Skip to main content
Download PDF

Androgen receptor expression and clinical significance in breast cancer

World Journal of Surgical Oncology volume 23, Article number: 48 (2025) Cite this article

Abstract

Purpose

This study aimed to investigate the expression and clinical relevance of the androgen receptor (AR) in breast cancer.

Methods

This retrospective study examined the expression of AR in breast cancer and its correlation with patients’ clinicopathological and immunohistochemical characteristics. A total of 521 patient records were gathered and assessed. Patients were categorized as either positive or negative for AR expression, and statistical analyses were conducted using the chi-square test, logistic regression in SPSS 26.0, and Kaplan-Meier analysis.

Results

AR was detected in 83.7% of the 521 patients studied. There was a statistically significant difference in the prevalence of AR positivity among different molecular subtypes, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and epidermal growth factor receptor (EGFR) (P < 0.05). Logistic regression analysis further revealed that ER and PR positivity were identified as risk factors for AR expression, and Kaplan-Meier curve analysis demonstrated the potential of AR as a prognostic indicator for breast cancer outcomes. Additionally, AR positivity was associated with a favorable prognosis.

Conclusions

The results suggest a strong correlation between AR expression and ER and PR co-expression in breast cancer. Additionally, AR positivity in the absence of ER and PR expression is associated with a favorable prognosis, indicating potential therapeutic value as a novel target in breast cancer treatment. Particularly in endocrine resistance or triple-negative breast cancer (TNBC), AR may serve as a significant prognostic indicator, warranting further investigation.

Introduction

Global cancer statistics for the year 2022, as derived from updated estimates by the International Agency for Research on Cancer (IARC), indicate that there were approximately 20 million new cancer cases and 9.7 million cancer-related deaths. Female breast cancer accounted for 2.3 million new cases (11.6%) and 665,684 deaths (6.9%). Breast cancer remains the most prevalent cancer among women. Projections based on demographic trends suggest that the number of new cancer cases could rise to 35 million by 2050. Consequently, it is necessary to strengthen the diagnosis and treatment of breast cancer [1].

Breast cancer, characterized by its hormone-dependent nature, frequently presents immunohistochemical markers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), and Ki-67. Notably, AR and ER, both belonging to the steroid nuclear receptor family, exhibit analogous three-dimensional structures [2]. The AR is primarily associated with the development of male reproductive organs and functions as a crucial molecular factor in the progression of prostate cancer. Recent studies have demonstrated that approximately 60% to 80% of breast cancer cases exhibit AR positivity [3]. The expression of AR varies significantly across different molecular subtypes of breast cancer and can inhibit tumor cell proliferation to some extent. Consequently, there has been growing interest in recent years in exploring AR as a novel therapeutic target for breast cancer. Numerous early-phase clinical trials have been conducted to assess the safety and efficacy of various AR-targeted agents in the treatment of breast cancer [4]. This is particularly evident in cases where ER-positive cancers exhibit resistance to anti-estrogen treatments, as well as in patients with ER-negative breast cancer or HER2-positive breast cancer [5,6,7]. Clinical trials examining targeted therapies for AR have shown efficacy benefits in patients with breast cancer, indicating promising treatment options for individuals with AR-positive breast cancer [7,8,9]. While androgen receptor-targeted therapies demonstrate potential, these therapeutic strategies remain in the clinical trial phase and have not yet been widely implemented in clinical practice.

Epidermal growth factor receptor (EGFR) is not routinely done for breast cancer. But the EGFR signaling pathway in breast cancer cells is intricately linked to tumor progression, metastasis, and resistance to therapeutic interventions. Modulation of the EGFR signaling cascade influences not only the proliferation and invasiveness of tumor cells but also enhances the survival and maintenance of breast cancer stem cells (BCSCs), thereby potentially increasing tumor aggressiveness [10, 11]. Besides, activation of AR exerts an anti-tumor effect by suppressing the PI3K/AKT pathway downstream of EGFR [12, 13]. The co-expression of EGFR and AR occurs, adding to the complexity and therapeutic challenges of triple-negative breast cancer (TNBC) [14, 15].

