Go To Main TNBC Website


  New Posts New Posts RSS Feed - Tumor unresponsive to Chemo
  FAQ FAQ  Forum Search   Events   Register Register  Login Login

Tumor unresponsive to Chemo

 Post Reply Post Reply
Author
MarkH34 View Drop Down
Newbie
Newbie


Joined: Jul 07 2016
Status: Offline
Points: 8
Post Options Post Options   Thanks (0) Thanks(0)   Quote MarkH34 Quote  Post ReplyReply Direct Link To This Post Topic: Tumor unresponsive to Chemo
    Posted: Jul 07 2016 at 11:59pm
Hello,

My wife was diagnosed with triple negative, grade 3, node negative, 2.0 cm breast cancer 3 months ago. She was advised to do neoadjuvant chemo before surgery. She has gone through 3 rounds of TC, and today she had an ultrasound that showed no change in tumor size since diagnosis. ~ 2.0 cm still.

The doctors are now going to discuss changing her chemo drugs to see if she has a better response to something else. I believe AC + T was a possibility and/or carbo.

Needless to say, we were pretty disheartened that the tumor which should have responded well to chemo (grade 3, very high ki67) has not. I know the advantage of doing neoadjuvant treatment is that in cases like this they can switch drugs.

Has anyone switched chemo drugs in the middle of neoadjuvant treatment and had a better response? We are worried that we will still won't see any response with other treatments.

Thank You.

Back to Top
denise07 View Drop Down
Senior Member
Senior Member


Joined: Jun 26 2010
Location: pa
Status: Offline
Points: 997
Post Options Post Options   Thanks (0) Thanks(0)   Quote denise07 Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 12:18am
Hello,
Sorry you are going through this they will find the correct cocktail that will destroy that tumor ugh there are so many ups and downs going through treatments. I had ac+t and so far doing well that was the only chemo I got 6 rounds plus radiation 
and my tumor was the same size as your wife.I wish the best for you both it will all work out.
Denise 
DX Idc 10/07,st2,gr3,2/6 lymphnodes
Back to Top
Tulips View Drop Down
Senior Member
Senior Member
Avatar

Joined: May 04 2015
Location: RI
Status: Offline
Points: 388
Post Options Post Options   Thanks (0) Thanks(0)   Quote Tulips Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 7:08am
Hi Mark,
So sorry for what you both are going through.  It is not uncommon for tumors to respond to different chemos differently.  Probably the most common regimen now is for people to have AC and then T or T and then AC.  Very often, some people will have major shrinkage on one of those, and little change on the other (for some, it is the AC that is most effective, for others the T melts the tumor away).  So maybe hers will prove to be especially sensitive to Adriamycin (the "A" in AC, also known as Doxorubicin).  So yes, it's really lucky that she had neoadjuvant chemo, because this gives her another chance to find something more effective.  If she had surgery first, and then TC, she would have just mistakenly assumed/hoped that the TC was helping, although her cancer doesn't sound responsive to TC.
I have come across a few posts from women who had a tumor not shrink on neoadjuvant chemo (or even grow), who had their doctors instead rush them to surgery.  But to me, it seems to make sense to use it as an opportunity to test another chemo, esp if it isn't growing.
In the end, there are many of us who end up with residual cancer after neoadjuvant chemo at the time of surgery.  I am one of those people.  Actually, statistics show that about 2/3 of us end up with residual.  My tumor did shrink before surgery, from 2.2 cm to .8 cm, but that still puts me in the residual  cancer camp.  All is not lost for us!  Many, many, many people survive with this situation.  Perhaps their cancer never sent out troops to the rest of their body, so although the chemo didn't really work, it wasn't needed at all because the cancer stayed confined to the tumor.  Or perhaps somehow the chemo worked on the rogue cells that were traveling, but not the primary tumor for some reason.  So even if the chemo doesn't completely work, things can still be ok.  Plus, there is new evidence that trying certain chemos after surgery for people with residual cancer can help reduce risk.  Particularly, a recent study showed taking Xeloda for 6-8 cycles after surgery reduced risk for TNBC women with residual cancer by 42%.  I am currently taking my 6th round of Xeloda, and I do feel like it is extra protection.  If your wife is BRCA+, carboplatin may be a very good option for her, too.  Or maybe even a parp inhibitor.  My point is just that she still has many options for reducing risk--I'm not a doctor so of course I don't know what makes the most sense in her case.
Good luck!
Tulips
Dx April 2015 IDC TN 2.2 cm, Grade 3, Chemo started May 2015: Taxol/Carbo then AC, Lx with SNB Nov 2015, 33 Rad Dec 2015-Feb 2016. 6 months Capecitabine starting March 2016
Back to Top
Tulips View Drop Down
Senior Member
Senior Member
Avatar

