Dr. Eric Winer on Aromatase Inhibitors (SABCS 2009)

Thanks Yaz,

A lot of us have been saying there is no survival advantage for adjuvant Arimidex. Nobody believed us. Now when a famous cancer doctor from Dana Farber says the same thing more people will realize we are all looking at the same studies.

I saw this video when it first came out of the San Antonio Breast Cancer Symposium but it disappeared. Glad you found it.  http://www.youtube.com/watch?v=lX2hjjtqGZU&feature=related

 ! thanks

It's good to see Dr. Winer agrees with us Natural Girls-- that Arimidex has no survival benefit.

Think of the poor women who won't get the chance to see the video.

he does still prescribe them so obviously thinks there is a benefit, as he says in the video and here:

http://www.nccn.com/component/content/article/57-cancer-answers/244-cancer-answers-aromatase-inhibitors.html 

For the benefit of anyone who can't see the video in Yazmin's link, I've made a transcript of it.  This took quite awhile, but I'm pretty sure it's a word-for-word transcription.  Please let me know if I mis-typed anything. Now maybe we can see what Dr. Winer was actually saying at that meeting.

+++++++transcript begins+++++++++++

Eric P. Winer on Hormonal Therapy in Breast Cancer at SABCS 2009

"So, it’s now been about eight years since we had the first results reported from studies looking at aromatase inhibitors in the adjuvant setting, and there have been multiple studies. 

"These have included studies that have compared tamoxifen versus an aromatase inhibitor as the initial therapy; studies that have looked at a crossover approach where 5 years of tamoxifen is compared to 2 to 3 years of tamoxifen followed by an AI; and then of course there’s the MA-17 approach where after 5 years of tamoxifen women were randomized to an aromatase inhibitor versus a placebo.

"Looking at all of those studies I think what we can say is that the aromatase inhibitors given at some point in time to a post menopausal woman decrease the risk of a recurrence.

"The impact on survival is far, far more modest. In some of the studies there has been absolutely no improvement in survival; in some there’s been a slight trend; in others it’s just barely reached statistical significance.  With time, we may see a little more, but it’s probably not going to change that much unless we come up with a way of changing our approach.

"Today we heard results here in San Antonio from the TEAM trial that compared 5 years of exemestane versus a couple of years of tamoxifen followed by exemestane.  And, similar to the results seen with BIG 1-98, where the same question was addressed with letrozole, there really was no striking difference between the arms.  Whether a woman received tamoxifen first followed by exemestane, or exemestane for the entire 5 years, didn’t seem to matter.  She had the same outcome when all was said and done at the end of 5 years.

"One of the big questions when doctors are talking to patients about adjuvant hormonal therapy in the post-menopausal setting is side effects, and how to put together a regimen with the fewest side effects.  And, very clearly, the aromatase inhibitors and tamoxifen have different side effects. 

"Tamoxifen has a slightly increased risk of endometrial cancer and blood clots and is associated with vaginal problems – vaginal discharge and sometimes some bleeding.

"On the other hand, the aromatase inhibitors are associated with a variety of musculoskeletal problems. There is the increased risk of osteoporosis and fracture, some of which – perhaps most of which – can be ameliorated with bisphosponates.  And, then there is this syndrome of arthralgias and tenosynovitis that can be very troubling to people, and keeps about, probably, 5 to 10 percent of patients from taking the aromatase inhibitors after they’ve started it.  They actually come off therapy.

"Given the data, what my feeling is, is that we should be picking the adjuvant hormonal therapy that a patient is most likely to take.  If she doesn’t take therapy, she can’t be helped by it.  If she has a lot of side effects with therapy, she is unlikely to take it.  So, we really have to work toward tolerability, and that’s going to vary from patient to patient."

+++++++++transcript ends+++++++++++++

Now, maybe it's just me, but what I'm understanding is that, in every study to which he is referring, the aromatase inhibitor was being tested against tamoxifen or against a tamoxifen/AI combination (in sequence).  The only exception was with the MA-17 study in which women were randomized to an AI or a placebo after they had already been on tamoxifen for 5 years. There, the AI offered no additional survival benefit after the 5 years of tamoxifen.

So, except for the MA-17 study, his comment about there being "absolutely no improvement in survival," or possibly just a "slight trend" toward improved survival, with an AI, was in studies where the effect of the AI was compared to the effect of tamoxifen (or the combination).  Dr. Winer even says, "... there was no striking difference between the arms" in the TEAM trial and BIG 1-98; then he re-states what those "arms" were for the TEAM trial:  tamoxifen first (for 2 years) followed by exemestane, or exemestane for the entire 5 years.

I made the transcript because I am concerned that some readers will misinterpret this thread to mean Dr. Winer is saying there is no survival benefit at all with AI's.  Instead, he is saying that they compare pretty closely with tamoxifen with respect to survival -- there is no advantage to taking an AI rather than tamoxifen.  In the last section of the video, he emphasizes that doctors need to help their patients choose which of those two routes -- tamoxifen versus AI -- is the most tolerable.

otter

Thank you, Otter....that's how I read it too.

