# Bacteriotherapy in Breast Cancer
## 1 Introduction  
Breast cancer is the second most common cause of cancer-related mortality among women around the world. It is one of the most frequently diagnosed cancers in women and it has a high incidence rate in all countries [1]. According to the last estimate from the World Health Organization (WHO), in 2018, there were over two million new cases and it is estimated that 627,000 women died of the disease, which is approximately 15% of all cancer-causing deaths among women. We know cancer is a complicated disease result of genetic, epigenetic and environmental factors. Thus, it needs a range of treatment modalities and management [2, 3]. Traditional and widely used treatments for cancer, including surgery, radiotherapy, chemotherapy, and some modern treatments (hormone-based therapy, stem cell therapies, immunotherapy, anddendritic cell-based immunotherapy) all have their own limitations. As an example, chemotherapeutic agents have nonspecific toxicity toward normal body cells [4; 5]. Moreover, chemotherapy, in some cases, can lead to the formation of multidrug resistance cells. Due to the complications of chemotherapy, scientists have focused on examining the potential of using bacteria and their products to make new cancer medicines with low toxicity or without any side effect on normal cells. Genetic engineering has been used in bacteria therapy and has led to greater efficacy with minimal side effects. Some of genetically modified non-pathogenic bacterial species are more successful due to their selectivity for cancer cells with low toxicity for normal cells [6]. Metastatic cells can alter host cells, inhibit the mechanisms of normal growth of cells, and increase the rate of development of cell clones that produce neoplasm [7]. Thus, the treatment of cancer includes inducing apoptosis and decreasing or inhibiting the proliferation of tumor cells. Several bacterial strains have been identified and have natural oncolytic potential to penetrate, invade, and colonize in breast tumor [8]. Although many bacteria are carcinogens and tumor promoters [9; 10; 11; 12; 13; 14; 15], some have shown great potential towards cancer therapy. Several species of bacteria have shown an impressive ability to invade and colonize solid tumors, which has often led to neoplasm growth retardation and tumor clearance [6]. Different strains of _Clostridia_, _Lactococcus_, _Bifidobacteria_, _Shigella_, _Vibrio_, _Listeria_, _Escherichia_, and _Salmonella_ have been evaluated against cancer in animal models [6]. However, some of these bacteria, such as _Bifidobacterium longun_ and _Clostridium novyi_ strains, are capable of colonizing the hypoxic area of the tumor, and therefore destroy the tumor cells [16; 17]. Some others such as the attenuated auxotrophic mutants of the _Salmonella typhimurium_, one of the most efficient antitumor bacteria, can invade and destroy many types of cancer cells in vitro and replicate in toxic and hypoxic tumor regions in vivo [18]. For the first time, a bone surgeon, [PERSON], used bacteria as an anticancer agent, known as [PERSON]'s toxins. He injected a mixture of two heat-inactivated bacteria, _Streptococcus pyogenes_ and _Serattia marcescence_, into more than 1000 patients with malignancy. Tumor regression was observed in many patients and 30 cases were completely treated [19]. Despite these great results, over time, development of other therapeutic approaches, such as radiation therapy and chemotherapy, caused the use of [PERSON]'s toxins to gradually disappear. However, recent immunological studies suggest that the general principles of [PERSON]'s toxins are correct because some cancers are sensitive to the enhancement and improvement of the patient's immune system [20; 21]. In spite of the side effects, bacteria-mediated tumor therapy (BMTT) has been used to control cancer for a long time. To use BMTT, it is necessary to maintain the balance between their side effects, such as infection, and its therapeutic effects.