Recent Advances in Optimizing Radiation Therapy Decisions in Early Invasive Breast Cancer

Abstract

Adjuvant whole breast irradiation after breast-conserving surgery is a well-established treatment standard for early invasive breast cancer. Screening, early diagnosis, refinement in surgical techniques, the knowledge of new and specific molecular prognostic factors, and now the standard use of more effective neo/adjuvant systemic therapies have proven instrumental in reducing the rates of locoregional relapses. This underscores the need for reliably identifying women with such low-risk disease burdens in whom elimination of radiation from the treatment plan would not compromise oncological safety. This review summarizes the current evidence for radiation de-intensification strategies and details ongoing prospective clinical trials investigating the omission of adjuvant whole breast irradiation in molecularly defined low-risk breast cancers and related evidence supporting the potential for radiation de-escalation in HER2+ and triple-negative clinical subtypes. Furthermore, we discuss the current evidence for the de-escalation of regional nodal irradiation after neoadjuvant chemotherapy. Finally, we also detail the current knowledge of the clinical value of stromal tumor-infiltrating lymphocytes and liquid-based biomarkers as prognostic factors for locoregional relapse.

The Residual Cancer Burden index as a valid prognostic indicator in breast cancer after Neoadjuvant chemotherapy

“…Young age is a known risk factor for long-term survival in patients who undergo breast-conserving surgery and are not treated with NAC [31,32]. This view was veri ed by a meta-analysis of large-scale prospective tests of breast-conserving surgery, which suggested that younger female patients had a higher 10-year locoregional recurrence rate(LRR) [33]. Nevertheless, once the patients were treated with NAC, we could not able to assess the role of age in predicting survival outcomes.…”

Ki67 assessment protocol as an integral biomarker for avoiding radiotherapy in the LUMINA breast cancer trial

“…Adjuvant whole‐breast radiation to the conserved breast is the standard of care for early invasive breast cancer. The benefits of adjuvant radiation in reducing the risk of relapse and breast cancer‐associated mortality 1,2 must be balanced against the risks of acute and late radiation‐induced adverse effects 3 …”

“…The use of validated biomarkers to guide adjuvant radiation therapy decisions is not well established and the American Society of Clinical Oncology maintains that clinicopathological factors are not sufficient in themselves to identify women <70 years of age whose risk is sufficiently low that adjuvant radiation after breast‐conserving surgery can be safely avoided. Thus, biomarker‐driven de‐escalation of radiation in low‐risk patients (T ≤ 2 cm, node‐negative, estrogen receptor/progesterone receptor [ER/PR]‐positive, and HER2‐negative) is under active investigation 3 . In this context, Ki67 represents a widely available, inexpensive biomarker that can be used to identify a molecularly low‐risk group 4 …”

“…The benefits of adjuvant radiation in reducing the risk of relapse and breast cancer-associated mortality 1,2 must be balanced against the risks of acute and late radiation-induced adverse effects. 3 The use of validated biomarkers to guide adjuvant radiation therapy decisions is not well established and the American Society of Clinical Oncology maintains that clinicopathological factors are not sufficient in themselves to identify women <70 years of age whose risk is sufficiently low that adjuvant radiation after breast-conserving surgery can be safely avoided. Thus, biomarker-driven de-escalation of radiation in low-risk patients (T ≤ 2 cm, node-negative, estrogen receptor/ progesterone receptor [ER/PR]-positive, and HER2negative) is under active investigation.…”

“…Thus, biomarker-driven de-escalation of radiation in low-risk patients (T ≤ 2 cm, node-negative, estrogen receptor/ progesterone receptor [ER/PR]-positive, and HER2negative) is under active investigation. 3 In this context, Ki67 represents a widely available, inexpensive biomarker that can be used to identify a molecularly lowrisk group. 4 LUMINA is a biomarker-directed single-arm prospective cohort study designed to evaluate the risk of ipsilateral breast tumour recurrence in the absence of whole-breast radiation, in postmenopausal women with T1N0 breast cancer undergoing breast-conserving surgery and endocrine therapy, who have molecularly identified low-risk disease: Luminal A subtype as defined by immunohistochemistry (IHC).…”