Progesterone receptor inhibits aromatase and inflammatory response pathways in breast cancer cells via ligand-dependent and ligand-independent mechanisms

Aromatase (product of CYP19 gene), the critical enzyme in estrogen biosynthesis, is up-regulated in 70% of all breast cancers and is highly correlated with cyclooxygenase 2 (COX-2), the rate-determining enzyme in prostanoid biosynthesis. Expression of COX-2 also is correlated with the oncogene HER-2/neu. The efficacy of current endocrine therapies for breast cancer is predicted only if the tumor contains significant amounts of estrogen receptor. Because the progesterone receptor (PR) is an estrogen-induced target gene, it has been suggested that its presence may serve as an indicator of estrogen receptor functional capacity and the differentiation state of the tumor. In the present study, we tested the hypothesis that PR serves a crucial protective role by antagonizing inflammatory response pathways in the breast. We observed that progesterone antagonized the stimulatory effects of cAMP and IL-1beta on aromatase, COX-2, and HER-2/neu expression in T47D breast cancer cells. These actions of progesterone were associated with increased expression of the nuclear factor-kappaB inhibitor, IkappaBalpha. In 28 breast cancer cell lines, IkappaBalpha expression was positively correlated with PR mRNA levels; overexpression of a phosphorylation-defective mutant of IkappaBalpha inhibited expression of aromatase, COX-2, and HER-2/neu. Moreover, in breast cancer cell lines cultured in the absence of progesterone, up-regulation of endogenous PR caused decreased expression of aromatase, COX-2, and HER-2/neu expression, whereas down-regulation of endogenous PR resulted in a marked induction of aromatase and HER-2/neu mRNA. Collectively, these findings suggest that PR plays an important antiinflammatory role in breast cancer cells via ligand-dependent and ligand-independent mechanisms.     

The Effect of Tamoxifen on Expression of ER,PR, Cerb-B2, and ki-67 in C3H Mice Spontaneous Breast Cancer Model and The Relation with Chemotherapeutic Effect

To explore the effect of tamoxifen on expression of ER, PR, Cerb-B2, and ki-67 in C3H mice spontaneous breast cancer model and further explore its relation with chemotherapeutic effect. Forty male C3H mice with spontaneous breast cancer aged 10 months were selected, and randomly divided into model group and tamoxifen group, with 20 mice in either group. Model group received intraperitoneal injection of normal saline, tamoxifen group received 5 mg/Kg tamoxifen injection. Tumor volume was measured every 3 days for 12 days in total. After that the mice were killed to weigh the tumor for tumor growth inhibition rate calculation; breast cancer specimen was collected, and immunohistochemistry was used to detect ER, PR, Cerb-B2, and ki-67 positive cells, western blot was used to detect expression of ER, PR, Cerb-B2, and ki-67 in breast cancer. The tumor growth inhibition rate of tamoxifen on mice was 61.56 %. Compared with model group, tumor weight in mice from tamoxifen group was significantly lower, tumor growth rate in tamoxifen group was significantly lower than model group; immunohistochemical staining results showed that compared with model group, ER, PR, Cerb-B2, and ki-67 positive cells in tumor of tamoxifen group were significantly lower (P < 0.05). Among them, ki-67 expression in tamoxifen group was negative; western blot semi-quantitative results were in accordance with immunohistochemistry results. Tamoxifen is effective on C3H mice spontaneous breast cancer. After being treated with tamoxifen, expression levels of ER, PR, Cerb-B2 and ki-67 are changed, and change of ER, PR, Cerb-B2, and ki-67 can predict the therapeutical effect of tamoxifen.     

Molecular markers of epithelial-to-mesenchymal transition are associated with tumor aggressiveness in breast carcinoma

