PMID- 35248011
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20220316
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 22
IP  - 1
DP  - 2022 Mar 5
TI  - Comparison of tumors with HER2 overexpression versus HER2 amplification in 
      HER2-positive breast cancer patients.
PG  - 242
LID - 10.1186/s12885-022-09351-4 [doi]
LID - 242
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive tumors are 
      defined by protein overexpression (3+) or gene amplification using 
      immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), 
      respectively. HER2-positive tumors have historically included both IHC(3+) and 
      IHC(2+, equivocal)/FISH(+) tumors and received the same treatment. Differences in 
      biology between these two tumor types, however, are poorly understood. 
      Considering anti-HER2 drugs bind directly to HER2 protein on the cell surface, we 
      hypothesized anti-HER2 therapies would be less effective in IHC(2+)/FISH(+) 
      tumors than in IHC(3+) tumors, leading to differences in patient outcomes. 
      METHODS: A total of 447 patients with HER2-positive invasive carcinoma who 
      underwent curative surgery were retrospectively investigated. HER2 status was 
      assessed in surgical specimens, except in patients who received neo-adjuvant 
      chemotherapy, where biopsy specimens were employed. RESULTS: Age, tumor size, 
      lymph node status and ER status were independent factors relating to 
      disease-free-survival, but no difference was observed between IHC(3+) and 
      IHC(2+)/FISH(+) tumors. Kaplan-Meier analysis found patient outcomes did not 
      differ, even after stratifying into those that did (n = 314), or did not 
      (n = 129), receive chemotherapy with anti-HER2 drugs. In 134 patients who 
      received NAC, pathological complete response rates in IHC(3+) and IHC(2+)/FISH(+) 
      tumors were 45% and 21%, respectively. Survival after developing metastasis was 
      significantly shorter in the IHC(2+)/FISH(+) group. CONCLUSIONS: The prognosis of 
      patients with IHC(2+)/FISH(+) tumors did not differ from IHC(3+) tumors. However, 
      the significance of HER2 protein overexpression in relation to treatment response 
      remains unclear and warrants further investigations.
CI  - (c) 2022. The Author(s).
FAU - Horimoto, Yoshiya
AU  - Horimoto Y
AUID- ORCID: 0000-0001-8935-0768
AD  - Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 
      Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan. horimoto@juntendo.ac.jp.
AD  - Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 
      Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan. horimoto@juntendo.ac.jp.
FAU - Ishizuka, Yumiko
AU  - Ishizuka Y
AD  - Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 
      Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
FAU - Ueki, Yuko
AU  - Ueki Y
AD  - Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 
      Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
FAU - Higuchi, Toru
AU  - Higuchi T
AD  - Department of Breast Oncology, Japanese Red Cross Saitama Hospital, 1-5 
      Shintoshin, Chuo-ku, 330-8553, Saitama, Japan.
FAU - Arakawa, Atsushi
AU  - Arakawa A
AD  - Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 
      Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
FAU - Saito, Mitsue
AU  - Saito M
AD  - Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 
      Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
LA  - eng
GR  - JP17K16517/Japan Society for the Promotion of Science/
PT  - Comparative Study
PT  - Journal Article
DEP - 20220305
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/genetics
MH  - Breast Neoplasms/*genetics/mortality/therapy
MH  - Carcinoma/*genetics/mortality/therapy
MH  - Chemotherapy, Adjuvant
MH  - Female
MH  - Gene Amplification/*genetics
MH  - Gene Expression/*genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Prognosis
MH  - Receptor, ErbB-2/*metabolism
MH  - Retrospective Studies
MH  - Treatment Outcome
PMC - PMC8897871
OTO - NOTNLM
OT  - Breast cancer
OT  - HER2
OT  - Immunohistochemistry
OT  - In situ hybridization
OT  - Trastuzumab
COIS- The authors have no conflict of interest to declare.
EDAT- 2022/03/07 06:00
MHDA- 2022/03/17 06:00
PMCR- 2022/03/05
CRDT- 2022/03/06 20:24
PHST- 2021/08/22 00:00 [received]
PHST- 2022/02/28 00:00 [accepted]
PHST- 2022/03/06 20:24 [entrez]
PHST- 2022/03/07 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2022/03/05 00:00 [pmc-release]
AID - 10.1186/s12885-022-09351-4 [pii]
AID - 9351 [pii]
AID - 10.1186/s12885-022-09351-4 [doi]
PST - epublish
SO  - BMC Cancer. 2022 Mar 5;22(1):242. doi: 10.1186/s12885-022-09351-4.