What My Patients Are Asking: Explain the New Breast Cancer Staging Guidelines

Jamie DePolo: Hello! Welcome to the Breastcancer.org podcast! I’m Jamie DePolo, senior editor at Breastcancer.org. Our guest today is Brian Wojciechowski, M.D., who practices medical oncology in Delaware County, Pennsylvania at Riddle, Taylor, and Crozier hospitals. Dr. Wojciechowski also serves as Breastcancer.org's medical adviser. A native of South Philadelphia, he trained at Temple University School of Medicine and Lankenau Medical Center. Dr. Wojciechowski is a sought-after speaker on the topics of medical ethics and the biology of cancer.

In this What My Patients Are Asking podcast, we’re going to talk about the 2018 updates to the breast cancer staging system. Dr. Wojo, welcome to the podcast!

Dr. Wojciechowski: Thanks for having me again, Jamie.

Jamie DePolo: Always a pleasure! In 2018, the American Joint Committee on Cancer, which is commonly called the AJCC, updated the breast cancer staging guidelines. The changes were [that] they added other information that helped determine how a cancer stage is determined. Somebody had said to me, this makes determining the stage of a breast cancer more complex, but also more accurate.

So we still have the T, N, and M parts of the staging system. So I was thinking to start, if you could explain what those three parts are, and then we’ll talk about the new parts.

Dr. Wojciechowski: Well, classically, Jamie, tumors have been staged based on their anatomic features and the anatomic features that determine prognosis. It’s basically how far the cancer has spread and how invasive the cancer is. And this comes from back in the day when the main treatment for cancer was surgery.

So you have T, N, and M as part of the classical staging system. The “T” stands for tumor, and it’s determined by the size and the extent of the primary tumor. So for example, how big is the tumor in greatest dimension? Does it invade into adjacent structures like the chest wall or the nipple or the skin? The “N,” as in Nancy, stands for node, and that’s determined by the involvement of the regional lymph nodes. And these are the regional lymph nodes, so they’re typically, for breast cancer, nodes in the breast or in the armpit. Once nodes get outside that area, say to high up in the neck, they’re considered something different, and that brings us to the last letter, the “M,” as in Mary, which is metastatic. The M is determined by the presence or absence of what we call distant metastatic disease — so beyond the regional lymph nodes. So for example, bone involvement, lung, liver, and that sort of thing.

Now, this does not include the other, more modern aspects of staging — what we call non-anatomic or biologic factors — such as estrogen, or that sort of thing. But T, N, and M are the classic cancer staging letters.

Jamie DePolo: Perfect! Thank you. So my understanding is in 2018 the AJCC added tumor grade, estrogen and progesterone receptor status, HER2 status, and Oncotype DX recurrent score information to that TNM system. So to help us understand again, can you explain what each of those are?

Dr. Wojciechowski: So, classically as I had said before, and historically, the staging was based on the anatomic extent of the cancer, and that’s still the main way it’s staged. But as time has passed, doctors have recognized that non-anatomic factors about a cancer can provide additional prognostic information above and beyond just the size of the tumor and whether it’s in the lymph nodes or not.

So these include more about the tumor biology and the genetics of the tumor itself. So first, we talked about tumor grade. That’s the first thing you asked. Tumor grade refers to how the tumor looks under the microscope, and the more the tumor looks like the tissue of origin — in this case, normal breast tissue — the less aggressive the tumor is and the lower the grade. Now, higher-grade tumors are more aggressive, more likely to grow, invade, and spread, and these bear very little resemblance to normal breast tissue. High-grade tumors have cells that look irregular, non-uniform, and appear to be dividing rapidly. Under the microscope they look very ugly, very far from normal breast tissue.

The next was estrogen and progesterone status. These determine the sensitivity of the cancer to hormone therapies such as tamoxifen or aromatase inhibitors. And generally speaking, if a cancer is positive for estrogen and progesterone, it has a better prognosis than if it isn’t. So that’s why these are added to the staging system.

The same could be said for HER2 status. When you see HER2, this adds more prognostic information as well, because HER2-positive tumors are more aggressive. But on the flip side, it also indicates that that tumor is sensitive to the various drugs that target HER2 such as Herceptin, Perjeta, and Kadcyla.

And then last but not least, of course, is the Oncotype, which is a very sophisticated test on the tumor itself that helps determine not only how aggressive the cancer is, but also whether or not the patient will benefit from chemotherapy. These are called genomic tests. Now, there are other genomic tests out there, but so far Oncotype has the best data, and it’s the only one that is formally included in the new staging.

Jamie DePolo: And it sounds like, to me anyway, not being a doctor, that as treatments have been developed that target the specific characteristics of a cancer, it’s made the staging system evolve because now, as you said, a breast cancer that was HER2-positive was considered to be more aggressive before there were treatments that targeted that HER2. Now that there are, while the cancer is more aggressive still, we know we have treatments that can help.

Dr. Wojciechowski: That’s right, and you can downstage it.

Jamie DePolo: So in your mind, or can you help us understand, is it just that we have more information about the cancer so that makes the staging more accurate?

Dr. Wojciechowski: Yeah, so if we get more information about the cancer, particularly from the biological tests, we can tell whether or not a cancer is more aggressive or less aggressive. So not all cancers at the same stage are created equal.

Another way of saying it is that for two cancers that have the same anatomic stage — that is the TNM stage — the prognosis could be widely different because of the biologic features, and they could have a very different prognosis.

Jamie DePolo: And I guess I’m wondering, too, looking forward, as we get more drugs that target specific aspects, specific biological aspects, of the cancers, like I know there’s an immunotherapy approved for breast cancer now but it seems to work best in cancers with high levels of PDL1. So conceivably, as time goes on, I can see the staging guidelines being updated again to include PDL1 information.

Dr. Wojciechowski: Yeah, I think there’s a very good possibility of that happening, especially if immunotherapy moves up to the early-stage cancers, because right now it’s only approved for metastatic triple-negative cancers whose tumors express PDL1 on their tumor-infiltrating lymphocytes. So in the future I think we should expect more and more changes to the staging system to incorporate the biologic markers, not just the anatomical.

Jamie DePolo: One of the experts I spoke to said that the updated staging guidelines really are catching up to how people diagnosed with cancer are treated. And I feel like we’ve talked about it, but I’m wondering if you could just explain that a little bit because I just want to make sure everyone understands.

Dr. Wojciechowski: Yes. I think it’s key to remember that not all cancers of the same stage are created equal. For example, a hormone-receptor-positive cancer that is stage I is very unlikely to need chemotherapy, and a triple-negative cancer that is stage I is much more likely to need chemotherapy. So the new staging will reflect these clinical differences.

Jamie DePolo: And to help me better understand, could you give us one or two examples — you choose — the characteristics of the cancer and how under the old staging guidelines it would be staged as a specific level, and under the new staging guidelines maybe it gets upstaged or downstaged, just so we can have a couple examples of… let’s really hear about it?

Dr. Wojciechowski: Yeah, I remember when we first covered this in 2018. This really blew my mind, finding out how the stages could change. I’m going to give you an example. So just imagine a tumor that is larger than 5 centimeters [cm], so what we would consider a big tumor, and if it was involved in, say, three lymph nodes in the armpit. Now, before the new staging system, this would have been considered a stage IIIA.

Jamie DePolo: That’s because of the size and the lymph node invasion, correct?

Dr. Wojciechowski: That’s right, and we would have considered this to be a very poor prognosis tumor with a high chance of growing and spreading and all that. But now, you could actually have a tumor that is bigger than 5 cm and is in four lymph nodes in the armpit, but if it’s estrogen-receptor- and HER2-positive — remembering that those two markers actually give us more treatment options and improve the prognosis — the stage of that tumor will now be downstaged to a stage IB.

Jamie DePolo: Wow, so it actually goes down two stages. It goes from a IIIA to a IB.

Dr. Wojciechowski: Yeah, which is totally crazy if you think about how many lymph nodes are involved and the size of the tumor. Now, it’s important to remember that that didn’t change the treatment. So most patients with this particular tumor that we’re talking about are going to get chemo and HER2-targeted therapy and hormone therapy. So it didn’t change the treatment, but it changed the stage to better reflect prognosis, which is the key.

So a good staging system will give you: A, a good sense of how far the tumor has spread and how invasive, and B, a good sense of prognosis. That’s what this new staging system really adds that we didn’t have as much before.

Jamie DePolo: I know this is all incredibly complicated, I’ve looked online and I’ve done research, and I’ve seen these incredible charts that seem to go on for pages and pages and pages. You know, starting out at one side, if this, and this, and this, then this. And it’s really hard to figure out the stage of a cancer now. So I’m wondering, obviously you’re a doctor, so this is your area of expertise, but are there any good apps that can help people if they just want information for themselves, or is it really they need to talk to their doctors?

Dr. Wojciechowski: Yeah, this is where we put in the disclaimer, “Don’t try this at home.”

Jamie DePolo: [laughs] Okay. Yeah.

Dr. Wojciechowski: It’s really complicated. It’s even complicated for doctors to figure this out. When I figure out the stage now, I use an algorithm on my computer and then I double check it against my own knowledge. So I’m not aware of any apps that could do this, and I wouldn’t recommend it either. I mean, you can get a general sense from looking at websites like the American Cancer Society or Breastcancer.org, but really, this is something you want to go through with your physician, and it’s extremely important to get it right.

Jamie DePolo: In your practice, have you seen these new staging guidelines — I know you said that treatments weren’t changing — but have you seen the staging of the cancers change, and how is that affecting the people you treat?

Dr. Wojciechowski: So, we have seen stages change. It doesn’t change the treatment, as I mentioned above, but like I said, it does give you a better sense of the prognosis, and believe me, patients are quite happy to be told, "Well, you know, before it was considered stage III and now it’s stage I." So it definitely brings people peace of mind and gives me a better sense of prognosis.

Jamie DePolo: To my mind, too, and correct me if I’m wrong, it seems like it’s a little more realistic, too, because someone who’s diagnosed with stage IIIB breast cancer, that’s very concerning because as you said earlier, your prognosis is not that great. I mean it’s not terrible, but still, it’s stage IIIB. And if now, that same cancer, because of the biological characteristics, is stage I, the prognosis is just that much more rosy.

Dr. Wojciechowski: You know, words mean a lot to cancer patients. I mean, I’ve had people flip out because they heard the word "metastatic," and even though I had told them before it was stage IV and the two words mean the exact same thing, to hear the word metastatic was traumatic. So words mean a lot, and to hear that you’re stage III versus stage I, I think can make a huge difference for peace of mind for patients and their families.

Jamie DePolo: I agree. I agree. So sort of to wrap up, if someone’s been diagnosed with breast cancer — and is just diagnosed, obviously — and has questions about the staging, is the best thing to do to talk to the oncologist?

Dr. Wojciechowski: I think anyone on the treatment team should be able to figure this out. I mean, speaking as a medical oncologist, we do try and do it by the book. It’s conceivable that some docs out there might not be aware of the new system or might not yet be getting into the habit of using it, so I think it’s not unreasonable for patients who are educated on this to just talk to their doctor about it and say, "Hey, are you using the new staging system and if so, is my stage going to change?"

Jamie DePolo: Dr. Brian, thank you so much. This has been really helpful.

Dr. Wojciechowski: You’re welcome. It’s been a pleasure.