In the Clinical Case Discussions session at the 2023 SABCS®, a multidisciplinary panel reviewed audience-described real-world clinical cases and their questions and concerns. The session was highly interactive, allowing audience members to bring forward challenges or uncertainties in choosing optimal care and treatment for patients with breast cancer (BC) in routine practice.
The session, moderated by Matthew P. Goetz, MD, Professor of Oncology and Pharmacology at Mayo Clinic Rochester, is available on demand for registered participants of the 2023 SABCS® through March 31, 2024, on the meeting platform.
The panel included Andrea V. Barrio, MD, FACS, Associate Attending Surgeon at Memorial Sloan Kettering Cancer Center; Nadia Harbeck, MD, PhD, Director of the Breast Center at the University of Munich, Germany; Bev Lewyn, Patient Advocate, founder of TheBevStrategy.com for patients; Erica L. Mayer, MD, MPH, Director of Breast Cancer Clinical Research at Dana-Farber Cancer Institute; Lori Pierce, MD, Professor and Vice Provost for Academic & Faculty Affairs at the University of Michigan; Barbara Pistilli, MD, Medical Oncologist at Gustave Roussy, Villejuif, France; Aleix Prat, MD, PhD, Cancer Center Director of Hospital Clinic Barcelona, Catalonia, Spain; and Hope S. Rugo, MD, Medical Oncologist at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center.
The role of surgery and radiation in stage IV disease and duration of immunotherapy with pembrolizumab
Although systemic therapies are the mainstay of advanced/metastatic BC management, surgery and radiotherapy (RT) may be useful for achieving locoregional disease control.
The panel considered the case of a 48-year-old premenopausal woman with poorly differentiated invasive ductal carcinoma (IDC) of the breast that was ER+ (30%), with a triple-negative (TN) lesion in the lymph node (LN) and contralateral DCIS. There was no distant disease, except for a solitary mass in the abdominal wall, which was also TN. The abdominal lesion was resected with negative margins, followed by immunotherapy (I/O) per the KEYNOTE (KN)-522 regimen. The patient also underwent a double mastectomy and achieved pathologic complete response (pCR). The panel discussed these questions:
- What is the role of surgery and RT in this context?
- What is the optimal duration for KN-522 pembrolizumab regimen?
- Should endocrine therapy (ET) be considered?
Dr. Pierce said, “This is a great case for multidisciplinary discussion.” She added that surgery or focused radiation, but not both, can be considered. However, the patient needs to understand that these approaches would provide locoregional disease control, with low likelihood of survival improvements.
Regarding the duration of I/O, Dr. Rugo asked whether PD-L1 status had been assessed, as data shows that low-ER+ BC tend to be high PD-L1. Although the optimal I/O duration in this setting is currently not known, treatment continued for two years in KN-355, and prolonged I/O is associated with toxicity risk, Dr. Rugo has extended treatment for five years in similar contexts.
Given the low but significant ER-positivity of the tumor, Dr. Harbeck noted that not only ET but also CDK4/6 inhibitors (CDK4/6is) could be considered. She added that patient discussion around a more limited benefit with ET is important. I/O per the KN-355 regimen, if the tumor was PD-L1+, would also be an option.
Dr. Goetz added, “We have begun to see the use of pembrolizumab for ER+ disease. It is critical for oncologists to know that there has been no ability to combine abemaciclib (a CDK4/6i) with immune checkpoint inhibitor (ICI) therapy.”
He cautioned against tendencies to combine CDK4/6i with ICIs due to risk of severe immune-related toxicity.
Local recurrence despite ‘optimal’ ET in the context of hormone receptor-positive disease
A 48-year-old patient with multicentric grade 2 hormone receptor (HR)-positive/HER2-negative/LN-positive/low Ki67 lobular carcinoma, developed chest wall recurrence despite receiving anastrozole, an aromatase inhibitor (AI) for more than five years. The AI therapy followed bilateral mastectomy, LN resection, and adjuvant chemotherapy (CT). The recurrent lesion was ER-positive/PR-negative/HER2-negative, with high Ki67. The locally recurrent tumor was resected, with negative margins. The panel explored the value of CT and extension of radiation for this patient.
Dr. Pierce noted that although chest wall recurrences are not common, it is the most common site of subsequent recurrences. Optimal RT would involve locoregional radiation of the chest wall but not comprehensive RT.
Dr. Mayer said, “Patients with chest wall recurrence are at higher risk of distant metastases, and it is a great thing that in this patient, her PET scan was negative.” She then reviewed systemic therapy options. Given the younger age and higher recurrence risk, she favored a comprehensive CT approach. The panel agreed that a different AI (fulvestrant) would be the reasonable next step.
Dr. Rugo raised the possibility, although controversial, of combining fulvestrant with a CDK4/6i, although neither is FDA-approved in this setting. Dr. Goetz concurred, stating, “This is an area of active controversy as there are no data for a role of CDK4/6i.” Evidence for benefit with CT is also absent, but responses to CT are heterogeneous. He added that Oncotype DX may help assess CT sensitivity.
Drs. Harbeck and Rugo noted differences between the United States and EU regarding the use of CDK4/6is.
Use of ado-trastuzumab emtansine (T-DM1) in the context of tumor evolution from HER2-positive to HER2-negative status
Among patients with HER2-positive BC, those with residual invasive disease after neoadjuvant therapy (CT and HER2-targeted therapy) have worse outcomes than those with pCR. T-DM1 is now the standard-of-care in this setting, based on the reduced risk (by 50%) of invasive disease recurrence or death with T-DM1 compared to trastuzumab, in the KATHERINE study.
The panel discussed systemic therapies, including T-DM1, in the context of a premenopausal patient with HR-positive/HER2-negative residual disease following treatment for a breast tumor with lobular features that was HR-positive/HER2-positive (IHC 3+, ISH+) at diagnosis. The patient received adjuvant anthracycline, discontinued due to persistent neuropathy.
Dr. Pistilli noted ET may be the best option in the context of HR-positive residual disease. Given premenopausal status, she added AI with a CDK4/6i as another option, if CDK4/6i are approved in this setting. The panel agreed on concurrent use of T-DM1 with ET.
Dr. Goetz said, “One of the take-home messages here is that, in a tumor that was originally HER2-positive, [that] at the time of surgery it was HER2-negative does not preclude the use of T-DM1,” especially considering the analyses from the KATHERINE trial. Neuropathy is important to manage, and a CDK4/6i can also be considered.
In addition to the cases described here, the panel reviewed other cases representing tumor evolution (change in BC subtype), challenges with distinguishing secondary tumors from a new primary tumor, treatment planning for RT (e.g., matched fields for lesions in the neck and breast), and use of adjustments in anthracycline/paclitaxel regimens for older patients/based on toxicity risk.
For more information on clinical topics, check out the session Clinical Controversies, presented at the 2023 SABCS® on Thursday, December 7. It is available on demand through March 31, 2024.