all right welcome back so this particular lecture is about subtypes of breast cancer I told you in the last lecture that breast cancer is very very common and I don't want you to get the impression that these are all just because it comes from the breast that these are all the same kind of cancers the breast has different kind of tissues in them and depending on where the tissue comes from you can do you can define a biological subtype and there's few there's molecular subtype which allow for different kind of clinical treatment and so these would be called clinical subtypes so we can subdivide breast cancer both by the cell of origin which would be the biological subtype or the way we treat it which would be the clinical subtype and I want you to understand the differences between these alright so here we have a cross-section of the breast again what you see is different kind of tissues the most common the absolutely most common kind of place from which a breast cancer arises is the ducts those are the milk ducts that connect the lobules right here so the endocrine tissues that make milk with the nipple up front right here it's these ducts right here now tell you why that is such a common site in the next video but it's these ducts from which most breast cancer arises so really when we say breast cancer very often we call it a ductal carcinoma ductal because it comes from the ducts in a carcinoma is a cancer of the epithelial layer of tissues so epithelial layers are linings or coverings of tissues and it is the lining of those ducts from which the most common kind of breast cancer the doctor carcinoma arises if it comes from the milk glands itself could you say we're a rare subtype it would be called a lobule carcinoma and then there's other ones there's even a kind of breast cancer which only I think occurs in about two to five percent of breast cancer cases that is called a inflammatory breast cancer in which there is no primary tumor we cannot identify a primary tumor we know that the whole breast is becomes inflamed and that cells spread very rapidly and kill the patient but there is no tumor that we can define in again this dr. carcinoma right here there is a solid tumor which can be palpable so it can be felt or it can be imaged them and we do mammography screening that's what might look like so you can see this white area here right that's a tumor of the ducts right here that also show up in light okay so that would be a biological subtype so that mean I say breast cancer which you can really a substitute is ductal carcinoma by far the most common biological subtype now then we have clinical sometimes by the way this is my favorite picture of the whole entire year I took this from a promotional material from MD Anderson MD Anderson Cancer Center and it shows a very happy woman right here laying naked on the table with breast cancer and a breast cancer oncologist who looks to be about 19 okay so if you want to have cancer you should go to MD Anderson but anyway I just put as a background right here I want to talk about the clinical subtypes so again a clinical subtypes differs from a biological subtype because it's entirely based on molecular biology or more importantly treatment methodology if we have a kind of cancer for which a treatment works rationally works then that is the clinical subtype and it doesn't matter what the cell of origin is if that's the indicated treatment that makes the subtype then that qualifies as a clinical sometimes and in breast cancer we have three clinical subtypes the first one about 70% of breast cancer is estrogen receptor-positive or progesterone receptor positive sometimes we just call them hormone receptor positive I generally just call a are positive because that's the most income thing so what that means is that the cells in this breast cancer express estrogen receptor okay so this is a steroid hormone a sex hormone receptor which is cytoplasmic right so a sex hormone is completely hydrophobic so it can go through membranes just fine so it's receptor is found in the cell right here so it's not a cell surface receptor which we very often have for hydrophilic molecules so it's in the cytoplasm right here and it binds to estrogen and causes changes now tell you what these changes are in the next video so if a breast cancer has either estrogen receptor or progesterone receptor and this is important appropriately expressed so it retains this this is normal normal breast tissue has both estrogen receptor and progesterone receptor okay if it has these then it is of the STG receptor positive variety most cancers are and thus are the best outcome cancers most survivable breast cancers about 15% of breast cancers are her2 positive but we called her2 positive and it's a bit of misnomer because estrogen receptor-positive means it expresses breast it expresses estrogen receptor and that's normal when we say her2 positive it is an inappropriate and over expression in not right of the her2 receptor the her2 receptor is a growth factor receptor that sits on the cell surface and gobbles up growth factors from the environment and then tells the cell to divide and divide and divide and if you have a normal amount of her 2 then your cells react to signal cues from the environment into growth factors from the environment in a normal way but if you have an inappropriate over expression now you have a growth advantage you can actually grow with more vigorously if you will that's a hallmark of this particular kind of cancer the reason why it's a clinical subtype is because we have a drug with which we can target this the reason why this is a clinical subtype is because we have drugs that can target estrogen and progesterone biceps that's what makes them clinical I don't care if this cancer came from the duct or the lobules or even any other tissues of the breast as long as it has these features I can treat them appropriately and then the last one has neither okay it's we call them triple negative they don't express estrogen receptor they don't express progesterone receptor and they don't over express her2 and those are the most difficult ones to treat because the absence of a target means that your drugs are impotent a drug that works against estrogen receptor wouldn't do anything against the cancer that doesn't express the target if the cell doesn't over express her - then I can treat it with anti her - I mean I could but it wouldn't do anything and so these are really they grow independently of this growth factor pathway and the estrogen that pathway right here and by far the biggest killers out there in the in the breast cancer field so this is a best scenario kind of cancer this is a worst-case scenario but the reason why that clinical subtypes is again it's entirely defined by you have drugs against this we have different drugs against this we have nothing that we can treat these with in a rational fashion