Joined: May 04 2015
Location: RI
Status: Offline
Points: 388
Post Options Post Options   Thanks (0) Thanks(0)   Quote Tulips Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 7:12am
Oh, also, sometimes the imaging is just wrong.  There are cases when people still felt the tumor, or the scans show the tumor is still there, and then when the patient goes for surgery, it turns out that the remaining stuff there is just dead, necrotic tissue--the chemo worked to kill the tumor but instead of melting away, the dead cells are still there.  So there is also hope that that happened!
(In my case, the imaging was wrong in the other direction....I had an MRI after the Taxol/Carbo phase, and it looked like my tumor was completely gone.  I then had AC and then surgery.  Was surprised to find tumor still there.  So imaging is not perfect, and it may prove to be a better situation for your wife than the scans are showing!)
Dx April 2015 IDC TN 2.2 cm, Grade 3, Chemo started May 2015: Taxol/Carbo then AC, Lx with SNB Nov 2015, 33 Rad Dec 2015-Feb 2016. 6 months Capecitabine starting March 2016
Back to Top
gordon15 View Drop Down
Senior Member
Senior Member


Joined: Jun 22 2015
Location: San Diego CA
Status: Offline
Points: 779
Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 2:19pm
Mark: Tulip's right, from everything I have read the Adrymycin is often instrumental in killing the bc, my wife had it in 2008 (non-TNBC) and couldn't have more this time, it can cause heart damage and their is a lifetime limit dose.

I believe almost all TN cancers are Grade 3. 2cm is not a large tumor. Was that from MRI? Because MRI usually measures larger than US, I assume she had a sentinel node biopsy? Or no uptake on PET/CT from nodes in armpit?

If they're sure no node cancer, if it was my wife I'd certainly consider surgery asap, just my opinion, we'd certainly discuss. Of course, if she has a recurrance down the road they would want to give some chemo then, and it might be a whole better drug if that's years away, if at all. Or they irradiate too. An annual PET/CT picks up 4mm lesions now and larger.

Or you get another opinion even another onco in same office, my wifes breast onco has partner and specializes in all types of cancer, so he confers with him, then w/ surgeon.

Did the ultrasound say tumor "cystic" ? It's good they did US after 3 (half way, that's what should be done, they did one after 2 with my wife, her surgeon said there should be some change after 1 chemo, if not after 2, she would go to surgery. However, my wife's tumor was 4.5cm TNBC/metaplastic/squamous, so very aggressive and she didn't want to mess around changing drugs, which wasn't necessary, she went ahead. Very common for tumor to become cystic as chemo works, becomes less vascular I believe.

Tulip is right also about neoadjuvant chemo complete response is only about 33% of time I think, a partial response is still good and even if doesn't shrink, could be necrosis, although I think here should be some activity softening, something after 3 therapies.
wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017
Back to Top
MarkH34 View Drop Down
Newbie
Newbie


Joined: Jul 07 2016
Status: Offline
Points: 8
Post Options Post Options   Thanks (0) Thanks(0)   Quote MarkH34 Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 5:00pm
Thanks for the replies and reassurances.

When she did her initial workup, they had her do an MRI after her first ultrasound and biopsy. The MRI showed the tumor at being 1.4 cm even though the ultrasound said 2.0. The surgeon said that they would go by the ultrasound measurement.

I don't have the ultrasound report in front of my so I can't answer about the "cystic" portion.

After her MRI, they saw one node that they thought was suspicious, so they ordered a core needle biopsy. That showed negative, as well as the initial tumor biopsy being negative for lymphatic / vascular invasion. She had no other tests done.

Her next round of chemo would have been in about 10 days, so we have some time to discuss with the oncologist what our next steps are. The breast surgeon did the 2nd ultrasound in her office, and was going to speak to the oncologist on the next steps.

It's been quite a roller coaster ride, as her initial biopsy had this tumor as an ER+ tumor with ER 42.1% staining, and PR 9.9% staining. Thus we had an oncotype dx test ordered, and her result for that came back triple negative with a score of 53! So it went from a somewhat favorable prognosis, to triple negative, and now an ineffective round of chemo. =(

I asked the oncologist before the ultrasound what he would probably recommend if it hadn't changed, and he said probably 4 round of AC, then surgery, then T afterward. I'm guessing that's the compromise before jumping straight to surgery? But we will see what he says after talking to the surgeon.
Back to Top
MarkH34 View Drop Down
Newbie
Newbie


Joined: Jul 07 2016
Status: Offline
Points: 8
Post Options Post Options   Thanks (0) Thanks(0)   Quote MarkH34 Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 5:03pm
Originally posted by MarkH34 MarkH34 wrote:


After her MRI, they saw one node that they thought was suspicious, so they ordered a core needle biopsy. That showed negative, as well as the initial tumor biopsy being negative for lymphatic / vascular invasion. She had no other tests done.


