Case Overview: A 57-Year-Old Woman with HR+/HER2- Metastatic Breast Cancer


Expert oncologist Hope Rugo, MD, FASCO, reviews the diagnosis and treatment of a 57-year-old woman with HR+/HER2- metastatic breast cancer (mBC).

Case: A 57-Year-Old Woman with HR+/HER2- Metastatic Breast Cancer


  • A 57-year-old postmenopausal woman with a personal history of breast cancer presented with sternal pain during a followup appointment

Patient history

  • She was diagnosed with stage I ER+/HER2- disease 8 years ago, at 49 years of age
    • At the time, she was prescribed 5 years of adjuvant letrozole treatment, which she completed 3 years ago

Physical exam, clinical workup, and imaging

  • Mid-sternum tenderness to palpation
  • Slight elevation in ALP, all other lab testing unremarkable
  • Bone scan showed uptake in sternum, scapula, lumbar spine, iliac crest
  • Chest/abdomen/pelvis CT revealed sclerotic bone lesions
  • Iliac bone biopsy confirmed ER+/HER2- metastatic breast cancer
    • NGS on biopsy sample was negative for mutations
  • ECOG PS=1


  • The patient received letrozole and ribociclib as first-line treatment for metastatic disease
  • 24 months after treatment initiation, CT showed enlargement of bone lesions and a single new 2-cm liver lesion
    • Liquid biopsy/ctDNA testing revealed an ESR1 mutation
  • The patient then started on elacestrant 345 mg once daily


Hope Rugo, MD, FASCO: Hello, I’m Dr Hope Rugo from the University of California San Francisco Helen Diller Family Comprehensive Cancer Center in San Francisco, California. I’ll be discussing a patient case of HR [hormone receptor]–positive, HER2 [human epidermal growth factor receptor 2]–negative metastatic breast cancer. This patient is a 57-year-old postmenopausal woman with a personal history of breast cancer, who presents with sternal pain during her follow-up appointment. She was initially diagnosed with stage I, ER [estrogen receptor]–positive, HER2- breast cancer 8 years ago, when she was 49 years old. At that time, she was prescribed 5 years of adjuvant letrozole, which she completed 3 years ago.

She has tenderness on examination to palpation of her mid-sternum. Our laboratory studies, obtained the same day, show a slight elevation in alkaline phosphatase but are otherwise normal. A bone scan shows multiple areas of uptake in bone, including sternum, scapula, lumbar spine, and iliac crest, and a CT scan of chest, abdomen, and pelvis shows sclerotic bone lesions. A biopsy for iliac bone confirms ER+, HER2- metastatic breast cancer. Next-generation sequencing on the bone biopsy was negative for mutations, and her ECOG performance status is 1, with only slight tenderness in her sternum as a symptom. She has no other sites of bone pain. At that time, we started treatment with letrozole and ribociclib as first-line therapy for metastatic disease. Twenty-four months after starting this treatment, her scan showed new bone lesions and a single 2-cm liver lesion, but she was largely asymptomatic. Liquid biopsy for ctDNA [circulating tumor DNA] revealed an ESR1 mutation. She was then started on elacestrant, 345 mg once daily.

The first question is whether a patient like this is representative of the patients we see in clinical practice who have hormone receptor–positive HER2- metastatic breast cancer. Of course, having bone-only metastatic disease is a very common presentation, although we also see patients who present initially with visceral metastases. Having this sort of presentation, with sclerotic bone lesions, is quite common. The 24-month duration of disease stability and response, with a CDK4/6 inhibitor and an aromatase inhibitor, is also quite common. We see acquisition of ESR1 mutations in a large number of patients. It’s estimated to be 40% in the second- or third-line setting. This is quite common. We also see these visceral metastases popping up when endocrine resistance begins. In the second- and third-line settings, I start to see the initial appearance of liver or lung disease. It’s common in patients with hormone-sensitive disease to present with 1 or 2 liver lesions, not a field of disease. The same is true for lung lesions. You’ll see a single nodule or 2, and these are asymptomatic without laboratory abnormalities. This is a common presentation.

Transcript edited for clarity.

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