Related Experiment Video
Updated: Sep 30, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Changes in Triple-Negative Breast Cancer Molecular Subtypes in Patients Without Pathologic Complete Response After
Hiroko Masuda1,2, Kenichi Harano3, Sakiko Miura4
1Department of Breast Surgical Oncology, Showa University, Tokyo, Japan.
Purpose:
Lehmann et al have identified four molecular subtypes of triple-negative breast cancer (TNBC)-basal-like (BL) 1, BL2, mesenchymal (M), and luminal androgen receptor-and an immunomodulatory (IM) gene expression signature modifier. Our group previously showed that the response of TNBC to neoadjuvant systemic chemotherapy (NST) differs by molecular subtype, but whether NST affects the subtype was unknown. Here, we tested the hypothesis that in patients without pathologic complete response, TNBC subtypes can change after NST. Moreover, in cases with the changed subtype, we determined whether epithelial-to-mesenchymal transition (EMT) had occurred.
Materials And Methods:
From the Pan-Pacific TNBC Consortium data set containing TNBC patient samples from four countries, we examined 64 formalin-fixed, paraffin-embedded pairs of matched pre- and post-NST tumor samples. The TNBC subtype was determined using the TNBCtype-IM assay. We analyzed a partial EMT gene expression scoring metric using mRNA data.
Results:
Of the 64 matched pairs, 36 (56%) showed a change in the TNBC subtype after NST. The most frequent change was from BL1 to M subtypes (38%). No tumors changed from M to BL1. The IM signature was positive in 14 (22%) patients before NST and eight (12.5%) patients after NST. The EMT score increased after NST in 28 (78%) of the 36 patients with the changed subtype (v 39% of the 28 patients without change; P = .002254).
Conclusion:
We report, to our knowledge, for the first time that the TNBC molecular subtype and IM signature frequently change after NST. Our results also suggest that EMT is promoted by NST. Our findings may lead to innovative adjuvant therapy strategies in TNBC cases with residual tumor after NST.
Insights
Triple-negative breast cancer (TNBC) molecular subtypes and immunomodulatory (IM) signatures can change after neoadjuvant systemic chemotherapy (NST). These changes suggest that epithelial-to-mesenchymal transition (EMT) is promoted by NST, potentially impacting treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Triple-negative breast cancer (TNBC) exhibits distinct molecular subtypes (basal-like 1, basal-like 2, mesenchymal, luminal androgen receptor) and an immunomodulatory (IM) signature.
- Previous research indicated that TNBC response to neoadjuvant systemic chemotherapy (NST) varies by molecular subtype.
- The impact of NST on TNBC molecular subtypes remained largely unknown.
Purpose of the Study:
- To investigate whether TNBC molecular subtypes change after NST in patients who do not achieve a pathologic complete response.
- To determine if epithelial-to-mesenchymal transition (EMT) occurs in TNBC cases where the subtype changes post-NST.
Main Methods:
- Analysis of 64 matched pre- and post-NST tumor samples from the Pan-Pacific TNBC Consortium dataset.
- TNBC subtyping was performed using the TNBCtype-IM assay.
- Epithelial-to-mesenchymal transition (EMT) was assessed using a partial EMT gene expression scoring metric from mRNA data.
Main Results:
- A significant subtype change was observed in 56% of patients after NST, most commonly from basal-like 1 to mesenchymal.
- The immunomodulatory (IM) signature prevalence decreased post-NST.
- The EMT score significantly increased in patients with a subtype change compared to those without.
Conclusions:
- TNBC molecular subtypes and IM signatures frequently change following NST.
- NST appears to promote EMT in TNBC.
- These findings may inform novel adjuvant therapy strategies for TNBC patients with residual disease after NST.
