ILC - The Odd One Out?

This is a repost from a few pages back, with numerous updates.

Despite the chronically understudied nature of ILC, the needle of research progress is slowly moving forward.
I often wonder how I can accelerate progress. Unfortunately, I'm not a scientist but I'm a good internet researcher and can pass on information.
There are ways YOU can help accelerate the slow pace of ILC research, which could benefit everyone reading this. I'll get to that below.

Now, the ILC news.

ILC Conference:
The first international ILC Symposium will be happening later this year (September 29 – 30, 2016), in Pittsburgh, Pennsylvania, USA.
http://upci.upmc.edu/WCRC/ilcSymposium.cfm
Registration details will be posted soon. It will be open to patients and advocates.
I created a separate thread, here, and will update it with details as I receive them.
The chair of the event is Dr. Steffi Oesterreich, who runs the Pitt Lab with dedicated ILC researchers.
The co-chairs are:
Dr. Nancy Davidson, Director of Pitt Cancer Institute and was recently elected as President of the AACR.
Dr. Otto Metzger of Dana–Farber Cancer Institute (Harvard). Otto has a solid history in breast cancer research, and was involved in the Big 1-98 trial which revealed the AI, Letrozole (Femara), was better than Tamoxifen for postmenopausal (postM) ILC patients. Otto also spent some time at "Institut Jules Bordet" in Belgium, which has a nest of lobular researchers (including Desmedt and Sotiriou who are authors of recent important Lobular research, below).
Two Keynote talks will be given by Dr. Patrick Derksen (University Medical Centre, Utrecht, Netherlands) and Dr. Mitch Dowsett (Royal Marsden, London, UK).
Dr. Derksen runs a breast cancer lab with ILC researchers.
Dr. Mitch Dowsett's bio can be read here.

- what is being done for metastatic ILC
- what should be done for premenopausal ILC
- what can be done to improve imaging diagnostics
- how can liquid biopsies be used to gauge tumor load and/or therapy success

The goal will be to help focus clinicians and scientists on these issues.

ILC Research Papers:
Multiple papers have been released during the last ~6 months which clearly indicate Lobular as a distinct breast cancer entity. No surprise, right?
Whether or not your Oncologist agrees is a different topic, but feel free to print and hand these papers over if they frown on this notion. Despite this slow paradigm shift, clinically, little can be done to change breast cancer guidelines, so broadly speaking, don't expect to receive different treatment anytime soon. [Please correct me if I'm wrong, since I often look at the disease from my wife's pre-menopausal perspective, where there are zero ILC studies].

- TCGA paper: In the US, ILC samples were collected from the TCGA and analyzed by a collection of different research facilities which revealed molecular differences between ILC vs. IDC. Despite the vast heterogeneity they were able to organize ILC into three subtypes, which some of you discussed in this thread.
The research resulted in this paper by Perou (2015) and this editorial by Gatza & Carey (2016):
Perou (2015): http://www.cell.com/cell/abstract/S0092-8674%2815%2901195-2
Gatza & Carey (2016): http://jco.ascopubs.org/content/early/2016/03/31/JCO.2015.66.3872.full

- Institut Jules Bordet paper: In Europe, a similar large ILC study was conducted which revealed the uniqueness of ILC.
That paper can be read here.
Desmedt (2016): http://jco.ascopubs.org/content/early/2016/02/24/JCO.2015.64.0334
All of these research papers will serve as a good resource for future studies / trials / drug development.

RATHER Project:
- The "RATHER" consortium in Europe may be a good source for ILC targeted therapies.
RATHER is multi-institution collaboration focused on these two areas: 1. ILC, 2. Triple Negative
Here is their January 2016 progress report. It essentially reveals that they finished Phase I of an ILC clinical trial and starting the Phase II "Poseidon" ILC clinical trial in Spring (now).
http://www.ratherproject.com/news.php#y5
- Poseidon Clinical Trial:
This Phase II trial involves a targeted therapy drug called a PI3K inhibitor (a Roche/Genentech drug also known as: Taselisib or GDC-0032). The research papers discussed above revealed that ~50% of ILC has PI3K pathway activation, so blocking this pathway, in theory, will inhibit the cancer.
I haven't been able to identify this Phase II trial on clinical trials.gov, but here is the Phase I trial webpage: https://clinicaltrials.gov/ct2/show/NCT02285179
"Trial to Evaluate the Safety and Effectiveness of GDC-0032 When Given Alongside Tamoxifen (Poseidon)"
Enrollment locations include: Netherlands (Amsterdam), Spain (Barcelona), UK (Cambridge), and France.
Interestingly, this PI3K inhibitor, Taselisib, is already being tested in 8 different clinical trials for metastatic breast cancer in the US.
Would anyone care to know which ones?

