What about other kinds of trials?
Not randomized control trials.
We talk about cohort trials and case control trials.
Cohort trials, as you can imagine, take a cohort or a group of patients.
And then you can follow these patients and
see which patients develop an outcome and which patients don't.
So you take a group of patients and
you say I'm going to follow these patients forward.
Half of these patients smoke.
Half of these patients don't smoke.
We'll see who develops lung cancer.
That gives you a sense.
Case control trials are similar but almost backwards.
So you have cases of patients who had breast cancer and
controls who didn't get breast cancer.
And then you go backwards and
you see what are the ideologic factors that may have led to those outcomes?
This brings us to the last set here,
which is prospective studies, ones that go forward in time.
These are often randomized control trials or cohort studies where we're
following a group of patients over time versus retrospective studies.
So studies where we go back in time, we look at data and we say, what caused this?
What can we dig it out from the data that we already have historically,
that may have led to these outcomes?
Now, this is a key slide, especially for those of you who may be in this field and
often are trying to remember all of the key trials that have really
brought us to where we are in breast cancer management.
It's funny because a lot of this seems like alphabet soup.
Different trials with different letters and different numbers,
trying to remember what all of these are.
But these are really landmark trials,
many of which we've talked about during this course.
Remember the NSABP B-04 study?
That was the study that randomized people to radical mastectomy where we
removed the pectoral muscles and all of the lymph nodes to total mastectomy and
the finding was that survival was the same.
So, we really didn't need to take out muscles and all of the lymph nodes.
Critical information as we moved forward because now, we don't do that.
The NSABP-06 trial similarly was a landmark trial.
This was the trial that randomized people to having a total mastectomy which
remember with standard of care, just back in the 60s,
to now breast conserving surgery.
And the finding that these two were equal means that we can give patients these
options.
Remember back to the surgery section of this course?
That was a critical element in what we talked about.
What about the NSABP B-14 study?
This was a study that looked at tamoxifen in estrogen receptive
positive invasive cancer.
Now this has become standard of care.
B-18 was the neo-adjuvant chemotherapy study.
Remember the study that had patients who were randomized to either receive
chemotherapy followed by surgery?
Or surgery followed by chemotherapy?
Remember how that trial found that the survival rates were the same?
So now we can offer patients either of these two strategies and
we know the advantages and disadvantages of each.
What about B-20?
B-20 was the study that actually looked at chemotherapy, and
showed that chemotherapy in breast cancer made a difference.
B-24 started to look at DCIS, that pre-cancer, and
the fact that tamoxifen could benefit patients, particularly now
who have ER-positive DCIS, and that has become standard of care.
What about B-32?
B-32 was the trial that looked at sentinel node biopsy, and showed that really,
survival was the same, whether you did a sentinel node biopsy followed by
axillary node dissection only if the sentinel node was positive, or
if you did an axillary node dissection on everybody.
Revolutionized standard of care.
The B-35 trial looked at aromatase inhibitors in DCIS.
B-39 is looking at accelerated partial breast irradiation.
B-42 was extended adjuvant therapy, so
do you only need five years of hormonal therapy or is ten years really better?
Some of these we're still waiting for the long-term results, more trials.
MA-17, a great trial, looking at extended adjuvant therapy after tamoxifen.
So this randomized patients who had had five years of
tamoxifen to placebo versus an aromatasin inhibitor.
Remember, placebo, because standard of care was only five years, and so
they gave half the patients a placebo, half the patients an aromatase inhibitor
after they had finished five years of tamoxifen.
And this is another study that shows you the value of regulatory oversight,
because this study was stopped early, why?
Because the Data Safety and Monitoring Board,
who is looking at this trial as it's going along, found while the study
was going along that one arm was doing much better than the other arm.
So they unblinded the trial, and what did they find?
They found that the people in the aromatase inhibitor arm were doing better
than the placebo arm.
Remember, placebo was standard of care.
And so, the patients who were on the trial,
those were the first patients to find out the results of this study and
it was opened up to the world so that everyone now knew,
that extended adjuvant therapy had a benefit over five years of tamoxifen.
Again, practice changing results from clinical trials.
MA-20 was just recently reported showing the benefit of extended radiation fields.
Z-11 has become practice changing even though it didn't
find a statistically significant difference between the two arms.
Remember, this was a non-inferiority trial,
that means that instead of trying to find that one arm was better than the other,
it was trying to find that two arms were equal,
one arm of course was doing less, so would have less morbidity.
Even though the Z-11 trial did not meet it's target accrual,
sadly because too few surgeons put their patients on the trial,
too few patients participated in the trial, it still became practice changing.
Because we looked at the data and found, you know what, maybe we don't need
to do an axillary node dissection even if patients have positive nodes.
Again, clinical trials hugely important.
The Zed-1071 trial looked at sentinel node biopsy after neoadjuvant chemotherapy.
We had usually forced people to have a sentinel node biopsy before,
that meant two operations, but this trial demonstrated that it was
feasible to do a sentinel node biopsy after neoadjuvant chemotherapy.
Prevention trials, the P-1 trial, showed that tamoxifen
could reduce your risk of developing breast cancer by 50%.
STAR trial found that raloxifene had an equal reduction of risk.
We talked about these two when we looked at prevention.
Go back and check it out if you haven't already.
And then, newer trials are looking at Genomics.
So the TAILORx trial, just one of the many trials looking at how
we can use molecular biology to really tailor therapies.
All of these, I hope, give you a flavor of how important these clinical trials are,
how they really make a difference, and they're practice-changing.
So I hope that all of you get as excited as I am about clinical trials.
I really like this idea of patients and clinicians and
researchers looking down that microscope of clinical trials together.
Together, we are going to make treatment better and a brighter tomorrow.
So until next time, I'm Dr. Anise Chagpar.
Thanks so much for joining me.