HER2 overexpression and activation, and tamoxifen efficacy in receptor-positive early breast cancer.
OBJECTIVE
Tamoxifen is a partial ER antagonist that is highly effective in the treatment of receptor positive breast cancer. It significantly reduces recurrence and improves survival in both pre- and postmenopausal women. Unfortunately, many ER+ positive tumors progress despite tamoxifen treatment and until now, no possibility exists to prospectively identify tamoxifen-resistant tumors. It has been suggested that that in HER2 over-expressing tumors, cross-talk via activated HER2 receptors is a key mechanisms by which tumors become tamoxifen-resistant.


METHODS
We have therefore used immunohistochemistry to analyze the expression of HER2 and activated ptyr-1248 HER2 in 408 women of ER+, early breast cancer who had received at least 2 years of adjuvant tamoxifen. We then analyzed possible associations between HER2 and pHER2 expression, and prognostic parameters, and evaluated the effect of HER2 expression and survival.


RESULTS
With HER2 being positive in 12 of 208 (2.9%) of ER+ positive tumors, HER2 overexpression was found to be considerably less common in ER+ tumors than what has been thought previously. The majority of HER2 overexpressing tumors, however, also expressed the activated receptor form (r = 0.664; P < 0.0001). Both HER2 and pHER2 are moderately correlated with Grading (r = 0.138; P = 0.0052 and r = 0.118; P = 0.0241, respectively) and nodal involvement (r = 0.163; P = 0.0018 and r = 0.134; P = 0.016, respectively), but neither HER2 nor its activated form are significant predictors of RFS, DFS, or OS.


CONCLUSIONS
Taken together, we have demonstrated that in ER+ breast cancer, the HER2 receptor is commonly activated, but its low prevalence in ER+ tumors does not render it a useful prognostic parameter in tamoxifen-treated patients.
Singer
Christian F
CF
Division of Special Gynaecology, Vienna Medical University, Vienna, Austria. christian.singer@meduniwien.ac.at
Gschwantler-Kaulich
Daphne
D
Fink-Retter
Anneliese
A
Pfeiler
Georg
G
Walter
Ingrid
I
Hudelist
Gernot
G
Helmy
Samir
S
Spiess
Anne-Catherine
AC
Lamm
Wolfgang
W
Kubista
Ernst
E
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; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D012189:Retrospective Studies; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen