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Old 06-13-2007, 06:12 AM   #1
aquinis2000
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From our own Dr. Slamon.......comments

I found this very interesting, just wondering how the rest of you felt.



By Robert Bazell Chief science and health correspondent Updated: 5:52
p.m. ET June 5, 2007 What if an estimated 100,000 breast cancer patients
got drugs that did nothing to combat their cancer, but put them at risk
for heart failure and leukemia?


That is the implication of new research that was presented in private
session at this week’s meeting of the American Society of Clinical
Oncology(ASCO) in Chicago.


The research, from Dr. Dennis Slamon, chief of oncology at the
University of California, Los Angeles, suggests that the most widely
used chemotherapy drugs may not benefit most women. Although the
research hasn't been published or peer-reviewed yet, it is expected
to be soon.


The drugs are a common class of treatments called anthracyclines,
including doxorubicin, epirubicin, and mitoxantrone. Since their
introduction in the 1980s anthracyclines have replaced older
chemotherapy drugs in the combination therapies given to women.
Administered in the months after surgery and radiation, the chemotherapy
is intended to reduce the chances of a life-threatening recurrence of
cancer, especially in women at high risk for relapse.


Early on, researchers understood that anthracyclines could cause heart
failure in some patients. Recently, evidence has accumulated about the
additional risk of leukemia, which can strike years or decades after the
treatment.


Evidence for the effectiveness of anthracyclines versus the older drugs
remained murky. Then, a 1998 meta-analysis (a study of all the previous
studies) found the anthracyclines did a 4 percent better job at
preventing recurrence. Despite their side effects, that study elevated
the drugs to the standard of care.


Treating many to help few The UCLA research questions that treatment.


Slamon played a key role in the discovery and development of the hugely
successful breast cancer drug Herceptin. Herceptin, which changed the
way the disease is treated, specifically targets a gene called Her-2
that is overexpressed in 20 percent to 25 percent of breast cancers (a
gene is overexpressed when its effect becomes excessive in the body).
Herceptin’s success proved that breast cancer is not one disease, but
many, with each benefiting from a tailored treatment.


In this latest study, Slamon looked at a more recently discovered gene
called Topoll-2, which is sometimes, but not always, overexpressed
along with Her-2. Anthracyclines stop breast cancer because they
target Topoll-2.


Slamon examined tissue samples from more than 2,000 women who took part
in seven clinical trials. His analysis showed that anthracyclines work
only in women who overexpress the Topoll-2 gene. Such women account for
8 percent of breast cancer cases.


The anthracyclines — with all their side effects — have almost no effect
in 92 percent of breast cancer cases.


“It seems apparent that we are treating patients who don't need the drug
to get at that group who have a huge benefit,” Slamon told me. “And now
we need to direct our therapy and target it more specifically.”


'Exciting result' Even when other cancer doctors were willing to use
anthracyclines only as targeted therapy, they couldn’t. There is no
commercial test yet for the Topoll-2 gene, although there likely will be
in a few months.




Nevertheless, Johns Hopkins breast cancer specialist Dr. Nancy Davidson
calls the findings “an exciting result.”


“It's early; it's provocative. We are waiting to see it go through peer
review in the usual fashion,” says Davidson, who is incoming president
of ASCO. “But there's a lot of buzz.”


Fran Visco, a cancer survivor and president of the National Breast
Cancer Coalition, agrees the work needs to be published and peer-
reviewed — very soon.
“This is going to be a sea change in how we treat breast cancer,” she
told me. “There is no reason we shouldn't be moving very quickly to
publish it and quickly to figure out how we're going to implement it in
practice. Women deserve no less.”
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Old 06-13-2007, 07:21 AM   #2
mts
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This is amazing stuff. Thank goodness for the brainiacs out there that are working on this...


Maria (MTS)
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Old 06-13-2007, 07:22 AM   #3
MJo
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I would expect insurance companies to get behind this, since it will save them money. I took the triple whammy treatment -- AC Taxol Herceptin. My ejection fraction rate went down and I had to stop Herceptin at 9 months. However the treatment was the best available at the time -- only one year ago!! Changes are coming so fast. A woman in my support group last night commented that in 10 years new cancer patients will look back on our treatment protocols and shudder.
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IDC, Stage I, Grade 2
Oncotype DX Score 32
Her2++ E+P+, Node Neg.
Lumpectomy 11/04/05 Clear Margins
3 Dose dense AC (Couldn't tolerate 4)
4 Dose dense Taxol & Herc. (Tolerated well)
36 weeks Herceptin (Could not complete one year due to decrease in MUGA score)
2 years of Arimidex, then three years of Femara
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Old 06-13-2007, 08:18 AM   #4
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Barbaric

I agree, I think this and future generations will look back on these chemos as primitive and barbaric treatments. For me, the horror of cancer never really hit until I suffered through chemo for three months; that's what really screwed me up, the chemo, not the cancer. Thanks for the interesting post.
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Dx Nov.04 - Stage 1, Grade 3, widespread high grade DCIS, Paget's disease of nipple, 8mm tumor invasive DC (ductal carcinoma), ER/PR-, HER2+++
Nov.04 - left mast., clear margins, 6 of 6 nodes clear
Feb.05 - began EC chemo, 4 rounds (every 3 weeks)
Aug.05 - began Herceptin every 3 weeks for 1 year
Aug.06 - ended treatment
NED
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Old 06-13-2007, 09:01 AM   #5
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My comments would not be printable! So happy I refused AC.
Thanks for posting this.
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Old 06-13-2007, 09:20 AM   #6
Hopeful
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Grace,

This is one of the many reasons I declined chemo - I just plain do not trust it. I have felt all along (and continue to believe) that the lack of chemo, as currently administered, will not make the difference between whether or not my disease progresses - if it does, it would have, anyway. It also disturbs me that the initial treatment for bc seems pretty much the same, whether you are Stage I, II or III: how can a "one-size-fits-all" approach possibly work for a disease as heterogenerous as bc? Needless to say, on the heels of the article from the March 9th New York Times posted in this forum under the title, "A Must Read," I am not surprised at this revelation. What does suprise me is that it took this long to become public knowledge.

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Old 06-13-2007, 09:23 AM   #7
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I hope this continues to be looked at as well. Given some ohter research that Lani posted a while back I think that adria may have contributed to my mets from the stage I dx. Tamox didn't help either-oh to be able to have a 'do over'!

thanks for the article
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dx stage I 2/2000*er/pr+; her- per IHC*lumpectomy*4 rounds A/C*30 rads*tamoxifen*dx stage 4 5/2002*huge mets to liver*tiny mets to lungs*stopped tamoxifen*5/02 taxotere/xeloda*her 2 checked with FiSH-her2+++herceptin *2/03 stopped chemo femara w/herceptin*zolodex*04 switched to aromasin w/herceptin*05 high estrogen tx*11/05taxol/carbo*7/06 stopped chemo; megace/herceptin*9/06navelbine/herceptin*5/07tykerb/xeloda great response*4/08 progression in liver; ooph/ faslodex /herceptin
6/08 began Herceptin DM-1
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Old 06-13-2007, 11:09 AM   #8
Mary Anne in TX
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Is it the different chemos or the damage done to the immune system that causes the most harm?

ma
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Diag. 12/05 at age 60
Stage II, Grade 3, 4.5 cm primary tumor
ER/PR- Her2 +3 strongly positive
Her2 by FISH 7.7 amplified
vascular invasion
Ki67 20% borderline
Jan - March '06 Taxotere/Adriamycin X 3 to try to shrink tumor - it grew
April '06 Rt Modified Radical Mas, 7 of 9 nodes positive
April - Aug. '06 Herceptin/Taxol/Carboplatin X 8 (dose dense)
Sept - Dec. '06 Navelbine/Herceptin x 8 (dose dense)
Radiation & Herceptin Jan. 22 - March 1, 2007
Finished Herceptin Dec. 10 '08! One extra year.
Port removed August, 2012.
8 1/2 years since diagnosis! 5 1/2 Years NED!
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Old 06-13-2007, 11:14 AM   #9
StephN
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Cool Back to the future ...

Hi everyone -
Thanks Aquinis.
Here is a link from ASCO Dec of 2005:
http://her2support.org/vbulletin/sho...ghlight=TopoII

This was the first I had heard of the importance of TOPOII and anthracycline efficacy.

I was fortunate to be present and helping represent this web site at that time. Christine and Joe wanted to go hear Dr. Slamon as he was first on the schedule the opening morning. So, I and a couple others manned our booth on the exhibition floor. I could see some of that presentation as a huge screen was positioned at one end of the large room for overflow from the main hall.

