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Differential effects of oral contraceptives on lymph node metastasis in breast cancer: role of tumor size as an effect modifier.

Created on 17 Jul 2026

Authors

Yang Saimei, Su Qiu, Xie Baodong

Published in

Journal of mammary gland biology and neoplasia. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Lymph node metastasis (LNM) is a critical determinant of breast cancer prognosis. While oral contraceptives (OC) are associated with breast cancer risk, their relationship with LNM-particularly in understudied populations like Morocco-remains unclear. This study investigates whether tumor size modifies OC-LNM associations in Moroccan patients.
We analyzed 356 breast cancer cases from Morocco's National Institute of Oncology(2009). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for OC-LNM associations were estimated using multivariable logistic regression, stratified by tumor size (≤ 2 cm vs. > 2 cm). Multiplicative and additive interactions between OC use and tumor size were assessed.
After full adjustment for clinicopathological factors, OCs use was associated with reduced LNM risk in tumors ≤ 2 cm (OR = 0.08, 95% CI: 0.02-0.47, P = 0.005) but increased risk in tumors > 2 cm (OR = 1.97, 95%CI: 1.04-3.76, P = 0.039). Significant multiplicative interaction (P = 0.047) and evidence of additive interaction (RERI = 1.72, AP = 0.69) suggest tumor size acts as an effect modifier, though the precision of the additive interaction estimate is limited (AP 95% CI: 0.30-1.07).
Tumor size critically modifies OC-LNM relationships, with protective effects in small tumors and risk-promoting effects in large tumors. This heterogeneity underscores the need for size-stratified assessments in breast cancer management.

PMID:
42467122
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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