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 : 25 - 60 % 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) 151 - 157

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) 159 - 164

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. 12-14)• 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) 717 - 722

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 : 1817 - 26

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

- 2003 : nog geen definitieve uitspraak

hieromtrent

Mammographic breast density as a biomarker of effects of isoflavones on the female breast.

Breast Cancer Res 2002, 4 : 1 - 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