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As every other tumor, a malign breast tumor is an uncontrollably and abnormally growing mass1. Currently, every year there are more than 1.3 million women diagnosed with this disease around the world, making it the second most common form of cancer; the most common form is lung cancer2. This disease is also ranked as the most common non-cutaneous form of cancer in women since more than 200,000 women in the United States only are diagnosed with breast cancer yearly3. Grayson2 stated that the survival rates for the before mentioned disease have greatly improved over the past decades. This data has been demonstrated since by the 1990's, there were 77% alive women that had been diagnosed with breast cancer up to 10 years before, according to the author. Later on, in 2011, breast cancer survivors accounted approximately for 23% of all cancer survivors and 40% of the 5.8 million female survivors4. Even though there has been a great increase in survivability, there still are approximately half-a-million women that die from this terrible disease annually2. Breast cancer has turned out to be the most common malignant disease predominantly in women, which presents a lifetime risk of at least 8%. This disease is known to be the leading cause of death for women6-10.
The most common methods used to diagnose breast cancer are mammography, fine needle aspiration (FNA) with visual interpretation and surgical biopsy5. The ability of these methods to truly diagnose cancer is: mammogram - 68% - 79%, FNA with visual interpretation - 65% - 98% and surgical biopsy - 100%11. According to Street12, when it comes to the diagnostic procedures sensitivity, the mammography lacks it and in FNA varies, since it is a result of visual interpretation. This author also stated that while surgical is very accurate, it is also an expensive, intrusive and time-consuming method.
Breast cancer is usually a disease in older women; it is known to occur in approximately 25% of women that are younger than 50 years old13. However, lately, there has been a huge increase in the number of breast cancer diagnosis in younger women14. During the past decade, a decrease has been shown in the mortality rate for breast cancer majorly in younger women, which results from the application of adjuvant therapy15, which will be discussed later in this review.
Currently, the most used treatments for breast cancer are chemotherapy, radiotherapy and mastectomy (which has been becoming less and less used as the years pass by). But, studies have shown that there are certain bacteria that have the ability to potentially be used as a safe treatment for breast cancer and other types of cancer as well. Bacterial treatment for cancer has been proposed and studied since late 19th century.
It has been shown that bacteria possesses specific capabilities that make them great anticancer agents16. Since their genetics can be manipulated, this means that bacteria can be engineered to overcome all or many of the limitations of current cancer therapies16. Breast cancer treatments, such as chemotherapy and radiotherapy, have limitations. For example, these treatments are known to be toxic to normal tissue and are not capable of destroying all cancerous cells17-19. These factors prevent an effective treatment and are definitely associated with increased mortality and morbidity16.
Over the past one hundred years, many bacteria have been studied as potential anticancer agents16 and have shown to accumulate in tumors, including Salmonella19, Escherichia20, Clostridium21,22, Bifidobacterium23, Caulobacter24, Listeria25,26, Proteus27 and Streptococcus28. Figure 116 shows how bacteria can be the perfect anticancer agent and how it has been studied more and more as time has passed by.
Adapted from Reference 16.
This review will give an overview of breast cancer and its' treatments. The purpose is to study the diverse cancer treatments, especially the ones that are not as radical as chemotherapy and/or mastectomy. It will focus on the most recent bacterial treatment discoveries for breast cancer.
Most used treatment or therapy
The type of breast cancer treatment or therapy that doctors decide to use in each individual relies on certain specific characteristics, such as the mass' histopathology, size of the tumor, the receptor status of estrogen and progesterone and lymph node infiltration29. The different types of therapy are: surgery (lumpectomy or mastectomy), chemotherapy, radiotherapy, hormonal therapy and immunotherapy30. Wolters et al30 stated that chemotherapy is the treatment of choice when the tumor has a higher risk of recurrence, for example, the tumor is more than 1cm in size or it has positive lymph nodes. Table1 shows the screening recommendations and the suggested time of examination for different types o cancer.
