H. J. G. Desiree van Den Bongard

Purpose: This study investigated patterns of care and oncological outcomes in patients with ipsilateral breast tumor events (IBTE) after prior breast-conserving surgery (BCS) treated with curative intent. Methods: A retrospective cohort study was conducted on IBTE patients treated in 2016–2017 at 34 Dutch hospitals. Patient and characteristics, along with treatment details were collected and descriptive statistics were used for analysis. Overall survival (OS), disease-free survival (DFS) and breast cancer-specific survival (BCSS) were evaluated by using Kaplan-Meier analyses. Results: Of the 486 IBTE patients, 75.1% were diagnosed more than 5 years after the primary tumor, 87.4% had invasive breast cancer, and 12.6% DCIS. Distinguishing true recurrences from second primaries was not possible. Among invasive IBTE, 70 (14.6%) had primary DCIS and 350 (72.8%) an invasive primary tumor. Most IBTEs (54.9%) were T1, grade II (46.5%), and ER/PR+/HER2− (61.7%). Seventy-two (14.8%) patients received neoadjuvant systemic therapy. Salvage mastectomy was performed in 435 (89.5%) patients, while 51 (10.5%) underwent repeat BCS; 60.8% of these received postoperative whole-breast re-irradiation. Among mastectomy patients, 411 (94.5%) had prior radiotherapy; 13.1% received repeat radiotherapy, either alone (24.1%) or with hyperthermia (75.9%). Adjuvant systemic therapy was administered to 64.9%. After a median follow-up of 37 months, 83 (17.4%) developed a subsequent event: 33 (39.8%) second IBTE, 9 regional recurrences, and 41 (49.4%) distant metastases. Three- and five-year OS was 89% and 72.5%, respectively. Three- and five-year DFS was 85.5% and 69.9%, respectively. Three- and five-year BCSS was 95.1% and 86%, respectively. Conclusions: Salvage mastectomy was the predominant treatment for IBTE, although repeat BCS with re-irradiation is increasingly performed in selected low-risk patients. Survival outcomes were favorable. The study highlights the need for tumor re-assessment and emphasizes the variability in IBTE management, underscoring the need for standardized treatment guidelines.

This study examined gene expression profile (GEP) use in relation to reimbursement policies and chemotherapy administration, both for patients with and without GEP indication. Women aged ≥ 18–69 years and diagnosed with early‐stage breast cancer between January 2011 and June 2024 were selected from the Netherlands Cancer Registry. GEP use in relation to reimbursement policies and GEP result in relation to chemotherapy administration was analysed using flowcharts and a trend line. For patients with GEP indication, logistic regression analyses were conducted to determine if the reimbursement periods influenced the GEP use, and GEP use was analysed per region in the Netherlands and incidence year using trend lines. In total, 138,765 patients were included. Among 17,525 patients with GEP indication, proportions of patients who received a GEP were higher during retrospective reimbursement (25%) and publicly known reimbursement (37%) compared with no reimbursement (9%) and differed across regions in the Netherlands. Proportions of patients who did not receive chemotherapy were higher for patients who had a low‐risk MammaPrint (93%) or Oncotype DX (97%) result compared with patients who had a high‐risk MammaPrint (17%) or Oncotype DX (15%) result. Among 13,003 patients with GEP indication who did not receive GEP, 52% did receive chemotherapy. Approximately one‐third of patients who met GEP criteria and were eligible for publicly known reimbursement received a GEP. Appropriate follow‐up steps and further research seem required to analyse reasons for not ordering a GEP in times of reimbursement, since GEP results help chemotherapy decision‐making.

European Organization for Research and Treatment of Cancer trial EORTC 22922/10925 evaluated internal mammary and medial supraclavicular (IM‐MS) lymph node irradiation (IM‐MS‐RT) in patients with stage I–III breast cancer. Eligible patients had involved axillary nodes and/or centrally/medially located tumors regardless of nodal involvement. The primary end point was overall survival, secondary end points were disease‐free survival, distant metastases‐free survival, breast cancer mortality, and any breast recurrence. Between 1996 and 2004, 4004 patients were randomized. The median patient age was 54 years. At a median follow‐up of 22.2 years, 1550 (38.7%) patients died, of whom 796 (51.4%) died from breast cancer. At 20 years, the overall survival rate was 61.8% in the control group versus 61.0% in the IM‐MS‐RT group (hazard ratio [HR], 1.00; p = .967); the disease‐free survival rate was 49.0% versus 48.2%, respectively (HR, 0.97; p = .515); and the distant metastases‐free survival rate was 59.8% versus 58.9%, respectively (HR, 0.97; p = .578). The breast cancer mortality rate was 22.4% in the control group and 18.6% in the IM‐MS‐RT group (HR, 0.82; p = .006), whereas the rate of deaths not from breast cancer or from unknown causes was 15.8% versus 20.4%, respectively (HR, 1.26; p = .002). Lung fibrosis, cardiac fibrosis, and cardiac diseases were more frequent after IM‐MS‐RT versus no IM‐MS‐RT (6.3% vs. 3.2%, 2.7% vs. 1.7%. and 15.2% vs. 11.7%, respectively); and the rates of severe cardiac and lung morbidities (scores of 3 or 4) were 1.9% versus 1.7% and 0.3% versus 0.0%, respectively. Breast cancer mortality at 20 years was statistically significantly lower after IM‐MS‐RT, but deaths not from breast cancer increased after 15 years, resulting in no long‐term benefit of IM‐MS‐RT on overall survival. Therefore, the authors strongly call for very long‐term follow‐up of treatments for prognostically favorable cancers such as breast cancer.

Background: Over the past decade, post-mastectomy radiotherapy (PMRT) is indicated more frequently in breast cancer treatment, especially in patients with involved axillary lymph nodes. However, PMRT is associated with high complication rates and less satisfactory cosmetic results when combined with immediate breast reconstructions. This has led to ongoing controversy regarding breast reconstruction and radiotherapy, often postponing the reconstruction until long after PMRT has been completed. Preoperative radiotherapy, also known as neoadjuvant radiotherapy (NART), is emerging as a safe and promising alternative with the potential to allow immediate reconstruction without the negative effects of radiotherapy on the reconstructed breast. However, data on the complication rates and patient-reported outcomes (PROs) after NART followed by mastectomy and breast reconstruction are still limited. Methods: This is a multicenter, prospective, single-arm pilot study including breast cancer patients requiring mastectomy and PMRT, who desire immediate breast reconstruction, either implant-based or autologous. The primary objective is to assess complications three months after the last planned reconstructive surgery. The secondary objectives are to evaluate patient-reported health-related quality of life (HR-QoL), patient- and physician-reported cosmetic results, and pathological response. Discussion: The primary outcome of this pilot study is to provide further evidence to determine whether NART is a viable alternative to PMRT in terms of complication rates when combined with immediate breast reconstruction. The secondary outcomes will enhance our understanding of patients’ HR-QoL and cosmetic outcomes. If NART proves to be a safe alternative, this pilot study will lay the foundation for a national multicenter randomized controlled trial to evaluate long-term HR-QoL and oncological outcomes.

Background: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. Methods: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. Discussion: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. Trial registration: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).