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. 2025 Jul 18:6:1002331.
doi: 10.37349/etat.2025.1002331. eCollection 2025.

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

Federica Martorana  1   2 , Sabrina Nucera  1   2 , Gianmarco Motta  1   2 , Maria Vita Sanò  2 , Carlo Carnaghi  2 , Marialuisa Puglisi  3 , Claudia Gelsomino  3 , Giuseppe Corsaro  3 , Chiara Conti  1   2 , Lucia Motta  1   2 , Giuliana Pavone  1   2 , Stefano Marletta  2 , Giada Maria Vecchio  4 , Gaetano Magro  4 , Giuseppe Catanuto  2 , Gaetano Castiglione  2 , Francesco Caruso  2 , Antonio Rizzo  2 , Michele Caruso  2 , Paolo Vigneri  1   2
Affiliations

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

Federica Martorana et al. Explor Target Antitumor Ther. .

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Oncotype DX; breast cancer; hormone-receptor positive; recurrence score.

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Conflict of interest statement

Antonio Rizzo and Stefano Marletta who are the Guest Editors of Exploration of Targeted Anti-tumor Therapy had no involvement in the decision-making or the review process of this manuscript. The other authors declare that they have no conflicts of interest related to the present work.

Figures

Figure 1
Figure 1
Recurrence score (RS) distribution according to menopausal status, using the standard threshold for high-risk definition
Figure 2
Figure 2
Progesterone receptor (PgR) distribution according to recurrence score (RS) category in pre-menopausal (A) and post-menopausal (B) patients, and the area under receiver operating characteristic (ROC) curve for RS prediction based on PgR levels in pre-menopausal (C) and post-menopausal (D) patients
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