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Old 01-06-2010, 02:28 PM   #1
hutchibk
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Posts: 3,519
Breast Cancer Gene Linked To Disease Spread Discovered

http://www.sciencedaily.com/releases...0105131216.htm

ScienceDaily (Jan. 9, 2009) — A team of researchers at Princeton University and The Cancer Institute of New Jersey has identified a long-sought gene that is fatefully switched on in 30 to 40 percent of all breast cancer patients, spreading the disease, resisting traditional chemotherapies and eventually leading to death.

The gene, called "Metadherin" or MTDH, is located in a small region of human chromosome 8 and appears to be crucial to cancer's spread or metastasis because it helps tumor cells stick tightly to blood vessels in distant organs. The gene also makes tumors more resistant to the powerful chemotherapeutic agents normally used to wipe out the deadly cells.
__________________
Brenda

NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)

Nov'03~ dX stage 2B
Dec'03~
Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~
Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~
micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~
micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg

Apr'07~
MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~
Started Tykerb/Xeloda, no WBR for now
June'07~
MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~
MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~
PET/CT & MRI show NED
Apr'08~
scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~
MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~
dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~
Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~
new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~
new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~
25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.

"I would rather be anecdotally alive than statistically dead."
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Old 01-06-2010, 07:04 PM   #2
Cal-Gal
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Posts: 309
Re: Breast Cancer Gene Linked To Disease Spread Discovered

wow--how interesting!!!!

I wonder how you get the test for that? similar to BRCA?
__________________
DX: 11/08 Age: 53
Surgery: 1/09
Bilat Mastectomy, no reconstruction
ILC-4 tumors-1.7 cm,1.5 cm (2).8 cm
DCIS-11 cm
All tumors Grade 3
All tumors ER-0%/PR-0%
All tumors HER2+
IHC-all tumors Overexpression/borderline
FISH 2 tumors Her2-Negative
FISH 2 tumors Her2+ Equivocal
Stage I, 0/1 nodes
LVI-Indeterminate(treated as positive)
SPR Score 8/9
Ki-67 20%
BRCA genetic test 1/2=negative
Chemo: 6 rounds TAC Feb-June 2009 w/Neulasta
Herceptin: 6/12/09-6/4/10 52weeks
HNPCC genetic test: negative
Port Placement-9/23/09 Port Removal 6/25/10
Echo's every 3 months-All normal
2/09 Staging PET/CT showed 0.2 micronodule upper R lobe-lung-Onc does not think this is mets--
6/5/09 AND 10/09 CT scan 0.2 micronodule unchanged
1/10-PET/CT-uptake in nasopharynx-
1/10-MRI All normal
6/10-Bone Scan-clear
12/10-PET/CT-All Clear-NED
12/11-PET-All Clear-NED

12/12-PET-All Clear-NED
12/13-CT w/contrast Head, Torso-All Clear
12/14-CT w/contrast Head-All Clear
2/15-Core needle biopsy-R scar line

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Old 01-06-2010, 08:12 PM   #3
v-ness
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Location: western ma
Posts: 280
Re: Breast Cancer Gene Linked To Disease Spread Discovered

god, i would not even want to know.
__________________
8/09 - IDC 1.8 cm triple positive, lumpectomy left breast
10/09 began chemo (taxotere & carboplatin) and weekly herceptin.
1/21/10 finished chemo, continued on herceptin every 3 weeks until 10/2010.
2/10 began 7 wks of radiation
6/10 mom dies of primary peritoneal ovarian cancer
8/10 got my last remaining ovary out
10/10 mammogram all clear
3/11 MRI shows 5 'spots' in right breast, largest 1 cm unidentifiable on US
needle biopsy proved the largest to be old inflamed cyst -phew!
7/10 switched to Arimidex
8/9 switched to Femara - allergic to arimidex
Femara made me lose hair quickly so switched to Aromasin
Aromasin made my hair fall out too and the bone pain was too much.
back on Tamoxifen 1/2013.
blood clot from trains and planes 5/2014 so on coumadin per onco for as long as i am on tamoxifen
tamoxifen was supposed to be up with my 5 yrs in may but my boyfriend was diagnosed with stage 4 colon cancer so i am staying on tamoxifen indefinitely because i want some ammo against BC, given the stress. lost my husband in only 10 wks in 2007 to stage 4 esophageal cancer.
cancer's screwing with another man i love
2/2016 - 6yrs in remission, off tamoxifen and off coumadin - yay!
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Old 01-06-2010, 09:19 PM   #4
hutchibk
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Re: Breast Cancer Gene Linked To Disease Spread Discovered

I found these two paragraphs at the end of the article particularly interesting:


"Once the team had identified the specific gene, its scientists were able to re-examine the tumor samples. "By analyzing 250 breast tumor samples from patients, we found that this gene is amplified and overexpressed in over 30 to 40 percent of breast cancer cases," Kang said. "This indicates that new drugs against Metadherin may potentially benefit a large population of breast cancer patients."


"Breast cancer is caused by a malignant tumor that develops from cells in the breast. The most common sign of breast cancer is a new lump or mass in the breast. Scientists once thought that breast cancer spreads first to nearby tissue and underarm lymph nodes before spreading to other parts of the body. They now believe cancer cells may break away from the primary tumor in the breast and begin to metastasize even when the disease is in an early stage."
__________________
Brenda

NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)

Nov'03~ dX stage 2B
Dec'03~
Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~
Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~
micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~
micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg

Apr'07~
MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~
Started Tykerb/Xeloda, no WBR for now
June'07~
MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~
MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~
PET/CT & MRI show NED
Apr'08~
scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~
MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~
dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~
Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~
new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~
new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~
25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.

"I would rather be anecdotally alive than statistically dead."
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Old 01-06-2010, 11:11 PM   #5
BarbM
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Join Date: Oct 2007
Location: Scottsdale,AZ
Posts: 43
Re: Breast Cancer Gene Linked To Disease Spread Discovered

This is big news!!!! Maybe explains being stage 4 right from the start AND getting minimal mileage out of chemos. I would love to know....the drug to switch it off can't come quick enough!
__________________
Dx 5/1/07 (age 47), Left IDC
ER less than 5% +, PR -, HER+ FISH 5.4
Lumpectomy 5/07, Quadrantectomy 6/07
AC 7/07 -10/07, Liver mets dx 9/07 (liver bx)
Taxotere/Herceptin 10/07 -12/07
Herceptin only 1/08 - 7/08
Mastectomy 3/08, RADS 4/08 - 5/08
Brain MRI 5/08 clear
Gemzar/Herceptin 7/08-9/08
Lymphedema 8/08
RADS/Hyperthermia 10/08-11/08
Abraxane/Herceptin 12/08-3/09
Doxil/Herceptin 3/09 to 5/09
Xeloda/Tykerb 6/09-10/09
Navelbine/Xeloda/Tykerb 10/09-12/09
Tykerb/Herceptin 1/11/10
Tykerb/Herceptin/Ixempra 2/1/10
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Old 01-07-2010, 05:49 AM   #6
v-ness
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Join Date: Nov 2009
Location: western ma
Posts: 280
Re: Breast Cancer Gene Linked To Disease Spread Discovered

i agree about wanting a drug faster than the speed of light for all those who need it now and for those who might in the future. i just found the 30-40% sentence a bit terrifying and also the idea of testing positive for this gene before there is even anything available to combat it since drugs take so long to develop.

the line about cells breaking away from the tumor breaking away at an early stage struck me because my oncologist and her partner, and no doubt many, think that all humans have cancer cells developing and circulating in our systems at all times and that our immune systems fight them back. i remember just before i was diagnosed i'd had a complete blood count and my primary care doc was a little concerned about my lymphocyte number being too high, she thought i might have a virus and should have my blood re-done again in 2 wks. meanwhile, i felt fine, but i had just found the lump above my breast. i called and asked if the lump could have anything to do with my blood results and was told no. however, i checked with my shrink, who orders the CBC's every three months. come to find out the very same numbers were normal in january, a little up in march (when i had my mammo that showed nothing), and higher than normal range in august when i found the tumor. when he ran the very same test again in november voila, my lymphocytes were right back in Normal range after the tumor was removed and i was on chemo. to me, that means my immune system had indeed been fighting something and that something was cancer. i don't believe the spike was just coincidental.

anyway, i guess part of me is happy that scientists have found this gene and can now work on doing something about it - but the other part of me is freaked out that it even exists and that all the efforts i am currently going through - chemo and herceptin and later radiation and tamoxifen - could be for naught because a gene might have already made the decision.

