Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 1;8(4):e251888.
doi: 10.1001/jamanetworkopen.2025.1888.

Clinical Characteristics and Survival Outcomes of Metastatic Invasive Lobular and Ductal Carcinoma

Akshara S Raghavendra  1 , Roland Bassett Jr  2 , Senthil Damodaran  1 , Carlos H Barcenas  1 , Jason A Mouabbi  1 , Rachel Layman  1 , Debu Tripathy  1
Affiliations

Clinical Characteristics and Survival Outcomes of Metastatic Invasive Lobular and Ductal Carcinoma

Akshara S Raghavendra et al. JAMA Netw Open. .

Abstract

Importance: Comparing the clinical and molecular features of metastatic invasive lobular carcinoma (mILC) and metastatic invasive ductal carcinoma (mIDC) is essential to enhance understanding of breast cancer biology and improve personalized treatment approaches.

Objective: To compare mILC and mIDC in terms of survival outcomes and to investigate the association of clinicopathologic characteristics with those outcomes.

Design, setting, and participants: This cohort study included adult patients at the University of Texas MD Anderson Cancer Center with their first metastatic diagnosis occurring between January 1997 and December 2020. Patient records were obtained from an institutional database. The study follow-up concluded in July 2023, and data were analyzed from July to December 2024.

Exposure: Diagnosis of mIDC and mILC.

Main outcomes and measures: Progression-free survival (PFS), overall survival (OS), and disease-free interval (DFI) were estimated using the Kaplan-Meier method. Survival distributions were compared using the log-rank test. Multivariable Cox proportional hazards regression was used to assess the association of metastasis onset, estrogen receptor (ER) expression level, and tumor grade with OS and PFS.

Results: The analysis included a total of 9714 patients (9628 women [99%]), 8535 with mIDC and 1179 with mILC. The median age at metastasis was 53.3 years (range, 17.6-62.0 years). Generally, patients with mILC were older and had lower nuclear grade tumors and fewer metastasis sites than patients with mIDC. Patients with mILC had longer PFS (median, 0.65 years; 95% CI, 0.58-0.74) than patients with mIDC (median, 0.46 years; 95% CI, 0.45-0.48) (hazard ratio [HR], 0.78; 95% CI, 0.73-0.84; P < .001). For OS, patients with mILC had longer OS (median, 3.06 years; 95% CI, 2.87-3.29) than patients with mIDC (median, 2.60 years; 95% CI, 2.52-2.67 years) (HR, 0.91; 95% CI, 0.84-0.98; P = .01). Overall, patients with mILC had longer DFI than patients with mIDC (HR, 0.69; 95% CI, 0.64-0.75; P < .001). At initial diagnosis, patients with mILC were less likely to present with visceral metastasis (522 patients [44.3%]) than patients with mIDC (4909 patients [57.5%]). A higher proportion of patients with mILC (931 patients [79.0%]) than patients with mIDC (5431 patients [63.6%]) had bone-only metastasis.

Conclusions and relevance: In this cohort study, patients with mILC had longer OS and PFS than those with mIDC. Metastasis onset, ER positivity, and tumor grade were associated with survival outcomes, and distinct metastatic patterns of mIDC and mILC were also associated with survival for mIDC and mILC, which may help guide more personalized treatment strategies for each subtype.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Damodaran reported receiving grants from EMD Serono, Novartis, Taiho, Sermonix, AstraZeneca, Daiichi Sankyo, Medilink, Guardant, and Duality Bio (all paid to their institution) outside the submitted work. Dr Mouabbi reported receiving personal fees from BostonGene, Gilead, Novartis, and AstraZeneca and serving as chair of the scientific advisory board of the Lobular Breast Cancer Alliance outside the submitted work. Dr Layman reported receiving grants from Accutar Biotechnology, Eli Lilly, Novartis, Celcuity, Pfizer, Arvinas, and Puma; and personal fees from Eli Lilly, Novartis, Pfizer, Celcuity, Gilead Sciences, and Biotheryx outside the submitted work. Dr Tripathy reported receiving clinical research grants (paid to institution) from Novartis, AMBRX, and TVARDI and honoraria for consulting from Gilead, Menarini, Personalis, Pfizer, Roche, Sermonix, Novartis, Puma Biotechnology, Jazz Pharmaceutics, and AMBRX. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Patient Enrollment Flowchart
MBC indicates metastatic breast cancer; mIDC, metastatic invasive ductal carcinoma; mILC, metastatic invasive lobular carcinoma.
Figure 2.
Figure 2.. Proportion of Patients With Metastases
When biopsy findings were unavailable, bone marrow involvement was determined on the basis of blood count results and morphologic findings. mIDC indicates metastatic invasive ductal carcinoma; mILC, metastatic invasive lobular carcinoma.
See this image and copyright information in PMC

References

    1. Makki J. Diversity of breast carcinoma: histological subtypes and clinical relevance. Clin Med Insights Pathol. 2015;8:23-31. doi:10.4137/CPath.S31563 - DOI - PMC - PubMed
    1. Martinez V, Azzopardi JG. Invasive lobular carcinoma of the breast: incidence and variants. Histopathology. 1979;3(6):467-488. doi:10.1111/j.1365-2559.1979.tb03029.x - DOI - PubMed
    1. Borst MJ, Ingold JA. Metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast. Surgery. 1993;114(4):637-641. - PubMed
    1. Mouabbi JA, Hassan A, Lim B, Hortobagyi GN, Tripathy D, Layman RM. Invasive lobular carcinoma: an understudied emergent subtype of breast cancer. Breast Cancer Res Treat. 2022;193(2):253-264. doi:10.1007/s10549-022-06572-w - DOI - PubMed
    1. Dossus L, Benusiglio PR. Lobular breast cancer: incidence and genetic and non-genetic risk factors. Breast Cancer Res. 2015;17(1):37. doi:10.1186/s13058-015-0546-7 - DOI - PMC - PubMed

Publication types