ILC - The Odd One Out?

My mother had  pre-menopausal BC, and I've always assumed that is where my genetic risk came from, but neither of her two sisters have had any problems and both have lived until their late 80s. She did have a first cousin on her father's side who had pre-menopausal BC, but that's it. Both of her parents lived until old age (for the time) and died of strokes.  But - my father died from lung cancer in his early 50s (which I've always chalked up to being a lifelong smoker), and his sister died in her early 60s from cancer - I'm not entirely sure what - stomach, but possibly metastatic BC, as she had some surgery in her early 40s (no one ever talked about anything, so I've never been sure what happened, and at this point everyone on that side of the family is gone). She went quickly - about 3 months between diagnosis and death. But she was also a life long heavy smoker. Both of my paternal grandparents lived until their 80s and had no cancer. So, I don't know what is going on - whether it's genetic, epigenetic, whether my father's and aunt's cancer was smoking specific, etc (but they're a lot of smokers who never develop lung cancer, so who knows).

Great thread MmeJ. I'm also a research sleuth and appreciate the ILC vs. IDC questions you have presented. The lack of targeted ILC therapy and poor understanding of the molecular characteristics is a concern.

My wife is a childhood survivor of cancer from the 1980's. 30 years later, at age 45, she was diagnosed with Stage 2A ILC. Like most others with ILC, she's ER+/PR+, HER2-. Lots of genetic tests were done (ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, NBN, PALB2, PMS2, PTEN, RAD51C, SLX4, STK11, TP53). Test results were all negative, except for a couple VUS's in the ATM gene, but considered benign.

When she was first diagnosed with ILC, I was concerned about, among other things, the Tamoxifen resistance issue in ILC vs. IDC. I emailed a top BC oncologist at a reputable research university. The response was: "lobular cancer is different in appearance and some markers, but it is still treated based on its biology, not based on being lobular vs ductal". I never bothered to question the response because I'm not armed with enough education. However it's clear I need to connect with Lobular researchers for a better response. Anyway, I thought I'd chime in here with her family history for cancer.

1. Paternal Grandfather: Died ~69 Pancreatic cancer
2. Paternal Grandmother: Died ~66; Mets. either Esophageal or Ovarian cancer [Inconclusive origin]
3. Maternal Grandmother: Age ~early 80s had Breast cancer (unclear what type, Lumpectomy performed), Died in 2012 at age 93 of natural causes
4. Paternal Grandmother Sibling 1: Age ~31 Had Uterine cancer, Died ~46 of Lung cancer [Heavy smoker though]
5. Paternal Grandmother Sibling 2: Died ~86; Mets. Pancreatic & Liver cancer. [Inconclusive origin]
6. Misc - Uncle & numerous cousins have had the following:
- Second cousin 1: Breast cancer (Died in 2013 at age 64; Dx in 2000 with IDC at age ~51, told it was aggressive & possibly triple negative. No one remembers specifics)
- Second Uncle 1: Rectal cancer; Dx ~12 years ago. Still alive.
- Second cousin 2: Leukemia; Just Dx in 2014, age 63, Still alive.
- Third cousin 1: Brain cancer at age ~23 (15 years ago). Still alive.

There are numerous other family members that lived cancer free. I don't put much stock into cancer diagnoses at later ages in life, since gene mutations "add up" the longer you live. It's people that get cancer at a young age which makes me wonder if a genetic predisposition for mutations might exist.
I shared this family history with the docs. They didn't seem to put much thought into the distant relatives and focused more on first degree connections (mom, dad, siblings). So far, Mom/Dad have not shown any signs of cancer and they are in late 60s/early 70s.

There is no cancer history on my dad's side of the family.  My mom had bladder cancer, but it's thought that was a result of smoking years ago.  A cousin was diagnosed last year with stage 1 IDC, but hers is a result of lots of radiation treatments for Hodgins years ago. So no family history of anything related to breast cancer.  Until my diagnosis... So I'm really the odd one out!

Hi bc101, I am always searching for information on Lobular Breast Cancer on the Internet. It's really interesting reading but hard to follow if you're not Einstein, especially the information about genes and genetic markers etc. However along the way you do learn things I guess. Sometimes the information is contradictory, some say ILC has better prognosis, some say ILC doesn't have better prognosis, some say it has better short term prognosis but worse long term prognoses? So I guess you have to take it all with a grain of salt. It seems they have known about Lobular Breast Cancer since the 1940's however because it's not as common as Ductal not as much research has been done on it. Cases of Lobular are increasing, some say it's due to Hormone Replacement Therapy so I think they are starting to do more research on it now. In New Zealand we don't get the chance to have the Onco testing or Genetic testing, so I try and find out as much about this as possible, because I want to know if my daughter is possibly going to get this dreaded disease. From what I have read some are starting to think Lobular is from the Paternal side, maybe I choose to believe this because it makes me feel better that my daughter won't take after me, I don't know?

Fizzdon (and those with moms with lung cancer) my speed reading over the last months since diagnosis gave me the same impressions of ilc. My dads side had the pancreatic and stomach lymphoma. My mom ,however, was a smoker and died within 5 months of small cell lung cancer....

@bc101
I wish this forum had the ability to reply using quoted text. I'll reply by putting your questions/comment in italics.

"how is it that your wife was tested for so many genetic markers? "
Well, I'm not sure where you live. We live near the Silicon Valley, so I imagine genomics testing is standard. Maybe not? We went to Stanford University, a great research / teaching school. During tumor board, we met with geneticists who suggested we do testing.
Perhaps the core reason for the genetic tests is her age of 45. Also, I mentioned earlier, she had a childhood cancer at 15, totally unrelated to her BC (at least that's the prevailing opinion). Two different cancers before the age of 45 probably warrants some genetic scrutiny.

"Did your wife donate blood to participate in cancer research studies? "
In terms of research studies, I don't think she did anything out of the ordinary. She participated in a Vitamin D trial before surgery, but don't think that has much relevance.

"Also, what kind of treatment has she undergone? "
After some back 'n forth on treatment options, she opted to simply do Tamoxifen until early December when the next round of results are revealed from the SOFT & TEXT clinical trial at the annual San Antonio Breast Cancer Symposium, www.sabcs.org (which I imagine is on everyone's radar). That will tell us if we need to pivot treatment and begin ovarian suppression and then do AIs, etc.

So in a nutshell, the BMX surgery took care of the tumor. The Tamoxifen should take care of any CTC's.
BMX = No radiation recommended.
Oncotype 11 = No chemo recommended.

Just a note for others reading and getting ready for treatment... a MX does NOT guarantee you won't need rads. I had very close margins after my MX and rads were recommended, despite no positive nodes and a low oncotype score.

For those that are interested, I reached out to the researchers who are looking at ways of devising new cancer classification systems based on their molecular structure which can lead to more appropriate treatments. I asked if Lobular carcinoma is different in molecular structure than Ductal carcinoma and if it warranted different treatment.
I received two replies, which were interesting, but couldn't answer the question. I'll only paste the relevant info. You'll notice that they seemed focused on basal like cancers.

Reply 1:
"Lobular cancers are nearly always luminal, not basal, so they are the 'garden-variety' breast cancers that all hang together and apart from the basals, which are the ones that are a lot like squamous cancers of the head/neck or lung. Lobulars are different from ductals, but not so different that they constitute an extremely different kind of cancer. Mostly they are missing sticky proteins called cadherins, which is part of why they form little lines and are kind of hard to find."

Reply 2:
"The recent TCGA study evaluating breast cancer in the context of other cancer types does not explicitly distinguish lobular and ductal carcinomas. But my understanding is that the lobular cases are co-clustered with other luminal ductal cases, and are molecularly very distinct from basal breast cancers.
TCGA breast group is currently working on addressing the exact question you posed, looking for differences between lobular and ductal cases that appears otherwise molecularly similar (i.e. of the luminal subtype)."

