Tumor mutational burden status and clinical characteristics of invasive lobular carcinoma of the breast.

Background

High tumor mutational burden (TMB-H) is an established biomarker for a favorable response to immune checkpoint inhibitors. However, tumor mutational burden (TMB) in invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) has not been sufficiently investigated.

Methods

We collected data of patients with ILC or IDC from the Center for Cancer Genomics and Advanced Therapeutics database between June 2019 and August 2023. Furthermore, we examined the clinicopathological factors and TMB status.

Results

Patients with ILC (n = 170) had a median TMB score of 4.00 mut/Mb (interquartile range, 2.00-7.14 mut/Mb), whereas those with IDC (n = 2598) had a score of 3.90 mut/Mb (2.00-6.00 mut/Mb). TMB-H was more common in patients with ILC than in those with IDC (18.2% vs. 10.1%, P < 0.001), particularly in the ER+ /HER2- subtype. Multivariate analysis revealed that the pathological diagnosis of ILC (P = 0.006), tissue samples collected from metastatic sites (P < 0.001), and older age (50 years, P < 0.001) were independent factors for TMB-H.

Conclusions

Patients with ILC were more likely to have TMB-H than those with IDC. The findings of this study would be invaluable in selecting treatment strategies for patients with ILC.

COI Statement

Declarations. Conflict of interest: YT received a research grant from Eli Lilly and speaker honorarium from Chugai, MSD, Eli Lilly Japan K.K., Pfizer, Dai-ichi Sankyo, and AstraZeneca. MI received a research grant from AstraZeneca and Pfizer and speaker honorarium from Chugai., MSD, Eli Lilly, Pfizer, Kyowa Kirin, Taiho, and Exact Sciences. TK received a speaker honorarium from Chugai, Daiichi Sankyo, Pfizer, Novartis Pharma, Eli Lilly, Eisai, Kyowa Kirin, and Celltrion. YA received a research grant from Chugai, Kyowa Kirin, Nippon Kayaku, Mochida Pharma, Taiho, Daiichi Sankyo and BeiGene and speaker honorarium from Chugai, MSD K.K, Eli Lilly, Kyowa Kirin, Nippon Kayaku, Novartis Pharma, Daiichi Sankyo, Taiho, Ono, Guardant Health, and AstraZeneca. KM, SM, and NT have no conflict of interest. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individuals who agreed to be registered in the C-CAT database.

References:

• Van Baelen K, Geukens T, Maetens M, Tjan-Heijnen V, Lord CJ, Linn S, et al. Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer. Ann Oncol. 2022;33:769–85.
• Adachi Y, Asaga S, Kumamaru H, Kinugawa N, Sagara Y, Niikura N, et al. Analysis of prognosis in different subtypes of invasive lobular carcinoma using the Japanese National cancer database-breast cancer registry. Breast Cancer Res Treat. 2023;201:397–408.
• Emens LA, Adams S, Barrios CH, Diéras V, Iwata H, Loi S, et al. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Ann Oncol. 2021;32:983–93.
• Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21:1353–65.
• Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9:34.