Radiotherapy With And Without Concurrent Cisplatin For Unresectable Or Inoperable Locally Advanced Triple Negative Breast Cancer

The purpose of this study is to assess acute toxicity, tumor response, loco-regional control, and distant metastasis free survival in patients who had unresectable or inoperable locally advanced triple negative breast cancer treated with radiotherapy with or without concurrent cisplatin. A retrospective review of locally advanced breast cancer patients treated with radiotherapy at a single institution was performed with approval of the institutional review board. Patients with biopsy-proven, triple negative breast cancer (TNBC) and measurable disease involving the breast/chest wall or regional lymph nodes which was treated with radiotherapy were included. Patients who had palliative radiotherapy to locoregional disease (≤30Gy) were excluded from the analysis. Prior and concurrent systemic therapy was recorded. A review of all available clinical, imaging and pathologic data was performed to assess the acute toxicity(RTOG grade); tumour clinical response(RECIST) and pathologic response when available. Forty patients with unresectable/inoperable TNBC were treated with radiotherapy between 2008 and 2015. Median age was 53.5 and the median follow-up was 12.3 months. Twenty-six (65%) patients received both anthracycline/taxane based chemotherapy prior to radiotherapy; 3 (7.5%) patients had at least one cycle of anthracycline or taxane, and the remaining patients did not due to age/co-morbidities/metastatic disease. Mean radiation dose was 65Gy (range 40-81Gy), with concurrent cisplatin given in 19 (47.5%) patients. The most common concurrent cisplatin doses administered were weekly 25-30mg/m2. The goal of treatment in most cases was to shrink the tumour so that surgery could be performed or to provide loco-regional control of advanced disease. Twenty-three patients (57.5%) developed grade 2-3 acute skin toxicity. One case of grade 4 hematologic toxicity, neutropenia, was documented with concurrent cisplatin and radiotherapy. In 16 of 25 (64%) cases, unresectable, non-metastatic TNBC was rendered operable and patients proceeded to have definitive breast surgery. When surgery was possible, the pathologic complete response rate was 37.5% (6 of 16). Clinical complete and partial response rates were 20% and 52.5%, respectively. Seven patients (17.5%) had loco-regional progression within 3 months of treatment completion. At last follow-up, 21 (52.5%) patients had died from breast cancer. Six (15%) patients were alive with no evidence of locoregional recurrence or distant disease, with median follow-up of 59 months in this sub-group. Patients who have locally advanced TNBC which is resistant to anthracycline and taxane based chemotherapy are at a very high risk of developing metastatic disease. However, some patients treated with high dose radiotherapy and concurrent cisplatin can achieve partial or complete clinical response, conversion to resectable disease and long-term tumour control.