Case Presentation: A 72-Year-Old Woman With HR+/HER2- mBC

Virginia Kaklamani, MD: Okay, so this is our first case of HER2-negative metastatic breast cancer. This is a 47-year-old premenopausal patient. She presented with a newly discovered mass in her left breast and palpable axillary lymph nodes. Her clinical workup included abdominal and chest-pelvic CT, which showed a mass in the upper outer quadrant and two metastases in the right hepatic lobe. According to the biopsy, it showed invasive ductal carcinoma: ER 100%, PR 89%, HER2 0; FISH is negative. So, she is not HER2-low, but she is HER2-zero. The Ki-67 was 64%, which is on the high side. A lumpectomy and sentinel biopsy were performed; the tumor was 5.8 cm with three positive lymph nodes for metastatic disease. So, how do we approach this patient in the first-line setting and what factors into our decision on how to treat the patient? When assessing the type of breast cancer and the burden of disease, and considering her performance status is 47, she is young. Her markers, ER 100% and PR 89%, indicate strong ER and PR positivity. Therefore, I would consider this tumor to be endocrine sensitive. As I have not treated her yet, I don't have any other markers of endocrine sensitivity, but the assumption is she will have a recurrence-sensitive disease. Looking at the burden of disease, she only has two foci of metastatic disease in her liver. In this case, we want to be more aggressive. The Ki-67 is 64%, indicating a high proliferative tumor. Single-agent endocrine therapy would not suffice; a combination with a CDK4/6 inhibitor would be a good option. Elizabeth, how do you decide between the three different CDK4/6 inhibitors in terms of adverse events?

Elizabeth Diaz, PA-C: Well, palbociclib is generally easier to tolerate. Although ribociclib may be preferred based on data from last year, it should not be used in patients with liver or cardiac dysfunction, which may impact the choice. Some patients may have already benefitted from a cyclin in the agonist setting.

Virginia Kaklamani, MD: Ribociclib is the one with an overall survival benefit. However, both palbociclib and abemaciclib have progression-free survival benefits. Regarding the toxicity profile, ribociclib and palbociclib tend to cause more neutropenia, while abemaciclib is associated with more diarrhea. All three are acceptable options, included in the NCCN guidelines, and FDA-approved for first-line therapy in the metastatic setting.