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  • Introduction Despite advances in the

    2019-06-25

    Introduction Despite advances in the treatment of early stage breast cancer, bone remains the most common site of distant Pemetrexed [1]. The consequences of bone metastases include reduced survival, morbidity, pain and reduced quality of life [2]. While the care of these patients is multidisciplinary, possibly the most attention in recent decades has been given to the role of bone-targeted agents (BTAs) such as bisphosphonates and denosumab. Clinical trials of BTAs have shown statistically significant reductions in the incidence of, and time to, skeletal related events (SREs) (defined as need for surgery or radiotherapy to bone, pathological fractures, spinal cord compression, hypercalcemia) and reduced bone pain in patients with bone metastases from breast cancer [3–7] (Table 1). As a result of these trials, BTAs have become a standard of care, with treatment starting at the time of bone metastasis diagnosis until evidence of a substantial decrease in performance status [8,9]. With the widespread use of BTAs there is a growing body of data that suggests that their benefits in routine clinical practice are more modest than that observed in randomised trials [10–14] (Table 2). We therefore decided to evaluate the incidence, consequences, and management of bone metastases in an unselected cohort of breast cancer patients at a large Canadian cancer centre. In addition, we assessed less commonly reported clinical outcomes of importance to patients and the health care system, such as the use of opioids and the need for hospitalization due to skeletal complications.
    Methods
    Results
    Discussion The impact of bone metastases from breast cancer on patients\' survival, quality of life, mobility and functional independence are well recognized. However, despite the multidisciplinary nature of care of these patients, in recent decades the focus of randomised trials has been predominantly on the benefits of BTAs on SREs. The purpose of the current paper was deliberately broad and designed to assess the consequences of the occurrence of bone metastases in patients treated outside of the clinical trial setting. We also wished to informally compare our findings and other retrospective and clinical trial datasets. We also attempted to evaluate potential predictive for identifying patients at different risk for developing SREs [15–17]. As an overview of the cohort characteristics it is interesting simple observation that despite advances in adjuvant therapy that the proportion of patients with bone metastases remains the same (70%) as originally reported over 30 years ago [1]. As with other series, patients with bone metastases appear to have a favorable survival with a median overall survival from diagnosis of metastatic disease of 40.0 months (IQR 22.3–93.3 months) [13,18–20]. In our current series, most patients with bone metastases received a BTA starting soon after being diagnosed with bone metastases (median 1.5 months (IQR 0.8–3.30)). Patients were continued IV bisphosphonates every 3–4 weeks in most cases until significant deterioration or death, as per treatment guidelines [8]. It is of note that the incidence of SREs in patients who received a BTAs in our study was 62% with the majority of first SRE (75/155, 48.4%) occurred either before commencing a BTA or within 1 month of starting a BTA. The incidence of SREs prior to bone-targeted therapy is in keeping with the literature [3,21]. This likely reflects the imaging that is performed when the patient is being worked up for her new symptoms and therefore the suspicion of bone recurrence is being raised. For example, in our series 40% of patients had significant pain at the time of diagnosis of bone metastases, and it is therefore not surprising that palliative radiotherapy (an SRE) was offered in order to achieve pain relief. Indeed, in our study the most frequent SRE was radiotherapy with pain and prevention of fraction or spinal cord compression as indication for treatment.