Cancer cells proliferate using various mechanisms. One mechanism of preventing
tumor cell growth is blockade of the
cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors -
ribociclib,
palbociclib, and
abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive
ductal carcinoma. She was treated with
letrozole and
ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started
palbociclib but experienced elevated
transaminases within two weeks, needing discontinuation of
palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed
disease progression, and she was started on
fulvestrant. We considered adding
abemaciclib, but the patient declined and has had stable disease for more than a year on
fulvestrant. CDK 4/6 inhibitors are used to treat metastatic
breast cancer and are generally well tolerated. The most common side effect is
neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in
hormone-positive metastatic breast
cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the
drug, and we must continue to assess the risk versus benefit profile when offering them to our patients.