PMID- 36859733
OWN - NLM
STAT- MEDLINE
DCOM- 20230424
LR  - 20230424
IS  - 1880-4233 (Electronic)
IS  - 1340-6868 (Linking)
VI  - 30
IP  - 3
DP  - 2023 May
TI  - ER-/PR+ breast cancer is controlled more effectively with an inflammatory 
      inhibitor than hormonal inhibitor.
PG  - 436-452
LID - 10.1007/s12282-023-01437-6 [doi]
AB  - BACKGROUND: The anti-estrogen tamoxifen is a highly effective hormonal therapy 
      for hormonal-positive (HR+) breast cancer patients; however, the estrogen 
      receptor-negative, progesterone receptor-positive (ER-/PR+) subtype does not give 
      the benefits of tamoxifen. Therefore ER-/PR+ breast cancer has a poor clinical 
      outcome, and novel drug therapy for ER-/PR+ breast cancer could benefit these 
      patients. METHODS: 53,805 gene expressions were characterized into HR+ BC and 
      triple-negative breast cancer (TNBC) and analyzed through Breast Cancer Gene 
      Expression Miner in 4319 breast cancer patient samples. The clinical outcomes 
      including overall survival, distant metastasis-free survival, and relapse-free 
      survival were obtained from the PrognoScan database containing 1190 human breast 
      cancer patient samples. To determine the function of ERalpha and inflammation-related 
      genes such as USP1, CDC20, and CASP1, we used the CRISPR-Cas9 system or gene 
      knockdown (KD) system. To check tumor cell proliferation and migration of ERalpha KO 
      breast cancer cell line, we used tamoxifen and the inflammation inhibitor 
      Ac-YVAD-CHO. For further confirmation, cancer growth was checked with the 
      inflammation inhibitor in ERalpha KO breast cancer cell line using a 
      three-dimensional (3D) organoid tissue culture system (ex vivo). RESULTS: We 
      found that gene expression in ER-/PR+ hormonal-positive breast cancer is 
      positively related to ER-/PR- very similar to TNBC, not other HR+ breast cancer 
      using a 4319 breast cancer patient database. Especially, inflammation-related 
      genes, USP1, CDC20, and CASP1, which are highly expressed in TNBC, are also 
      upregulated in ER-/PR+ HR+ breast cancer. Suppression of USP1, CDC20, and CASP1 
      inhibited tumor cell growth and metastasis in ERalpha KO (ER-/PR +) cell lines. 
      Interestingly, loss of ERalpha in HR+ cell lines is not responsive to tamoxifen, but 
      highly sensitive to the inflammation inhibitor, Ac-YVAD-CHO. In in vitro and ex 
      vivo (3D organoid) models, inflammation inhibitor-specific blocks ER-/PR+ tumor 
      proliferation and migration. CONCLUSIONS: These findings suggest that an 
      inflammation inhibitor might be a potential option for therapy for ER-/PR+ HR 
      breast cancer patients.
CI  - (c) 2023. The Author(s), under exclusive licence to The Japanese Breast Cancer 
      Society.
FAU - Song, Christine
AU  - Song C
AD  - Division of Radiology, Mayo Clinic, Rochester, MN, 55905, USA.
AD  - Mayo High School, Rochester, MN, 55904, USA.
FAU - Kendi, Ayse Tuba
AU  - Kendi AT
AD  - Division of Radiology, Mayo Clinic, Rochester, MN, 55905, USA.
FAU - Shim, Ji Yeon
AU  - Shim JY
AD  - College of Nursing, Dankook University, Cheonan, Chungcheongnam, 31116, Republic 
      of Korea.
FAU - Jung, Dawa
AU  - Jung D
AD  - U&Hang Clinic, Asan, Chungcheongnam, 31514, Republic of Korea.
FAU - Kang, Pil Soo
AU  - Kang PS
AD  - U&Hang Clinic, Asan, Chungcheongnam, 31514, Republic of Korea.
FAU - Lowe, Val J
AU  - Lowe VJ
AD  - Division of Radiology, Mayo Clinic, Rochester, MN, 55905, USA. vlowe@mayo.edu.
FAU - Lee, SeungBaek
AU  - Lee S
AD  - Division of Radiology, Mayo Clinic, Rochester, MN, 55905, USA. 
      lee.seungbaek@mayo.edu.
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 
      Rochester, MN, 55905, USA. lee.seungbaek@mayo.edu.
LA  - eng
PT  - Journal Article
DEP - 20230301
PL  - Japan
TA  - Breast Cancer
JT  - Breast cancer (Tokyo, Japan)
JID - 100888201
RN  - 0 (Estrogen Receptor alpha)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, Progesterone)
RN  - 0 (Antineoplastic Agents, Hormonal)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Breast Neoplasms/drug therapy/genetics/pathology
MH  - Estrogen Receptor alpha/metabolism
MH  - *Triple Negative Breast Neoplasms/drug therapy/genetics
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Tamoxifen/pharmacology/therapeutic use
MH  - Receptors, Estrogen/metabolism
MH  - Inflammation/drug therapy
MH  - Receptors, Progesterone/metabolism
MH  - Antineoplastic Agents, Hormonal/pharmacology/therapeutic use
OTO - NOTNLM
OT  - Ac-YVAD-CHO
OT  - CDC20
OT  - Caspase-1
OT  - ER-/PR+ hormonal breast cancer
OT  - Inflammation inhibitor
OT  - Tamoxifen
OT  - USP1
EDAT- 2023/03/02 06:00
MHDA- 2023/04/24 06:42
CRDT- 2023/03/01 23:59
PHST- 2022/08/07 00:00 [received]
PHST- 2023/02/08 00:00 [accepted]
PHST- 2023/04/24 06:42 [medline]
PHST- 2023/03/02 06:00 [pubmed]
PHST- 2023/03/01 23:59 [entrez]
AID - 10.1007/s12282-023-01437-6 [pii]
AID - 10.1007/s12282-023-01437-6 [doi]
PST - ppublish
SO  - Breast Cancer. 2023 May;30(3):436-452. doi: 10.1007/s12282-023-01437-6. Epub 2023 
      Mar 1.