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Advanced breast cancer (BC) includes locally advanced and metastatic disease and constitutes about 6–10% of cases of BC at presentation in industrialised nations and up to 60–80% in developing countries with limited or basic resources, as defined in the Breast Health Global Initiative Guidelines.1–3 A significant number of patients with primary early BC at presentation continue to relapse and present with metastatic disease. Median survival of patients with metastatic BC (MBC) is between two and three years.4
Recent data using modern systemic chemotherapy and hormone and targeted therapy give better but still modest results.5
Once BC recurs, the goal of treatment of MBC is control of disease and palliation of symptoms for as prolonged a time as possible, with as few adverse effects as possible. This goal of prolonging life quantitatively and qualitatively may translate into improved disease-free survival (DFS) and overall survival. Improvement of overall survival may be achieved in a greater percentage of patients with minimal quantity of disease and so-called oligometastatic BC.
Early-detected local recurrences can be treated with local mastectomy with/without radiation therapy and result in cure.7 In patients with single-site and oligometastatic BC, modern aggressive therapy has been shown to result in an improvement of survival.8
This article will review recent advances in the treatment of MBC and discuss tailoring decision-making in order to achieve maximal therapeutic benefit with least toxicity while having an ultimate goal of palliation and/or cure.
Definitions, Prognosis and Predictive Factors
Although MBC at presentation is chemonaïve, most patients with the more common MBC at recurrence have already had either adjuvant chemotherapy and/or targeted hormone therapy (HT). More than 50% of recurrences occur after five years from diagnosis, with many recurrences reported even after 10 or 20 years or more.9 Factors that predict early recurrences (within two to three years of diagnosis) include stage of disease, patient age, menopausal status, pathology of tumour, hormonal receptors, HER2 receptors, uPA, gene signature profiles, tau gene and P53 gene, as well as the optimality of treatment modality that was applied at the time of initial diagnosis. Gene microarrays in BC improve prediction of local and distant metastasis,10–12 as well as local recurrence.
Tailoring of therapy to each individual patient involves making a choice of therapy based on factors that affect prognosis and are known to predict response to the type of available drugs and treatment. These factors include longer versus shorter disease-free interval since diagnosis of primary BC, age, menopausal status, site(s) of recurrence (soft tissue and bone versus visceral), volume of recurrent disease and effects on other organ functions, performance status and significant underlying disease, as well as tumour characteristics such as hormone responsiveness status, HER2/neu receptor status and prior adjuvant therapy. Additional important and practical aspects include availability and accessibility of multiple diagnostic and therapeutic modalities to the patient, as well as the level of resources of the country of residence1 and the patient’s personal preference and resources.