Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status.
BACKGROUND
Most women with oestrogen receptor (ER) positive primary breast cancer receive adjuvant tamoxifen after surgery. The measurement of tumour biomarkers should allow better selection of patients for such treatment or for therapies such as aromatase inhibitors.


METHODS
Histopathological blocks of primary breast cancer patients who had been randomized to receive 2-years tamoxifen or no adjuvant therapy in two mature randomised clinical trials were retrieved. Immunohistochemical staining for ER, progesterone receptor (PgR), HER2 and epidermal growth factor receptor (EGFR) was undertaken. The primary endpoint was relapse free survival.


RESULTS
813 patients were included in the study. Benefit from tamoxifen was seen in ER-positive patients [Relative risk (rr) 0.77, ci 0.63-0.93]. ER-negative patients also showed a strong trend to benefit from tamoxifen (rr 0.73, ci 0.52-1.02) which was largely confined to the PgR-positive group. Amongst the ER-positive group, PgR-positive and PgR-negative patients showed similar benefit (rr 0.81; ci 0.65-1.02 and 0.70; ci 0.49-0.99, respectively). Patients positive for HER2 did not benefit significantly (rr 1.14; ci 0.75-1.73) but this group was small.


CONCLUSIONS
Measurement of PgR status in ER-negative patients defines a group of patients that benefit from tamoxifen but would be excluded from tamoxifen therapy on the basis of ER status alone. The data are consistent with HER2 positive tumours being resistant to tamoxifen.
Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK. mitch@icr.ac.uk
M
M
Dowsett
J
J
Houghton
C
C
Iden
J
J
Salter
J
J
Farndon
R
R
A'Hern
R
R
Sainsbury
M
M
Baum
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen