Highlight 2

The second daily highlight on SABCS 2023 is done by Dr Christophe Van Berckelaer, a gynaecological oncologist at the University Hospital Antwerp.  He selected five presentations from the general session 2, all about the local treatment of breast cancer.

The first study presented by Dr Van Berckelaer is the OPBC05/EUBREAST-14R/ICARO study. This study, involving nearly 600 patients from 62 centers, aimed to assess outcomes in those with residual isolated tumour cells. Of the 182 who underwent axillary lymph node dissection, 30% had additional positive nodes, yet only 12% had micro or macrometastases. Importantly, the 5-year isolated locoregional recurrence rate was low (1.1% vs. 1.7%), and there was no significant difference in any invasive recurrence (19% vs. 16%). These results support omitting axillary lymph node dissection in such cases, though limitations include a short median follow-up (3.2 years) and a retrospective design. Notably, the question remains whether patients with isolated tumour cells require additional axillary radiotherapy (NSABP51).

In the second study, Dr Van Berckelaer presented a meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group, examining two key comparisons in axillary treatment modalities. The first analysis compared less versus more axillary surgery, revealing a rare occurrence of isolated ipsilateral axilla recurrence (55/20285), twice as common in the less axillary surgery group but without impacting mortality. Across both older and newer studies, less axillary surgery showed no association with distant recurrence or mortality, while more axillary surgery correlated with increased lymphoedema. The second comparison evaluated axillary lymph node dissection versus axilla radiotherapy, with no significant differences in outcome parameters but a higher incidence of lymphoedema in the axillary lymph node dissection group. These findings underscore that axillary surgery does not significantly impact survival or local control but plays a crucial role in guiding subsequent therapeutic decisions.

The SENOMAC trial addresses lingering uncertainties in axillary management post-ACOSOG Z0011 and AMAROS trials. This clinical non-inferiority trial encompasses 2540 patients with T1-T3 invasive breast cancer and clinically node-negative status. Patients underwent either completion axillary dissection or none after a positive sentinel node. The estimated 5-year recurrence-free survival showed no significant difference between standard care (88.7%) and the intervention group (89.7%), confirming the non-inferiority of axillary dissection omission. The study prompts consideration for low-risk subsets, advocating for randomised trials exploring nodal radiotherapy necessity in patients with 1-2 positive sentinel lymph nodes.

The NRG Oncology/NSABP B-51/RTOG 1304 phase III randomised trial scrutinised the efficacy of adjuvant regional nodal irradiation (chest wall irradiation + RNI after mastectomy or whole breast irradiation + RNI after lumpectomy) in clinically N+ patients rendered ypN0 post-neoadjuvant chemotherapy. With 1556 participants and a median follow-up of 59.5 months, the primary endpoint, invasive breast cancer recurrence-free interval, exhibited no significant difference between groups, extending to disease-free and overall survival. Subgroup analyses, including treatment modalities (breast-conserving therapy vs. mastectomy, axillary lymph node dissection vs. sentinel node dissection), revealed no disparities. While a slight trend towards more locoregional recurrence emerged without radiation, the low case numbers (11 vs. 5) yielded a p-value of 0.09. Overall, the findings suggest the safe omission of regional nodal irradiation in patients with initially positive axillary nodes converted to ypN0 after neoadjuvant chemotherapy. However, the study acknowledges limitations being the unknown number of patients with isolated tumour cells and the need for extended follow-up.

The five-year outcomes of the IDEA trial explore endocrine therapy without radiotherapy after breast-conserving surgery in postmenopausal patients aged 50-69 with genomically selected favourable Stage I breast cancer. The CALGB 9343 and PRIME II studies have hinted at reasonable 10-year recurrence rates without radiotherapy in select women aged 70+ and 65+, raising the question of personalised treatment approaches based on tumour biology. In this prospective multicenter cohort trial, a genomic assay determined which younger post-menopausal patients could safely forgo radiotherapy after breast-conserving surgery. With 200 enrolled patients and a median follow-up of 5.2 years, the study reports an excellent 100% survival, with only 2 recurrences within 5 years and 6 occurring later. Notably, no distant recurrences were observed. Compliance was robust, and the study suggests a very low 5-year risk of recurrence using genomic assays alongside traditional clinical and biological factors for treatment selection. While acknowledging the need for longer follow-up and emphasising the necessity of ET compliance, the authors cautiously endorse the potential of personalised treatment strategies in this context.

References:

Montagna G. et al., Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study – SABCS 2023, #GS02-02

Mannu G. et al., Overview of Axillary Treatment in Early Breast Cancer: patient-level meta-analysis of long-term outcomes among 20,273 women in 29 randomised trials -SABCS 2023, #GS02-05

de Boniface J. et al., Recurrence-free survival following sentinel node-positive breast cancer without completion axillary lymph node dissection – first results from the international randomized SENOMAC trial. – SABCS 2023, #GS02-06

Mamounas E. et al., Loco-Regional Irradiation in Patients with Biopsy-proven Axillary Node Involvement at Presentation Who Become Pathologically Node-negative After Neoadjuvant Chemotherapy: Primary Outcomes of NRG Oncology/NSABP B-51/RTOG 1304 – SABCS 2023, #GS02-07

Jagsi R. et al., Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer –  SABCS 2023, #GS02-08