Her2 and progesterone receptor status are not predictive of response to fulvestrant treatment.
OBJECTIVE
It has been hypothesized that response to endocrine therapy for breast cancer depends on Her2 and progesterone receptor status, grading, and tumor proliferation rate. In this study, we evaluated factors that are potentially predictive of response and time to progression in patients treated with fulvestrant.


METHODS
One hundred fifty-five patients were included and followed prospectively. Patients received fulvestrant at standard dose by i.m. injection. Response was evaluated every 3 months using International Union Against Cancer criteria. Time to progression and overall survival were estimated with the Kaplan-Meier product limit method. A multivariate analysis was done to evaluate factors potentially influencing response and time to progression.


RESULTS
We observed a partial response in 19 patients (12.3%), stable disease > or =6 months in 56 patients (36.1%), stable disease >3 months but <6 months in 7 patients (4.5%), and progressive disease in 73 patients (47.1%). Median time to progression was 5 months, and median overall survival was 27 months. Probability of achieving clinical benefit was significantly associated with a low proliferation rate (P = 0.015), nonvisceral metastatic sites (P = 0.023), and first-line therapy (P = 0.023). First-line therapy was also associated with prolonged time to progression (P = 0.003).


CONCLUSIONS
Response rate and time to progression are shown to be independent of Her2 status, grading, and progesterone receptor status. This is probably caused by the unique mechanism of action associated with fulvestrant: Due to receptor down-regulation, it blocks nuclear, cytoplasmatic, and membrane-bound estrogen receptor. Therefore, it seems to inhibit the cross-talk between growth factor receptor signaling and estrogen receptor in a more effective manner.
First Department of Medicine, Medical University of Vienna, Vienna, Austria.
Rupert
R
Bartsch
Catharina
C
Wenzel
Gabriela
G
Altorjai
Ursula
U
Pluschnig
Robert M
RM
Mader
Michael
M
Gnant
Raimund
R
Jakesz
Margaretha
M
Rudas
Christoph C
CC
Zielinski
Guenther G
GG
Steger
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D018450:Disease Progression; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004958:Estradiol; D000077267:Fulvestrant; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone