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You
are here: Home: Meet
The Professors Vol. 1 2003: Case
5
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Presentation: |
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This woman in her 40s presented with 2-cm, hard,
right breast mass within a 4-cm area of mild erythema and a
palpable 2-cm, hard, ipsilateral axillary lymph node |
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Breast biopsy revealed a high-grade infiltrating
ductal carcinoma |
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ER: 70 percent positive with moderate staining,
PR: 20 percent positive with moderate staining |
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MIB-1 block: 80 percent positive; HER2 1+ by
IHC, negative by FISH |
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Biopsy of overlying skin revealed lymphatic channels
plugged with carcinoma |
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Staging scans of chest, abdomen, pelvis and bone
were all negative |
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CA 27.29 was 48 U/mL |
Primary therapy: |
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Received neoadjuvant AC x 4, tumor became nonpalpable
after the first cycle; patient continued menstruating |
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Mastectomy, no residual tumor |
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Patient declined recommendation of four cycles
of taxane therapy postoperatively |
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Received regional radiotherapy and adjuvant tamoxifen |
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Three months after beginning adjuvant tamoxifen,
patient developed pulmonary embolus |
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Warfarin started, tamoxifen continued |
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Key discussion points: |
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Patient compliance with adjuvant therapy |
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Pulmonary embolus during adjuvant tamoxifen
in a premenopausal patient |
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Dr Perez: The patient’s
refusal of a postoperative taxane reminds me of the challenge we
face when we know the data, we have enough experience to match
the data to the patient in front of us, and the patient still refuses
our treatment recommendation. This is always a difficult situation
because we want our patients to receive the best therapy and to
survive this disease, but at the same time, we have to respect
their wishes, which is obviously what Dr Brooks did in this situation.
When the disease recurs, we can’t help wondering what would
have happened if the patient had followed our initial recommendations.
Dr Brooks: Three months after
the patient began adjuvant tamoxifen she developed a pulmonary
embolus and was hospitalized for about one week. It was significant
pulmonary embolus, but being a half-time hematologist, I continued
her on tamoxifen and put her on a full dose of warfarin. She was
still having regular menstrual periods. Clearly, the four cycles
of AC did not ablate her ovaries.
Dr Love: Dr Robert, what would
you have done in this situation?
Dr Robert: I would have done
everything Dr Brooks did up to the point of the pulmonary embolus.
This is retrospective, but in this ER-positive, premenopausal woman
on tamoxifen, when she had her pulmonary embolus, I would have
had her ovaries removed. This cancer is behaving a bit aggressively,
and there is a meta-analysis of randomized trials looking at ovarian
ablation via LHRH analog plus or minus tamoxifen that shows the
combination is better (Table 8). One could extrapolate and use
an aromatase inhibitor. Today, I would consider the options of
tamoxifen plus Coumadin® versus a bilateral oophorectomy, and
then add an aromatase inhibitor when she progresses.
Dr Love: Dr Brooks, can you
give us some more follow-up on this patient?
Dr Brooks: One year after completing
her radiation therapy, her tumor markers were elevated. We did
not suspect hepatic metastases, and her liver was not easily palpable;
however, her liver function tests were markedly elevated, and a
CT scan of her abdomen showed very extensive and impressive disease.
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Case continued: One year after
radiation therapy, while on tamoxifen |
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Patient was asymptomatic but CA 27.29 was 186
U/mL; CT scan of the abdomen showed extensive hepatic metastasis |
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Liver function studies were abnormal — elevated
alkaline phosphatase, bilirubin
1.8, transaminases in the 100s |
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Dr Love: Dr Robert and Dr Perez,
what would you do at this point?
Dr Robert: I saw a similar patient
not long ago. Her CA 27.29 was 14,000 U/mL and her liver function
studies were abnormal. She was naïve to any chemotherapy,
so an anthracycline-based regimen was an option, but I don’t
routinely use these up front for metastatic disease. I started
the patient on weekly carboplatin/paclitaxel and I would have done
the same for Dr Brooks’ patient. I think there is an advantage
to giving the weekly regimen in a patient with increased LFTs in
whom you need to be careful about giving a taxane. When you give
it weekly, you can see how they react and then decide if they can
tolerate day eight or not. If not, you can postpone it, as opposed
to giving it every three weeks.
Dr Perez: Regarding the weekly
regimen, I think the issue that Nick brings up is appropriate.
It’s important to remember the relationship between liver
enzymes and toxicities associated with taxanes. Clearly, the last
thing we want to do is harm the patient.
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Case continued: Patient enrolled
in a study comparing carboplatin/paclitaxel versus weekly paclitaxel
and randomized to weekly paclitaxel, 90 mg/m2 |
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Received 10 doses over 11 weeks, missed one dose
because of myelosuppression |
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While on treatment, CA 27.29 rose from 186 to 4,600 U/mL;
repeat abdominal
CT showed massive ascites |
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Taken off clinical trial and within two weeks
developed hepatic encephalopathy
necessitating hospitalization |
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Dr Love: Dr Brooks, at this point
what happened with the patient?