This study scrutinized the clinicopathological records of 521 female breast cancer patients, evaluating AR expression in relation to clinicopathological features and prevalent immunohistochemical characteristics. The primary objective of the study was to investigate the potential prognostic and therapeutic implications of AR in the context of breast cancer subtype.

Methods

Study population

This retrospective cohort study examined the electronic medical records of 521 female patients diagnosed with primary breast cancer, and used the pathological findings of resection specimens obtained through radical surgery samples for analysis between 2020 and 2022 at Linyi People’s Hospital. All patients provided informed consent for the use of their anonymized data for research, outcomes, or educational purposes at the time of treatment. Ethics approval was granted by the Science and Technology Ethics Committee of Linyi People’s Hospital (Approval number: 202311-H-047).

The study’s inclusion criteria consisted of female patients diagnosed with breast cancer confirmed by pathology, who had all signed informed consent. Exclusion criteria included male patients and those with concurrent primary diseases.

Detection

Immunohistochemistry

Immunohistochemistry (IHC) was performed using the SP two-step method. The process involved deparaffinization of tissue sections, followed by washing with PBS, inhibition of endogenous peroxidase activity for antigen retrieval, additional PBS washes, application of primary and secondary antibodies, visualization with DAB, termination of color development with water, counterstaining of the nucleus, differentiation with water, dehydration, mounting, and observation under a microscope. ER used CONFIRM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody (Cat: 790–4325) in Roche. PR use CONFIRM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody (Cat: 790–2223) in Roche. Ki-67 used Ki-67 mouse monoclonal antibody (Cat: ZM-0166) in ZSGB-Bio. and AR used Rabbit Anti-Human Androgen Receptor Monoclonal Antibody Reagent (Cat: ZA-0554) in ZSGB-Bio. EGFR used Epidermal Growth Factor Receptor Antibody Reagent (Cat: ZM-0088) in ZSGB-Bio.

Fluorescence in situ hybridization assay

Fluorescence in situ hybridization (FISH) was utilized to identify gene amplification in cases where the HER2 result was determined to be 2+. The Her-2 probe (Cat: F.01359) was purchased from Guangzhou LBP Medicine Science & Technology Co., Ltd. The tissue samples underwent a series of sequential steps including baking, lost-wax technique, wax removal, permeabilization, water washing, digestion, washing, dehydration, and drying. The probe mixture was applied to the hybridization area of the tissue section, covered with a slice, sealed with rubber cement, and placed in the hybridizer. After hybridization, the rubber cement was removed, followed by washing, drying, and capping of the specimen. The specimens were examined using a fluorescence microscope to identify the presence or absence of amplification of the HER2 gene, allowing for the classification of negatives and positives.

Criteria for judgement

ER, PR, AR, EGFR and Ki-67

ER, PR, AR, and Ki-67 exhibited nuclear localization, with positive staining characterized by brownish-yellow granules in the nucleus. EGFR, on the other hand, was localized in the cell membrane. The established positive thresholds for ER, PR, and AR immunohistochemical testing were defined as ≥ 1% [16]. The evaluation criteria for EGFR were determined using the DAKO HercepTest scoring system and graded semi-quantitatively based on the ratio of positive cells to total observed cells: reactions with ≤ 10% positive cells were classified as negative (-). In comparison, those with > 10% positive cells were classified as positive (+). A cut-off value of 20% was utilized to distinguish between high and low PR expression levels, with > 20% indicating high expression and ≤ 20% indicating low expression. The threshold of Ki-67 is 20%, with values ≥ 20% classified as high expression and < 20% classified as low expression.

HER2

The results were analyzed based on specific criteria for staining intensity and distribution on a per-slice basis, with scores ranging from 0 to 3 + indicating varying levels of staining in invasive cancer cells. An IHC score of 3 + was determined to indicate HER2 positivity, whereas scores of 0 and 1 + were indicative of HER2 negativity. Patients with an IHC score of 2 + necessitated additional evaluation through FISH testing [17].

