Biologically informed decision-öaking for PMRT in pT3N0M0 luminal breast cancers (Protocol MF22-02): International multicenter real-world data

Abstract

Background: Current guidelines do not list definitive recommendations for postmastectomy radiation therapy (PMRT) in patients with luminal pT3N0M0 breast cancer (BC). Increased data suggests de-escalation of radiation therapy (RT) in genomically defined biologically favorable luminal BCs. The goal of this study is to determine whether PMRT can be safely omitted for this specific subgroup of patients. Methods and materials: Two hundred and 2 women from 16 centers with pT3N0M0 hormone receptor (HR) positive, HER2 negative BC who underwent mastectomy were retrospectively analyzed. No patients received neoadjuvant chemotherapy. Three patients were excluded because of positive surgical margins. Patients were divided into 2 groups: PMRT (n = 130) and no PMRT (n = 69). Groups were compared in terms of overall survival (OS), loco-regional recurrence (LRR) rate, and distant metastases (DM) in light of the Magee Equations Score (MS), menopausal status/age, axillary surgery, pathology, lymphovascular invasion (LVI), adjuvant chemotherapy, and adjuvant endocrine therapy. Results: The majority of the patients had invasive ductal carcinoma (49%, n = 98). There was no significant difference regarding tumor size, axillary surgery, and adjuvant endocrine therapy between the 2 groups (P = .82, P = .28, P = .12, respectively). LVI was 19% (n = 39), and it was greater in the PMRT group (25% vs. 10%; P = .01). Patients in the PMRT group received more chemotherapy (66% vs. 30%; P < .001), had more grade 3 tumors (28% vs. 9%, P = .005), and were more premenopausal (49% vs. 22%; P = .0001). At a median follow-up of 51.3 months for the no PMRT group and 65.9 months for the PMRT group (P = .041), 9% (n = 6) of patients from the no PMRT group and 2% (n = 3) from the PMRT group developed LRR (P = .047). There was no difference in local recurrence (1% in no PMRT group vs. 2% in PMRT group; P = .7) and distant recurrence (7% in no PMRT group vs. 3% in PMRT group; P = .16) in patients who received PMRT and no PMRT. Further comparison of the LRR in the no PMRT and PMRT groups in patients with an MS < 18 did not show a significant difference (3% vs. 4%; P = .64). However, among patients with an MS ≥ 18, no PMRT group had a higher LRR rate compared to the PMRT group (11% vs. 2%; P = .01). In patients with an MS ≥ 18, the administration of PMRT correlates with statistically significantly better LRR-free survival (HR 0.19; 95% CI 0.05-0.79; P = .02). Conclusions: Our findings imply that when considering PMRT for patients with pT3N0M0, HR-positive, and HER2-negative BC, clinicians can benefit from a combination of pathological risk factors and recurrence prediction models. Patients with MS < 18 experience a comparable rate of recurrence irrespective of PMRT, while those with MS ≥ 18 have higher rates of LRR and thus should not omit PMRT.