Early-Stage Breast Cancer Care: Treatment Selection Strategies and Challenges

Announcer:
You’re listening to Project Oncology on ReachMD. On this episode, Dr. Adrienne Waks will share key highlights from her session at the 2024 San Antonio Breast Cancer Symposium, which focused on the treatment of small tumors in the early-stage setting. Dr. Waks is an Associate Director of Breast Oncology Clinical Research at the Dana-Farber Cancer Institute and an Assistant Professor of Medicine at Harvard Medical School. Let’s hear from her now.

Dr. Waks:
When I’m selecting a treatment for a patient with a stage I HER2-positive breast cancer—which generally that patient has gone to upfront surgery and I’m considering what systemic therapy to treat them with in the adjuvant setting—certainly I consider the size of their cancer. We’re talking only about stage I tumors, so only tumors that go anywhere from microinvasion up to and including 2 cm, but within that size range, I certainly consider the size of the tumors.

As I went through some of the data in my talk at San Antonio this year, I think if the patient has a tumor in the T1c size range, so between 1.1 and 2.0 cm, it’s pretty unequivocal that I’m going to give that patient a systemic therapy regimen unless they have enormous comorbidity or toxicity considerations that I have to weigh. In the T1b size range which would be from 6mm to 10mm, I’m going to treat most of those patients with a systemic regimen in the adjuvant setting. And then the microinvasive and the T1a range, so up to and including 5mm and then smaller than that, I have a real discussion with the patient about the potential pros and cons. So the size of the tumor and specifically whether it’s in the T1a, T1b, or T1C size range is probably the biggest thing I consider when I’m deciding if I’m going to give an adjuvant chemotherapy plus HER-2-targeted regimen or not.

Another thing that comes into consideration, regardless of size range, is the patient’s fitness, age, and even comorbidities and functional status. I’m obviously, as with anything across all of oncology, more likely to treat a patient when I’m not as worried about the toxicity of my therapy, especially in a relatively low-risk setting like a smaller HER2-positive stage I cancer. So as with all systemic therapy decisions, that comes into play.

And then the last thing is the hormone receptor status. We know that about 2/3 of stage I HER2-positive breast cancers are also hormone receptor-positive. For all of those patients in the stage I range, I offer them and encourage them to at least try systemic endocrine therapy. And certainly for a patient who’s in that T1a size range or maybe the small end of the T1b size range, if they’re strongly ER-positive and I’m really convinced that they’re going to take their endocrine therapy, I may be a little more comfortable omitting the chemo and HER-2-directed therapy because I know I have a different systemic agent that I can offer them with probably enormous benefit.

I think a big challenge when we are faced with a patient with a small HER2-positive or stage I HER2-positive breast cancer is the question of, how low do you go? How small of a cancer does it have to be in order for me to say, “I don’t recommend chemotherapy, and I don’t recommend HER2-targeted therapy.” We really have minimal evidence to guide us in answering that question and making the best decision for an individual patient. You know, should a 4mm cancer be treated? What’s the magnitude of benefit for treating a 4mm cancer? What about a 6mm cancer? Is it really that different from a 4mm cancer? Does it matter if that cancer is hormone receptor-positive or hormone receptor-negative in addition to being HER2-positive? We really have almost no data and certainly no prospective data to guide us when we try to counsel our patient on what are the potential benefits that you’re missing out on if I don’t give you adjuvant chemotherapy or HER2-directed therapy, so  that’s a big challenge in the clinic for us to know what are the potential benefits of these therapies, especially for cancers that are in the small T1b/T1a range. Again, I think for the T1c cancers, there’s not really a question there. Those all do need systemic therapy.

Something we also run into a lot clinically is our patients with HER2-positive microinvasive disease. So usually these patients mostly have DCIS, but then they have one or three or sometimes 15 plus foci of microinvasion. That’s technically a stage I HER2-positive breast cancer. What is the risk to that patient with or without adjuvant systemic therapy? A question that comes up a lot is, Does the number of foci matter? Does a patient who has 30 foci of microinvasion need systemic therapy more than the patient who has 3 foci of microinvasion? I think that’s a clinical challenge that we don’t have a lot of a lot of data or very little data to guide us on.

And then lastly, I think a big challenge is for the clinical T1c and 0 patients who, again, we’re for sure going to give them some chemo; we’re for sure going to give them some HER2-directed therapy. The question that comes up there is, should we give them our therapy in the neoadjuvant setting or in the adjuvant setting? And this comes up a lot especially because we know that if you have a clinical T1c N0 HER2-positive tumor—so this patient hasn’t yet gone to surgery and obtained pathologic staging—about 25 percent or 1 in 4 of those patients who are clinically node-negative with tumor size in the T1c range will go to surgery and then have pathologic nodal positivity. And then clinically, that’s always a really challenging scenario because we know we would have wanted to treat that patient in the neoadjuvant setting had we known that they had nodal disease.

Announcer:
That was Dr. Adrienne Waks discussing the treatment of small tumors in the early-stage breast cancer setting, which she spoke about at the 2024 San Antonio Breast Cancer Symposium. To access this and other episodes in our series, visit Project Oncology on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!