HER2 FISH

The determination criteria for dual probe analysis of HER2 status include a HER2/CEP17 ratio ≥ 2.0 and an average HER2 copy number per cell ≥ 4.0, which is classified as FISH positive. In cases where numerous HER2 signals are clustered together, a direct classification of FISH positive is warranted. Conversely, if the HER2/CEP17 ratio is ≥ 2.0 but the average HER2 copy number per cell is < 4.0, it is advisable to increase the number of cells counted. If the result remains unchanged after this adjustment, the case will be classified as FISH negative. If the HER2/CEP17 ratio is less than 2.0 and the average HER2 copy number per cell is greater than or equal to 6.0, it is advisable to augment the cell count. If the outcome persists unaltered, it will be deemed FISH-negative. Conversely, if the cell count is increased and the result remains consistent, it will be classified as FISH-positive. The HER2/CEP17 ratio < 2.0, mean HER2 copy number/cell ≥ 4.0 and < 6.0 indicates uncertainty regarding the potential benefit of anti-HER2 targeted therapies for patients with non-3 + IHC results. Further evidence-based medical rationale is needed. It is advised to analyze at least 20 nuclei for signal recounting and to conduct a combined assessment of both IHC and FISH results if discrepancies arise. If this condition persists, it is recommended that a notation be included in the FISH report indicating that the determination of HER2 status in these patients should be conducted in conjunction with the IHC findings. In cases where the IHC result is 3+, the HER2 status is deemed positive. Conversely, if the IHC result is 0, 1+, or 2+, the HER2 status should be classified as negative. Additionally, a HER2/CEP17 ratio of < 2.0 and an average HER2 copy number per cell of < 4.0 should be considered indicative of a negative FISH result.

Molecular phenotype

As outlined in the 2021 Chinese Association Against Cancer Breast Cancer Diagnosis and Treatment Guidelines and Specifications. TNBC is identified by the absence of ER, PR expression, and HER2 amplification. This subtype of tumor is recognized for its aggressive nature and is linked to unfavorable clinical prognoses. Luminal A: ER/PR (+) and PR high expression HER2(-), Ki-67 lower; Luminal B (HER2-): ER/PR (+), HER2 (-) and Ki-67 high or PR low expression; Luminal B (HER2+): ER/PR (+), HER2(+) and any Ki-67; HER2 positive: HER2(+), ER、PR (-); TNBC: ER, PR and HER2(-).

Statistical analysis

Descriptive statistics were computed for patient clinicopathological data based on their AR status. For statistical analysis, tumors were categorized as either positive or negative for AR expression. The clinicopathological data were analyzed by calculating frequencies and percentages. The association between AR status and patient characteristics was evaluated using the chi-square test. Risk factors for and prognostic indicators of AR expression in breast cancer patients were assessed using logistic regression and the Kaplan-Meier plotter database, respectively. Overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) were analyzed, and survival curves were generated. A significance level of α = 0.05 was utilized for a two-sided test. Statistical analysis was conducted using SPSS 26.0 for all data.

Results

Expression of AR in clinicopathologic features

A total of 521 patients diagnosed with breast cancer were included in the study, with an overall AR positivity rate of 83.7% (436/521). The age range of the patients was 30 to 84 years, with a mean and standard deviation age of 52.7 ± 10.2 years.

Analysis of AR positivity rates across different histological types (I, II, and III) revealed rates of 88.9%, 86.0%, and 79.1%, respectively, with no statistically significant differences observed (P > 0.05). Similarly, AR positivity rates in different age groups (< 60 years and ≥ 60 years) were 84.6% and 80.5%, respectively, with no significant variation (P > 0.05). Additionally, no statistically significant difference was found between AR positivity rates in cases with vascular invasion (85.3%) compared to those without (83.5%) (P > 0.05). As per the 2021 Chinese Association Against Cancer guidelines for the diagnosis and treatment of breast cancer, the rates of AR positivity in various subtypes of breast cancer, including Luminal A, Luminal B (HER2-), Luminal B (HER2+), HER2+, and TNBC, were found to be 90.0%, 87.1%, 96.5%, 81.1%, and 32.7%, respectively. These differences were determined to be statistically significant (P < 0.05). Table 1 was shown.

Table 1 Clinicopathologic features and immunohistochemical characteristics
Full size table

Expression of AR in immunohistochemical indices

Table 1 demonstrated that in breast cancer, the AR-positive rates of the ER-positive and ER-negative groups were 90.1% and 60.9%, respectively, with a statistically significant difference (P < 0.05). Similarly, the AR-positive rates of the PR-positive and PR-negative groups were 90.3% and 65.7%, respectively, with a statistically significant difference (P < 0.05). Additionally, the AR-positive rates of the HER2 positive and HER2 negative groups were 90.6% and 81.1%, respectively, with a statistically significant difference (P < 0.05). The AR-positive rates in the Ki-67 high-expression and low-expression groups were 83.6% and 84.1%, respectively, with no statistically significant difference (P > 0.05). Conversely, the AR-positive rates in the EGFR-positive group and the negative group were 73.9% and 95.6%, respectively, demonstrating a statistically significant difference (P < 0.05). The AR positivity rate was found to be significantly higher in the ER, PR, and HER2 positive group compared to the ER, PR, and HER2 negative group in breast cancer. Conversely, the AR positivity rate was higher in the EGFR-negative group than in the EGFR-positive group.

AR-positive staining was observed as the presence of brownish-yellow granules within the nucleus. Notably, some level of AR positivity persists even in cases where ER and PR are negative (Fig. 1).

Fig. 1
figure 1

Pathologic findings of breast cancer. A HE and IHC staining in AR expression for the histology type. B The positive expression of AR across various molecular subtypes of breast cancer. C The positive expression of AR across different immunohistochemical indices. The Nottingham grading system classifies tumors into three distinct grades based on morphological characteristics. Grade I is characterized by a predominantly glandular architecture, minimal nuclear polymorphism, and a low mitotic index. Grade II represents an intermediate category between Grades I and III, exhibiting moderately pleomorphic nuclei and a medium mitotic count. Grade III is defined by a solid nest structure, prominent nucleoli in tumor cells, and a high frequency of observable mitotic figures

Full size image

Logistic regression analysis of AR with immunohistochemical indicators

Breast cancer, being a hormone-dependent tumor, may involve interactions among various hormones. The risk factors included histological grade, molecular phenotype, vascular invasion, neurology invasion, ER status, PR status, HER2 status, Ki-67 and EGFR status which associated with positive AR expression were examined using univariable logistic regression analysis. If P < 0.05, this risk was been included in multiple logistic regression analysis, and using stepwise regression to choose the significant of risk factor. Stepwise regression screening determined that molecular phenotype, ER, and PR were significant risk factors influencing positive AR expression (P < 0.05). The odds ratio (OR) for HER2 + was 20.067 (95% CI: 6.036–66.707), showing that HER2 + patients were 20.067 times more likely to be AR-positive compared to TNBC patients. The OR for positive ER status was 10.745 (95% CI: 1.741–66.335), indicating that patients with positive ER status were 10.745 times more likely to have positive AR status than those with negative ER status. The OR value of 6.797 (95% CI: 1.675–27.581) indicated that patients with positive PR were 6.797 times more likely to have positive AR status than those with negative PR. Please refer to Tables 2 and 3 for further details.

Table 2 Univariable logistic regression for AR
Full size table
Table 3 Multiple logistic regression for AR
Full size table

Relationship between AR and breast cancer prognosis

The Kaplan-Meier plotter database analysis of breast cancer revealed that patients with high AR expression exhibited significantly improved OS, RFS, and DMFS compared to those with low AR expression (HR = 0.53, P < 0.05 for OS and RFS; HR = 0.63, P < 0.05 for DMFS, Fig. 2) and in luminal A, the RFS had a statistically significant difference between high-AR and low-AR (P < 0.05).

