Time-dependent relevance of steroid receptors in breast cancer.
OBJECTIVE
To analyze the time-dependent prognostic role of the investigated variables, considered, when appropriate, on a continuous scale, for the purpose of evaluating and describing the interrelationships between clinically relevant patient and tumor characteristics (age, size and histology, and estrogen receptor [ER] and progesterone receptor content) and the risk of new disease manifestation.


METHODS
We applied a flexible statistical model to a case series of 1,793 patients with axillary lymph node-negative breast cancer with a minimal potential follow-up of 10 years. To avoid a potential confounding effect of adjuvant treatment, only patients given local-regional therapy until relapse were considered.


RESULTS
ER content and tumor size (adjusted for all the other covariates) showed a time-dependent relationship with the risk of new disease manifestations. In particular, ER content failed to show a prognostic effect within the first years of follow-up; thereafter, a positive association with risk of relapse was observed. For tumor size, within the first years of follow-up, the risk of relapse was directly related to size for only tumors up to 2.5 cm in diameter; thereafter, the impact on prognosis progressively decreased.


CONCLUSIONS
The availability of a long follow-up on a large breast cancer series, as well as the use of innovative statistical approaches, allowed us to explore the functional relation between steroid receptors and clinical outcome and to generate a hypothesis on the involvement of ER in favoring long-term metastasis development.
Coradini
D
D
Unità Operativa Determinanti Biomolecolari nella Prognosi e Terapia, Milan, Italy. coradini@istitutotumori.mi.it
Daidone
M G
MG
Boracchi
P
P
Biganzoli
E
E
Oriana
S
S
Bresciani
G
G
Pellizzaro
C
C
Tomasic
G
G
Di Fronzo
G
G
Marubini
E
E
D000328:Adult; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016013:Likelihood Functions; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D011987:Receptors, Steroid; D013997:Time Factors
D011987:Receptors, Steroid