I'm sure there will be some nay-sayer along to dispute what you have written, however......

Otter, I read the NCCN guidelines and on adjuvant therapy there are different decision trees: 1)pre-menopausal--5 years tamoxifen and if still premenopausal after 5 years, no further treatment.

(Although I know MOTC has been transitioned to lupron/Armidex--so guidelines are guidelines, not absolute instructions.)

2)Premenopausal without a shift to post menopausal during tamoxifen treatment: 5 years tamoxifen, followed by 5 years AI.

I seem to be in the latter group, and while I want to do everything possible, and I see one of Dr. Winer's colleagues at DFCI, who writes the NCCN guidelines, I'm reluctant to take 10 years of adjuvant therapy if there is not a tremendous benefit, and the benefit out weighs the risks.

My DFCI onc, Burstein, said at the last visit that safety issues were still being worked out, prior to that he said, I would definitely be in the 5 years tamoxifen, followed by 5 years of an AI.

Kira (scheduled for my second D&C on tamoxifen, for polys--but no sign of menopause yet...)

Thanks so much Yasmin, for posting this informative link.  I am going to start tamoxifen on the 17th of Feb.  I am on the cusp of peri and post menopause.  The stress of being diagnosed with breast cancer gave me a period in June but prior to that I had only had one period that year.  So..I am not a candidate for AI's.  I am leaning toward sticking to tamoxifen for the entire five years if the SE's are tolerable.

Thanks for the transcript, otter!!

That's how I understood it, too. No benefit from AIs over Tamox, but SOME hormonal is needed. Take the one that treats your body best if you have to take one at all.

But if you have problems with both types?? Make your decision and move forward, like I did.

"Recurrence" encompasses "local" and "distant".  Distant = mets.

Hello BC sisters, this the first time I have posted on this thread. I have been reading everyones posts and it is alot to take in. I am taking Femara and have been since Oct. 2009. I started off okay but since last Oct. it has been down hill baby! Pain is crazy. Now my fingers are curled when I wake up. So for 24 hours a day, I feel like a truck ran over me. My Onc told me to climb the mountain....meaning get over it. I take Vit D3, Calcium/Mag, Glutemine, Vicodin to ease the pain and a sleeping pill to sleep so I don't feel the pain. I am pretty much done with this! Four more years...I can't imagine!. I am 61 and always been very active but now I am a pill-popping, in pain all day woman. This Femara is to block the estrogen, right? I have reasearched Natural supplements which do the same....I think. Myomin is one and Chrysin is another. Anyone know about this. I need to look at Dr. Winer's video. I am going to try to find it now. Help anyone!!!! I appreciate it.

I can't help but wonder if my mets started after ending my 5 years on tamoxifen/Femara since I had no node involvement.  Will probably never know.

ktmimi2 What's with your onc? There are other Als to try. I have read that Arimidex can have fewer SE for some women (the generic might have a few more SE than non generic). Has your onc tried other Als. What you describe seems unacceptable IMO.

SoCalLisa, one onc I sought for a second opinion had your regimen, that is, 1 yr of Tamox before AIs. I think the reasoning is that if you were still menstruating before treatment there's a chance you're still premenopausal after chemo. I decided to go with Femara straight away. And yes, it felt like being run over by a truck and then flattened by a whole convoy of them.

Karen, recurrence is when the cancer comes back either locally or as mets. Disease free survival is the period when they can't find any cancer in your body, when you haven't had a recurrence. This is usually distinguished from overall survival which is the period you're alive, with disease or not, whether it's cancer that kills you or not. That's my understanding. And my understanding is also that Dr. Winer was talking about survival advantage comparing tamoxifen and AIs.

I noticed that you've stopped AIs for 10.5 months, Karen. I just wanted to say that I did take a one-month break this summer and it is nowhere near as bad this second time around after that break. Having said that I'm procrastinating on scheduling my 3-month check up. They always find something they need to biopsy which so far always turns out clear. Great but nerve-wracking!

Changing to a different AI is also an option. I had horrible pain on Arimidex, but did well on Femara and Aromasin.

Wow, Otter - thanks so much for the transcript! 

You said (copied here for emphasis!), "I am concerned that some readers will misinterpret this thread to mean Dr. Winer is saying there is no survival benefit at all with AI's. Instead, he is saying that they compare pretty closely with tamoxifen with respect to survival -- there is no advantage to taking an AI rather than tamoxifen. In the last section of the video, he emphasizes that doctors need to help their patients choose which of those two routes -- tamoxifen versus AI -- is the most tolerable. "

Seems to me Dr. Winer's bottom line is AIs and Tamoxifen BOTH offer survival benefits over taking nothing at all, and the benefit is similar for both.  

<sigh...> I'm triple negative and, sadly, neither are helpful in my case.