Fig. 2
figure 2

Kaplan-meier plot for androgen receptor and breast cancer prognosis. A overall survival (OS). B recurrence-free survival (RFS). C distant metastasis-free survival (DMFS). D RFS for TNBC. E RFS for luminal A. F RFS for luminal B. G RFS for HER2+. X axis represents survival time, Y axis represents survival rate. If HR < 1, indicating a protective factor, and HR > 1, indicating a risk factor. were compared between high and low expressions using the Log-rank test. If P < 0.05, it showed a statistically significant difference between high and low expressions. OS is defined as the duration from the date of breast cancer diagnosis to the date of death from any cause. RFS is measured from the time of breast cancer diagnosis to the occurrence of the first disease recurrence. DMFS is the interval from the initial breast cancer diagnosis to the onset of distant metastases. Red indicates the group with high expression levels, whereas black denotes the group with low expression levels

Full size image

Discussion

AR is emerging as an important factor in the pathogenesis of breast cancer. AR exhibits different behaviors depending on the breast cancer molecular subtype. In the context of molecular typing for patients diagnosed with breast cancer, the rates of AR positivity in various subtypes, including Luminal A, Luminal B (HER2-), Luminal B (HER2+), HER2+, and TNBC, were found to be 90.0%, 87.1%, 96.5%, 81.1%, and 32.7%, respectively. Notably, the positivity rate of AR was observed to be significantly higher in the ER, PR, HER2, and EGFR positive groups compared to the negative groups. Logistic regression analysis further revealed that ER positivity and PR positivity were identified as risk factors for AR expression, and Kaplan-Meier curve analysis demonstrated the potential of AR as a prognostic indicator for breast cancer outcomes. Research indicates that AR demonstrates high levels of co-expression with ER and PR. Furthermore, even in cases where ER and PR are negative, AR may exhibit positive expression and be associated with a favorable prognosis. AR predicts response to chemotherapy in breast cancer patients [18, 19]. Contemporary studies in the field of breast cancer treatment are concentrated on identifying novel molecular targets to address and overcome resistance mechanisms [20].

AR is expressed in 80% to 90% of ERα + breast cancers. The ratio of AR to ER in breast cancer dictates the response to AR-targeted therapies [21]. AR agonists exhibit tumor suppressive effects in ER-positive breast cancer, combination of AR agonists with conventional therapy can improve treatment response in breast cancer patients [22]. Enobosarm has anti-tumor activity in patients with ER-positive, HER2-negative advanced breast cancer, supporting further clinical investigation of selective AR activation strategies for the treatment of AR-positive, ER-positive, HER2-negative advanced breast cancer [14]. HER2-positive breast cancer patients with high AR expression levels may achieve higher pathological complete response (pCR) rates when treated with neoadjuvant dual-blocked therapy, 59.69% patients achieved pCR [5]. Anti-androgens have been evaluated in clinical trials for AR-positive TNBC, demonstrating a clinical benefit rate of 29% at six months [23].

TNBC poses a significant challenge in treatment due to its high heterogeneity and lack of well-defined therapeutic targets [24]. TNBC represents up to 20% of all breast cancer variants, an aggressive disease with poorer outcomes compared to other breast cancer subtypes. No targeted therapies are currently approved for TNBC, and newer treatment approaches are seriously needed. Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC [25]. However, the precise role of AR in TNBC and the mechanisms underlying the reduction of tumor burden with AR-targeted therapy remain largely unknown [18]. Enzalutamide has demonstrated favorable efficacy and tolerability in clinical trials involving patients with advanced AR-positive TNBC [25]. Additionally, these findings support the continued evaluation of AR-targeted therapies for breast cancers [26,27,28]. Next to AR expression, the incorporation of additional tumor characteristics will potentially make AR targeting a more valuable therapeutic strategy in breast cancer [29]. Clinical evidence suggests a role for anti-androgen therapies such as bicalutamide, enzalutamide and abiraterone, offering an interesting chemo-free alternative for chemo-unresponsive patients, and therefore potentially shifting current treatment strategies [30]. Targeting AR has shown great therapeutic potential in TNBC. The tumor microenvironment is an important factor affecting the response of TNBC patients to AR-targeted therapy. In hypoxic conditions, the survival strategies of tumor cells may affect the response to treatment [31, 32]. The presence or absence of biomarkers, such as PR and HER2 expression, can also affect the efficacy of AR-targeted therapy [31, 33]. AR may maintain a tumor cell population with stem cell characteristics in TNBC, and the inhibition of AR can effectively reduce the survival ability of these tumor cells, thereby enhancing the effect of chemotherapy [18]. The luminal androgen receptor (LAR) subtype is characterized by high expression levels of AR and is often associated with specific gene expression signatures that include genes linked to the androgen receptor signaling pathway [34]. For patients with the LAR subtype, therapies that target the androgen receptor may offer an advantageous treatment strategy, distinguishing them from patients with other subtypes who may not benefit from similar approaches. Furthermore, combining androgen receptor antagonists with traditional chemotherapy has shown promise, opening avenues for novel therapeutic regimens in TNBC management.

