Case 1: High-Risk, HR+/HER2- Early-Stage Breast Cancer
Experts in breast cancer review the case of a 54-year-old postmenopausal woman with stage IIB, high-risk, HR+ early-stage breast cancer and discuss factors to consider when assessing risk for systemic occurrence.
Joyce O’ Shaughnessy, MD: Thank you for joining us for this Targeted Oncology™ Virtual Tumor Board, which is focused on practice updates in hormone receptor–positive early breast cancer. In today’s presentation, my colleagues and I will review 3 clinical cases. We’ll discuss approaches to treating patients with hormone receptor–positive early breast cancer, controversial and evolving cases, and share our perspective on key clinical trial data that will help us in our decision-making.
I’m Joyce O’Shaughnessy, a breast medical oncologist from Baylor University Medical Center, Texas Oncology, and US Oncology in Dallas, Texas. I’m happy to be joined by 3 of my colleagues, Dr Heather McArthur, a breast medical oncologist from UT Southwestern Medical Center, my neighbor here in Dallas; Dr Massimo Cristofanilli, a breast medical oncologist at Weill Cornell Medical College in New York City; and Dr Sunil Badve, a breast pathologist from Winship Cancer Institute at Emory University in Atlanta, Georgia. Thank you all very much for being here. It’s good to be here with you. It’ll be good to discuss these cases with you.
We’ve picked 3 cases that give us a lot of food for thought in our practices. These are areas of evolution in our management, so we’ll get some good discussion going so you’ll be able to hear different vantage points about how to treat these early-stage patients. I’m going to present the first case and then go through some data, then we’ll have even more in-depth discussion. This is a patient with high-risk hormone receptor–positive HER2-negative early breast cancer, and we’re going to be looking at the role of adjuvant CDK4/6 inhibition.
This patient is a 54-year-old postmenopausal woman who presents with a newly diagnosed mass in her right breast. Imaging shows a 2.3-cm solid mass in the upper outer quadrant and no suspicious axillary adenopathy. Core biopsy shows invasive ductal carcinoma. It’s grade 3, estrogen receptor 100%, progesterone receptor 94%, HER2 1-plus, FISH [fluorescence in situ hybridization] negative, and Ki67 is 46%. She goes to surgery first and has lumpectomy and sentinel lymph node biopsy. Her tumor size is 2.2 cm, and 2 of 3 axillary lymph nodes are positive for metastatic disease. She has her breast cancer sent for the 21-gene recurrence score, and it comes back in the high-risk range at 33. She’s a pathologic T2N1M0 patient with stage IIB breast cancer with grade 3 high recurrence score.
Let’s start with a few general impressions about this breast cancer. What’s her degree of risk for systemic recurrence? What are the factors that concern you most about her risk? What would you estimate her risk of recurrence to be? Is there anything in her cancer that would make you concerned that her cancer could be endocrine therapy-resistant, such that she would need chemotherapy in particular? I’ll start with Massimo. Massimo, what risk do you think this woman carries?
Massimo Cristofanilli, MD, FACP: She has a high clinical risk and high molecular risk. She has positive lymph node, high Ki67, relatively large size of the tumor, and her recurrence score is 33. She’s a relatively young postmenopausal woman. Based on these considerations, she has a significant risk of recurrence that would benefit from chemotherapy and endocrine therapy. We don’t know if the single-agent endocrine therapy that we use today is going to be reducing or eliminating as much of the risk as possible. What else can we do? It’s difficult to predict primary resistance to endocrine therapy based on these risk factors, especially if you use chemotherapy followed by endocrine therapy.
Joyce O’ Shaughnessy, MD: Thanks. Heather, what would you estimate her risk is? Are there any reasons you’re a little worried that she might not benefit from endocrine therapy?
Heather McArthur, MD: The rule of thumb that we used to use when I was going through training was 10% for every cm of disease and 7% for every lymph node involved. Using that particularly elegant rule of thumb, I estimate her risk at about 40% over 5 years. I wonder about high Ki67 without chemotherapy. When the tumors are low in terms of their ER [estrogen receptor] positivity, I tend to innately lean more toward chemotherapy, given the growing body of data indicating that those low ER-positive tumors behave biologically more like triple-negative breast cancer. That would be a feature that I’d consider here. It’s not appropriate to her, but I’d consider it.
Joyce O’ Shaughnessy, MD: Thank you. That’s a good point. That’s 1 of your key things, a tip-off: low ER. Sunil, how about you from a pathology standpoint? What things do you look at that say, “This one may not be a great responder to endocrine therapy?” Does Ki67 help us?
Sunil Badve, MD, FRCPath: Absolutely. Whenever we have grade 3 tumors, there’s a chance of ER positivity. It’s about a 50% chance, while with grades 1 and 2, the chances of ER positivity is at least 90% to 95%. When you have these grade 3 tumors with a high Ki67, you worry about it. Ki67 has been used to determine responses to therapy, as we’ll discuss later. But we don’t have much in terms of pathology, as Massimo already mentioned. There aren’t any hard and fast rules that one can use to determine which of these patients are going to be resistant, so you have to take everything into consideration. The ball is in the oncologist’s court rather than the pathologist’s court in determining the likelihood of response and what possible therapy should be prescribed to the patient.
Joyce O’ Shaughnessy, MD: Thank you. We’ll come back and pick your brain a little more about the Ki67 in just a bit.
Transcript Edited for Clarity
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