Interview
with Neil Love, MD from Breast Cancer Update for Medical Oncologists,
Program 2 2000
Play
Audio Below:
There
is no question about what adjuvant chemotherapy has an effect ,
independent of ovarian ablation. How do we know that? Well, we know,
for example, that it works and prolongs or improves outcomes in
patients who are receptor-negative. We also know that it has an
impact certainly on disease-free survival, and some impact also
on survival in women who don’t have ovaries; in other words,
in postmenopausal women although the effects are very small. But
now we are getting into a new era where we are beginning, I think,
to look more carefully at the interaction between these two and
the two observations that have to do with chemotherapy studies that
I think are very important.
I
really began looking at this when the statistician for the Intergroup
study comparing four cycles of CA with four cycles of CA plus four
cycles of Taxol, did an unplanned sub-set analysis. I emphasize
that because it doesn’t quite have the same scientific validity,
it wasn’t something we thought about and worked out a scientific
hypothesis and then tested. But in that particular trial all women
who were receptor-positive were given five years of tamoxifen. We
found that, overall, adding four cycles of Taxol to four cycles
of CA was far superior than four cycles of CA. But when we looked
at it separately in the women who are receptor-positive and receptor-negative,
we found that the effect was much greater in the receptor-negative
patients than in the receptor-positive. Now the difference wasn’t
actually statistically significant, but nonetheless the trend was
very strong.
If
we looked at it in terms of those who got tamoxifen versus those
who did not get tamoxifen, we saw exactly the same thing. That is,
if the patient had gotten tamoxifen there was a much smaller additional
benefit from adding Taxol than if the patient hadn’t gotten
tamoxifen. So we can’t say whether this is an interaction between
chemotherapy and ER or chemotherapy and tamoxifen. Now, it came
as a shocker to me because we had previously shown that chemotherapy
is about as effective in the ER-negative and the ER-positive patients
who have metastases so I expected that would be the case here. Then
went back to look at the overview and sure enough, in the overview
you find the same phenomenon. This has nothing to do Taxol whatsoever,
but in the overview, whether you’re looking at younger women
or older women – makes no difference, makes no difference whether
you’re looking at receptor-positive versus receptor-negative
or tamoxifen versus no tamoxifen. The affects of giving chemotherapy
in those patients who had gotten tamoxifen or who were receptor-positive
– probably most of them got tamoxifen – is pretty small
compared to the effects in the receptor-negative. But, again, in
the overview they’re not statistically significant, they’re
just very strong trends.
Well,
that’s one of the things that just happened in this last year.
I mean, the overview, a most recent one, and those data really became
apparent to everybody in October of ’98. I presented the Taxol
study in May of 1998 and then in May of 1999. We saw these LHRH
agonist data that I described, medical ovarian ablation versus chemotherapy
or combinations of, say, Zoladex and tamoxifen versus one. And as
those data then kind of came along, I came to the point – more
than I’ve ever been before – of concluding that a substantial
part of the benefit from chemotherapy in younger women is due to
the effects on the ovaries in receptor-positive patients. And I
think now the burden of proof has to be on those who want to use
chemotherapy in that group of patients to show, not only that there’s
an affect – and I think there’s an effect – but how
big. Is it enough that really is worth the extra toxicity? So I
think we have switched from asking what does Zoladex, or what does
tamoxifen, add to chemotherapy. The question, in ER-positive patients,
what does chemotherapy add to tamoxifen in older women or what does
chemotherapy add to Zoladex and tamoxifen in younger women?
Combined
endocrine therapy for breast cancer - New life for an old idea? Davidson, N. E. (Reprint available from: Davidson NE Johns Hopkins
Oncol Ctr 1650 Orleans St,Rm 409 Baltimore, MD 21231 USA). Journal
of the National Cancer Institute 92(11):859-860, 2000 Jun 7. No
abstract
