"Hidden margins"...This explains a lot

[Tom]

I found this article from Penn's Oncolink fascinating, and really not unexpected. I guess I never trusted microscopically visible margins to begin with. Now it seems there are secondary "margins" of a very different nature.

http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&Year=2006&Month=07&id=13 317

Genomic instability in normal breast tissue may alter treatment
Megan Rauscher
Reuters Health
Posting Date: July 11, 2006

Last Updated: 2006-07-11 15:30:45 -0400 (Reuters Health)

NEW YORK (Reuters Health) - An analysis of breast tissue adjacent to tumors shows that genomic instability, a prerequisite of virtually all tumors, occurs in fields of histologically normal tissues outside the tumor margins.

This supports the concepts of "field cancerization," or a "cancer field effect," Dr. Jeffrey K. Griffith told Reuters Health. These concepts were introduced to describe "areas within tissues consisting of histologically normal, yet genetically aberrant, cells that represent fertile grounds for tumorigenesis," he and his colleagues explain in the July 1st International Journal of Cancer.

The research team, from the University of New Mexico School of Medicine in Albuquerque, used two validated markers of genomic instability -- telomere DNA content and allelic imbalance -- to define the extent and spatial distribution of genomic instability in two independent cohorts of breast tumors and their matched histologically normal adjacent tissues.

Shortened telomeres (to a level outside the range seen in > 95% of all normal tissues) and unbalanced allelic loci were present in tumor tissue as well as in 50% to 75% of tumor-adjacent, histologically normal tissue specimens at distances at least one centimeter from visible tumor margins.

"Although the extent of these genetic changes decreases as a function of the distance from the visible tumor margin, unbalanced loci are conserved between the surrounding tissues and the tumors, implying cellular clonal evolution," the authors note.

Dr. Griffith said there are two important implications of this study. The first concerns assessment of surgical tumor margins, which are conventionally defined by histological criteria.

"Since histologically normal, yet genetically aberrant, cells might represent the source of local and/or distant recurrent disease, they should be identified and removed," he told Reuters Health. "Thus, the evaluation of tumor margins should include molecular, in addition to histological, criteria."

The second implication involves risk assessment and cancer prevention. "We hypothesize that the development of the field of genetically aberrant cells is an early step in cancer progression," Dr. Griffith said. "If so, biomarkers that detect the field prior to the development of frank cancer could potentially identify women at early stages of cancer progression," he added.

Int J Cancer 2006;119:108-116.

[StephN]

... that the trend in breast conserving surgeries is really wrongheaded??

I asked for a mastectomy and was told that the new data showed that I would do just as well with a lumpectomy. chemo and rads. Two surgeons were not in favor of a mast for me.

Maybe in my case it did not matter by then as it was already in my axilla nodes and overtaking nodes in my breast. But, my intuition told me to take the whole breast and be rid of it.

My cancer came raging back very quickly.

[R.B.]

Interesting post.

I did a search and found this which links p53 to telomeres.

RB


http://focus.hms.harvard.edu/1999/Ma...99/briefs.html

P53 May Induce Death in Cells with Short Telomeres
As a cell ages, the ends of its chromosomes—the telomeres—are worn away, and the cell receives a signal to stop dividing or die. A study in the May 14 Cell by Lynda Chin and Steven Artandi (colead authors), working in the lab of Ronald DePinho, professor of medicine at Dana-Farber, implicates the tumor supressor p53 in triggering the death of cells with shortened telomeres, and suggests that complete loss of p53 activity combined with some telomere loss can lead to accelerated cancer formation.
Using cells from mouse strains in which the telomeres is shortened to different degrees, the authors found that severe telomere shortening triggers DNA damage checkpoints, activating p53 and causing cell death, senescence, or both. So they explored what would happen in the absence of p53, by creating mice that both have shortened telomeres and lack p53.
Surprisingly, they saw two distinct responses. Progressive telomere shortening usually results in germ cell apoptosis. Removal of p53 prevents apoptosis in animals with partial telomere loss. But in animals with shorter telomeres, germ cell death proceeds whether p53 is there or not. The results suggest that there are two triggers for cell death in response to telomere loss, only one of which is dependent on p53 activity.
These results, together with those showing that telomere-p53-deficient cells are more likely to become cancerous, lead the authors to suggest that lack of p53 permits a cell to pass through an early checkpoint, but lack of telomeric structures eventually causes massive chromosome instability and death for most cells.
In a related article in Cell, members of the DePinho lab report tumor reduction in mice with impaired telomeres but intact p53 activity, further evidence of the need for telomeres in cancer cells and the role of p53 in catching those cancer cells without them.

