Breast tumor exhibits great heterogeneity and several subgroups. Based on the immunohistochemical expression of hormone receptors, these subtypes are typically divided into four categories: estrogen receptor positive (ER+), progesterone receptor positive (PR+), human epidermal growth factor receptor positive (HER2+), and triple-negative breast cancer(TNBC), which lacks the expression of any of the previously mentioned receptors 4. Based on these types cancer cell lines are characterized using the same nomenclature, i.e., luminal A, luminal B, HER2 positive, and triple negative subtypes, with triple negative cells being further divided into A and B to cover its heterogeneity and widely used in the name of basal A and B 5.

Curcumin extracted from Haridra was tested on MCF-7 breast cancer cell line resulting in cell apoptosis acting through p53-dependent pathway 6. It also possesses inhibitory effect on cell proliferation when tested on MDA-MB-231 and BT-483 cell lines in a time- and dose-dependent manner. Along with anti-proliferative effect, it inhibits/downregulates NF-κB expression 7. Its antiproliferative effects are estrogen dependent in ER positive MCF-7 cells, being more prominent in estrogen-containing medium and in the presence of exogenous 17-beta estradiol 8. As a phytoestrogen, curcumin competitively blocked endogenous estrogen, which also helped to slow the proliferation of breast cancer cells 9. Curcumin substantially reduced the onset of mammary adenocarcinoma on the fourth day following DMBA injection in an animal study of breast cancer 10. In a xenograft mice model of human breast cancer, the combination of curcumin and paclitaxel (Taxol) significantly reduced lung metastasis of breast cancer in comparison to either curcumin or paclitaxel alone 11.

Haridra was assessed both therapeutically and prophylactically, by using two different routes of administration, i.e., oral, and topical. It showed a considerable anticancer activity against MNU-induced mammary cancer in rats, the anticancer activity was more pronounced and significant, especially with topical application, in preventative treatment groups. When compared to the therapeutic treatment groups, the preventive topical administration of turmeric showed a better degree of tumor development inhibition and significant reduction in mean tumor volume. When compared to the other groups, prophylactic topical administration of turmeric has demonstrated higher effectiveness in lowering tumor incidence rates 12.

50% methanolic extract of its stem shown substantial anticancer activity against MDA-MB-231 human breast cancer cell line in vitro. Its chloroform fraction also inhibited growth of MDA-MB-231 and MCF-7 breast cancer cells by inducing ROS abrogated apoptosis 13, 14. Similarly, ethanolic extract of Guduchi shows cytotoxic effect in dose dependent manner on MCF-7 and MDA MB 231 breast cell lines by apoptosis and arresting the cell cycle at G2/M phase 15. Secondary metabolites including anthraquinones, terpenoids, saponins, rutin and quercetin are pharmacologically active compounds identified which are responsible for breast cancer combating effect 14, 16. Compound formulation prepared from Guduchi significantly inhibit tumor progression of DMBA induced breast tumor in Sprague-Dawley rats 17.

A research group induces tumor in mice by injecting human breast cancer cells. While cancer propagates, mice were given with basal diet for 8 weeks after cancer cells’ injection. One group was fed with 10% flax seeds while another group continued basal diet. Rate of cancer growth was reduced by 45% by flax seeds. Mammary glands morphogenesis in mice is improved by flax seeds. The examination of female mice fed with 10% flax seeds diet showed improved number of terminal end buds and terminal ducts in their mammary glands. They have extra epithelial cell division. All females show increased differentiation. Relatively low incidence of breast tumor has been shown by female after injection of carcinogens in mammary glands. As a result, increased differentiation in mammary tissues of mouse, prevention of malignancies, reduction of tumor development are possible by flax seeds in female offspring, making less vulnerable to carcinogens 18, 19, 20.

Thymoquinone extracted from N. sativa was treated to MDA-MB-468, T-47D and MCF-7 cells, and its anticancer efficacy was assessed. It upregulated the expression of p53 gene which is tumor suppressor. Procaspase-3 and Bax are translated upregulated, which promotes G(1) phase arrest. Additionally, downregulation of the gene expression of survivin, Bcl-2, and Bcl-xL together with inhibition of cyclin D1 and cyclin E, PARP cleavage. It shows anti-metastatic effect on triple-negative MDA-MB-231 breast cancer cells by downregulating the expression of CXCR4 in a dose dependent manner 21, 22, 23. Higher concentration of N. sativa Linn. seed oil (50 g/mL) altered the morphology of breast cancer cells and reduced their viability and proliferation 24.

It shows significant antiproliferative and antimotility effect against MCF-7 and MDA-MB-231cell lines by activating caspase 9 indicating cytotoxicity by apoptosis 25. Another study reported that fresh garlic extract ceased the proliferation and changed morphology of MCF 7 breast cancer cell line due to phenotypical changes occurred 26. Diallyl sulfide extracted from Garlic inhibited growth of MDA-MB-468 cancer cell line significantly. When it is tested in vivo in Ehrlich Ascites Carcinoma (EAC) tumor induced Swiss albino mice it effectively reduced tumor growth. The probable action of cell death is due to apoptosis by enhancing the expression of caspase-3 and hindering p53's oxidative destruction as it is a tumor suppressor protein 27. Garlic acts as preventive food to fight against primary breast carcinoma proved by a case control study on 345 patients. Thus, intake of garlic was linked to a lower incidence of breast cancer 28, 29.

