BC genomic analysis reveals invasive lobular carcinoma subtypes

wallycat

http://www.sciencedaily.com/releases/2015/10/15100...

Lojo

I'm working on getting access to the full text of this, but this news summary is a little more detailed than the science daily one

https://www.genomeweb.com/cancer/molecular-study-l...

Lojo

Ok - just got the full text. It's exceedingly dense, and has a lot of gene-specific information in it.

I did find this public link, that might be of interest - an open dataset of lobular info http://cbio.mskcc.org/cancergenomics/tcga/brca_tcg...

My first impression is that they've identified genetic signatures of three specific ILC subtypes that could facilitate differential / targeted treatment. Also, that the proliferative and reactive subtypes have significantly different prognoses / disease specific survival.

From the results "Lastly, we determined that reactive-like ILC patients had a

significantly better disease-specific (DSS) (p = 0.038, HR: 0.47)

and overall survival (OS) (p = 0.023, HR: 0.50) compared to

proliferative ILC patients in the METABRIC dataset, which has

a median follow-up of 7.2 years (compared to the TCGA median

follow-up of less than 2 years), (Figure 5D). Consistent with

these results, patients with more proliferative lobular tumors

(i.e., greater than the median PAM50 proliferation signature

score) had worse DSS (p = 0.025, HR: 2.0) and a tendency

toward worse OS (p = 0.058, HR: 0.63) compared to patients

with a lower proliferation score (Figures S5N–S5O). No significant

differences in DSS or OS were identified between

the immune-related subgroup and either the proliferative or

reactive-like subgroup. These results are consistent with previous

studies reporting that the reactive stromal phenotype is

associated with a good prognosis in breast cancer while proliferation

is one of the strongest indicators of worse outcome in

luminal/ER+ breast cancers (Ciriello et al., 2013b)."

What I'm wondering and haven't been able to decipher yet is whether some of the genes examined in the Oncotype test will allow for classification of these ILC subtypes (and if it can be done retrospectively). I'll read it again when I have a chance to think more clearly, but I think this is one of the more important lobular papers to come out recently.

Lojo

I looked through the list of genes examined by the Oncotype test, and the only one that is also mentioned (I think) in the current paper is CD68, which is a proliferation marker and is more highly expressed in the proliferative type compared with the reactive type.

wallycat

Great info! At this point, a lot of this information is just facts we really can't do much with. I'm hopeful these sorts of research projects will help target specifics; to have a herceptin-like arsenal for lobular would be awesome.

JohnSmith

1. Thanks for starting this thread. Actually, this news is old news. Well, sorta... It was originally announced at the May 2014 TCGA Symposium, in this 15 video called: "Genomic Characterization of ILC"
It's presented by Michael Gatza, the same UNC researcher quoted in the sciencedaily.com article.
In the video, he describes the different "classes" of ILC. i.e. Reactive, high immune signaling, proliferation subtypes.

In addition, at last years 2014 SABCS, a couple large talks focused on the discovery of these subtypes, as shown in the video, here: "SABCS 2014 - Improved Understanding of Lobular Breast Cancer".

------------
2. I'm going to add info from the original media article, to make keywords and concepts "searchable" for other members of the forum interested in ILC research.
The following is from Cell.com, published in early Oct 2015.
"Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer"

Highlights
- ILC is a clinically and molecularly distinct disease
- ILCs show CDH1 and PTEN loss, AKT activation, and mutations in TBX3 and FOXA1
- Proliferation and immune-related gene expression signatures define 3 ILC subtypes
- Genetic features classify mixed tumors into lobular-like and ductal-like subgroups

Summary
ILC is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including:
- 127 ILC
- 490 IDC
- 88 mixed IDC/ILC.
Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched (i.e. over-expressed) features.
PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes.
Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity.
Conversely, GATA3 mutations and high expression characterized Luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC.
Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

End of Abstract.
------------

3. The following are quotes from the media article from sciencedaily.com, followed by my questions (in italics).
"Breast cancer genomic analysis reveals invasive lobular carcinoma subtypes"

"We revealed that ILCs are genetically distinct, and that there are biologically defined subgroups of the disease that could have important clinical implications," said the study's senior author Charles M. Perou, PhD, a UNC Lineberger member. "Lobular cancers are not a single homogeneous group, but may represent at least three different diseases that appear to differ in their microenvironmental features, and which also show differences in outcomes."