i have herceptin this morning and definitely plan to ask my oncologist about this. my husband died of stage 4 cancer only 10 wks after diagnosis so i guess perhaps i have that coloring my reaction. the anniversary of his death is a week from today and i have noticed that i am not the same person i was a couple weeks ago about anything having to do with this disease. valerie
__________________
8/09 - IDC 1.8 cm triple positive, lumpectomy left breast
10/09 began chemo (taxotere & carboplatin) and weekly herceptin.
1/21/10 finished chemo, continued on herceptin every 3 weeks until 10/2010.
2/10 began 7 wks of radiation
6/10 mom dies of primary peritoneal ovarian cancer
8/10 got my last remaining ovary out
10/10 mammogram all clear
3/11 MRI shows 5 'spots' in right breast, largest 1 cm unidentifiable on US
needle biopsy proved the largest to be old inflamed cyst -phew!
7/10 switched to Arimidex
8/9 switched to Femara - allergic to arimidex
Femara made me lose hair quickly so switched to Aromasin
Aromasin made my hair fall out too and the bone pain was too much.
back on Tamoxifen 1/2013.
blood clot from trains and planes 5/2014 so on coumadin per onco for as long as i am on tamoxifen
tamoxifen was supposed to be up with my 5 yrs in may but my boyfriend was diagnosed with stage 4 colon cancer so i am staying on tamoxifen indefinitely because i want some ammo against BC, given the stress. lost my husband in only 10 wks in 2007 to stage 4 esophageal cancer.
cancer's screwing with another man i love
2/2016 - 6yrs in remission, off tamoxifen and off coumadin - yay!
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Old 01-07-2010, 06:49 AM   #7
schoolteacher
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Location: Georgia
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Re: Breast Cancer Gene Linked To Disease Spread Discovered

Thanks for the article Brenda. I am like the rest of the women wanting a drug to shut this off.

Amelia
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Old 01-13-2010, 05:26 PM   #8
hutchibk
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Posts: 3,519
Re: Breast Cancer Gene Linked To Disease Spread Discovered

Here's another very interesting find about curbing metastatic breast cancer...

A compound found in cannabis may prove to be effective at helping stop the spread of breast cancer cells throughout the body.

The researchers point out that while their findings are promising they are not a recommendation for people with breast cancer to smoke marijuana. They say it is highly unlikely that effective concentrations of CBD could be reached by smoking cannabis. And while CBD is not psychoactive it is still considered a Schedule 1 drug.

http://www.sciencedaily.com/releases...1123211703.htm
__________________
Brenda

NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)

Nov'03~ dX stage 2B
Dec'03~
Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~
Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~
micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~
micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg

Apr'07~
MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~
Started Tykerb/Xeloda, no WBR for now
June'07~
MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~
MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~
PET/CT & MRI show NED
Apr'08~
scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~
MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~
dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~
Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~
new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~
new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~
25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.

"I would rather be anecdotally alive than statistically dead."

Last edited by hutchibk; 01-14-2010 at 01:04 AM.. Reason: add info
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Old 01-13-2010, 10:03 PM   #9
Rich66
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Location: South East Wisconsin
Posts: 3,431
Re: Breast Cancer Gene Linked To Disease Spread Discovered

The cannabinoids may be useful to ER- but not ER+.

Although they don't seem to know how to target Metadherin directly, some of the pathways it triggers seem to be familiar and have various potential blockers:

Clin Cancer Res. 2009 Sep 15;15(18):5615-20. Epub 2009 Sep 1.
The multifaceted role of MTDH/AEG-1 in cancer progression.

Hu G, Wei Y, Kang Y.
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Cancer is the result of the progressive acquisition of multiple malignant traits through the accumulation of genetic or epigenetic alterations. Recent studies have established a functional role of MTDH (Metadherin)/AEG-1 (Astrocyte Elevated Gene 1) in several crucial aspects of tumor progression, including transformation, evasion of apoptosis, invasion, metastasis, and chemoresistance. Overexpression of MTDH/AEG-1 is frequently observed in melanoma, glioma, neuroblastoma, and carcinomas of breast, prostate, liver, and esophagus and is correlated with poor clinical outcomes. MTDH/AEG-1 functions as a downstream mediator of the transforming activity of oncogenic Ha-Ras and c-Myc. Furthermore, MTDH/AEG-1 overexpression activates the PI3K/Akt, nuclear factor kappaB (NFkappaB), and Wnt/beta-catenin signaling pathways to stimulate proliferation, invasion, cell survival, and chemoresistance. The lung-homing domain of MTDH/AEG-1 also mediates the adhesion of tumor cells to the vasculature of distant organs and promotes metastasis. These findings suggest that therapeutic targeting of MTDH/AEG-1 may simultaneously suppress tumor growth, block metastasis, and enhance the efficacy of chemotherapeutic treatments.

PMID: 19723648 [PubMed - in process]
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Mom's treatment history (link)
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Old 01-14-2010, 03:37 AM   #10
Ellie F
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Join Date: Feb 2009
Posts: 1,526
Re: Breast Cancer Gene Linked To Disease Spread Discovered

Hi all
Very interesting about cannabis oil's anti tumour effect! This first came to my attention last year when a friend sent me a link to a man ?in Canada/Alaska who was growing cannabis, making the oil and giving it to friends with cancer. He had had amazing results with advanced cancers. Unfortunately the authorities had got wind of this and the legal process kicked in. I then discovered the research Brenda has linked.I had hoped for clinical trials from this but nothing has appeared yet. Am going to try to e-mail again to see where it is up to.
Thanks for the reminder, so much happens that it's easy to lose focus
Ellie
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