HELP!!! Misdiagnosed: NOT HER+ but "Basal-Like" BC
 

I want to make others aware of my story & need for accurate DX & 2nd. opinions on path. I was dx over 2 yrs ago with Her2+ BC. IDC & DCIS GR3,
T1CNO. ER6/PR-, ki67-94, MBR-9/9, DCIS-comedo. Very aggressive BC. Had
lump, ACT/DD, T/DD, 36rads/boost, 52 wks Herceptin. Dev. cardiomyopathy
EF started at 65 prior to Herc. & to 41 during it. Never stopped it. Herc. ended in Feb. EF now only at 49. Docs. say o.k.? Was on Arimadex switched to Femara d/t (bad joint stiffness hands/feet, etc.) Since only borderline ER+ had orig. path retested to see if I could stop AI if ER was -. Path now tested on Surg. exc. tumor was ER-/HER+. Then told that core biopsy specimen more accurate! It came back ER 1-5 on C/biopsy & HER2 FISH 1.1 neg. In the same week I also read that both Adriamycin & Taxol were probably ineffective for me d/t ER+ as well as the Herceptin since I was orig. dx as HER+. The lab it was now tested at is tops in BC & Dr. Allen Gown who did tests is world renown pathologist. They use more accurate tests on FISH with a rabbit antibody instead of mouse & count more cells on slide to determine results. (Lab: Phenopath - Seattle, Washington)

At this point, being completely crazy from info. overload & fear, I asked Dr. Gown if there were any other tests that would be beneficial for me to be performed. Thus, he did: p53, p63, EGFR, c-kit gene 145kd, & cytokeratins
5 & 6. Results were + on each one for a new BC variant called "basal-like".
This newly defined group comprises approx. 15% of BCs. It usually consists
of triple - (ER-/PR-/Her2-), younger women, & most often African Americans, & BRCA 1+. However, I was 51 at dx, caucasian, BRCA-, & ER low+(1-5). So I fit into about less than 3% of this group & all BCs. It is worse than HER+BC d/t huge risk of relapse, poor survival outcome, & no
targets known at this time for treatment. Also, so new, most docs don't even
know what it is or what to do about it. Can't qualify for clin. trials d/t all the
tx. I have already had. Currently NED but watching some spots lung/liver.

I was told by path. that many labs are now doing 2 FISH tests for more
accurate results if unsure or HER at 2+ (equivocal). Please be sure to
have any path. retested at top labs who specialize in BC if in doubt or for
2nd. opinions. I feel that I went thru all of this for the last few yrs. & am now at square 1 all over. However, this time there is no wonderful support
group like this site for me and I'm having to do research to figure out who
the top MD's are with exp. in this type of BC. Unfortunately, I live in Vegas
& the care is horrible here with no major teaching/research facilities. I have
gone back on Femara for lack of anything else other than faith/luck/prayers.
I hope my story may be helpful to others & if anyone knows about what I have or has suggestions/recommendations/etc., I would love to hear from you. This site helped me greatly, was a lifeline to me, all this time thinking I was HER2+. Everyone is incredibly knowledgeable, helpful, willing to share, and concerned about each other. Kudos & thanks to Joe and his wife for providing this site for all of us! I have some research articles I can e-mail
on Core BX vs Surg. Excised Tumors & on testing for Basal-like BC. You can
"Google" Basal-like BC too. Let me know if I can help anyone with the info.
I am learning & acquiring. I am a retired RN

Dear Shelli,
am pressed for time right now...wanted let you know that basal cell BC can be associated with carrying a BRCA mutation....

http://cat.inist.fr/?aModele=afficheN&cpsidt=16820759

Did Myriad do your bRCA testing? When did they do it?
Marcia

Dear Shelli,
Unfortunately everything I was able to find confirms what you already have been told. It sounds as though you have been dealing with top notch pathologists.
There are phase2 clinical trials going on right now for those who are BRCA+ and progressed on their last chemo regimen. The drug is called a PARP inhibitor (Poly (ADP-ribose) polymerase (PARP) , I am wondering if they would consider letting you into the trial based on your tumors characteristics ...
here is a little more on PARP

http://www.inotekcorp.com/content/parp.asp

Will let you know if I find out anything more. Perhaps one of our resident brilliant researchers will have more to contribute!
Hugs,marcia

Shelli, try contacting Lani or Becky. They has drug combo ideas for my triple neg friend. Best wishes, Bev

I was under the impression that basal bc is triple negative bc. I didn't think it was a rare kind of bc at all. Maybe I am wrong.

Karen

Basal BC is not a newly daignosed type
 

It is a molecular subtype --one of the four/five described by Charles Perou et al. Various other researchers have bickered about whether some her2+s fall within the basal phenotype, whether there should be just 3 or 4 or 5 or 6 subtypes, where her2+ER+s fit in etc. Excellent papers have been written by Charles Perous as well as Laszlo Pusztai, whom I have heard speak at at least 3 and 6 conferences, respectively.

I looked up your Phenopath and it is a private company not owned by Wall Street, but still owned by Doctor's (for profit). This is the first time I have heard of them (doesn't mean much), however you may want to seek out the publications of a woman who has a similar company but works extensively with MDAnderson researchers and clinicians and has published (jointly with them) many important articles on her2+ breast cancer including those looking for IHC markers of response to tykerb, etc. Her name is Sarah Bacus and her company is Targeted Molecular Diagnostics.

