"The lack of benefit for patients who were positive for oestrogen but negative for progesterone suggests that a functional oestrogen receptor is needed for letrozole to have an effect," said principal investigator Paul E Goss, MD, director of breast cancer research, Cancer Center of Massachusetts General Hospital, Boston, Massachusetts, United States.

Dr. Goss, who presented the findings on behalf of the MA.17 Collaborative Trialists group, noted in his March 23^rd presentation that the findings pertained to patients who were previously treated with tamoxifen for 5 years.

He and his coinvestigators reviewed the findings for the MA.17 trial to resolve some discrepancies in previous research regarding progesterone receptor status and response to aromatase inhibitors, he explained. The MA.17 trial randomised 5187 postmenopausal women who were free of breast cancer after 5 years of tamoxifen therapy, and who were then switched to 5 years of either letrozole or placebo.

After a median follow-up of 30 months, the hazard ratio (HR) for disease-free survival was 0.58 for those treated with letrozole compared with the overall population (P =.00004). The researchers noted that 97.4% of these patients had tumours that were positive for either oestrogen or progesterone receptors.

Data regarding oestrogen and progesterone receptors status were available for 4653 of the women. The investigators conducted retrospective exploratory analysis on these patients to compare time to recurrence in the 4 receptor subgroups: 1) those positive for both oestrogen and progesterone receptors; 2) those positive for oestrogen but negative for progesterone receptors; 3) those negative for oestrogen but positive for progesterone receptors; and 4) those negative for both receptors.

The intent-to-treat analysis showed that improved disease-free survival associated with letrozole treatment was associated with a hazard ratio of 0.49 for the 3809 in group 1, with an event rate of 3% in the letrozole group and 6% in the placebo group. The placebo patients in each group served as reference for defining the HR.

The HR for the 636 patients in group 2 was 1.21, with a 6% event rate in the treatment group and of 5% in the placebo group. For the 200 patients in group 3, the HR was 0.62 (4% vs 5%, respectively).

No events were documented among the 8 patients in group 4. The difference in disease-free survival was particularly significant between those with oestrogen and progesterone receptor positivity and those with oestrogen positivity who were negative for progesterone receptors, the investigators reported (P =.02).

The HRs for distant disease-free survival and overall survival for women with positive receptors of both types were 0.53 and 0.58, respectively.

Dr. Goss stressed that physicians should interpret the results cautiously, since the analysis was not part of the original MA.17 trial design.


[Presentation title: NCIC CTG MA17: Updated Analysis on Disease Free Survival (DFS) According to Estrogen Receptor and Progesterone Receptor Status of the Primary Tumor. Abstract 350]

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