Radiation therapy for brain metastases in breast cancer patients

Abstract

Most randomized comparison trials (RCTs) investigating treatments for brain metastases (BM) have included BM from any origin; as a result, more than half (52.4-77.0%) of the BM in these trials originated from the lungs (mostly non-small-cell lung cancer, NSCLC), with the breasts being the origin in only 6.8-19.0% of cases. In addition, patients with poor systemic status (KPS \ 70) were not included in these trials. Hence, before we can apply RCT-based information to the daily clinical treatment of BM from breast cancers, it will be crucial to differentiate the characteristics of BM originating from NSCLC and BM originating from breast cancer. Although stereotactic radiosurgery (SRS) is widely used in Japan, level-1 evidence suggests that the benefit of using SRS in addition to whole-brain radiation therapy (WBRT) has been proven only for patients with a single BM. Treatment with SRS alone, which is widely used in Japan, seems attractive because it could avoid the risk of long-term adverse effects of WBRT. However, level-1 evidence suggests that the omission of WBRT results in a high frequency of brain tumor recurrence (BTR). In an RCT between SRS-alone and SRS ? WBRT conducted in Japan, we found that patients who had a single BM and no extracranial metastases had a low risk of developing BTR after initial brain management (low-risk group) compared with those who had 2 or more BM and extracranial metastases (high-risk group). In order to meet the criteria of ''low-risk'' BTR, patients also should have good systemic status (KPS 3 70). Epidemiologic data suggest that the prognosis is twice as likely to be poor in patients with BM from breast cancer (RPA III = KPS \ 70) than in patients with BM from NSCLC (40 vs. 20%); in addition, the probability of brain-only metastases in patients with breast cancer is less than half that in patients with NSCLC (20-25 vs. 60-75%). Considering these findings, we should be aware that most patients with BM from breast cancer are not good candidates for SRS alone, and, therefore, the role of WBRT is still important in the era of modern radiation techniques.

Prognostic significance of pathological complete response following neoadjuvant chemotherapy for operable breast cancer

“…Whole brain radiation therapy (WBRT) is a mainstay of treatment for brain metastasis. However, the deterioration of cognitive function due to late radiation toxicity following WBRT is an important issue among long-term survivors (22). If brain metastases are few and small, stereotactic radiotherapy, which is less invasive and more effective than WBRT, may be elected (23).…”

The Role of Whole Brain Radiation Therapy for the Management of Brain Metastases in the Era of Stereotactic Radiosurgery

“…In recent years, this percentage has increased due to advances in imaging technologies and the treatment of systemic disease [2]. BMs may develop as a single lesion in the brain, oligometastatic status (2)(3)(4), and multiple metastatic status [3]. In the reports published in the 1990s, the rate of patients presenting with a single BM was approximately 50%.…”

“…In the reports published in the 1990s, the rate of patients presenting with a single BM was approximately 50%. In the reports at the end of the subsequent decade, it was in the range of 25%-35% regardless of the type of primary cancer; this likely reflects the improvement of detectability of small metastases owing to advances in the technology of magnetic resonance imaging (MRI) [4]. In general, patients with brain metastases have a poor prognosis, with an average survival time of 1-2 months when treated with steroid therapy only.…”

“…Risk of developing distant brain metastases (BMs) after initial treatment according to the risk factors identified in JROSG 99-1 From Aoyama[4]; with permission BTR brain tumor recurrence High-BTR-risk group (two or more BM, existence of extracranial metastases) BTR-risk group (single BM, no extracranial metastases)…”

Heregulin (Neuregulin)/HER3 signalling increases invasive behaviour of HER2-positive breast cancer cells

“…Metastasis is the main reason for morbidity and mortality in breast cancer patients and the major metastatic sites in breast cancer are bone, lung and liver and the brain. Despite improvements in systemic therapies, currently there is no treatment strategy with proven efficacy against metastatic breast cancer (Aoyama, 2011).…”