# Worse survival despite indolent features for triple-negative invasive lobular carcinoma: a Swedish nationwide registry-based study

## TL;DR

This study finds that triple-negative invasive lobular breast cancer has worse survival despite appearing less aggressive, especially in older patients.

## Contribution

Identifies triple-negative invasive lobular carcinoma as a distinct subgroup with unique clinical and survival characteristics.

## Key findings

- TNBC–ILC patients had worse overall and disease-specific survival despite lower tumor grade and Ki-67 levels.
- Older TNBC–ILC patients were less likely to receive adjuvant chemotherapy and had the poorest 5-year survival rates.
- Machine learning highlighted age and tumor size as key predictive features for TNBC–ILC.

## Abstract

To evaluate differences in clinical outcomes, treatments received, recurrence, and sociodemographic characteristics in patients with triple-negative breast cancer (TNBC) classified as invasive lobular carcinoma (TNBC–ILC) or invasive carcinoma of no special type (TNBC–NST).

Using national registry data, we conducted a retrospective, population-based cohort study of 6449 women diagnosed with primary TNBC (stratified by histological subtype) in Sweden (2007–2021). Clinical and treatment data were analyzed using descriptive statistics, logistic regression, machine learning (Boruta/XGBoost), and Cox proportional hazards models adjusted for patient age, tumor size, grade, nodal status, comorbidities, and receipt of adjuvant chemotherapy (ACT).

TNBC–ILC accounted for 2.7% of all TNBC cases and affected older patients (median age 70 vs 62 years). Compared to TNBC–NST, TNBC–ILC had lower Ki-67, fewer high-grade tumors, higher T stage, and greater socioeconomic vulnerability. Machine learning identified age and post-operative tumor size as key predictive features of TNBC–ILC. ACT was administered to 40% of TNBC–ILC versus 59% of TNBC–NST cases (P < 0.001), with a survival benefit observed only in TNBC–NST. TNBC–ILC patients aged 50–64 years were less likely to receive ACT. Despite lower proliferative activity, TNBC–ILC was associated with worse overall (OS; adj-HR 1.39, 95% CI 1.04–1.86) and disease-specific survival (DSS; adj-HR 1.98, 95% CI 1.41–2.79), particularly in patients ≥ 50 years of age. TNBC–ILC patients ≥ 75 years had the poorest 5-year survival (DSS 55%; OS 42%).

TNBC–ILC is a distinct subgroup with older age, lower grade and Ki-67, undertreatment, and poorer survival, emphasizing the need for age- and subtype-specific treatment strategies.

The online version contains supplementary material available at 10.1007/s10549-025-07862-9.