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is a transient process occurring during developmental stages and carcinogenesis, characterized by phenotypic and molecular alterations, resulting in increased invasive and metastatic capabilities of cancer cells and drug resistance. Moreover, emerging evidence suggests that EMT is associated with increased enrichment of cancer stem-like cells in neoplastic tissues. We interrogated the molecular alterations occurring in breast cancer using proposed EMT markers such as E-cadherin, vimentin, epidermal growth factor receptor (EGFR), platelet-derived growth factor (PDGF) D, and nuclear factor κB (NF-κB) to decipher their roles in the EMT and breast cancer progression. METHODS: Fifty-seven invasive ductal adenocarcinomas of the breast were assessed for the expression of E-cadherin, vimentin, EGFR, NF-κB, and PDGF-D using immunohistochemical analysis. Tumors were categorized into three groups: A (ER+, and/or PR+, HER-2/neu-), B (ER+, and/or PR+, HER-2/neu+), and C (triple-negative: ER-, PR-, and HER-2/neu-). Immunostained slides were microscopically evaluated and scored using intensity (0, 1+, 2+, and 3+) and percentage of positive cells, and data were statistically analyzed. RESULTS: Membranous E-cadherin was positive in all 57 cases (100%), whereas cytoplasmic E-cadherin was predominantly positive in groups B and C compared with group A (21%, 7%, and 0%, respectively). All group A cases were negative for vimentin and EGFR. There was statistically significant increased expression of vimentin (P < .0002), EGFR (P < .0001), and NF-κB (P < .02) in triple-negative cases when compared with groups A and B. CONCLUSIONS: Vimentin, EGFR, and NF-κB were significantly increased in triple-negative tumors, which is consistent with the aggressiveness of these tumors. These markers could be useful as markers for EMT in breast cancers and may serve as predictive markers for designing customized therapy in the future.     

Evaluation of HER-2/neu in serum and tissue of primary and metastatic breast cancer patients using an automated enzyme immunoassay

Serum HER-2/neu concentrations were evaluated in 172 healthy subjects, 176 primary and 55 metastatic breast cancer patients, employing a new automated assay (Bayer Immuno 1 serum HER-2/neu). Using 13 ng/mL as the cutoff, abnormal HER-2/neu serum levels were found in 8% (14/176) of primary and 50.9% (28/55) of metastatic breast cancer patients. Both in primary and metastatic breast cancer a significant relationship was found with the stage of the disease when serum HER-2/neu was considered as a categorized variable (p=0.0003 and p=0.02, respectively), but not when it was taken as a continuous variable (p=0.247 and p=0.146, respectively). Moreover, we evaluated the correlation between Immuno 1 HER-2/neu and Oncogene Research Products ELISA assay in 53 normal subjects, 46 primary and 34 metastatic breast cancer patients. The correlation was relatively good (p<0.0001), although substantial differences could be found in single cases. The Immuno 1 assay was also evaluated for the first time in breast cancer tissue. The method, which showed good performance both in terms of imprecision and linearity, was used to measure HER-2/neu protein in 140 cytosol samples from primary breast cancer tissue and in homogenates from 40 matched cases. The correlation between the two matrixes was very close (p<0.0001). By contrast, no correlation was found between serum and matched cytosol (p=0.101) or homogenate samples (p=0.511).     

Identification of oestrogen,progesterone receptor and human epidermal growth factor receptor 2 expression in mediastinal metastases of breast cancer obtained by endobronchial ultrasound‐guided transbronchial needle aspiration

Background

In breast cancer patients, the expression statuses of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are crucial in the choice of treatment. Receptor expression in metastatic lesions can differ from the primary tumour. The aim of our study was to analyse the utility of endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) to obtain samples allowing the identification of ER, PR and HER2 expression in patients with mediastinal metastases of breast cancer.

Patients and methods

The clinical files of all patients with a final diagnosis of breast cancer mediastinal metastases diagnosed by EBUS‐TBNA in our institution were retrospectively analysed. The ability of EBUS‐TBNA to obtain samples that allowed hormone receptor and HER2 expression analysis was calculated.

Results

Twenty‐four patients were included. ER, PR and HER2 assessments could be performed in 22, 20 and 22 patients, respectively. In 20 of the 24 patients it was possible to investigate all three types of receptor expression. In the remaining four cases, where ER, PR or HER2 expression tests could not be performed, it was due to a lack of tissue. In cases with adequate results for EBUS‐TBNA and the primary tumour agreement was greater for ER (16/19) and HER2 (12/14) than PR (8/17). Based on receptor status, there was a change in the choice of treatment for five patients.

Conclusion

In patients with breast cancer mediastinal metastases, ER, PR and HER2 expression can be assessed in samples obtained by EBUS‐TBNA whenever a sufficient tissue sample is collected.     

三羟异黄酮对HER-2／neu高表达乳腺癌细胞血管生成相关因子表达的影响

三羟异黄酮(genistein)是大豆中的一种非营养成分,其结构与黄酮化合物类似,能竞争性地与雌激素受体结合,故称之为植物雌激素(phytoestmgen)。它具有广泛的生物学作用,如抗肿瘤、抗病毒、抗真菌、抗氧化、抗突变、抗高血压、抗增生等,其中genistein抑制肿瘤的血管生成是当前研究的热点之一。     

三羟异黄酮对HER-2/neu高表达乳腺癌细胞血管生成相关因子表达的影响

三羟异黄酮(genistein)是大豆中的一种非营养成分,其结构与黄酮化合物类似,能竞争性地与雌激素受体结合,故称之为植物雌激素(phytoestrogen)。它具有广泛的生物学作用,如抗肿瘤、抗病毒、抗真菌、抗氧化、抗突变、抗高血压、抗增生等,其中genistein抑制肿瘤的血管生成是当前研究的热点之一。肿瘤的血管生成是肿瘤进一步生长转移的基础,该过程受肿瘤细胞和血管内皮细胞分泌的血管生成相关因     

老年乳腺癌患者的临床病理特点及其辅助治疗模式的研究

目的:探讨老年乳腺癌患者的临床病理特点及其辅助治疗模式,为老年乳腺癌患者的临床治疗提供参考。方法:选取2008年1月-2012年1月期间我院收治的50例老年乳腺癌患者作为研究对象,同时选取同期收治的50例中青年乳腺癌患者,比较两组患者的临床病理特征,并采用新辅助内分泌疗法治疗本组50例老年乳腺癌患者,治疗4个月后观察治疗效果。结果:老年乳腺癌患者的病灶5cm比例以及ER和PR阳性率均明显高于中青年患者,两组患者数据比较差异有统计学意义(P0.05);老年乳腺癌患者的淋巴结转移率、Ki67阳性率以及HER-2阳性率均低于中青年患者,两组患者数据比较差异均有统计学意义(P0.05);本组50例老年乳腺癌患者治疗总有疗效为82.0%,ER、PR均为阳性患者的治疗有效率为90.0%,明显高于ER和PR非双阳性患者(76.9%,57.1%),数据比较差异均有统计学意义(P0.05);TNM I期患者的治疗有效率为93.8%,明显高于TNM II期(76.9%)或TNM III期患者(20.0%),数据比较差异均有统计学意义(P0.05)。患者在治疗期间均未出现严重不良反应。结论:老年乳腺癌患者的生物学行为较好,病灶大、淋巴转移率低以及ER和PR阳性率高;新辅助内分泌治疗老年乳腺癌患者,尤其对ER、PR均为阳性以及TNM分期低的患者临床效果安全有效,不良反应发生率低,值得临床推广应用。     

Molecular subtype is determinant on inflammatory status and immunological profile from invasive breast cancer patients

Breast cancer consists in a chronic inflammatory disease with multiple biological and clinical behaviors. Based on high throughput technologies data, this disease is currently classified according to the molecular expression of estrogen (ER), progesterone (PR) and human epidermal growth factor (HER-2) receptors. In this study, we defined the inflammatory profile of the main molecular subtypes of breast cancer patients: luminal (ER and PR positive, HER-2 negative), HER-2 enriched (HER-2 positive) and triple negative (ER, PR and HER-2 negative). Cytokines panel was assessed by measurement of TNF-α, TGF-β, IL-1, IL-10 and IL-12 plasmatic levels. Oxidative profile was assessed by determination of lipid peroxidation, total antioxidant capacity of plasma, malondialdehyde levels, carbonyl content and nitric oxide (NO). Clinical data were correlated with inflammatory findings. Our findings demonstrated that patients bearing the luminal subtype displayed high TNF-α, TGF-β and enhanced oxidative stress levels associated with reduced IL-12. HER-2-enriched group exhibited higher levels of TNF-α, IL-12 and TGF-β associated with enhanced oxidative stress. Triple-negative subtype exhibited the most aggressive profile of disease behavior, with reduction in both TNF-α and TGF-β, with high levels of lipid peroxidation and NO. The clinical importance of our findings lies in the fact that the inflammatory status varies in distinct ways due to molecular subtype of breast cancer, opening potential therapeutic targets to future therapies.     