What still stands out in my mind is Christine (this site's founder) coming back to the booth and telling me that she finally realized why Adriamycin had not worked for her OR me! What a knockout punch that was! Since I had aggressive disease and bad nodes I had taken one of the new dose dense trials of Adria, getting 12 weekly doses.

You bet your bottom dollar I have wondered if cytoxin, cisplatin or 5FU would have stopped my cancer. I also had Taxotere after the Adria, but it seems my markers were up then to almost 100 and only came down after the Taxotere. But my cancer was already on the march so with the Adria not working it may not have much mattered what I took afterwards.
Since that time, the other drugs I have taken for mets worked. I am NED still.
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MY STORY SO FAR ~~~~
Found suspicious lump 9/2000
Lumpectomy, then node dissection and port placement
Stage IIB, 8 pos nodes of 18, Grade 3, ER & PR -
Adriamycin 12 weekly, taxotere 4 rounds
36 rads - very little burning
3 mos after rads liver full of tumors, Stage IV Jan 2002, one spot on sternum
Weekly Taxol, Navelbine, Herceptin for 27 rounds to NED!
2003 & 2004 no active disease - 3 weekly Herceptin + Zometa
Jan 2005 two mets to brain - Gamma Knife on Jan 18
All clear until treated cerebellum spot showing activity on Jan 2006 brain MRI & brain PET
Brain surgery on Feb 9, 2006 - no cancer, 100% radiation necrosis - tumor was still dying
Continue as NED while on Herceptin & quarterly Zometa
Fall-2006 - off Zometa - watching one small brain spot (scar?)
2007 - spot/scar in brain stable - finished anticoagulation therapy for clot along my port-a-catheter - 3 angioplasties to unblock vena cava
2008 - Brain and body still NED! Port removed and scans in Dec.
Dec 2008 - stop Herceptin - Vaccine Trial at U of W begun in Oct. of 2011
STILL NED everywhere in Feb 2014 - on wing & prayer
7/14 - Started twice yearly Zometa for my bones
Jan. 2015 checkup still shows NED
2015 Neuropathy in feet - otherwise all OK - still NED.
Same news for 2016 and all of 2017.
Nov of 2017 - had small skin cancer removed from my face. Will have Zometa end of Jan. 2018.
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Old 06-13-2007, 11:21 AM   #10
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Daughter pre-med

I remain hopeful that the coming years will produce better treatment for all cancer patients. My youngest daughter is a pre-med student at the Univeristy of Illinois, and she is very committed to research and solutions for cancer patients. She also is a very strong women who will never settle for a mans answer to anything! My breast cancer has changed how she views everything about cancer. In my own nieve (sp) way, I soothe my soul by telling myself that I possibly got bc so she could become one of the dedicated folks trying to make a difference.
Gives me consolation in the wee hours of the morning.
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Old 06-13-2007, 11:35 AM   #11
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Even though there are those few whose TOPO II resulted in benefit, I am very thankful that this information is becoming more available in behalf of so many, and particularly in behalf of those who are least likely in the first place to have any recurrence at all.

The lack of general awareness of this information from Slamon to me is a lot like the lack of acknowledgement about chemobrain... as well as like the failure to deal honestly with loss of libido (i.e., if you are not the patient and you don't have bc, and you want everybody to think in the most hopeful positive direction, other problems aren't important and are ignored....) There is such a huge tendency for "group thinking" in oncology, that a drug that was known to only provide 4% improvement in the first place was adopted as standard treatment for the majority. Truly tragic.

Thanks so much for posting this info.

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Old 06-14-2007, 06:56 AM   #12
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Even though this research is still VERY early and not 'proven', I'm glad my onc was up to date, and decided it was worth checking out. She requested a TOPO II test for me (and surprisingly, I didn't have any problems from my insurance company). As a result, I had an alternative chemo, not AC.

I keep watching for more research on this. Thanks for posting it.


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Dx July 2006 IDC 1.8cm, ER-/PR- HER2+ (FISH 7), KI67 High (60%) grade 3, TOPO II neg
Aug2006: lumpectomy, SNB (4 nodes neg), Stage 1
Jan 2007:
Finished 6 cycles of TCH (Taxotere, Carboplatin, Her ceptin). Then Herceptin every 3 weeks.
Feb 2007: Completed Radiation
May 2007: Stopped Herceptin due to low LVEF (49%)
July 2007: LVEF now 44% -- starting Coreg
May 2008: Heart NORMAL! Yippee.
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