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Old 11-25-2007, 11:12 AM   #1
Vic
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Post "Los Angeles Times" article on Herceptin and high school science project

For those of you not in the L.A. area, here's a great article from today's "Los Angeles Times" newspaper (11.25.7). The key paragraph is: "Sarah's work in the lab indicates that in the types of breast cancer that Herceptin treats -- 25% to 30% of breast cancer diagnoses, by Kane's estimate -- a gene strand called t-Darpp causes resistance to the drug."

Equally amazing is that these are two high school students. Enjoy the article.

Vicki Z

Girls track breast cancer puzzle


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[COLOR=#333333! important]An 'impressive' science project by teenage cousins looks at why some cases are drug-resistant. They will present findings in New York.[/COLOR]
[COLOR=#999999! important]By Daniela Perdomo, Los Angeles Times Staff Writer
November 25, 2007 [/COLOR]
The science fair poster on the floor in Sarah Waliany's living room in Arcadia has an arts-and-crafts element to it. Glittery pipe cleaners, green and red, are bent to resemble gene strands, while blobs of gold and red glue represent cells.

"I couldn't get the breast tumor cells to stop clumping together," Sarah, 16, said, referring to the red cotton balls attached elsewhere to the poster board.

Its homemade texture, combined with the erratic bursts of color, makes it easy to mistake the poster for a simple science fair project. In reality, several medical researchers say, the results presented on the fluorescent paper could have important implications in understanding why some breast cancers are drug-resistant.

Sarah, who has been working on this research for precisely "20 and a half months," will showcase her work in front of a national audience Dec. 2, when she and her cousin and research partner, Shelina Kurwa, 17, fly to New York as finalists in the Siemens Competition in Math, Science & Technology. Sarah did the lab work, while Shelina anchored the literature research and helped develop the theory behind their project.

The competition, sponsored by the Siemens Foundation (whose parent company is Siemens AG, the engineering conglomerate) and the College Board, attracted 1,641 submissions by high school students across the country. Sarah and Shelina won the regional competition at Caltech on Nov. 10.

Sarkis Mazmanian, an assistant professor of biology at Caltech, was the lead judge on the 10-person panel that reviewed Sarah and Shelina's project and unanimously gave it first prize. He called the girls' research "novel and creative" and said it was graduate-level work.

"We were impressed with how clear it was that the girls were the driving force in this research," Mazmanian said. "That is exceedingly impressive for a student at any age."

Some of the girls' precociousness may be a result of their upbringing. Shelina is the daughter of an ophthalmologist; Sarah's father is an oncologist, her mother a cell biologist.

"Science has been second nature to me -- in the car, we didn't sing songs, we learned about anatomy," Shelina said.

This is not the cousins' first foray into a major science competition together. In 2005, they were Siemens regional semifinalists for their attempt to infuse lettuce -- grown in Sarah's backyard -- with vitamin C.

This year's project has clear clinical implications, the judges said. Both Shelina and Sarah say they were motivated to work in breast cancer research after several friends' mothers were diagnosed with the disease.

"This happens to all children of physicians, who are exposed to very sick patients," said Dr. Bud Kurwa, Shelina's father.

"They generate questions: 'How does this happen? What can I do?' And they realize science is the means to answering these questions."

Sarah sought to answer a perplexing question: Why do some breast cancer patients develop resistance to the cancer drug Herceptin?

She began her work nearly two years ago when she started an internship at the Beckman Research Institute at the City of Hope in Duarte. Her mentor there, Susan E. Kane, a cancer researcher and associate director of the institute, said Sarah applied for the internship when she was 14 -- an unusually young age -- and had to wait until she turned 15 to start work.

"I quickly realized she was smarter than I am," Kane said.

Sarah's work in the lab indicates that in the types of breast cancer that Herceptin treats -- 25% to 30% of breast cancer diagnoses, by Kane's estimate -- a gene strand called t-Darpp causes resistance to the drug.

Shelina's investigation of literature on the subject added to the conclusions Sarah drew from her lab results.

According to Kane, 70% of women treated with Herceptin do not respond to the drug. Knowing which gene strand causes this resistance "will save precious time and materials."

Sarah and Shelina seem excited but not overwhelmed by the implications of their research. They do, after all, have other interests.

Shelina founded a Renaissance Club at Westridge School for Girls in Pasadena, writes fantasy stories, designs websites, and recently guest-edited a health feature for Seventeen magazine.

Sarah, a junior, edits the Flintridge Preparatory School's student newspaper and founded a science journal there. She also volunteers at the San Gabriel Hospital's children's ward.

The girls jokingly admit they get tired of each other "maybe a little" (they live a few blocks apart). And they still have more other teenage concerns. Sarah doesn't yet drive and hasn't had time to prepare for the driving test. She's been in the lab.

daniela.perdomo@latimes.com
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Old 11-25-2007, 03:04 PM   #2
pffida
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Response to LA Times Article

I read the article in the paper this morning and was concerned about the following statement, "According to Kane, 70% of women treated with Herceptin do not respond to the drug. Knowing which gene strand causes this resistance "will save precious time and materials."

That's the first time I've heard that Herceptin doesn't work 70% of the time. Has anyone else heard that?
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Diagnosed 11/06; IDC
Stage 1, Grade 2
MRM 12/06; 19 nodes removed, all negative
ER/PR-, HER2+++
  • 4 rounds AC - every 3 weeks
  • 3 rounds Taxol + Herceptin - every 3 weeks (developed allergy to Taxol so stopped treatment)
  • Weekly Herceptin after Herceptin-induced cardiomyopathy from treatments every 3 weeks
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Old 11-25-2007, 05:17 PM   #3
SoCalGal
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can't wait to forward to my kids

All my kids ever did in high school was ask me for money and complain about their curfew.

It didn't occur to me to tell them to stop complaining and try to cure cancer.

LOL. Flori

PS - never heard that 70% statistic. Hope it's WRONG.
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1996 cancer WTF?! 1.3 cm lumpectomy Er/Pr neg. Her2+ (20nodes NEGATIVE) did CMF + rads. NED.
2002 recurrence. Bilateral mastectomy w/TFL autologous recon. Then ACx2. Skin lymphatic rash. Taxotere w/Herceptin x4. Herceptin/Xeloda. Finally stops spreading.
2003 - Back to surgery, remove skin mets, and will have surgery one week later when pathology can confirm margins.
‘03 latisimus dorsi flap to remove skin mets. CLEAN MARGINS. Continue single agent Herceptin thru 4/04. NED.
‘04 '05 & 06 tiny recurrences - scar line. surgery to cut out. NED each time.
1/2006 Rads again, to scar line. NED.

3/07 Heartbreaking news - mets! lungs.sternum. Try Tykerb/Xeloda. Tykerb/Carbo/Gemzar. Switch Oncs.
12/07 Herceptin.Tykerb. Markers go stable.
2/8/08 gamma knife 13mm stupid brain met.
3/08 Herceptin/tykerb/avastin/zometa.
3/09 brain NED. Lungs STABLE.
4/09 attack sternum (10 daysPHOTONS.5 days ELECTRONS)
9/09 MARKERS normal!
3/10 PET/CT=manubrium intensely metabolically active but stable. NEDhead.
Wash out 5/10 for tdm1 but 6/10 CT STABLE, PET improving. Markers normal. Brain NED. Resume just Herceptin plus ZOMETA
Dec 2010 Brain NED, lungs/sternum stable. markers normal.
MAR 2011 stop Herceptin/allergy! Go back on Tykerb and switch to Xgeva.
May-Aug 2011 Tykerb Herceptin Xgeva.
Sept 2011 Tykerb, Herceptin, Zometa, Avastin.
April 2012 sketchy drug trial in NYC. 6 weeks later I’m NED!
OCT 2012 PET/CT shows a bunch of freakin’ progression. Back to LA and Herceptin.avastin.zometa.
12/20/12 add in PERJETA!
March 2013 – 5 YEARS POST continue HAPZ
APRIL 2013 - 6 yrs stage 4. "FAILED" PETscan on 4/2/13
May 2013: rePetted - improvement in lungs, left adrenal stable, right 6th rib inactive, (must be PERJETA avastin) sternum and L1 fruckin'worsen. Drop zometa. ADD Xgeva. Doc says get rads consultant for L1 and possible biopsy of L1. I say, no thanks, doc. Lets see what xgeva brings to the table first. It's summer.
June-August 2013HAPX Herceptin Avastin Perjeta xgeva.
Sept - now - on chemo hold for calming tummy we hope. Markers stable for 2 months.
Nov 2013 - Herceptin-Perjeta-Avastin-Xgeva (collageneous colitis, which explains tummy probs, added Entocort)
December '13 BRAIN MRI ned in da head.
Jan 2014: CONTINUING on HAPX…
FEB 2014 PetCT clinical “impression”: 1. newbie nodule - SUV 1.5 right apical nodule, mildly hypermetabolic “suggestive” of worsening neoplastic lesion. 2. moderate worsening of the sternum – SUV 5.6 from 3.8
3. increasing sclerosis & decreasing activity of L1 met “suggests” mild healing. (SUV 9.4 v 12.1 in May ‘13)
4. scattered lung nodules, up to 5mm in size = stable, no increased activity
5. other small scattered sclerotic lesions, one in right iliac and one in thoracic vertebral body similar in appearance to L1 without PET activity and not clearly pathologic
APRIL 2014 - 6 YRS POST GAMMA ZAP, 7 YRS MBC & 18 YEARS FROM ORIGINAL DX!
October 2014: hold avastin, continue HPX
Feb 2015 Cancer you lost. NEDHEAD 7 years post gamma zap miracle, 8 years ST4, +19 yrs original diagnosis.
Continue HPX. Adding back Avastin
Nov 2015 pet/ct is mixed result. L1 SUV is worse. Continue Herceptin/avastin/xgeva. Might revisit Perjeta for L1. Meantime going for rads consult for L1
December 2015 - brain stable. Continue Herceptin, Perjeta, Avastin and xgeva.
Jan 2016: 5 days, 20 grays, Rads to L1 and continue on HAPX. I’m trying to "save" TDM1 for next line. Hope the rads work to quiet L1. Sciatic pain extraordinaire :((
Markers drop post rads.
2/24/16 HAP plus X - markers are down
SCIATIC PAIN DEAL BREAKER.
3/23/16 Laminectomy w/coflex implant L4/5. NO MORE SCIATIC PAIN!!! Healing.
APRIL 2016 - 9 YRS MBC
July 2016 - continue HAP plus Xgeva.
DEC 2016 - PETCT: mets to sternum, lungs, L1 still about the same in size and PET activity. Markers not bad. Not making changes if I don't need to. Herceptin/Perjeta/Avastin/Xgeva
APRIL 2017 10 YEARS MBC
December 2017 - Progression - gonna switch it up
FEB 2018 - Kadcyla 3 cycles ---->progression :(
MAY30th - bronchoscopy, w/foundation1 - her2 enriched
Aug 27, 2018 - start clinical trial ZW25
JAN 2019 - ZW25 seems to be keeping me stable
APRIL 2019 - ONE DOZEN YEARS LIVING METASTATIC
MAY 2019 - progression back on herceptin add xeloda
JUNE 2019 - "6 mos average survival" LMD & CNS new single brain met - one zap during 5 days true beam SBRT to cord met
10/30/19 - stable brain and cord. progression lungs and bones. washing out. applying for ds8201a w nivolumab. hope they take me.
12/27/19 - begin ds8401a w nivolumab. after 2nd cycle nodes melt away. after 3rd cycle chest scan shows Improvement, brain MRI shows improvement, resolved areas & nothing new. switch to plain ENHERTU. after 4th cycle, PETscan shows mostly resolved or improved results. Markers near normal. I'm stunned but grateful.
10/26/20 - June 2021 Tucatinib/xeloda/herceptin - stable ish.
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Old 11-25-2007, 05:56 PM   #4
Becky
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I actually heard that about half will become resistant. If you think about the adjuvant Herceptin trial where it decreased recurrence by 52% then that number is about right.

However, I believe there are many, many paths that contribute to resistance (if you want to actually call it that). For example, if a woman were ER/PR+ but did not take an anti-hormonal but took Herceptin - her cancer would probably grow due to estrogen or progesterone as those pathways are not blocked. But lets say they are also blocked and the cancer still grows, I think it is because this woman is also positive for something else. Something that isn't tested for or even discovered yet. The Herceptin is working on the Her2, the Arimidex is working on the ER/PR but something else is not blocked (ie: Her 1 or Her 3, IGFR or something not yet even imagined).

Also, sometimes women have a Her2 receptor that is a different shape than normal or the external domain is missing. This is called the truncated version (H95) and then Herceptin doesn't fit or doesn't have a key to lock onto.
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Kind regards

Becky

Found lump via BSE
Diagnosed 8/04 at age 45
1.9cm tumor, ER+PR-, Her2 3+(rt side)
2 micromets to sentinel node
Stage 2A
left 3mm DCIS - low grade ER+PR+Her2 neg
lumpectomies 9/7/04
4DD AC followed by 4 DD taxol
Used Leukine instead of Neulasta
35 rads on right side only
4/05 started Tamoxifen
Started Herceptin 4 months after last Taxol due to
trial results and 2005 ASCO meeting & recommendations
Oophorectomy 8/05
Started Arimidex 9/05
Finished Herceptin (16 months) 9/06
Arimidex Only
Prolia every 6 months for osteopenia

NED 18 years!

Said Christopher Robin to Pooh: "You must remember this: You're braver than you believe and stronger than you seem and smarter than you think"
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Old 11-25-2007, 09:44 PM   #5
Jean
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Wink

Becky Dear,
As usual we can count on you...to keep things in order and present a clear understanding...I am wondering...what the heck were you doing
while you were in High School?

Flori - glad you have that beautiful humor! Love it.


Regards,
Jean
__________________
Stage 1, Grade 1, 3/30/05
Lumpectomy 4/15/05 - 6MM IDC
Node Neg. (Sentinel node)
ER+ 90% / PR-, Her2+++ by FISH
Ki-67 40%
Arimidex 5/05
Radiation 32 trt, 5/30/05
Oncotype DX test 4/17/06, 31% high risk
TOPO 11 neg. 4/06
Stopped Arimidex 5/06
TCH 5/06, 6 treatments
Herceptin 5/06 - for 1 yr.
9/06 Completed chemo
Started Femara Sept. 2006
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Old 11-26-2007, 10:54 AM   #6
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LOL, Jean I was wondering the same thing re Becky! Floris comment has me thinking as well, perhaps I need to lock my daughter into the bedroom with her biology book?!
nawww...it will never happen!
These high school ladies are very impressive...YOU GO LADIES!!! FIND OUR CURE!
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