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Background  It is well recognised that access and receipt of appropriate guideline recommended treatment with systemic anti-cancer therapies for secondary breast cancer is a key determinant in overall survival. Where there is disparity in access this may result in unwarranted variation and disparity in outcomes. Individual, clinical and wider contextual factors have been associated with these disparities, however this remains poorly understood for women with secondary breast cancer. The purpose of the review is to examine individual, clinical and contextual factors which influence access to evidence-based systemic anti-cancer therapies for women with secondary breast cancer. This will include barriers and facilitators for access and receipt of treatment and an exploration of women and clinicians experience and perspectives on access.    Methods  A mixed methods approach with a segregated design will be used to examine and explore factors which influence access to systemic anti-cancer therapies for women with secondary breast cancer. Electronic databases to be searched from January 2000 onwards will be EBSCO CINAHL Plus, Ovid MEDLINE, Ovid EMBASE, PsychINFO and the Cochrane Library and JBI database. This will include NHS Evidence which will be searched for unpublished studies and gray literature.  Title and abstract citations and full-text articles will be screened by the author and second reviewer. Data will be extracted by the author and validated by the second reviewer.  An overarching synthesis will be produced which brings together quantitative and qualitative findings. Methodological quality and risk of bias will be assessed using the Mixed Methods Appraisal Tool.    Discussion  Understanding individual, clinical and wider contextual factors associated with access and receipt of systemic anti-cancer therapies for secondary breast cancer is a complex phenomenon. These will be examined to determine any association with access. Review findings will be used to guide future research in this area and the development of an evidence-based service level intervention designed to address unwarranted variation in access based upon the Medical Research Council (MRC) approach to the development, implementation and evaluation of complex interventions.    Systematic review registration  The review protocol has been registered in PROSPERO  CRD42020196490 .    Supplementary Information  The online version contains supplementary material available at 10.1186/s13643-021-01761-y.

Access to systemic anti-cancer therapies for women with secondary breast cancer—protocol for a mixed methods systematic review