NEWS OF SAN ANTONIO SYMPOSIUM!!!!!!

matic22 · December 2007

Hi ladies!

Just leting you know that 70-gene signature predicts outcome in breast cancdr patients with 1-3 positive nodes so you can cancel chemo if you are low risk patient.Look at the article;)=kind regards!I hope you are all doing well!

The link:

http://www.abstracts2view.com/sabcs/view.php?nu=SABCS07L_630

And if you can not open it, I also put down the article;:

[1064] The Amsterdam 70-gene signature predicts outcome in breast cancer patients with 1-3 positive axillary lymph nodes.

Mook S, Rutgers EJT, Peterse JL, Nuyten DSA, Horlings H, van de Vijver MJ, van 't Veer LJ. Netherlands Cancer Institute, Amsterdam, Netherlands

Introduction
The axillary lymph node status is considered to be the most powerful prognostic factor for operable breast cancer, with a direct relationship between number of positive nodes and disease outcome. However, approximately 30% of lymph node-positive patients will remain free of distant metastases without adjuvant chemotherapy. Identifying patients with lymph node-positive disease who are at low risk of recurrence might lead to changes in guidelines for adjuvant chemotherapy. The aim of this study was to identify a low risk group with an excellent disease outcome in breast cancer patients with 1-3 positive lymph nodes, using the 70-gene signature (MammaPrint).
Methods
One-hundred-six patients with 1-3 positive lymph nodes were separately selected from the previous described series of 295 patients (Van de Vijver et al. NEJM 2002). Patients were diagnosed between 1984 and 1995 at the Netherlands Cancer Institute, and under the age of 53 at diagnosis. Tumors were primary invasive breast carcinomas less than 5 cm, treated by modified radical mastectomy or breast-conserving therapy, including dissection of the axillary lymph nodes. Eighty-two percent received adjuvant systemic treatment, consisting of chemotherapy (59,4%), hormonal therapy (12,3%) or a combination (10,4%). Gene expression signatures had been obtained previously; clinical follow-up data were updated.
Results
Of the 106 patients 18 developed distant metastasis, and 88 were free of disease at a median follow-up of 10.3 years. The median time to distant metastasis was 2.8 years. Using the 70-gene signature 43 patients were classified as having a good-prognosis signature, while 63 patients were classified as having a poor-prognosis signature. At 10 years, the probability of remaining free of distant metastases and overall survival was 94% (SE 4%) and 97% (SE 3%) in patients with a good-prognosis signature versus 66% (SE 7%) and 62% (SE 7%) in those with a poor-prognosis signature, respectively. The estimated hazard ratio (HR) for overall survival in the poor-prognosis signature group as compared with the good-prognosis signature group was 7.0 (95% CI 2.1-23.3). When adjusted for clinicopathological prognostic factors, the 70-gene signature was the strongest predictor with an estimated HR for overall survival of 4.2 (95% CI 1.0-17.7). Other independent prognostic factors were angioinvasion and adjuvant systemic therapy with hazard ratios of 2.7 (95% CI 1.1-6.7) and 0.3 (95% CI 0.1-0.8) respectively.
Conclusion
Our results show that the 70-gene signature outperforms other prognostic factors in selecting a low risk group that has a 10-year survival of > 90%. After validation in an independent sample series the prognostic value of the 70-gene signature in patients with 1-3 positive nodes will be prospectively validated in the MINDACT trial. Incorporation of the 70-gene signature in clinical decision-making for patients with 1-3 positive nodes may lead to reconsider the need of adjuvant chemotherapy.

wallycat · December 2007

Matic,

can you elaborate on this test? 70-gene test...I assume this is similar to the oncotypeDX, but that one only uses 21 genes.

Very interesting....

I'm curious what the TailorX will show and whether that will move the cut off higher or lower for the mid-range group.

As always, thank you for sharing!!

nash · December 2007

Wallycat, until Matic checks back in, I thought I'd chime in that my onc said the 70-gene test is called Mammoprint. You're right--it's the same concept as Oncotype, but with more genes.

JoelKM · December 2007

What's significant about this study is that we may be able to identify node positive BC patients who could avoid chemotherapy altogether. At this point, all node positive patients receive chemotherapy. Both Mammoprint and Oncotype DX track one another very closely. So in theory, both tools can be used with equal effectivness. This is very exciting news indeed.

nagem · December 2007

But it seems to be an option for hormone positive folks only? I'm a weirdo with lobular hormone-negative her2neu-positive cancer. I assume it has no relevance for someone like me?

nash · December 2007

nagem, I know Oncotype is just for hormone positive, so I would assume the same is true of Mammoprint. The way my onc explained it, Oncotype measures how sensitive the tumor is to hormone therapy, and that's how they come up with the risk of recurrence and benefit of chemo.

