Managing Recurrent Metastatic ER+/HER2- Breast Cancer

Sara M. Tolaney, MD, MPH:This is the case of a 58-year-old woman who has a history of a hormone receptor—positive,HER2-negative breast cancer. She had received adjuvant hormonal therapy with an aromatase inhibitor and had taken that for 5 years. About 13 months after discontinuing the aromatase inhibitor, she had imaging done for other reasons and was found to have 4 lung nodules as well as enlarged mediastinal and hilar lymph nodes that were suspected for recurrence of her original breast cancer. She had a biopsy done of 1 of the mediastinal nodes, and it did confirm that this was consistent with her original breast primary and was a hormone receptor—positive,HER2-negative breast cancer.

Because this patient recurred just over a year since completion of her adjuvant aromatase inhibitor therapy, it does make you think that perhaps she was resistant to her original aromatase inhibitor. Someone who presents with metastatic hormone receptor—positive disease is thought to have a prognosis with about a 3½- to 4-year survival. Certainly, we continue to do better and better, but that’s about average.

In terms of selecting therapy, because she recurred so soon after her aromatase inhibitor, I usually think of starting a different hormonal therapy and will often elect to use fulvestrant in this case. Because of all the very encouraging data looking at combination therapy with endocrine therapy and CDK4/6 inhibition, in this particular case I would recommend using fulvestrant with a CDK4/6 inhibitor, and this particular patient did start on fulvestrant with abemaciclib.

In general, when a patient recurs with metastatic disease, I think it’s very important to obtain a biopsy at the time of recurrence. One reason is to be able to recheck receptor status. We do know that about 10% to 15% of patients will change receptors. Of those patients who perhaps start out with a hormone receptor-positive disease, about 10% to 12% will lose their hormone receptor. And so it is important to recheck, because certainly that is critical in making treatment decisions, to know if this patient still has ER [estrogen receptor] and/or PR [progesterone receptor] on the surface of their cancer cells.

However, I think as our treatments are improving, we are learning that it may also be important to personalize therapy. So having a better understanding of the genomic alterations that may be driving that cancer may help you decide which treatment regimens to use. Particularly in patients who have metastatic hormone receptor—positive disease, we have now learned that patients who have aPIK3CAmutation will benefit from a very specific PI3 kinase inhibitor called alpelisib when given in combination with fulvestrant. So knowing if a patient has aPIK3CAmutation will influence treatment decisions.

We’re also learning that patients who haveESR1mutations may not be sensitive to aromatase inhibition. And so a better understanding whether this patient has anESR1mutation may also influence treatment decisions. So again, I think at the time of recurrence it is important to obtain a biopsy, not only to recheck receptors but also to be able to obtain genomic information.

Transcript edited for clarity.

Case: A 58-Year-Old Woman With Metastatic ER+ Ductal Carcinoma

• 58-year-old woman with estrogen-receptor-positive (ER+), progesterone-receptor-negative (PR-), HER2-negative (HER2-) invasive ductal carcinoma (IDC) of L breast; she completed adjuvant anastrozole for 5 years
• Now, 13 months later, she presents with 4 small (<1.0 cm) asymptomatic lesions in the left lung and mediastinal and hilar lymphadenopathy.
• Mediastinoscopy was performed and confirmed ER+ PR- Her2- carcinoma
• ECOG PS: 0
• The patient was started on abemaciclib + fulvestrant