Additional value of the 70-gene signature and levels of ER and PR for the prediction of outcome in tamoxifen-treated ER-positive breast cancer.
BACKGROUND
Breast cancer patients with node positive disease can have an excellent outcome with tamoxifen only. It is unclear whether analysing both the 70-gene signature and hormone receptors provides superior prediction of outcome in tamoxifen-treated patients than either alone.


METHODS
Three series were evaluated: 121 patients (81% node positive) received adjuvant tamoxifen, 151 patients did not receive tamoxifen (10% node positive) and 92 patients received tamoxifen for metastatic disease. The 70-gene signature was analysed using MammaPrint. Oestrogen receptor (ER) and progesterone receptor (PR) immunohistochemistry was evaluated following St. Gallen Consensus (Highly Endocrine Responsive: ER and PR ≥ 50%, Incompletely Endocrine Responsive: ER and/or PR low or either one absent).


RESULTS
In patients treated with adjuvant tamoxifen, both the 70-gene signature (adjusted for Endocrine Response Categories HR 2.17, 95%CI 1.01-4.66) as well as the Endocrine Response Categories (adjusted for 70-gene signature HR 6.35, 95%CI 1.90-21.3) were associated with breast-cancer-specific-survival (BCSS). Also in patients treated with tamoxifen for metastatic disease, combined analysis of the 70-gene signature and ER/PR revealed additional value (multivariate Cox regression, p = 0.013). In patients who did not receive tamoxifen, only the 70-gene signature was associated with outcome.


CONCLUSIONS
In the series analysed, the 70-gene signature was mainly a prognostic factor, while ER and PR levels were mainly associated with outcome after tamoxifen. Combination of these three factors may improve outcome prediction in tamoxifen-treated patients.
Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
M
M
Kok
R H
RH
Koornstra
S
S
Mook
M
M
Hauptmann
R
R
Fles
M P
MP
Jansen
E M
EM
Berns
S C
SC
Linn
L J
LJ
Van 't Veer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen