We’ve
done some interesting work on the biological effects on aromatase
inhibitors versus the biological effects on tamoxifen. What we found
was that if you give an aromatase inhibitor – during treatment
and after three months – there’s a marked effect on tumor
proliferation. So, things like anastrozole and letrozole, we believe,
switch-off proliferation in the tumor. Tamoxifen has a much greater
variable effect. First of all, it doesn’t switch off proliferation
in all tumors. The proliferation goes down in some, up in others
and stays the same in a few tumors, but tamoxifen has a different
effect in that the glandular differentiation of the tumors increases
in about half the tumors. So, where a tumor did not have any glands,
glands appear. And when you look at the grade of the cancer at the
start of treatment and at the end of treatment, about 50% of cancers
actually move grade.
So
if you got a grade three cancer moving to grade two or grade two
moving to a grade one. This happens with letrozole or aromatase
inhibitors and tamoxifen but in different ways. So with the anastrozole
or letrozole you get less proliferation, so that if you look at
the mitotic index – which is one of the three components of
grade – the mitotic index changes in the aromatase treated
patients. Whereas in the tamoxifen patients you don’t get the
same consistent effect on mitotic index, but you do get this effect
on glandular differentiation. So poorly differentiated tumors become
better differentiated. It’s almost as though you were de-differentiating
tumors,
And
I think that’s interesting that you get in this differential
effect with the two drugs, and that is potentially interesting for
the combination of anastrozole and tamoxifen, because it might mean
that the two are working in different ways that you’ll get
an additive effect.
Similarities
and distinctions in the mode of action of different classes of antioestrogens
[Review]. Wakeling, A. E. Endocrine-Related Cancer. 7(1):17-28,
2000 Mar. No abstract
Approaches
targeted to estrogen receptors for treatment of tamoxifen-resistant
breast cancer: A brief overview. Terakawa, N. Oncology. 59(Suppl 1):3-4, 2000. No abstract
