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Select Excerpts from the Interview
Tracks 1-2
DR LOVE: You’ve had a major leadership role in studying markers of
prognosis and response to treatment. Where do you see the Oncotype DX
assay fitting into clinical practice?
DR HAYES: Our diagnostic skills and capabilities are primitive right now. We
know that 80 to 85 percent of node-negative patients will never experience
disease recurrence after surgery and radiation therapy no matter what we do,
especially if they have ER-positive disease and receive endocrine therapy. Yet
many of those women are also administered chemotherapy because we want
to make sure we see the mortality reductions we believe are derived from
adjuvant chemotherapy in those patients who do benefit.
There are women with node-negative disease who will experience a recurrence and would have benefited from chemotherapy. However, we don’t know who they are. I believe the days of using anatomic prognostic factors are coming to an end. Biological factors have been used for many years, ever since Jensen and McGuire told us about ER (Horwitz 1978) and Slamon told us about HER2 (Slamon 1987).
What we need to do is get smarter about identifying the patients who have a high chance of recurrence and a high chance of benefiting, not just from chemotherapy but from specific types of chemotherapies. I’m optimistic we can do this.
In addition to ER, PR and HER2, we have had an enormous explosion in molecular biology. Now we have the ability to look at not just expression of multiple genes, but also at abnormalities in multiple genes at once — not just genes that are present in the tumor, but also genes that we inherit, which may ultimately affect how our cancers behave or how we behave when we’re exposed to therapies.
I believe Oncotype DX is a good assay. The developers and the investigators with whom they’ve collaborated have done all the things I would ask them to do to develop a new assay. They started out by asking, “What’s the question?”
The question for many of us is about this group of patients — those with node-negative, ER-positive disease. If we assume they’ll all receive hormone therapy, the question is, “Which of those patients still has a high risk of recurrence?” More importantly, “In which of those patients is chemotherapy likely to be of benefit?”
Track 6
DR LOVE: How does tumor size fit into treatment decision-making for
patients with node-negative tumors?
DR HAYES: I’m increasingly less enthusiastic about tumor size. Tumor size, to
me, doesn’t mean a lot biologically. I’m not sure what tumor size reflects in
terms of the odds of the cancer being able to metastasize, other than perhaps
the tumor was growing quickly and became big before you picked it up, or
that the tumor’s been there a long time. I believe the biology within the tumor
is more important than size.
DR LOVE: What do we know about the Oncotype DX assay in larger tumors?
DR HAYES: All we know is from what was in the NSABP data (Mamounas
2005). I can’t document this, but I believe patients in the critical B-14 and
B-20 trials evaluating Oncotype DX tended to be those who had something
that suggested to their doctor that they had a worse prognosis.
I was an active clinician just starting my practice in the days when B-14 and B-20 were launched. Most of us were skeptical that adjuvant systemic therapy would be of much benefit in node-negative patients. So the only ones we encouraged to participate in those studies were those we perceived were not going to do well.
This is total speculation, but one would guess that the patients on those studies probably have a slightly worse prognosis than the patients who didn’t get on those studies.
We can now estimate the odds of benefit from chemotherapy with relative certainty or the relative ability to be pretty accurate. We can run through the numbers and tell a patient that she would improve her chance of being disease-free by two percent or five percent or 10 percent.
Overall in this country, life-threatening complications occur in about one percent of patients who obtain standard chemotherapy in the adjuvant setting for breast cancer — whether that’s infection, bleeding, a second malignancy such as leukemia or heart failure.
In my clinic, if a woman is otherwise healthy and I calculate that she has a five percent or more benefit, I recommend treatment. If it’s one or two percent, I don’t. If it’s three to five percent, I don’t know what to do.
Track 11
DR LOVE: What’s your take on the cardiac risk associated with adjuvant
trastuzumab-containing chemotherapy regimens?
DR HAYES: The studies have been remarkably consistent. Across the board,
for patients who previously received an anthracycline, about a five percent
incidence of cardiac dysfunction can be measured by external monitoring with
a multiple-gated acquisition (MUGA) scan or echocardiogram. About a one
percent incidence of symptomatic congestive heart failure is seen. About 75
percent of those, maybe higher, seem to be reversible when you stop the drug.
I tell my patients there’s a five percent risk of having some dysfunction that you probably won’t even know about, but there’s a one percent incidence of being symptomatic.
The big fear is whether those patients who had the reduction in cardiac function might, in the long run, be at higher risk for long-term cardiac problems. It may be that when you stop the drug, the cardiac dysfunction goes away and they never have trouble again. We just don’t know.
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