate” the need for breast surgery in some subjects after NST.
Dr Henry Kuerer, PhD, lead author of the study and executive director of Breast Programmes and Robinson Endowed Distinguished professor at MD Anderson Centre at the University of Texas, told Medical News Today: “This is the beginning of a new field that is rapidly advancing. The plane has left the gate and is now on the runway. It is clear that targeted systemic therapies are greatly improving, from about a 12% pathologic complete response 20 years ago to 70% in triple-negative breast cancer today.”
The study was recently published in The Lancet Oncology.
Studying the effects of neoadjuvant systemic therapy
For the study, the researchers enrolled 50 female participants with an average age of 62 in a clinical trial. Among them, 38 were white, 10 were black, and two were of other ethnicities.
While 58% had HER2-positive breast cancer, the remaining 42% had triple-negative breast cancer. Exclusion criteria for the trial included the progression of cancer to more than 20% of breast tissue and evidence for cancer spread to distant areas of the body.
All participants underwent standard NST regimens as recommended by their oncologists. Afterward, they underwent a breast biopsy. Whereas 38% still had breast cancer after NST, 62% had a complete pathological response and thus no longer had the condition.
Study participants who did not show histological evidence of residual cancer did not have breast surgery. However, those that did had standard breast and nodal surgery.
All subjects underwent radiation therapy followed by physical examinations every six months for an ongoing five-year period.
The researchers noted that all subjects who were tumour-free after NST remained cancer-free after a median follow-up of 26.4 months. They wrote that these findings are important as recurrences of triple-negative breast cancer and HER2-positive breast cancer tend to occur within a few years of treatment.
They also noted that more than half of the subjects without a complete response after NST had a complete response after surgery.
Developments in breast cancer treatment
When asked why some people may no longer need surgery after NST, Dr Bhavana Pathak, board certified hematologist and medical oncologist at Memorial Care Cancer Institute at Orange Coast Medical Centre in California, who was not involved in the study, said: “Certain types of breast cancer (triple negative or HER2) tend to respond well to systemic therapy. We say systemic therapy rather than chemotherapy, as our therapies have evolved to use immunotherapies and biological therapies (i.e, targeted antibody treatment). With these systemic therapies, there is a range of responses, but up to a 60% chance of having a complete pathologic response (tumour going away) after therapy.”
More clinical trials are still needed
The researchers concluded that additional clinical trials are needed to evaluate their findings.
“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,” Kuerer said.
Study details
Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial
Prof Henry Kuerer, Prof Benjamin Smith, Prof Savitri Krishnamurthy, Prof Wei T Yang, Prof Vicente Valero, Prof Yu Shen, et al
Published in The Lancet Oncology on 25 October 2022
Summary
Background
Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided 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 an image-guided VACB-determined pathological complete response.
Methods
This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1–2N0–1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using 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.
Findings
Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled 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 tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred.
Interpretation
Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed.
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