# Correlation between histopathological features and recurrence score according to menopausal status in HR+/HER2– breast cancer patients: a retrospective study

**Authors:** Federica Martorana, Sabrina Nucera, Gianmarco Motta, Maria Vita Sanò, Carlo Carnaghi, Marialuisa Puglisi, Claudia Gelsomino, Giuseppe Corsaro, Chiara Conti, Lucia Motta, Giuliana Pavone, Stefano Marletta, Giada Maria Vecchio, Gaetano Magro, Giuseppe Catanuto, Gaetano Castiglione, Francesco Caruso, Antonio Rizzo, Michele Caruso, Paolo Vigneri

PMC · DOI: 10.37349/etat.2025.1002331 · Exploration of Targeted Anti-tumor Therapy · 2025-07-18

## TL;DR

This study explores how histopathological features relate to a genomic recurrence score in breast cancer patients, finding differences based on menopausal status.

## Contribution

The study reveals how menopausal status affects the relationship between histopathological features and genomic recurrence scores in breast cancer patients.

## Key findings

- In pre-menopausal patients, PgR% predicted a higher recurrence score (RS > 16).
- Post-menopausal patients showed significant correlations between RS and Ki67% and PgR%.
- Histopathological features correlated differently with RS based on menopausal status.

## Abstract

Clinico-pathological features have traditionally guided prognosis and adjuvant therapy for breast cancer (BC) patients. In the past decade, genomic tests such as Oncotype DX entered clinical practice to refine risk stratification and predict chemotherapy benefit for hormone-receptor positive (HR+)/human epidermal growth factor-receptor 2 negative (HER2–) BC patients after surgery. This is a retrospective analysis to investigate the correlation between histopathological parameters and recurrence score (RS), accounting for menopausal status.

Data on HR+/HER2– early BC patients who underwent Oncotype DX were collected using an institutional database. Clinico-pathological characteristics were retrieved. Linear regression was used with RS as a continuous outcome, while logistic regression was performed for pre- and post-menopausal patients, dichotomizing RS at thresholds of 16 and 25, respectively.

A total of 180 women were included (35% pre-menopausal, 65% post-menopausal). Median age was 57.5 years. Most patients had pT1, pN0, G2 BC, with median estrogen receptor (ER) expression of 95% and a median Ki67 of 25%. Median RS was 16 [interquartile range (IQR) 12–22] in the overall cohort, 15 in pre-menopausal, and 17 in post-menopausal women. In the entire cohort, RS significantly correlated with G3 (P = 0.01), Ki67% (P < 0.0001), ER% (P = 0.03), and progesterone receptor (PgR)% (P < 0.0001). In pre-menopausal patients, only Ki67% (P = 0.02), ER% (P = 0.01), and PgR% (P < 0.0001) showed significant correlations, while in post-menopausal patients, G3 (P = 0.03), Ki67% (P = 0.001), and PgR% (P < 0.0001) achieved statistical significance. Logistic regression analysis showed that in pre-menopausal patients, PgR% predicted RS > 16 [odds ratio (OR) 0.95, P = 0.001]. In post-menopausal women, Ki67% (OR 1.08, P = 0.031) and PgR% (OR 0.95, P < 0.0001) predicted RS > 25.

In this patient cohort, classical clinico-pathological features showed varying correlations with RS, depending on menopausal status. These findings highlight the complexity of risk stratification, suggesting that further research is needed to better understand the factors influencing RS and its clinical utility.

## Linked entities

- **Proteins:** EREG (epiregulin), PGR (progesterone receptor)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}
- **Diseases:** BC (MESH:D001943)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12290898/full.md

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Source: https://tomesphere.com/paper/PMC12290898