Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity-From Bench to Bedside.
anti-HER2/neu
chemotherapy
ovarian toxicity
trastuzumab
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
07 Dec 2020
07 Dec 2020
Historique:
received:
20
10
2020
revised:
23
11
2020
accepted:
01
12
2020
entrez:
10
12
2020
pubmed:
11
12
2020
medline:
11
12
2020
Statut:
epublish
Résumé
Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, is considered a standard treatment in addition to chemotherapy in the adjuvant setting for HER2/neu-positive breast cancer, yet its impact on fertility and ovarian reserve remains obscure. We aimed to study the effect of anti-HER2/neu on chemotherapy-induced ovarian toxicity in both clinical and preclinical settings. We prospectively enrolled breast cancer patients below the age of 42 years who were treated with chemotherapy with or without trastuzumab into the study. Anti-Müllerian hormone (AMH) was measured 6 and 12 months post-chemotherapy as an ovarian reserve indicator. In the animal model, pubertal mice were injected with cyclophosphamide or paclitaxel with or without anti-HER2/neu, or saline, and sacrificed 1 week or 3 months later. Ovarian apoptosis, proliferation and vascularity were measured by immunohistochemistry and ovarian reserve was measured by morphometric analysis and serum-AMH. Thirty-three patients with early breast cancer were enrolled into the study. Nineteen patients had HER2/neu negative cancer and were treated with chemotherapy and 14 had HER2/neu positive cancer and were treated with chemotherapy and trastuzumab. In all patients, AMH levels declined to undetectable values immediately post-treatment, but regained for 57.1% of the HER2/neu positive cohort and 36.8% of the negative cohort ( Our results indicate that trastuzumab may alleviate chemotherapy-induced ovarian toxicity that may be mediated via its effect on ovarian vasculature.
Sections du résumé
BACKGROUND
BACKGROUND
Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, is considered a standard treatment in addition to chemotherapy in the adjuvant setting for HER2/neu-positive breast cancer, yet its impact on fertility and ovarian reserve remains obscure. We aimed to study the effect of anti-HER2/neu on chemotherapy-induced ovarian toxicity in both clinical and preclinical settings.
METHODS
METHODS
We prospectively enrolled breast cancer patients below the age of 42 years who were treated with chemotherapy with or without trastuzumab into the study. Anti-Müllerian hormone (AMH) was measured 6 and 12 months post-chemotherapy as an ovarian reserve indicator. In the animal model, pubertal mice were injected with cyclophosphamide or paclitaxel with or without anti-HER2/neu, or saline, and sacrificed 1 week or 3 months later. Ovarian apoptosis, proliferation and vascularity were measured by immunohistochemistry and ovarian reserve was measured by morphometric analysis and serum-AMH.
RESULTS
RESULTS
Thirty-three patients with early breast cancer were enrolled into the study. Nineteen patients had HER2/neu negative cancer and were treated with chemotherapy and 14 had HER2/neu positive cancer and were treated with chemotherapy and trastuzumab. In all patients, AMH levels declined to undetectable values immediately post-treatment, but regained for 57.1% of the HER2/neu positive cohort and 36.8% of the negative cohort (
CONCLUSIONS
CONCLUSIONS
Our results indicate that trastuzumab may alleviate chemotherapy-induced ovarian toxicity that may be mediated via its effect on ovarian vasculature.
Identifiants
pubmed: 33297351
pii: biomedicines8120577
doi: 10.3390/biomedicines8120577
pmc: PMC7762209
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Israel Science Foundation
ID : 1816/13
Références
Am J Physiol. 1999 Dec;277(6):H2205-11
pubmed: 10600838
Fertil Steril. 2011 Apr;95(5):1535-43
pubmed: 21272867
Breast Cancer Res Treat. 2015 Jun;151(3):589-96
pubmed: 25981899
Endocrinology. 2015 Oct;156(10):3818-27
pubmed: 26252060
Oncotarget. 2018 Mar 23;9(22):15931-15941
pubmed: 29662617
Cancer Cell. 2010 Aug 9;18(2):160-70
pubmed: 20708157
Cancer Chemother Pharmacol. 2009 Jan;63(2):219-28
pubmed: 18365198
PLoS One. 2013 Sep 20;8(9):e75157
pubmed: 24073244
Oncotarget. 2019 Jan 29;10(9):926-929
pubmed: 30847021
Biomed Opt Express. 2014 Jun 16;5(7):2247-61
pubmed: 25071962
Int J Gynaecol Obstet. 2015 Oct;131 Suppl 1:S36-9
pubmed: 26433503
Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12492-7
pubmed: 25114230
Hum Reprod. 2015 May;30(5):1089-101
pubmed: 25796551
Mol Hum Reprod. 2015 Dec;21(12):885-93
pubmed: 26443807
PLoS One. 2011;6(9):e23492
pubmed: 21931602
Oncologist. 2015 Sep;20(9):985-91
pubmed: 26099742
Cancer Immunol Immunother. 2011 Mar;60(3):339-48
pubmed: 21086124
Clin Cancer Res. 2005 Mar 1;11(5):2008-17
pubmed: 15756027