| Tracks 1-7 |
| Track 1 |
Introduction |
| Track 2 |
Use of biomarkers to select
adjuvant hormonal therapy |
| Track 3 |
Sequencing adjuvant tamoxifen
and anastrozole: Five-year
analysis of ABCSG-8 |
| Track 4 |
Benefit of delayed therapy with
letrozole observed in MA17 |
|
| Track 5 |
Up-front hormonal therapy in
pre- and perimenopausal
patients |
| Track 6 |
Duration of hormonal therapy |
| Track 7 |
Potential benefit of identifying
patients with de novo
tamoxifen resistance |
|
|
Select Excerpts from the Breast Cancer Update Meet The
Professors Session, held at the 28th Annual San Antonio
Breast Cancer Symposium, December 8-11, 2005
Track 2
 DR LOVE: Can you review data presented here on biomarkers to identify
subgroups of patients who would benefit from a specific endocrine therapy? |
DR RAVDIN: The ATAC trial found that the extra advantage of an aromatase
inhibitor — in this case, anastrozole — was seen strongly only in the patients
with ER-positive, PR-negative disease (Dowsett 2005). This finding was
based on 6,000 patients, and it had a very large p-value.
However, the BIG FEMTA study, which compared letrozole to tamoxifen as
up-front therapy, did not find a significant difference in the efficacy of these
agents relative to the status of the progesterone receptor (BIG 1-98 Collaborative
Group 2005). The BIG investigators also evaluated the HER2 status
of roughly 4,000 patients because data suggest that aromatase inhibitors may
be more effective in tumors that are HER2-positive and ER-positive. They
conducted a well-controlled study and found no significant difference on the
basis of HER2, either.
The relationship between hormone receptor status and the impact of
endocrine therapy was also examined in the NCIC-CTG MA17 trial. This trial randomly assigned patients who had taken five years of adjuvant tamoxifen
to five years of letrozole versus a placebo. Patients with ER- and PR-positive
disease particularly benefited from letrozole (Goss 2005).
However, patients with ER-positive but PR-negative disease received no
additional benefit from letrozole compared to tamoxifen. Interestingly enough,
that observation is exactly opposite to the ATAC observation.
At this point, we have no way in clinical practice to specifically select patients,
and in this state of uncertainty, an aromatase inhibitor is probably the better
adjuvant endocrine therapy for postmenopausal patients with ER-positive
breast cancer.
DR LOVE: An updated analysis was presented on the MA17 trial, which
examined patients who had originally received a placebo and then switched to
letrozole after the unblinding. Could you comment on that data?
DR RAVDIN: Paul Goss presented follow-up data on patients who participated
in the Canadian trial comparing letrozole versus a placebo after completing
five years of adjuvant tamoxifen. When they broke the code at two and a half
years, some of the placebo patients decided to switch to letrozole and a few
chose no further therapy. The patients who went on to take letrozole had
much lower recurrence rates, even though some of them had been off any
endocrine therapy for four years.
This analysis suggests that even years after stopping tamoxifen, patients can
gain benefit from an aromatase inhibitor. In my practice, that means some of
my patients, particularly the patients at high risk who have already been off
tamoxifen for a year, should consider taking an aromatase inhibitor, specifically
letrozole, because it’s the only one that has been tested in this context.
DR LOVE: A rerandomization of all the patients who completed letrozole on
MA17 is underway to compare another five years of letrozole to no further
therapy. What do you think this will show?
DR RAVDIN: Aromatase inhibition probably should be continued indefinitely,
and my opinion is based on two factors. One is that if a patient stops
an aromatase inhibitor, her hormone levels will, of course, recover. Second,
it may be more difficult to develop resistance to estrogen deprivation than
it is to develop resistance to tamoxifen. Tamoxifen is an agonist/antagonist,
and preclinical work has shown that it can be reinterpreted as an estrogen
by cancer cells, but I can’t conceive of a pathway that would reinterpret no
estrogen as an estrogen.
Select publications