Just to add, she did have the oncotype dx done, as mentioned. She also had genetic testing done to test for BRCA which also came back negative.
Back to Top
gordon15 View Drop Down
Senior Member
Senior Member


Joined: Jun 22 2015
Location: San Diego CA
Status: Offline
Points: 779
Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 5:24pm
Mark- not to worry you further, it really sounds like good doctors,  but needle biopsies are often false negative, the lymph nodes are fatty and slip around a lot(actually the fatty coating on the nodes called hipia I think- is often gone when they are cancerous, it's what they look for right away)  and the technicians will tell you that. Also a small 1mm carcinoma in a 4-5mm node can be missed by the needle. My wife's 4 nodes were enlarged, one to over a cm, and PET/CT lit-up, yet the needle biopsy said no cancer, the report said to investigate further.

 The chemo killed the cancer in the nodes(pCR), and all but 1.2 cm in the tumor, they think it was possible the metaplastic/ squamous portion of the tumor was resistant to the chemo, and the complete response in the lymph nodes was that the metaplastic didn't get there.

They tested for 7 genes/all neg, androgens -receptive neg too.





Edited by gordon15 - Jul 08 2016 at 5:33pm
wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017
Back to Top
MarkH34 View Drop Down
Newbie
Newbie


Joined: Jul 07 2016
Status: Offline
Points: 8
Post Options Post Options   Thanks (0) Thanks(0)   Quote MarkH34 Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 5:37pm
Originally posted by gordon15 gordon15 wrote:

Mark- not to worry you further, it really sounds like good doctors,  but needle biopsies are often false negative, the lymph nodes are fatty and slip around a lot(actually the fatty coating on the nodes called hipia I think- is often gone when they are cancerous, it's what they look for right away)  and the technicians will tell you that. Also a small 1mm carcinoma in a 4-5mm node can be missed by the needle. My wife's 4 nodes were enlarged, one to over a cm, and PET/CT lit-up, yet the needle biopsy said no cancer, the report said to investigate further.

 The chemo killed the cancer in the nodes(pCR), and all but 1.2 cm in the tumor, they think it was possible the metaplastic/ squamous portion of the tumor was resistant to the chemo, and the complete response in the lymph nodes was that the metaplastic didn't get there.

They tested for 7 genes/all neg, androgens -receptive neg too.




Yes, it is possible that the node biopsy missed it. Still, the course of treatment wouldn't change... chemo + surgery. Is there more we can do?
Back to Top
gordon15 View Drop Down
Senior Member
Senior Member


Joined: Jun 22 2015
Location: San Diego CA
Status: Offline
Points: 779
Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 6:01pm
A compromise plan like that makes sense. Let us know how she's doing. If node(s) not abnormal, and no tumor lymph/vascular invasion that's really good for outcome. 
wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017
Back to Top
mainsailset View Drop Down
Senior Member
Senior Member
Avatar

Joined: Jul 27 2008
Location: Washington State
Status: Offline
Points: 4952
Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2016 at 9:16pm
Hi Mark, sorry to be late.
   I was on a clinical trial, at my 4th week my doctor couldn't discern any change in the tumor size or a softening. But on 5th week it was as if it melted away, dramatic change!
   As long as you are taking the time to consider options you might ask your wife's team about clinical trials that they can offer. Not all doctors' offices have access to all clinical trials, which is to say your team may not discern that there's a good match available, but it's worth consideration.
   You probably know that there are 6 subtypes of Tneg and they react differently to various chemos. The initial biopsy may offer a determination of what subtype she has and that may help in the decision making.
   Please know that we're all here to help, I found my roughest spots were when there wasn't a plan in place that I could get behind. The questioning is just downright awful, so this is just a nudge to say keep at it, the right answer will come.
Best,
Mainy
dx 7/08 TN 14x6.5x5.5 cm tumor

3 Lymph nodes involved, Taxol/Sunitab+AC, 5/09 dbl masectomy, path 2mm tumor removed, lymphs all clear, RAD 32 finished 9/11/09. 9/28 CT clear 10/18/10 CT clear
Back to Top
gordon15 View Drop Down
Senior Member
Senior Member


