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Topic: Metastasis study looks good for ILC

Forum: ILC (Invasive Lobular Carcinoma) — Just diagnosed, in treatment, or finished treatment for ILC.

Posted on: Sep 10, 2019 08:13PM

jessie123 wrote:

Researchers at the Johns Hopkins Kimmel Cancer Center discovered that a cell adhesion protein, E-cadherin, allows breast cancer cells to survive as they travel through the body and form new tumors, a process termed metastasis. Their conclusions, obtained through laboratory experiments and in mouse models, help explain how metastasis works in the most common form of breast cancer, invasive ductal carcinoma. E-cadherin appears to limit molecular stresses within the cancer cells and allow them to survive long enough to form new tumors. The finding, published online in the Sept. 4 issue of Nature, could lead to new ways to prevent breast cancers from recurring in patients.

"Previously, researchers thought that it was essential for cancer cells to lose E-cadherin in order to metastasize," says study leader Andrew Ewald, Ph.D., professor of cell biology and co-director of the Cancer Invasion and Metastasis Program at Johns Hopkins Kimmel Cancer Center. "This was difficult to reconcile with the fact that breast tumors in patients typically continue to express E-cadherin. Our study was designed to test the role of this protein during metastasis."

The overwhelming majority of breast and other cancer deaths are caused by metastasis; consequently, preventing metastasis is a crucial cancer research goal, he says.

Scientifically, metastasis is characterized by many separate stages, including when cancer cells invade healthy breast tissue, escape the primary tumor, enter and survive within blood vessels, exit into new organs, then survive and seed a new tumor in a distant organ, such as the lungs.

Cancer cells break free from the primary tumor early in metastasis and much research has focused on how cancer cells stick together at the molecular level, through the protein E-cadherin. In some cancers, such as a form of breast cancer known as invasive lobular carcinoma, genetic mutations that eliminate E-cadherin appear to be pivotal for metastasis to occur.

However, other types of cancer -- such as invasive ductal carcinoma, the most common form of breast cancer, responsible for more than 80% of all breast cancer diagnoses -- retain this protein or even overexpress it, a discrepancy that scientists couldn't explain.

To investigate this discrepancy, Ewald and his colleagues tested the role of E-cadherin in three experimental models of invasive ductal carcinoma that represent common subtypes of human breast cancer: luminal, basal, and triple negative breast cancer. These subtypes have different patterns of gene expression and different average patient outcomes.

First, they tested the role of E-cadherin during cancer invasion. Across all three models, loss of the E-cadherin gene dramatically increased the cancer cells' ability to invade healthy tissue. For example, in a mouse model, tumors that made E-cadherin invaded along 6% of their tumor borders, while those without E-cadherin invaded along 82% of their borders.

However, losing E-cadherin sabotaged every other biological stage of metastasis in all three breast cancer models, in both lab experiments and animal models. Cells without E-cadherin got lost while migrating and died in large numbers at every step after leaving the primary tumor. The few that did manage to migrate and survive didn't proliferate in new organs and rarely formed new tumors, Ewald reports.

"The good news," he says, "is that our study reveals that the process of metastasis, even in ideal laboratory settings, appears to be exceedingly inefficient." Research suggests that about 99% of cells that leave primary tumors die and never form new tumors.

The study results suggest that breast cancer cells need adhesive connections to survive and eventually spread and kill patients. "Our future research aims to understand how to target the survival signals related to E-cadherin and prevent metastases from forming, thereby saving patients' lives," Ewald says.

Story Source:

Materials provided by Johns Hopkins Medicine. Note: Content may be edited for style and length.

Dx 11/2018, LCIS/ILC, Left, 2cm, Stage IB, Grade 2, 0/2 nodes, ER+/PR+, HER2- Surgery 2/21/2019 Lumpectomy: Left; Lymph node removal: Sentinel Radiation Therapy 4/14/2019 Whole-breast: Breast
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Sep 10, 2019 08:59PM FarAwayToo wrote:

But ILC patients still develop metastasis, unfortunately.

My tumor was never explicitly classified as ILC, but it was completely lacking E- Cadherin. That doesn't mean I'm safe. I read somewhere that E-Cadherin negative cells most likely regain the expression of E-Cadherin at some point of metastatic process.

