News: DCIS shouldn't be called cancer?

Recall, I said I asked one of the researchers at Sloan Kettering a few questions about DCIS.  Here is what the researcher said:

  A) I recall you mentioning that the DCIS grading system was not the same as the grading system for invasive BC. Why have many of us with mucinous BC have DCIS of a different grade? Why does this occur?

Reply: A) You are indeed right that grading is not necessarily done in the same way for DCIS and invasive BC. The histological grade of invasive BC is a composite of three parameters: 1) tubule formation (how much a tumor has retained normal breast duct structures); 2) nuclear grade (size and shape of the tumor cell nuclei); and 3) mitotic rate (number of dividing cells). Each of these parameters gets a score between 1 and 3. The total score can therefore range from 3 to 9, where a total score of 3–5 is grade 1 (also called low grade or well differentiated), 6-7 is grade 2 (also called intermediate grade or moderately differentiated), and 8-9 is grade 3 (also called high grade or poorly differentiated). Given that DCIS grows inside a duct, it cannot retain a duct structure in itself (parameter 1), so usually the grade of DCIS is determined by parameter 2 only, the nuclear grade, which may be a reason for a discordant grade between DCIS (nuclear grade only) and invasive BC (histological grade out of 3 parameters).

Whilst high-grade DCIS is often associated with high-grade IDC , it is not unusual to see a low- or intermediate-grade DCIS associated with an intermediate- or high-grade invasive breast cancer, respectively (even when the grading is done in the same way). Why does this occur? It is thought that the estrogen receptor-positive invasive BC may progress from low to high grade due to the accumulation of stochastic genetic events, much more quickly than the DCIS (see also the last point on the bottleneck). By the time the diagnosis is made, the invasive BC may have acquired many more faults in the DNA than the DCIS, which is why the grade may be distinct. Alternatively, some have argued that the invasive BC may not always arise from a given DCIS (as DCIS is not uncommonly multifocal), and that these are independent events, which is another explanation for this phenomenon.

2)    There is respective correlation between low and high grade DCIS and invasive BC. Is that correct?

Reply: That’s correct a high-grade DCIS usually evolves to high-grade invasive BC, whereas low-grade DCIS often, but not always, evolves to low-grade or intermediate-grade invasive BC.

3)    You are more interested in the biological components of the lesion and place less emphasis on the grading.  

Reply: We are interested in the genetic aberrations required for a DCIS to progress to invasive BC to help us understand the biological process itself. In the long-term, we would of course like to use this information to develop markers that could help us predict which DCIS are likely to progress to invasive BC, and which are likely to stay within the duct and never progress.

 Jorge is a firm believer in the clinically relevant information offered by grading, but we both acknowledge the fact that it is an imperfect tool that can be complemented (and not necessarily replaced) by additional molecular methods that may tell us i) who needs systemic treatment, ii) what the best treatment for an individual patient is. Germane to this endeavor is the understanding of the biological and molecular phenomena involved in the progression from DCIS to invasive breast cancer. Without knowing how this happens, the predictors developed would only constitute ‘black boxes’.

4)    Could you tell me what you mean by "evolutionary bottleneck?"

Reply: In population genetics a “bottleneck” refers to a reduction in size of a population due to a catastrophic event, for example an earthquake. Given that the population size reduces, such events also reduce the variation in the pool of genes that is passed on to the next generation. The survivors of such events are often the “fittest” individuals. We propose that a similar event is happening when a DCIS is progressing to invasive breast cancer. The bottleneck for the tumor cells is to break through the walls of the milk duct and survive and grow in a new environment (loads of fat tissue, other cell types and the immune system – hence, lots for the tumor cells to contend with). We further propose that not all cells within a DCIS are equal in terms of their genetic make-up and that only those cells, which harbor a certain constellation of genetic aberrations (i.e. the fittest cells), are able to progress to invasive breast cancer. If you like the theory of species put forward by Darwin, this is simply an exercise of applying Darwin’s thinking (and the thinking of his successors in evolutionary theory) to the question of the development and progression of breast cancer.

Beesie...oh, but they should be listening to you!

Beesie....hmmmm....I had Stage 1, Grade 1 mucinous BC. My DCIS was Grade 2... Based on what the folks at Sloan said, if my intermediate DCIS had the potential to become a more aggressive BC, perhaps I should have been treated even more aggressively...But I wasn't. My treatment protocol was based on the invasive component of my disease and ultimately, my treatment was little different from how we presently treat most DCIS. With that said, I've always wondered if I was over treated.



Furthermore, I learned something new from the Sloan researchers. They mention the bottleneck and Darwin's survival of the fittest in describing some cells that turn invasive and break through the duct to become invasive. This is interesting and similar to how invasive cells behave. Not all invasive cells are alike. Last year a researcher reported that he doubted the accuracy of the genetic tests that we have to determine how aggressive a tumor is and the need for chemo. He postulated that if the "wrong" part of the tumor specimen is studied, you might not get accurate information.



So, it seems that not all DCIS cells behave alike nor do invasive cells either. Yet, once a lesion is identified, whether non-invasive or invasive, all patients still need to make treatment decisions based on imperfect information.

The really scary thing is...many women on this forum have been diagnosed with DCIS, but surgery has revealed IDC as well. So to not treat would have been deadly.



Paula

Very interesting discussion...

You also have to consider a lot comes with the pathologist. My last surgical biopsy showed "rare ductal changes," "unusual calcifications" and "crushed artifacts." After multiple ADH lumpectomies and an insane family history, I decided to get a mastectomy rather than go through another lumpectomy. I had some very interesting reactions when I sent my results to prospective plastic surgeons. Three would not even discuss anything with me because they feared a high stage cancer. Another said it was classic DCIS.

In the end, all of those strange things came back as ALH - the ducts in that area were fine!

One more thing to nbnotes... Nearly every female on my mother's side (including my mother) has had breast cancer with ovarian and cervical cancer thrown in. Everyone who has been tested is BRACA negative. Mayo Jacksonville is starting a study to try to identify an additional gene. They are looking for families of cancer clusters with no BRACA. You might want to check it out. 

Well, I did say: "That could be a reasonable first step, if the NCI is really itching to make a change now".  That's the context of my suggestion that perhaps grade 1 DCIS could be moved over and reclassified as a pre-cancer. I agree completely that we should not be making any changes until we have better information about the biological factors that influence the risk level of DCIS; I think I've made my position on this clear in my other 53 excruciatingly long posts in this thread!   But we are having this discussion because a working group has suggested to the NCI that ALL DCIS be reclassified as a pre-cancer.  If the powers that be really feel that the line in the sand between pre-cancer and cancer is not in the right place, then moving the line one notch (moving over just grade 1 DCIS) is not as drastic as what has been suggested, which is to move it over three notches (moving all of DCIS).  Moving just grade 1 DCIS would also be consistent with the DIN classificiations.

About 6 or 9 months ago, someone came to the board with a diagnosis of something like 3mm of grade 1 DCIS.  She was frightened and was contemplating having a BMX. I spent a lot of time digging into the research to see what I could find about the risk level associated with grade 1 DCIS.  In the past I'd tended to focus my reading more on aggressive DCIS and DCIS-Mi, because that's my diagnosis, so I admit that I was surprised at what I found about low grade DCIS.  First, one of the concerns everyone has is that some IDC might be found together with the DCIS.  In the case of grade 1 DCIS, if the area of involvement is small, that almost never seems to happen.  It can happen if the grade 1 DCIS is large or multi-focal; but even then, it doesn't happen often. Having large or multi-focal grade 1 DCIS is also rare; more often, grade 1 DCIS is confined to a single spot and it's a relatively small area.  Then there's the question as to what might happen to grade 1 DCIS if it's left untreated.  Certainly it can develop into IDC. I don't have time to dig out the studies now, but I believe that the consensus from the studies is that approx. 25% - 30% of low grade DCIS will develop to become invasive cancer over a 30 year time period.  I also believe (but I would need to recheck the studies) that most often, it takes 10 years or more before we see this type of progression.

So that means that grade 1 DCIS does come with risk, but it's usually not a short-term risk.  Of course ADH comes with risk too so I don't think the eventual goal would be to only reclassify those cases of DCIS that have no risk - if that was the goal, then ADH and other high risk conditions would actually have to be reclassifed now as being pre-invasive cancer/DCIS because these conditions do lead to the development of IDC in a percentage of cases.  The goal in reclassifying DCIS is move over those cases that are low enough risk that there is greater benefit to the patient (from an overall health standpoint) to do just a small excision and then watch & wait (or maybe just watch & wait without excision), vs. identify and treat the diagnosis as cancer and pull out the big guns. 

Does all grade 1 DCIS pass the "low enough risk" bar today?  Probably not, and it certainly would be better if we had a better understanding of the biological factors that influence the evolution of DCIS before any changes are made.  But frankly, I think there may be enough evidence to suggest that low grade DCIS that is small in size and in a single focus might pass the bar.

Of course then there are the issues that screening is not effective at catching the early changes that we need to monitor.  That's one of the biggest concerns for me.  But that's the same issue for ADH, isn't it?

VR, I wouldn't say that having grade 2 DCIS meant that you should have been treated more aggressively.  I just think that having grade 2 DCIS meant that you should have been treated.  And you were.  Keep in mind that Dr. Esserman's position is that "If it doesn't look like high-grade DCIS, we should leave it alone. We would eliminate two thirds of all biopsies if we did..."  So she wouldn't even have wanted you to have a biopsy, never mind an excision. 

redsox, that's a great point! 

Interesting too is that the question about a name change has been going on much longer with LCIS than with DCIS. LCIS is generally not considered to be 'cancer' - there is less debate and disagreement about LCIS than there is with DCIS - and that's because with the exception of pleomorphic LCIS, usually LCIS cells don't evolve to become invasive cancer.  Instead, LCIS is seen to be a marker that indicates an increased risk that breast cancer might develop in either breast.   For years there was discussion about changing the name of LCIS to remove the word "carcinoma".  What was proposed, and what LCIS is called in some (but very few) circles, is Lobular Neoplasia.  It seems however that this name never 'took', and for the most part LCIS is still called LCIS.  Even the NCI and the AJCC staging manual still use the term LCIS.

So if the name "LCIS" hasn't been changed, despite general agreement that LCIS is not breast cancer, and if any over-treatment concerns have been addressed through better communications with patients, why all the fuss about DCIS?

I agree, Redsox...they all suck anyway.

Soteria, I just heard the news a short time ago.  I'm shocked and just so sad. 

This news certainly puts our quibbling about what DCIS is called into perspective.

VR and Ballet: On prior pages you both praise "women's health centers" and getting results the same day. What do you mean?  I went to a a breast center screening facility and I never received results in one day. Is a breast center screening facility not a women's health center?  As a matter of course, everyone came in, then went home and received a letter in the mail a few days later.

Well VR, your current facility is unusual, in that you get to meet with the radiologist even if there are no suspicious findings.  I had that years ago, but not recently.  It must be very reassuring. Even at my esteemed facility (up there with M D Anderson), you don't meet with the radiologist unless you need a biopsy.  The piece of paper they hand the patients, as they leave, also doesn't have a BIRADS score on it, but the patients do eventually get copies of the imaging report from their MD at the hospital (the final report isn't available immediately), with the BIRADS score on it.  I am only getting diagnostic imaging now, so I don't know how they handle screening patients (e.g. do they get same day results?).

What this facility does have is the most advanced imaging quality I have ever seen.  At my previous facility (also part of a large teaching hospital), my dense breast tissue showed up as snow.  At this facility, the imaging is much more clear.

I had a BS at one facility tell me that all the imaging I'd had done at another facility (diagnostic, including mammos, US, galactogram, MRIs) was crap.  Not the word she used, but that was the message, after her breast center's radiology team reviewed all of it.  I moved my case to a large city where I could get the immediate diep reconstruction not available to me at home, and understandably the new BS needed to investigate my needs on her own before agreeing to do a bmx. To this day, I don't know what to believe about what was said. I sure don't think that the quality of imaging is universal, and it's very sad to think that where you live dictates the quality of what should be delivered as a matter of standard protocol.

My sister had breast cancer at 26, it got into the lymph nodes, my mother then got diagnosed when she was 73, in her lymph nodes, I was diagnosed with dcis at 52, that didnt show up on mammogram or sonagram, just a dillon nuclear scan, my cousin was also diagnosed with cancer. I had a mastectomy. There is no way that I could have just watched and waited, especially with all of us having the same estrogen positive.

There are now breast density laws in effect in some states:  Connecticut, California, New YOrk, Texas, Virginia, Hawaii, Maryland, Tennessee, Alabama, Nevada, and Oregon.

And so, in these states, mammogram screening places MUST tell you about breast density, and if you are dense, what the limitations of screening are and what further recommendations should or should not be for you personally...Unfortunately for me, this law was NOT in effect in New York during the years leading up to, and including, the year of my diagnosis (back when I had my breasts and was regularly screened).   Ballet, I must have gone where you go, as it is in NYC and  "up there" with MD Anderson ;o)  For years, at this top notch  screening for breast cancer - only center, I never met with a radiologist after my routine mammograms.  When there was something irregular, then you met the radiologist, and additional imaging was done on site, immediately following. This happened a couple of times. Neither time resulted in anything other than a benign finding, ultimately.  As stated earlier, mammograms missed my dcis/idc completely.

Of course, I am glad for all other women that this law has now been passed and is in effect in New York and ten other states.  Hopefully, Carol57, every state will soon pass this law and then there may be a more national standard of care where everywhere, women are informed of their density and women are informed of mammogram limitations and any further screening recommendations.  If you do not live in one of those states, then you must take it upon yourself to seek out the breast density information as VR explains.  VR, if you do not live in one of the states with the density law, then you are certainly at a great place which is acting as if the law exists as it should exist!  Really, this should be basic standard of care.  We forget though that basic standard of care is different from excellent care.  Standard of care is routine,  everywhere. Excellent care: much harder to find.  Excellent care is more personalized, in my opinion, more nuanced.   I seek excellent care, within the limits of my health insurance. Unfortunately, that's a big limitation, for doctors who want to give excellent care, too. Always it involves more time in discussion, if not more testing (!).

Even though this seems a little off topic  to the DCIS discussion/recommendations,  it does relate. Recall: the professional breast cancer radiologists' society opposed the passing of this beast density law in New York.  They had their reasons which I disagreed with. Something about giving the patient too much information that the patient can misconstrue and not understand, and become insecure and seek further unnecessary testing, etc. etc. Kind of like what we are reading about now with regard to DCIS, and supposedly why it should be  renamed and possibly not treated as aggressively.  

I oppose, based on my personal experience, giving patients LESS information in the paternalistic sense that 'we don't know' how to handle the information.  As I said when I first posted on this thread, in my opinion doctors have a responsibility, a job, to COMMUNICATE with patients.  I know many doctors, like others who deal with the public- aren't necessarily good at it (not the skills tested for med school admission!) or that interested in it.  It is the doctor's job to give us the information that affects our health, and to educate us as to context, limits. The decisions must be ours.  My biggest regret is that I did not have the information I should have had. It is now legislated that radiologists/doctors must provide it.  I blame my prior doctors to some extent but I also blame myself for not digging into it and finding out. I hope to never be in that situation again. That's part of why I post here! To share, to learn.  I unfortunately am a skeptical, somewhat difficult, patient now as I now no longer accept all that I am told as being the full story.  And it's not any fault of my  wonderful doctors since my diagnosis. It's all their predecessors...! 

Jessica...I am all too aware of the position taken by the radiologists' professional organizations when the issue of over diagnosis and over treatment are discussed. Recently, radiologist Handel Reynolds broke ranks and wrote a 92 page gem of a book about the political controversy created by the mammography debate. After reading the book, I wrote to Dr. Reynolds. I thanked him for writing such a bold, courageous and thoughtful book.