Significato degli estrogeni
circolanti nel carcinoma
della mammella
Alfredo Berruti
Oncologia Medica
Dipartimento di Scienze Cliniche e
Biologiche
Università di Torino
Azienda Ospedaliera San Luigi
di Orbassano
Oestrogen levels in tissues such as the breast are higher
than those in serum and levels in malignant tissue are
higher
than 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
Dowsett M et al 2007
some uptake from the circulation.
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. 2008;17(3):614-20
[Cancer Res 2007;67(5):2062–71
Conclusioni
Livelli elevati di estrogeni circolanti
1) Aumentano l’incidenza
2) Condizionano il fenotipo
3) Influenzano la prognosi
dei carcinomi mammari umani
Problemi di dosaggio:
Modalità di conservazione
Variabilità inter-laboratorio
Inaffidabilità dei dosaggi per valori molto bassi
Limitano l’impego clinico di questo parametro