Breast Cancer Clinical Case Review

Deborah Toppmeyer, MD, director of the Stacy Goldstein Breast Center and professor of medicine at Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, presents the results and discusses considerations after progression for patients with locally advanced or metastatic HR-positive breast cancer.

Editor’s note: The following is an automatically generated transcript of the above video.

"How did our patient do? The patient had a very nice initial response to first line therapy. After four months of therapy, her breast mass was no longer palpable. Re-staging studies were performed that showed a significant improvement in the breast mass and axillary lymph node, and the multiple liver lesions were markedly improved as well. The bone scan demonstrated decreased uptake in the areas of previously identified osseous metastases.

And of note, patients should be treated with either denosumab or zoledronic acid given every three months with zoledronic acid, to mitigate the risk of skeletal events. And this particular patient was started on zoledronic acid every three months. However, after two years of therapy, the patient's tumor markers began to rise and re-staging studies unfortunately demonstrated progression of disease in the liver.

So what's next and what do we do after progression on a CDK 4/6 inhibitor? And performance of endocrine monotherapy tends to be somewhat poor post-CDK 4/6 inhibition. So is there a role, however, for continuation of a CDK 4/6 inhibitor beyond progression with a different hormonal partner, or which patients derive benefit from targeting PIK3CA, AKT, or the mTOR pathway?

So after progression on a CDK 4/6 inhibitor, biomarking testing is strongly recommended to inform the next treatment. Tumor sequencing or ctDNA can be used. ctDNA obviously is quite easy. And the NCCN guidelines strongly recommend testing, especially for PIK3CA and ESR1, where we have obviously clear agents that can be used in this setting. So based on the results of next-gen sequencing, the current recommendations are if less than 12 months of first-line CDK 4/6 inhibitors, if there is a PIK3CA mutation, one can consider alpelisib plus fulvestrant or capivasertib plus fulvestrant. If there is no mutation identified, everolimus plus endocrine therapy or one can consider an alternate CDK 4/6 inhibitor and endocrine therapy partner, based on the maintained trial. In this trial, the majority of patients were switched from palbociclib to ribociclib in combination with a different hormone partner and clearly there was benefit, so this is also an option available. If there is an ESR1 mutation identified, then patients would be eligible for elacestrant.

Currently, we do not have data of elacestrant in combination with a CDK 4/6 inhibitor. Those studies are ongoing. Certainly if there is rapidly progressive visceral disease, then I would certainly switch to chemotherapy or consider an antibody drug conjugate.

I think in summary, we have a great number of targeted therapies that we can combine with hormonal therapy, with our goal being to delay giving chemotherapy for the longest time possible. I think this translates into a huge quality of life benefit for our patients, and again, allows us to stretch out the time where we have sequential options prior to embarking on chemotherapy that overall will improve quality of life and survival, and again, has really changed the overall landscape of progression in this particular subclass of breast cancer."