Joined: Jun 22 2015
Location: San Diego CA
Status: Offline
Points: 779
Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post Posted: Jul 09 2016 at 3:41pm
Mark- this long article covers a lot on TNBC chemo options, very technical.

https://cme.dannemiller.com/articles/activity?id=502&f=1
wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017
Back to Top
HoneyBee View Drop Down
Newbie
Newbie
Avatar

Joined: Aug 07 2016
Location: VA
Status: Offline
Points: 12
Post Options Post Options   Thanks (0) Thanks(0)   Quote HoneyBee Quote  Post ReplyReply Direct Link To This Post Posted: Aug 08 2016 at 8:48pm
Check out the meds bing used at this trial in Richmond. Might be worth asking your doctor about as well. 
Back to Top
MarkH34 View Drop Down
Newbie
Newbie


Joined: Jul 07 2016
Status: Offline
Points: 8
Post Options Post Options   Thanks (0) Thanks(0)   Quote MarkH34 Quote  Post ReplyReply Direct Link To This Post Posted: Aug 17 2016 at 2:08pm
Hello Everyone,

I just wanted to post an update and hopefully see if anyone has any insight on current progress.

So, the decision was made to switch chemo to AC x 4 -> Surgery -> Then T and maybe Carbo.

We are 1 week out from the 2nd round of AC currently. Unfortunately, although it wasn't measured, the tumor doesn't seem to be changing much in size.

The strange thing is that the area around the tumor is filling up with lots of fluid after each round of chemo.

The surgeon has aspirated the fluid with each round and has had it tested, no cancer cells were found. The surgeon doesn't have a definite answer on what the fluid is, after speaking to the tumor board, and other surgeons / oncologists at MD Anderson, they are in agreement that it is a good sign and that the chemo is doing something to the tumor, but until they remove it, they won't know quite what.

Apparently, this type of fluid build up is pretty rare, as the current staff and MD Anderson has seen it very rarely. Has anyone ever heard of this kind of reaction or have more information? I haven't been able to find anything online. The oncologist thinks that parts of the tumor could be just dead cells at this point.

There was actually fluid build up after the initial rounds of TC as well, just not as much as now.

Appreciate if anyone has any research or insight on the matter.

Thanks.
Back to Top
gordon15 View Drop Down
Senior Member
Senior Member


Joined: Jun 22 2015
Location: San Diego CA
Status: Offline
Points: 779
Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post Posted: Aug 19 2016 at 7:17pm
Mark- After my wife had 2 sessions/chemo (carboplatin/gemzar) they did an ultrasound, and the technicians said "the tumor is now "cystic" but it wasn't fluid around the tumor, but interactions on the tumor itself, as the chemo effected the tumor. Not sure what to say about fluid around the tumor, it's amazing you have docs to analyze that fluid, it sound like you have good care.

I've read-up a bunch on this: chemo actually breaks down all the tissue in the breast, and it rebuilds after finishing therapies, ask your wife's oncologist if it's normal for a breakdown of tissue (cystic), which means the chemo could have positive results, if your wife finishes it,unfortunately, we never know until the pathologist analyzes the surgically removed tissue, and reports.




Edited by gordon15 - Aug 19 2016 at 7:22pm
wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017
Back to Top
MarkH34 View Drop Down
Newbie
Newbie


Joined: Jul 07 2016
Status: Offline
Points: 8
Post Options Post Options   Thanks (0) Thanks(0)   Quote MarkH34 Quote  Post ReplyReply Direct Link To This Post Posted: Aug 21 2016 at 4:21pm
Originally posted by gordon15 gordon15 wrote:

Mark- After my wife had 2 sessions/chemo (carboplatin/gemzar) they did an ultrasound, and the technicians said "the tumor is now "cystic" but it wasn't fluid around the tumor, but interactions on the tumor itself, as the chemo effected the tumor. Not sure what to say about fluid around the tumor, it's amazing you have docs to analyze that fluid, it sound like you have good care.

I've read-up a bunch on this: chemo actually breaks down all the tissue in the breast, and it rebuilds after finishing therapies, ask your wife's oncologist if it's normal for a breakdown of tissue (cystic), which means the chemo could have positive results, if your wife finishes it,unfortunately, we never know until the pathologist analyzes the surgically removed tissue, and reports.


Hi Gordon,

Did your wife's tumor shrink and turn cystic? What was the final pathology report after her surgery compared to the original biopsy? Did she get a PCR?

Thanks.


