how many started out with DCIS with or without microinvasion

[Lani]

a few of you have posted that you started out with DCIS and then went on ...even to Stage IV

This has concerned many with DCIS, as the oncologists' mantra has seemed to be that it need only be treated with surgery and radiation.

Almost all DCIS does not recur distally or even spread to the lymph nodes according to the literature it seems, and about 60% of them are her2+ it seems. Yet some on this site are wondering how small a her2 tumor has to be such that they can just have surgery and radiation and "not have to worry about it"

Jean recently found out that her DCIS with microinvasion (.3mm) had a very high OncoDx score--OncoDX is not officially meant or validated for DCIS, only for Stage I node negative ER+ invasive ductal carcinoma.Nevertheless, Dr. Slamon felt, as small as it was, that her her2+ area of microinvasion warranted treatment with chemo and herceptin.

I post an abstract showing that someone is looking to find which markers on DCIS might portend a more aggressive behavior and ask all those who started out with a Diagnosis of DCIS to help share info so others starting with DCIS can get a handle on the situation.

I know very little about DCIS--I first started looking it up when asked by an oncologist to try to explain to a reluctant patient something about breast cancer and her2neu to help explain why she couldn't just pretend everything was ok and no treatment was needed when her DCIS with microinvasion suddenly became associated with a lymph node which appeared and grew tremendously over four weeks' time. She thought I explained things well, but actually the whole experience was a bust. (as I posted previously).
I had not looked up DCIS before then really and haven't made it my baileywick, but it seems like an area where there is still a tremendous amount of knowledge lacking.

Jean asked me why I thought there wasn't general knowledge or agreement on what is going on with DCIS with microinvasion especially with her2+ status. We agreed to try to start a roll call to see if the her2group could produce enough information to attract a researcher or Genentech. If a certain profile of DCIS with microinvasion and her2 postivity can be asociated with a substantial risk of distant recurrence, they might be able ton alter the natural history of the disease AND market their drug to more people.

Please list age at dx, pre or post menopausal status, size of dcis, whether microinvasion(s) and size of microinvasion, her2 status by IHC or FISH in the DCIS, ER and PR status, grade of DCIS, type of surgery you had, margins of surgery, whether you had radiation therapy, hormonal therapy, any other therapy. How long until recurred, where, subsequent treatment.

It seems we must try to push to move "science" along sometimes...

Thanks to all who join in!

Lani

Appl Immunohistochem Mol Morphol. 2005 Mar;13(1):14-8. Related Articles, Links

Correlation of HER2 gene amplification with expression of the apoptosis-suppressing genes bcl-2 and bcl-x-L in ductal carcinoma in situ of the breast.

Siziopikou KP, Khan S.

Department of Pathology, Rush University Medical Center, Chicago, IL 60612, USA. Kalliopi_P_Siziopikou@rush.edu

The protein product of the HER2 oncogene is overexpressed in an estimated 25 to 30% of breast carcinomas and is considered an indicator of poor clinical outcome. The bcl-2 and the bcl-x-L genes are the 2 main genes of the bcl-2 gene family that suppress tumor cell death/apoptosis. HER2 gene amplification is also described in a percentage of cases of ductal carcinoma in situ (DCIS) of the breast. However, the relationship of such overexpression with the apoptosis-suppressing genes is currently unknown. A total of 37 consecutive cases of DCIS were immunostained for HER2 overexpression (clone CB11, Ventana), and expression of bcl-2 and bcl-x-L. DCIS cases were graded using the criteria of Holland et al. HER2 overexpression was scored 0 to 3+; 0 and 1+ were considered negative staining and 2+ and 3+ were considered positive staining. HER2 gene amplification was also confirmed with fluorescent in situ hybridization (FISH). HER2 was positive in 22 of the 37 DCIS cases (60%) in accordance with previous reports. Immunohistochemical overexpression of HER2 was also highly correlated with HER2 amplification by FISH. HER2 overexpression (confirmed by FISH) was mostly seen in grade II (9 of 17) and grade III (9 of 12) DCIS lesions. Only 1 of the HER2-amplified cases was a grade I lesion. Furthermore, HER2 overexpression correlated with the presence of necrosis (P=0.003). Similarly, of the cases overexpressing HER2 at the highest level (3+), 90% were grade II or grade III lesions. A total of 73% of these cases also exhibited necrosis. Overexpression of HER2 3+ was also highly correlated with the presence of the apoptosis-suppressing gene bcl-x-L (coexpression in 87% of cases, P=0.01) but not with the prototype apoptosis-suppressing gene bcl-2 (coexpression in 50% of cases, P value not significant). First, in DCIS overexpression of HER2 the majority of grade II and grade III lesions is seen, and this correlates with the presence of necrosis. Second, HER2 overexpression is also highly correlated with the expression of the apoptosis-suppressing gene bcl-x-L, but not with the prototype apoptosis-suppressing gene bcl-2. These differences may prove useful in defining groups of DCIS lesions with enhanced tumor cell growth and propensity for progression to invasion.

[VaMoonRise]

Hi Lani,

I am so glad that you brought this subject up. This subject has plagued me night and day, as you read further into my post you will understand why.

I was first diagnosed with DCIS in March of 2004 at the age of 36 through a mammogram, pre-menopausal. Mammogram showed microcalcifications in left breast. I had a stereotactic biopsy which showed DCIS solid comedo type, the malginant cells lining the ducts are a variable nuclear grade II - III, no invasion identified, left breast, superficial, are nineteen 0.2 cm in diameter light tan tissue cores with the lengths ranging from 0.2 to 2.2 cm, left breast, deep, are fifteen 0.3 cm in diameter light tan tissue cores with the lengths ranging from 0.3 to 1.6 cm.

Surgical Pathology Report

Estrogen Receptor - Positive (Positive > 5% nuclear staining)
Progesterone Receptor - Positive (Positive > 5% nuclear staining)
HER-2/neu - Positive for gene amplification (FISH)

Synoptic Report:

Specimen type - Lumpectomy
Tumor Site - Left Breast
Tumor Type - Ductal Carcinoma In Situ
Nuclear Grade - III
Pattern - Solid, cribriform and micropapillary with focal central necrosis.
Margin - negative for malignancy.
Distance of Tumor to nearest Margin - Less than 1 mm.

Comment:

Ductal carcinoma in situ is present in approximately 30% of the tissue sections. It is seen in the region of the biopsy cavity and several centimeters away from it.

I underwent a lumpectomy and had radiation everyday for 8 weeks. I thought I was lucky to have caught it so early and thought that I was now in the clear. Unfortunately in December 2006 I came down with a gall bladder attack and when they went in to surgically remove it they found cancer spread extensively throughout my liver. I also have two spots on my spine. I am currently in a clinical trial consisting of Herceptin, Taxol and Lapatinib. I also receive Zometa once a month. I still have a difficult time understanding how I went from being DCIS stage "0" to now being stage "4" in such a short time. I can't help but play the "What If Game." What if they had removed lymph nodes, what if they had done a mastectomy, what if they had put me on Tamoxifen or Herceptin? I can't help but wonder if my outcome would still be the same.

I read this interesting article after the fact, too bad I hadn't read it sooner. I hope all women read it.

http://www.annalssurgicaloncology.or...t/full/8/8/617

I hope more research is done about DCIS and the way it is currently treated so that no other woman ever has to go through what I have been through.

Please keep me posted as to any further info or questions that arise from this topic, and thank you so much for bringing the topic back up again.

Sincerely,
Nicola

[Jean]

dx. with microinvasion of in situ duct carcinoma (DCIS)
Bloom Richardson grade 1
3MM microsopic
No angiolymphatic invasion is identified
DCIS is predominantly cribriform type with intermediate grade nuclei
The resection margins are free of invasive and in situ carcinoma
Microcalcification are associated with DCIS
FISH test - Her2 +++ positive
Estrogen Recetpor: 90% positive
Progesterone Receptor 1% negative
Proliferation Index: 40%
Sentinal Node biopsey - Negative
Onctoype DX test - recurrance score high range 31%

Was advised to treat with lumpectomy - had 25MM clean margins
Radiation 32 treatments
Arimidex

After Oncotype test score came back in the high range saw Dr. Slamon
who advised chemo/taxol/herceptin. I am now one yr. out!
Will begin treatments in the next two weeks.
Dr. Slamon ordered TOPO 11 test (will get results this week)
and also having PTEN test done which is a predictor of who will respond to
herceptin.
Have also contacted Dr. Greene in Penn U - for information on trial for blood test to test for her2 neu proteins. (will know more this week)

I have decided that the dr. are treating the early stagers not as serious
as they should and WE MUST be diligent in our medical needs. I am just sorry I lost the time - but hopefully I will catch up now. I had PET scans and CT scans plus bone scans done, all came back NED (thank God). I am approaching this now as if I found my cancer 6 months ago and going after it with a strong approach. Even though small tumors and node negative are favorable factors I no longer believe that is enough to base treatment decisions on. The make up of the tumor like your own personal fingerprint is the key.
I think all early stagers need to be very careful and ask what your Ki-67 level is - since that is a strong indicator.

Thank you Lani for Posting, I hope that some solid research will come form this.

Regards,
Jean

[mekasan]

I underwent a mast due to DCIS, but 2 IDC tumors werefound in the tissue after it was test.

[Lani]

I wonder whether an MRI preop could have detected the DCIS better and directed the surgeon better where to biopsy (or to do an excisional biopsy)--MRI is still in its early stages and has false positives, but if you or someone you know were to go through this again on your other breast (hopefully not!!!!!) it might be something to think of. I also wonder whether in some patients there is not ectopic(out of its normal location) breast tissue in the axilla (armpit) which is the invasive component which is treated with the radiation and never identified, except for the fact that it let loose the metastatic cells early which come back to wreak havoc.

Also from what I understand 2mm is considered the best margin to have, even for DCIS. Best to look this up, as I would not want to be wrong!

Just things to think about. Not to dwell on, just for those faced with this for the first (or second) time to consider.

They need to do a lot more research on DCIS it seems!

Thanks for your input!

Lani

[mekasan]

I had an MRI on both breasts, two ultrasounds by different techs and two sets of mammos. My biospy was Mammo guided. Either the tumors grew during the month btw the MRI and the Mast or the density of my breast plus the DCIS presence masked the tumors. Either way, its all in storage somewhere and no longer in me. I had the other breast removed after chemo. A preop MRI showed a small tumor. Core biospy said benign fatty deposit. After Mast path showed nothing.

[mom22girlz]

This is all my report says:
The breast tissue aggregates to 4 cm in greatest dimension. Multiple sections of breast biopsy show extensive ductal carcinoma in situ (cribform, micropapillary and solid type) with high grade cytology. Blocks (7 and 9) show foci of microinvasive carcinoma with surrounding stromal reaction. Sections of the surgical resection margin show no evidence of malignancy.

ER 2+
PR 2+
Her2 3+
FISH results 25 cells examined her-2/neu signals to chromosomes 17 signals calculated. Ratio was 6.41, indicating amplification of this gene.

I will meet with my onc. with in next 2 weeks. He feels it is okay to finish radiation and then do tamox. I am not so sure. I want the onco test and he thought he had enough info to go on now. At one time he said he would allow me to take herceptin if I wanted, but at the last appt. said this would be unnecessary. I'm confused and scared.

I am 47, pre-menopausal.
Any advice is welcomed.
Susan

[RobinP]

DCIS which is high grade comedo type, which typically forms a palpable mass, can invade to become an invasive cancer, especially if it is not promptly treated and allowed to grow over 2.5 cm large. Comedo DCIS is usually er, pr negative and her2+ so if it invades, the invasive component is usually the same, her2+.

My suggestion for anyone with DCIS with microinvasion is to have sentinel node dissection in order to see if invasion occurred. Also, examine your pathology report to see if LVI or lymphovascular invasion was found. A positive node and or positive LVI may prompt you to do Herceptin if your microinvasion is her2+ by FISH.

I also have heard that Dr Slamon recommends Herceptin, even for the smallest amount of her2+ disease, which correlates what Lani wrote above about giving Hercetpin for her2+ microinvasive bc. Perhaps this is an aggressive approach, I can't say for sure. What is needed are clinical trials for microinvasive her2+ bc and small invasive bc with and without Herceptin to fully address these gray zone areas.

ps. Lani if you don't mind my asking are you a bc survivor or a health care worker with bc patients? Thanks for your post and input here.

Addendum:

Just thought this below article correlated well with your above article post Lani on bcl2. At least bcl2 is not usually associated with her2....

bcl-2 Is a Prognostic Marker in Breast Cancer Independently of the Nottingham Prognostic Index

Grace M. Callagy1,4, Paul D. Pharoah2, Sarah E. Pinder1,3, Forrest D. Hsu5, Torsten O. Nielsen5, Joseph Ragaz7, Ian O. Ellis6, David Huntsman5 and Carlos Caldas1 Authors' Affiliations: 1 Cancer Genomics Program, Department of Oncology, Hutchison-Medical Research Council Research Centre, University of Cambridge; 2 Cancer Research UK, Department of Oncology, Strangeways Research Laboratory; 3 Department of Histopathology, Addenbrooke's Hospital, Cambridge, United Kingdom; 4 Department of Pathology, National University of Ireland, Galway, Ireland; 5 Genetic Pathology Evaluation Centre of the Department of Pathology and Prostate Research Centre, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, British Columbia, Canada; 6 Department of Histopathology, Nottingham City Hospital, Nottingham, United Kingdom; and 7 Oncology Health Center, McGill University Health Center, Montreal, Quebec, Canada

Requests for reprints: Carlos Caldas, Department of Oncology, Hutchison-Medical Research Council Research Centre, Level 3, University of Cambridge, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2XZ, United Kingdom. Phone: 44-1223-331989; Fax: 44-1223-331753; E-mail: cc234@cam.ac.uk.

Purpose: Prognostication of breast cancer using clinicopathologic variables, although useful, remains imperfect. Many reports suggest that gene expression profiling can refine the current approach. Alternatively, it has been shown that panels of proteins assessed by immunohistochemistry might also be useful in this regard. We evaluate the prognostic potential of a panel of markers by immunohistochemistry in a large case series to establish if either a single marker or a panel could improve the prognostic power of the Nottingham Prognostic Index (NPI). We validated the results in an independent series.

Experimental Design and Results: The expression of 13 biomarkers was evaluated in 930 breast cancers on a tissue microarray. Eight markers [estrogen receptor (ER), progesterone receptor (PR), Bcl-2, cyclin E, p53, MIB-1, cytokeratin 5/6, and HER2] showed a significant association with survival at 10 years on univariate analysis. On multivariate analysis that included these eight markers and the NPI, only the NPI [hazard ratio (HR), 1.35; 95% confidence interval (95% CI), 1.16-1.56; P = 0.0005], ER (HR, 0.59; 95% CI, 0.39-0.88; P = 0.011), and Bcl-2 (HR, 0.68; 95% CI, 0.46-0.99; P = 0.055) were significant. In a subsequent multivariate analysis that included the NPI, ER, and Bcl-2, only Bcl-2 (HR, 0.62; 95% CI, 0.44-0.87; P = 0.006) remained independent of NPI (HR, 1.50; 95% CI, 1.16-1.56; P = 0.004). In addition, Bcl-2, used as a single marker, was more powerful than the use of a panel of markers. Based on these results, an independent series was used to validate the prognostic significance of Bcl-2. ER and PR were also evaluated in this validation series. Bcl-2 (HR, 0.83; 95% CI, 0.71-0.96; P = 0.018) retained prognostic significance independent of the NPI (HR, 2.04; 95% CI, 1.67-2.51; P < 0.001) with an effect that was maximal in the first 5 years.

Conclusion: Bcl-2 is an independent predictor of breast cancer outcome and seems to be useful as a prognostic adjunct to the NPI, particularly in the first 5 years after diagnosis.

[Ginagce]

I'm sorry I can't be more specific about this but I too was diagnosed with DCIS in left breast and LCIS in both breasts in 1997. At the time my husband was just getting out of rehab after a combination of hospital and rehab stays of 7 months. I was working full time an hour each way from our home and at that point was the sole supporter and insurance carrier for both of us. Needless to say life was rather crazy. I took a lot of notes and have all the specifics but have not been able to find them yet. I saved this post hoping I would by now but again, things got hectic....and you know the rest.

At the time I did a ton of research on DCIS (all I could find anyway) and got 3 opinions from the 3 major NCI cancer centers in Philadelphia. One said get bilateral mastectomies as this stuff is "a bad actor" if it returns; another said have lumpectomies and do nothing else;and the third said lumpectomies and radiation on the DCIS side. Basically, DCIS was relatively new on the scene and most things I read (Susan Love etc.) said that it was more or less a crap shoot as they didn't find it much with older mammogram technology.

I considered the bilateral briefly but realized very quickly that I could not take care of my husband if I had that kind of surgery.

I opted for the lump's and rads.

In 2004 a mammogram found a 1cm tumor in my non-radiated side. Bilateral mastectomies revealed another tumor, similar size, in the radiated side. This one had not shown up on the mammograms. A sentinel node biopsy done at the time of the mastectomy surgery revealed spread to my lymph nodes on the radiated side.

The original statement that if this "stuff" returns it's a "bad actor" was correct.

My stats in 04 were ER+ PR+ and Her2+.

After bilaterals, chemotherapy and coming up on 1 year of herceptin, I am officially NED.

I hope and pray that I remain so.

If it will help you to know my pathology info from 97, I will continue to look for it. Please let me know.

Ginagce

[Ginagce]

my husband had non-hodgkins lymphoma. He died in 1998. After that I ran as fast as I could from cancer and all things related. It was only with this diagnosis that I think I really recognized that I did indeed have cancer and begin to actively manage and track information.

Ginagce

[DeborahNC]

I had lumpectomy and 33 rads in Sept. 2004 for DCIS. It was comedo type, high grade, ER+, 3 cm., but not tested for HER gene amplification. I refused Tamoxifen.

I progessed to Stage 1, DCIS and .7 cm IDC 2 years later. My surgeon told me that my decision not to take Tamoxifen was wise as it would not have prevented recurrence due to my ER status.

I read extensively on DCIS the first go around. The most interesting aspect was that if science could figure out how the cells in the duct lining kept DCIS contained IDC could be prevented. I don't know of any studies are ongoing on this.

[Roz]

I had 3 DCIS and one Inflammatory BC in the one breast. Who knows why? It was just so.