Menopausal hormone therapy and breast cancer risk: impact of different treatments. The European Prospective Investigation into Cancer and Nutrition.
Menopausal hormone therapy (MHT) is characterized by use of different constituents, regimens and routes of administration. We investigated the association between the use of different types of MHT and breast cancer risk in the EPIC cohort study. The analysis is based on data from 133,744 postmenopausal women. Approximately 133,744 postmenopausal women contributed to this analysis. Information on MHT was derived from country-specific self-administered questionnaires with a single baseline assessment. Incident breast cancers were identified through population cancer registries or by active follow-up (mean: 8.6 yr). Overall relative risks (RR) and 95% confidence interval (CI) were derived from country-specific Cox proportional hazard models estimates. A total of 4312 primary breast cancers were diagnosed during 1,153,747 person-years of follow-up. Compared with MHT never users, breast cancer risk was higher among current users of estrogen only (RR: 1.42, 95% CI 1.23-1.64) and higher still among current users of combined MHT (RR: 1.77, 95% CI 1.40-2.24; p = 0.02 for combined vs. estrogen-only). Continuous combined regimens conferred a 43% (95% CI: 19-72%) greater risk compared with sequential regimens. There was no significant difference between progesterone and testosterone derivatives in sequential regimens. There was no significant variation in risk linked to the estrogenic component of MHT, neither for oral vs. cutaneous administration nor for estradiol compounds vs. conjugated equine estrogens. Estrogen-only and combined MHT uses were associated with increased breast cancer risk. Continuous combined preparations were associated with the highest risk. Further studies are needed to disentangle the effects of the regimen and the progestin component.
Department of Community Medicine, University of Tromsø, Tromsø, Norway. kjersti.bakken@uit.no
Kjersti
K
Bakken
Agnès
A
Fournier
Eiliv
E
Lund
Marit
M
Waaseth
Vanessa
V
Dumeaux
Françoise
F
Clavel-Chapelon
Alban
A
Fabre
Bertrand
B
Hémon
Sabina
S
Rinaldi
Véronique
V
Chajes
Nadia
N
Slimani
Naomi E
NE
Allen
Gillian K
GK
Reeves
Sheila
S
Bingham
Kay-Tee
KT
Khaw
Anja
A
Olsen
Anne
A
Tjønneland
Laudina
L
Rodriguez
Maria-José
MJ
Sánchez
Pilar Amiano
PA
Etxezarreta
Eva
E
Ardanaz
Maria-José
MJ
Tormo
Petra H
PH
Peeters
Carla H
CH
van Gils
Annika
A
Steffen
Mandy
M
Schulz
Jenny
J
Chang-Claude
Rudolf
R
Kaaks
Rosario
R
Tumino
Valentina
V
Gallo
Teresa
T
Norat
Elio
E
Riboli
Salvatore
S
Panico
Giovanna
G
Masala
Carlos A
CA
González
Franco
F
Berrino
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology; D003718:Denmark / Q000453:epidemiology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005060:Europe / Q000453:epidemiology; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D005858:Germany / Q000453:epidemiology; D006115:Greece / Q000453:epidemiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009664:Norway / Q000453:epidemiology; D017698:Postmenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries / Q000706:statistics & numerical data*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D011795:Surveys and Questionnaires; D013548:Sweden / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology