metoprolol ER + hydrochlorothiazide (Selopress Zok / Dutoprol)

The 21-gene recurrence score assay as a tool for predicting recurrence risk and guiding adjuvant treatment selection in early breast cancer.

Martínez-Pérez Carlos C, Tramonti Giovanni G, Kay Charlene C, Taylor Karen K et al.

Estrogen receptor-positive (ER+), HER2-negative breast cancer is the most common breast cancer subtype. While adjuvant endocrine therapy reduces recurrence risk, identifying which patients benefit from the addition of chemotherapy remains a key clinical challenge. The Oncotype DX® 21-gene Recurrence Score assay (Exact Sciences, via Genomic Health, Inc.) was developed to address this by quantifying distant recurrence risk and informing chemotherapy decisions in early-stage ER+/HER2- disease. This diagnostic profile reviews the development, validation, and clinical evidence for Oncotype DX, including findings from the TAILORx and RxPONDER prospective trials and the subsequent development of hybrid tools integrating genomic and clinicopathological data. Alternative multiparameter molecular tests (MammaPrint, Prosigna, EndoPredict, Breast Cancer Index) are summarized and compared. We review international guideline recommendations, decision impact studies, cost-effectiveness evidence, and ongoing trials. Oncotype DX has strong prognostic evidence and has meaningfully reduced chemotherapy use, though its case as a biomarker predictive of therapeutic effect from chemotherapy rests on trial designs with important limitations. Its independent prognostic contribution beyond comprehensive clinicopathological assessment requires further clarification, and cost-effectiveness varies substantially by indication and healthcare setting.

From integrative diagnostics to personalised management: a framework combining molecular and spatial immune profiling in NSMP endometrial carcinoma.

Zhong Lan L, Song Liang L

Endometrial carcinoma (EC) of the No Specific Molecular Profile (NSMP) subtype, the largest molecular category, exhibits marked clinical heterogeneity that challenges morphology-based risk assessment. Two complementary biomarker categories have demonstrated independent prognostic value: protein-level markers (L1CAM, oestrogen receptor [ER], and progesterone receptor [PR]) detectable by routine immunohistochemistry and spatially resolved cancer-immune phenotypes (SCIs) that characterize the tumour immune microenvironment. This review synthesises evidence for both, highlighting that they are often considered in isolation. We argue that their systematic integration is essential for a more precise diagnostic framework. We articulate the biological rationale and propose a testable "dual-risk" hypothesis, whereby combined molecular and immune profiling could identify extreme-risk populations. Realising this integrative model requires overcoming standardisation hurdles, but it represents a critical step towards predictive, functionally informed stratification to guide personalised adjuvant therapy decisions, including intensification and de-escalation. We emphasise that this framework remains a testable hypothesis requiring prospective validation before clinical application.

Clinical impact of 18F-FES PET/CT-detected ER-positive conversion in metastatic breast cancer with ER-negative primary tumors.

Feng Sanxing S, Xie Yizhao Y, Liu Cheng C, Li Yumeng Y et al.

Receptor discordance between primary and metastatic breast cancer is increasingly recognized and may influence treatment decisions in metastatic breast cancer (MBC) patients. 18F-fluoroestradiol (18F-FES) PET/CT enables non-invasive whole-body assessment of estrogen receptor (ER) expression and may provide additional information beyond tissue-based evaluation. This study aimed to investigate the clinical significance of 18F-FES-positive conversion in patients with MBC whose primary tumors were ER-negative, and to evaluate the potential role of 18F-FES PET/CT in treatment stratification. This retrospective study screened 1330 patients with metastatic breast cancer who underwent 18F-FES PET/CT, identified 51 patients with ER-negative primary breast tumors, and finally included 40 evaluable patients in the analysis. 18F-FES positivity was defined by focal uptake visually distinguishable from local background together with a lesional SUVmax ≥ 1.8. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. 18F-FES-positive conversion occurred in 37.5% (15/40) of patients. Primary progesterone receptor (PR) positivity was more frequent in patients with 18F-FES-positive conversion than in those without conversion (60.0% vs. 24.0%; P = 0.042). After imaging, endocrine-based therapy predominated among patients with 18F-FES-positive conversion whereas chemotherapy was more common in 18F-FES-negative patients. Patients with 18F-FES-positive conversion showed significantly longer PFS than those remaining 18F-FES-negative (median PFS, 15.2 vs. 7.3 months; P = 0.005). ER-positive conversion assessed by 18F-FES PET/CT can occur in clinically selected patients with metastatic breast cancer and ER-negative primary tumors. 18F-FES PET/CT may provide clinically meaningful information for treatment stratification in this patient population.

ASO Author Reflections: Can We Preserve Fertility without Compromising Oncologic Outcomes?: Preoperative Oncofertility for ER-Positive Breast Cancer.

Chen Jennifer H JH, Peregrin-Alvarez Irene I, Warneke Carla L CL, McKenzie Laurie J LJ et al.