I'm due to stop Tamoxifen this spring and have the same questions.  I'm
wondering if I should take Femara?  

From the Susan Love website:

Letrozole (Femara) After Tamoxifen: New Data, New Questions

In an early release article published on the New England Journal of Medicine
website (www.nejm.org) on October 9, researchers announced that they stopped a
randomized trial that had enrolled postmenopausal women with early-stage breast
cancer who had already been treated with five years of tamoxifen after their
interim results found letrozole (Femara) to be superior to a placebo.

Studies have shown that taking tamoxifen for five years reduces the risk of
recurrence for women with early stage breast cancer, and that the benefit from
taking the drug appears to persist even after the drug has been stopped.

But with the introduction of the aromatase inhibitors‹drugs that stop
estrogen production and keep estrogen out of breast cells in a way different
than tamoxifen does‹another question had to be answered: What would happen if
a woman began taking an aromatase inhibitor‹in this case letrozole‹after
taking five years of tamoxifen?

To test that question, researchers randomized 5187 women who had finished five
years of tamoxifen to either letrozole or a placebo. At the first interim
analysis, which was done after women had been in the study for an average of
2.4 years, the researchers found that there had been 75 local or metastatic
recurrences of breast cancer or new primary cancers in the other breast in the
letrozole group, compared with 132 in the placebo group.

Specifically,
In terms of local recurrences (recurrence in the same breast): Letrozole: 14
(0.5%)        Placebo: 30 (1.1%)

In terms of distant recurrences (metastases): Letrozole: 47 (1.8%)      
Placebo: 76 (2.9%)

In terms of new cancers in the other (contralateral) breast: Letrozole 14
(0.5%)        Placebo: 26 (1%)

The total: Letrozole: 75 (2.9%)        Placebo: 132 (5%)

Another way to say this is that 5% of the women in the placebo group had a
recurrence compared to 2.9% of the women who had been given letrozole.

Because this benefit was so clear, the independent data and safety monitoring
committee overseeing the study recommended that the trial be stopped so that
all of the women enrolled in the study could benefit from letrozole.

But stopping the study raises new questions.

Because the study was stopped early, we don¹t know how long letrozole should
be taken to get the maximum benefit. (Very few women in the study actually took
letrozole for the full five years.) Also, because the study was stopped early,
we don¹t know what the long-term complications of letrozole are. This is a
concern because the aromatase inhibitors have been found to increase a woman¹s
risk for developing osteoporosis. In fact, the study found that there were new
diagnoses of osteoporosis in 5.8 percent of the women in the letrozole group
compared with 4.5 percent of the women in the placebo group.

The women who will benefit the most from taking letrozole after tamoxifen will
be those who had the highest risk for recurrence before starting on tamoxifen.
For those women who have a low risk of recurrence, it will be necessary to
weigh the benefit letrozole may provide with the risk of osteoporosis.

Some women may be thinking, why take one drug after the other; why not take
them both together? The answer to this question lies in the ATAC trial, which
studied tamoxifen and the aromatase inhibitor Arimidex. This trial randomized
women to Arimidex, tamoxifen, or Arimidex and tamoxifen together, and found
that the women who took both drugs actually had a higher risk for recurrence
than did the women who took only Arimidex or tamoxifen.

The bottom line: This is an important study, and letrozole is going to be an
important new option for many women who have completed five years of tamoxifen.
What we can't forget about, though, are the side effects that accompany
letrozole, and those have to be factored into the decision-making process,
especially for women at low risk for recurrence.

Hopefully nothing happens.  There isn't anything that can protect your body
from bc forever, and all tamoxifen does is reduce the chance.  It's been proven
to lose it's effectiveness after 5 years, which is why women only take it that
long - there's no benefit to taking it longer.  

My bc was almost 2 years ago, so I'm able to view it as part of my past.  It's
not my present, and not my future.  When the 5 years is up I'll be glad I don't
have to try to remember to take the pills twice a day, and won't bother seeing
the oncologist once a year - I'll just be a normal healthy person!

Sue - DivaofDVC   aka WDW1972
DVC '97   OKW, Beach Club, Vero Beach, & Hilton Head

Bea, if you take Tamoxifen for five years without mets or a recurrence
you're done.  That's what you could call 'working without a net'. I
guess  :)

There's no evidence to suggest Tamoxifen longer than five years makes
one any safer and there *is* evidence that long-term Tamoxifen
increases the likelihood of uterine cancer.

We can't say that tamoxifen will protect you from recurrence forever, but
tamoxifen does appear to have a "persistence" effect after treatment has
ended. The Early Breast Cancer Trialists' Collarborative Group produced a
paper* that demonstrated this effect a few years back.

Here are two tables of number from that paper. You'll have to edit them to
get the columns to line up. I've supplied handy vertical slashes to help.

