ESTRO 2024 - Abstract Book

S74

Invited Speaker

ESTRO 2024

University of Edinburgh, Institute of Genetics and Cancer, Edinburgh, United Kingdom

Abstract:

Adjuvant radiotherapy (RT) after breast conserving surgery (BCS) remains the standard of care for most patients with early breast cancer. However a 'one size fits all approach' is no longer appropriate.RT imposes time and cost burdens on patients and is expensive in terms of RT resources. Trials to deescalate postoperative RT in this setting have focussed on older, hormone receptor positive (HR+) women with small tumours at low risk of local recurrence after BCS. The landmark CALGB 9343 and PRIME II trials have underpinned the option of omission of RT. The CALGB 9343 trial included 636 women aged =/> 70 years with T1N0M0 ER positive tumours. PRIME II included 1326 women =/> 65 years with pTI,2 (=/<3cm),N0,M0 tumours but excluded those with a combination of lymphovascular invasion and grade III histology. Both studies showed similar modest reductions in 10 year risk of local recurrence (LR) from RT (10% to 1-2%). Recommendations for omission of RT in PRIME II were confined to grade I-II tumours since few patients with grade III tumours were randomised. A planned subgroup analysis of a limited number of patients with low ER tumours showed the LR rate without RT was 19.1% The authors cautioned against omission of RT in this subgroup. Neither trial showed any significant difference in overall survival from the omission of RT. Nor in PRIME II was there any adverse effect of RT omission on metastasis free survival. Current guidelines of the National Comprehensive Cancer Network (NCCN) support hormonal therapy alone for patients 70 years or older with early hormone sensitive tumours after BCS and the UK National Institute for Care and Excellence (NICE) guidelines allow the omission of RT in women with T1,N0,M0 grade 1-2 tumours along as they receive at least 5 years of adjuvant endocrine therapy.Selection for omission of RT has become nuanced and finely balanced with the advent of ultrahypofractionated radiotherapy and accelerated partial breast irradiation which are more convenient and less toxic for patients. In parallel local recurrence rates after breast conserving therapy have been falling due to factors including screening, closer attention to surgical margins, more effective systemic therapy and radiotherapy. Decision aids may assist patients in weighing up the balance of benefits and risk of RT or its omission and the complexities involved. Ongoing biomarker - based studies (EXPERT, PRECISION,PRIMETIME, DEBRA, IDEA, LUMINA) are seeking to refine selection for omission of RT. The LUMINA study of 501 hormone receptor positive patients aged 55 years or older (with a median age of 67 years) in pT1,N0 grade 1-2 luminal A tumours with margins =/> 1mm treated with adjuvant endocrine therapy without RT showed a 5 year cumulative incidence of local recurrence of 2.3% with only one breast cancer death. The IDEA trial selected patients with low clinical and genomic risk to omit RT and treated with adjuvant endocrine therapy alone after BCS in 200 women aged 50-69 (mean age 62 years) with pT1,N0 breast cancer. Low genomic risk was defined as an Oncotype DX score of =/<18.The 5 year freedom from recurrence was 99% with only 2 local recurrences. The investigation of multigene signatures of breast cancer radiosensitivity to select low risk, ER positive HER-2 negative patients who have minimal benefit from RT shows promise. A meta-analysis of 623 patients from three historical breast conservation trials (Swedish, Canadian and Scottish) showed that the Profile for Omission of Local Adjuvant Radiotherapy (POLAR) was not only prognostic for local recurrence but predictive of radiotherapy benefit. Further confirmatory studies will be needed in more contemporary datasets. The PROSPECT trial used preoperative MRI to identify patients with truly localised disease to omit RT after BCS in women =/> 50 years with non triple negative breast cancer,cTIN0. In 201 (45%) of 443 patients eligible to omit RT the LR rate was 1% (median follow up 5.4 years).

In summary, current evidence supports selection of women aged =/> 65 years with pT1,T2 (=/< 3cm),N0, hormone receptor positive, HER-2 negative, grade 1-2 tumours for the option of omission of RT post BCS.