"We treat them similarly to their more common ductal counterparts, but in part because that is because we have a poor understanding of the biology underlying lobular carcinomas," Lisa Carey, MD, co-director of the UNC Breast Center, physician-in-chief of the N.C. Cancer Hospital, said. "Gaining insight into the molecular basis for ILC may allow us in the future to tailor treatments specifically for them."

Based on gene expression data, TCGA researchers identified three subtypes of the disease.
Patients with the (1) "reactive-like" subtype had significantly better overall survival compared with patients with the (2) "proliferative" subtype. And while the researchers did not find significant differences in survival for patients in the third (3) "immune-related" group, they did find that those patients had higher levels of immune system-related functions and high expression of a number of oncology drug targets.

To recap, those ILC subtypes are:
1. proliferative (worse prognosis of the three)
2. reactive-like
3. immune-related
Number 2 & 3 were defined by unique features of the microenvironment.
The reactive-like phenotype showed fibroblasts or other types of stromal cell infiltrates.
The immune-related phenotype expressed Immune cell infiltrates, which make them particularly attractive for Immunotherapy drugs.

Some questions:
In the "immune-related" group, the study said: "patients had higher levels of immune system-related functions"
- What does this mean exactly?
"and high expression of a number of oncology drug targets".
- What are the drugs that target these over-expressed genes and which clinical trials are using them?

"The researchers also found increased activity of a signaling pathway called the PI3K/AKT pathway in ILC. Based on the findings, the researchers believe that investigative drugs that target this pathway may be a particularly attractive for this breast cancer type."
- Again, what are the investigative drugs they are referring to and which clinical trials are using them?

"The study also reaffirmed a previous finding that loss of the function of a molecule called E-cadherin (Ecad) is the hallmark of ILC, and it uncovered new mutations in genes that regulate estrogen receptor signaling in these cancers."
"Estrogen receptor signaling is a driver of breast cancer growth for most breast tumors, including lobular cancers," Perou said. "We found that there are known regulators of estrogen receptor signaling that are mutated in these cancers. One of these looks to be mutated in lobular cancers, and that's a gene called FOXA1, and another is mutated in ductal cancers, and that's a gene called GATA3. This could eventually tell us something about the responsiveness of these cancers to hormone therapy."
- Could this be one explanation for why ILC responds less favorably to endocrine therapy than IDC? i.e. Tamoxifen?

Anyway, I imagine the first question anyone with ILC is asking is... what subtype am I?
There's no clinical diagnostic test to answer this question (yet). This requires additional validation studies.

BarredOwl

"The researchers also found increased activity of a signaling pathway called the PI3K/Akt pathway in ILC. Based on the findings, the researchers believe that investigative drugs that target this pathway may be a particularly attractive for this breast cancer type."
- Does anyone know which investigative drugs they are referring to?

Numerous agents are in development targeting the PI3K/AKT pathway, also referred to as the PI3K/AKT/mTOR pathway, for a variety of different cancer types (not just breast cancer). In other cancers, resistance to such targeted agents as single agents is sometimes observed, so they are also being used/investigated as part of combination therapies.

I don't know what particular agents these authors have in mind, but here is some information about the use of inhibitors that target this pathway in the breast cancer setting in general, including Everolimus (AFFINITOR), an oral mTOR inhibitor:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC410771...

Cut-and-paste this link:

http://www.ascopost.com/issues/november-1-2014/novel-agents-may-address-endocrine-therapy-resistance.aspx

BarredOwl

[Edited to make second link operable]

Lojo

This too

http://www.prnewswire.com/news-releases/pi3k-akt-signaling-pathway-in-cancer-drug-pipeline-update-2015-300104946.html

Tannyh

1. I acquired the entire article. I carefully compared gene mutations listed in article to FOUNDATION ONE MUTATION LIST. I THEN COMPARED MY SPECIFIC MUTATIONS TO THOSE IN THE THREE SUBTYPES. Of course I had CDH1, and a TP53 mutation but my others were not listed in the article. These include FGFR1, PIK3C2B equivocal, and a  ZNF703. Not sure where this leaves me in relation to the subtypes. I have Classic ILC, ER/PR+, HER-, with a Ki-67 below 10%, low mitotic rate, Eleston Grade ll. BLASTIC BONE METS. Not sure where this leaves me. I do not have a GAT MUTATION. I was not tested for FOXA  but  I do not have a FOXL2 or FOXP1 mutation. 
   

Kathy044

I would be satisfied just to learn what the difference in activity there might be between a reactive like and a proliferative tumour so will try to get access to the article. I notice that a cancer research centre in Vancouver is involved in the study - wonder if they included any samples from the tumour bank.

Kathy

JohnSmith

This was published on pubmed a couple days ago: "Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer".
This is the European portion (by the RATHER consortium) of ILC research that parallels the Oct 2015 TCGA ILC study, discussed above.

Abstract
ILC is the second most frequently occurring histological breast cancer subtype after IDC, accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC.
Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC.
We identified two main subtypes of ILCs:
(i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models;
(ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q.
Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.
PMID: 26729235

fizzdon52

That's awesome John but can you please translate into English (or American) for a dummy like me?

Lojo

I was just able to access the full text via that link above. It is one of the more statistically and gene dense papers I've read, but let me see if I can sum it up in simpler terms. They analyzed samples from ILC tumors, looking at gene expression for a variety of genes, and also looked at chromosomal abnormalities (the gain of 1q and 8q mean that the the long arms of the chromosomes have been duplicated in their entirety). They then did some fancy statistical sorting of the altered gene expression patterns in the tumor samples and came up with two types based on which sets of genes were altered. One set had genes broadly involved in immune response and another set had alterations that they termed "hormone" related. What they then did (that the other paper didn't, I think) was to categorize the subtypes according to survival at 10 yrs. Tumors that had "high mutation" had low survival at 10 yrs, compared to those with lower mutation. There's more detail -- one gene in particular seems to play an important role. I'm a little unclear on the relationship between their immune and hormone subtypes and the low/high mutation categories (which is what they tied survival with). They also evaluated the immune/hormone gene patterns and suggested that DNA damaging drugs might be more effective against the immune type and antihormonal drugs against hormone types.

 

JohnSmith-- can you cut through the distinction between the immune/hormone types and the survival curves for high mutation ?

Lojo

Full text http://www.nature.com/articles/srep18517

Lojo

From the end of the Discussion

"In addition to the two ILC subtypes that we characterized, we also found associations between molecular features of ILC and clinical outcome: based on the mutation rate and eIF4B level of the tumours, we were able to distinguish three subgroups with different prognosis. Together, these characterizations may help to guide the treatment of ILC through the identification of patients that may benefit from specific targeted, chemo- and/or immune-therapies. Broader genomic profiling will be important to understand the molecular factors contributing to the high mutation rate observed in some patients."

Upon reading this more closely, I think what they're saying is that they've been able to categorize ILC into two subtypes (immune and hormone) and that separately the mutation rate seems to be strongly correlated with outcome. Interestingly, they said the immune and hormone subtypes spanned typical luminal A and B groupings.

wallycat

I just read the Nature article and was thoroughly scared, never mind confused, again.

I'm nearing the 10 year mark and the areas where they say ILC goes to are hard to detect....

I get there are no tests routinely used, at the moment, to tell those of us with ILC as to which category we fall into. Sure is a crappy cancer, isn't it.

I was unable to determine if the Immune had a better outcome because of the chemo options that do affect it or just in general, better outcome --yet these were the her2+ and the er- types. I'm probably interpreting things incorrectly. This is great that there are some docs willing to focus on this at least.

Leslie13

I don't see that the research is explaining which subtypes have better and worse outcomes.

I am a research subject at a med school and have had extensive testing. I asked to receive a more extensive explanation of my Cancer's genetic profile after reading the article. I know they have it.

I'd like to know if I should be doing my bucket list more quickly.

Leslie13

I asked my Dr. to provide me with more complete genetic info since I'm a research subject at a medical school and I know they have more complete info than has been shared with me. I suspect I'm in one of the higher risk groups of ILC so make sure I'm working on my bucket list

JohnSmith

Thanks for the link Lojo.

High mutation rate and eIF4B level stratify patients into three distinct outcome groups:
1. High mutation rate - poor survival
2. eIF4B Low - good survival
3. eIF4B High - poor survival, unless treated with anti-hormonal therapy

On a different topic, I looked at the 39 page pdf file, under Supplementary information, found here:
www.nature.com/article-assets/npg/srep/2016/160105... (add the words .pdf to the end of this nature.com link to activate the url and download the file. The forum doesn't allow for .pdf links)
Within this pdf file is a particularly troubling illustration, posted below.
Look at Figure S22, called "Possible Treatment Effect", specifically Illustration B "With Hormonal treatment".
Within the decision tree, those with a "high mutation rate" did better without hormonal therapy. It appears hormone treatment accelerated disease progression. Am I interpreting this right?

Some research groups have pointed fingers at ESR1 mutations as the cause for hormone treatment failure, for example here. Is it possible that this ILC subset harbors ESR1 mutations (or other estrogen related mutated genes) and experience accelerated progression due to the use of hormone therapy? Is this some type of "evolutionary pressure" leading to greater heterogeneity? If I'm interpreting this correctly, this could have clinical ramifications on the use of anti-hormonals for this minority subset.
I understand this is research and needs to be validated, but are there clinical trials exploring alternatives to anti-hormonals, like Immunotherapy?
Aren't there drugs in trial to deal with the hormone related resistance issues like ESR1?
Have IDC researchers stratified subtypes and discovered similar issues and if so, can ILC researchers leverage that knowledge?

Or, am I getting wound up about an insignificant illustration and misguided interpretation?

Lojo

JohnSmith, I would say that it's in the supplement because it was deemed less critical to the overall study, and as for reassurance, it looks like the high mutation rate + hormonal treatment had a tiny sample size (5, if I'm reading it correctly), so in terms of a worse outcome for high mutation rate plus hormonal treatment, vs high mutation without hormonal treatment -- I don't think much can be concluded -- though it does seem to reinforce that high mutation rates=poor outcome.

JohnSmith

In terms of stratifying Overall Survival (OS), I believe this is accurate:
A. High mutation rate - poor survival
B. eIF4B Low - good survival
C. eIF4B High - poor survival, unless treated with anti-hormonal therapy
** What is eIF4B? Is it only significant in ILC or is it a marker in other cancers too?

Some other questions / thoughts...

1. At a high level, my biggest gripe is the lack of ILC specific therapies. Since clinical trials are the only way to change this, what trials exist (or are planned) that exploit (or could validate) the new TCGA and/or METABRIC data?
For example, there's been trials targeting the PI3K pathway (with mixed success), but what about trials that might target the other ILC mutations?
Also, what about Immunotherapy trials? I realize most, if not all, have zeroed in on TN and HER2+ (both rare in ILC), but is there any new data to suggest ILC patients might benefit from existing/planned Immunotherapy trials?

2. Also, is there any effort to compile a list that matches clinical trials to these new ILC mutations?
It would seem logical to have a such a resource, especially if it broke down (in layman's terms) why a trial matches a mutation, thus allowing overworked clinicians (who may not be advocating for their minority represented ILC patients) to tailor potential targeted treatment.

Lojo

I looked into eIF4b a bit, and at a basic level, it is a translation initiation factor critical for binding of mRNA to begin protein synthesis. The link below is dense, but it says that several other important pathways regulated by other genes of interest to BC and ILC in particular converge on eIF4b and connects it with growth factor regulation.

 

http://www.uniprot.org/citations/16763566

 

Tannyh

There are Immune therapy trials under way with MED I4736 which blocks PD-1. This is a programmed cell death protein. Check NIH CLINICAL TRIALS. Tremlimumab is drug involved in this study. I can't pry certain genetic and genomic info that I know a well-known research facility has on me! I agreed to this once upon a time, but the world of significant mutational treatment has changed since I signed that 3 years ago. Time to unblinded

JohnSmith

"Genomic Targets for Lobular Breast Cancer May Allow Individualized Treatment" [Desmedt et al]

Source: http://www.medscape.com/viewarticle/859610

Published March 1, 2016
[apparently, this data was presented at the 2014 SABCS. Why are they just releasing this now?]

Several genomic targets could allow individualized treatment of invasive lobular breast cancer (ILC), researchers say.

"The most surprising finding for us was the difference between lobular and ductal tumors regarding alterations affecting the estrogen receptor (ER) and its transcription factor complex," Dr. Christine Desmedt, from Institut Jules Bordet, Brussels, Belgium, told Reuters Health. "Another surprising feature was that some of the lobular histological subtypes were enriched for specific recurrent genomic alterations."

Women with ILC are typically treated as those with invasive ductal breast cancer (IDC), the most common type, because of the relative paucity of information dedicated to ILC.

Dr. Desmedt and colleagues assessed genomic alterations in 360 cancer-related genes in 630 women with primary ILC and correlated those alterations with clinical and pathologic features.