The prognostic role of AR was reported using Kaplan-Meier curves, by separating cases into high-AR vs. low-AR. high-AR had a better survival than low-AR, especially in Luminal A. Studies have suggested that in many cases of ER-positive breast cancer, the interaction between AR and ER may be a key factor affecting the estrogen signaling pathway. This interaction may lead to resistance to endocrine therapy in tumor cells [35, 36]. Some experiments have shown that AR can not only act as a signaling pathway for promoting tumor growth, but also may inhibit the function of ER through a competitive mechanism [37].

Selection bias and information bias may affect the accuracy and reliability of study results. A prospective design was been adopted in future studies which include a broader patient population. This will help to improve the quality of the data and the credibility of the results.

In conclusion, the high co-expression of AR with ER and PR, as well as the positive expression of AR in ER and PR-negative cases, underscores its significance [38]. Expression of AR in women with breast cancer is associated with better OS and DFS irrespective of co-expression of ER [27]. In summary, the significant co-expression of AR with ER and PR, along with the positive expression of AR in cases lacking ER and PR, highlights the importance of AR in these contexts.

Conclusion

According to the results, we can find a strong correlation between AR expression and ER, PR co-expression in breast cancer. Additionally, AR positivity in the absence of ER and PR expression is associated with a favorable prognosis, indicating potential therapeutic value as a novel target in breast cancer treatment. Despite the therapeutic potential of AR expression in certain breast cancer subtypes, there may be significant variability in patient response to AR-targeted therapy. This may be due to the tumor microenvironment, patient genetic background, or other molecular markers. In the further, we will explore the use of AR-targeted therapies in clinical practice, including evaluating their efficacy and safety in different patient populations.

Data availability

No datasets were generated or analysed during the current study.

References

  1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63.

    Article  PubMed  Google Scholar 

  2. Yu X, Yi P, Hamilton RA, et al. Structural insights of transcriptionally active, full-length androgen receptor coactivator complexes. Mol Cell. 2020;79:812-823 e814.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Nita I, Nitipir C, Toma SA, et al. Correlation between androgen receptor expression and immunohistochemistry type as prognostic factors in a cohort of breast cancer patients: result from a single-center, cross sectional study. Healthcare (Basel). 2021;9:277.

    Article  PubMed  Google Scholar 

  4. Jahan N, Jones C, Rahman RL. Androgen receptor expression in breast cancer: implications on prognosis and treatment, a brief review. Mol Cell Endocrinol. 2021;531:111324.

    Article  PubMed  CAS  Google Scholar 

  5. Li N, Wu J, Qi X, et al. Correlation between androgen receptor expression and pathological response rate in pre-operative HER2-positive breast cancer patients. J Cancer Res Clin Oncol. 2023;149:10109–17.

    Article  PubMed  CAS  Google Scholar 

  6. McNamara KM, Sasano H. Androgen and breast cancer: an update. Curr Opin Endocrinol Diabetes Obes. 2016;23:249–56.

    Article  PubMed  CAS  Google Scholar 

  7. Kono M, Fujii T, Lim B, et al. Androgen receptor function and androgen receptor-targeted therapies in breast cancer: a review. JAMA Oncol. 2017;3:1266–73.

    Article  PubMed  Google Scholar 

  8. Choupani E, Mahmoudi Gomari M, Zanganeh S, et al. Newly developed targeted therapies against the androgen receptor in triple-negative breast cancer: a review. Pharmacol Rev. 2023;75:309–27.

