for Jean, Robin P and all those who started with DCIS with microinvasion (recognized

[Lani]

or not)
2 November 2006
Sentinel node biopsy prudent in microinvasive DCIS
The risk–benefit balance favors performing sentinel lymph node (SLN) biopsy in all women with ductal carcinoma in situ with microinvasion (DCISM), Italian oncologists believe.

Giorgio Zavagno (University of Padova, Italy) and fellow researchers reviewed the outcomes of SLN in a series of patients with DCISM. They obtained data on 43 women with this a rare form of breast cancer who were treated at one of six institutions over a five-year period.

DCISM was diagnosed on the basis of one or more areas of invasion beyond the basal membrane, none exceeding 1 mm, Zavagno et al explain in their report, which appears in The Breast journal.

A total of 69 SLNs were excised, with positive results in four women (micrometastasis in one and macrometastases in three). All four women were subsequently found to have axillary macrometastases.

The authors say that DCISM "must be considered true invasive breast cancer" as it has a well-established potential to spread to the regional lymph nodes.

Nevertheless, the indications for axillary lymph node dissection in DCISM patients have always been controversial in view of the significant morbidity and low likelihood of finding positive nodes.

"The introduction of SLN biopsy has changed the terms of the problem," write Zavagno et al. "This procedure incurs low morbidity and allows a more thorough histologic examination, thus improving the probability of a positive nodal finding."

The authors conclude that, given the relative frequency of SLN metastases in this series, SLN biopsy should be performed when microinvasive foci are found at histology.



The Breast 2006; Advance online publication

http://www.journals.elsevierhealth.c...01640/abstract

[Lani]

I hope posting this where readership is higher helps prevent newly diagnosed
patients with microinvasion from having as much difficulty as you two have had figuring out which way to go treatment-wise. Other articles have tried to look at the character of the DCIS ie, her2+ or not, how high the ki-67 is, etc in deciding which DCIS need a SLN biopsy. Interestingly, in this study one of the patients with micrometastasis only in the sentinel node had macrometastasis in other nodes--I suppose that means it probably was not her "sentinel" node and makes you wonder what technique(s) were utilized to decide which was the sentinel node.
Hope this helps!

[RobinP]

Thanks, Lani, but I did have a real invasive her2+ cancer too and a positive sentinel node.

[Lani]

RobinP
Senior Member

Join Date: Nov 2005
Location: upstate NY- Pine City- near Itaca and Corning, NY
Posts: 429

Becky, how are ya, probably on the chat now, ah? Well, anyway I agree on multiple medical opinions, perhaps more than two. Here's why. A certain major NY City cancer center, that I am not suppose to disclose due to a legal payoff to me for their mistake, misdiagnosed me on my second pathology opinion.

I had a lumpectomy locally where only DCIS was found. Then the major cancer center did a second opinion and agreed it was only DCIS. Then I had a mastecomty with sentinel due to large size of DCIS. That's when the micro met node was found and they didn't know what to make of it for prognosis, particulary since I had only DCIS. Then they said do CMF for six month, just to be safe. Anyway, after I was done CMF, I had the lumpectomy slides checked since I finally noticed that my pathologist at the major cancer center was not "breast pathologist but anotomical". So I had their " breast pathologist" check the slides for a third time and that's when the freaking invasive 4mm her2+ bc was found. And the orginal pathologist at the major cancer center was required to admend his records. In other words, he agreed he made an error. Scary story, isn't it from a major cancer center?

Just emphasizes the importance of second and/or third opinions!!

[RobinP]

Lani 43% of DCIS is also her2+, according to the recent DCIS article you posted. I wonder how many DCIS + microinvasive would be recommended to have Herceptin or even chemo for that matter. When I was at Sloan-Kettering in 2002, they told me that DCIS+ microinvasion was not treated with chemo or Herceptin unless the node was positive. I think we are in a paradigm shift now, with the above type of article you posted, where you may see more treatment offered for microinvasive bc.

[Lani]

where they suggested intraductal Herceptin therapy for DCIS!