TABLE 1 .Â Surveillance and screening recommendations for survivors of breast cancer
Every 4-6 mo for 5 y
Consider magnetic resonance imaging and genetic testing
Cervical cytologic tests
Assess for menopausal symptoms
Uterine cancer evaluation
Assess for abnormal bleeding, particularly in tamoxifen users
Endometrial sampling if bleeding present
BRCA carriers: ovarian cancer evaluation
Ultrasound and CA-125 yearly
Risk-reducing surgery and genetic testing
Colorectal cancer screening
Colonoscopy every 5-10 y, beginning at age 50 y
Hemoccult testing annually
Osteoporosis: postmenopausal women
Dual energy x-ray absorptiometry scan every 2 y
Prevention with calcium/vitamin D and bisphosphonates
Salani. Gynecologic care for breast cancer survivors. Am J Obstet Gynecol 2012. Taken from reference 9
The most relevant therapeutic treatments regarding adjuvant therapy are chemotherapy, surgery, such as breast-conserving therapy, mastectomy, axilla dissection and sentinel-node biopsy, radiation, therapy after breast-conserving therapy and mastectomy and endocrine therapy mostly for pre- and post-menopausal patients30.
Radiotherapy is the treatment option when the patient had a breast-conservative surgery and/or if the patient is in high risk of recurrence after a mastectomy31. Andersen and Kehlet31 stated that radiotherapy can be applied in two different ways, either towards the residual breast or chest wall or towards the axillar and clavicular area. These authors also stated that the radiation field extension really depends on the status of the disease when diagnosed and on the radicalism of the surgical procedure. While, endocrine therapy includes selective estrogen receptor modulators (SERM) such as tamoxifen and aromatase inhibitors31, which are discussed in more detail below.
Andersen and Kehlet31 stated that women that are in a pre-menopause stage should be indicated to receive tamoxifen for five years as the treatment of choice. Estrogen receptor inhibitors, such as Tamoxifen, are also used as treatment for patients with breast tumors that are expressing high levels of estrogen and progesterone receptors31. Recently, the aromatase inhibitors (a new group that inhibits the estrogen synthesis) are being implemented as treatment of breast cancer patients that already went through menopause29,32,33. This new group of estrogen synthesis inhibitors, because of its low levels of toxicity are becoming more and more attractive rather than tamoxifen29. However, Wiechec and Hansen29 mentioned that the genetic profile of each patient has a great role in the outcome of every treatment.
There is also the neo-adjuvant therapy, either radiotherapy or chemotherapy. Neo-adjuvant radiotherapy is usually used in early diagnosis to decrease as much as possible the size of the tumor before the patient undergoes surgery30. Also, as neo-adjuvant therapy, chemotherapy is performed prior to surgery, instead of after surgery as it has been done for so many years34,37.
More recently, the use of neo-adjuvant chemotherapy (NAC) is being used as treatment of earlier-stage breast cancer patients35-37 with the purpose of diminishing the tumor's size as much as possible so that a patient that would need a mastectomy, could be able to receive breast-conserving surgery (BCS) instead36-41. An animal model has supported the idea suggesting that NAC may be able to decrease the micro-metastases potential, which at the same time supported that the increase in breast cancer patient's survival is related to the control of micro-metastases37,42,43.
In clinical settings, NAC seems to be equivalent or even better than the systemic therapy performed as adjuvant treatment after surgery37. Furthermore, NAC has been shown to increase the rates of BCS instead of mastectomy36-41, as previously mentioned. But, there are some standard indicators (i.e. size of tumor or number of lymph nodes) that do not apply as neo-adjuvant, since systemic therapy greatly diminishes and potentially eliminates the cancer37.
Recently developed treatments
There are some other new treatments that are being discovered. The main purpose of all these new treatments is to downgrade the negative effects of the chemotherapy. These treatments are directed only towards the malign cells. Nowadays, breast cancer still is a major health concern. Even though there are very effective treatments, it still is a very dangerous disease44.
One huge concern regarding current treatments such as chemotherapy is developed resistance. In "Advances in breast cancer treatment: the emerging role of ixabepilone", Frye44 stated that there is a complication on how to manage metastatic breast cancer (MBC) due to the developed resistance that has been shown to occur in some patients. The following are some essential elements in the treatment for breast cancer44 that are also a component of neo-adjuvant therapy: antimicrotubule agents (i.e. docetaxel and paclitaxel) and anthracyclines (i.e. epirubicin). However, the previously mentioned author mentioned that there are already some patients that have developed resistance to this medications. Due to this reason, new research is being made in agents that have a potential activity in drug-resistant tumors, according to Frye44.
It has also been demonstrated that there is a new class of microtubule-stabilizing agents with great potential activity against some anti-microtubule cell lines, the epothilones44. In the previously mentioned study, it has been shown that ixabepilone is also a potential treatment option for those breast cancer patients that are resistant to taxanes. This new option has also the ability to overcome chemotherapy-induced resistance and has been shown to work properly in MBC's minimal and heavily pre-treated patients44. The detailed mechanism of epothilones can be found in reference 48.
