Breast cancer : brain metastases and treatment aspects

Abstract: Background: In Sweden breast cancer is the most common malignant cancer disease among women, with 8000 new individual cases each year. The prognosis is generally very good, but nevertheless many patients still die of breast cancer every year. The general aim of this thesis is to gain increased knowledge of brain metastases due to breast cancer, including incidence, predictors and treatment aspects and better knowledge of the potential benefit of low-dose aspirin among women with breast cancer in different stages. Patients, methods and results: In study I and II we aimed to assess if the incidence of brain metastases have increased in Sweden over time. In study I, all Swedish patients with breast cancer during 1998-2006 were identified from the Swedish National Cancer Register. These individuals were matched to the National Patient Register to get information on admissions to hospital due to distant metastases. In the cohort of 50 528 identified breast cancer patients, 696 (1.4%) had admissions to hospital due to brain metastases. Patients were at 44% increased risk of being admitted to hospital with brain metastases if diagnosed with a primary breast cancer in 2004-2006 compared with 1998-2000. In study II we used the BcBaSe cohort (based on three quality-of-care registers in the Stockholm-Gotland, Uppsala-Örebro and the North region). Here, we identified all women with a first breast cancer 2002-2012 (N=30 996) and used ICD-codes for distant metastases from both non-primary outpatient care and hospital admissions. Overall, 789 (2.5 %) patients were registered with brain metastases at diagnosis or during follow-up. According to preliminary results, patients diagnosed with breast cancer in 2009-2012 were at a 37% increased risk of developing brain metastases compared with the period 2002-2004. In study III we aimed to evaluate survival and level of care following whole brain radiotherapy due to brain metastases among breast cancer patients in Stockholm. We identified 241 patients treated at the Karolinska University hospital radiotherapy units 1999 to 2012. We gathered data on outcome and prognostic factors including level of care before and after the radiotherapy treatment through reviews of the patients’ medical files. Median survival following whole brain radiotherapy was 2.9 months and 57 (24%) of the patients could never be discharged from hospital-care. Patients with poor performance status (WHO 3-4) had a median survival of 0.9 months and women with triple-negative primary tumors a median survival of 2.0 months. Poor performance status and being admitted to hospital before radiotherapy were associated with increased risk of not coming home. In study IV we aimed to evaluate if low-dose aspirin use may have a role in the treatment of breast cancer, accounting for clinical characteristics. In this study we used the BcBaSe linkage to identify a cohort of 21 414 women diagnosed with a primary stage I-III breast cancer and 621 women diagnosed in stage IV 2006 to 2012. We analysed information from Swedish health-care registers on dispensings of low-dose aspirin, comorbidity and dates and causes of death. We found no clear association between low-dose aspirin use and breast-cancer specific death overall, nor with risk of recurrence in a subgroup analysis. A possible benefit was however noted in women with smaller breast cancer tumors, stage I, which warrants further study. Discussion: The incidence of brain metastases in breast cancer appears to have increased in Sweden in recent years perhaps due to improved disease control outside of the brain. When a decision is made of treating brain metastases in breast cancer with whole brain radiotherapy, we should take into account the patient’s need of hospital care before treatment, performance status and choice of level of care in the late palliative stage of disease and the end-of-life period, since the median survival is short and many patients can never be discharged from the hospital after whole brain radiotherapy. Low-dose aspirin use in breast cancer does not seem to have any clear role in improving outcomes for breast cancer patients.