Just as they are just now separating out the different kinds of breast cancer which each have different behaviors and need different treatments, they are starting to do the same with DCIS and recognizing that(at least some) her2neu+ DCIS with
certain other characteristics are probably just precursors of her2+ bc that you happened to catch early. We certainly live in interesting times! Hopefully these things will be sorted out soon enough for others to be treated differently (and better!) than is often currently the case. As these things are better understood, treatment can only improve.

[Jean]

It is extremely important to pursue and have additonal opinions. As I have always said, this DCIS has been treated as if a woman is a little bit pregnant!
For me my DCIS was invasive and SN was negative, KI-67 levels were extremely high (red flag) yet the dr. also at major NY cancer center insisted on NO treatment..... My mind could not get around their theory.
Thank God for this site and Dr. Slamon...it helped open the doors finally for my
treatment. I just pray each day that the delay in my treatment does not harm me.

Thank you Lani for the post - I hope that other woman in the early stages
pursue their dx. with knowledge and vigor.

Jean

[RobinP]

I believe late Herceptin and chemo has efficacy. The late Herceptin group in the HERA is already demonstrating early signs of benefit, several months out. Well, you got chemo in reasonable timing too, before any reoccurence! Take care.

[mom22girlz]

I tried very hard to get more treatment for my DCIS with microinvasion,
her2+ breast cancer. I got 2 opinion and neither felt chemo or herceptin was necessary. At first the 2nd opinion dr. said i could have herceptin without chemo, but when it came down to it, he said he didn't think I'd reoccur. My first mammo is Nov. 15 and I am sooo nervous. Should I do anything else at this point? My lumpectomy was in February, 2006. Thank you for all your help and support. Susan

[mcgle]

Susan

I know exactly how you feel as I am in the same boat. My first post-op mammo is next Monday. Like you, I am HER2+, but received neither chemo nor herceptin; they were not considered necessary. However, I am worried…<?XML:NAMESPACE PREFIX = O /><O:p< font O:p<>

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2. How strongly HER2+ are you? I am weakly positive on the FISH scale (2.71), but positive nonetheless.<O:p< font O:p<>

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[mom22girlz]

My FISH was 6.41. The onc said this was high. I don't really know what that means because he also said if you're positive, you're positive. Do you have any plans to check into something else? I am ER/PR + so I now take tamoxifen. Thank you so much for your reply. It is nice to know there are others who feel the same way. Let me know if you have any new information. Sincerely, Susan

[RobinP]

I believe that I've read that only invasive breast cancer of 2mm or more can form blood vessels to spread. Under 2mm, such as in pure microinvasion, theorectically shouldn't be able to spread. I must stress PURE micro-invasion here. I think that rare cases of microinvasive relapse occurs when something is missed in pathology that is more than a micro invasive or when there is an unusal drop mets in surgery. Did you have any lymphatic/vascular invasion?- LVI? Did you have a sentinel node dissection to check for spread as that would be another indicator for relapse risk. If you had a positive node or LVI, you may consider late Hercepetin.Good luck.

WARNKING- double check your pathology. Remember I was misdiagnosed three times by pathologists!!! Twice locally in Elmira, NY's XXXXX's path lab and once by a pathologist at the PRESTIOUS major cancer center in NY city,XXXXX-Kettering. Shocker, isn't it?

[mcgle]

Robin<O</O

Six lymph nodes removed and all clear. No vascular invasion. My tumour was removed during two core biopsies, so they guesstimate it was under a cm. At excision, there was 2.4 cm of intermediate and high grade DCIS.

Here in the UK, they don’t do the Ki-67 test, so I don’t know the proliferation rate. Neither do I know the genetic make-up of the tumour. This is probably down to lack of funds, and not many people have private medical insurance.

So sorry you were messed around.

Mcgle

[RobinP]

<table border="0" cellpadding="0" cellspacing="3" width="98%"><tbody><tr><td nowrap="nowrap" valign="top" width="1%">Abstract No:

</td> <td valign="top" width="99%"> 10507

</td> </tr> <tr> <td nowrap="nowrap" valign="top" width="1%">Citation:

</td> <td valign="top" width="99%"> Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 10507

</td> </tr> <tr> <td nowrap="nowrap" valign="top" width="1%">Author(s):

</td> <td valign="top" width="99%"> P. Meijnen, M. C. Van Rijk, H. S. Oldenburg, C. E. Loo, R. A. Valdés Olmos, O. E. Nieweg, J. L. Peterse, M. J. Van de Vijver, E. J. Rutgers

</td> </tr> <tr> <td nowrap="nowrap" valign="top" width="1%">Abstract:

</td> <td valign="top" width="99%"> Background: About 20% of ductal carcinoma in situ (DCIS) lesions diagnosed by stereotactic core needle biopsy (SCNB) are shown to be invasive on postoperative pathology examination. Sentinel lymph node biopsy (SLNB) is an accurate method of evaluating axillary lymph nodes in patients with invasive breast cancer. The aim of this study was to review our experience with lymphatic mapping in patients with a SCNB diagnosis of pure DCIS, to evaluate the DCIS underestimation rate and consequently the risk of lymph node metastases. Methods: Files from 160 patients diagnosed with pure DCIS by SCNB between July 1999 and March 2005 were retrieved from our database. Patients with DCIS were selected for SLNB if there was concern for presence of an invasive component on the basis of size, palpability or imaging. Results: The median age of the study group was 55 years (range 29-85 years) and median DCIS size on mammography was 25 mm (range 4-96 mm). Thirty-six (23%) out of the 160 women underwent a SLNB. Macrometastases in the sentinel node were detected in seven (19%) patients and one (3%) patient was found to have a micrometastasis. Twenty (56%) of these 36 patients had invasive lesions on final pathology. Of the 124 women who did not receive SLNB, 29 (24%) turned out to have invasive lesions on postoperative evaluation. In total, 49/160 (31%) patients with pure DCIS diagnosed by SCNB had invasive breast cancer (range pT1mic-pT2) on final pathology. Finally, 88 patients underwent lymphatic staging by SLNB, basal node sampling or complete axillary lymph node dissection. Nodal involvement was present in 14 (16%) out of these 88 patients with initially diagnosed DCIS: 36% in patients with invasive breast cancer and 2% with pure DCIS on final pathology. Conclusion: Postoperative pathology examination of the specimen demonstrates DCIS underestimation in nearly one third of SCNB diagnosed DCIS patients. SLNB is of benefit for these patients as in 19% of the patients who undergo a SLNB macrometastatic disease in the sentinel node can be found.


</td></tr></tbody></table>

[P-3] Micrometastases in the sentinel node: take it or leave it?

According to this abstract, the primary tumor is of more importance than sentinel, though other medical opinions may vary...

