Are Androgen and Estrogen Receptors in DCIS Patients Prognostic Indicators of Relapse Independently of Treatment?

Abstract

Ductal carcinoma in situ (DCIS) is a highly heterogenous tumor that is now more frequently diagnosed because of the increased number of screening programs. Women with DCIS are mainly treated with conservative surgery almost always followed by radiotherapy. Although conventional biomarkers, i.e. ER, PgR, Ki67, and HER2, have been extensively investigated in invasive tumors, little is known about their role in DCIS, especially that of the androgen receptor (AR). In the present study, the expression of conventional biomarkers and AR was determined by immunohistochemistry in 85 DCIS samples from patients monitored for a maximum of 13 years: 43 patients were treated with quadrantectomy and 42 patients underwent quadrantectomy and radiotherapy. Of these, 5 and 11 patients relapsed, respectively. Our findings showed that ER and PgR were higher in nonrelapsed than in relapsed patients (P=0.025 and 0.0038). In contrast, AR expression and the AR/ER ratio were higher in relapsed patients than in the nonrelapsed group (P=0.0069 and 0.0012). At the best cut-off value of 1.1, the AR/ER ratio showed an overall accuracy of 92% and 80% in predicting in situ relapse or progression to invasive carcinoma in DCIS patients treated with surgery and those treated with surgery plus radiotherapy, respectively. AR would therefore appear to be an independent prognostic biomarker in the latter group. Our preliminary results highlight the potentially important role of the AR/ER ratio as a predictive indicator of DCIS relapse, independently of treatment.

Androgen receptor in breast cancer: The “5W” questions

“…However, there are data about the role of AR/ER ratio as unfavorable prognostic marker only in invasive primary tumor of early BC patients and different cut off values have been used (13,24). Similarly, we previously highlighted the unfavorable prognostic role of the AR/ER ratio in patients with in situ ductal carcinoma, independently of treatment (77,78). About invasive luminal cancers, we found a potential role of AR/PgR ratio > 0.96 in predicting the efficacy of first-line endocrine treatment in HR+ advanced BC (81).…”

“…It was demonstrated that the AR/ER ratio was statistically higher in relapsed patients of both case series, independently of the treatment, with high AUC values (92% and 80%), in patients treated with surgery and surgery plus radiotherapy, respectively. Taken together these data suggested that the hormone receptor expressions together with AR, could be important prognostic markers able to increase the accuracy in terms of relapse prediction for patients with DCIS ( 77 – 79 ).…”

“…Patients with breast in situ tumors are routinely treated with surgery and radiotherapy (and Tamoxifen in some cases). In this context, the prognostic and predictive role of specific markers, including AR, for clinical outcome in this population was investigated by Ravaioli et al (77,78). In these retrospective studies, series of matched DCIS relapsed and non-relapsed cases, treated with quadrantectomy and quadrantectomy plus radiotherapy were analyzed, highlighting that AR and AR/ER ratio play an unfavorable prognostic role independently of the treatment.…”

TRPM4 is overexpressed in breast cancer associated with estrogen response and epithelial-mesenchymal transition gene sets

“…Interestingly, TRPM4 is highly expressed in androgen-sensitive prostate cancers required for their aggressive phenotypes [19,20]. Moreover, AR is expressed in all grades of breast DCIS that confers unfavorable prognosis [65][66][67], and TRPM4 was also expressed in all DCIS cases examined in this study. The similarities in the expression profile of TRPM4 and AR in DCIS, breast and prostate cancers suggest a connection of TRPM4 with AR signaling pathway in tumors, and this warrants future investigations.…”