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The Professors Vol. 1 2003: Case
3
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5 years ago, the patient in her 50s, received
ACT followed by tamoxifen for ER/PR-positive, HER2-negative
breast cancer |
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Returns for routine follow-up, while on tamoxifen,
with mild shortness of breath and fatigue |
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Chest X-ray and CT: Multiple small pulmonary
nodules (largest 1.5-cm) |
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Key discussion points: |
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Discuss goals of treating metastatic
breast cancer |
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Chemotherapy versus endocrine therapy
in metastatic disease |
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Sequential single agents versus combination
chemotherapy in metastatic disease |
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Selection and scheduling of taxanes |
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Combining trastuzumab with chemotherapy
in the metastatic setting |
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Determining ER- and PR-positivity |
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Optimal dosing of docetaxel |
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Dr Love: What kind of questions
did this woman ask you about what to expect in the future? What
was her overall approach to this in terms of how aggressive to
be in treating the disease?
Dr Wilson: Like
most patients with metastatic disease, she experienced some shock
at the diagnosis. She was able to appreciate that she still had
a very good quality of life without major symptoms and that we
had an approach to fight this. She also has good family support
from her husband and her children.
I stressed that while we didn’t expect to cure her, we
had number of treatment options available. I also emphasized my
expectation that a strong patient with relatively few symptoms
would do well for a relatively long time. She certainly wanted
to be treated, but she wanted treatment that would not significantly
interfere with her life, because to that point, her symptoms were
not interfering with her daily activities.
Dr Love: Debu, how would you
think through this case?
Dr Tripathy: I tell patients
that there is a spectrum of disease, ranging from chronic to a
more acute and life-threatening disease. I try to give them a sense
of what they might expect from different therapies, both in terms
of the likelihood of response and toxicity. Finally, I give them
my recommendation balancing these two issues.
In this case, I would start her on a hormonal therapy with an
aromatase inhibitor. I would follow symptoms closely, but the lungs
are an area one could follow most accurately with CT scans.
Dr Love: One of the things I
find most interesting about interviewing research leaders and interacting
with physicians in practice is that there is a real dichotomy in
some situations. In this patient, I think the lung metastases and
shortness of breath would make many physicians nervous. I’m
not saying what is right or wrong, but I think many community-based
oncologists would start this woman on chemotherapy. One strategy
I often see in this kind of situation is to use chemotherapy to
elicit a response and then switch to hormonal therapy.
Dr Harth: I agree. Not having
seen the patient, I would choose chemotherapy first, because the
suggestion of shortness of breath is unnerving. In addition, this
patient progressed on tamoxifen. In my experience, those patients
do not do as well on hormonal agents. I would treat her with chemotherapy
initially and then start her on an aromatase inhibitor.
Dr Brooks: I’d like to
dissent. Aromatase inhibitors work pretty quickly, and I believe
you can start patients like this on an aromatase inhibitor and
follow tumor markers, CT scans and symptoms. I don’t think
you lose very much, because if the tumor responds, you have a therapy
that may work for 6, 12, 18, 24, or more months. This is your opportunity
to “hit it out of the ball park” with essentially no
symptoms.
If you put this patient’s disease into remission with chemotherapy
and then use aromatase inhibition, you don’t know if you
are looking at a nice remission from chemotherapy or a small hormone
effect. As long as you have time, trying hormones first is preferable.
Dr Love: When we face the decision
between hormonal therapy and chemotherapy, we classically think
about how quickly we need a response. This is based on the idea
that hormones don’t work as fast as chemotherapy. However,
Mike Dixon, who studies neoadjuvant endocrine therapy, says that
changes occur in the biopsy within days after an aromatase inhibitor
is started. Debu, how much do we really know about how long it
takes to have an effect with hormonal therapy versus chemotherapy?
Dr Tripathy: We know very little
about the timing of response. This has typically not been reported
in clinical trials, so it’s hard to determine. I can’t
answer on a clinical basis, although, as you pointed out, studies
have looked at the biological effects, examining proliferative
status, and shown very rapid effects.
People also have the common conception, which may or may not
be true, that visceral disease responds less often to hormonal
therapy than nonvisceral disease. In most of the hormonal therapy
trials, the response rates are generally comparable between soft
tissue and visceral disease.
I agree with Dr Harth that the likelihood of response with an
aromatase inhibitor is probably slightly lower in this patient;
however, the speed of response and the ability to monitor the patient
for a response is such that using an aromatase inhibitor is a reasonable
option.
Dr Love: Let’s change
some of the variables in this case and see how it affects treatment.
Andy, assume this patient had much more shortness of breath and
the chest CT scan was much worse — she’s not ready
to be hospitalized, but you’re a little bit concerned about
her situation. What would you recommend?
Dr Seidman: A single-agent taxane
would be the standard of care in that situation.
Dr Love: Okay, now we’ll
go even further and say that she’s very short of breath and
has lymphangitic disease. Dr Seidman: I
would stand by my original answer to give her a single-agent taxane.
Dr Tripathy: I disagree with
Dr Seidman here. Although I very rarely use combination chemotherapy,
I probably would in this situation because the patient is in visceral
crisis. I agree with Dr Seidman that the long-term survival may
not be different with combination versus sequential therapy; however,
in this patient, a higher chance of response might justify the
added toxicity of a combination. I try to estimate the degree of
benefit for a patient based on symptoms — the more symptoms,
the greater the potential benefit, which might outweigh the added
toxicity of combination therapy.
The docetaxel/capecitabine combination is a completely reasonable
choice for this situation. There is a published trial demonstrating
a benefit, and this patient has not previously received a taxane
(Figure 2, Table 3). One could consider a combination of anthracyclines
and taxanes, but this patient has previously received anthracyclines.
Dr Love: Dr Aks, how would you
have managed this patient’s disease if she were very symptomatic?
Dr Aks: Because
of the pending respiratory failure that you suggested, I would
have been very aggressive and taken my chances with at least a
doublet to try to avoid the crisis of ventilator support. I would
be comfortable with a taxane and capecitabine. Could either Dr
Seidman or Dr Tripathy comment on the recent emerging data on combining
taxanes with carboplatin in this clinical setting?
Dr Seidman: There is a much
higher level of evidence supporting the addition of carboplatin
in the HER2-positive setting than in the HER2-negative setting.
Nick Robert presented data from the US Oncology trial last December
in San Antonio, in which the addition of carboplatin to paclitaxel
and trastuzumab significantly improved patient outcome. The Phase
II data for paclitaxel and carboplatin in HER2-negative tumors
are also impressive.
Dr Tripathy: A platinum-containing
combination would be reasonable as would vinorelbine in combination
with taxanes and a variety of others. Data have been published
on many combinations in the Phase II setting, but there are not
many randomized studies in HER2-negative populations, by which
we can compare outcomes and toxicities relative to a single agent.
This is one of the reasons I chose the particular combination of
docetaxel and capecitabine.
I must emphasize, as we discussed, that treating breast cancer
is an art, and one has to look at and be able to present numerous
options to patients. Sometimes, I present these multiple options
to my patients just to illustrate the number of possibilities available
to them. In the end, I’m not as dogmatic with my patients
as I may be in this setting. I think it’s only fair to say
that there are several reasonable regimens, including the platinum-based
regimens.
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