‘De-escalation’ - reducing surgery, radiation and even medicines when treating low-risk breast cancer – was discussed in depth at the recent San Antonio Breast Cancer Symposium (SABCS).

Breast cancer treatments can have significant long-lasting side effects and there is a big international research push to find out if less treatment can be given without compromising safety or effectiveness.

In his presentation on treating low-risk* early-stage hormone receptor positive (HR+) breast cancer, Professor Icro Meattini from the University of Florence asked the question ‘Radiation therapy or endocrine therapy: which one to omit?’

(*Low-risk typically means a small, low-grade tumour, clear margins after surgery and no cancer in the axillary (armpit) lymph nodes.)

Prof. Meattini explained that both endocrine therapy (ET) (aromatase inhibitors or tamoxifen) and radiation therapy (RT) after breast-conserving surgery have been proven to reduce local recurrence (the cancer coming back to the same breast). ‘Are there any cases where you could safely omit one or the other?’ he asked. He then looked at potential criteria that could be used to select suitable patients.

Age

Perhaps older women could safely omit RT and avoid local recurrence. Using results from two clinical trials, CALGB 9343 and PRIME-II, with patients aged 65 and over, Prof. Meattini concluded that no, age alone would not be suitable for selecting patients. In both trials, women who had omitted RT were significantly more likely to have local recurrences 5 or 10 years after surgery than those receiving ET and RT (approx. 10% vs 2%). Overall survival did not differ between the two groups.

Biology

He then considered if tumour biological markers could be used to select patients for omitting RT. The LUMINA trial omitted RT for women with Ki67 scores less than or equal to 13.25%. After five years, 2.3% had had a local recurrence. Prof. Meattini considered that Ki67 alone would not be a good selection criterion. He noted the unreliability of Ki67 measures; when the researchers re-checked Ki67 before starting the trial they found that 30% of patients had a different score from their original one.

The current PRIMETIME trial aims to use clinical features and biomarker test results to identify a ‘very-low-risk’ group that could safely omit RT. This study has a patient-centred design (patients helped to develop decision aids), quality-assured centralised Ki67 testing and is the first UK biomarker-directed RT-omission trial. Five-year local recurrence < 4% is the expected outcome.

Genomics

Several trials are looking at using genomic test scores as a way to select patients to omit RT. For example, EXPERT uses patients with a PAM-50 Luminal A Risk of Recurrence score < 60 and DEBRA uses Oncotype DX Risk Score < 18.

Five-year results from IDEA, where patients aged 50-69  with small tumours and no cancer in their lymph nodes, ER+PR+HER2-, margins > 2 mm and Oncotype DX risk scores < 18 were given ET and no RT, showed that 3.3% (50-59 years) and 3.6% (60-69 years) had recurrence ‘events’ in the same breast. Prof. Meattini suggested that these results could provide a benchmark for other studies.

Work continues to find more precise genomic and molecular biomarkers, rather than generalised ‘risk scores’, that could aid decisions about treatment de-escalation.

Endocrine therapy

Could endocrine therapy be safely omitted by some patients?

The 10-year BASO trial looked at both RT and ET omission. Local recurrence rates per annum were: 2.2% for those receiving surgery only and no RT or ET, 0.8% for those receiving RT only, 0.8% for those receiving ET only and 0.2% for those receiving RT and ET.

Restrospective studies have looked at the outcomes for women who received only RT after surgery for low-risk HR+ early breast cancer. A Swedish study showed no differences compared with those receiving RT and ET in overall survival, progression free survival or distant recurrence. Both groups had similar very low local recurrence rates (<5% over 15 years). A Canadian study had similar results, with local recurrence rates (over 73 months) of 2.0% for RT alone. 5.0% for ET alone, 2.9% for RT + ET and 4.2% for surgery alone.

Prof. Meattini concluded that RT alone is an effective and pragmatic option for women older than 70 years with low-risk HR+ early breast cancer. He noted that poor adherence to ET substantially limits the effectiveness of ET-only strategies.

What if local recurrence is not the main target?

To truly optimise treatments for low-risk HR+ early breast cancer, a patient-centred, multidisciplinary approach is needed. Maintaining health-related quality of life (HRQOL) is a central goal in treatment planning, not simply minimising the risk of local recurrence. Prof. Meattini stated that decision-making should include: risk-benefit analysis of treatments, evaluation of baseline comorbidities and life expectancy, and incorporation of individual care needs and preferences.

Very few published trials include HRQOL as a measurable endpoint. The EUROPA trial compares patients receiving ET alone with those receiving RT alone after surgery. The primary endpoints are ipsilateral (same) breast tumour recurrence at 5 years and HRQOL Global Health Status. Two-year results show that ET causes a greater reduction in HRQOL than RT.

Which kind of radiation therapy?

Perhaps RT could be made better and more precise rather than being omitted. RT techniques could be further refined to optimise outcomes and HRQOL for suitable patients. The FAST-FORWARD trial confirms that one-week whole breast irradiation achieves outstanding ten-year outcomes. Other trials are looking at partial breast irradiation and short-course nodal radiotherapy.

Could imaging have a role to play?

The PROSPECT trial used MRI to define truly localised cancers eligible for omission of RT. Interestingly, MRI detected occult malignant lesions in 11% of the patients enrolled. Once these were taken out of the no-RT group, the five-year results showed only 1% local recurrence. This suggests that in other studies many of the recurrences recorded were actually occult disease that had been missed at the beginning of the trial. A new trial, PROSPECTIVE is currently under way to validate the idea of using MRI to screen patients before deciding whether to omit RT or not.

Less is more only when it is enough

Prof. Meattini ended his presentation by calling for researchers to personalise optimisation within trials, integrating pathology, biology, imaging and patient preference to maintain outcomes and improve quality of life.

Patient perspectives are important

De-escalation can mean that patients and clinicians are presented with a range of treatment programme options, requiring careful effective communication, presenting the clinical evidence clearly and taking into account patient preferences, values and attitudes to risk. This ‘shared decision-making’ is increasingly being discussed at breast cancer scientific meetings by clinicians, researchers and patient advocates.

At this SABCS session, US patient advocate Marylinn Minor summed this up. ‘De-escalation is important. Communicate it as equivalent, not risky, not an after-thought. Listen to your patients, understand their personal attitudes to risk and what matters to them. Do not let clinical habit dictate your recommendations.’

22 December 2025