4.Chemotherapy

Chemotherapy is the process of eliminating cancer cells with the help of specific medications. It may be administered both before and after surgery, depending on the patient's health. Docetaxel, Paclitaxel, Platinum agents (cisplatin, carboplatin), Vinorelbine (Navelbine), Capecitabine (Xeloda), Liposomal doxorubicin (Doxil), Cyclophosphamide (Cytoxan), Carboplatin (Paraplatin), and other drugs are included in chemotherapy, according to the American Cancer Society [39]. However, it has a number of negative side effects. The following are some of the most frequent breast cancer treatment regimens.

#### *The Future Perspectives of Drug Repurposing and Treatment for the Drug Resistant Breast… DOI: http://dx.doi.org/10.5772/intechopen.100143*

**Cyclophosphamide** is used to treat breast cancer metastases by preventing DNA replication and cell division. This prodrug is converted into active metabolites by hepatic intracellular enzymes (i.e. 4 hydroxy cyclophosphamide, aldophosphamide, acrolein and phosphor amide mustard). The medication has been utilised in the treatment of breast cancer as an adjuvant therapy in conjunction with CMF or an anthracycline.

Platinum compounds such as **Carboplatin and Cisplatin** are used to treat breast cancer as monotherapy or in conjunction with other cancer treatments. Platinum compounds have been investigated for their effect on DNA structure and stability, and a variety of platinum-DNA adducts have been discovered in vivo and in vitro. The impact of these different lesions on DNA replication, their potential to introduce mutations, and their susceptibility to DNA repair methods have all been measured in the early studies. Platinum (IV) compounds may cause further DNA damage, perhaps as a result of the cell's conversion to platinum (II) compounds. About 20–35 percent of patients with metastatic breast cancer who were receiving monotherapy responded to carboplatin treatment. The medicines Gemcitabine and Taxanes are often used in conjunction with Platinum compounds.

**Capecitabine** is a fluoropyrimidine oral prodrug that, when converted to 5-FU by the thymidine phosphorylase enzyme, has comparable effects as 5-FU infusion. It has been used in conjunction with taxanes to treat metastatic breast cancer that has progressed.

**Gemcitabine** (also known as difluorodeoxycytidine) is a pyrimidine nucleotide that inhibits RNA synthesis and DNA replication and is used to treat malignancies of the lung, bladder, and breast. Weekly IV injections of gemcitabine are well tolerated.

**Vinorelbine** binds to tubulin, causing mitotic metaphase to be disrupted. According to several studies, this medication has shown encouraging effects in advanced breast cancer.

Although metastatic or secondary breast cancer is difficult to cure, it may be managed for years. Chemotherapy may be used to control metastatic breast cancer and slow or stop its progression. It may also be used to reduce the severity of certain symptoms. Other treatments may be started before to or concurrently with chemotherapy.

### 5.Aromatase inhibitors

These are compounds that target aromatase, the enzyme complex that is responsible for the last step in the synthesis of oestrogen, in order to reduce oestrogen formation. Letrozole, exemastane, and anastrozole are examples of third-generation aromatase inhibitors that are currently used. A randomised clinical study that looked at the efficacy of these chemicals in treating women with advanced breast cancer found that they are quite beneficial. Females treated with aromatase inhibitors had a lower risk of developing contralateral breast cancer than women treated with tamoxifen, according to a clinical trial [40].

#### 6.Anti–angiogenesis drugs

Antiangiogenic therapy for breast cancer has a lot of potential and several ongoing studies are attempting to better understand the optimal care settings and mediator selection. Research suggests a link between endocrine resistance and cancer dependency on angiogenic networks in patients with oestrogen receptor positive tumours, suggesting a possible therapeutic benefit in combining endocrine treatment with antiVEGF mediator. Results from randomised clinical trials highlight the wide range of responses to antiVEGF therapy, indicating that a better selection of patient subgroups is needed to maximise the benefits of these treatments. The identification

of biomarkers for treatment response is a single area of intense interest, however most studies to far have failed to find a correlation between cancer-associated indicators such as cancer mutations and EGF expression and scientific response.

## 7.Radiation therapy

Radiation treatment is beneficial in early breast cancer patients, according to Zhou et al. This research looked at 143 women who had breast conserving surgery and received either regular or intraoperative radiation treatment. There was substantial local control of the tumour after 54 months of follow-up. Radiation treatment uses high-energy beams to destroy cancer cells. Only the cells that are treated are affected by this treatment. After breast cancer surgery, radiation treatment may be used to eliminate any residual cells in the chest region [41].

#### a.Brachytherapy

It's a type of radiation treatment. Accelerated partial breast irradiation is a term that comes to mind. It just focuses radiation in the general region where the cancer was discovered. This might potentially eliminate the need for whole-breast radiotherapy. The number of management sessions is also reduced.

#### 8.Protein tyrosine kinase inhibitor

**Lapatinib** is an orally active, reversible EGFR and HER2 tyrosine kinase inhibitor whose primary mechanism of action tends to be driven by HER2. When trastuzumab-treated HER2-positive breast cancer developed, lapatinib was authorised for use in combination with capecitabine; it's also utilised as a first-line treatment for HER2-positive metastatic breast cancer in combination with letrozole. Lapatinib and chemotherapy combined achieved a 22 percent response rate and a 27 percent clinical value rate in patients who had previously been treated with trastuzumab, and as prophylaxis, it achieved 12.4 percent to 25 percent clinical value rates; however, constrained resistance to lapatinib was observed in some cases [42, 43].

## 9.Gene therapy for carcinoma of the breast

Gene therapy is a kind of treatment that attempts to correct particular molecular defects related to breast cancer growth and progression. Cancer development is linked to mutated BRCA1 and p53 genes, which have been identified as cancer genetic markers. [44]. Cancer gene modification techniques may allow for selective targeting without presenting substantial hazards to non-cancer cells since cancer cells are the only ones that suffer mutational inactivation of gene activity in these circumstances. Even BRCA1 and p53 have been found to limit tumour cells without mutations in these genes, suggesting that so-called gene modification methods may be more effective than previously believed. These and other genes have been discovered as possible targets for gene substitution therapy as cancer genetics has become more well-known. Early patient investigations using BRCA1 and p53 gene therapy have shown a lot of encouraging indications of effectiveness, but they have also highlighted areas where additional clinical trials are required before these treatments may be widely utilised in breast cancer patients.

#### 10.Cancer stem-cell therapy for breast cancer

The cancer stem-cell idea is based on recent breast biology studies. According to two key aspects of this theory, cancer arises in progenitor cells or mammary

#### *The Future Perspectives of Drug Repurposing and Treatment for the Drug Resistant Breast… DOI: http://dx.doi.org/10.5772/intechopen.100143*

stem cells as a result of a dysregulation of the normally tightly controlled mechanism of self-renewal. As a result, cancers contain a cellular component that retains basic stem-cell functions including self-renewal, differentiation, and tumorigenesis while also being accountable for cellular heterogeneity. Advances in the stem-cell field have assisted the identification of stem cells in both normal and malignant breast tissue. The finding of these stem cells has assisted in identifying the origins of human breast cancer's genetic complexity. In the early diagnosis, prevention, and treatment of human breast cancer, the cancer stem-cell hypothesis is critical. Dysregulation of stem cell renewal pathways is linked to both sporadic and hereditary breast cancers. These abnormal stem cells might be utilised to create novel cancer prevention methods. Moreover, because breast cancer stem cells may be resistant to chemotherapy and radiation, efficient targeting of this cell type may be required for the development of novel effective treatments for breast cancer.
