How Her2+ BC patients develop brain metastases
 

City of Hope researchers find how HER2-positive breast cancer patients develop brain metastases

March 2, 2017 at 8:53 PM
Ninety percent of cancer deaths are from cancer spread. Breast cancer patients, for example, typically do not die because cancer returns in their breast, they die because it spreads to other parts of their body. The most dangerous of which is the brain. Approximately 40 percent of all women with HER2-positive breast cancer will develop brain metastases. Now City of Hope researchers have found how this happens.

Breast cancer cells wrap themselves in reelin -- a protein typically found only in the brain -- that allows the cells to disguise themselves as "friend and not foe," avoiding a system in the brain designed to detect enemy cells. From these disguised cells, new deadly brain tumors form.

"More women than ever are surviving breast cancer only to die from breast tumors growing in their brains years after they've been declared cancer-free," said City of Hope dual trained neurosurgeon and scientist Rahul Jandial, M.D., Ph.D., who led the study available online and slated for the upcoming print publication of the Clinical & Experimental Metastasis, the journal for the Metastases Research Society. "I wanted to understand why women with HER2-positive breast cancer (around 20 percent of all breast cancers) have higher rates of brain metastases than women with other breast cancer subtypes and in turn, find their biological Achilles heel to develop new medicines."

After performing brain surgery, Jandial and his team took leftover tissue samples and compared them to breast cancer tissue removed from mastectomies in the same women. They compared the expression of proteins and found that reelin expression was low in primary breast cancer tissue. However, its expression was significantly higher in HER2-positive breast cancer metastasizing to the brain.

"The cells are essentially able to act as spies that look like citizens," said Jandial. "They release a mesh of protein and escape the brain's natural defense weapons, causing tumors to grow in the brain."

Understanding these mechanisms is an important step in developing new therapies to treat brain cancers -- especially for metastatic cancers. Metastases are responsible for 90 percent of all cancer deaths, and patients diagnosed with brain metastases only have a 20 percent chance of surviving a year after diagnosis.

Source:
City of Hope

Re: How Her2+ BC patients develop brain metastases
 

Approximately 40 percent of all women with HER2 positive breast cancer will develop brain metastases. I am shocked by this statement! Any thoughts please?

Re: How Her2+ BC patients develop brain metastases
 

I am shocked, too. And somewhat scared

Re: How Her2+ BC patients develop brain metastases
 

I had stage 3C bc with an inoperable tumour in my supraclavicular node....sort of leading to the brain I thought. I was very nervous of this possibility as was my doctor. So far so good. When I was diagnosed the odds were very low of my survival as they were older stats. I came to believe that statistics are not necessarily to be believed.

touch wood. lol

Cathy

Re: How Her2+ BC patients develop brain metastases
 

From your mouth...

Re: How Her2+ BC patients develop brain metastases
 

I’m more scared with the “patients diagnosed with brain metastases only have a 20 percent chance of surviving a year after diagnosis”, especially since 40% of women with HER II positive breast cancer are expected to get brain metastases. Let’s hope they come up with a new therapy to treat brain metastases soon! Very scary!

¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬ ¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬
12/15 – First mammogram
01/16 – Second mammogram and ultrasound.
01/16 – Meet surgeon and go for third mammogram, second ultrasound and biopsy. Surgeon confirms cancer in left breast and lymph nodes and sets surgery date.
01/16 – Chest scan and bone scan done– all looks good.
02/16 – Surgery - left breast mastectomy and 16 lymph nodes removed (8 had cancer).
02/16 – CT scan done – small nodules on lung but Doctor advises it’s post surgical. They will continue to monitor just in case.
03/16 – Meet radiation oncologist and find out results of Pathology Report. I’m told that I have locally advanced breast cancer, based on the size of my tumour (7 cm!) and the fact that they found cancer cells in eight lymph nodes. I’m also told that I’m HER 2 positive, with high levels of estrogen and progesterone and that my cancer is stage 3, grade 2.
03/16 – Meet oncologist and am told that my cancer is actually grade 3, and that I should have done chemo before surgery. Too late now!
03/16 – Start first of six doses of chemo (Carboplatin and Docetaxal) and Herceptin (for 18 months).
04/16 – Have port put in.
04/16 – Get second dose of chemo, but Docetaxal is left out due to liver enzymes being high. I was unable to get a full dose of Docetaxal after my first treatment.
06/16 – Finished chemo! One month off and then I start radiation.
06/16 – Start Tamoxifen.
07/16 – First radiation treatment – 24 more to go!
08/16 – Went for Genetic Testing to see if I have the BRCA gene. Tested negative for BRCA I and II
08/16 – Radiation oncologist biopsies “scar tissue” on my chest wall. I am told that I have a local recurrence and need to have rush surgery.
09/16 – Meet surgeon who advises that I need to meet with a plastic surgeon, as they will need to do a skin graft to close me up after surgery. Meet plastic surgeon and all looks good. A surgery date is set for October 4.
09/16 – Go for rush ultrasound, bone scan, breast MRI and CT scan.
09/16 – Meet oncologist who advises that the ultrasound and bone scan results look good, and that MRI shows three small masses at surgery site, but lymph nodes are clear. Still awaiting the results of the CT scan, but we are positive it will look good.
09/16 – Get a call from my oncologist, who advises that CT scan shows small spots on my lungs, and a large lymph node in the middle of my chest. This means the cancer has spread! She looks into getting me funded for TDM-1 and cancels my surgery.
10/16 – Meet oncologist, who advises that I have to take Perjeta before I can take TDM1. I start Perjeta/Herceptin every three weeks for an indefinite amount of time, and Taxol, which I will take two weeks in a row with one week off and then two weeks in a row for 8-16 treatments. Stop Tamoxifen.
10/16 – Meet surgeon, who reviews my CT scan and advises that the spots on my lungs may not be cancer, and that he doesn’t see a lymph node in my chest. He thinks it’s a spot on my lung. I’m feeling very confused! He advises that my oncologist doesn’t want me to have surgery to remove the three small masses on my scar line, as she wants to use them as a way to determine if the treatment is working. He advises that if they have not shrunk in 6 months, he will revisit surgery.
10/16 – CEA blood test to determine Tumour markers. Results were normal (2.7). My doctor advises that this could mean two things: (1) that the treatment is working, and the tumours are shrinking, or (2), that I'm one of those people who never get elevated CEA levels. Given that some people never get an elevated CEA level, this test doesn’t seem very accurate to me! Asked for PET scan, but am told I don’t qualify.
10/16 – Brain MRI – NED!
11/16 - CA-15-30 blood test – Tumour markers are normal at 19.
11/16 – Second CEA blood test – Tumours markers are still normal at 1.6 Second CA-15-30 blood test – Tumour markers are still normal at 19
11/16 – Develop lymphedema and have to wear a sleeve
12/16 – CT Scan shows that the tumors on my lungs and the lymph node in the middle of my chest are shrinking, and that some have resolved. Also, the small masses along my scar line are no longer visible. This means the medication is working!
12/16 – Small “pimple” shows up where old tumour on chest wall was located. Doctor is going to monitor it for now.
01/17 – A second “pimple” shows up on chest wall, as well as a small lump under the skin. My doctor thinks it’s scar tissue and will monitor it for now.
0/17 – Started to develop severe back pain – worried the cancer has spread to my spine.
03/17 – Third CEA blood test and CA-15-30 blood test – awaiting results.
03/17 – CT Chest scan to see if there’s improvement to chest and lungs – awaiting results. If results are good, I get to stop taking Taxol!
03/17 – Second brain MRI scheduled for end of month.

Re: How Her2+ BC patients develop brain metastases
 

I was told I had a 40% chance of recurrence if I just had surgery and no chemo, Herceptin, radiation, etc. So maybe that is the 40% they are referring to? That is my hope anyway! Cancer just sucks....no two ways about it!

Re: How Her2+ BC patients develop brain metastases
 

I just went through my notes, and my doctor told me that with just surgery, there is a 35% chance of the cancer coming back, however, radiation brings it down to 16%, and chemo brings it down even lower. I did all three and still had a recurrence, so I guess these statistics don’t apply to me!

¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬ ¬¬¬¬¬¬¬¬¬¬¬¬¬¬¬
12/15 – First mammogram
01/16 – Second mammogram and ultrasound.
01/16 – Meet surgeon and go for third mammogram, second ultrasound and biopsy. Surgeon confirms cancer in left breast and lymph nodes and sets surgery date.
01/16 – Chest scan and bone scan done– all looks good.
02/16 – Surgery - left breast mastectomy and 16 lymph nodes removed (8 had cancer).
02/16 – CT scan done – small nodules on lung but Doctor advises it’s post surgical. They will continue to monitor just in case.
03/16 – Meet radiation oncologist and find out results of Pathology Report. I’m told that I have locally advanced breast cancer, based on the size of my tumour (7 cm!) and the fact that they found cancer cells in eight lymph nodes. I’m also told that I’m HER 2 positive, with high levels of estrogen and progesterone and that my cancer is stage 3, grade 2.
03/16 – Meet oncologist and am told that my cancer is actually grade 3, and that I should have done chemo before surgery. Too late now!
03/16 – Start first of six doses of chemo (Carboplatin and Docetaxal) and Herceptin (for 18 months).
04/16 – Have port put in.
04/16 – Get second dose of chemo, but Docetaxal is left out due to liver enzymes being high. I was unable to get a full dose of Docetaxal after my first treatment.
06/16 – Finished chemo! One month off and then I start radiation.
06/16 – Start Tamoxifen.
07/16 – First radiation treatment – 24 more to go!
08/16 – Went for Genetic Testing to see if I have the BRCA gene. Tested negative for BRCA I and II
08/16 – Radiation oncologist biopsies “scar tissue” on my chest wall. I am told that I have a local recurrence and need to have rush surgery.
09/16 – Meet surgeon who advises that I need to meet with a plastic surgeon, as they will need to do a skin graft to close me up after surgery. Meet plastic surgeon and all looks good. A surgery date is set for October 4.
09/16 – Go for rush ultrasound, bone scan, breast MRI and CT scan.
09/16 – Meet oncologist who advises that the ultrasound and bone scan results look good, and that MRI shows three small masses at surgery site, but lymph nodes are clear. Still awaiting the results of the CT scan, but we are positive it will look good.
09/16 – Get a call from my oncologist, who advises that CT scan shows small spots on my lungs, and a large lymph node in the middle of my chest. This means the cancer has spread! She looks into getting me funded for TDM-1 and cancels my surgery.
10/16 – Meet oncologist, who advises that I have to take Perjeta before I can take TDM1. I start Perjeta/Herceptin every three weeks for an indefinite amount of time, and Taxol, which I will take two weeks in a row with one week off and then two weeks in a row for 8-16 treatments. Stop Tamoxifen.
10/16 – Meet surgeon, who reviews my CT scan and advises that the spots on my lungs may not be cancer, and that he doesn’t see a lymph node in my chest. He thinks it’s a spot on my lung. I’m feeling very confused! He advises that my oncologist doesn’t want me to have surgery to remove the three small masses on my scar line, as she wants to use them as a way to determine if the treatment is working. He advises that if they have not shrunk in 6 months, he will revisit surgery.
10/16 – CEA blood test to determine Tumour markers. Results were normal (2.7). My doctor advises that this could mean two things: (1) that the treatment is working, and the tumours are shrinking, or (2), that I'm one of those people who never get elevated CEA levels. Given that some people never get an elevated CEA level, this test doesn’t seem very accurate to me! Asked for PET scan, but am told I don’t qualify.
10/16 – Brain MRI – NED!
11/16 - CA-15-30 blood test – Tumour markers are normal at 19.
11/16 – Second CEA blood test – Tumours markers are still normal at 1.6 Second CA-15-30 blood test – Tumour markers are still normal at 19
11/16 – Develop lymphedema and have to wear a sleeve
12/16 – CT Scan shows that the tumors on my lungs and the lymph node in the middle of my chest are shrinking, and that some have resolved. Also, the small masses along my scar line are no longer visible. This means the medication is working!
12/16 – Small “pimple” shows up where old tumour on chest wall was located. Doctor is going to monitor it for now.
01/17 – A second “pimple” shows up on chest wall, as well as a small lump under the skin. My doctor thinks it’s scar tissue and will monitor it for now.
0/17 – Started to develop severe back pain – worried the cancer has spread to my spine.
03/17 – Third CEA blood test and CA-15-30 blood test – Both normal at 2.5 and 25
03/17 – CT Chest scan to see if there’s improvement to chest and lungs – awaiting results. If results are good, I get to stop taking Taxol!
03/17 – Second brain MRI scheduled for end of month.

Re: How Her2+ BC patients develop brain metastases
 

My take away from all this is there's a reason it is called the practice of medicine. The doctors and medical teams are doing the best they can trying to deal with this "moving target" called cancer.

Re: How Her2+ BC patients develop brain metastases
 

Statistics don't apply to individual persons (or actions) ever, they are just data put into a certain perspective.

Since people aren't logical but emotional beings they're not equipped to judge their personal risk logically but are directed by hope and fear. We need just enough fear to watch out for ourselves and plenty of hope to keep going.

And while each of us will end up as a data point in one of those statistics, these don't determine our personal future. They are just a tool to give us clues about how best to proceed.

Re: How Her2+ BC patients develop brain metastases
 

I will have to get a closer look at the work they have done with this, to see whether they are talking about detecting the reelin protein solely by actual tissue sampling, or whether there is a current form of imaging that can detect it.