[Tom]

Good for you Steph. I'm glad you went with your intuition on that decision. I'm not making any recommendations to anyone that is about to have surgery, but I was very concerned when Mom's surgeon assured me that her choice of clear margin thickness was satisfactory to her. Of course Mom's cancer had already developed micromets in her axilla, but they were not examined more closely partially due to the "clear margins" found during the actual surgery.



R.B.,
I am and have been for some time, fascinated by the whole telomere story. They are thought to be, by some researchers, the link to immortality of sorts, as they are the biological aging clock for individual cells. I think they will be found to also be one of the prime suspects in many cancers, as they are supposed to let the cell know that it's "time to drink the hemlock ". Telomeres may be a two-edged sword. If you mess with them, they could let bad things happen, as is the case when they don't do their job. It will get interesting down the road.

Tom

[R.B.]

More on telemores.

All this begs the question if oestrogen (telemore protector anti-inflamatory? see below) is indeed the bady?? -- Or is it something else lack of omega three blocking of pathways and vast excess (in evolutionary terms) of omega six consequent oxidative stress self fuelling unbreakable cycle as oestrogen tries to moderate inflamation via omega three??????????

Interesting article linking to inflamatory pathways oxidative stress etc.(below)

Inflamatory pathways - See posts on omega six and Greek diet re COX 2 inflamatory pathways and cancer.

The comments on oestrogen as an anti inflamatory are interesting, and something I had not seen before.

I post these conjectures as a wandering true amateur with very limited knowledge in case thought provoking for those who may be able to make better sense of it.

IF oestrogen is an anti inflamatory (see below) and one role is to mitigate the omega six AA eicosanid pathways then the body may produce oestrogen in response to series 2 inflamatory agents.

PGE2 has been reported as uprating p450 which uprates oestrogen which uprates growth factors.

In a situation of excess omega six / AA it may not be possible to damp down the inflamation leading to a self fuelling cycle as oestrogen tries to damp down the inflamation and AA keeps upgrading it PGE2 etc.

If one mechanism of damping is production of series three eicosanoids, could a role of oestrogen be to uprate FAS and preferentially omega three (pregnanacy lactation DHA required by infant.)

In the absence of adequate supply of ALA the omega three percussor - or blockage of the FAS pathways by excess omega six, trans fats etc - no DHA EPA would be produced so no moderating series three eicosanoid.

At the same time "permenantly" high oestrogen casued by excess inflamatory factors PGE2 etc would possibly partially activate pregnancy implatation / breast activation type activity in the breast as well as uterous.

Pregnacy produces increased demand for DHA production.

Could this combination of factors with high oxidation stress due to constant inflamatory pressure, combined with a self-fuelling cycle of forcing oestrogen levels up as the body tries to activate the FAS pathway to make DHA both for milk provision and series three eicosanoid inflamatory damping have implications fro some tyes of breast cancers?.

Trials I have seen suggest the same growth factors are involved in attachement in the placenta etc. (see below)

Interesting growth factors were higher in the placenta in pre-eclampsia and DHA has been reported as moderating the condition.

My searches did not find much on pregnancy and HEr 2 growth factors - should their be more corss exchange of ideas - or have I not searched with the right words.

Clearly from what I have seen the derivates of omega six AA have very fundamental roles in the body and reproduction what ever link they have to inflamatory disease and BC. The complexity is truly wonderous.

Thanks for the post Tom that lead on on this latest wander.

RB













http://72.14.221.104/search?q=cache:...ient=firefox-a


Increased adiposity is associated with a rise in systemic inflammation (1-4) and oxidative stress (5,6).
Both processes may accelerate telomere erosion in leukocytes, because inflammation enhances the
turnover rate of leukocytes and oxidative stress heightens the loss of telomeric repeat per cell replication (7). Such mechanisms provide a potential explanation for findings of accelerated leukocyte telomere attrition with a rise in insulin resistance and a gain in the body mass index (BMI) in a
longitudinal study (8), and the inverse correlations of leukocyte telomere length with insulin resistance (unpublished data), serum leptin and BMI (9) in cross-sectional analyses of relatively large populations. What’s more, it appears that leukocyte telomere dynamics (telomere length and attrition rate) are influenced not by the body mass per se, but by mechanisms linked to obesity, expressed in elevated insulin resistance and leptin levels........

......Another alternative explaining the absent association between leukocyte telomere length and insulin resistance in postmenopausal women is the dramatic decline in overian steroid hormones— particularly estrogen—during the postmenopausal period. Estrogen may be linked to leukocyte Page 10
10 telomere dynamics through its anti-inflammatory and anti-oxidant attributes and by its ability to stimulate telomerase, a reverse transcriptase that elongates telomere ends (24). Estrogen is a potent anti-inflammatory agent, because it lowers the production of cytokines, including
the pro-inflammatory, tumor necrosis factor-α (TNF-α) (25-28). Depending on tissues examined, insulin resistance may arise from or be caused by oxidative stress (29-32). One of the factors that defend against oxidative stress is estrogen (32-34). The anti-oxidant activity of estrogen may also mediate its anti-diabetic property (35). Estrogen serves as an anti-oxidant by mechanisms that are not fully elucidated, but appear to be exerted via membrane/cytoplasmic receptors (36). Estrogen stimulates the mitochondrial superoxide dismutase (Mn-SOD) and glutathione peroxidase (Gpx) (32),
two powerful enzymes engaged in the metabolism of reactive oxygen species. Since neither Mn-SOD nor Gpx have an estrogen responsive element in their promoter regions, a direct genomic effect in
this stimulation is unlikely................



http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum


1: J Endocrinol. 2000 May;165(2):443-56.Click here to read Links
Placental lactogen-I gene activation in differentiating trophoblast cells: extrinsic and intrinsic regulation involving mitogen-activated protein kinase signaling pathways.

* Peters TJ,
* Chapman BM,
* Wolfe MW,
* Soares MJ.

Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

Trophoblast giant cells are one of the primary endocrine cell types of the rodent placenta. Placental lactogen-I (PL-I) is the initial prolactin (PRL) family member expressed as trophoblast giant cells differentiate. In this report, we use the Rcho-1 trophoblast cell line as a model for studying the regulation of PL-I gene expression during trophoblast giant cell differentiation. Evidence is provided for trophoblast cell expression of epidermal growth factor receptor (EGFR), ErbB2, fibroblast growth factor receptor 1 (FGFR1), transforming growth factor-alpha, and heparin-binding EGF. EGF and FGF-2 stimulated PL-I mRNA and protein accumulation and PL-I promoter activity in a concentration-dependent manner. These latter growth factor actions on PL-I promoter activities were specifically inhibited by cotransfection with dominant negative constructs for EGFR and FGFRs respectively. Utilization of the mitogen-activated protein kinase (MAPK) pathway by EGF and FGF-2 in trophoblast cells was demonstrated by growth factor stimulation of a Gal4 DNA binding/Elk1 transactivational domain fusion construct, and more specifically by activation of extracellular signal regulated kinase and p38 MAPK. PL-I gene activation was also sensitive to disruption of MAPK and activation protein-1 (AP-1) signaling pathways. In conclusion, autocrine/paracrine pathways involving EGFR and FGFR1, MAPK and AP-1 are shown to participate in the regulation of the PL-I gene in differentiating trophoblast cells.