ILC Biomarker Clinical Trial: * For newly diagnosed patients, who have NOT had surgery yet.
- The University of Pittsburgh, the most visible (perhaps only US based) research facility with dedicated ILC researchers, launched the Lobular Biomarker clinical trial late last year. Enrollment is quite challenging due to the low volume of patients diagnosed with ILC and the potential geographical constraints.
Despite this, it's a critically important trial to help guide patients towards better therapies since no one really knows what is truly effective. About the only conclusion that has been made comes from the BIG 1-98 trial that told us AI's are generally better than Tamoxifen for postM patients.
Here's the Press release announcing the Pitt ILC trial: http://www.upmc.com/media/NewsReleases/2015/Pages/junkowitz-ilc-trial.aspx
and the trial enrollment details: https://clinicaltrials.gov/ct2/show/NCT02206984
* We need "newly diagnosed" patients for this, who have NOT had surgery yet. If you notice a new ILC patient, please consider telling them about this trial. Research progress is only made with clinical trial participation.

Modeling ILC in the Lab:
- A Netherlands based research Lab recently developed the first working ILC mouse model. This model allows researchers to study the interplay between loss of Ecadherin and PI3K activation and test various drug inhibitors against common ILC gene mutations and a bunch of other science that is beyond my understanding.
It's a bit shocking to think a model didn't exist before.

ImmunoOncology (IO).
As many are aware, some metastatic cancer patients are achieving complete remission with IO drugs and in most cases, without the side effects from conventional therapy. This is obviously a big deal. The idea of harnessing the immune system has always been a sound approach, but it's in the last few years that we've achieved broader clinical success. To be clear, most success stories are in blood, skin, lung cancers, etc. In terms of breast cancer, I know of one Stage IV patient who has been in remission using IO. She participated in a Phase IA trial of the Mammaglobin-A IO vaccine and been in remission for a couple years now. A larger Phase IB trial has now been launched, here.
Over 250+ IO clinical trials exist for breast cancer. While that is great, there is still much dogma among Oncologists who believe that breast cancer, especially ER+ disease, is not very immunogenic. For example, a common argument is that only the most mutant cancers are responding to Immunotherapy. Melanoma and lung cancer responses are good examples since they harbor a vast amount of mutations. Cancers with a lower mutational load aren't believed to respond as favorably. Since breast cancer, especially ER+ ILC, tends to have less mutations, many in Oncology are stuck in the dogma that they won't be as responsive. With today's existing Immunotherapy options, this may be partially true. But, as estrogen / immune system pathways are uncovered, mutational load won't be a defining criteria for response. Inevitably, "basic science" discoveries will lead to a new generation of Immunotherapies that will generate durable responses for breast cancer patients, including those with ILC.
To summarize, there's no theoretical reason why immunotherapy shouldn't be applicable to all tumor types. It's important that science pursues this approach.
The immune system has evolved to be exquisitely specific, and specificity is the holy grail of cancer therapy. Tumors are heterogeneous and ever evolving, so drugs that are designed to kill cancer cells directly by targeting cell-intrinsic pathways inherently select for resistant clones that can lead to relapse. In contrast, immune cells harnessed by IO are like a "living drug", and can generate a coordinated and adaptive anti-tumor response with capacity for memory, potency and specificity that is not achievable using any other therapeutic modality.
Now that IO has achieved success for some cancer types, the paradigm shift has begun and spawned a flurry of investment. Advances will be accelerated by these IO initiatives:
- The US Government's National Cancer Moonshot (PMI), which hopes to receive $1 billion by next year for 8 areas of cancer research including IO initiatives.
https://www.whitehouse.gov/the-press-office/2016/02/01/fact-sheet-investing-national-cancer-moonshot
- The Cancer MoonShot 2020 initiative - led by Oncology maverick and billionaire, Dr. Patrick Soon-Shiong
www.cancermoonshot2020.org
- John Hopkins University $125 Million IO research facility
http://hub.jhu.edu/2016/03/29/cancer-immunotherapy-center-bloomberg-kimmel
- Sean Parkers $250 Million - Parker Institute for Cancer Immunotherapy
http://www.bloomberg.com/news/articles/2016-04-13/sean-parker-gives-250-million-for-cancer-therapy-research

ILC patients might want to appreciate Sean Parker's involvement. Why? Because he was particularly close to the late Laura Ziskin, who succumbed to ILC after being diagnosed in 2004. Laura started Stand Up 2 Cancer (SU2C) in 2008 with Katie Couric and others. Just before Laura died in 2011, Sean is quoted as saying "I'm going to spend the rest of my life curing cancer. There are not going to be any more 'Lauras' in the world." The quote can be found in the May 2016 issue of Fortune magazine, as well as this link: "Can Sean Parker Hack Cancer?" The article discusses the last ditch efforts to get Laura into early stage Immunotherapy clinical trials at Fred Hutch Research Center in Seattle. (Fred Hutch has been in the news recently for generating amazing blood cancer remissions).
Rita Wilson (who was recently diagnosed with ILC) and husband Tom Hanks attended Parker's event that announced his ambitious IO initiative in April 2016.
The point is that perhaps Parker is partial Lobular disease, due to his close bond to Laura. Maybe, just maybe, a slice of the $250 Million could be siphoned off for Lobular IO. Probably wishful thinking but it is tempting to speculate the possibilities.

MBCproject: [www.mbcproject.org] * You can make a difference in ILC research progress!
This is aimed at metastatic ILC patients (hopefully some still visit this section of the forum).
As a minority, all stages of ILC disease suffer from numerous issues that prevent research advancement. Metastatic ILC patients can make a difference by participating in the Metastatic Breast Cancer (MBCproject). This Broad Institute / Dana-Farber research initiative works directly with patients to accelerate discoveries in metastatic breast cancer. There are a number of noteworthy goals of this amazing project. One is to analyze the DNA of patients' metastatic disease and compare against normal tissue to identify unique cancer targets. This precision medicine approach requires a large sampling size (statistical power). In other words, the power of "Big Data". Simply put, the more patients that participate, the more robust the data becomes. The large volume of data can reveal unique patterns emerging from the 'noise' and this information can be exploited with new therapies.
Again, ILC is a minority. Strength can be found in numbers. The more ILC patients that participate, the better the odds that discoveries are made from this "Big Data" analysis. Please consider getting involved!

Here's the MBCproject info:
MBCproject website: www.mbcproject.org
617-800-1622
info@mbcproject.org
Broad Institute of MIT and Harvard in Cambridge, Massachusetts

The Stage IV section of the forum has a good thread, here: "Metastatic Breast Cancer Project - Great research"

On social media recently, a metastatic ILC patient inquired about this project. I'll paraphrase the reply from the MBCproject lead researcher:
"This is Dr. Wagle from the #MBCproject. I spoke at the recent 'Living Beyond Breast Cancer' conference about lobular breast cancer. We are definitely interested in metastatic lobular breast cancer. We would be very pleased to have more patients with metastatic lobular breast cancer sign up for the study. Rest assured that as we get more and more patients with lobular breast cancer signing up and sharing their tissue, we will be investigating this important subtype along with others."
To me, this sounds like they haven't done much with ILC, perhaps due to lack of ILC participation.
Is this a visibility problem?
Are Stage IV ILC patients not aware?
What are the concerns from ILC patients that prevent them from participating in this project?

More to follow.

- John

Thank you! The more updates from you, the more hope for us!

This is great. Im asking my MO to attend. Sent her registration link

Thanks John!

The registration for this is starting today. https://upci.upmc.edu/wcrc/ilcSymposium/agenda.cfm

This is the registration page. Patients/advocates $50 for the entire event. No link to the registration form yet. https://upci.upmc.edu/wcrc/ilcSymposium/registration.cfm

I contacted Lindsay Surmacz about the lack of link for registration and she is getting back to me.

John,

Thanks for posting-saw your FB post as well. This paper was interesting. Still would like to see more discussion and studies of premenopausal patients and ILC. I thought the quote that was directed to the TEAM and BIG1-98 results was interesting-"the early switch strategy (in TEAM) might well have muzzled the treatment interactions seen in the BIG 1-98 trial." Do you interpret that to mean that up front tamoxifen and then switching to AI is worse than AI for 5 years

I have a friend who did well on Tamoxifen but progressed on Femara!! Go figure!

fizzdon52 - wondering about the shocking SE's from Femara you mentioned. I've only been on it for a few months but other than a bad day (which might have been attributable to the Zometa infusion I had just received), my SE's have been tolerable.

Did you take it previously and have bad SEs? If so, what were they and how long had you been on Femara before they started? (I want to be prepared).

Thanks!!

Sunnyone, Please remember that not everyone has side effects on the AI's. I was one of the unlucky ones that suffered side effects on them all. That said, I did take them for 3 1/2 years before I said enough. I know gals who had few to NO side effects. All the best to you. Karen

Sunnyone22, I've been on Femara for about a year and half, and I'm doing well with it. I had a Zometa infusion a month ago (insurance wouldn't approve Prolia without trying Zometa first), and that knocked me for a loop for a few days. "Flu-like symptoms" for sure! Last week I developed a floater in my eye which could be simply because I'm 51, but I'm going this morning to get it checked out. If it can be attributed to Zometa in any way, that will be the evidence I need to get insurance approval for Prolia.

Hi Sunnyone from memory my symptoms started a month or so after I started, they built up gradually. I do sometimes wonder if it was the combination of Letrozole and Zoladex injections. I remember stopping the injections but still having the symptoms so who knows! Good luck to you

Dear Sunnyone:  I never had side effects from the Arimidex/Anastrazole.  However, I was not in menopause or even perimenopause when I was dx with bc.  I had to have zoladex shots to suppress my ovaries so that I could take Anastrazole.  I did not want to take an extra drug so I had an oophorectomy after 3 zoladex shots so that I could stop taking zoladex.  I was medically induced into menopause on the same day that I started Anastrazole. 

What I can say is that I have gained weight and my sex drive has diminished.  (SUCKS!! Did I say, SUCKS!!)  I am not dry. Yay.  However, I don't know whether these symptoms are due to menopause, Anastrazole, or a combination of both.  Therefore, these may be symptoms of Anastrazole but I am not sure.  I never had bone or joint pain with Anastrazole. 

I have been taking Anastrazole for 1 year and 9 months.  I had osteopenia when I had my bone density scan when I started Anastrazole.  I will have my next scan in October.  I do not yet know whether I am losing bone density.  Otherwise, I am fine with Anastrazole.  It is my best safeguard against a recurrence so I take Anastrazole every morning. 

Good luck.

What are Zometa and Prolia used for?

Jess78-

Welcome! We're glad you've found us, and hope you find this community to be a source of support as continue your treatment. We're all here for you!

The Mods

Thank you for the welcome!

BlueKoala - another Qld! It's so interesting listening to other stories and finding similarities in our histories. So much we don't know it seems.

AC chemo hasn't made any change to my periods - other than becoming like clockwork but still heavy. Be interesting to see if the Paciltaxel forces the menopause.

Seems so unfair to read so many young women facing the same thing. I am thankful that I finished my family before going through this.

This is the study that made me beg for Prolia:

http://www.breastcancer.org/research-news/prolia-r...

My MO thinks Zometa is a reasonable alternative, but I haven't had a chance to talk with her about it directly. The floater I have is just another thing for the "getting older" list, but I will ask my MO when I see her 6/27 if there are any other reasons why we could appeal the insurance company's decision. Zometa can be hard on kidneys, so my lab work may give us some info we can use. I haven't had any issues with my gums that I can attribute to Zometa.

jess 78, welcome aboard! This site has been a tremendous help to me since I was diagnosed. What a paradox -- we all wish we didn't need this but are so grateful for it!

I am sending hugs, luck, health, and prayers to all of you.

I am a DES daughter.