Auswirkungen unterschiedlicher Hormon-Ersatz-Therapielinien auf die mammographische Dichte

Studien haben gezeigt, dass die Brustdichte mit dem Brustkrebsrisiko in Zusammenhang steht. Die Brustdichte ist ein spezialisierter und starker Prädiktor zur Abschätzung des Brustkrebsrisikos. Die Weiterentwicklung der Mammographietechnik durch digitale Bildverarbeitung, wodurch die Brustdichte im...

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Bibliographic Details
Main Author: Rieger, Philipp
Contributors: Wagner, Uwe (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2016
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Studies have shown that breast density is related to the risk of breast cancer in women. Mammography technology with digital image processing to measure breast density can always be improved, and with the implementation of social networks leads to a great social and scientific progress in the early detection of breast cancer. The subject of our study was to examine changes in the ACR-Score in women under two frequently used hormonal therapies after a 24 month treatment. The other objectives were to examine whether the ACR change depends on the hormonal treatment and whether the ACR-Score change depends on the baseline value. In our study, breast density was measured before (baseline) taking either of the hormonal therapies Activelle® and Tibolon, and after 24 months of continuous use by 32 women. Activelle® is a continuous-combined estrogen-progestogen preparation. It consists of 1 mg estradiol (E2) and 0.5 mg norethisterone acetate (NETA). Estrogen-progestin combination drugs lead to an appreciable increase in density of mammary parenchymal cells compared with pure estrogens. The influence of breast density takes place on a pathophysiological level. There is a change in endogenous collagen, epithelial cells and adipose tissue. Therefore the sensitivity of mammography can be limited. Tibolon is a representative of the class of substance STEAR (selective tissue estrogenic activity regulator) and is converted by its metabolism to 3 active metabolites that have estrogenic, progestogenic and androgenic characteristics. As a result a proliferation of mammary gland tissue does not take place. Clinical and experimental studies describe that Tibolon leads to no significant increase in breast density. The statement of mammography is therefore not impeded. The assessment of breast density was made by two independent physicians. The classification of breast density was carried out according to ACR type. All variables in our study were statistically evaluated. Basic parameters were age, height, weight, BMI, age at menarche, menopausal status, smoking and ACR type. All parameters were statistically distributed normally. There were no significant differences between the groups at the beginning of the study. The average age of the subjects was about 7 years below the known average menopause age. The influence of endogenous hormones may therefore be regarded as low. The BMI was measured with an average of 25.8, menarche occurred on average at 13.6 years of age and the average ACR-type was II. Approximately one-third of the patients were smokers. After 24 months of hormone therapy, approximately 30% of women showed an increase in breast density under each treatment regime (31.3% in the Activelle®- and 31.3% in the Tibolon group). We see an increase in breast density among patients undergoing Activelle® hormone therapy between 5.2 to 12.7% (mean 8.9%). This corresponds to the results of previous literature. Under Tibolon breast density increases by 12.1%. According to previous studies Tibolon increases mammographic breast density significantly less than a traditional hormone therapy. The increase in breast density in our study was significant in both groups. Our use of a longer study protocol (24 months) compared to previous publications (6 and 12 months) may be a cause for the observed increase in breast density among Tibolon in our study. Tibolon represents an alternative to traditional hormone therapy during treatment of climacteric complaints of postmenopausal women. According to previous studies the advantage of Tibolon was the fact that it did not cause to a significant increase in breast density during treatment. The sensitivity of mammography was not restricted. Therefore, in recent years, women with increased breast cancer risk (familial breast cancer, women who are themselves suffering from breast cancer) were preferably treated with Tibolon. However, particular concerns exist over Tibolon therapy after the publication of the LIBERATE trial, which was terminated early due to increased incidence of breast cancer recurrences. In our study results, we see in healthy women a significant increase in breast density under prolonged intake of Tibolon. Whether this would have led to an increase in the number of women who develop breast cancer, has not been tested in the small number of women in our study. Long-term studies with larger numbers of patients and longer treatment durations are needed to prove a breast density change under the applied hormone therapy regimens to estimate an associated breast cancer risk better. Breast cancer risk by a possible increase in breast density during long-term use of Tibolon needs to be reassessed particularly. A more accurate, objective measurement of breast density is needed. The subjective assessment of mammographic density by 2 independent observers may be replaced in the next few years by improving the technology to assess mammographic breast density by fully automatic precise measurements. There is still a great need for research.