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Supplement: Section 9
Section 9
Neoadjuvant
systemic therapy
OVERVIEW
Randomized clinical
trials have demonstrated that while neoadjuvant systemic therapy
downstages tumors and improves the chance for breast conservation,
disease-free and overall survival seem to be about the same compared
to using treatment postoperatively. A new generation of studies
is evaluating a variety of strategies including taxanes, dose intensive
chemotherapy and endocrine treatment, particularly with the third-generation
aromatase inhibitors. The neoadjuvant setting is also being utilized
to evaluate new systemic agents and predictors of tumor response,
including DNA microarray analysis.
EFFECT
OF PREOPERATIVE CHEMOTHERAPY ON LOCAL-REGIONAL DISEASE IN WOMEN
WITH OPERABLE BREAST CANCER: FINDINGS FROM NATIONAL SURGICAL
ADJUVANT BREAST AND BOWEL PROJECT B-18
(Closed to Accrual) Protocol |
Fisher
B et al. J Clin Oncol 15:2483-2493,1997. Abstract
|
NEOADJUVANT
ENDOCRINE THERAPY
Neoadjuvant
therapy allows you to determine in a couple of months whether or
not an agent is going to have a favorable impact as opposed to giving
a drug blindly for years after local therapy and hoping that it
will do good. There are a lot of data for chemotherapy, and I am
certain that similar data will emerge for endocrine therapy. The
limited studies that were done in ER-positive, postmenopausal women
showed a very high degree of antitumor activity in patients treated
with aromatase inhibitors. In one trial, anastrozole showed dramatic
tumor reductions - 70% or 80% of the patients showed objective shrinkage
of their disease and close to two-thirds of the women became candidates
for breast preservation after approximately four months of therapy
with anastrozole.
-Aman
Buzdar, MD
NEOADJUVANT
CHEMOTHERAPY
I view induction
chemotherapy as a positive trend, because you do not lose anything,
and there is a higher likelihood of being able to do a lumpectomy
with a much better cosmetic result. It also provides an in vivo
chemosensitivity assay. This trend will also allow us to start looking
at minimally invasive surgery to the primary tumor. I predict that
in the next decade we will move away from axillary node dissection,
and sentinel node biopsy may be a transition maneuver in this regard,
because people do not yet feel totally comfortable giving up the
nodal status information. But once we start using systemic therapy
first, the remaining question relates to treatment of what's left
of the primary tumor. The research question then would be, "Do
you need to take the patient to the operating room at all?"
-Eva
Singletary, MD
NEOADJUVANT
THERAPY AND BREAST PRESERVATION
What has
always impressed me about neoadjuvant endocrine therapy is that
if patients are selected properly, a similar change in tumor volume
can be achieved as with chemotherapy. It requires a slightly longer
time period, but there are far fewer side effects. Our quality of
life studies show that patients don't seem to mind taking neoadjuvant
endocrine therapy for a few months, because there are very few side
effects.
We have a
group of elderly patients who avoid medical care, because they don't
want to undergo extensive surgery. Many of the tumors in these women
are quite large and estrogen receptor-rich. After neoadjuvant endocrine
therapy, mastectomy is usually not required, and patients can have
much less deforming surgery...
...Our initial
work with tamoxifen led us to look at some of the more active agents
- the aromatase inhibitors. And what impressed us as soon as we
started to use the aromatase inhibitors was that we seemed to be
getting much quicker responses and much greater responses in terms
of percentage reduction in tumor volume. If you give tamoxifen,
it takes four to five weeks to build up adequate levels in the circulation.
If you give an aromatase inhibitor, it works immediately. So maybe
it's just that with tamoxifen if you treat them for three months,
you don't really get three months of effective treatment. With aromatase
inhibitors, you can get quite marked effects with reductions in
tumor volume within four weeks.
-J
Michael Dixon, MD, FRCS
MICROCALCIFICATIONS
AND DCIS
We have greatly
increased our use of neoadjuvant cytotoxic therapies in patients
in whom we would like to facilitate breast conservation. The critical
rate-limiting step is the presence of malignant microcalcifications.
The Italians taught us a few years ago that neoadjuvant therapy
is great for invasive disease, but it is not great for DCIS. So
the presence of widespread malignant microcalcifications should
be considered today a contraindication to trying to use these drugs
to conserve the breast.
-Patrick
Borgen, MD
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