Nearly two-thirds of specimens (65%) had mutations in CDH1, and 50% of the tumors had mutations in at least one of the three key genes of the phosphatidylinositol 3-kinase (PI3K) pathway (PIK3CA, PTEN, and AKT1).
JS Note: This is a core reason why the ILC "POSEIDON" Clinical Trial was launched in Europe, discussed here.

HER2 was mutated in 5.1% of samples, and HER3 was mutated in 3.6%.
JS Note: This ties into Dr. Bidard's forum thread: "HER3, a new target in stage IV breast cancer (lobular subtype++)". He encourages Metastatic Lobular patients to get HER2 (ERBB2) and HER3 (ERBB3) gene mutation testing. Remember, this has nothing to do with HER2 expression (either HER2+ or HER2-), the biomarker everyone has tested during diagnosis or recurrence. This deals with the somatic mutation of the actual HER2 & HER3 gene.

The researchers also identified mutations in FOXA1 (9.0%), GATA3 (7.3%), and other transcriptional regulators as well as significant copy number gains in ESR1.
JS Note: This may tie into the forum thread: "Liquid biopsy detects ESR1 mutations that cause AI failure".

TP53 and HER2 mutations were more frequent in high-grade, highly proliferative tumors, whereas PIK3CA mutations were associated with low proliferative tumors.

Different genomic alterations prevailed in the various histologic subtypes of ILC, according to the February 29 online report in the Journal of Clinical Oncology, here.

"Our paper is the first to clearly point out, in a sufficiently large cohort of well-annotated primary invasive lobular cases, that the prevalence of HER2 and HER3 mutations is significantly higher than in primary IDC," Dr. Desmedt said. "Recent evidence points toward dual HER2/HER3 blockade (e.g., pertuzumab plus trastuzumab) as a possible means to inhibit cancer growth in the presence of HER3 mutations."

"Since AKT1-mutated tumors are more frequent in lobulars (4% and nearly absent in ductals) and are associated with short-term risk of relapse, and given the existence of drugs targeted (to) this alteration, lobular histology may actually be considered as an inclusion criterion for trials using agents targeting this alteration," she explained.

"Although the prognostic value of some of these variables has been demonstrated for the first time in this study (such as the association of HER2 and AKT1 mutations with increased risk of early relapse), we expect that these and others might also contribute to differential response to various treatments, especially endocrine treatments," Dr. Desmedt concluded. "Altogether, this means subtype-specificity should be addressed in the design of studies that will come in the future, and that we will need to focus on the mechanisms of endocrine sensitivity and resistance that may be specifically involved in lobular breast cancer (FOXA1 mutations, GATA3 mutations, ESR1 gains)."

"Given the higher prevalence of HER2, HER3, and AKT1 mutations in ILC than in IDC and the existence of drugs that target these alterations, we recommend the characterization of ILC tumors for these genes," the researchers conclude. "In addition, FOXA1 mutations and ESR1 gains urgently deserve dedicated clinical investigation, especially in the context of endocrine treatment."

The authors reported no funding.

SOURCE: http://bit.ly/1ndiYT4

J Clin Oncol 2016.

ShetlandPony

Thanks, JohnSmith. Every time you post something like this, I read it with my Foundation One report in hand.

Regarding E-cadherin--Loss of E-cadherin is supposed to be a hallmark of ILC. I finally got around to asking my onc why my pathology report from the 2014 biopsy shows ILC with high ER+PR+ and Her2-, but--get this--positive for E-cadherin. She said that shows the tumor was mixed lobular and ductal. But recently, somewhere here on the discussion boards (I can't find the thread), there was a link to the study below that showed 23% of the study sample ILC was positive for E-cadherin. Does anyone know anything about this subject? I wonder if the primary tumor was palpable for this reason? Positive for E-cadherin seemed to be a good prognostic factor for early-stage ILC in the study. Obviously not good enough for me, but still, maybe it is a small hopeful note? Interestingly, my Foundation One report does show a CDH1 mutation. I hope this is the right thread to bring this up. I figure y'all are more likely to know something about this.

http://onlinelibrary.wiley.com/doi/10.1111/his.125...

JohnSmith

Two news items today.

1. This short video just surfaced on the internet today.
"Dr. Charles Perou on Molecular Differences in Lobular Breast Cancer"
It's a recap of the TCGA Lobular subtype data released in Oct 2015.