Edited by MarkH34 - Aug 21 2016 at 10:45pm
Back to Top
MrsBraly View Drop Down
Newbie
Newbie
Avatar

Joined: Dec 21 2015
Location: Longview, TX
Status: Offline
Points: 9
Post Options Post Options   Thanks (0) Thanks(0)   Quote MrsBraly Quote  Post ReplyReply Direct Link To This Post Posted: Aug 22 2016 at 10:32am
Hi Mark,
 
I wanted to share with you my tumor story.  I was on a trial, double-blind study of 12 weekly Taxol with Carbo added every 3rd week, also Velaparib, a pill everyday. (Tulips was also on the same study, I believe.)  I know I was receiving the Carbo because my last dose my Onco upped it and my numbers tanked.  Very clever how the doctors get around double-blind studies. ;) 
 
My original tumor was 2.4cm, initially shrunk in size, (by feel only) and then grew to 3.3cm, MRI confirmed.  During the A/C chemo, there was no change in the tumor size.  It didn't shrink, but it didn't grow either.  When I had surgery the pathology came back 1mm residual cancer which is hardly anything! 
 
I know how difficult it is to be going through this and wanting immediate results.  I kept hoping week after week that this stupid tumor would just dissolve!  Everyone's cancer is different because everyone's cells are different.  That's why there is no one cure.  I believe the A/C was instrumental in my tumor but for some people it's the Taxol.  I wish I could give you definite answers.  I can only give you my experience.
 
You and your wife are in my thoughts and prayers! Keep the faith!


Edited by MrsBraly - Aug 22 2016 at 10:38am
DX 11/20/15, Age 49, IDC-TNBC Stage IIb Gr 3, 2.4cm, ki-67 87% BRCA- 12 weekly Taxol and 4 bi-weekly A/C completed 5/9/16 BI-MX and beginning of recon 6/10/16.
Back to Top
gordon15 View Drop Down
Senior Member
Senior Member


Joined: Jun 22 2015
Location: San Diego CA
Status: Offline
Points: 779
Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post Posted: Aug 22 2016 at 5:52pm
Mark, MrsB , and Everyone: When my wife started Carboplatin/Gemzar chemo before surgery, she had a tumor about 4cm,..... after (2) treatments, technician said "it's cystic now"... turned liquid." Normally the ultrasound techs won't voice their opinion unless you ask, fyi.
Even then, that might contradict the pathology report results.

Mark, after this, the surgeon and oncologist decided to proceed with all 6 treatments. Bear in mind, my wife (if I remember your wife's situation) has a more aggressive situation in as much as MRI/PET/CT indicated 3-4 abnormal lymph nodes and large tumor.

My wife's tumor shrunk by about 75% (not a pCR) but a "partial pathological response"
A "pCR" is a "pathological Complete Response" which only occurs in about 25% of patients (some here can correct me on the percentage, maybe it's 30%) I consider 75% as a victory.

The chemo resulted in a pCR (100%) in my wife's lymph nodes.

Mark: The final biopsy after chemo was not different than the biopsy. I have tremendous faith in pathologists. From our experience. The pathology report indicated that there was 25% (approximate) carcinoma still in her tumor after neoadjuvant chemo of Carbopltin/Gemzar. As I said, but the lymph node cancer was killed.

My wife's and other(s) oncologist's opinions think "perhaps" the "metaplastic/squamous" part of her tumor formed a resistance to the chemo, and that did not get to her lymph nodes in the armpit.

This isn't your wife's concern, just for overview, or whatever...

I think and cystic change is part of the chemo working, as I have outlined, cystic, also means "less vascular" from all my reading, this may not apply to your wife, but my wife had "vascular invasion" by the tumor, so when showed "cystic" ,that means a breakdown of vascular, which in my wife's case was good. It means the chemo is most likely working to breakdown the cancer cells. Actually, if you research Carboplatin-Gemzar, one chemical breaks down the cancer cell, and the other goes in and does other work. I hope you appreciate my simplification, I majored in art. :~)

Hope this helps, please keep us updated.








Edited by gordon15 - Aug 22 2016 at 5:58pm
wife: IDC/Lobular Stage2B 2008 lumpectomy/TAC+rads
TNBC Stage 3A/w/metaplastic/squamous Nov2015 Carboplatin-Gemzar chemo/masectomy Taxolchemo+rads 4-16
PET scan stable 9-2016/ 1-2017
Back to Top
 Post Reply Post Reply
  Share Topic   

Forum Jump Forum Permissions View Drop Down

Forum Software by Web Wiz Forums® version 11.05
Copyright ©2001-2016 Web Wiz Ltd.