Chemohormonal therapy in premenopausal node-positive, receptor positive breast cancer: An Eastern Cooperative Oncology Group phase III intergroup trial (E5188, INT 0101)
Reviewer: Neha Vapiwala, MD
Last Modified: June 1, 2003
Presenter: N. E. Davidson Presenter's Affiliation: Eastern Cooperative Oncology Group Type of Session: Scientific
The benefits of combined chemotherapy and endocrine therapy in premenopausal pts with node-positive, hormone receptor-positive breast cancer are a topic of much research. The benefit of chemotherapy in node-positive breast cancer is well established. Hormonal manipulation includes both central ovarian suppression as well as selective estrogen receptor modulating drugs. The purpose of this study is to investigate the best combination of such combined therapy regimens, specifically with regards to survival benefit, acceptable toxicity and effect on hormone levels. The study was designed to compare relative risks, disease-free interval, and disease-free survival rates for three different treatment arms, ranging from chemotherapy alone, to chemotherapy with ovarian suppression with or without tamoxifen. The authors also looked at the toxicities of the various treatments as well as the objective effects on hormone levels.
Materials and Methods
1,504 eligible pts enrolled between 7/1989 and 2/1994
Premenopausal, node positive, steroid receptor positive, no evidence of locally advanced disease
Stratified by number of nodes, timing of study treatment administration relative to initial surgery, and progesterone receptor status
Arm I = (CAF) Chemotherapy consisting of CAF x 6
Arm II = (CAFZ) Above + goserelin x 5 yrs
Arm III = (CAFZT) Above + tamoxifen x 5 yrs
median follow-up 9.6 yr
Local recurrence rate hazard ratios
CAFZ vs. CAF = 0.93 vs. 0.90
CAFZT vs. CAFZ = 0.73 vs. 0.73
CAFZ vs. CAF = 0.88 vs. 0.85
CAFZT vs. CAFZ = 0.91 vs. 0.90
No major difference in hazard ratios seen over time
In women < 40 yrs old, estradiol hormone levels were most affected by goserelin. This difference did not hold in women over 40 yrs of age.
In women who are not amenorrheic after chemotherapy, a trend was seen toward disease-free survival benefit with goserelin.
Tamoxifen benefit greatest in women >/= 40 yrs old or who ARE amenorrheic after chemotherapy.
In premenopausal women with node positive, hormone receptor positive breast cancer, tamoxifen + anthracycline-based chemotherapy improves relapse-free survival.
There is no significant effect on 9-yr relapse-free survival with the addition of LHRH analogue ovarian suppression to chemotherapy. A beneficial effect of LHRH analogue is primarily seen in a subgroup of women under 40 yrs old and who are not amenorrheic post-chemotherapy.
This study helps strengthen the evidence for the role of tamoxifen in premenopausal women with node positive, hormone receptor positive breast cancer. There is a significant disease-free survival advantage seen with its use, particularly in postmenopausal women 40 yrs of age or older. The authors do note a trend towards survival benefit with the addition of goserelin to chemotherapy in subgroup analysis of women under 40 yrs of age or who are not amenorrheic. Its use in the whole cohort of women, however, did not show a survival advantage. The authors report limitations in this study, specifically its retrospective nature and the lack of a chemo + tamoxifen arm for comparison. Nonetheless, the data from this study do shed light on the value of chemohormonal combination therapy in node positive, hormone-positive breast cancer. Future studies should perhaps focus on prospective evaluation of overall survival in premenopausal women post-chemotherapy, as these data are still needed.
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