Falk: So there are receptors in addition to estrogen receptors that have helped in that thinking. If I were listening and I wanted to understand these different receptors, all that have funny names that distinguish one kind of breast cancer from the other. Let’s walk through those different word choices and what they really mean to a patient who’s listening to their physician tell them their cancer is “estrogen-receptor positive,” or other receptor positive. Help me with all of that.
Carey: So when we categorize breast cancers, we do it on the basis of the clinical extent of the cancer, which is an old-fashioned way – Stages One, Two, Three and Four.
Falk: What does that mean?
Carey: That means, how big is the cancer, and where has it spread to? Stage One, for example, are very small tumors that haven’t left the breast. They’re really encased within the breast tissue itself. They’re not in local lymph nodes, they aren’t in any other organs. Stages Two and Three are a little bit bigger or they have started to spread locally, and Stage Four is cancer that has spread into distant organs. We think of Stages One, Two, and Three as being curable, Stage Four as being controllable but not curable. That nomenclature and the old, sort of way of looking at cancer, including breast cancer, as an anatomic disease still exists and is still important.
To this anatomic categorization scheme, now we have factors that represent the biology of the breast cancer, and there are old-fashioned ones-the estrogen receptor and the progesterone receptor, which give us a sense of the hormonal sensitivity of the cancer—those have been tested for years and years, although the testing techniques have gotten better recently compared to what they did in the olden days.
There’s another test that we use right now, and that’s for a protein called HER2. HER2 is a gene that creates a more aggressive kind of breast cancer when it’s turned on. In about twenty percent of breast cancers it’s turned on and it’s not regulated the way normal genes are managed. Actually the cancer cell no longer can regulate its own growth. In those breast cancers, the cancer tends to be much faster growing and we can test for it. It’s also important because we have drugs against it. So, just as we have anti-estrogens, now we have anti-HER2 drugs. Those are the three factors that we test for now, in part because they give us a hint about biology and also because we have drugs against these particular factors.
Falk: Estrogen, progesterone, and HER2.
Carey: Correct.
Falk: If you have any of those receptor markers, it helps you identify a prognosis and it also helps you identify treatment options.
Carey: Absolutely. We treat them differently.
Falk: The word choice “triple negative,” that implies all three of those receptors are not expressed or available in the tumor. Is that right?
Carey: That’s right. It means they are negative for all three which means we have chemotherapy to offer, but we don’t have any of the targeted therapies at this time, although this is an area of very active research. Now it is important to note—and this is something that I think sometimes gets missed, because the Internet is full of stories about triple negative and how it’s aggressive and has fewer treatment options—the truth is, that many triple negatives, if not most, are actually still curable, we just don’t have targeted therapies.
Falk: When you use the word “curable,” what does that mean? Cure for the rest of the person’s life? They don’t have to need screening, or follow-up? What’s the breast cancer definition of “cure”?
Carey: The breast cancer definition of cure is that you live a long and healthy life and you die of something else, with no evidence of your cancer coming back once you finish the initial round of treatments.
Falk: That’s just a remarkable statement to be able to make.
Carey: Well, years ago—my grandmother died of breast cancer in the 1960’s. And into the early ‘70’s, more than half of women who were diagnosed with breast cancer died of it. That number’s now twenty percent or a little less.
Falk: And it’s against this progress then that you can overlay the genetic studies that people like Chuck Perou have been doing, and hopefully that’s going to lead to further refinements in our thinking about these diseases.
Carey: You know, it already has. Among the things that have come out within the last ten years are really applying these genetic tests to existing cancers and trying to get additional information beyond ER, PR, and HER2. For example, the molecular subtypes of breast cancer that Chuck first discovered—those particular subtypes have been now turned into a genetic test that you can use to help gauge, within hormone receptor positive breast cancer, whether a cancer’s more or less likely to do well with just anti-estrogen therapy—and there’s actually several commercial tests that do exactly that. They help us decide who needs chemo, and who can get just an anti-estrogen pill for five or ten years, and not have to have additional therapy. That kind of application of these genetic tests is where we want the whole field to go.
