Is breast cancer risk the same for all progestogens?
The population-based case–control study CECILE investigated the impact of various menopausal hormone therapy (MHT) products on breast cancer (BC) risk in 1,555 postmenopausal women [1]. The case group (n = 739) included incident cases of in situ (!) or invasive BC in postmenopausal women. The control group (n = 816) included women from the general population within predefined quotas by age and socio-economic status (SES). While quotas by age were applied to obtain similar distributions by age among controls and among cases, quotas by SES in control women were applied to reflect the distribution by SES of women in the general population in the study area. Data of participants were obtained by a structured questionnaire during in-person interviews, and from pathology reports if applicable, respectively. Women were divided into current and past MHT user. MHTs were classified in estrogen-only therapy (ET), estrogen combined with progestin therapy (EPT) and tibolone. EPT was subdivided in three subtypes according to the progestogen constituent: natural micronized progesterone, progesterone derivatives, and testosterone derivatives. In comparison to never MHT users, any current or past MHT use (ET, EPT, tibolone) was not associated with an increased BC risk. However, in subanalysis BC risk was significantly increased for current use of EPT for 4 or more years (n = 73 cases and n = 56 controls, adjusted OR 1.55; 95 % CI 1.02–2.36). Within the group of current EPT users for 4 or more years, 14 cases had used estrogens combined with micronized progesterone (n = 17 controls), and 55 a combination with a synthetic progestogen (n = 34 controls), respectively. Compared to never MHT use, current use of EPT containing a synthetic progestogen for 4 or more years was associated with a significantly increased BC risk (adjusted OR 2.07; 95 % CI 1.26–3.39), but EPT containing micronized progesterone was not (adjusted OR 0.79; 95 % CI 0.37–1.71). 73 % of current MHT users started treatment within the first year of onset of menopause. Early EPT (n = 52 cases and n = 38 controls, adjusted OR 1.65; 95 % CI 1.02–2.69), but not early ET, starters had a significantly higher BC risk compared to never MHT users. In contrast, MHT initiation beyond 1 year after menopause was not associated with an increased BC risk. The authors concluded that: (1) ET and EPT containing natural progesterone did not increase BC risk whereas, (2) BC risk was increased in users of tibolone or EPT containing a synthetic progestogen, respectively, and that (3) MHT use early after onset of menopause was associated with an increased BC risk as compared to women who delay MHT beyond 1 or more years.
Department of Obstetrics and Gynecology, University of Berne, Bern, Switzerland, petra.stute@insel.ch.
Petra
P
Stute
D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced*; D016022:Case-Control Studies; D004967:Estrogens / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011372:Progestins / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012306:Risk; D011795:Surveys and Questionnaires; D013997:Time Factors
D004967:Estrogens; D011372:Progestins