Dx 8/31/2017, IDC, Right, 2cm, Stage IIA, Grade 2, 0/4 nodes, ER+/PR+, HER2- Dx 9/15/2017, DCIS, Left, 3cm, Stage 0, Grade 1, 0/3 nodes, ER+/PR+, HER2- Chemotherapy 9/29/2017 Adriamycin (doxorubicin), Cytoxan (cyclophosphamide), Taxol (paclitaxel) Hormonal Therapy 2/22/2018 Zoladex (goserelin) Surgery 2/27/2018 Mastectomy: Left, Right Surgery 2/28/2018 Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Hormonal Therapy 4/4/2018 Femara (letrozole) Surgery 8/20/2018 Prophylactic ovary removal; Reconstruction (left): Saline implant; Reconstruction (right): Saline implant
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Sep 10, 2019 09:54PM Meow13 wrote:

One of my tumors was absent of e-cadherin the other was highly expressive. They were both 1cm and close to the surface no additional spread of disease was found. Luckiky no skin or lymph nodes were involved crossing my fingers that surgery got everything.

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Sep 12, 2019 05:19PM nash wrote:

ILC metastasizes all the time. So do ILC mets regain expression, as FarAwayToo noted? Both of my primary tumors and my local recurrence lacked e cadherin, and then I developed brain mets. No biopsy was done before treatment for the mets due to location within my brain, so there’s no way to know.

Stage IV Pleomorphic ILC, initially diagnosed at age 38 Dx 6/7/2007, ILC, Left, 2cm, Stage IIA, Grade 2, 0/4 nodes, ER+/PR+, HER2- (FISH) Surgery 7/19/2007 Lumpectomy: Left; Lymph node removal: Sentinel Chemotherapy 8/1/2007 CAF Radiation Therapy 12/27/2007 Whole-breast: Breast, Chest wall Hormonal Therapy 3/1/2008 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Dx 4/24/2015, ILC, Left, 1cm, Stage IA, Grade 2, 0/10 nodes, ER+/PR+ Surgery 5/15/2015 Mastectomy; Reconstruction (left): Latissimus dorsi flap Dx 2/1/2018, ILC, Right, 6cm+, Stage IIIA, Grade 3, ER+/PR+ Chemotherapy 2/15/2018 Cytoxan (cyclophosphamide), Taxol (paclitaxel), Taxotere (docetaxel) Dx 6/20/2018, ILC, Both breasts, 6cm+, Stage IV, metastasized to brain/bone, Grade 3, ER+/PR+ Radiation Therapy External: Brain Hormonal Therapy Faslodex (fulvestrant), Zoladex (goserelin) Targeted Therapy Ibrance (palbociclib)
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Sep 12, 2019 05:49PM jessie123 wrote:

Farawaytoo --- but the hallmark of ILC is the lack of E- Cadherin. Maybe, as in your case, some IDC doesn't express E-Caderin and maybe later it can regain the expression. I don't think (could be wrong) that's how ILC works. I would love to know how many ILC patients do go on to metastasis. It's hard to find statistics because the only information I have found lumps IDC and ILC together. Guess that will be my next search.


Dx 11/2018, LCIS/ILC, Left, 2cm, Stage IB, Grade 2, 0/2 nodes, ER+/PR+, HER2- Surgery 2/21/2019 Lumpectomy: Left; Lymph node removal: Sentinel Radiation Therapy 4/14/2019 Whole-breast: Breast
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Sep 12, 2019 06:04PM jessie123 wrote:

Nash -- I sent that post before I read yours. How do you know ILC gains E-cadherin expression? Are there articles about it? I'm really curious to learn more about this. Have you found any statistics on the percentage of ILC patients who go on to metastasize? I don't know much about pleomorphic ILC -- how does it differ from non-pleomorphic ILC? Even though my treatment is over I still have so many questions.

Dx 11/2018, LCIS/ILC, Left, 2cm, Stage IB, Grade 2, 0/2 nodes, ER+/PR+, HER2- Surgery 2/21/2019 Lumpectomy: Left; Lymph node removal: Sentinel Radiation Therapy 4/14/2019 Whole-breast: Breast
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Sep 12, 2019 06:17PM - edited Sep 12, 2019 06:49PM by trinigirl50

This Post was deleted by trinigirl50.
trinigirl50 Dx 3/7/2015, ILC, Left, 6cm+, Stage IIIC, Grade 2, 20/24 nodes, ER+/PR-, HER2- Surgery 3/7/2015 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Prophylactic mastectomy: Right Chemotherapy 4/14/2015 AC + T (Taxotere) Hormonal Therapy 9/14/2015 Arimidex (anastrozole), Femara (letrozole) Radiation Therapy 10/1/2015 Whole-breast: Breast, Lymph nodes
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Sep 12, 2019 06:25PM trinigirl50 wrote:

Just today I read about a very large study and the role of ecadherin loss. In a nutshell it said that ecadherin loss was not a predictor of reoccurence or metastases. It acknowledged that there were other discussions to do with ecadherin loss but it was a very large study over a long period (using data from different studies). I will dig it out tomorrow. It was recent as well, although not as recent as the article posted. Also the posted article was geared towards testing of IDC cancers, not ILC.

As far as I am aware from my layman's research, ILC women metastasize the same as IDC women, not more frequently (as has been often postulated) but not any less either. Later reoccurence and to more unusual areas is the major difference. Also hard to see on scans so later to diagnose.


trinigirl50 Dx 3/7/2015, ILC, Left, 6cm+, Stage IIIC, Grade 2, 20/24 nodes, ER+/PR-, HER2- Surgery 3/7/2015 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Prophylactic mastectomy: Right Chemotherapy 4/14/2015 AC + T (Taxotere) Hormonal Therapy 9/14/2015 Arimidex (anastrozole), Femara (letrozole) Radiation Therapy 10/1/2015 Whole-breast: Breast, Lymph nodes
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Sep 12, 2019 06:47PM trinigirl50 wrote:

https://www.nature.com/articles/s41598-018-23733-4

That's the article I was referring to.


trinigirl50 Dx 3/7/2015, ILC, Left, 6cm+, Stage IIIC, Grade 2, 20/24 nodes, ER+/PR-, HER2- Surgery 3/7/2015 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Prophylactic mastectomy: Right Chemotherapy 4/14/2015 AC + T (Taxotere) Hormonal Therapy 9/14/2015 Arimidex (anastrozole), Femara (letrozole) Radiation Therapy 10/1/2015 Whole-breast: Breast, Lymph nodes
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Sep 12, 2019 06:55PM - edited Sep 12, 2019 06:56PM by trinigirl50

This Post was deleted by trinigirl50.
trinigirl50 Dx 3/7/2015, ILC, Left, 6cm+, Stage IIIC, Grade 2, 20/24 nodes, ER+/PR-, HER2- Surgery 3/7/2015 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Prophylactic mastectomy: Right Chemotherapy 4/14/2015 AC + T (Taxotere) Hormonal Therapy 9/14/2015 Arimidex (anastrozole), Femara (letrozole) Radiation Therapy 10/1/2015 Whole-breast: Breast, Lymph nodes
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Sep 12, 2019 07:01PM trinigirl50 wrote:

jessie123

Check out lobularbreastcancer.org

Or there is an ILC FB group as well. Lots of info there on ILC. It isn't as well documented simply because less women get it. It has only recently started to get individual attention.



trinigirl50 Dx 3/7/2015, ILC, Left, 6cm+, Stage IIIC, Grade 2, 20/24 nodes, ER+/PR-, HER2- Surgery 3/7/2015 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Prophylactic mastectomy: Right Chemotherapy 4/14/2015 AC + T (Taxotere) Hormonal Therapy 9/14/2015 Arimidex (anastrozole), Femara (letrozole) Radiation Therapy 10/1/2015 Whole-breast: Breast, Lymph nodes
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Sep 12, 2019 08:34PM jessie123 wrote:

Thanks -- I''m a member of the FB group, but I get better information from this group -- maybe it would help if I posted a question on that group. I want to know what percentage of IL cancers metastasize. I know they metastasize later than IDC, but I just can't find what the percentage is. The lobular bc.org site is good and I like to listen to their seminars, but I always seem to miss them and they are difficult to understand. I've also read that ILC has a greater mortality rate than IDC, but that's probably because it's so difficult to diagnosis. For some reason I don't worry much about mine recurring. I think that's because I have 3 close friends who have had ILC -- one was 25 years ago. They are all fine. I also think I'm not over the shock of having had cancer. It's like I had oral surgery and now I'm well. However, in the evenings I start thinking about it again.

Dx 11/2018, LCIS/ILC, Left, 2cm, Stage IB, Grade 2, 0/2 nodes, ER+/PR+, HER2- Surgery 2/21/2019 Lumpectomy: Left; Lymph node removal: Sentinel Radiation Therapy 4/14/2019 Whole-breast: Breast
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Sep 12, 2019 08:40PM FarAwayToo wrote:

Nash, I think that sometimes metastatic tumor cells have E-Cadherin expression and sometimes they don't. It looks like E-Cadherin is only part of the picture. It sure helps distinguish ILC from IDC, when pathologists are in doubt, but there are probably other factors that influence cell adhesion.

jessie123 - there were no cells in the biopsy specimen or my left-over tumor (after chemo) that expressed E-Cadherin, which is why they said "complete loss of E-Cadherin". I guess, I still don't know though if it really means my tumor was ILC. On my post-mastectomy pathology it was classified as "invasive mammary with lobular features". My oncologist told me that it could still be IDC, due to certain features (it imaged and presented as a very distinct lump, which is not often the case with ILC). Guess, I don't know where I belong :)


trinigirl50, I think I've seen similar studies, and basically most of them conclude that E-Cadherin doesn't play into prognosis, other factors, such as grade, size, node positivity and hormone status do (but this is not new). It's interesting how they broke down quite a few categories trying to find patterns with HRT use, number of pregnancies etc.

I suddenly remembered what my oncologist said at the very beginning: ILC is "mom's cancer", meaning it's more frequent in women who have had at least one live birth, often more. Looking at the study, there were 51 nulliparous women with lobular histology. Perhaps it's more common in women who went through pregnancy and live birth, but it's not a "pre-requisite" .

Dx 8/31/2017, IDC, Right, 2cm, Stage IIA, Grade 2, 0/4 nodes, ER+/PR+, HER2- Dx 9/15/2017, DCIS, Left, 3cm, Stage 0, Grade 1, 0/3 nodes, ER+/PR+, HER2- Chemotherapy 9/29/2017 Adriamycin (doxorubicin), Cytoxan (cyclophosphamide), Taxol (paclitaxel) Hormonal Therapy 2/22/2018 Zoladex (goserelin) Surgery 2/27/2018 Mastectomy: Left, Right Surgery 2/28/2018 Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Hormonal Therapy 4/4/2018 Femara (letrozole) Surgery 8/20/2018 Prophylactic ovary removal; Reconstruction (left): Saline implant; Reconstruction (right): Saline implant
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Sep 12, 2019 09:28PM jessie123 wrote:

FarAwaytoo --That is exactly what my biopsy result said --- mammary carcinoma with lobular features. My surgeon kept saying that was lobular, but I had read that it could also be a mixture. She would not budge and I began to distrust her. However, her specialty is breast and endocrine cancer and she has been practicing for years at a teaching hospital. In the end after surgery it was just lobular. Mine also presented as a lump. That is how I found it myself. It was a hard, non moving lump. I had two biopsies at two different hospitals.and both radiologist had a very difficult time getting the sample. They kept losing it and had to try multiple times.

By the way - I was born in Boulder when my dad was in school. Also, as far as being a "moms" cancer - I never had children. I blame my nightly wine.

Dx 11/2018, LCIS/ILC, Left, 2cm, Stage IB, Grade 2, 0/2 nodes, ER+/PR+, HER2- Surgery 2/21/2019 Lumpectomy: Left; Lymph node removal: Sentinel Radiation Therapy 4/14/2019 Whole-breast: Breast
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Sep 13, 2019 10:17AM trinigirl50 wrote:

I haven't seen a study that extrapolates ILC from IDC when it comes to percentages that will metastasise, probably because overall ILC is only 10-15% of all breast cancers, so they lump them together.

There was a couple of threads about early stage cancer that reoccurs, and if I remember correctly, the percentage of early stage (1-3) cancers that advanced was between 28 and 30%, this was not separated into ILC and IDC. So if you don't take into account tumour grade, size, node negative, ER PR Her2 status, histology etc etc and all the things that Drs use to determine your personal chance of recurrence or mets, and go to the worst case overall scenario, then you have a 28-30% chance of it advancing.

I never read that ILC has a greater mortality rate than IDC. But I would also assume if it does, its because it's usually discovered when its already locally advanced.



trinigirl50 Dx 3/7/2015, ILC, Left, 6cm+, Stage IIIC, Grade 2, 20/24 nodes, ER+/PR-, HER2- Surgery 3/7/2015 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Prophylactic mastectomy: Right Chemotherapy 4/14/2015 AC + T (Taxotere) Hormonal Therapy 9/14/2015 Arimidex (anastrozole), Femara (letrozole) Radiation Therapy 10/1/2015 Whole-breast: Breast, Lymph nodes
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Sep 13, 2019 12:26PM OnTarget wrote:

Jessie123- my biopsy said mammary cancer with ductal and lobular features on the left side. The pathology after BMX said ILC for the same side. I am not sure of the reason for the change in my case, but I feel that the pathology from the BMX is right.

Diagnosed at 42, Oncotype score 16, ITC in one node- considered node negative Dx 4/8/2019, ILC, Left, 3cm, Stage IB, Grade 2, 0/3 nodes, ER+/PR+, HER2- Dx 4/23/2019, ILC, Right, <1cm, Stage IA, Grade 2, 0/2 nodes, ER+/PR+, HER2- Surgery 5/15/2019 Lymph node removal: Sentinel; Mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Hormonal Therapy 6/13/2019 Zoladex (goserelin) Chemotherapy 8/5/2019 Cytoxan (cyclophosphamide), Taxotere (docetaxel) Surgery 11/5/2019 Reconstruction (left): Silicone implant; Reconstruction (right): Silicone implant

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