Another recent treatment is the Intensity-modulated radiotherapy (IMRT). This treatment consists of the use of multiple intensity levels beams for any single beam, which allows the distribution of the dose to be much more directed to the cancerous cells than conventional radiotherapy, as described in "Intensity-modulated Radiotherapy in the Treatment of Breast Cancer" by Dayes et al45. This new treatment is ideal for complex cases since its approach is that it allows the dosage to be measured depending on the patient's anatomy, which definitely shows positive results, due to the fact that avoids radiation penetration in organs near the tumor45. IMRT has shown a decrease in toxicity in disease sites such as neck cancer46 and prostate cancer47.
Brief history of bacterial therapy for cancer
The bacterial use as an anticancer agent was recognized approximately hundreds of years ago48. W. Busch and F. Fehleisen, German physicians, noted regression in some types of cancer after an accidental infection with erysipelas (Streptococcus pyogenes or S. pyogenes) that occurred to some of their hospitalized patients93. Later on, W. Coley, an American physician, also observed that one of his cancer patients began to recover after an erysipelas infection; Coley then began to document the use of bacteria and its toxins as anticancer agents48. In the late 1800's, he developed a vaccine composed of killed S. pyogenes and Serratia marcescens, stimulating an infection with fever, but with no risks of developing an actual infection94,95. The vaccine had a positive outcome for melanomas, carcinomas, sarcomas, myelomas and lymphomas48. In many cases, the patients had a successful, complete and prolonged regression of a late stage malign tumor96. 'Coley toxins' are some toxic bacterial derivatives that were studied for a possible potential as an anticancer agent97, and their early success provided a base for many of the advances in cancer immunotherapy48.
Bacteria as cancer treatment
Patyar et al48 stated that, as previously mentioned, there are certain bacteria that can be well studied as potential anticancer drugs and even for gene therapy vectors. The authors also mentioned that anaerobic bacteria spores are also considered a possibility as anticancer treatment since they are known to only reach, germinate and become active in an area that is oxygen starved, such as tumors.
Bacterial toxins in cancer
Bacterial toxins, such as endotoxins, have already been studied as anticancer agents48. They have shown to have a positive outcome in tumor destruction49. In "Bacteria in cancer therapy: a novel experimental strategy" by Patyar et al48, the authors proved that bacterial toxins are not only able to eradicate cancerous cells, but, they proved that at lower levels they are capable of altering and/or controlling differentiation, proliferation and apoptosis of these cells. However, these alterations can also be capable of initiating carcinogenesis, cellular aberrations or can even inhibit the controls of non-cancerous cells48.
Cellular proliferation has been shown to be promoted by the cytotoxic necrotizing factor, which is also able to impede cell differentiation50. Therefore, bacterial toxins in general or in combination with anti-cancer therapy are another potential treatment that has shown to have a positive outcome in cancer patients49.
Bacterial toxins for breast cancer treatment
Studies done in mouse models have demonstrated that a vaccine based on an attenuated form of Listeria monocytogenes has the ability to destroy all breast cancer metastases and primary tumors51. Another study also done in mouse models showed that a recombinant strain of Salmonella typhimurium (S. typhymurium), obviously in an attenuated form, is capable of promoting growth inhibition of primary tumors and to stop the dissemination of pulmonary metastases48. In both of these studies, the antitumor activity outcome was positive, without significant toxicity56.
Bacterial toxins are known to be great cytotoxic agents19. One important bacterial toxin that induces apoptosis by forming pores in the mammalian cell membrane is Cytolisin A (ClyA)53,54, a native bacterial protein53,55. It has been proven that tumor growth can be reduced with some of the Escherichia coli (E. coli) or S. typhimurium that express ClyA53-55.
One important component of all this process is the tumor necrotic factor alpha (TnFÎ±) family. This family contains three cytotoxic agents that are very relevant to breast cancer treatment: TnF-related apoptosis-inducing ligand (TARIl), FAS ligand (FASl) and TnFÎ± 23-2719. These cytotoxic agents are proteins that are capable of inducing apoptosis in a very selective manner, compared to normal non-cancerous cells56,57, through death receptor pathways activating caspase 8 and 3, which are a crucial mediators in apopotosis56. If a cell has an FAS receptor, FASl will be able to induce cell apoptosis57. The other two proteins have shown to have an impact in breast, lung, pancreatic, ovarian, bladder, prostate, colon tumors and in many other sites as well56,58. The main concern with this cytotoxic agents is that all three have shown to be hepatotoxic and have a short circulatory half life56,59-61. This two deficiencies have been shown when the agents are being administered systemically as drugs56,59-61.