PMID: 10810308 [PubMed - indexed for MEDLINE]


1: J Neurosci. 1999 Nov 15;19(22):9913-27.Click here to read Links
Neuregulins signaling via a glial erbB-2-erbB-4 receptor complex contribute to the neuroendocrine control of mammalian sexual development.

* Ma YJ,
* Hill DF,
* Creswick KE,
* Costa ME,
* Cornea A,
* Lioubin MN,
* Plowman GD,
* Ojeda SR.

Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton, Oregon 97006, USA.

Activation of erbB-1 receptors by glial TGFalpha has been shown to be a component of the developmental program by which the neuroendocrine brain controls mammalian sexual development. The participation of other members of the erbB family may be required, however, for full signaling capacity. Here, we show that activation of astrocytic erbB-2/erbB-4 receptors plays a significant role in the process by which the hypothalamus controls the advent of mammalian sexual maturation. Hypothalamic astrocytes express both the erbB-2 and erbB-4 genes, but no erbB-3, and respond to neuregulins (NRGs) by releasing prostaglandin E(2) (PGE(2)), which acts on neurosecretory neurons to stimulate secretion of luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual development. The actions of TGFalpha and NRGs in glia are synergistic and involve recruitment of erbB-2 as a coreceptor, via erbB-1 and erbB-4, respectively. Hypothalamic expression of both erbB-2 and erbB-4 increases first in a gonad-independent manner before the onset of puberty, and then, at the time of puberty, in a sex steroid-dependent manner. Disruption of erbB-2 synthesis in hypothalamic astrocytes by treatment with an antisense oligodeoxynucleotide inhibited the astrocytic response to NRGs and, to a lesser extent, that to TGFalpha and blocked the erbB-dependent, glia-mediated, stimulation of LHRH release. Intracerebral administration of the oligodeoxynucleotide to developing animals delayed the initiation of puberty. Thus, activation of the erbB-2-erbB-4 receptor complex appears to be a critical component of the signaling process by which astrocytes facilitate the acquisition of female reproductive capacity in mammals.

PMID: 10559400 [PubMed - indexed for MEDLINE]
Related Links


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

Glia-to-neuron signaling and the neuroendocrine control of female puberty. [Recent Prog Horm Res. 2000] PMID: 11036938
Normal female sexual development requires neuregulin-erbB receptor signaling in hypothalamic astrocytes. [J Neurosci. 2003] PMID: 12514220
Glial-neuronal interactions in the neuroendocrine control of mammalian puberty: facilitatory effects of gonadal steroids. [J Neurobiol. 1999] PMID: 10453054
Epidermal growth factor tyrosine kinase receptors and the neuroendocrine control of mammalian puberty. [Mol Cell Endocrinol. 1998] PMID: 9722176
Neuron-to-glia signaling mediated by excitatory amino acid receptors regulates ErbB receptor function in astroglial cells of the neuroendocrine brain. [J Neurosci. 2003] PMID: 12574420

See all Related Articles...

Display

[R.B.]

And another link to reproduction - growth factors involved at a very fundamanental level.


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_DocSum

1: Dev Biol. 1999 Nov 15;215(2):399-406.Click here to read Links
Members of the ErbB receptor tyrosine kinases are involved in germ cell development in fetal mouse gonads.

* Toyoda-Ohno H,
* Obinata M,
* Matsui Y.

Department of Cell Biology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1, Seiryo-machi, Sendai, Miyagi, 980-8575, Japan.

To isolate the genes involved in mouse primordial germ cell (PGC) development, we carried out subtraction cDNA cloning between PGC-derived embryonic germ (EG) cells and inner cell mass-derived embryonic stem cells. Among the genes preferentially expressed in EG cells, we found a gene encoding a receptor tyrosine kinase ErbB3. By in situ hybridization and immunohistochemical staining, the expression of ErbB3 as well as that of ErbB2, a coreceptor for ErbB3, was detected in PGCs in genital ridges at 12.5 dpc (days postcoitum). The expression was, however, downregulated at 14.5 dpc when the PGCs underwent growth cessation. Neuregulin-beta, a ligand for ErbB2 and ErbB3, was also expressed in genital ridges. In addition, a recombinant Neuregulin-beta enhanced the number of PGCs in 12.5-dpc embryos in culture. Taken together, these observations suggest that ErbB signaling controls the growth or survival of PGCs in genital ridges. Copyright 1999 Academic Press.

PMID: 10545246 [PubMed - indexed for MEDLINE]

[Emmay]

My sister was told that having a breast-conserving lumpectomy would be just as effective as a mastectomy, so she had the lumpectomy for the 2.3cm tumor, clear margins, no positive lymph nodes. She wasn't even done with chemo when she found two local recurrences 6 months after the lumpectomy, which then, of course, mandated a mastectomy. Her oncologist said a recurrence that soon while still on the strongest chemo was very unusual. She started Herceptin soon after the mastectomy, had radiation to the site of the mastectomy, and 5 months after completing radiation she was diagnosed with brain mets. I can't help but wonder - if she'd had a mastectomy initially instead of a lumpectomy, and if Herceptin had been available then for earlier stage bc - if the cancer might have been fully arrested.

As I have said before on this site.....I had clear margins but they found a tumor in my supraclavicular node. If you have a breast tumor with positive nodes....doesn't that say that the margins are NOT clear. The lack of logic in this just baffles the mind!!! RB my understanding is that the ER pathway is not understood. I only wish it was.

Cathy

[StephN]

TOm -
I guess I was not clear in my post - too busy mulling over the info you put up.

I was talked out of the mastectomy. The tumor was close to the chest wall, but they thought they had a wide enough "clear" margin. I am not a busty person, so did not have a whole lot of room.

Several women here have posted having a mastectomy when the margins are not clear after initial lumpectomy was tried. Hopefully better imaging will save these double surgeries.

I did have breast MRIs just prior to my lumpectomy which were supposed to give an accurate picture of my disease at that time.

[dlaxague]

This information about margins doesn't fit with the many studies that show similar survival outcomes for lumpectomy vs. mastectomy. Even local recurrence figures are not drastically different.

In reading the responses to this interesting article, it seems that we are beginning to compare apples and oranges. Dirty margins and unstable adjacent tissue would be most relevant to local recurrences. Distant metastasis have little relationship to tumor margins, unless they happen after/from a local recurrence. If distant mets happen, those cells were out of the barn before the door was closed (with whatever surgery was done), and imho distant mets probably happen vascularly, with spread to lymph nodes simply being a marker for ability of the cancer to move distant from the tumor. It's not as if most (or any?) distant metastatic spread is thru lymphatics, right?

Debbie L.

[StephN]

Hi -

In response to the above.
My lumpectomy was supposed to have the "classic" clear margins, but the lymph nodes were already affected with the sentinal node biopsy. Then the lower axilla was resected and 5 of 15 nodes positive.

I was stage IIb and still considered "high risk" due to HER2 status.

If the sentinal node and those adjoining are positive, but tumor is confined to the capsule as in my case, there are more than likely "hidden" margins with the problems outlined in the article.

To me the cancer cells can get out through any channel they choose.

[Tom]

Steph,

I apologize. it was my understanding that you DID insist on a mastectomy. From a closer examination of your post however, I believe the only thing you had to gain by getting the mastectomy originally, was a reduced chance of LOCAL recurrence, as you indicated that you already had axillary involvement. My Mom's tumor was right up against the chest wall, and I knew then it was going to be trouble. My mistake with Mom was not being forceful in seeing to it that the surgeon did a sentinel node biopsy. That would most likely have shown the micrometastes in her axilla, that went on to develop into a 12/20 node involvement over the following months, requiring her to go through a level II axillary dissection, rather than a radiotherapy approach to the axillary micromets. The surgeon took one enlarged node at the time of the original surgery, and found it to be free of malignant cells, giving all involved a false sense of well being regarding axillary spread. When she subsequently discovered that the cell type was not estrogen sensitive, as she virtually assured me it would be earlier, the poop hit the fan. The lumpectomy was suggested based on the suppostion that the tumor was ER+ and would be easily managed even without rads, but Tamoxifen alone. Her plan was to deal with any local recurrence through additional surgery later. So much for pre-surgical assumptions without biopsy.

Debbie,

My understanding of this disease, is that lymphatic spread is the most likely first route of the cancer, followed by vascular invasion. Surgical biopsy either prior to or during surgery, can be a crap shoot with respect to identifying metastatic prognosis. If you don't happen to find an invaded lymph duct or blood vessel in the slice being studied, you can't conclude that there is neither type of spread happening at the tumor bed site. Of course, as you mentioned, the lymph node studies, whether via sentinel node biopsy or extensive dissection, are the primary indicator used to determine risk of metastasis. I feel that the examination of the surgical margins is but one of a series of what amount to "clues" to metastatic risk, rather than a very accurate marker of such risk, and that the surgical margin taken predicts only the odds of local recurrence, if even that. It has been shown of course, that even women with extensive identified distant metastases prior to any surgery, benefit from attempts to remove as much of the primary tumor as possible, as this reduces the tumor overall tumor load, and improves the effectiveness of subsequent chemotherapy of any kind. If anyone has seen, heard, or read anything different than what I have described, by all means, please correct me.

Tom

[mts]

I was wondering if the recurrances your sister had were actually tumors that were already there from the beginning... Does she have dense breast tissue? Did she have a breast MR aside from the usual mammo at diagnosis? I had my MRI after my lumpectomy and two more tumors were found adjacent to the original tumor... and I had clear margins after the first lumpectomy. I think all the previous conversation regarding growth factors and lymphatic spread etc are important, but accurate physical imaging is very important too so we can decide what course of treatment to take.

Maria

[Shell]

Tom-

don't beat yourself up over the treatment your mom got - I had neo-adjuvant chemo, then lump, then SNB, (all clear, but a few micromets), then chemo again, then radiation and more chemo - and I still had my first reoccurrence to the axilla lymph nodes...
Shell

[dlaxague]

Hmm, 'can't figure out how to select out your words, Tom, and reply to your points one by one. When I choose "reply with quote", I can't see the quote. Anyway....

I don't know that lymphatic invasion precedes vascular. Do you have evidence to support that? How then to explain distant mets when lymph nodes are not involved? Again, I think that lymph node involvement is just a convenient and obvious marker of metastatic abilities of that particular cancer, an ability that not all cancer seems to have. But absence of lymph node involvement yet later distant mets doesn't mean that axillary involvement was necessarily missed, does it? The axilla could indeed be clear (as opposed to involvement being missed), and the surgical margins be clear, yet the cancer could have moved into the bloodstream before surgery and some of those cells could have found safe haven in the site of eventual mets. How they do that, how to know which cancer CAN do that, and how they evade tx there is the mystery. One of the mysteries.

As for removing the tumor and/or all the cancer cells being important to prognosis - yes, it's important to remove the primary, but the picture gets muddier when trying to prove the importance of removing cancer in lymph nodes. Logic tells me that should be important, but there's not much research to support it. I've know women who have declined axillary dissection even when there was clinically-evident lymph node involvement there, if the nodes shrank during neoadjuvant chemo. Their oncologists could not provide evidence that removing those involved nodes would change the outcome.

I think (hope) that what we're discussing about margins and lymph node status will become moot, as far as using the information prognostically or predictively. I hope that soon we'll look mostly at cell characteristics and from that will know the degree of threat of distant metatastatic potential of each tumor and be able to treat it accordingly, and with the best treatment for that particular tumor. But we're not there yet.

The bit about removing the primary even with concurrent extensive distant mets is so intriguing. There's got to be more to it than simply tumor load, because we know that in women with extensive distant mets (who had the primary removed at primary diagnosis), there is rarely an advantage to doing surgery to decrease the tumor load (unless it's one isolated and accessible site) and that the cancer responds (or not) to the treatment pretty much regardless of tumor load (ie, many large lung mets may shrink to nothing, just as a few small single ones would do).

So many questions yet to answer. Interesting discussion - thank you!
Debbie L.

[VaMoonRise]

Hi, Everyone, it has been a while since I last posted anything. I have been tied up with the research focus group survey lately. I am still on the clinical trial of Herceptin, Taxol, Tykerb (Lapatinib) and Zometa. I am tolerating the side effects fairly well and am responding greatly to the treatment.

I am not sure if this is relevant to the topic or not. You all seem much more knowledgeable on the subject than I but I found the discussion to be very interesting.

I was first diagnosed with DCIS stage "0" in March of 2004. I went through a lumpectomy and radiation with no node removal. They even went back in a second time and removed more tissue to recheck the margins which once again came back clean. They assured me that they had removed all of the microcalcifications that were present and that I was now cancer free. I continued to have mammograms and checkups done every six weeks. I thought that I was very blessed to have caught it so early and was thankful that I didn't have to have a mastectomy.

In December of 2005 I came down with a gall bladder attack and when they went into remove it they were shocked to find cancer spread extensively throughout my liver, I also have two spots on my spine. The doctors seemed to be completely baffled as to how this could have happened. The only explanation they had was that a stray cell must have been missed and that it had entered into the blood stream. They still do not believe that there was any node involvement and they keep telling me that even if they had removed the entire breast that the results would still be the same. I have been plagued with the over whelming feeling that if I had opted for a mastectomy instead of a lumpectomy that I may not be sitting where I am today.

I worry about other women who are initially told that they have DCIS and are stage "0." I worry that this could happen to them too. I kept hoping that new research would come out that would possibly change the way they go about diagnosing and treating DCIS and other early stage breast cancers.

Some of what I have read here on these posts regarding this topic of hidden margins is difficult for me to understand. Are these new findings suggesting that new techniques should take place in the initial diagnoses and treatment of early stage breast cancers?

Can someone please explain these findings and what they mean in laymen terms that I can better understand.

Thank you so much everyone, I truly appreciate all of your great insight and depth of knowledge on the subject.

Sincerely,
Nicola

Nichola;

I think it is possible that your cancer simply did not travel via the underarm lymph nodes. My nodes were negative but the cancer had chosen another way to spread.....upwards via my supraclavicular node where a 1 cm tumor was found. I think it is fairly obvious in my case that the cancer was also other places as well. I received agressive chemo with AC and Taxol and commencing the last Taxol (4 of each AC and Taxol) herceptin followed by radiation, arimidex and now actonel. My worry now is that I have been off herceptin for 3 months (began it in July, 2005) and worry about spread. I do not trust clear margins period.....never have. My view is that all with her2+ bc regardless of stage should get chemo.

Cathy

[Jean]

Interesting - from the on start of my dx. I have not trusted the facts given to me by the dr. It just did not make sense - many many women who were early stagers with no node involvement - were having progression. When I asked one onc did he believe that the main pathway was the lymph nodes? He stated that 25 yrs ago that was the belief - but that today we know that the blood circulatory system can pass the cells. As one oncology resource nurse told me from NCH - compare the lymph node to a basket that sits in the drain of a sink. It's purpose is to catch and filter out - now that basket has small tiny holes does any food particles get past the basket such as a small tomato seed? These cancer cells love to travel and set up shop elsewhere - my margins were large 25MM after removal of a 3MM tumor. (I was not impressed nor did I feel it was as favorable ) as the surgeon said it was. Was not or never will be comfortable making treatment decisions based on these factors. Rather I am deeply convinced (as Debbie) that the cell characteristics are the factors to examine. I do feel that a short time from now the future treatments will be decided upon the character of the tumor and the cells. For those that are early stagers way too many are experiencing recurrance! Currently many early stagers are now approaching their treatment decisions based on different factors. There is a study being conducted at Cornell with early stagers node negative - where the surgeon is doing a bone biopsey along with lumpectomy to test for the presence T cells. I had tried to get into this trial but was unable. I have lost two friends who both made the decision to have a mastectomy both were early stagers - they did not have any radiation.. I lost both of them within ten years! Much has changed in the last 8 yrs. since I lost them in the treatment of bc. The information the dr. gathers about a tumor's margins is important for treatment but does not usually influence your prognosis or the likelihood of recovery without metastasis or recurrence. We must always remember our bodies are complex and there are still many unanswered questions. I am doing all I can to deal with my bc (I like Cathy) believe in aggessive treatment against an aggessive disease. I am concerned for the newly dx. women who are told "don't worry we caught it early" I shake when I hear that. Being a history buff I often think of the Civil War when the poor soliders had their limbs removed without anesthesia, sounds mid evil. Well I feel the same sense of mid evil practice when a onc. says your tumor is small therefore your lucky...your cancer was caught early..etc. well that does not mean that it has not already moved along. Also, it is important to realize that while mastectomy removes nearly all of the breast tissue, a small amount remains. So, although this operation markedly reduces the risk, a cancer can still develop in the breast tissue remaining attached to the skin after surgery. There has been great documentation on women with a small tumor who choose lumpectomy and radiation can expect the same chance of survival as those who choose mastectomy. There are many many questions yet to be answered. I pray each and everyday for all of us and I desperately pray for a major break through on cancer treatment. I even dream of it and when I wake up I am sad - because it is a dream. But I will not give up my dreams. As my husband said to me during my herceptin treatment today - "Now it is in God's hands"


Jean

New to site tonight, reading with interest as I was diagnosed in April with HER-2 multifocal via core needle biopsy. Chose to research and decided on Burzynski targeted therapy with antineoplastons as this seems to be a "whole body" cancer; why cut/irradiate/non-selectively medicate was my thinking when it can be addressed on the genetic level. Talked to patients, most of whom had gone traditional route and, failing that, had turned to Burzynski protocol with success. I am three weeks into therapy, daily taking liquid and tablets -- no side effects. Herceptin infusions every two weeks.
As far as clear margins, ScienceDaily reported on new imaging technique for use during surgery; worth a google.
Hope this helps others; I have been blessed by your postings and information. -- tina in texas

[dlaxague]

Hi Nicola,

You asked: Some of what I have read here on these posts regarding this topic of hidden margins is difficult for me to understand. Are these new findings suggesting that new techniques should take place in the initial diagnoses and treatment of early stage breast cancers?

Can someone please explain these findings and what they mean in laymen terms that I can better understand.

I don't think that these findings are suggesting anything yet. They're really just asking more questions, based on their observations about cells in the vicinity of the cancer. Researchers are looking at the cells near the cancer from many different perspectives, because they're realizing that there is interaction between them and the cancer cells themselves. The way that interaction goes probably has much to do with what happens regarding cancer growth. Although they're learning more and more about this, each new understanding brings yet more questions to be answered and it will probably be awhile before this knowledge translates to understanding about better treatment.

The particular study that started this discussion has interesting implications. What if they DID find a biomarker that could "detect the field prior to the development of frank cancer"? What would they DO about that? Mastectomy seems harsh enough for DCIS - would women want that solution for a condition that may or may not someday become cancer? Our perspective (women already diagnosed) may not be the same as the average woman-on-the-street's, and I hope that in addition to looking ways to detect this "early" stage of precancer, they are making progress re: what to do when it's found. Many questions remain - the first that occurs to me is to wonder how many breasts have these abnormal cells (and perhaps the theoretical biomarkers that accompany them), yet never develop cancer? It's interesting information for discussion and brain-play but nowhere near to being useful in real life (yet).

Debbie L.