The Evolution of Early-Stage HR+ Breast Cancer Management

Mark Pegram, MD: Good day. My name is Mark Pegram, and I’m from Stanford University, where I’m a medical oncologist and I treat a lot of patients with breast cancer. I’m here to participate in today’s OncLive® Insights® into the treatment of hormone receptor [HR]–positive breast cancer.

Lee Schwartzberg, MD, FACP: Hello, everyone, and thanks for joining us for this talk. I’m Lee Schwartzberg. I’m a breast medical oncologist as well, and I’m at the University of Nevada, Reno.

Mark Pegram, MD: Lee, we’ve been asked to talk about the treatment of early stage hormone receptor–positive breast cancer. To open that discussion, could you provide a quick overview of how you treat early stage hormone receptor–positive disease and how that treatment has evolved over the years?

Lee Schwartzberg, MD, FACP: Sure. This has been an area of active development over the last couple of decades. The basic theme has been that we’ve moved from decision-making about adjuvant therapy. We’re mainly talking about adjuvant systemic therapy, whether it’s chemotherapy or endocrine therapy. Early stage HR-positive breast cancer represents two-thirds of all diagnosed breast cancers. HR-positive, HER2 [human epidermal growth factor receptor 2]–negative is the group we’re mainly focusing on.

There was an NCI [National Cancer Institute] directive almost 20 years ago to treat people with tumors greater than 1 cm with chemotherapy, regardless of biomarkers, but we’ve learned that the biology is as important as the clinical features of the cancer. Stage I or II cancers don’t necessarily have to be treated with chemotherapy. It’s based on the biology of the tumor, and we have a number of tools we’ll talk about to help us determine the biology of the tumor. We have a number of tools to help us with refined clinical characteristics that we use to make decisions. The big overarching theme is that we use a combination of both clinical and biological features to make a decision on adjuvant systemic therapy.

Mark Pegram, MD: Lee, what struck me historically is how good tamoxifen is as treatment for early stage hormone receptor–positive breast cancer. I remember being struck by the Early Breast Cancer Trialists’ Collaborative Group presentation of over 10,600 patients with hormone receptor–positive early breast cancer. They published this in 2011, so it was a long time ago. Tamoxifen in the adjuvant setting reduces recurrence by about 39% and has a proportional reduction of mortality of 30%. Despite the advent of important drug classes, like the aromatase inhibitors, for patients who may not be able to tolerate that class of drugs, tamoxifen is a really good standby. It’s a fantastic drug. Had it been invented in the modern era, it no doubt would have gotten a standing ovation at an ASCO [American Society of Clinical Oncology] plenary session.

Lee Schwartzberg, MD, FACP: I completely agree. In fact, tamoxifen has been to some extent de-emphasized in today’s era, particularly among young trainees. I often say that I believe tamoxifen has saved more lives in medical oncology than any other drug in the world.

Mark Pegram, MD: I still believe it’s the most widely prescribed oncology product on the planet. It was for many years, and that statement is still true to this day. The other thing that struck me historically was the development of multigene assays; for example, Oncotype [DX Breast Cancer Recurrence Score] based on the NSABP B-20 data and other data sets. That was a sea change. Suddenly we could readily identify low-risk populations for whom chemotherapy was no longer necessary, despite the Saint Gallen [International Breast Cancer Consensus Conference] and NCI directive back in the day to consider systemic adjuvant chemotherapy for node-negative tumors over 1 cm [in size]. Now we absolutely know, based on biology, that that isn’t true.

For the first time, biology trumped clinical stage, because breast cancer isn’t just 1 disease. It’s a collection of many diseases, as we now know. Assays like Oncotype, MammaPrint, and some others made a huge impact on that fact for node-negative patients and now postmenopausal patients with 1 to 3 positive lymph nodes. That’s another huge group of patients for whom chemotherapy may no longer be indicated if they have a low-risk recurrence score, whereas in the past we treated all node-positive patients the same. They all got chemotherapy. That has been a huge sea change.

As you rightly mentioned, the other interesting fact about the TAILORx trial is the fact that we still need to integrate clinical pathologic parameters to determine risk for premenopausal patients in particular with recurrence scores in the range of 16 to 25, for example. You could still identify high-risk groups that have relatively low recurrence scores and still seem to benefit from chemotherapy.

Lee Schwartzberg, MD, FACP: Exactly. And to go back historically for our audience, you mentioned NSABP B-20 and NSABP B-14. These studies were looking at endocrine therapy alone or in the form of tamoxifen added to chemotherapy. What isn’t recognized is that chemotherapy became the adjuvant systemic therapy of choice back in the day, even in HR-positive, HER2- breast cancer. Then the data showed that tamoxifen added to it made a difference. Now we’ve completely flipped the paradigm, because in many patients who are HR-positive, the endocrine treatment may be all we need. Oncotype fomented a revolution in what we’re seeing today, which is thinking about de-escalation of therapy once we get to a point where we have effective therapies and the luxury of trying to de-escalate them without impairing the efficacy. Of course, that’s what we want for our patients: to treat them optimally, not more aggressively than they need.

Transcript edited for clarity.