ESTRO 2024 Congress report
1. Symposium “More to the nodes, less to the breast?”
One of the hot topics in current breast cancer treatment is the optimisation of the irradiated volume, which was discussed at ESTRO’s 2024 annual meeting during the symposium entitled “More to the nodes, less to the breast?”, which was held on Monday 6 May. The omission of radiation therapy to treat breast cancer in selected patients was discussed by Ian Kunkler, lead investigator of the PRIME 2 trial [1], which explored the possibility of omitting postoperative radiotherapy in selected older adults who had undergone breast-conserving surgery after early-stage breast cancer. The ongoing biomarker-guided studies will help to refine the selection of patients with very low risk, small, oestrogen-receptor positive (ER+), pN0, human epidermal growth factor receptor 2 (HER2)-negative tumours that might forego radiotherapy. Additionally, today’s routine practice with ultra-hypofractionated radiotherapy and partial breast irradiation might be an alternative to endocrine therapy (ET), such as is being investigated currently under the EUROPA trial, with very limited side effects and inconvenience [2]. Molecular signatures of radiosensitivity (e.g., POLAR) may help to classify low-risk ER+, HER2-negative tumours and better select patients who are unlikely to benefit from radiotherapy [3]. However, genomic tests have to be validated in future trials before they can be brought into routine clinical practice. Ongoing research on biomarkers, in studies such as LUMINA and IDEA, will refine the criteria for consideration of radiotherapy omission, and will lead to the possibility of personalised treatment strategies that are based on specific tumour characteristics [4, 5]. In conclusion, the omission of radiotherapy and/or ET after breast-conserving surgery should today involve shared decision-making with full information on the potential benefits and risks of all the available adjuvant treatments.
Jana de Boniface presented the international SENOMAC trial, which involves the evaluation of the omission of complete axillary lymph node dissection (cALND) after a positive sentinel lymph node biopsy in breast cancer patients [6]. Among 2766 patients, the five-year recurrence-free survival rate was comparable between those treated solely with sentinel lymph node biopsy and those who underwent cALND, with rates of 89.7% and 88.7% respectively. These findings add to current knowledge as they expand the group of patients for whom cALND can be replaced by nodal radiotherapy and adjuvant systemic therapy [6]. In addition, the SENOMAC trialists and the Danish Breast Cancer Group (DBCG) are performing a dosimetric analysis of the irradiation volumes to provide high-quality data to improve guidance on radiation therapy volumes and doses.
2. Update on Breast Cancer Studies
IRMA study: a phase III trial in which treatment via accelerated partial breast irradiation (APBI) is compared with that via whole breast irradiation (WBI) in early-stage breast cancer patients after breast-conserving surgery. The study enrolled 3309 patients across 35 centres, aged ≥49 years, with invasive breast cancer ≤ 3cm, pN0-1. Patients were assigned to receive either APBI (38.5Gy in 10 fractions twice daily) or WBI, with adjuvant systemic therapy according to institutional guidelines. The primary endpoint was ipsilateral breast tumour recurrence (IBTR) after five years. Results showed a 0.9% and 0.7% cumulative incidence of five-year IBTR after APBI and WBI, respectively. No significant differences were observed for other oncological outcomes. Of note: only 59% of the patients received ET, although 95% were ER+, which cannot be entirely explained by the contribution of 830 patients from The Netherlands (where the standard treatment for low-risk patients is no adjuvant systemic therapy). This finding is similar to that of the DBCG partial breast irradiation study (54% received ET, although 100% were ER+).
DBCG Skagen trial 1: a phase III randomised trial in which two radiotherapy regimens were compared in 2946 N+ breast cancer patients who showed indications for loco-regional radiotherapy for unilateral, early, high-risk breast cancer. These patients had no prior cancer and were willing/able to participate in the 10-year follow-up. The two regimens were 40Gy/15 fractions vs. 50Gy/25 fractions. All volumes were delineated according to the ESTRO guidelines. Analysis of recurrence sites revealed that the majority of loco-regional recurrences (59/60) were detected within the tissue volume that had received 95% of the prescribed radiotherapy dose. This finding supports the reliability of ESTRO contouring recommendations for target volume delineation.
REQUITE programme: in this study, image-based data were used to explore the relationship between radiotherapy dose and acute and persistent pain in the breast, arm, and shoulder after breast radiotherapy. Data from 923 breast cancer patients who had received radiotherapy after breast-conserving surgery revealed significant associations between radiation dose in specific anatomical sub-regions, including the breast, level 1, and the pectoralis major, with the presence of acute and persistent pain in the shoulder and arm. This study underscores the importance of considering homogeneity and conformality of radiation dose distribution to better understand and learn how to avoid adverse effects.
DBCG IMN2 study results: this population-based cohort study evaluated the benefit of internal mammary node irradiation (IM-RT) in right-sided N+ breast cancer patients. A cohort of 4541 patients was treated between 2007 and 2014 through loco-regional radiotherapy. A median follow-up of 13.6 years revealed a significant improvement in 15-year overall survival rates for right-sided patients who had received IM-RT compared with left-sided patients who did not (65.1% vs. 61.0%). Treatment with IM-RT was also associated with a significant reduction in breast cancer-specific mortality rates and distant recurrences. No notable increase in long-term cardiac events was observed. These findings reinforce the clinical utility of IM-RT.
Meta-analysis by the Early Breast Cancer Triallists Collaborative Group of radiotherapy to the regional nodes: the triallists’ group demonstrated the benefit of loco-regional radiotherapy on any recurrence, on breast cancer survival and overall survival rates, for trials that had been initiated after 1989. The absolute benefit was associated with the number of involved lymph nodes: 2.3%, 2.9% and 4.3% for any recurrence and 1.6%, 2.7% and 4.5% for breast cancer mortality, for pN0, pN1-3 and pN4+ categories of cancer, respectively. The proportional benefit of regional nodal irradiation seemed greater when tumours were medially or centrally located, compared with lateral tumours. Furthermore, radiotherapy-induced eradication of internal mammary lymph nod (IMN) tumoural deposits could be reflected mainly in reductions of distant recurrence, which is the endpoint of interest in IMN irradiation [7]
We hope to meet all of you for many more interesting topics and studies at the ESTRO 2025 Congress in Vienna!
Yasemin Bolukbasi
Department of Radiation Oncology, Koc University, School of Medicine, Istanbul
Davutpasa Caddesi, Istanbul, Turkey
Dr Youssef Ghannam
Gustave Roussy, Radiation Oncology Department, Villejuif, France
Report coordinated by the ESTRO breast cancer focus group
References
1. Kunkler, I.H., et al., Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol, 2015. 16(3): p. 266-73.
2. Meattini I, eet al. Exclusive endocrine therapy or partial breast irradiation for women aged ≥70 years with luminal A-like early-stage breast cancer (NCT04134598 - EUROPA): Proof of concept of a randomized controlled trial comparing health-related quality of life by patient-reported outcome measures. J Geriatr Oncol. 2021 Mar;12(2):182-189.
3. Sjöström, M., et al., Development and Validation of a Genomic Profile for the Omission of Local Adjuvant Radiation in Breast Cancer. J Clin Oncol, 2023. 41(8): p. 1533-1540.
4. Whelan, T.J., et al., Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer. N Engl J Med, 2023. 389(7): p. 612-619.
5. Jagsi, R., et al., Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA. J Clin Oncol, 2024. 42(4): p. 390-398.
6. Boniface, J.d., et al., Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases. New England Journal of Medicine, 2024. 390(13): p. 1163-1175.
7. Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials. Lancet, 2023. 402(10416): p. 1991-2003.