I'm still receiving annual breast MRI's and annual mammograms (alternating 6 months apart), although I haven't had an onc since 2006. (I never did any trastuzumab, and chose to discontinue tamoxifen fairly early on.)

I had a definite memory deficit this spring that was concerning, but with no physical evidence to support anything but doing serial mini-mental exams for future comparisons, I had to use a pick, hammer and shovel to get any brain imaging done. A noncontrast brain MRI showed nothing. Which is what it would show if noncontrast brain imaging doesn't detect the reelin.

A.A.

Re: How Her2+ BC patients develop brain metastases
 

I wish I didn't read this.

Re: How Her2+ BC patients develop brain metastases
 

Dee- try not to let this kind of info get into your head (pun intended). What is missing from this (and most) studies is info as it relates to people going thru current day protocol. The 40% or 4% or 1% or whatever - you finished your treatment and you deserve to act and live as if you are cured. Or in lifelong remission. It will give you a better quality of life, and in general the "what if's" rob us of time. Sorry that you are so worried, the more time that passes, the braver you will feel.
And just for the record, I had a single brain met in 2008, and am quite fine and still going strong.
ANything is possible.
Knowledge is power :)

Re: How Her2+ BC patients develop brain metastases
 

SoCalGal,

Thank you for the encouraging words. I needed them.
I have been getting in my head lately and some days I feel cancer is ALL I think about.
After reading your signature, I am most impressed with your outlook and your tenacity. You are amazing-thank you again. xo

Re: How Her2+ BC patients develop brain metastases
 

I would imagine this article also applies to all forms of cancer and not just breast cancer.

Re: How Her2+ BC patients develop brain metastases
 

To my sisters that have had brain mets....how was it first detected?
Scan, or did you have symptoms?

Re: How Her2+ BC patients develop brain metastases
 

Seven years after finding Brain mets on a MRI scan (November 2 2009) and five years after new brain mets and 20 to 25 spine mets (December 15, 2011) my wife is still alive. Doctors are now finding they have to do MRI scans of the brain and spine for HER+ patients for six to ten years. The problem has been that most doctors don't know what to do. I have helped a significant number of patients get Intrathecal Herceptin (now paired with a chemotherapy also IT) with pretty decent results. The problem is that a clinical trial takes took long to recruit a patient, so they are rarely healthy enough to participate. I challenge doctors with how many patients do they have that have gone into remission. Then I say that the vast majority of the patients that have tried the MD Anderson protocol have gone into remission. There is hope for patients, but you have to ask your doctor to look at the treatments. That can be hard for a medical professional's ego. If you run into CNS mets from HER+ ask about this treatment. If your doctor says it does not work, ask for the evidence in clinical trials or other documented cases.
There is the ability to raise the 20% to 90% or higher, but it takes patients asking the question.

Re: How Her2+ BC patients develop brain metastases
 

Seven years is incredible, thank you for the information provided in your posts.

Re: How Her2+ BC patients develop brain metastases
 

RolePaul could you specify whether the "brain mets" and "spine mets" your wife had were parenchymal or leptomeningeal?

Re: How Her2+ BC patients develop brain metastases
 

Sorry to be off the board so long. There were other matters that were pressing. My wife had leptomeningeal Brain mets. She was treated with IT Herceptin and Toptoecan. She is in remission.
The 40% mets to the brain really meant that 40% of the women that had mets were found to have mets in the brain/spine at autopsy or based on MRI scans. Brain/Spine mets are typically more slow growing than other organs, but can be devastating when they occur. I still recommend, as I did in November 2008, that if mets are found that a brain MRI scan also occur. If you do the math, the number of patients that are likely to have death occur from brain mets is 850 to 2000 patients per year. There are many proposed therapies, but I think the success of 80 to 100 mg of IT Herceptin (with or without Toptoecan) has shown real promise in the treatment of patients. Xeloda/Tykerb has shown benefits, as has OMT 380 for those patients who do not respond to surgery and radiation. I have helped many (over 35) women get this treatment. It is hard for me to recommend something different at this point, but I hope to do so in the future.
Nina started IT Herceptin at half dose on Jan 2012, and full dose on Feb 8 2012. She is still alive and doing well. The percentage of patients with both deep brain and lepto mets who have responded well to this treatment is over 80%. Start with a request for Compassionate care as soon as you find the CNS mets, and fight hard. The ability to get the meds and to get US Insurance to pay for it is 100% at this point. Getting compassionate care from your cancer center is getting easier as well. Let me know if you need help. I am not a doctor or medical practitioner, so this is a recommendation from someone with a lot of experience in helping patients with this issue.