I am not recommending them (although RobinP did, which is how I learned about their services) as I am not in a position to, but remember that RobinP, also a nurse, was able to talk to them and decide which IHC tests would be most helpful in deciding whether to take late herceptin (PTEN was one, as if she was PTEN negative, there would probably be herceptin resisitance de novo) They, reasonably, prefer to test you for things for which there are established treatments available (hence c-kit which is quite rare in breast cancer). I can only hope they will see your dilemna as you do and help out your oncologist despite the fact that you have already received treatment and are currently NED (thank goodness)

These for profit organizations normally do their work for clinical trial projects and other researchers as I understand it. Because they are for profit and interface with the public, they offer tests not usually available at university/cancer center pathology departments.

I once helped a friend in Denmark send his wife's speciment slides to MD Anderson for a second pathologic opinion. I learned the address and phone number from the website (this was 3.5 years ago) She had triple negative bc and they did report out her EGFR IHC RESULT. I have no idea what they are offering now, but your oncologist could look into it I suppose.

I went to a recent lecture at Stanford on the topic as well as the three day AACR meeting on advances in breast cancer research in October as well as (trying to keep up on) my reading of the literature (I read on many other things as well!)

I would ask your onc if he would agree to a a serum her2ECD as many papers have shown her2- tumors metastasizing as her2+ making herceptin theoretically helpful in a subgroup of those who are her2- (her2ECD IS PRESENT EVEN IN THOSE WHO ARE NOT METASTATIC, but shouldn't be positive in any but the tiniest amounts if you are her2-, according to my reading). Several papers by Allan Lipton and Walter Carney among others discuss this.

I will also try to check with Dr. Deng, whose company offers a different technology for checking for circulating tumor cells and characterizing them by IHC to see if they have anything to offer, but again, this is a company aiming to be for profit.

If you oncologist could be in touch with Laszlo Pusztai at MDAnderson(who has developed a method to use multigene arrays to predict chemo and antihormonal responsiveness as well as prognosis--not yet commercially available or FDA approved) or someone in the pathology department there (try to google phone number for MDAnderson second pathologic opinions) tell him the dilemna and ask, who in the pathology department might inform you of your options for further testing

According to the two latest conferences I have attended there are several new and much more effective treatments for triple negative bc (including carboplatin and PARP inhibitors).
Hope this has helped!

Shelli couldn't you consult at
 

any one of the two designated cancer centers in the LA area (UCLA, City of Hope) or two in the SF Bay area (UCSF, Stanford)? THEY ARE not so far away and there is a service called Angel Flight (Name?) which flies cancer patients for free for treatments (I suppose that includes consults)

PARP info
 

Hi Shelli,
I do know of 4 women on the PARP trial through Cedars-Sinai in LA. One of them posts here, under "Swanky". Three of them on PARP are all having very POSITIVE results. (tumor reduction in only 4 weeks, ned in 8 weeks, etc). If you send a message to Lea "swanky" she can tell you the name of her oncologist. Thank you for sharing your story. --Flori

fyi
 

ABSTRACT: Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas [Breast Cancer Research]
Introduction: Breast cancer is a heterogeneous group of tumors and can be subdivided on the basis of histopathological features, genetic alterations and gene-expression profiles. One well-defined subtype of breast cancer is characterized by lack of HER2 gene amplification and estrogen- and progesterone receptor expression ("triple negative tumors"). We examined the histopathological and gene expression profile of triple negative tumors to define subgroups with specific characteristics, including risk of developing distant metastases.
Methods: 97 triple negative tumors were selected from the fresh-frozen tissue bank of the Netherlands Cancer Institute and gene expression profiles were generated using 35K oligonucleotide microarrays. In addition, histopathological and immunohistochemical characterization was performed and the findings were associated to clinical features.
Results: All triple negative tumors were classified as basal-like tumors based on their overall gene expression profile. Hierarchical cluster analysis revealed five distinct subgroups of triple negative breast cancers. Multivariable analysis showed that a large amount of lymphocytic infiltrate (hazard rate (HR) = 0.30, 95% confidence interval (CI) 0.09-0.96) and absence of central fibrosis in the tumors (HR= 0.14, 95% CI 0.03-0.62) were associated with distant metastasis-free survival.
Conclusions: Triple negative tumors are synonymous with basal-like tumors and can be identified by immunohistochemistry. Based on gene-expression profiling, basal-like tumors are still heterogeneous and can be subdivided in at least five distinct subgroups. The development of distant metastasis in basal-like tumors is associated with presence of central fibrosis and a small amount of lymphocytic infiltrate.

Thank you everyone who have replied to my post!
 

I really appreciate all of your helpful information and am digesting it all and
will respond back shortly. My life has been crazy lately! Had out-of-town company visiting, then went to Democratic Debate by CNN in Vegas per invite of Hillary Clinton. Was recently on stage with Hillary at a health care forum she had here. I am very involved in health care reform, an advocate & activist just trying to "fight the fight" and make a difference for all! Unfortunately, despite the pleasurable time, it has been a really bad week for me, as my lil dog "Kabuki", a black/white Shih Tzu of 15 wonderful years (never got married or had kids, she was my little girl) has peacefully gone to doggy heaven. I am still traumatized and trying to adapt. Hope everyone has a very healthy & happy Thanksgiving! Thanks again for your wonderful information and help.