Ashwagandha leaves aqueous extract was shown to have anticancer properties, which were examined in vitro and in vivo tests utilizing the MCF-7 cell line in a dose dependent manner 30. Withaferin A decreases mouse tumor size and area which support its use in the treatment of pulmonary metastasis of breast tumors after injection in a mouse model 31. Ashwagandha extract reduced the growth of xenografted tumors by 60% compared to the untreated control, preventing the proliferation of xenografted MDA-MB-231 cells in nude mice after 8 weeks of therapy. Additionally, in vitro MDA-MB-231 cell growth was suppressed by its root extract. Using the MDA-MB-231 cell line and 4T1 cell line, respectively, human xenograft and mouse mammary carcinoma models were employed to demonstrate dose-dependent delay of tumor development and the occurrence of metastatic lung nodules. Standard W. somnifera root extract and Withaferin A produced a minimally harmful inhibition 32, 33. When cells were treated with withania, a concentration-dependent decline in cell viability was seen. Administration of withania slowed the development of tumors in MDA-MB-231 xenografts made from female nude athymic mice. Additionally, the mechanism of FOXO3a and Bim in Withania-mediated apoptosis in xenografts was examined. There is evidence that FOXO3a and Bim are involved in the control of Withania-mediated apoptosis from the tumors of mice treated with Withania, which showed decreased cell proliferation and enhanced apoptosis 34. W. somnifera with chemotherapy and chemotherapy alone (control) were evaluated for effectiveness in a prospective, non-randomized clinical study of female breast cancer patients. The patients received a vegetarian capsule containing 2 g of withania root extract orally during their chemotherapy treatment. This study concluded that the addition of W. somnifera to chemotherapy might reduce fatigue and enhance quality of life in breast cancer patients 35.

Breast cancer cell lines A431 and MDA-MB231 are highly responsive to andrographolide (ANDR), a pharmaceutical component derived from A. paniculata. It has the potential to be developed as a therapeutic target in breast malignancies since it inhibits MMP-7 production through TIMP1 up-regulation, inhibits breast cancer invasion, and operates via the NFkB signal transduction pathway without triggering pyroptosis 36 . In another study the growth of several cancer cell lines, including MDA-MB-231, BT-549, MCF-7, MDA-MB-361, and T47D, was markedly inhibited by andrographolide. When studied in vivo it decreased tumor angiogenesis and proliferation in human breast cancer xenograft model. It could suppress the proliferation and angiogenesis of breast cancer cells through disrupting the p300/COX-2 and VEGF signaling pathway 37.

Also, by lowering THOC1-promoted cancer stem cell features, andrographolide inhibits the malignancy of triple-negative breast cancer 38. It inhibits each stage of cancer development through lipid dependent cancer pathways. It is believed that to maintain the growth of cancer, cancer cells can endure the undesired metabolic effects of plasma lipid levels. As a result of changes in cholesterol, lipid raft amount and structure may directly affect signal transmission, which results in oncogene activation 39.

Methanolic extract of the plant shows potential anticancer activity against MCF-7 cancer cell line 40. By changing the Chk-2 signaling pathway in MCF-7 breast cancer cells, the 4'-Demethyl-Deoxypodophyllotoxin Glucoside from P. hexandrum shows potential anticancer properties 41. Podophyllotoxin present in the root of P. hexandrum was able to inhibit MCF-7 human breast cancer cell line about 50% at a dose of 1 nM 42. After 48 hours of treatment, podophyllotoxin-polyacrylic acid conjugate micelles exhibit significantly (p 0.01) increased in vitro cytotoxicity against both sensitive and resistant human breast cancer cells (MCF-7 and MDA MB-231) 43.

By reducing cell motility and colony formation in breast cancer cell lines, moringa extracts serve as an anti-cancer agent. Upon treatment with the extracts of Moringa leaves and bark, low cell survival, high apoptosis, and G2/M enrichment were also found 44. There was a clear cell growth inhibition of human breast cancer cell lines MCF-7, MDA-MB-468, and MDA-MB-231 in a dose and specific duration for the inhibition of cells after different doses of plant leaf extract were taken and introduced into cancer cell lines 45. Rutin, Vicenin-2, and Quercetin-3-O-glucoside,phytochemicals from Moringa shows highest binding energy to BRCA1 gene, the inherits of which are diagnosed with Breast cancer 46.

Breast cancer induced in mice using the carcinogen DMBA, P. niruri exhibits anti-angiogenic activity and suppress inflammatory pathways 47. Four species from Phyllanthus genus were known to cause apoptosis and hinder the metastasis of breast carcinoma cells (MCF-7). By inhibiting the extracellular signal-related kinase (ERK) pathway and decreasing the production of matrix metalloproteins 2 and 9, Phyllanthus species reduced the metastasis and proliferation of breast cancer. The four Phyllanthus species' most probable targets for preventing MCF-7 metastasis are the ERK and hypoxia pathways 48. P. niruri in combination with Curcuma longa exhibited potential anticancer property. In silico analysis of Curcumin and Phyllanthin causes marked metastatic inhibition of Breast cancer through various pathways 49.

Piperine, a chief alkaloid component present in P. longum has showed potent anticancer effect dose dependently against 4T1 tumor growth and remarkably inhibit lung metastasis of 4T1 mammary carcinoma in vitro and in vivo model 50. Also, it acts in breast cancer through various mechanisms such as diminished cell cycle, increased cell apoptosis, MDR inhibition, signaling pathway inhibition, and decreased metastatic promoters 51.