I'll continue to seek for researchers to answer some of the questions brought up in this thread. I'm not sure where the OP (MmeJ) went, but she brought up some interesting thoughts.
I may poke around the University of Pittsburgh and email the Lobular "experts". Most should remember it was them who were responsible for the 2013 research discussing the ILC / Tamoxifen resistance issue. Link: ILC cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response.

Great info, John.  Your posts are very much appreciated. 

MsP

thanks for the research, John. I would say that the second study, which looks interesting, would exclude many of us here because it seems the majority were premenopausal at the time of Dx. 

This was interesting reading. I am 10 years postmenopausal yet my MO at Dana Farber has just put me on 2 years tamoxifen followed by 3 on AI to minimize effect on bones and also hair loss as I have very thin hair. Prior to consult I was sure I would just be put on AI. - postmenopausal/ILC. I am thinking it may in part be due to my low oncotype dx score but of course I forgot to ask....

bc101, for sure call your doctor or genetic counselor. The panels on the market now go far beyond the basic BRCA 1/2 and cost way less since the Supreme Court invalidated the Myriad company patents last year making insurance coverage not as much of a problem. 

My clinic told me that there are tons of people they would like to contact and offer follow-up testing to but they can't due to ethical and legal constraints. The more of us who contribute to the data base of knowledge, the better!

I was 38 when I was Dx with stage 4 70 % mets to bone. 

Sorry all- I didn't realize when I deleted my entry above it wouldn't delete the whole thing! After reading through much more of this thread, I wanted to change my post and share information that is more similar to what many of you have shared. This entire thread is really interesting...

I was dx at 36 with ILC stage IIA. I had BMX and reconstruction (fyi my "healthy" breast had tons of "pre-cancerous" spots). Oncotype score was 19. Dr prescribed 5yrs Tamoxifen, but I only took it 3 ½ yrs bc of severe side effects. 

This past June (6 ½ yrs later), I was dx at age 43 with a recurrence in 3 nodes under my arm, 6 nodes up into my chest wall and a tiny tumor that managed to find a bit of remaining breast tissue next to my implant. It's a rare and lucky presentation that's technically considered stage IV but is curable (HUGE blessing the cancer found that breast tissue and not another organ...), so my dr tells me "it's more like stage IIIb or c." Treatment began July 19th with 12 weekly doses of Taxol. Then I'll have 4 doses of FAC over 12 weeks, a Level 2-3 Axillary Dissection, 33 rounds of radiation (and possible implant removal before and replacement after) and either ovary removal or shots to guarantee early menopause.  

My history prior to ILC: 5'8", 126lbs, very inconsistent with exercise, probably drank more than the average but not extreme (typically red wine or vodka), had headaches daily from age 12-32 that stopped when thyroid was removed due to cancer- papillary carcinoma (leading me to believe I had an undiagnosed thyroid issue most of my life). Cumulative birth control over my life 10-15 years. Endometriosis throughout my 20s with 3-4 surgeries and 6 mos of Lupron. Despite this, I got pregnant easily, had one child at 29 and another at 31, then after my thyroid issues was unable to get pregnant ever again (have no idea if they're related). I also have a tilted/reversed uterus (my mom's dr prescribed something to help her get pregnant, but says she's almost sure it wasn't DES). Other than that, I was dx at 38 with ADD and have been super-sensitive to most meds since I was a child (neither of which probably have any importance, but thought I'd mention everything).

Family History: My mother and my maternal grandmother's 4 sisters were dx with IDC pre-menopause. My maternal grandmother was dx with IDC at age 88. My maternal grandfather was dx with prostate cancer at 87. The daughter of one of the aunts mentioned above was dx with ovarian cancer at age 40. Even beyond that, the incidence of cancer on my maternal grandmother's side of the family is extremely high (esophageal, colon, possibly brain, etc). I've tested negative for BRCA1, BRCA2, PTEN and everything on the BreastNext test, though my doctors continue to tell me there's no doubt my cancer is genetic. They also say the fact I'm the only one with ILC in my family doesn't make any difference (something about them being so similar biologically); their thought is I just "happened" to end up with ILC instead of the more common IDC.

Endometriosis, tilted uterus, underactive thyroid, huge stress, family problems and loss, serious money worries