Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors--International Breast Cancer Study Group.

Abstract

PURPOSE:

To centrally assess estrogen receptor (ER) and progesterone receptor (PgR) levels by immunohistochemistry and investigate their predictive value for benefit of chemo-endocrine compared with endocrine adjuvant therapy alone in two randomized clinical trials for node-negative breast cancer.

PATIENTS AND METHODS:

International Breast Cancer Study Group Trial VIII compared cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for 6 cycles followed by endocrine therapy with goserelin with either modality alone in pre- and perimenopausal patients. Trial IX compared three cycles of CMF followed by tamoxifen for 5 years versus tamoxifen alone in postmenopausal patients. Central Pathology Office reviewed 883 (83%) of 1,063 patients on Trial VIII and 1,365 (82%) of 1,669 on Trial IX and determined ER and PgR by immunohistochemistry. Disease-free survival (DFS) was compared across the spectrum of expression of each receptor using the Subpopulation Treatment Effect Pattern Plot methodology.

RESULTS:

Both receptors displayed a bimodal distribution, with substantial proportions showing no staining (receptor absent) and most of the remainder showing a high percentage of stained cells. Chemo-endocrine therapy yielded DFS superior to endocrine therapy alone for patients with receptor-absent tumors, and in some cases also for those with low levels of receptor expression. Among patients with ER-expressing tumors, additional prediction of benefit was suggested in absent or low PgR in Trial VIII but not in Trial IX.

CONCLUSION:

Low levels of ER and PgR are predictive of the benefit of adding chemotherapy to endocrine therapy. Low PgR may add further prediction among pre- and perimenopausal but not postmenopausal patients whose tumors express ER.

• Authors: Giuseppe Viale, Meredith M Regan, Eugenio Maiorano, Mauro G Mastropasqua, Rastko Golouh, Tiziana Perin, Robert W Brown, Anikó Kovács, Komala Pillay, Christian Ohlschlegel, Stephen Braye, Piergiovanni Grigolato, Tiziana Rusca, Richard D Gelber, Monica Castiglione-Gertsch, Karen N Price, Aron Goldhirsch, Barry A Gusterson, Alan S Coates
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 9 Pg. 1404-10 (Mar 20 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18349391 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Biomarkers, Tumor
• Receptors, Estrogen
• Receptors, Progesterone
• Tamoxifen
• Goserelin
• Cyclophosphamide
• Fluorouracil
• Methotrexate

Topics

• Adult
• Aged
• Antineoplastic Agents, Hormonal (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (chemistry, drug therapy, surgery)
• Chemotherapy, Adjuvant
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Female
• Fluorouracil (administration & dosage)
• Goserelin (administration & dosage)
• Humans
• Immunohistochemistry
• Menopause
• Methotrexate (administration & dosage)
• Middle Aged
• Neoplasms, Hormone-Dependent (chemistry, drug therapy)
• Predictive Value of Tests
• Receptors, Estrogen (analysis)
• Receptors, Progesterone (analysis)
• Tamoxifen (administration & dosage)
• Treatment Outcome