Nonsurgical Treatment With Radiotherapy in Early-Stage Breast Cancer

Can Surgery Be Omitted in Early-Stage Breast Cancer? A New Threshold for De-escalation With Endocrine Therapy and Ablative Radiotherapy

A New Frontier for De-escalation in Breast Cancer: Smarter Treatment Rather Than Simply Less Treatment

The history of breast cancer treatment is, in one sense, a history of seeking treatment that is less traumatic yet equally safe. At one time, more extensive surgery was thought to produce better outcomes in breast cancer. Over time, randomized studies showed that breast-conserving surgery and radiotherapy could provide survival outcomes similar to mastectomy in suitable patients. Axillary surgery was subsequently reduced, radiotherapy courses became shorter, and even omission of radiotherapy in some older, low-risk patients began to be discussed.

Yet most of these studies shared one feature: surgery remained central. De-escalation generally meant reducing postoperative radiotherapy, axillary intervention, or the intensity of systemic treatment. The study presented at ESTRO 2026 focuses on a much more radical question: if the tumor can be eliminated completely using nonsurgical methods in selected patients, and this can be confirmed by biopsy, is surgery truly mandatory?

This question is particularly important in hormone receptor-positive, HER2-negative early-stage breast cancer. This subtype is often a slower-moving group of diseases, sensitive to endocrine therapy and with more predictable biology. Nevertheless, pathological complete response rates with conventional neoadjuvant endocrine therapy are generally low. Adding ablative, highly precise radiotherapy to endocrine therapy is therefore a new and noteworthy biological strategy.

A Phase 2 Study in 20 Highly Selected Patients

This prospective phase 2 study enrolled 20 eligible patients with hormone receptor-positive, HER2-negative, stage I, nonlobular breast cancer. Patients had to be aged 50 or older, have an Oncotype DX score of 25 or below, and have low-risk tumor biology. These selection criteria are crucial because the study focused on a biologically most suitable, low-risk subgroup rather than the general breast cancer population.

Patients first received endocrine therapy for 3 months. They were then restaged and underwent definitive ablative radiotherapy. The radiotherapy dose was 37,5 Gy / 5 fractions and fractions were delivered every other day. An MR-linac was used whenever possible; 80% of patients could be treated with an MR linear accelerator, while the remaining patients received treatment with a linac equipped with CT-on-rails infrastructure.

Biopsy-Confirmed Pathological Complete Response Is Required to Omit Surgery

The most critical aspect of the study is that surgery was not omitted automatically. Approximately 6–12 months after radiotherapy, patients underwent percutaneous, vacuum-assisted, image-guided core biopsy. If the biopsy demonstrated a pathological complete response, surgery was not recommended, and the patient entered follow-up without surgery.

This approach addresses the fundamental safety question in studies of surgery omission: is imaging alone sufficient? Most likely not. Advanced imaging, changes in tumor volume, and extensive sampling with vacuum biopsy are therefore combined to try to reduce the risk of microscopic residual disease.

Pathological Complete Response: pCR in 10 of 19 Biopsies

In the study, 95% of patients underwent biopsy assessment; one patient declined biopsy. A pathological complete response was found in 10 of the 19 patients who underwent biopsy. This corresponds to a 53% pCR rate . The confidence interval is wide (95% CI: 30%–73%) because the number of patients is small; nevertheless, this rate is noteworthy for HR+/HER2-negative low-risk disease.

The difference between 6 and 12 months is biologically interesting. Treatment responses in HR-positive tumors often develop more slowly. An early biopsy may therefore capture a biological response that is not yet complete. The apparently higher pCR rate at the later time point supports the idea that the effects of endocrine therapy and radiotherapy may produce tumor eradication over time; however, this interpretation must be confirmed in larger studies.

No Progression Was Observed in Patients Who Omitted Surgery

The median follow-up in patients who could omit surgery was 37,3 months . During this follow-up, the disease progression rate was reported as %0 . In the overall study context, the 3-year progression-free survival rate was %92 . One patient died from causes unrelated to breast cancer.

The Roots of Surgery Omission: First Less Surgery, Then Less Radiotherapy, and Now Nonsurgical Treatment

The concept of reducing treatment in breast cancer is not new. The transition from radical mastectomy to more limited surgery was one of the greatest paradigm shifts in breast cancer treatment. Axillary dissection was subsequently reduced in selected patients, and sentinel lymph node biopsy became standard. In radiotherapy, lengthy regimens became shorter; partial breast irradiation, ultrahypofractionation, and omission of radiotherapy in some older, low-risk patients were discussed.

This new study, however, occupies a different place along that historical trajectory. Most earlier de-escalation studies asked, “Which treatment can we reduce after surgery?” Here, the question is, “Is there biological residual disease that makes surgery truly necessary?” This is a deeper inquiry that could change the philosophy of breast cancer treatment.

First Tested in TNBC and HER2-Positive Disease; Now Extending to HR-Positive, Low-Risk Disease

Nonsurgical treatment for breast cancer was previously considered particularly in early-stage triple-negative and HER2-positive breast cancer. These subtypes may achieve higher pathological complete response rates with neoadjuvant chemotherapy and targeted therapies. In modern prospective studies led by MD Anderson, surgery was omitted in some patients with pCR confirmed by image-guided vacuum biopsy after neoadjuvant treatment, followed by standard radiotherapy and follow-up.

In the 5-year results published in 2025, no breast cancer recurrence was reported during a median follow-up of 55,4 months in 31 patients with early-stage TNBC or HER2-positive breast cancer who had biopsy-confirmed pCR after neoadjuvant systemic treatment and did not undergo surgery. These data are highly impressive; however, the biology, dynamics of treatment response, and patient population differ from those of the HR+/HER2-negative low-risk study at ESTRO 2026.

Why Are These Data More Surprising in HR-Positive Disease?

Pathological complete response rates after neoadjuvant systemic treatment can be high in triple-negative and HER2-positive breast cancers, making surgery omission seem more biologically understandable. In HR-positive, HER2-negative low-risk disease, however, expecting pCR with conventional neoadjuvant endocrine therapy is generally unrealistic. These tumors often shrink with treatment and their proliferation decreases, but complete pathological disappearance is rarer.

What makes the ESTRO 2026 study interesting is therefore the addition of highly precise, ablative-dose radiotherapy to endocrine therapy. The aim is not merely to shrink the tumor, but to eradicate all viable cancer cells in the primary tumor bed without surgery. A pCR rate of approximately 53% is a noteworthy signal for this patient biology.

For Whom Could This Approach Be Considered?

The most mistaken conclusion to draw from this study would be that surgery is no longer necessary in early-stage breast cancer. Patient selection was extremely narrow and careful. Patients had stage I, HR-positive, HER2-negative disease with nonlobular histology, an Oncotype DX score of 25 or below, and were over 50 years old. The decision to omit surgery was also made only when pCR was confirmed by post-treatment biopsy.

Not Standard Today, but Paving the Way for Tomorrow’s Studies

This study is not large enough to change current practice. There are only 20 patients, no randomized comparison, and follow-up remains limited for breast cancer. Because the risk of late recurrence in HR-positive breast cancer can extend over many years, excellent control at 3 years is exciting but insufficient.

Nevertheless, these data are extremely important. They move the nonsurgical approach beyond speculation and make it a prospective, biopsy-confirmed, technology-supported field of research. The biomarker signal in the study—namely the association of tumor volume and volume reduction after endocrine therapy with pCR—also suggests that patients could be selected more intelligently in the future.

Seeking the Same Assurance With Less Burden, Rather Than Simply Less Treatment

6 Critical Questions That Larger Studies Must Answer

An Early but Serious Signal for Nonsurgical Breast Cancer Treatment

This phase 2 study presented at ESTRO 2026 brought greater scientific visibility to the concept of nonsurgical treatment in early-stage, HR-positive, HER2-negative, low-risk breast cancer. In a highly selected group of 20 patients, vacuum-assisted biopsy performed after 3 months of endocrine therapy and ablative radiotherapy at 37,5 Gy/5 fractions identified a pathological complete response in 53% of patients. No progression was observed during a median follow-up of 37,3 months in patients who could omit surgery.

These findings do not mean that surgery is no longer necessary in early-stage breast cancer. Instead, they point to a possible future in which we can determine more intelligently when surgery is truly needed. The key is to combine biology, imaging, ablative radiotherapy technology, and pathological confirmation.

The future of breast cancer treatment lies not only in more powerful drugs, but also in more refined strategies that reduce unnecessary burden, preserve patients’ bodily integrity and quality of life, and maintain oncological safety. This study offers a small but highly noteworthy window into that future.