CherylRubie · December 2007

I'm pretty sure that Mammaprint requires fresh tissue, i.e., test must be done at the time of surgery. So unless it is routinely offered, most recently diagnosed women would not know to ask for it. My onc didn't even offer me Oncotype. When I asked her about it, she told me that she was sure I would be low risk, so that's why she didn't mention it (I was low risk, but not as low as she thought, I was 12). Oncotype, on the other hand, can be used with frozen tissue of the type that must be preserved for ten years for everybody who has had breast cancer. Also, I believe that, although the genes measured are for the most part quite different, Oncotype and Mammaprint correlate fairly well with one another. There are a couple of other gene tests out there as well, but I can't remember their names. Here, we will not have results of TailorX for some time; I think they may even still be recruiting for it.

By the way, you can get some of the info from SABCS through webstreaming; at least you could last year. Also, I paid $25 and got a copy of all of last year's abstracts; I'm betting it will be available for this year as well.

Cheryl

matic22 · December 2007

Hi ladies!

Yes,this is called Mammaprint.You are right:)

I would really like to do one of this test for my Mum"s tumour so if you have any ideas or experience with it, just let me know, will you:=)?She had 2 positive nodes, microscopic deposits, however I do believe that long term prognosis has nothing to do with limited nodes positive, but IT DEPENDS ON the genes of the tumour that show us biology of every single tumour.So, that is the reason I would do the test for my mum to know what are the scores and if there are high, to do more hormonal therapy beyond 5 years of adjuvant hormonal therapy.I would pay it, there is no problem because I can see here in our country doctors usually ask me,what about money.I mean-what about it?I will be the one I will pay for that test, not them, is not it correct;:)?

Dear nagem!

Yes, oncotype DX is only for ER+ patients, but I think amsterdam 70-genes signature is for ER- as well.I just think so, I am not sure.

As far as I have done a research on this oncotype(we also can see some results of some women who post their posts here in this forum) that even if the cancer is stage I and node negative, usually those grade III, will have high scores,that is the reason I am interested in intermediate lobular classical carcinoma-what scores will it have?

Kind regards ladies and hope you are doing well.

Extra hi to SherriG,LauraGTO, and Elizabeth.I think of you many times and my Mum also say hello to you:)

Matic

Elizabeth06 · December 2007

Matic,

With time constraints, I'm not able to check info on bc.org as much as before, but whenever I can it's always such a pleasure to read your posts!

I'm glad your Mom is doing well and I wanted to include a link from the recent San Antonio Breast Cancer Symposium which ran from Dec. 13^th to Dec. 17^th of this year regarding the Oncotype DX test for node positive.

I've had the same thoughts as you in regards to your Mom, since I've already under gone chemo, what would be the purpose of the test......however I would still like to know what my actual "recurrence" score really was. If I took chemo needlessly in the past, well nothing can change that, what's done is done. But curiosity has the best of me and I still would like to know more about the fate of my diagnosis acccording to the Oncotype guidelines.

There is much research on the molecular types of BC, and I'll forward the current info on the Luminal-A/Normal-Like categories that most "classical" ILC's seem to fall into.

http://www.abstracts2view.com/sabcs/view.php?nu=SABCS07L_630

(edited this post so the link would appear)

matic22 · December 2007

Dear Elizabeth06!

I am also so happy when I see your post;)I am glad you are doing well.If I am not wrong, you are now almost 5 years after diagnosis of ILC, arent you?That is so great. Are you still on Arimidex?Keep staying on AI, for more 2 years, if you do not have any SES because hormonal therapy is one of best for ER+++ ILC.I would like to ask you about some woman. You said once to me you have a friend who also had some micrometastatic deposits in lymph nodes and did the oncotype DX ??I do not remember the scores you told me but I remember that her tumour size was 3,5 cm and the scores were low.Do you maybe know how low and I know it was also classical ILC , do you maybe also know grade of the tumour?I would be so grateful to you to let me know these scores.

What I am thinking about is that most of women with classical ILC that do not have many positive nodes and highly ER and PR receptors, do not need anthracyclines but better drugs for them would be taxanes, for example regimen Taxotere ,Cytoxan(TC).

