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. 2022 Mar:6:e2000368.
doi: 10.1200/PO.20.00368.

Changes in Triple-Negative Breast Cancer Molecular Subtypes in Patients Without Pathologic Complete Response After Neoadjuvant Systemic Chemotherapy

Hiroko Masuda  1   2 , Kenichi Harano  3 , Sakiko Miura  4 , Ying Wang  5 , Yuko Hirota  4 , Oi Harada  1   6 , Mohit Kumar Jolly  7 , Yuki Matsunaga  1 , Bora Lim  2   8 , Anita L Wood  2 , Napa Parinyanitikul  9 , Hee Jin Lee  10 , Gyungyub Gong  10 , Jason T George  11   12   13 , Herbert Levine  14 , Jangsoon Lee  2   8 , Xiaoping Wang  2   8 , Anthony Lucci  2   15 , Arvind Rao  5 , Brock L Schweitzer  16 , O Rayne Lawrence  16 , Robert S Seitz  16 , Stephan W Morris  16 , David R Hout  16 , Seigo Nakamura  1 , Savitri Krishnamurthy  2   17 , Naoto T Ueno  2   8
Affiliations

Changes in Triple-Negative Breast Cancer Molecular Subtypes in Patients Without Pathologic Complete Response After Neoadjuvant Systemic Chemotherapy

Hiroko Masuda et al. JCO Precis Oncol. 2022 Mar.

Abstract

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.

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Conflict of interest statement

Hiroko MasudaSpeakers' Bureau: AstraZeneca, Chugai Pharma, Lilly, Novartis, EisaiResearch Funding: Eisai, Lilly (Inst) Kenichi HaranoHonoraria: AstraZeneca, Chugai Pharma, Eisai, MSD K.K, TakedaConsulting or Advisory Role: Takeda, Lilly Japan, AstraZeneca, Chugai PharmaResearch Funding: Merck, Daiichi-Sankyo Oi HaradaConsulting or Advisory Role: Philips Japan Bora LimHonoraria: Department of Defense, San Antonio Breast Cancer symposiumConsulting or Advisory Role: AstraZeneca, Novartis, Natera, LillyResearch Funding: Genentech, Merck, Puma Biotechnology, Calithera Biosciences, Takeda Napa ParinyanitikulConsulting or Advisory Role: Roche, MSD OncologySpeakers' Bureau: Novartis, Roche, Pfizer, AstraZeneca Hee Jin LeeStock and Other Ownership Interests: NeogenTC Corp Gyungyub GongConsulting or Advisory Role: Roche Jangsoon LeeResearch Funding: AnHeart Therapeutics, CytoDyn, ChemDiv Anthony LucciSpeakers' Bureau: Exact Sciences Arvind RaoHonoraria: Cambridge Healthtech InstituteConsulting or Advisory Role: Genophyll LLC, Voxel Analytics LLCResearch Funding: Agilent (Inst)Patents, Royalties, Other Intellectual Property: Patents pendingTravel, Accommodations, Expenses: Cambridge Healthtech Institute Brock L. SchweitzerEmployment: OncoCyteResearch Funding: OncoCyte (Inst)Patents, Royalties, Other Intellectual Property: I am included as an inventor on pending patents for the 27-gene algorithm used for classifying tumors Robert S. SeitzEmployment: OncoCyteLeadership: OncocyStock and Other Ownership Interests: OncocyConsulting or Advisory Role: Thermo Fisher Scientific Stephan W. MorrisEmployment: Greenfire Bio David R. HoutEmployment: Insight Genetics, OncoCyteLeadership: Insight GeneticsStock and Other Ownership Interests: OncocytePatents, Royalties, Other Intellectual Property: I hold patents with Insight Genetics, but no royaltiesTravel, Accommodations, Expenses: Insight Genetics Seigo NakamuraHonoraria: Chugai Pharma, Daiichi Sankyo Co Ltd Naoto T. UenoHonoraria: Kyowa Hakko Kirin, Amgen, Chugai/Roche, Henry Stewart Talks, Taiho Pharmaceutical, Eisai, Rakuten Medical, Daiichi Sankyo, Pfizer, Novartis, Gilead Sciences, Puma BiotechnologyConsulting or Advisory Role: Daiichi Sankyo, Immunomedics, KeChow Pharma, Phoenix Design, Takeda, OncoCyteResearch Funding: Medivation, Bayer, Amgen, Puma Biotechnology, Merck, Daiichi Sankyo, Celgene, GlaxoSmithKline, Kyowa Hakko Kirin, Bio-Path Holdings, Novartis, Sysmex, Preferred MedicineNo other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Distribution of triple-negative breast cancer subtypes before NST (core needle samples) for patients who did not have pathologic complete response (n = 64). BL, basal-like; LAR, luminal androgen receptor; M, mesenchymal; UNS, unstable.
FIG 2.
FIG 2.
Distribution of triple-negative breast cancer subtypes after NST (surgical samples) for patients who did not have pathologic complete response (n = 64). BL, basal-like; LAR, luminal androgen receptor; M, mesenchymal; UNS, unstable.
FIG 3.
FIG 3.
Post-NST triple-negative breast cancer subtypes for patients in each pre-NST subtype group. BL, basal-like; LAR, luminal androgen receptor; M, mesenchymal; UNS, unstable.
See this image and copyright information in PMC

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