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DR RAPPAPORT: This is a 41-year-old,
premenopausal woman with infiltrating
ductal carcinoma of the breast,
metastatic to six lymph nodes. She had
a modified radical mastectomy and has
been treated with four cycles of AC at
this point. The tumor is ER- and PR-positive
and HER2-positive by FISH.
DR LOVE: Aman, how would you treat
this patient?
DR BUZDAR: For this young lady, who
has a very high risk of recurrence, we
have an effective therapy that has been
shown to reduce the risk of recurrence.
I would discuss with her the
potential benefits of trastuzumab and
that convincing evidence exists that
we can reduce her risk of recurrence
by more than 50 percent. In spite of
chemotherapy and the positive hormone
receptor status, she still has a very
high risk of recurrence and I, personally,
would be very much in favor of
using trastuzumab as an addition to her
therapy.
DR LOVE: What specific chemotherapy
and when would you add the trastuzumab?
DR BUZDAR: If she just was finishing
the last of four cycles of AC, I would
give trastuzumab with a taxane, and
most of the data we have are with
paclitaxel (Perez 2005, Romond 2005).
I personally would use trastuzumab
concomitantly with the taxane-based
therapy because of the positive impact
when given concurrently and the lack
of benefit when it was given sequentially
that we saw in the Intergroup
trial. That is one area of discordance
between the US trial, in which I have
more faith, and the European HERA
trial, which shows a very similar degree
of benefit to the combined analysis
(Piccart-Gebhart 2005). In the HERA
trial, the choice of chemotherapy was
up to the physician.
DR LOVE: When would you start
hormonal therapy in this patient, and
what agent would you use?
DR BUZDAR: My understanding is that
in these trials, hormonal therapies were
started after the completion of chemotherapy
concomitantly with trastuzumab.
We have utilized that approach
in the neoadjuvant and adjuvant
settings.
DR LOVE: If this patient continues to
menstruate through the chemotherapy,
what hormonal therapy would you use?
DR BUZDAR: In a patient who
continues to menstruate, I still believe
that tamoxifen is the standard of care.
Of course, there are a number of
ongoing randomized adjuvant trials in
which pharmacological intervention
and the substitution of tamoxifen with
an aromatase inhibitor and an LHRH
agonist is being evaluated; we should
have some preliminary data from these
in the next year or so.
DR LOVE: I assume you would use
trastuzumab for a total of one year, as
was used in the adjuvant trials.
DR BUZDAR: Yes, because we need to
use the therapy as it was used in the
study where the data were collected.
DR LOVE: Bill, how do you approach
patients who have been treated in the
past for HER2-positive disease and
have not received trastuzumab?
DR GRADISHAR: This harkens back to
the release of the MA17 data and then
seeing patients who completed adjuvant
tamoxifen six months or a year ago.
Do you institute another endocrine
maneuver? I think that’s one of the big
questions we are going to be facing
with delayed trastuzumab. The data we
have from trials long ago, tracking the
recurrence of breast cancer over time,
are instructive because we know that
even after five years — be they node-negative
or node-positive, but particularly
if they are node-positive — there’s
a fraction of patients who are going to
continue to be at risk for recurrence,
even though the peak recurrence may
be within the first few years.
So with that as the background, I think
for a patient who has completed chemotherapy,
it is reasonable to consider
trastuzumab. The big question is, How
long since the completion of chemotherapy?
Six months? A year? Two
years? If a patient had six or 10 positive
nodes and were out six months or a
year, I would still have the discussion
about the data and consider adding
trastuzumab, even though it doesn’t
directly duplicate the trial design.
DR LOVE: In terms of hormonal
therapy, do you agree with Aman that
in this patient you would use tamoxifen
alone? I’m not certain whether this
patient would be eligible for the TEXT
or SOFT trials, but would you consider
ovarian suppression and an aromatase
inhibitor in this patient off protocol?
DR GRADISHAR: I believe tamoxifen
remains the standard for this type of
patient. The data we have available on
ovarian suppression with tamoxifen or
an aromatase inhibitor are still relatively
limited, so I would still view tamoxifen
as the optimal therapy.
DR LOVE: Kent, there were a fair
number of patients in the HERA study
who had node-negative disease but not
too many in the combined NSABP/
NCCTG analysis. Do you think that
the concept of relative risk should be
applied when considering trastuzumab
in patients with node-negative disease
who have received chemotherapy and
hormonal therapy?
DR OSBORNE: First of all, we should
stop stratifying patients for treatment
by node-negative versus node-positive
disease. That’s only one of many factors.
A patient with a high-grade, large
tumor that is node-negative may have
a much worse prognosis than a patient
with node-positive disease and two
positive receptors. I would look at the
patient’s risk of recurrence and base my
decision on the risk of recurrence, and
even though she’s node-negative, I’d
treat her.
DR LOVE: Dr Rappaport, would you
follow up with what happened to this
patient?
DR RAPPAPORT: I plan to talk to her
about starting a taxane and trastuzumab
concomitantly. I am wondering whether
we should give her an LHRH agonist,
or should we use tamoxifen? Also, if
she is on an LHRH agonist, do we
start either tamoxifen or an aromatase
inhibitor?
DR LOVE: Peter, what about the issue
of patients who cease menstruating with
chemotherapy? How do we determine
whether they’re postmenopausal and
whether to consider an AI?
DR RAVDIN: One of the things that’s
been frustrating is to use serum estradiol
and gonadotrophin levels to define the menopausal status of women who have
become postmenopausal on chemotherapy.
This patient is relatively young,
so if she stops menstruating, there’s a
reasonable chance that she’s going to
start menstruating again.
In this type of patient, I still prefer
tamoxifen rather than an aromatase
inhibitor. If she receives tamoxifen,
and at the end of two years she hasn’t
menstruated and her estradiol levels are
low, then you can switch her. Incidentally,
tamoxifen usually pushes up
the estradiol levels and makes it more
obvious that a patient is premenopausal,
so that if you drew an estradiol
level after two years and it was in the
postmenopausal range, and you wanted
to start her on an aromatase inhibitor,
I think there’s very little chance that
she would start menstruating at that
point (2.1).
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