As indicated earlier in this thread, those ILC subtypes are:
A. proliferative
B. reactive-like
C. immune-related
Phenotypes B & C were defined by unique features of the micro-environment.
The reactive-like phenotype showed fibroblasts or other types of stromal cell infiltrates.
The immune-related phenotype expressed Immune cell infiltrates, which make them particularly attractive for Immunotherapy drugs, discussed at a high level here.

2. He also mentioned FOXA1 gene mutations in ILC, which interestingly, made the news today in a separate announcement by the Mayo Clinic, who elucidated on the mechanics of the FOXA1 gene. That news release is here: FOXA1 found to control specificity of cancer cells

JohnSmith

Yesterday, we had a different research group publish news about the recent ILC studies that have been performed here in the US using TCGA data as well as in Europe using the METABRIC data.

The most recent news is called: "Another Breast Cancer Entity Confirmed: Genomics of Invasive Lobular Breast Cancer"

It's led by UNC researcher, Gatza, who reported early ILC research at the 2014 SABCS which is briefly discussed above, in this thread.

Also, Belgium-based Christine Desmedt and Christos Sotiriou summarized the European METABRIC ILC data last month here:
"Genomic Characterization of Primary Invasive Lobular Breast Cancer"

This latest news release, released yesterday in the JCO, has a nice summary in the final paragraph, which states:
"Desmedt et al,2 in concert with similar initiatives published within the past few months,3 have extensively characterized the genomic landscape of ILC and have produced remarkably consistent results that identify at least three significantly altered and therapeutically relevant pathways. These are an important first step to understanding ILC as well as the potential treatment implications of this unique biologic subset of breast cancer. It is now clear that ILC and IDC are distinct molecular diseases, a fact that should be considered in future experimental and therapeutic initiatives."

Great!

Who in the breast cancer industry has the leadership skills to organize and launch ILC clinical trials that exploit some of these ILC mutations?
This research, while wonderful, won't change guidelines in the clinic unless trials are launched.

JohnSmith

Just published. Lobular breast cancer Q&A via OncLive.com. It discusses the 3 "potential" subtypes of lobular breast cancer, which require more study.

http://www.onclive.com/web-exclusives/perou-shares-how-deeper-sequencing-of-genome-helps-define-treat-breast-cancer-subtypes

As a caretaker to an ILC patient, I appreciate that researchers are collaborating to conduct larger studies, but still, the ILC research community is still quite small and the pace of science is too slow for those that are already dealing with a metastatic situation.
More needs to be done.
- Does anyone have ideas on how to accelerate research progress for ILC?
- What can patients / caretakers do to help?

CCS648

This is a really interesting study.

http://onlinelibrary.wiley.com/doi/10.1111/1754-94...;jsessionid=A937730D3B0E40E58FF578CB746CCB18.f03t04

It essentially says that some lobular bone Mets may not show up on a Bonescan, even though they show on a CT.

funthing42

Thank you for posting this information. It is so overwhelming.

The research alone . My onc is finally trying to figure out why mine keeps coming back. X3 recurrence . I stopped my hx line after the skin mets. I was suppose to have a 4% chance it would come back after lthe 2009 umpectomy and some rads and hormonal therapy. So thank you .

Strange my Onc just now mentioned I had some slight lobular features. Not to mention now they finally know that Her2 is not so straight forward.

I really wish they would dig deep into the pathology reports and molecular dx of cancer as oppose to Ok well this should do the trick attitudes. It should be something a patient gets automatically prior to throwing chemical treatment at it.

momallthetime

WOW this is such a high caliber thread. I just perused through for now. I have been trying to get more info. I just looked over my daughter's pathology report, I have looked it over many times, but the more I learn then when I look at it again, I understand all I did not.

Anyway at the original DX she was: ER+PR15% Her2- (checked by 2 institutions), now I see it says with Solid tumor type with Lobular involvement, What does that mean? I know literally what it means, but what does it mean to Her. Also extensive nodule involvement. DCIS.

Fast forward, METS to the bones, in her mid 20's, last yr due to much aggressive progression, she did a rebiopsy, results: ER+ PR (<1) Her+ (fish +++), so everyone got excited but so far none of the promised wonderful therapies for Her2+ have been taking. She is now taking a mix of Her2+ and Her2- treatments, with a new look due to the understanding of Her2 being much more complex than just positive or negative.

But would someone here be able to explain to us if the Lobular involvement would have an effect in the treatment? Could the doctors be looking at it more closely and come up with a more targeted treatment? No doctor has mentioned the Lobular involvement, either they overlooked it or it does not matter?

TIA so much,