PMID- 25655898
OWN - NLM
STAT- MEDLINE
DCOM- 20170124
LR  - 20240330
IS  - 1880-4233 (Electronic)
IS  - 1340-6868 (Print)
IS  - 1340-6868 (Linking)
VI  - 23
IP  - 3
DP  - 2016 May
TI  - A randomized controlled study evaluating safety and efficacy of leuprorelin 
      acetate every-3-months depot for 2 versus 3 or more years with tamoxifen for 5 
      years as adjuvant treatment in premenopausal patients with endocrine-responsive 
      breast cancer.
PG  - 499-509
LID - 10.1007/s12282-015-0593-z [doi]
AB  - BACKGROUND: Luteinizing hormone-releasing hormone (LH-RH) agonists provide 
      effective adjuvant treatment for premenopausal women with endocrine-responsive 
      breast cancer. Here, we investigated appropriate treatment durations of an LH-RH 
      agonist, leuprorelin. METHODS: We conducted an open-label, randomized controlled 
      pilot study to evaluate the safety and efficacy of leuprorelin subcutaneously 
      administered every-3-months for 2 versus 3 or more, up to 5 years, together with 
      daily tamoxifen for 5 years in premenopausal endocrine-responsive breast cancer 
      patients. Primary endpoints were disease-free survival (DFS) and safety. RESULTS: 
      Eligible patients (N = 222) were randomly assigned to receive leuprorelin for 
      either 2 years (N = 112) or 3 or more years (N = 110) with tamoxifen for 5 years 
      after surgery. Leuprorelin treatment for 3 or more years provided no significant 
      difference in DFS rate over 2 years: 94.1 versus 91.8 % at 144 weeks (3 years) 
      after the second year (week 96) and 90.8 versus 90.4 % at the fifth year (week 
      240). The overall survival rate was 100 % for both groups during the third 
      through fifth year study period. There were no significant differences in the 
      incidence of adverse events (AEs) between the 2 groups: most AEs were rated grade 
      1 or 2. CONCLUSIONS: Adjuvant leuprorelin treatment for 3 or more years with 
      tamoxifen showed a survival benefit and safety profile similar to that for 2 
      years in premenopausal endocrine-responsive breast cancer patients. No new safety 
      signal was identified for long-term leuprorelin treatment. Longer follow-up 
      observation is needed to determine the optimal duration of leuprorelin treatment.
FAU - Shiba, Eiichi
AU  - Shiba E
AD  - Department of Breast Surgery, Osaka Breast Clinic, 1-3-4 Fukushima, Fukushima-ku, 
      Osaka, 553-0003, Japan. eshiba@goo.jp.
FAU - Yamashita, Hiroko
AU  - Yamashita H
AD  - Department of Breast and Endocrine Surgery, Nagoya City University Hospital, 
      Nagoya, Japan.
AD  - Department of Breast Surgery, Hokkaido University Hospital, Sapporo, Japan.
FAU - Kurebayashi, Junichi
AU  - Kurebayashi J
AD  - Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, 
      Japan.
FAU - Noguchi, Shinzaburo
AU  - Noguchi S
AD  - Department of Breast and Endocrine Surgery, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Iwase, Hirotaka
AU  - Iwase H
AD  - Department of Breast and Endocrine Surgery, Kumamoto University, Kumamoto, Japan.
FAU - Ohashi, Yasuo
AU  - Ohashi Y
AD  - Department of Integrated Science and Engineering for Sustainable Society, Chuo 
      University, Tokyo, Japan.
FAU - Sasai, Kiyofumi
AU  - Sasai K
AD  - Takeda Pharmaceutical Company Limited, Osaka, Japan.
FAU - Fujimoto, Tsukasa
AU  - Fujimoto T
AD  - Takeda Pharmaceutical Company Limited, Osaka, Japan.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150206
PL  - Japan
TA  - Breast Cancer
JT  - Breast cancer (Tokyo, Japan)
JID - 100888201
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 4TI98Z838E (Estradiol)
RN  - EFY6W0M8TG (Leuprolide)
SB  - IM
MH  - Adult
MH  - Antineoplastic Agents, Hormonal/administration & dosage/adverse 
      effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Bone Density/drug effects
MH  - Breast Neoplasms/*drug therapy/mortality
MH  - Chemotherapy, Adjuvant/methods
MH  - Disease-Free Survival
MH  - Estradiol/blood
MH  - Female
MH  - Humans
MH  - Leuprolide/administration & dosage/adverse effects/*therapeutic use
MH  - Middle Aged
MH  - Premenopause
MH  - Survival Rate
MH  - Tamoxifen/administration & dosage/adverse effects
MH  - Treatment Outcome
PMC - PMC4839052
OTO - NOTNLM
OT  - Adjuvant endocrine therapy
OT  - Disease-free survival (DFS)
OT  - Leuprorelin acetate
OT  - Premenopausal endocrine-responsive breast cancer
OT  - Safety
EDAT- 2015/02/07 06:00
MHDA- 2017/01/25 06:00
PMCR- 2015/02/06
CRDT- 2015/02/07 06:00
PHST- 2014/11/13 00:00 [received]
PHST- 2015/01/26 00:00 [accepted]
PHST- 2015/02/07 06:00 [entrez]
PHST- 2015/02/07 06:00 [pubmed]
PHST- 2017/01/25 06:00 [medline]
PHST- 2015/02/06 00:00 [pmc-release]
AID - 10.1007/s12282-015-0593-z [pii]
AID - 593 [pii]
AID - 10.1007/s12282-015-0593-z [doi]
PST - ppublish
SO  - Breast Cancer. 2016 May;23(3):499-509. doi: 10.1007/s12282-015-0593-z. Epub 2015 
      Feb 6.