Case Summary and Optimisms for Future Advancements

Joyce O’Shaughnessy, MD:There has been great progress in estrogen receptor [ER­]-positive, HER2-negative metastatic breast cancer recently. The CDK4/6 inhibitors are really a very important new therapeutic opportunity for patients because in the first-line setting, we’re having median progression-free survivals of over 2 years. Now we have the introduction of our first PI3K inhibitor in this population, albeit just for the 35% to 40% of women whose breast cancers have a somatic mutation in PI3K.

I am really looking forward to triplet trials in the first-line setting with endocrine therapy and aromatase inhibitor or fulvestrant with a CDK4/6 inhibitor combined with either alpelisib or everolimus. I think we really want to block the PI3 kinase pathway and the CDK4/6 with excellent inhibition of the estrogen receptor to really get dramatic and even more prolonged progression-free survival [PFS] for patients. There are these triplet studies ongoing right now, and I really look forward to those data in the future to see if we can truly make breast cancer into a chronic disease with extremely long progression-free survival in the first-line setting.

Transcript edited for clarity.

A 58-Year-Old Woman With Recurrent HR+ Breast Cancer

December 2013

• A 58-year-old postmenopausal woman was referred for further evaluation of a suspicious left-sided lesion found incidentally on routine mammogram
  • MRI revealed a 4.3-cm lesion in her left breast
  • PMH unremarkable
• She underwent lumpectomy with axillary staging
• Biopsy findings:
  • Histology: lobular carcinoma, grade 2
  • Hormone receptor status: ER+/ PR (-)
  • HER2,IHC 1+
  • OncotypeDx RS, 19
• Staging, T2N0M0
• ECOG 0
• She was started on adjuvant anastrozole

September 2018

• On routine follow-up, the patient reports increasing fatigue and intermittent bouts of abdominal pain with nausea
• CT with contrast showed several small lesions in the liver; biopsy confirmed metastatic disease.
  • The patient was started on ribociclib; anastrozole was changed to fulvestrant
  • Imaging at 3 and 6 months showed a partial response