These numbers are for recurrence-free survival of axillary node positive
women. About half the patients took tamox, the remainder took placebos. The
numbers for axillary node negative women are higher of course.

After following the patients for 5 years, the following number of patients
were recurrence-free:

Yrs trtmnt | Tamox | Placebo
1 | 58.3% | 50.2%
2 | 63.5% | 51.4%
5 | 75.6% | 58.3%

So for the group of women who took a pill for 1 year, 58.3% who took tamox
pills were recurrence-free and 50.2% who took placebo pills were
recurrence-free at the 5 year mark. For the 2 and 5 year treatment groups,
the differences are even larger.

After following the same patients for 10 years, the following number of
patients were recurrence-free:

Yrs trtmnt | Tamox | Placebo
1 | 44.2% | 36.7%
2 | 49.5% | 39.5%
5 | 59.7% | 44.5%

Look at the group of women who took tamoxifen for only 1 year. Even though
it's been 9 years since they've last taken a tamoxifen pill, they still have
an advantage over women who've never taken tamoxifen. Similar statements can
be made for the 2 and 5 year tamox treatment groups. This is where the
"persistence of tamoxifen benefits" statements come from.

Much more recently, fairly convincing evidence that taking letrozole, or
Femara, after tamoxifen can also help BC patients remain recurrence free for
at least a few years more was presented at the last SABCS and published** in
the New England Journal of Medicine. Letrozole is an aromatase inhibitor
(like Arimidex or anastrozole). The results were so good that the trial was
ended after only 2.4 years of followup - not the planned 5 years.

The researchers were roundly criticized for ending the trial early by other
researchers and patient advocates alike. The problem is that aromatase
inhibitors tend to decrease bone density  and weaken  the patient's bones.
How much does it weaken bone? Does it get progressively worse and worse or
does it stop after some time? How long does it take? Are there any other
long term side effects of profound estrogen depletion produced by letrozole?
Is this reduction in recurrence a lasting effect? Is it like tamoxifen where
the benefits of taking a pill every day end after a few years?

Well, I guess we'll never know until we do "field testing" on BC patients in
general - even then the results could be unclear because there is no control
group. One of those field testers could be my wife who stops tamoxifen in a
few months. How will you decide what the risks of letrozole are after your 5
years of tamoxifen are up?

Hope this helps, abstract for the NEJM paper is below.

Lance
*****

*Tamoxifen for early breast cancer: an overview of the randomised trials;
Early Breast Cancer Trialists' Collaborative Group;The Lancet; 351(9114), pg
1451

**A Randomized Trial of Letrozole in Postmenopausal Women after Five Years
of Tamoxifen Therapy for Early-Stage Breast Cancer
Goss P. E., et al
N Engl J Med 2003; 349:1793-1802, Nov 6, 2003

ABSTRACT

Background In hormone-dependent breast cancer, five years of postoperative
tamoxifen therapy -- but not tamoxifen therapy of longer duration --
prolongs disease-free and overall survival. The aromatase inhibitor
letrozole, by suppressing estrogen production, might improve the outcome
after the discontinuation of tamoxifen therapy.

Methods We conducted a double-blind, placebo-controlled trial to test the
effectiveness of five years of letrozole therapy in postmenopausal women
with breast cancer who have completed five years of tamoxifen therapy. The
primary end point was disease-free survival.

Results A total of 5187 women were enrolled (median follow-up, 2.4 years).
At the first interim analysis, there were 207 local or metastatic
recurrences of breast cancer or new primary cancers in the contralateral
breast -- 75 in the letrozole group and 132 in the placebo group -- with
estimated four-year disease-free survival rates of 93 percent and 87
percent, respectively, in the two groups (P0.001 for the comparison of
disease-free survival). A total of 42 women in the placebo group and 31
women in the letrozole group died (P=0.25 for the comparison of overall
survival). Low-grade hot flashes, arthritis, arthralgia, and myalgia were
more frequent in the letrozole group, but vaginal bleeding was less
frequent. There were new diagnoses of osteoporosis in 5.8 percent of the
women in the letrozole group and 4.5 percent of the women in the placebo
group (P=0.07); the rates of fracture were similar. After the first interim
analysis, the independent data and safety monitoring committee recommended
termination of the trial and prompt communication of the results to the
participants.

Conclusions As compared with placebo, letrozole therapy after the completion
of standard tamoxifen treatment significantly improves disease-free
survival.

Notice: Because of its potential therapeutic implications, this article was
published at www.nejm.org on October 9, 2003. It will appear in the November
6 issue of the Journal.

*Tamoxifen for early breast cancer: an overview of the randomised trials;
Early Breast Cancer Trialists' Collaborative Group;The Lancet; 351(9114), pg
1451