Low progesterone receptor levels in high-grade DCIS correlate with HER2 upregulation and the presence of invasive components

Hossein Schandiz; Lorant Farkas; Daehoon Park; Yan Liu; Solveig N Andersen; Jürgen Geisler; Torill Sauer

doi:10.3389/fonc.2024.1347166

Low progesterone receptor levels in high-grade DCIS correlate with HER2 upregulation and the presence of invasive components

Front Oncol. 2024 Jun 26:14:1347166. doi: 10.3389/fonc.2024.1347166. eCollection 2024.

Authors

Hossein Schandiz^{1

2}, Lorant Farkas^{2

3}, Daehoon Park³, Yan Liu^{2

4}, Solveig N Andersen², Jürgen Geisler^#^{1

2}, Torill Sauer^#²

Affiliations

¹ Department of Oncology, Akershus University Hospital (AHUS), Lorenskog, Norway.
² Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Pathology, Oslo University Hospital, Oslo, Norway.
⁴ Department of Clinical Molecular Biology (EpiGen), Akershus University Hospital (AHUS), Lorenskog, Norway.

^# Contributed equally.

Abstract

Objective: In this study, we investigated pivotal molecular markers in human high-grade breast ductal carcinoma in situ (DCIS). Expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor 2 (HER2) was measured among various subtypes (Luminal (Lum) A, LumB HER2^-, LumB HER2⁺, HER2-enriched and triple-negative).

Methods: In total, 357 DCIS cases were classified into respective subtypes, according to the 2013 St. Gallen guidelines. Each subtype was categorized into three subcategories: "Pure" (those without an invasive component), "W/invasive" (those with an invasive component), and "All" (the entire group of the given subtype). ER and PR expression were registered as intervals. Equivocal HER2 immunohistochemistry (IHC) cases (2+) were further investigated using dual-color in situ hybridization.

Results: The majority of patients (71%) were over the age of 50. We discovered no significant differences in the proportion of age between the "Pure" and "W/invasive" groups. There was no significant difference in ER/PR expression between "Pure" luminal subtypes of DCIS and "W/invasive" cases. We compared the HER2 IHC scores of "0", "1+", and "2+" among LumA and LumB HER2 subtypes and identified no statistically significant differences between "Pure" and "W/invasive" (p = 0.603). ER and PR expression ≥ 50% cutoff value was present in > 90% of all LumA cases. The incidences of cases with ER expression at cutoff values of < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). The proportion of cases with PR expression < 20% showed significant differences in the various luminal subtypes. In luminal B subtypes, low PR expression (< 20%) was significantly associated with both strong HER2 expression (3+) and the presence of an invasive component (p = 0.0001 and p = 0.0365, respectively).

Conclusions: ER and PR expression at ≥ 50% cutoff values were found in more than 90% of LumA cases. Samples with ER < 10% and ≥ 50% in LumA were significantly different compared to other luminal subtypes (p < 0.0001). Low PR expression in high-grade DCIS was strongly associated with HER2 overexpression (3+) and an invasive component (p = 0.0001 and p = 0.0365, respectively).

Keywords: HER2; ductal carcinoma in situ; hormone receptors; immunohistochemistry; in situ hybridization; invasive breast carcinoma; molecular subtypes; precision medicine.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Akershus University Hospital in Norway generously provided open-access funding. We extend our sincere appreciation to the National Network for Breast Cancer Research in Norway, Akershus University Hospital, Division of Medicine, and the University of Oslo, Faculty of Medicine (JG), for their valuable research support.