Dr Brooks: At that time, we
were participating in a trial comparing carboplatin/paclitaxel
versus paclitaxel, and she was randomized to paclitaxel. She received
10 weekly doses, but had a relentless rise in her tumor markers
and developed a palpable liver and massive acites. I took her off
the clinical trial and while we were discussing what to do next,
in sort of a heart-stopping fashion, she developed hepatic encephalopathy
and had be hospitalized.
Dr Love: Was this patient so
impaired that you couldn’t turn to her for a decision as
to whether she should be treated?
Dr Brooks: The hepatic encephalopathy
happened quickly and caught me off guard. The patient and I hadn’t
yet discussed what to do in a situation like this. At this point
she wasn’t in a coma, rather she was alert, but confused.
When she took narcotics, she was impaired. Her children were too
young, so I had “end-of-life” discussions with her
brother and sister. I explained that I didn’t think we would
be able to alter her course with treatment. They agreed to a DNR
order, but they wanted to try one more therapy because of her young
age.
Dr Love: Out of curiosity, do
most of you try to have those kinds of discussions earlier on?
It’s such a difficult topic to bring up. Dr Cohen?
Dr Cohen: We encourage patients
to execute a Durable Power of Attorney for Healthcare, so at least
there will be something on paper identifying a responsible person
who can make decisions when the patient is non compos mentis. But
as in this case, often it’s the last item on your agenda,
and you don’t want it to come up. And then when it does,
it's usually not convenient. So we tend to put it off more than
we should.
Dr Love: You had a very difficult
human decision to make at this point. Nick, what do you think you
would have done?
Dr Robert: Let me just say that
what’s even worse is being the on-call oncologist when this
patient comes in and you don’t even know them. It’s
a very unpleasant conversation to have with patients. You send
a mixed message, saying, “We’re trying to make you
better,” and then adding, “but what do you want us
to do when you’re near your death?” It is easier to
have that discussion in the office when the patient isn’t
doing so well, and it's easier to deal with the family then as
well.
At this point, if you are going to treat the patient, you’re
looking for a “Hail Mary” intervention. I’ve
heard anecdotes of similar patients having good responses. With
all the options you have after that, I wouldn’t start with
capecitabine, but I would consider liposomal doxorubicin HCL, vinorelbine,
and gemcitabine.
Dr Love: Dr Perez, the patient
has a bilirubin of 18. What would you have done at this point?
Dr Perez: This is a very difficult
situation from an ethical perspective. If I were going to treat
this patient, I would use capecitabine, because it is not metabolized
in the liver — that’s assuming she still has good renal
function. However, my general approach is not to treat a patient
with chemotherapy unless the patient can understand the risk/benefit
ratio.
Dr Harth: I agree with Dr Perez,
I wouldn’t treat this patient without her understanding the
implications. But even if she did understand, I would have serious
reservations about treating her given her performance status and
abnormal liver functions. I would do everything possible to explain
to her and her family that even though we have drugs available,
I don’t think they would offer her anything in terms of response,
and they have a lot of toxicity.
Dr Capistrano: I agree with
Dr Harth. It would be very difficult for me to treat this patient
with chemotherapy. I think chemotherapy is something patients have
to participate in, in terms of whether they want to continue therapy
or not. This patient’s performance status and abnormal laboratory
data almost preclude you from giving chemotherapy.
Dr Chittoor: I would not treat
this patient. I believe that from day one, this patient did not
have good insight into her disease or the implications of treatment.
I don’t believe treatment is justified in this case.
Dr Say: I agree. It’s
difficult to obtain an informed consent when the patient is confused.
In my experience, I’ve found the primary care doctor can
be very helpful at this point in obtaining a Durable Power of Attorney.
They have a long-term relationship with the patient, and we can
invoke their help.
Dr Love: Dr Brooks, can you
give us a follow-up on what happened?
Dr Brooks: I didn’t really
think of capecitabine as chemotherapy because of the favorable
risk/benefit ratio. While I feel patients need to consent to chemotherapy,
this family was pushing for treatment, and capecitabine seemed
like a good in-between solution. I gave a “Hail Mary” round
of capecitabine at a generous dose, and within three weeks her
bilirubin dropped to 3.2, her ascites resolved, and she went home.
Frankly, I was treating the family more than the patient when
this unexpected response occurred. She had one of the most dramatic
and fastest responses to capecitabine that I’ve ever seen.
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Case follow-up: |
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The patient did well for five months, but then
experienced right upper quadrant pain |
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CA 27.29 rose to 1100 U/mL |
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Patient switched to hormonal therapy with goserelin |
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CT scan and tumor markers are stable, although she still
has abnormal liver function that may be unrelated to the breast
cancer |
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