I wonder that because my mum also got Epidoxorubicin, which is an anthracycline.

Very kind regards to you, dear Elizabeth06:=)

Matic

minuet · December 2007

Here is some info on the oncotype scores for different histologies.

[3028] Gene expression by standardized quantitative RT-PCR in the special histologic subtypes of estrogen receptor positive invasive breast cancer.

Baehner FL, Watson D, Ballard JT, Palmer G, Shak S. Genomic Health, Inc., Redwood City, CA

Background: Most invasive breast cancers are characterized histologically as ductal, lobular, or mixed. We report here the gene expression profiles obtained by the 21 gene Oncotype DX assay in these cancers and in the special histologic subtypes.
Material and Methods: 25,475 tumors tested in the Genomic Health laboratory from July 2005 through April 2007 were ER positive by RT-PCR (ER 6.5 units). Academic surgical pathologists reviewed specimens for invasive carcinoma and histologic subtyping using World Health Organization criteria (IARC 2003). Quantitative expression of 16 cancer-related genes was measured using RT-PCR by Oncotype DX on a scale from 0 to 15 (relative to 5 reference genes), where a one unit increment is associated with a 2-fold change in expression. Recurrence Score (RS) was calculated using the published equation. The proliferation index (PI), a component of the RS, was calculated as the average of the expression of the five proliferation genes (CCNB1, Ki-67, MYBL2, STK15, and Survivin). Descriptive statistics for the RS, gene groups, the individual genes among the different subtypes were obtained.
Results: The vast majority of the cancers (94.5%) were ductal, lobular, or mixed. RSs, quantitative ER, and quantitative proliferation for each subtype are shown in the table below. For all subtypes including the rarer ones, a wide range of RSs was observed, and included all three RS risk categories. The RS, on average, was lower for the classic lobular, solid/alveolar lobular, mixed ductal/lobular, tubular, cribriform, mucinous, and papillary subtypes and was higher for the and medullary-like subtype. Medullary-like tumors (4 of 1000 cases) generally had lower ER and higher proliferation gene expression, which may make them more responsive to chemotherapy. Tubular cancers (9 of 1000 cases) rarely had high RSs, related in part to lower proliferation gene expression. The lower average ER expression for tubular cancers in this cohort may reflect submission of selected cases and not typical high ER cases for RS testing. The proportion of cases with RS<18, RS 18 30, and RS 31 and group gene expression values will also be presented.
Discussion: There is considerable variation in gene expression, as quantified by the Oncotype DX assay, both within and between the special subtypes of invasive breast cancer in this large observational cohort of estrogen receptor positive tumors.


Subtype	% of cases	RS (median)	RS (min)	RS (max)	Quantitative ER (median)	Proliferation Index (median)
Ductal	79.9	18.2	0	91	9.7	5.3
Lobular, classic	9.3	17.5*	0	65	9.5*	5.0*
Lobular, solid/alveolar	1.4	16.1*	0	62	10.5*	5.7*
Lobular, pleomorphic	0.7	18.9	1	71	9.6	5.3
Mixed	3.3	17.4*	0	80	9.7	5.2*
Tubular	0.9	15.2*	3	32	9.2*	4.3*
Cribriform	0.4	13.7*	0	54	10.1*	5.1*
Mucinous	3.2	16.6*	0	73	10.1*	5.2*
Micropapillary	0.4	20.0	0	74	10.1	5.8*
Medullary-like	0.4	33.1*	9	85	9.1*	6.5*
Papillary	0.2	7.8*	0	58	11.4*	5.7*

*Significantly different compared to ductal (p<0.05)

Friday, December 14, 2007 5:00 PM

minuet · December 2007

Sorry this didn't work and I'm too computer illiterate to set up a link. The median score for lobular is 17.4 and ranged from 0-65

classic ILC in this study. Matic I'm interested in how oncotype scores correlate to

other prognostic indicator such as ER, and PR status and grade in particular mitotic count. I e-mailed the company that does the testing but they had no data they could share with me. Just told me it is validated for ILC. My score was 15 with a grade 2 and mitosis scored 1. I don't know if I'm classic or not as my pathology report did not indicate this. Your comments of the different chemo is of interest. Why do you think taxanes or cytotoxin are of benefit to ILC? I had FEC...any comments. MO

matic22 · December 2007

Dear minuet!

It is okej and very welcome of you to post these findings.I am very happy for that. I am very glad your onco scores are low , so you are in a low risk group for metastases and I am sure you will be fine because you also had chemo and low scores, so both great points.I would ask you :did you have any node positive?I mean why was chemo recommended to you?What was the size of your lobular tumour? Well..I believe that oncotype scores correlate with all biological prognostic factors such as quantitative scores of ER,PR,HER-2, vascular invasion, cyclines,mitoses,and so on.BUT IT HAS NOTHING TO DO WITH STAGE ,I MEAN SIZE OF THE TUMOUR,. Because in the genes of every single tumour there is everything put down...every information...like in our genes.There is written down the colour of our eyes, skin and so on,do you know what I mean?That is the reason why I want to do this test so much because I believe nothing can replace the oncotype dx scores, because they give you the exact scores, the exact phenotype of your tumour, how it will behave during the long term follow up and in these genes there is everything.There is data of vascular invasion profile, proliferotic genes, ER,PR,genes and so on.That is the reason why I always say that nodes actually do not matter.Hormone receptors are much more important than nodes.I have seen many women doing extremelly well even with 20 nodes positive after many many years and stage I women dying because of breast cancer, but of course with high grade,ER PR HER-2 receptors negative, which is biologically very aggressive.Some people do not understand the mechanism why ER,PR negative breast cancer is so aggressive.Here is my explanation: Normal breast tissue is hormone dependent organ, so if the cancer(which is not normal tissue, it is neoplastic tissue but not so different from normal actually!!) remains hormone dependancy it is not so malignant, because it has kept this function of hormone sensitivity, ER,PR tumours have not.So,do you know see ...?it is so simple but however very complicated.

About taxanes my explanation would be: the majority of classical lobulars (not solid, pleomorphic variants!!) have mitotic activity 1, which is a very very slow growing cancer and the anthracyclines are best for tumours that have high mitoses because they inhibit mitotic activity,.Taxanes are drugs that destabilisize the microtubules(these are some structures that indirectly cooperate in mitoses of cells), so now you see the difference.:taxanes are better for breast cancer cells that are preparing to divide, anthracyclines are better for tumour cell that already divide rapidly.

I hope I am understandable:=)

I would really appreciate your pathology characteristics to let ne know, because I would be glad to have scores 15 on oncotype DX.

Kind regards and hope to hear from you soon:)Matic

msannie57 · December 2007

minuet--Oncotype DX does use hormone receptor scores and proliferation measures in the report. If you go to their website and click on the "Healthcare Professional" site you can get more information. (They'll never know!)

minuet · December 2007

Thanks Matic and Ann;

My pathology Matic is : Stage 2a multifocal ILC , tumour size not sure but first excision was 2.1 cm and multifocal and positivemargins. Further excision

revealed other focii of 7 mm and 1 mm and finally clean margins with mastectomy. My oncologist feels my tumour is 2.9 cm or more. My surgeon says you don't add the tumours up. I was ER+ @65% or 3/4 and PR+ @75 % or 4/4. My grade was 2 or 7/9

with tubules =3, nuclear=3 and mitosis = 1 or 1 mitosis /10 HPF; 400 field diameter .5; erb monoclonal and erb polyclonal were both negative, lymph node negative one slide showed probable LVI which really worries me. My oncologist says don't worry most tumours have this?? Don't understand why it says probable can't they tell or was it because I had a hematoma ....would that distort things?Cells stained positive for HMWCK and negative for e-cadherin. LCIS was also present extent not noted. I had the oncotype on my insistance but ended having chemo because of size and age 40 and possible LVI. I did 6 rounds of FEC. Would FEC be effective for lobular? thanks Minuet

matic22 · December 2007

Dear minuet!

Thanks for asking the question. FEC chemo is a good one, yes, also for lobular, I believe.MY mum also got EC chemo, without Fluorouracil.Which is quite the same regimen you got. You have to be glad your oncotype scores are low (15), so you have a very good prognosis within 10 years and later on.We all know that the most important time for prognosing is within 10 years, because most recurrences event during the first 10 years, later on it is very rare.So, I think it would also be okey to skip chemo in your case, but it is all right, better.But you have to focus now on hormone therapy,.It is very important for you to have the best hormonal therapy you can have.I would be aggressive as I could be with hormonal therapy because for these lobular tumours that are ER,PR+++ it is best to be treated with adjuvant hormonal therapy, if there is possibility with an AI(femara, arimidex, aromasin).They are all very good drugs.