    Article  PubMed  CAS  Google Scholar 

  9. Vasiliou SK, Diamandis EP. Androgen receptor: a promising therapeutic target in breast cancer. Crit Rev Clin Lab Sci. 2019;56:200–23.

    Article  PubMed  CAS  Google Scholar 

  10. Steelman LS, Fitzgerald T, Lertpiriyapong K, et al. Critical roles of EGFR family members in breast cancer and breast cancer stem cells: targets for therapy. Curr Pharm Des. 2016;22:2358–88.

    Article  PubMed  CAS  Google Scholar 

  11. Alanazi IO, Khan Z. Understanding EGFR signaling in breast cancer and breast cancer stem cells: overexpression and therapeutic implications. Asian Pac J Cancer Prev. 2016;17:445–53.

    Article  PubMed  Google Scholar 

  12. Koleckova M, Janikova M, Kolar Z. MicroRNAs in triple-negative breast cancer. Neoplasma. 2018;65:1–13.

    Article  PubMed  CAS  Google Scholar 

  13. Gupta GK, Collier AL, Lee D, et al. Perspectives on triple-negative breast cancer: current treatment strategies, unmet needs, and potential targets for future therapies. Cancers (Basel). 2020;12:12.

    Article  Google Scholar 

  14. Medic-Milijic N, Jovanic I, Nedeljkovic M, et al. Prognostic and clinical significance of PD-L1, EGFR and androgen receptor (AR) expression in triple-negative breast cancer (TNBC) patients. Life (Basel). 2024;14:14.

    Google Scholar 

  15. Qattan A, Al-Tweigeri T, Suleman K. Translational implications of dysregulated pathways and microRNA regulation in quadruple-negative breast cancer. Biomedicines. 2022;10:10.

    Article  Google Scholar 

  16. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol. 2020;38:1346–66.

    Article  PubMed  Google Scholar 

  17. Wolff AC, Somerfield MR, Dowsett M, et al. Human epidermal growth factor receptor 2 testing in breast cancer: ASCO-College of American Pathologists guideline update. J Clin Oncol. 2023;41:3867–72.

    Article  PubMed  CAS  Google Scholar 

  18. Barton VN, Christenson JL, Gordon MA, et al. Androgen receptor supports an anchorage-independent, cancer stem cell-like population in triple-negative breast cancer. Cancer Res. 2017;77:3455–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Witzel I, Loibl S, Wirtz R, et al. Androgen receptor expression and response to chemotherapy in breast cancer patients treated in the neoadjuvant TECHNO and PREPARE trial. Br J Cancer. 2019;121:1009–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Basile D, Cinausero M, Iacono D, et al. Androgen receptor in estrogen receptor positive breast cancer: beyond expression. Cancer Treat Rev. 2017;61:15–22.

    Article  PubMed  CAS  Google Scholar 

  21. Wei L, Gao H, Yu J, et al. Pharmacological targeting of androgen receptor elicits context-specific effects in estrogen receptor-positive breast cancer. Cancer Res. 2023;83:456–70.

    Article  PubMed  CAS  Google Scholar 

  22. Hickey TE, Selth LA, Chia KM, et al. The androgen receptor is a tumor suppressor in estrogen receptor-positive breast cancer. Nat Med. 2021;27:310–20.

    Article  PubMed  CAS  Google Scholar 

  23. Rhanine Y, Bonnefoi H, Goncalves A, et al. Efficacy of antiandrogens in androgen receptor-positive triple-negative metastatic breast cancer: real-life data. Breast. 2024;73:103667.

    Article  PubMed  Google Scholar 

  24. Thike AA, Yong-Zheng Chong L, Cheok PY, et al. Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer. Mod Pathol. 2014;27:352–60.

    Article  PubMed  CAS  Google Scholar 

  25. Traina TA, Miller K, Yardley DA, et al. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol. 2018;36:884–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Lanzino M, Sisci D, Morelli C, et al. Inhibition of cyclin D1 expression by androgen receptor in breast cancer cells–identification of a novel androgen response element. Nucleic Acids Res. 2010;38:5351–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Vera-Badillo FE, Templeton AJ, de Gouveia P, et al. Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:djt319.