Clostridium perfringens enterotoxin (CPE) has also shown to have some cytotoxic effect that ended up inhibiting tumor growth in vivo and turning the cancerous mass into a necrotic tumor; new research is being done on CPE for breast, gastric and colon cancers48. Since Clostridium perfringens can be so toxic to human and animal health, researchers are trying to prove that in fact CPE will lack toxicity if it's going to be administered in vivo62-64.
CPE treatment for breast cancer was also studied by Kominsky et al64. The authors showed how the proteins claudin 3 and 4 (CLDN 3 and 4), whose genes encode an important protein family in tight junction66, are normally expressed in primary breast tumors and cell lines. They have even been over expressed approximately 26% - 62% in primary tumors, compared to non-cancerous mammary epithelium64. Hewitt et al66 stated that lately, studies have shown that in some types of cancers, the gene expression of CLDN can be modified. Kominsky et al64 proposed that CLDN are a great potential breast cancer treatment since when these proteins are expressed, they are sensitized to CPE-mediated cytolysis, suggesting this as a local treatment. The previously mentioned authors showed a fast and mostly complete cytolysis when treating breast cancer cell lines with CPE expressing CLDN 3 and 4, in a dose-dependent manner64. On the other hand, Kominsky et al64 also noted that if a cell line was not expressing the proteins, they were totally resistant to the CPE's cytotoxic effects. The authors noted that their results were consistent with previous studies done with other cancer types. Therefore, they were able to confirm their results as a significant conclusion.
After completing that investigation, Kominsky et al64 studied the cytolytic effects of CPE in breast tumors in vivo. The authors were able to confirm that in animal models that were being administered with the proposed treatment, no systemic toxicity, such as ruffled fur, weight loss, huddling, etc, was shown. They also concluded that the cancerous mass volume did not increased during the two weeks of treatment, when they were being administered 2Î¼g of CPE as intra-tumoral therapy. At the same time, as they increased the CPE doses to 10Î¼g, the tumors were greatly reduced by the end of the two week treatment. Their research also showed CPE treatment of specific breast cell lines (i.e. T47D) resulted in a cancerous mass significant decreased volume and in cell necrosis. Kominsky et al64 ran other tests in which they were able to conclude that there is also susceptibility in primary breast cancer cells to the CPE cytolytic effects. They stated that this is can be mostly due to the CPE's binding to its receptors, which are CLDN 3 and CLDN 4, that are being expressed at the cell membrane.
In the case of Shiga toxins (Stxs) as breast cancer treatment, the complete cell line was studied and shown in "Induction of apoptosis by Shiga toxins" by Vernon Tesh67. Tesh stated that since there is already evidence that Stxs are capable of inducing apoptosis in some cells, it seemed interesting to study if these toxins could be used as chemotherapeutic agents. Johansson et al65 demonstrated that apoptosis induction in in vivo breast cancer cell lines varied greatly with Shiga toxin-1 (Stx1). Tesh67 was able to show that an important factor in Stx1 apoptosis is sensitivity, which is in direct correlation not only with Gb3 (a neutral glycolipid that binds to the toxin receptor), but also to the usage of PPMP, which is a drug that downregulates the production of glucosylceramide. This study also indicated that in the T47D-Gb3+ (Gb3-expressing) cell line, Stx1 apoptosis induction occurred if there were certain caspases and kinases present and active, caspases 8, 9 and 3 and phosphorylation of stress-activated proteins respectively. Gb3 is primarily expressed in breast cancerous masses' small arteries and arterioles; this was showed with immunohistochemical procedures that were done in 25 specimens, where 17 were Gb3+ 67.
Tesh's study67 suggests that there is a possibility that Stxs are capable of destroying the tumor's vascular network and of having cytotoxic effects on the cancerous cells as well. Gb3+ tumors are known to be really difficult to treat, so fortunately, Stx1 injections in animal models presenting human breast cancer tumors are having positive outcomes, since they are increasing apoptosis in the treated tissues and also have increased survival rates68.
