Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies.
BACKGROUND
The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS).


METHODS
A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models.


RESULTS
A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I(2) = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I(2) = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I(2) = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I(2) = 68.0%, Pheterogeneity = 0.044).


CONCLUSIONS
Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.
Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino-IST, Genova.
M
M
Lambertini
Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova.
M
M
Ceppi
Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino-IST, Genova.
F
F
Poggio
Fertility and Procreation Unit, Gynecologic Oncology Department, European Institute of Oncology, Milan, Italy.
F A
FA
Peccatori
BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
H A
HA
Azim
Department of Internal Medicine, University of Genoa, Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova, Italy.
D
D
Ugolini
Department of Medical Oncology, U.O. Oncologia Medica 2, IRCCS AOU San Martino-IST, Genova.
P
P
Pronzato
German Breast Group (GBG), Neu-Isenburg Sana-Klinikum Offenbach, Offenbach am Main, Germany.
S
S
Loibl
Cleveland Clinic Foundation, Taussig Cancer Institute, Cleveland.
H C F
HC
Moore
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
A H
AH
Partridge
Unit of Clinical Epidemiology, IRCCS AOU San Martino-IST, Genova.
P
P
Bruzzi
Department of Medical Oncology, U.O. Sviluppo Terapie Innovative, IRCCS AOU San Martino-IST, Genova, Italy lucia.delmastro@hsanmartino.it.
L
L
Del Mastro
D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D005260:Female; D005298:Fertility / Q000187:drug effects* / Q000502:physiology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000378:metabolism; D006801:Humans; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic / Q000379:methods*
D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone
breast cancer; fertility preservation; luteinizing hormone-releasing hormone agonists; ovarian function preservation; premenopausal patients