    Article  PubMed  Google Scholar 

  28. Kensler KH, Poole EM, Heng YJ, et al. Androgen receptor expression and breast cancer survival: results from the nurses’ health studies. J Natl Cancer Inst. 2019;111:700–8.

    Article  PubMed  Google Scholar 

  29. Venema CM, Bense RD, Steenbruggen TG, et al. Consideration of breast cancer subtype in targeting the androgen receptor. Pharmacol Ther. 2019;200:135–47.

    Article  PubMed  CAS  Google Scholar 

  30. Gerratana L, Basile D, Buono G, et al. Androgen receptor in triple negative breast cancer: a potential target for the targetless subtype. Cancer Treat Rev. 2018;68:102–10.

    Article  PubMed  CAS  Google Scholar 

  31. Zambelli A, Sgarra R, De Sanctis R, et al. Heterogeneity of triple-negative breast cancer: understanding the Daedalian labyrinth and how it could reveal new drug targets. Expert Opin Ther Targets. 2022;26:557–73.

    Article  PubMed  Google Scholar 

  32. Jinna N, Rida P, Smart M, et al. Adaptation to hypoxia may promote therapeutic resistance to androgen receptor inhibition in triple-negative breast cancer. Int J Mol Sci. 2022;23:8844.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Olsson M, Larsson P, Johansson J, et al. Cancer stem cells are prevalent in the basal-like 2 and mesenchymal triple-negative breast cancer subtypes in vitro. Front Cell Dev Biol. 2023;11: 1237673.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Hu T, Zhao G, Liu Y, et al. A machine learning approach to differentiate two specific breast cancer subtypes using androgen receptor pathway genes. Technol Cancer Res Treat. 2021;20:15330338211027900.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Early Breast Cancer Trialists’, Collaborative G. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386:1341–52.

    Article  Google Scholar 

  36. Mukherjee AG, Wanjari UR, Nagarajan D, et al. Letrozole: pharmacology, toxicity and potential therapeutic effects. Life Sci. 2022;310:121074.

    Article  PubMed  CAS  Google Scholar 

  37. Tenti S, Correale P, Cheleschi S, et al. Aromatase inhibitors-induced musculoskeletal disorders: current knowledge on clinical and molecular aspects. Int J Mol Sci. 2020;21:5625.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Anestis A, Zoi I, Papavassiliou AG, et al. Androgen receptor in breast cancer-clinical and preclinical research insights. Molecules. 2020;25:358.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

The study was funded by the Medical and Health Program of Shandong Province, China (NO. 202302060735).

Author information

Authors and Affiliations

  1. Biobank, Linyi People’s Hospital, Linyi, 276000, China

    Ningning Yao, Lei Han & Zhiyong Wei

  2. Department of Laboratory Medicine, Linyi Peoples’ Hospital, Linyi, 276000, China

    Han Sun

  3. Department of Scientific Research Management, Linyi People’s Hospital, Linyi, 276000, China

    Liangjian Zhou

  4. Department of Pathology, Linyi People’s Hospital, Linyi, 276000, China

    Zhiyong Wei

Authors
  1. Ningning Yao
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Lei Han
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Han Sun
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Liangjian Zhou
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Zhiyong Wei
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

N.Y: Writing - original draft. L.H: Formal analysis. H.S: Data curation. L.Z: Visualization, Validation, Investigation, Conceptualization. Z.W: Writing - review & editing, Supervision.

Corresponding authors

Correspondence to Liangjian Zhou or Zhiyong Wei.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Science and Technology Ethics Committee of Linyi People's Hospital (Approval number: 202311-H-047) and all patients provided informed consent for the use of their clinical information.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yao, N., Han, L., Sun, H. et al. Androgen receptor expression and clinical significance in breast cancer. World J Surg Onc 23, 48 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12957-025-03673-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12957-025-03673-w

Keywords

World Journal of Surgical Oncology

ISSN: 1477-7819

Contact us