Toxins in different types of cancer
There are some bacterial toxins that are being studied in other types of cancer. For example, alpha-toxin from Staphylococcus aureus, shiga-like toxins, cholera toxins and AC-toxin from Bordetella pertussis are or have been studied as anticancer agents for mesothelioma and small lung cancer cells48. In "Bacteria in cancer therapy: a novel experimental strategy", Patyar et al results showed that the AC-toxin's dose is directly correlated with an increase in cytotoxicity and apoptosis in both types of cancer. While, cholera toxins were not successful as apoptotic agents72.
On the other hand, Mycobacterium bovis Bacillus Calmette-Guérin's (BCG-CWS) cell wall skeleton has had a positive outcome if administered as an adjuvant for immunotherapy in patients that are suffering from different types of cancer73. Specifically in colon cancer, BCG-CWS has been shown to be a great possibility for treatment since it has been able to induct an autophagic cell death, mostly because of its' particular characteristic of radio-sensitizing48. Studies regarding BCG-CWS combined with ionizing radiation treatment have been made in both in vitro and in vivo and have resulted in possibly becoming a great strategy in the therapy of cancerous cells in the colon71. All the research done, up until now, states that there are some non-virulent bacterial that can be potentially considered as immunotherapeutic agents in cancer patients48, which brings hope to many people around the world.
Most of the anaerobic bacteria that have been discussed previously have the ability to form spores if they are at risk of dying48. Spores are usually formed in oxygen rich environments, so that they are able to survive rough conditions48. Patyar et al noted that once they reach a favorable environment (i.e. inside the tumor, where the tissue is dead), spores can germinate52, converting itself to the regular bacteria, which makes them an ideal idea for cancer treatment. The authors' study revealed that there was tumor lysis in animal models that were being administered intra-tumoral injections of Clostridium sporogenes spores. Positively, this spores were only detected in cancerous tissues, not in normal non-cancerous tissues in animal models that were being administered its dosage intravenously72. Another positive outcome that definitely needs to be taken into consideration is the fact that in healthy animals there wasn't any clinical toxicity expression even after large doses that were administered in the mice that were being tested48. Unfortunately, in animal models that suffered from cancer, toxicity was directly correlated to spore dose and tumor size73. Bacterial spores are not only being studied as anticancer agents. Due to their survival and specific-activation activity, spores are currently in research as vectors for gene therapy, cytotoxic peptides and therapeutic proteins48.
Metastasis is defined as new lesions in new organs that were formed after a series of steps in which cancerous cells do not stay within the primary site, but they start to migrate around the body74. For metastasis to occur, cancerous cells have to degrade and go across the extracellular matrix, intravasate, migrate through blood or lymphatic vessels, extravasate and establish in the secondary site75. Not many studies have been done successfully for metastasis since animal models are not completely capable of replicating the whole metastatic process79,80. To be an ideal model, the complete metastatic procedure would replicate successfully, including the establishment in the secondary site74.
Li and Feng79 described breast cancer as "the most common malignancy in women". They also stated that this type of cancer is the leading death cause due to its power for metastasis. It must be noted that an increase in plasticity with random cells in the environment, extracellular matrix and specifically with adjacent tumor cells is needed in order for the cancerous cells to complete the metastasis process79.
A common advanced breast cancer metastasis is the spread to the bones, which is known to be very painful80. Seventy percent of the advanced cases of malign breast tumors usually have a relapse in the bones80,82. Sloan and Anderson stated that this type of metastasis can comply with other diseases such as long bones fractures, osteoporosis, spinal cord compression and others. There is also a major concern with the patient's quality of life, due the fact that their survival median rate is only 3-5 months in total, if they are diagnosed with bone cancer as a result of a metastasis82. The need for effective therapy is reiterated specifically in these cases since, the morbidity associated with bone metastasis and the long clinical course of the disease in these patients is a known fact.
In "Regulation of Breast Cancer Metastasis by IGF Signaling", Sachdev also explains that metastasis is a really complex procedure with multiple steps that will only occur if there is a coordinated regulation (this process was described above). It is not very common that the complete procedure takes place successfully; only a low percentage of the cancerous cells are able to complete the whole process85. It should be noted that the previously mentioned author also understands that the decrease in breast cancer metastasis has something to do with the increase in screening, since patients are being diagnosed at a very early stage of cancer. At the same time, an increase in systemic therapy may be another reason why breast cancer mortality rates have decreased in the past decade or so85. Sachdev believes that this decrease can be happening thanks to the sub-clinical micro-metastasis treatment. Unfortunately, there has been some resistance developed to treatments such as tamoxifen. These treatments tend to have a positive outcome, but this is not one hundred percent guaranteed, leading to metastasis85. Sachdev concluded that to be able to treat or to give therapy to patients that are suffering from cancer metastasis, there is a need to understand the growth factor pathways, so that new treatment options could be manufactured and used successfully.
