The Emerging Roles of Steroid Hormone Receptors in Ductal Carcinoma in Situ (DCIS) of the Breast

Abstract Ductal carcinoma in situ (DCIS) is a non-obligate precursor to most types of invasive breast cancer (IBC). Although it is estimated only one third of untreated patients with DCIS will progress to IBC, standard of care for treatment is surgery and radiation. This therapeutic approach combined with a lack of reliable biomarker panels to predict DCIS progression is a major clinical problem. DCIS shares the same molecular subtypes as IBC including estrogen receptor (ER) and progesterone receptor (PR) positive luminal subtypes, which encompass the majority (60–70%) of DCIS. Compared to the established roles of ER and PR in luminal IBC, much less is known about the roles and mechanism of action of estrogen (E2) and progesterone (P4) and their cognate receptors in the development and progression of DCIS. This is an underexplored area of research due in part to a paucity of suitable experimental models of ER+/PR + DCIS. This review summarizes information from clinical and observational studies on steroid hormones as breast cancer risk factors and ER and PR as biomarkers in DCIS. Lastly, we discuss emerging experimental models of ER+/PR+ DCIS.

Download Full-text

Role of Androgen and Estrogen Receptors as Prognostic and Potential Predictive Markers of Ductal Carcinoma in Situ of the Breast

The International Journal of Biological Markers ◽

10.5301/jbm.5000163 ◽

2015 ◽

Vol 30 (4) ◽

pp. 425-428 ◽

Cited By ~ 13

Author(s):

Maria Maddalena Tumedei ◽

Rosella Silvestrini ◽

Sara Ravaioli ◽

Ilaria Massa ◽

Roberta Maltoni ◽

...

Keyword(s):

Breast Cancer ◽

Ductal Carcinoma In Situ ◽

Carcinoma In Situ ◽

Hormone Receptors ◽

Ductal Carcinoma ◽

Area Under The Curve ◽

Steroid Hormone Receptors ◽

Prognostic Indicators

Background Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has not been investigated as widely as invasive breast cancer. Thus, the search for biomarkers capable of identifying DCIS lesions that may recur or progress to invasive cancer is ongoing. Although conventional steroid hormone receptors, cell proliferation and other important tumor markers have been extensively studied in invasive tumors, little is known about the role played by androgen receptors (ARs), widely expressed in breast cancer, in DCIS. Methods We performed a retrospective study in a series of 43 DCIS patients treated with quadrantectomy only and followed up for a period ranging from 5 to 13 years, to evaluate the prognostic relevance of conventional biomarkers (estrogen receptor [ER], progesterone receptor [PgR], Ki67, human epidermal growth factor receptor 2 [HER2]) and AR. Results Our findings showed that AR and ER were not independent prognostic variables and that an AR/ER ratio cutoff of 1.13 showed a sensitivity of 75% and a specificity of 94% in predicting in situ relapse or progression to the invasive phenotype. Moreover, while the variables considered singly showed area under the curve (AUC) values ranging from 0.52% to 0.77%, the AR/ER ratio reached a very high AUC (0.92%). Conclusions These preliminary results highlight the potentially important role of AR and ER and, in particular, of their ratio, as prognostic indicators of DCIS evolution.

Download Full-text