Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France.
BACKGROUND
There is extensive epidemiological evidence that menopausal hormone therapy (MHT) increases breast cancer risk, particularly combinations of estrogen and progestagen (EP). We investigated the effects of the specific formulations and types of therapies used by French women. Progestagen constituents, regimen (continuous or sequential treatment by the progestagen), and time interval between onset of menopause and start of MHT were examined.


METHODS
We conducted a population-based case-control study in France in 1555 menopausal women (739 cases and 816 controls). Detailed information on MHT use was obtained during in-person interviews. Odds ratios and 95% confidence interval adjusted for breast cancer risk factors were calculated.


RESULTS
We found that breast cancer risk differed by type of progestagen among current users of EP therapies. No increased risk was apparent among EP therapy users treated with natural micronized progesterone. Among users of EP therapy containing a synthetic progestin, the odds ratio was 1.57 (0.99-2.49) for progesterone-derived and 3.35 (1.07-10.4) for testosterone-derived progestagen. Women with continuous regimen were at greater risk than women treated sequentially, but regimen and type of progestagen could not be investigated independently, as almost all EP combinations containing a testosterone-derivative were administered continuously and vice-versa. Tibolone was also associated with an increased risk of breast cancer. Early users of MHT after onset of menopause were at greater risk than users who delayed treatment.


CONCLUSIONS
This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone, frequently prescribed in France, was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.
Inserm (Institut National de la Santé et de la Recherche Médicale), CESP (Centre de recherche en Epidémiologie et Santé des Populations), Unit 1018, Villejuif, France ; University Paris-Sud, UMRS 1018, Villejuif, France.
Emilie
E
Cordina-Duverger
Thérèse
T
Truong
Antoinette
A
Anger
Marie
M
Sanchez
Patrick
P
Arveux
Pierre
P
Kerbrat
Pascal
P
Guénel
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D011372:Progestins / Q000009:adverse effects* / Q000627:therapeutic use; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors
D004967:Estrogens; D011372:Progestins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone