Incidences of breast cancer throughout long-term hormone replacement therapy.
OBJECTIVE
To report the main incidences related to diagnosis of breast cancer in a randomly selected cohort population of women treated with conjugated equine estrogens (CEE), always in conjunction with the opposed progestin, medroxy progesterone acetate (MPA) throughout prolonged oral administration.


METHODS
One hundred and seventy-eight women were subsequently studied before and during the treatment (cohort study). The profile of studied patients included family and personal histories, gynecological and breast examinations, basal hormonal levels, bone mass concentration (BMC) as well as total cholesterol levels and their fractions. The usual clinical cut off age was applied at the beginning of treatment according to following criteria: (a) women less than 60 years old (91.60%), and (b) women more than 60 years old (8.40%), by assuming that a primary protective effect of HRT might be lost or diminished after surpassing this age threshold. In all the treated women were thoroughly advised about the importance of diet, exercises and self-determination. Both oral CEE 0.625 mg/daily and either 2.5 mg/daily or 5 mg/daily of MPA were administrated in accordance with The American Fertility Society Meeting after 1995 (Seattle) recommendations, following two patterns: (1) cycles or perimenopausal women: from days 1 to 25, and (2) postmenopausal women, from Monday to Friday. No other specific treatments were prescribed. Statistical analysis was performed by using SPSS 12.0 and G-stat 2.0.


RESULTS
Evaluation of basal hormonal levels, BMC, cholesterol levels and their fractions were not included in the current study. Data from the statistical analysis of 178 treated women were as follow: mean duration of treatment 8.06 years for all women; in the younger age group 7.97, and in the older age group 9.04. Total of 1405.5 woman-years of follow-up, 119 women for more than 5 years (66.85%), and more times (68.18%) with CEE plus MPA 5 mg/daily regime. Dropouts occurred in 34 women (19.10%). Main incidences: no deaths occurred during the treatment. Four cardiovascular events (2.24%) were reported. No spontaneous bone fractures were documented. Nonetheless, there were 11 bone fractures of traumatic origin (6.17%), none of them hip fractures. Four breast cancer. Likewise, one diagnosis of breast cancer in each of 45 treated women from our series was evidenced. One hundred and twenty-one women (67.97%) without incidences.


CONCLUSIONS
In our cohort study advices on diet, exercises and self-determination were reinforced for 1405.5 woman-years of follow-up. Combined CEE plus MPA for more than 5 years are no more risk related to breast cancer and cardiovascular events versus shorter treatments. Long-term CEE plus MPA were well tolerated and we did not find statistical evidence which would allow deducing higher rates of morbidity in those entities. Likewise, no deaths were document during the treatments.
Cortés-Prieto
J
J
Medical School, University of Alcalá, C/ General Moscardo, no. 39, 28020 Madrid, Spain. jcortesp@sego.es
Juez-Martel
P
P
D000328:Adult; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005732:Gangliosides; D006801:Humans; D015994:Incidence; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D013997:Time Factors
D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP); D005732:Gangliosides; C056352:2-3-N-acetylneuraminyl-1-3-galactosyl-1-3-N-acetylglucosyl-1-4-galactosyl-1-glucosylceramide; D017258:Medroxyprogesterone Acetate