**1. Introduction**

Cancer is one of the most fatal diseases in the world, and breast cancer is the most incidence and mortality in women [1]. Breast cancer is a highly heterogeneous disease with morphological features and variable clinical outcomes. The clinical course, prognosis, and responsiveness to breast cancer treatment depend on their specific biological characteristics or classification. The immunohistochemical classification is based on hormone receptor (HR) expression (estrogen receptor [ER] and progesterone receptor [PGR]) and amplification of the human epidermal growth factor receptor ERBB2/HER2-: the HR-positive (luminal A or B), the HER2-positive and triple-negative (TNBC) subtypes [2, 3].

Overall, the systemic therapy administered consists of endocrine therapy for all HR+ tumors, immunotherapy plus chemotherapy for all HER2-positive tumors, and cytotoxic chemotherapy plus immunotherapy for TNBC [4–7]. It has been reported that long exposure to therapeutic agents may generate an adaptive cellular response that results in the induction of acquired drug resistance. So, the use of combination chemotherapy potentially provides advantages such as chances for increasing or maintaining efficacy and reduced or delayed development of drug resistance [8].

However, there are many factors involved in the failure of treatment, such as the expression of complement regulatory proteins (mCRP). These proteins have been reported to be up-regulated in several cancer cells and tumor tissues, as a mechanism to evade elimination by the complement system [9–11].

High expression of mCRP by cancer cells confers resistance against antitumoral therapies by controlling the activation of the complement cascade and regulation of intracellular complement signaling in cancer cells [11–15].

Herein, we summarize evidence related to mCRP tumoral activity in cancer cells and discuss the implications of its biological actions in anticancer therapy. Therefore, we will gather information about mCRP: (i) structural features; (ii) expression levels in breast cancer and relationship with prognosis; (iii) therapeutic resistance mechanisms; and (iv) several strategies to down-regulate mCRP in both activity and expression.
