Dr. Theresa L. Schwartz, Assistant Professor/St. Louis University, recently published a review of all of the current data on the characteristics, prognostic factors and treatment strategies for metaplastic breast cancer. The review is titled “Metaplastic breast cancer: histologic characteristics, prognostic factors and systemic treatment strategies” and can be found at this here. Dr. Schwartz graciously agreed to answer questions regarding her review and what she learned about metaplastic breast cancer.
Q: Some of us have been told “this is not breast cancer.” What are your thoughts on this? Our understanding is that MpBC doesn’t arise out of the same glandular tissue as IDC/ILC and some of our tumors contain no element of IDC/ILC at all. Your study discusses “Unsupervised clustering disclosed distinctive expression profiles between MBC and IDC.” which suggests that it is breast cancer.
A: I would say that MBC is definitely a breast cancer. Unfortunately, it has so many possible differentiation factors that it doesn’t look like the textbook breast cancer that accounts for almost all other cases. It appears to start within the functional unit of the breast (either duct or lobule), but goes through such significant changes (hence the metaplastic descriptor) that it just doesn’t look like your every day breast cancer under the microscope or based on how it acts. Now exactly why this is–I can’t say with certainty. However, all current research on the histology of MBC describes a cancer that started within the breast and subsequently went through one of several differentiation patterns to look very different from the most common histologic types of breast cancer.
Q: Is the Triple Negative aspect of the tumor relevant? Should we be classified as a separate tumor type since TNBC first line chemo regimens are not effective for as many as 50% of us?
A: The triple negative aspect is most definitely important. I don’t believe that it should be separated out as a something different because the triple negative descriptor just lets us know that the targeted therapies that are available to women who aren’t triple negative (anti-estrogen therapy, Herceptin) will not work in a patient who is triple negative. Being triple negative doesn’t change what type of standard chemo regimens would be recommended–it only dictates what targeted therapy a patient is a candidate for. And you are correct–most chemotherapy does not work on MBC. That is why targeted treatments aimed at what makes MBC tick are what further bench research should be focusing on.
Q: What is your opinion of the value of the sub-typing? Is there any clinical or prognostic value in knowing the sub-type of the tumor? Many of out tumors are a mixture of more than one of these elements. Spindle/squamous. Matrix-producing/spindle etc…
A: I don’t think the sub-typing adds to my clinical decision making at all. Hearing “metaplastic” is all I need. My treatment planning wouldn’t change based on the sub-type. Its really just a histologic descriptor. Hopefully one day that will change.
Q: We often hear about basal-like and claudin-low tumors. Is there any correlation between which sub-types (Spindle, squamous, carcinosarcoma) are basal-like and which are claudin-low? Is there anyway we can find out if our individual tumors are basal-like or claudin-low? Is there any clinical or prognostic value to the basal-like or claudin-low designations?
A: I honestly haven’t heard of any research looking into sub-types of MpBC based on basal like or claudin low histology. Since MpBC is so rare, they are usually grouped as one disease and just described as MpBC. Basal like and claudin low tumors are pretty similar–basically because they are both triple negative tumors. Right now, the histologic classification is most important for chemotherapy decision making. I am hopeful that one day we can look at a basal like or a claudin low or a luminal A or luminal B or a Her2 tumor and know exactly what chemo regimen is the most beneficial–meaning we would know exactly what makes that tumor grow and we target it. Plus, the claudin low classification is relatively new…only been out there for a few years. There is a lot of research yet to be done to figure out exactly what to do with it.
Q: I would like to understand why in most articles they say metaplastic is more aggressive and has a poorer prognosis. But when you read the newer stuff it says with treatment it has a similar prognosis. It’s confusing.
A: Metaplastic cancer is more aggressive. It is less responsive to chemotherapy and more likely to recur locally. We really just need to change gears on how we treat it–like going to the operating room first and treating systemically later. Breast cancer overall is a very survivable disease. I am wondering if you are referring to studies that have looked at outcomes based on stage. Stage IV standard breast cancer has the same poor prognosis as stage IV metaplastic breast cancer. The trick is detecting at an early stage and getting local control as soon as possible. But, without question, metaplastic cancer is a more locally aggressive tumor.
Q: At what point does a tumor become officially categorized as Metaplastic? How many of the abnormal cells have to be like that to get this classification?
A: It isn’t the number of cells exactly–it is really how the pathologist sees them under the microscope. And this may not be apparent on a core biopsy. I had a patient recently who had standard invasive ductal carcinoma on core needle biopsy and then metaplastic cancer on excision. Just depends on how it looks to the pathologist. And they don’t look at the entire tumor–they take representative sections and evaluate those. So as long as they see metaplastic changes, that’s probably all they would need to make the diagnosis.
Q: Is Squamous Cell Carcinoma the same as Metaplastic Carcinoma with squamous differentiation?
A: Squamous cell cancer is a cancer that started from the lining of something–GI tract, lungs, skin, bladder, etc. When we talk about squamous cell differentiation, we are indicating that under the microscope the lining of the lobule or the duct has changed in the same manner that a squamous cell cancer would–but it doesn’t exactly look like a standard squamous cell carcinoma. I know that is still a pretty vague answer, but I think this is a pretty difficult concept to grasp. So, they are very similar, yet not the same.
Q: For patients with an Osteoclastic Giant Cell sub-type, should they be concerned about taking supplements like Vit D or K or calcium or about getting a high intake of these through diet? Will that potentially activate the cancer?
A: I have no evidence of vitamin supplementation through diet or otherwise being a problem. Maintaining a healthy diet is actually of the utmost importance and until someone proves it wrong, getting all of the vitamins and minerals that your body needs is strongly encouraged. Your heart, bones, skin, vision, energy level and liver will thank you…
Q: Is there any data on LR or second tumors? How often are they the same kind of MpBC? Is it common for the second tumor to be more aggressive, graded higher, or a different sub-type?
A: I have not seen any data on the sub-type of MBC in a local recurrence. In fact, in the two patients that I have seen recur in the last two years, the pathology report doesn’t even describe the sub-type–metaplastic is really all we need to know from a clinical standpoint. However, if we get more targeted therapies in place, the sub-type can actually become a useful predictor of treatment response instead of just a pathologic adjective.
Q: We know MpBC tumors can over-express EGFR and can have Pi3K mutations, are there any other obvious targets we should be looking at to help improve MpBC prognosis? Your study discusses the P53 gene mutations specifically. Is this a targetable gene or pathway?
A: Table 2 in the article discusses the possible targets that could possibly be used for targeted therapy. There are several and we will hopefully see some research results in the future–unfortunately, creating a drug and getting it on the market usually takes decades. As for p53, it is less of a drug target and more of a reason that a tumor developed in the first place. p53 usually acts as a tumor suppressor. When there is a mutation in p53, that tumor suppression is lost–hence more tumor growth. We can’t really target this, but it is good to know where the genetic breakdown happened–mainly because that patient would also be at risk for many other cancers as well.
Q: Could you comment on the value of genetic testing or molecular profiling of tumors? Are all of the tests currently available the same or should we look for certain information when requesting such tests?
A: The value of molecular profiling is in determining what drugs can target which cancers. Not much you can
request necessarily because they are more of a guide for your medical oncologist to determine treatment strategies and they are pretty standardized. With future studies, these sub-types will hopefully become more and more important in determining chemotherapy regimens.
Q: Regarding your study, could you define carcinomatous component (CC) and a heterogeneous sarcomatous component (HSC) in plain English? I am familiar with the two theories of Epithelial to Mesenchymal transition and a stem cell origin for MpBC but in you discussion, I don’t follow the CC and HSC description.
A: This is a very difficult concept to explain–even in scientific terminology. The basic importance of it for metaplastic breast cancer is that MpBC looks like it has the characteristics of (and also acts like) both a carcinoma as well as a sarcoma. These two cancer types look differently, act differently and get treated differently–hence why MpBC can be so difficult for everyone involved to treat. The cells in the standard carcinoma pathway undergo a metaplastic change (at least that is the theory) and subsequently develop a MpBC.