Brain metastases (BM) from primary breast cancer can arise despite use of systemic therapies that provide excellent extracranial disease control. Local modalities for treating BM include surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). We sought to determine the benefits of SRS for management of BM arising from different biologic breast cancer subtypes. We reviewed records of 131 patients who received SRS for breast cancer BM between 2001 and 2013. Survival was estimated by the Kaplan–Meier method. Effects of tumor biology, number and location of lesions, and number of SRS sessions on survival were evaluated by Cox proportional hazards regression. Of the 122 patients with subtypes available, 41 patients (31 %) were classified as estrogen receptor positive/HER2 negative (ER+HER2−); 30 patients (23 %), ER+HER2+; 23 patients (18 %), ER−HER2+; and 28 patients (21 %), ER−HER2− (or triple negative breast cancer, TNBC). Median age at first SRS was 50 years. Median overall survival for ER+HER2−, ER+HER2+, ER−HER2+, and TNBC was 16, 26, 23, and 7 months, respectively (p < 0.001 for difference between groups). Patients with TNBC had the shortest time to retreatment with WBRT or SRS or death with hazard ratio of 3.12 (p < 0.001) compared to ER+HER2−. In all subtypes other than TNBC, SRS can provide meaningful control of BM even in the setting of multiple lesions and may be worth repeating for new lesions that develop metachronously. For patients with TNBC, prognosis is guarded following SRS, and there is an urgent need to develop more effective treatment strategies.
Commonly used adjuvant systemic therapies harbor high rates of severe short-term and long-term side effects but are often justified to patients because of curative intent in early stage breast cancer. One of the oldest and least toxic adjuvant regimens, oral cyclophosphamide given with intravenous methotrexate and 5-fluourouracil (CMF) has been largely abandoned because of the perception that it underperforms for survival outcomes compared to modern regimens containing anthracycline and/or taxanes. To address this misperception, we performed a review of all consecutive breast cancer patients at the Seattle Cancer Care Alliance over the past decade receiving 6 months of adjuvant CMF as their sole chemotherapy regimen and determined rates for relapse-free survival (RFS), overall survival (OS), and major organ toxicity. From January 2003 to August 2013, 248 patients (median age of 52 years at the start of chemotherapy) met criteria for inclusion in this series and had a median follow-up of 67 months. RFS and OS at 5 years was 94.5% (91.3-97.9%) and 98% (96-100%), respectively. The only major organ toxicity occurring in more than 5% of patients was Grade III neutropenia (18.1%). One patient died during therapy from pneumocystis pneumonia attributed to previously undiagnosed AIDS. In a modern cohort of patients thoroughly characterized for grade and hormone receptor status, CMF was a well-tolerated and effective adjuvant regimen for early stage breast cancer and should be considered for appropriately selected patients.
BACKGROUND: The addition of taxanes to anthracycline-based adjuvant chemotherapy has improved disease free survival (DFS) in women with high-risk early-stage breast cancer. Many studies have sought to optimize the dose intensity and density of these agents to produce improvements in outcome and tolerability. The purpose of this study was to assess the use of metronomic doxorubicin plus daily oral cyclophosphamide (AC) for 12 weeks followed by nab-paclitaxel (nP) for 12 weeks in this population. Those patients with Her2 positive disease were also given adjuvant trastuzumab. METHODS: A non-randomized phase II clinical trial was designed to (1) test the DFS at 2 years compared to historical controls, (2) assess dose intensity delivered, (3) assess use of nP in the adjuvant setting, and (4) evaluate toxicities associated with the regimen. Overall survival (OS) was a secondary outcome. The dosing of A was 24mg/m2 IV qweek and C was 60mg/m2 oral daily; nP, 100mg/m2 IV qweek. RESULTS: Sixty patients were enrolled on the study with a median follow-up of 6 years and a median age of 50 (range 30-69). 58% of patients had node positive disease. Receptor categories included hormone receptor positive (ER positive or PR positive) and HER2 negative (n=24; 40%); ER negative, PR negative, and HER2 negative (triple negative; n=19; 32%); or HER2 positive (n=17; 28%). DFS at 2 years was 93% (1 death, 3 recurrence) and at 6 years was 82%, comparable to historical controls. OS at 2 years and 6 years was 98% and 88%, respectively. Mean dose intensity was greater than 90% for AC and 88% for nP. Treatment was well-tolerated with the most common grade ≥3 toxicity being neutropenia and a 2% incidence of febrile neutropenia. Disease-free survival and overall survival at 2 and 6 years 2 year 6 year DFS %OS %DFS %OS %All patients93988288ER+ or PR+, HER2-921007979Triple negative89957989HER2+10010088100 CONCLUSSIONS: Patients achieved similar DFS to that seen in historical controls with similar rates of adverse events. Since nP dosing was 100 mg/m2, even with 88% dose intensity, the delivered taxane dose is greater than standard weekly paclitaxel. Notably disease control was particularly impressive in the triple negative subtype, which has been shown to benefit from nP over standard paclitaxel in the neoadjuvant setting in the GeparSepto (GBG 69) trial. Metronomic AC followed by nP is a safe, effective option for delivery of adjuvant chemotherapy for high-risk patients. Citation Format: Cho E, Wu Q, Rubinstein L, Linden H, Gralow J, Specht J, Gadi V, Ellis G. Weekly doxorubicin and daily oral cyclophosphamide followed by nab-paclitaxel for adjuvant therapy of high-risk localized breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-14-10.
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