Alfredo BerrutiOncologia Medica

Dipartimento di Scienze Cliniche e Biologiche

Università di TorinoAzienda Ospedaliera San Luigi

di Orbassano

Significato degli estrogenicircolanti nel carcinoma della mammella

Oestrogen levels in tissues such as the breast are higherthan those in serum and levels in malignant tissue are higherthan those in normal breast.

Postmenopausal breast tissue is able to maintain concentrations of oestradiol comparable with those in premenopausal breast tissue and 10–20 times higher than in plasma. The level of oestradiol in tissues is a consequence of the cumulative effect of the activities of the key enzymes involved in steroidogenesis within the tissue together with some uptake from the circulation.

Dowsett M et al 2007

J Natl Cancer Inst 2002;94:606–16

RESULTS

The relative risk of breast cancer associated with mammographic density (RR for highest quartile compared with lowest quartile = 3.8, 95% CI = 2.2 to 6.6; P trend <.001) changed little when the analysis was adjusted for circulating estradiol (RR = 3.9, 95% CI = 2.2 to 6.9; P trend <.001) or circulating testosterone (RR = 4.1, 95% CI = 2.3 to 7.2; P trend <.001).

Circulating levels of estradiol (RR = 2.4, 95% CI = 1.4 to 4.0) and of testosterone (RR = 2.0, 95% CI = 1.2 to 3.1) were both associated with breast cancer risk, before and after adjustment for mammographic density.

In a joint analysis of mammographic density and plasma testosterone, the risk of breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both (RR = 6.0, 95% CI = 2.6 to 14.0).

A similar pattern was observed in the joint analysis of estradiol and mammographic density (RR = 4.1, 95% CI = 1.7 to 9.8).

J Natl Cancer Inst 2007;99: 1178 – 87

J Natl Cancer Inst 2007;99: 1178 – 87

J Natl Cancer Inst 2006; 98: 1406 – 15

Circulating oestradiol levels may not correlate

directly with tissue concentrations but are still a useful,

accessible, overall indicator of metabolism in the peripheral

tissues and are becoming increasingly important in epidemiology

and breast cancer care management.

It is possible that those at increased risk of developing breast cancer by virtue of high oestradiol levels might benefit from endocrine chemoprevention.

However to incorporate oestradiol levels into risk algorithms for breast cancer, a clear picture is needed of which factors influence (i) normal physiological oestrogen levels in this group and (ii) the measurement of such levels.

JAMA. 2006;296:193-201

JAMA. 2003;289:3243-3253

JAMA. 2006;295:1647-1657

J Clin Oncol 21:4314-4321. 2003

Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer.

In 153 case-control pairs of perimenopausal and postmenopausal women women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis:

Total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence.

Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05).

Rock CL et al Cancer Epidemiol Biomarkers Prev. Rock CL et al Cancer Epidemiol Biomarkers Prev. 2008;17(3):614-202008;17(3):614-20

[Cancer Res 2007;67(5):2062–71]

Livelli elevati di estrogeni circolanti1) Aumentano l’incidenza 2) Condizionano il fenotipo3) Influenzano la prognosidei carcinomi mammari umani

Problemi di dosaggio:Modalità di conservazioneVariabilità inter-laboratorioInaffidabilità dei dosaggi per valori molto bassiLimitano l’impego clinico di questo parametro

Conclusioni