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| Status |
Public on Dec 20, 2011 |
| Title |
A phase II neoadjuvant trial of anastrozole (A), fulvestrant (F) and gefitinib (I - iressa) in patients with newly diagnosed estrogen receptor positive breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor (EGFR) can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.
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| Overall design |
We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant (AF) or anastrozole, fulvestrant, and gefitinib (AFG, also known as AFI) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining twelve patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (p value= 0.01) with a parallel reduction in the expression of the Cyclin D1 (p value=0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.
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| Contributor(s) |
Massarweh S, Tham YL, Huang J, Sexton K, Weiss H, Tsimelzon A, Bayer A, Rimawi M, Cai WY, Hilsenbeck S, Fuqua S, Elledge R |
| Citation(s) |
21792626 |
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| Submission date |
Nov 14, 2011 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Suzanne Fuqua |
| Organization name |
Baylor College of Medicine
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| Street address |
1 Baylor Plaza
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| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77030 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (22)
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| GSM832390 |
breast, pre AF treatment (H7_1349) |
| GSM832391 |
breast, post AF treatment (H8_1389) |
| GSM832392 |
breast, pre AF treatment (H15_1682) |
| GSM832393 |
breast, post AF treatment (H16_1717) |
| GSM832394 |
breast, pre AF treatment (H1_1278) |
| GSM832395 |
breast, post AF treatment (H4_1328) |
| GSM832396 |
breast, pre AF treatment (H12_1628) |
| GSM832397 |
breast, post AF treatment (H14_1659) |
| GSM832398 |
breast, pre AF treatment (H23_2233) |
| GSM832399 |
breast, post AF treatment (H24_2259) |
| GSM832400 |
breast, pre AFI treatment (H3_1296) |
| GSM832401 |
breast, post AFI treatment (H6_1346) |
| GSM832402 |
breast, pre AFI treatment (H11_1610) |
| GSM832403 |
breast, post AFI treatment (H13_1647) |
| GSM832404 |
breast, pre AFI treatment (H9_1575) |
| GSM832405 |
breast, post AFI treatment (H10_1594) |
| GSM832406 |
breast, pre AFI treatment (H2_1279) |
| GSM832407 |
breast, post AFI treatment (H5_1332) |
| GSM832408 |
breast, pre AFI treatment (H18_1930) |
| GSM832409 |
breast, post AFI treatment (H20_1950) |
| GSM832410 |
breast, pre AFI treatment (H17_1910) |
| GSM832411 |
breast, post AFI treatment (H19_1935) |
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| Relations |
| BioProject |
PRJNA148645 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33658_RAW.tar |
182.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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