Menopauze en borst Menopauze oestrogenen oestrogenenstimulatie ter hoogte van borst klierweefsel en steunweefsel en vetweefsel

Hormonen en borst (zie fig. 21.2) oestrogenen cortisol ductale groei groeihormoon prolactine lobulaire en alveolaire groei oestrogenen progesterone volwassen borstont- prolactine wikkeling groeihormoon

HRT en borst HRT borstinvolutie toename aantal ducti interlobulair steunweefsel nieuwe lobulivorming

Mammografische screening Borstkanker mortaliteit HRT mammografische densiteit sensitiviteit RX screening specificiteit RX screening

Mammographic density and breast cancer May obscure a small malignant lesion can be itself one of the signs of malignancy (high-density mammographic pattern is an independent risk factor for breast cancer)

Mammographic Density Assessment (Tabar-Dean) I - normal fibroglandular tissue with partial fatty replacement II - entirely fatty breast III - retroareolar periductal fibrosis IV - nodular structures with increased amount of periductal tissue V - homogenous fibrosis with unstructured ground-gloss appearance

Mammographic Density Assessment (Wolfe) N1 - normal breast tissue composed primarily of fat P1 - prominent ductal pattern in up to 25 % of breast volume P2 - prominent ductal pattern in > 25 % of breast volume DY - extremely dense parenchyma denoting possible connective tissue hyperplasia

Mammographic Density Assessment (Nottingham) Normal glandular dysplasia (light, moderate, severe) prominent ducts indeterminate

Mammografische densiteit (screeningsmammo in België) Type 1 : diffuus helder lipomateus weefsel type 2 : < 25 % dens weefsel type 3 : % dens weefsel type 4 : > 60 % dens weefsel

Mammographic density increase in women receiving different hormone replacement regimens. C.T. Ezel et al. Maturitas 40 (2001) Increase in mammographic density : continuous combined HRT ERT cyclic combined HRT tibolone (retrospective comparative study in 100 women during 4 years)

Effects of different types of HRT on mammographic density N. Colacurci et al. Maturitas 40 (2001) Increase in mammographic density : 43 % continuous combined HRT 35 % cyclic combined HRT 21 % ERT 10 % Tibolone 0 % controlegroep (100 patients with 1 year follow-up)

Maximale mitotische activiteit Endometrium : late follicularie fase (dd ) borst : late luteale fase (dd. 25) : maximale progesteronemie hypothese : progesterone in combinatie met de luteale fase oestradiol peak kan de mitotische activiteit ter hoogte van borstklierweefsel stimuleren en het borstkankerrisico doen toenemen (?)

Oestrogen and progesterone both stimulate breast cell division. However, the mitotic rate of breast cells is higher during the luteal phase of the menstrual cycle than during the follicular phase, suggesting that progesterone and estrogen together induce more mitoses than estrogen alone. Stromal edema is also greatest in the second half of the cycle, indicating the progesterone effect.

Cave : recent evidence suggests that progesterone is mitogenic in the breast, but the effects of progesteron may differ according to dosage, duration of exposure, and the estrogenic environment

Effects of tibolone and continuous combined HRT on mammographic breast density E. Lundström et al. Am J Obstet Gynecol 186 (2002) Increase in mammographic density : 48 % continuous combined HRT (estradiol 2 mg/ Neta 1 mg) 4 % tibolone (2.5 mg) 0 % controlegroep (placebo) (166 patients with 6 months follow-up)

Tibolone and breast = no stimulation of breast tissue = in cell cultures of normal and transformed breast epitelial cells, tibolone inhibits proliferation and stimulates apoptosis. = tibolone inhibits local sulfatase activity within the breast and may hereby reduce the formation of biologically active estrogenic compounds.

Tibolone and breast cancer risk = no human studies about this association = tibolone markedly inhibits breast all proliferation in both human and animal tissue studies = tibolone safe alternative for HRT in women with a high risk of breast cancer ??

Estrogen Replacement Therapy for menopausal women with a history of breast carcinoma. Results of a 5-year, prospective study Cancer 2002 ; 95 : ERT did not compromise disease free survival in select patients who were treated previously for localized breast carcinoma. Larger scale randomized trials are needed to confirm these findings.

Fyto-oestrogenen en de borst - mogelijks gunstig effect op de preventie of het verloop van borstkanker - werkingsmechanisme : onbekend : nog geen definitieve uitspraak hieromtrent

Mammographic breast density as a biomarker of effects of isoflavones on the female breast. Breast Cancer Res 2002, 4 : = Serms : breast density = Isoflavones : breast density = or (??? more studies !)

Phytoestrogens and Breast cancer risk = phytooestrogens =natural plant substances = three main classes : - isoflavones (genistein, daidzein,…) - coumestans - lignans = anticarcinogenic potential ? = significant estrogenic properties = no protective effect on breast cancer risk (prospective studies) = exception : phytoestrogens at adolescence phytoestrogens at very high doses = few prospective studies