Video
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC, opens a panel discussion surrounding the treatment pathways for patients diagnosed with early breast cancer.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Hello, and welcome to this AJMC Peer Exchange program titled “CDK4/6 Inhibitors in High-Risk Early Breast Cancer.” My name is Dr Kirollos Hanna. I’m the director of pharmacy at Minnesota Oncology, and I’m an assistant professor at the Mayo Clinic College of Medicine in Rochester, Minnesota. Joining me today is an esteemed panel of experts. First, I’d like to introduce Dr Jay Andersen, who is a medical oncologist and codirector of Compass Oncology Breast Specialists [in Tigard, Oregon]. Dr Heather McArthur, clinical director of breast oncology and Komen distinguished chair in clinical breast cancer research at the University of Texas Southwestern [in Dallas, Texas]. Dr Samyukta [Sam] Mullangi, a fellow in medical oncology at Memorial Sloan Kettering Cancer Center [in New York, New York]. And Dr Sarah Sammons, who is an associate director of the Metastatic Breast Cancer Program at Dana-Farber Cancer Institute [in Boston, Massachusetts]. Today, our panel of experts will provide an overview of the burden of disease in early breast cancer, review the treatment landscapes, and provide considerations for the use of CDK [cyclin-dependent kinase] 4/6 inhibitors, as well as discuss the future directions for CDK4/6 inhibitors in early breast cancer. Thank you. Let’s begin.
Jay, I’ll turn it over to you. Walk us through a [case of a] patient who is diagnosed with early breast cancer. What is a general clinical presentation of this patient? What do they look like, [what is] the burden of disease? I’d be interested to hear if there are specific biomarkers that we would identify in patients who are candidates for CDK4/6 inhibition.
Jay Andersen, MD: Fortunately, because of screening, most patients actually are diagnosed on screening mammography, which means usually they’re earlier stage vs prior to screening opportunities. Usually, they make their way from their breast imaging finding a suspicious mass [and go] into biopsy, confirming malignancy, and then [entering] the oncology world. They could see a surgeon first. They may see medical oncology first or second, and we work as a collaborative team to put together their optimal treatment management. We look at standard clinical pathologic features that gauge risk. I don’t think there is a universally accepted definition of high risk, but it’s a spectrum. Certainly, we look at the tumor stage, lymph node status, and grade. Then we look at phenotype, which looks at the estrogen receptor, progesterone receptor, and HER2 [human epidermal growth factor receptor 2] receptor, and that collectively informs the clinician about the stage and the general sense of risk. We may use other factors such as growth factor or [the] growth-proliferation index Ki-67, which may further inform us about the biology. Then we also may pursue genomic testing like MammaPrint or Oncotype DX to further inform.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: From that early breast cancer patient to a metastatic breast cancer patient, are there any differences there? How could these patients potentially defer?
Jay Andersen, MD: [There is a] big difference. So, metastatic stage 4 means they have disseminated disease away from the breast axillary region. We cannot cure metastatic disease, but we really are pushing that envelope and patients are sometimes living for years with stage 4 disease. [In] early-stage disease, the goal is curative intent. That’s where we really are focused on looking at their risk, putting together the treatment package that would optimize their odds of cure.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Heather, I’ll turn it over to you. What is generally the journey from diagnosis? Once that patient gets diagnosed with early breast cancer, you deem they are high risk. What does that journey usually look like for a patient? Is it initiating treatment right up front, surgical approaches? What is the role of adjuvant or neoadjuvant treatment? How does that look?
Heather McArthur, MD: As Jay eloquently pointed out, it’s a multidisciplinary approach, so typically, a patient, particularly one with high-risk disease, would see a surgeon, a medical oncologist, and maybe even up front a radiation oncologist, for those patients with very high-risk disease. Often we identify them using the conventional clinical and pathologic features that have been delineated. But we are often using a lot of genomic testing like Oncotype Dx or MammaPrint to understand and refine our understanding of prognosis and predictive impact, with chemotherapy specifically. So there are different guidelines for [patients who are] node negative and node positive; premenopausal and postmenopausal. But, typically, high-risk patients are treated with chemotherapy, which is typically months of chemotherapy, which could be administered in the preoperative or the postoperative setting. [Often for] our younger patients [it is] administered with ovarian suppression for fertility preservation, for example, and we’re actually going to see some data from the Oxford overview on ovarian suppression for our very high-risk patients [come from] this ASCO [American Society of Clinical Oncology] [annual] meeting. Then, typically, they’re facing 5 to 10 years of adjuvant endocrine therapy, with or without CDK4/6 inhibitors, which have recently become a standard of care for our high-risk populations.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: So it is quite a long journey, I would say.
Heather McArthur, MD: It’s a marathon. Not a sprint.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Absolutely. Sam, I’ll turn it over to you. What does the prevalence look like for this patient population? We obviously know that breast cancer is one of the top cancers in the United States [US], but this specific, high-risk early stage, does it make up most of the diagnoses for our patients? How does that generally look in clinical practice?
Samyukta Mullangi, MD, MBA: Breast cancer is incredibly common. It is the leading cancer diagnosis in [American] women today. In 2022, I think the American Cancer Society estimated that there were over 280,000 new cases of invasive breast cancer diagnosed, and another 50,000 of DCIS [ductal carcinoma in situ] or localized breast cancer. After lung cancer, it is the second leading cause of cancer death among women, and in Black and Hispanic women; in fact, it is the leading cause of cancer death. I would say in the last 4 decades, the research shows that cancer incidence has been increasing by about 0.5% per year. That is largely driven by early-stage as well as hormone receptor–positive disease types. Exactly the type of breast cancer that we’re talking about today. But over that same time frame, mortality rates have decreased. In fact, death rates have increased by about 43% in aggregate over that time period. So that’s over 480,000 cancer deaths averted.
At the start of 2022, the American Cancer Society estimated that there were about 2.1 million women in the US who had some kind of breast cancer history. A vanishingly small proportion of that, or about 4%, were folks living with metastatic disease, and an additional half of that, 4% were folks who would progress from an early-stage diagnosis. I would say that the story of breast cancer in the US is that it is, the vast majority of it is, about early-stage breast cancer as well as tremendous success with survivorship.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: I think to Heather’s point, and to your point as well, that reduction in mortality, and seeing this shift in CDK4/6 in this patient population being one of the standards of care, brings us some solace for this patient population and some potential treatment options.
Transcript edited for clarity.