Rutgers EJ.. The Netherlands Cancer Institute, Amsterdam, Netherlands

Early knowledge of nodal involvement in invasive breast cancer is thought to be valuable. In overt nodal involvement, so called macrometastatic disease, there is little discussion about the implications for prognosis and treatment. Its associated poor prognosis will always indicate adjuvant systemic and regional treatments: usually chemo- and endocrine therapy, complete axillary clearance, on indication followed by radiotherapy. The sentinel node (SN) procedure is a very reliable method of assessing axillary lymph node involvement in clinically node negative breast cancer and should be considered as standard of care. SN are now examined with great thoroughness and many protocols for this exist. The result is the frequent finding of the so called micrometastasis. What are the issues at stake?
The definition. Micrometastasis is defined as metastasis < 2mm in diameter and sub-micrometastasis or clusters of isolated tumour cells(ITC) < 0.2 mm in size. Micrometastases are found in about 30% of all tumour positive sentinel nodes.
The type of examination. One may add, over H-E staining, multiple slicing of the SN, staining with immunohistochemistry (IHC) or RT-PCR techniques with breast cancer related probes. Each step will lead to an 10% increase in finding small clusters of epithelial -cancer?- cells or RNA traces assumed to represent cancer cells. But are these cells viable, able to produce offspring and endanger the patient if left in situ? Or are this just innocent displaced cells. We performed an analysis of over 9000 published patients in whom the axilla was left untreated after a negative SN: after an average of 3 years of follow up, the clinical occurrence of metastasis was 0.4%, whilst the false negative rate after back up ALND in SN negative patients varies from 2-11%.
Predictor of non-SN involvement. This risk increases with tumor size, size and number of SN metastasis. In only ITC/sub-micrometastasis this risk is less then 10% where the involved non-SN frequently are macrometastatic as well.
The prognostic value. A number of studies suggest that such micrometastasis does not independently influence survival prognosis, if compared to tumour size and grade. So missing one micrometastasis by omitting multiple slicing and IHC would have hardly any influence in terms of prognostic information. Furthermore, many patients would have adjuvant systemic treatment based on primary tumour characteristics, which may be of much stronger prognostic value than nodal status.
In conclusion, one should not to look too hard for micrometastasis in the sentinel node. Effort in ascertaining the clinical relevance of such micrometastasis is surely the province of research, not for routine clinical practice. If micrometastasis (0.2 - 2.0 mm)are found, further axillary treatment (ALND if indication for adjuvant systemic treatments is uncertain) is warranted. If other nodes are negative or only micrometastatic, adjuvant treatment should only be based on primary tumor characteristics. In general, sub-micrometastasis (< 0.2 mm) or ITC can be ignored.

Saturday, December 16, 2006 9:00 AM

Plenary Lecture 3 (9:00 AM-9:30 AM)


<table with="95%" align="center" border="0" cellpadding="4" cellspacing="4"><tbody><tr><td>[21] Significance of sentinel lymph node micrometastasis on survival for patients with invasive breast cancer.

Cox C, Vrcel V, Riker A, White L, Allred N, Ramos D, Myers M, Dupont E, King J, Cantor A, Diaz N. H. Lee Moffitt Cancer Center, Tampa, FL

OBJECTIVE: The overall objective of this study was to test the impact of micrometastatic carcinoma detected by sentinel lymph node (SLN) biopsy on survival in invasive breast cancer patients. To do so, we compared survival outcomes in such patients with a negative SLN biopsy and the outcomes of those with micrometastatic disease in a SLN.
METHODS: The charts of 2145 invasive breast cancer patients with pathology reports of SLN with either micrometastatic or no metastatic disease were reviewed. The SLN HE and immunostained (cytokeratin) slides of patients with the diagnosis of micrometastatic carcinoma were analyzed and reclassified according to the 6^th edition of the AJCC Cancer Staging Manual. Tumor deposits > 0.2 mm but not > 2 mm were classified as N1mi. Patients with SLNs with isolated tumor cells not > 0.2 mm were classified as N0(i+). SLNs with no epithelial cells on either HE or immunostaining were classified as N0(i-). Kaplan Meier graphs of overall survival (OS) and disease free survival (DFS) were done.
RESULTS: Of the 2145 patients reviewed, 1854 (87%) were N0(i-). 291(13%) of our patients had single cells and/or small cell clusters or micrometastatic disease. 138 (6%) were reclassified as N1mi and 153 (7%) as N0(i+). OS and DFS of the patients with N1mi SLN differed significantly from patients with N0(i-) SLN (p=0.005 and 0.016 respectively; Figures 1 and 2).
CONCLUSIONS: The detection of micrometastatic carcinoma in the SLNs of invasive breast cancer patients, as presently defined by the AJCC, is a significant indicator of survival. Subset analysis of N0(i+) patients will be presented. Results of the ACOSOG Z0010 trial may validate the latter results and clarify the clinical significance of N0(i+) detected by SLN biopsy.





Friday, December 9, 2005 2:15 PM

General Session 4 (2:00 PM-3:30 PM)

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I was originally diagnosed with DCIS, comedo form, in New York, and the first surgeon I visited said a sentinel node biopsy was an absolute requirement with high grade DCIS. The second surgeon (the one who operated) also insisted on a SNB, whatever grade DCIS. Actually, she wanted permission to do more than just a SNB if she saw anything suspicious during surgery, and I refused. I'm wondering how a surgeon would even know that a woman had pure DCIS without the full pathology report after surgery?

Jean, my New York oncologist (NYU), in contrast to your New York doctor, insisted on both chemotherapy, taxol with carboplatin, and afterwards herceptin for a full year of treatment as soon as he knew I was HER2+ (4.7). He had to do quite a bit of tap dancing to convince me to do chemo, as I am Stage 1a (5mm), and I'm still not convinced he was right. You seem to have found yourself an unusually conservative oncologist if I judge by my treatment and that of other women here at NYU with similar pathologies.

If you would like his name, send me a private message, and I'll be glad to share it with you. The facility is also very nice and very well run. My doctor is a lovely person as well, kind and caring, and actually shaves his head from time to time when he has a new patient just starting chemotherapy to show solidarity. And it's not as though he looks like Yul Brenner--he actually looks rather awful without hair! But everyone loves him anyway.

[Mary Anne in TX]

Hey Lani and Robin....Thanks for continuing to "rattle the cages" in some needed areas! I am so grateful that my onc has been an "overachiever" in every way...treatment, concern, double checking, & sending me to the very best surgeon, radiation onc., radiologist, etc. One of my 2 adopted sisters found him for me and then called to be sure they accepted me when I called them the next morning! God is so good when we are so weak! ma

[RobinP]

for T1 cancers where traditionally prognosis is good:

http://www.annalssurgicaloncology.or...t/11/6/568.pdf

http://clincancerres.aacrjournals.or...act/12/22/6696

PS The above studies are interesting because they have lont-term follow-up of 8 and 15 years.

And a divergent opinion, where LVI positivity had more importance, in a SMALL study of 8 year follow-up: (PS not sure I give this same study much stock , especially since the decision of adj. therapy may be a life-saving one.)
http://www.blackwell-synergy.com/doi...X.2006.00267.x

To sum it up, overall, micromets and ITC in the sentinel appears to have a play in long-term relapse, and adjuvant therapy may have a role in relapse prevention.

Adj. tx. guidelines are for t1a lesions are aggressive, even without positive lymph node because, "Patients with high-grade tumors and/or LVI may have10-year RFS rates of less than 75% in the absence of systemictherapy. "...

http://jco.ascopubs.org/cgi/content/abstract/24/13/2113

[Jean]

Thanks Grace, always good to have a referral.
Dr. Slamon had referred me to an onc. that had worked on the Hera Trials
and he has been wonderful working along side Dr. Slamon during my chemo/herceptin treatment.

At the time of my dx. 4/05 the bible in NY at Sloan, Cornell and Mt. Sini was tumor size, grade, (my was 1) ...each time I mentioned about the Her2 portion of my dx. the dr. did not consider it was the most important part of my dx. esp. since I was ER postive...feeling that hormonal therapy
was my ticket along with radiation. But after reading and searching articles I just could not believe them. I kept hearing how many woman were node neg. and having recurrance. Which alerted me to search into the questions can a cell pass through and / or get through the blood system undetected? Can that happen more often than not. Please know that the dr. (onc's) that I saw are considered to be top men in their field. I discovered at that time 4/05 that the dr. in NY did not even recognize the Oncotype DX test (now it is used at Sloan) Timing is everything.
Early bc was and still is for the most a major controversy as far as treatment decisions, esp. when node negative along with the small tumor low grade. When I would mention information I would gather from our site one onc. answered "well it just is not the gold standard of treatment".
I began to wonder if they were more concerned about law suits regarding treatments outside the box. My tumor was 6mm after biopsey 3mm - the invasive portion was under 2mm and the margains were 25mm...but I still did not feel satisfied - considering the Her2. I would also like to share one onc. even told me how dangerous herceptin is to the heart and how dangerous it was, which upset my husband to a great degree. It was only after I insisted through my surgeon to have the Oncotype DX test performed - when that came back high risk the onc's then changed
their opinion. They wanted to give me A/C..at this point I made an appointment to see Dr. Slamon I had lost all trust. Now by this time there had been published articles from Dr. Slamon regarding TCH...but that was not mentioned either. Now when I saw Dr. Slamon he immediately said hemo/herceptin, even if I did not have the Oncotype DX test. He said my KI-67 level was enough to make the decision. So the grade, tumor size, etc. was not the only factor. I promote having more than one opinon (in my case I had three in NY) they all said the same, but later changed their dx. Goes to show and teach to be our own advocate. It was a learning experience for me, I was very innocent in the early days of dx. I thought or at best was under the silly impression that standard of care meant that the major hospital had the same treatment protacal for breast cancer. In those early days for the most part you are in a state of fear. Thank God for Joe and Christine and this site. I can not emphasize and praise enough the value of this site. The woman and men who share their knowledge and experiences always giving 200% of themselves. Christine
never gave up as we discussed my dx. and she insisted the dr. were wrong. At the time of my dx. it was timing and I think there was a shift in treatment here in NY. I just wish that more money was being spent on research for this dreaded disease. Trials take so long and many promising medicnes are not getting out of the lab. In the meantime we must do all we can to maintain a strong immune system, continue to study and learn all we can.


Jean

[Jean]

As I mentioned earlier - in the early days you are filled with fear.

I found this beautiful quote after I returned back from Calif. seeing
Dr. Slamon....and it said it all.

"You gain strength, courage, and confidence by every experience in which your really stop to look fear in the face. You must do the thing which you think you cannot do"

by Eleanor Roosevelet

Jean

Thanks Jean. It's interesting as we have exactly opposite stories. My cancer was 5mm and I felt that everyone was being too aggressive. I believe I have the largest margins in the history of breast cancer--the largest was 5cm and the smallest was 2cm. I was very angry at my surgeon because she wanted to do more than a SLN if she saw anything strange and I refused. I'm actually happy these days that she did leave such large margins, although maybe if I were younger I might feel differently. I am a bit lopsided.

And because just about everyone in my family has died of a heart condition (no one ever lived long enough to get cancer) I was very very concerned about taking herceptin. So I was the one kicking and screaming about my heart. My oncologist kept saying but you have a HER2+ cancer. However, he wasn't pushy when he saw me resisting; he let me come to my own decisions. But he's not at any of the hospitals you mentioned--he's at NYU, and I've been delighted with my care there in all respects. Love the nurses, the private rooms for chemo, mine is with a window seat, the gowns, the dressing rooms, the efficiency of the administration, everything. Can't recommend it too highly.

Dr. Volm even wanted me to get a second opinion and suggested Sloan, but I refused. I found he was reading Michael Dibdin's "Dead Lagoon," my favorite writer of Italian mysteries and my favorite mystery, so decided we were compatible and made my decision right then that he was the doctor for me. (I should say, I suppose, that I had read 700+ technical articles and abstracts on HER2+ breast cancer before my first visit so I did understand somewhat the issues involved.) I often make major decisions in this silly way--an instinct, I suppose, but thank goodness, this one (and marrying my husband) worked out beautifully for me.

I have a good friend who always insists on using the "Best Doctors" list and she's had the most horrific experiences. She's in despair at the moment because of a botched knee replacement by a 'best doctor." I keep telling her, throw the list away--most of the people who get on those lists are marketing experts not best doctors. Ask family and friends for referrals. And it sounds from your story that I'm right about those lists.

Sorry you had such a bad experience. I wish you had happened on Dr. Volm--you would have loved him. But I'm glad in the end you found a good medical team. It's very important, I believe, to trust your doctor and to leave when they don't make you comfortable. I changed my breast surgeon after surgery and am delighted with my new doctor, although I may have been a bit hard on the earlier one. But this is a learning process for sure.