[15] The impact of LHRH agonists on breast cancer recurrence and mortality: an overview of the randomized trials.

Cuzick J, on Behalf of the LHRH-Agonist Overview Group.. Wolfson Institute of Preventive Medicine, London, United Kingdom

Background: We have conducted an overview of trials employing LHRH agonists as adjuvant therapy for early pre-menopausal breast cancer.
Materials and Methods: The trials were of two basic types those which evaluated the addition of a LHRH-agonist to another agent, usually some form of chemotherapy, and those which compared a LHRH-agonist alone to chemotherapy. Other variations were use of tamoxifen either in all patients or only in the LHRH group as part of endocrine therapy. Most patients were oestrogen receptor positive and for uniformity all analyses are restricted to that group.
Results: Data has been received from all but three trials; at this stage a total of 6,437 ER positive patients from 13 different trials have been included of which 7 look at the addition of an LHRH agonist and 7 compared one to chemotherapy.
The addition of LHRH agonist plus tamoxifen compared to chemotherapy plus tamoxifen reduced recurrence rates by 18.5% (95% CI 45.6% reduction, 22.0% increase, P=0.320) and deaths after recurrence by 27.1% (95% CI 58.1% reduction, 26.9% increase, P=0.264). The addition of the combination LHRH agonist tamoxifen was not significantly different from chemotherapy only for breast cancer deaths (HR = 1.08, 95% CI 0.53 2.21, P=0.830) recurrence (HR=0.786, 95% CI 0.49 1.25, P=0.312). When comparing the addition of LHRH agonist alone to chemotherapy, the recurrence rates were reduced by 19.3% (95% CI 40.4% reduction, 9.2% increase, P=0.165) and deaths after recurrence by 29.6% (95% CI 55.4% reduction, 11.3% increase, P=0.133). The addition of an LHRH agonist (with or without tamoxifen) significantly reduced recurrence rates by 20.2% (95% CI 2.9% - 34.5%, P=0.024) and tend to reduce deaths after recurrence rates by 21.0% (95% CI 41.5% reduction, 6.6% increase, P=0.123).
The hazard ratio reduction of an LHRH agonist alone compared to chemotherapy was 12.2% (95% CI, 25.7% reduction, 3.7% increase, P=0.126) for breast cancer deaths and 1.2% (12.7% reduction, 11.8% increase, P=0.849) for recurrence, whereas the combination of an LHRH agonist plus tamoxifen compared to chemotherapy reduced the hazard ratio by 11.9% (95% CI, 32.6% reduction, 15.2% increase, P=0.354) for breast cancer deaths and 11.8% (27.0% reduction, 6.5% increase, P=0.192) for recurrence. Overall, the hazard ratio reduction of an LHRH agonist (with or without tamoxifen) compared to chemotherapy was 12.2% (95% CI, 23.8% reduction, 1.3% increase, P=0.075) for breast cancer deaths and 4.9% (14.3% reduction, 5.6% increase, P=0.347) for recurrence.
Results are preliminary and further data is expected and will be updated before the meeting. A fuller description of the results will be provided.
Discussion: We have found that for oestrogen receptor positive breast cancer, the addition of an LHRH agonist to chemotherapy significantly reduced the rate of cancer recurrences, although deaths from breast cancer were reduced less and were not significant. Further for this group of patients an LHRH agonist was as effective as chemotherapy for both breast cancer recurrence and deaths after recurrence. Confirmation of these results when all trial data is available is essential. Detailed analysis according to type of chemotherapy and other factors is ongoing.

Friday, December 15, 2006 10:30 AM

General Session 3 (9:30 AM-11:15 AM)