乳腺癌功能磁共振成像与生物学预后因子的研究进展

乳腺癌已成为女性最为常见的恶性肿瘤,如何对乳腺癌进行早期诊断、合理化治疗及判断预后意义重大。雌激素受体(ER)、孕激素受体(PR)、Ki-67、人表皮生长因子受体2(HER-2)等免疫组化指标在判断乳腺癌临床类型、转移情况及预后等方面具有重要作用。随着功能磁共振的发展,氢质子磁共振波谱(1H-MRS)、动态增强磁共振成像(DCE-MRI)、扩散加权成像(DWI)等被越来越广泛的用于乳腺组织的检查。研究功能磁共振与乳腺癌预后因子的相关性,对乳腺癌的临床分型、治疗及预后等方面有一定的指导作用。本文就相关进展进行综述。     

3, 3′-diindolylmethane Enhances the Effectiveness of Herceptin against HER-2/Neu-Expressing Breast Cancer Cells

Herceptin failure is a major clinical problem in breast cancer. A subset of breast cancer patients with high HER-2/neu levels eventually experience metastatic disease progression when treated with Herceptin as a single agent. Mechanistic details of development of this aggressive disease are not clear. Therefore, there is a dire need to better understand the mechanisms by which drug resistance develops and to design new combined treatments that benefit patients with aggressive breast cancer and have minimal toxicity. We hypothesized that 3, 3′-diindolylmethane (DIM), a non-toxic agent can be combined with Herceptin to treat breast cancers with high levels of HER-2/neu. Here, we evaluated the effects of Herceptin alone and in combination with DIM on cell viability, apoptosis and clonogenic assays in SKBR3 (HER-2/neu-expressing) and MDA-MB-468 (HER-2/neu negative) breast cancer cells. We found that DIM could enhance the effectiveness of Herceptin by significantly reducing cell viability, which was associated with apoptosis-induction and significant inhibition of colony formation, compared with single agent treatment. These results were consistent with the down-regulation of Akt and NF-kB p65. Mechanistic investigations revealed a significant upregulation of miR-200 and reduction of FoxM1 expression in DIM and Herceptin-treated breast cancer cells. We, therefore, transfected cells with pre-miR-200 or silenced FoxM1 in these cells for understanding the molecular mechanism involved. These results provide experimental evidence, for the first time, that DIM plus Herceptin therapy could be translated to the clinic as a therapeutic modality to improve treatment outcome of patients with breast cancer, particularly for the patients whose tumors express high levels of HER-2/neu.     

Serum Thyrotropin Concentrations are not Predictive of Aggressive Breast Cancer Biology in Euthyroid Individuals

Objective: The potential influence of hypothyroidism on breast cancer remains incompletely understood. The objective of this study was to investigate the relationship between serum thyrotropin (thyroid-stimulating hormone, TSH) concentration and markers of aggressive breast cancer biology as defined by receptor expression profile, tumor grade, and American Joint Committee on Cancer (AJCC) stage characteristics.Methods: This was a retrospective cohort study of patients from 2002 to 2014. All breast cancer patients who had complete receptor (estrogen receptor, ER; progesterone receptor, PR; and human epidermal growth factor receptor 2, Her2/neu) and prediagnosis serum TSH data (n = 437) were included. All patients had 1 of 6 receptor profiles: ER+ PR+ Her2/neu-, ER+ PR- Her2/neu-, ER+ PR+ Her2/neu+, ER+ PR- Her2/neu+, ER- PR- Her2/neu+, or ER- PR- Her2/neu-. Log-transformed serum TSH concentrations were analyzed using multinomial and logistic regressions to identify potential relationships with markers of breast cancer aggressiveness.Results: Increasing serum TSH concentration was associated with a lower probability of having the receptor expression profile ER+ PR+ Her2/neu+ compared to patients with the ER+ PR+ Her2/neu- profile (odds ratio [OR] = 0.52, P = .0045). No significant associations between other receptor expression profiles and serum TSH concentration were found. All time-weighted and unweighted median serum TSH concentrations were within normal limits. No significant associations between serum TSH concentration and tumor grade, overall AJCC stage, tumor size (T), lymph node positivity (N), or presence of metastasis (M) were observed.Conclusions: Serum TSH was not associated with markers of breast cancer aggressiveness in our cohort.Abbreviations: AJCC = American Joint Committee on Cancer ER = estrogen receptor Her2/neu = human epidermal growth factor receptor 2 M = metastasis N = lymph node positivity OR = odds ratio PR = progesterone receptor T = tumor size TSH = thyroid stimulating hormone UCLA = University of California Los Angeles     

Hormone receptor status, erbB2 expression and cancer stem cell characteristics of circulating tumor cells in breast cancer patients

The most important predictor for disease-free and overall survival of breast cancer patients is the presence of axillary lymph node metastasis. For surveillance during recurrence-free follow-up or in metastatic disease no marker is available at the moment. Several trials have shown the prognostic relevance of circulating tumor cells (CTC) in early and metastatic breast cancers. Indeed, only CTC that exhibit specific molecular characteristics including stem cell characteristics, could be able to create new metastasis. Hormone therapy or anti-erbB2 therapies are prescribed according to the hormone (ERα/PR expression) and erbB2 status of the initial tumor. Nonetheless, it appears that the CTC, and consequently the metastatic cells, may have a very different hormone and erbB2 status. An optimal individualized treatment could then be obtained by characterizing ERα and erbB2 status in the CTC and comparing it to the primary tumor.     

乳腺化生性癌的病理特征、复发和生存情况分析

目的:探讨乳腺化生性癌的病理特征、复发和生存情况。方法:选取我院于2002年1月至2015年12月期间收治的7例乳腺化生性癌患者临床病历资料进行回顾性分析,讨论乳腺化生性癌的病理特点和鉴别诊断、组织起源以及治疗预后等。结果:7例乳腺化生性癌PR、ER和HER-2均显示为阴性,广谱CK则显示为阳性;所有入选患者均显示EGFR阳性,其中有3例患者显示p53阳性,4例患者显示CK5/6阳性。此外,3例患者经腋窝淋巴结清扫后显示有2例患者出现腋窝淋巴结转移,4例患者经前哨淋巴结活检后结果:显示无癌转移。结论:乳腺化生性癌在临床上属于乳腺癌中较为罕见的亚型,其生物学行为和生存预后均不佳,HER-2和PR、ER等多显示为阴性,容易复发,目前主要治疗方法:为在手术治疗的基础上加以放射治疗。     

Clinical implications of HER-2/neu overexpression and proteolytic activity imbalance in breast cancer

The aggressive biological behavior of invasive and metastatic cancer is considered to be the most insidious and life-threatening aspect for breast cancer patients. It is mostly the result of changes in many molecular characteristics of tumor cells, including alterations in gene expression and the balance of proteolytic activity. The objective of this study was to determine the level of MMP-2, its natural inhibitor TIMP-2, their ratio and HER-2/neu as diagnostic and prognostic factors. Markers were analyzed in 240 tissue samples categorized into 96 benign breast disease and 144 breast cancer patients. Enzyme linked immunosorbent assay procedure was used to evaluate the level of MMP-2 and TIMP-2 in the cell lysate, HER-2/neu in the membrane fraction, and steroid hormone receptors (ER and PgR) in the cytosol fraction. Breast cancer patients were followed-up for three years. Receiver operating characteristic curves were used to determine the cutoff points for the investigated factors. Positive values for all investigated factors were significantly increased in breast cancer patients compared to benign ones. Mean levels for all investigated factors were significantly correlated with lymph node and hormone receptor status, while MMP-2 and TIMP-2 were correlated with tumor grade (P < 0.05). In Univariate analysis, positive MMP-2, MMP-2/TIMP-2, HER-2/neu overexpression, higher tumor grade, late clinical stages and positive lymph nodes status were significantly associated with relapse. By multivariate analysis, all aforementioned factors apart from tumor grade were independent variables. Thus, the investigated markers are constructive for biologic aggressiveness of breast cancer and MMP-2/TIMP-2 ratio might be a new significant marker in early diagnosis and estimate prognosis in breast cancer.     

Alterations of estrogen receptors, progesterone receptors and c-erbB2 oncogene protein expression in ductal carcinomas of the breast

Estrogens are important for stimulating the growth of a large proportion of breast cancers. Progesterone plays critical roles in breast development and tumorigenesis. The c-erbB2 gene (HER-2/neu) is a proto-oncogene expressed in 10-34% of breast cancers. Its expression is associated with poor clinical outcome. The hypothesis that the progression of in situ ductal carcinoma of breast to invasive ductal carcinoma is associated with alterations of ER, PgR and HER-2/neu protein expression was tested. Of 100 mastectomy specimens examined, all contained both ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC) not otherwise specified (NOS). The status of ER, PgR and HER-2/neu proteins was examined by immunochemistry. ER and PgR protein expression was scored as the mean value of positively stained cells. HER-2/neu protein expression was evaluated on ts staining pattern (0, 1+, 2+ and 3+). We found variations between DCIS and IDC with significant decrease of the mean values of ER and PgR positively stained cells in high-grade (Grade 3) IDC (ER: 49.2+/-10.3 vs. 30.8+/-5.5 and PgR: 40.0+/-10.0 vs. 22.3+/-5.1 in DCIS and IDC, respectively, P<0.05). Invasive carcinomas with lymph node metastases or lymphovascular invasion or both had lower mean values of ER and PgR positively stained cells compared to those without these features. In IDC (Grade 3), HER-2/neu protein expression values (1.2+/-0.2) were significantly high compared to DCIS (0.7+/-0.3, P<0.05). In addition, HER-2/neu protein expression values were significantly higher (P<0.05) in IDC with lymph node metastases or lymphovascular invasion (1.5+/-0.3) than those without these features (0.8+/-0.2). A significantly high mean (P<0.05) of ER and PgR positively stained cells was observed in postmenopausal females compared to premenopausal women. In contrast, high HER-2/neu expression values were seen only in premenopausal females. A significant positive correlation was observed between ER and PgR receptor expression (r=0.81). A low degree inverse correlation (r=-0.24, P<0.012) was found between ER+/PgR+ tumors and HER-2/neu expression. These findings substantiate the notion that breast cancer progression is often associated with alterations of ER, PgR and HER-2/neu expression. The underlying mechanisms of these alterations are open for further investigation.     

TOP2A and HER-2 gene amplification in fine needle aspirates from breast carcinomas

The TOP2A gene is located on chromosome 17 close to the HER-2 gene. It encodes an enzyme involved in the regulation of cell proliferation. Using fluorescence in situ hybridization (FISH), we have examined fine needle aspiration smears from 42 cases of breast carcinoma with probes for TOP2A, HER-2 and chromosome 17. We found that amplification of TOP2A is a frequent finding in breast cancer and is often but not exclusively accompanied by HER-2 gene amplification. It is associated with high histological grade and oestrogen receptor (ER) negativity. TOP2A deletions may also be associated with high histological grade and loss of ER. TOP2A amplification in the absence of HER-2 amplification may be associated with lower histological grade and ER positivity. Testing for TOP2A aberrations may be useful in the search for individually tailored treatment regimes for breast cancer.     

7,8-Dihydroxycoumarin exerts antitumor potential on DMBA-induced mammary carcinogenesis by inhibiting ERα, PR,EGFR, and IGF1R: involvement of MAPK1/2-JNK1/2-Akt pathway

Breast cancer (BC) is a persistent and impulsive metabolic disorder with the highest prevalence in women, worldwide. 7,12-Dimethylbenz(a)anthracene (DMBA) is a potent polyaromatic hydrocarbon (PAH)-based carcinogen producing mammary carcinomas in rats resembling the human hormone-dependent BC. 7,8-Dihydroxycoumarin (78DC) is a coumarin derivative that possesses diversified and favorable pharmacology profile to be considered in anticancer research against various malignancies. The present study was intended to investigate the antiproliferative and chemotherapeutic potentials of 78DC (20, 40, and 80 mg/kg BW) against DMBA (20 mg in olive oil)-induced mammary carcinoma Sprague-Dawley rats. We established the in silico approach for evaluation of the effect of 78DC on hormonal (estrogen receptor-α (ERα), progesterone receptor (PR)), growth factor receptors (EGFR and IGFR), 17β-hydroxysteroid dehydrogenase type 1 (17β-HD1), and aromatase. Effect of 78DC on estrogen synthesis, tumor growth, proliferation markers (Ki-67 and PCNA), cytokines (IL-10, IL-1β, IL-12), chemokine (MCP-1), and cellular expressions of ERα, PR, EGFR, IGF1R, p-MAPK1/2, p-JNK1/2, p-Akt, 17β-HD1, and aromatase was evaluated in mammary carcinoma bearing SD rats. DMBA induces large tumor burden and histological alterations in mammary gland with a subsequent increase in ERα, PR, EGFR, IGF1R, Ki-67, proliferating cell nuclear antigen (PCNA ), cytokines, and chemokine expressions. This was also correlated with the changes in rapid cell differentiation and proliferation. In contrast, 78DC treatment to the cancer-bearing animals abbreviated these changes and revealed to possess antitumorigenic and antiproliferative potentials. Further, a significant decrease in expressions of ERα, PR, EGFR, IGFR, p-MAPK1/2, p-JNK1/2, p-Akt, 17β-HD1, and aromatase signifies a reduction in estrogen sensitivity and secondary signaling pathways that may contribute to the prevention of tumor growth. The current findings revealed that 78DC potentially reduce cancer cell proliferation and reverted mammary cancer-induced changes in experimental animals in a dose-dependent manner.