A prospective phase II trial published in Radiotherapy and Oncology suggests that definitive stereotactic ablative radiotherapy combined with endocrine therapy may provide a nonoperative treatment option for carefully selected patients with favorable early-stage low-risk breast cancer.
The study evaluated whether patients with small, hormone receptor–positive and HER2-negative breast cancers could safely avoid surgery after receiving endocrine therapy and five-fraction SABR.
Although the findings are preliminary and based on a small cohort, the results offer an important signal for future breast cancer treatment de-escalation research.
Why This Study Matters
Early-stage hormone receptor–positive breast cancer generally has an excellent prognosis with standard treatment consisting of breast-conserving surgery, radiotherapy, and endocrine therapy.
Because outcomes are already favorable, researchers have increasingly explored whether some elements of treatment can be reduced or omitted without compromising cancer control.
Previous de-escalation studies have mainly focused on omitting radiotherapy or reducing endocrine therapy. Surgery omission has received much less prospective investigation in this biologically favorable group.
A nonoperative approach may be particularly relevant for older patients, those with significant comorbidities, or patients who strongly prefer to avoid surgery.
Trial Design
This prospective, single-center phase II trial enrolled 20 women aged 40 years or older with unicentric cT1N0M0 breast cancer.
Eligible tumors were hormone receptor positive, HER2 negative, nonlobular, and without lymphovascular invasion. All tumors were grade 1 or 2, and genomic risk was low according to age-specific Oncotype DX eligibility criteria.
The median age was 70.5 years.
Patients first received approximately 3 months of endocrine therapy. This was followed by definitive SABR delivered in five fractions.
The treatment approach was designed to ablate the intact breast tumor while limiting exposure to surrounding normal tissue.
Assessing Treatment Response
Between 6 and 12 months after SABR, patients underwent vacuum-assisted image-guided core biopsy of the treated tumor bed.
Patients with pathologic complete response were allowed to omit surgery.
Those with residual invasive disease were recommended to proceed with surgery, while patients with near-complete response were considered individually following multidisciplinary review and shared decision-making.
The study’s co-primary endpoints were the pathologic complete response rate and 3-year progression-free survival among patients managed without surgery.
Pathologic Response
Nineteen of the 20 enrolled patients underwent post-treatment biopsy.
Pathologic complete response was identified in 10 of 19 patients, corresponding to a rate of 53%.
Another 7 patients, or 37%, demonstrated near-complete response.
Taken together, nearly 90% of evaluable patients achieved either complete or near-complete pathologic response after endocrine therapy and SABR.
These findings suggest that favorable hormone receptor–positive breast cancers may be highly responsive to a carefully selected combination of endocrine treatment and ablative radiotherapy.
Outcomes Without Surgery
Twelve patients were ultimately managed without surgery.
After a median follow-up of 44.9 months, the estimated 3-year progression-free survival was 92%.
There were no local, regional, or distant breast cancer recurrences among patients who omitted surgery.
One patient died from a cause unrelated to breast cancer.
The observed 5-year progression-free survival signal was also encouraging, although the small cohort and limited number of events mean that longer follow-up is essential.
Patient-Reported Outcomes
Decisional regret remained low throughout follow-up and did not significantly increase over 36 months after SABR.
Breast-specific outcomes, including pain, cosmetic concerns, edema, and functional symptoms, also remained stable.
This is clinically important because a nonoperative treatment strategy should not only control the tumor but also maintain quality of life and patient satisfaction.
Some broader quality-of-life domains declined over time, although these changes may also reflect age, comorbidities, and other health factors rather than treatment alone.
The Role of Tumor Biology
Exploratory analyses suggested that stronger hormone receptor expression may be linked to a greater likelihood of complete response.
Higher estrogen receptor and progesterone receptor expression were separately associated with pathologic complete response.
Older age was also associated with a higher probability of response, potentially reflecting more favorable luminal tumor biology.
These findings raise the possibility that future nonoperative strategies could be guided not only by tumor size and stage but also by molecular and endocrine characteristics.
Why Biopsy Matters
A major challenge in omitting breast surgery is confirming that the tumor has been completely eradicated.
Imaging alone may not be sufficient to identify residual microscopic disease. For this reason, the protocol used vacuum-assisted image-guided core biopsy of the tumor bed after SABR.
This response-assessment strategy is central to the concept.
The study does not support simply giving radiotherapy and omitting surgery in all low-risk patients. Instead, it evaluates a highly selected and biopsy-guided approach in which surgery is omitted only after a favorable treatment response.
Limitations
The study included only 20 patients and was conducted at a single highly experienced institution.
It was nonrandomized and lacked a standard-treatment comparison group.
The cohort was highly selected, with small, low-grade, hormone-sensitive tumors and a median age above 70 years. The results therefore cannot be generalized to younger patients, larger tumors, higher-grade disease, lobular cancers, HER2-positive disease, or triple-negative breast cancer.
The follow-up period is also not yet sufficient to fully assess late local recurrence in hormone receptor–positive breast cancer, where recurrences may occur many years after treatment.
Pathologic complete response was assessed through biopsy rather than surgical excision, meaning that a small risk of unsampled residual disease remains.
Clinical Takeaway
This phase II study provides an important proof of concept.
In carefully selected patients with favorable early-stage hormone receptor–positive breast cancer, endocrine therapy followed by five-fraction definitive SABR produced substantial complete and near-complete pathologic response rates.
Among patients who avoided surgery, no breast cancer recurrences were observed during the available follow-up, and decisional regret and breast-specific patient-reported outcomes remained stable.
However, this approach remains investigational.
Larger prospective trials, stronger response-prediction tools, standardized post-treatment biopsy methods, and longer follow-up are needed before definitive SABR can be considered an alternative to surgery in routine breast cancer care.
For now, the study opens an important question for future de-escalation research
Can some biologically favorable breast cancers be treated effectively without an operation?
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