# Evaluation of Patterns of Recurrences in Patients With Breast Carcinoma: Are We Treating the Right Volumes, or Does the Tumor Biology Play the Role?

## TL;DR

This study examines where breast cancer recurs after treatment and finds that aggressive tumor biology and radiation coverage both play roles in recurrence patterns.

## Contribution

The study provides insights into the relationship between tumor biology and radiation therapy planning in locoregional recurrence patterns of breast cancer.

## Key findings

- 70% of recurrences occurred within RTOG-defined radiation therapy volumes.
- Patients with recurrences had more aggressive tumor features like triple-negative and HER2-positive subtypes.
- Most recurrences were diagnosed simultaneously with metastatic disease, indicating aggressive tumor behavior.

## Abstract

Purpose

The study's purpose is to evaluate the patterns of locoregional recurrences (LRRs) in women with breast cancer treated with curative intent surgery with conventional postoperative radiation therapy and to assess whether LRRs are mainly related to clinical target volume (CTV) coverage, tumor biology, or both.

Materials and methods

This was a retrospective observational study conducted between 2016 and 2023; 151 patients with histopathologically proven infiltrating ductal carcinoma (IDC) of the breast were included in the study. After modified radical mastectomy or breast-conserving surgery (BCS) with axillary dissection or sentinel lymph node biopsy, based on the indications, patients also received regional nodal irradiation (RNI). Patients were treated with 50 Gy in 25 fractions with an additional 10-16 Gy boost in 5-8 fractions in BCS patients by conventional field border-based plans on the linear accelerator. Patients who developed LRRs were studied and mapped for patterns of recurrences and compared with the Radiation Therapy Oncology Group (RTOG) guidelines of CTV delineation. All cases of bilateral breast cancer were excluded. In all cases, regional RNI, including supraclavicular and axillary lymph node irradiation, was done, while internal mammary chain (IMN) irradiation was done in 19% of cases only.

Results

Median follow-up was 60 months. Of 151 patients, 15 (10%) developed LRRs. When compared to the index population, 40% of the patients in the recurrence group had triple-negative breast carcinoma versus 35.1% in the index population group, and 27% in the recurrence group were human epidermal growth factor receptor 2 (HER2)-positive versus 17% in the index group. Five-year LRR-free survival, distant metastasis-free survival, and overall survival were 90.07%, 82.79%, and 89.41%, respectively. Most of the patients with recurrences had aggressive biological features with IDC grade 3 tumors in 10/15 (67%), >4 node-positive disease in 15/15 (100%), triple-negative tumors in 6/15 (40%), and HER2neu 3+ disease in 4/15 (26.67%) (three out of the four patients had taken one year of anti-HER2 therapy also). Lymphovascular invasion was observed in 10/15 cases (67%). In 10 (67%) cases, LRRs were diagnosed simultaneously as the metastatic disease, while five (33%) patients presented with distant metastases secondarily. Chest wall (local) recurrences occurred in 12 (80%) cases, which also had a marginal failure, i.e., at the posterior border of RTOG volumes; 13 (87%) regional recurrences were observed in 11 patients; of these, seven (53.8%) recurrences occurred in the supraclavicular fossa. Four (31%) recurrences occurred inside the RTOG level III axilla, and two (15%) recurrences occurred inside the RTOG volume in the IMN. Of all 13 regional recurrences, only 3/13 (23%) regional recurrences occurred outside RTOG CTV, while 10 (77%) recurrences occurred inside RTOG volumes.

Conclusion

Our study showed that LRRs predominantly occurred in patients with aggressive tumor biology. Approximately 70% of failures were covered inside RTOG volumes, which indicates that if RTOG volume-directed planning had been used for radiation treatment in such high-risk patients, these geographical misses could have been avoided. Adopting RTOG guidelines for volume delineation in high-risk cases with aggressive histology might be beneficial. However, further follow-up and meticulous documentation of the recurrences are needed to improve their understanding.