Disadvantages of bacterial treatment for cancer
In Patyar et al48 publication, "Bacteria in cancer therapy: a novel experimental strategy", the authors stated that toxicity due to high levels of dosage is definitely of high concern, since normally reduced doses imply reduced positive effects as anticancer agents. Another main concern regarding the use of bacteria for cancer therapy is the possible side effect of systemic infections, due to the fact that some of the bacteria that have been tested as potential anticancer agents are highly toxic to human health48; furthermore if it has been proven that even after removing the toxic genes from the bacteria, as is being done in a process known as combination bacteriolytic therapy, still ended up in ~15% - 45% mortality in animal models85 (a complete description of this treatment can be found in references 48 and 86).
Incomplete tumor lysis is yet another problem with bacteria as cancer treatment, since the therapy would not only require the bacteria with all its risk, but it would definitely require common methods, such as chemotherapy, 48 which is what is being trying to be avoided. Patyar et al understand that therapy for small non-necrotic metastasis is an even more difficult task to resolve; they all agreed that this may be the major mortality cause from cancer. In the case of bacteria based vector therapy, since intra-tumoral injections are needed to complete the treatment successfully, great accessibility is needed, if not, the task will fail87.
Mutations in bacterial genes or segments could conduce to heavy infections to immune-compromised patients or can the treatment can be a failure48. Much more research is needed for bacterial treatment for cancer to be considered a safe therapy method. Patyar et al concluded that even though many safety concerns have been studied, analyzed and resolved with recombinant DNA technology, still, this cannot be considered the safest method.
When it comes to CPE, Kominsky et al stated that even though this method has the ability to lyse cancerous breast tumors, it cannot be contemplated as a success treatment. All new and many current treatments share the same problem: to prevent it for being used constantly, a neutralizing antibody response is required64. Anti-enterotoxin antibodies were found after ingesting the treatment, which should be a positive thing, but it's not, since no protection was found in further treatments, as is noted in the previously mentioned authors research. As with Patyar et al, and mostly all the research done for this new treatment, Kominsky et al concluded that more studies are needed for the CPE's immune response to be confirmed when administered by all the different routes.
CPE's anticancer treatment faces even more problems. It was noted that this therapy does not possess the capability of penetrating solid tumors64. Kominsky et al found that if CPE was administered intra-tumoral, did lead to necrosis, but this was not always the case. New studies are being made to find alternatives that could penetrate better the cancerous masses64,90,91.
As with any new developed potential drug treatment, systemic toxicity is of high concern. Kominsky et al noted that this is of high risk in CPE therapy due to the fact that other important organs and tissues also express CLDN 3 and 4, which could result in systemic toxicity. This has already happened even with low dose administration, some symptoms such as loss of appetite and immobility were seen in animal model92. Until now, local injections, rather than intra-peritoneal, seemed to be the safest CPE's treatment method, according to Kominsky et al.
Breast cancer is a very common disease mostly in women and cannot be taken lightly. Fortunately, as time has passed by, the mortality and morbidity rates have considerably decreased. This is mainly due to available screening and early diagnosis, but also due to treatments. Formerly, the treatment was decided depending on the cancer stage when it was diagnosed and since there was not that much screening or awareness, most cases needed to be treated with mastectomy and chemotherapy. Even though these treatments work to remove the disease, they are still too radical. Due to how radical these treatment options are, scientists and researchers have been looking for alternative treatments such as bacterial treatment. Some of the bacteria or bacteria toxins that have been studied as potential cancer treatment are: Listeria, Clostridia, Salmonella, Shiga toxins, Shiga-like toxins and alpha toxins.
Many studies and experiments have been made regarding the bacterial toxin treatment for breast cancer. However, more studies need to be made in order to be able to completely understand and prove that the toxins work according to what is expected. There are many promising studies that will definitely be the ones to start with the bacterial toxin treatment for breast cancer in the near future. If this becomes the alternate treatment, instead of mastectomy, chemotherapy and radiotherapy, the future of breast cancer treatment looks very positive. Bacterial toxin treatment will reduce even more the mortality rates, the side effects, the risks and symptoms, compared to the actual treatment.