Treating Metastatic ER+ Breast Cancer

Gretchen G. Kimmick, MD, MS:For metastatic disease, like I said before, the goals are to keep the patient in good health and to try not to inconvenience them very much with the side effects of treatment. So, when she had cancer recur in her lungs in 2017, because she had minimal side effects—she was coming in and was feeling good—I would have selected an endocrine agent. At that point, the options for treatment would have been an endocrine agent, alone, or an endocrine agent with a drug that makes the endocrine agent work better—like a CDK [cyclin-dependent kinase]4/6 inhibitor or everolimus.

The standard of care for people on endocrine therapy, at that point in time, would have been to put her on fulvestrant, which she was started on with one of the CDK4/6 inhibitors because the response rate is higher and there is a longer time to progression of disease. That’s one difference in what I would do with a patient who now has a hormone receptor-positive breast cancer that has recurred. If her disease had been symptomatic—if she had come in with more lung disease or some other cancer site that was causing symptoms—I would have considered giving her chemotherapy instead of endocrine therapy. The response to chemotherapy is faster and she would get faster relief of symptoms. Then, I’d think about going back to endocrine therapy later, because it was a hormone receptor-positive cancer.

It’s not very common that women initially come in with metastatic disease, but when we meet women with metastatic disease who are not on endocrine agents—they stopped endocrine agents many years ago in the adjuvant setting, or they’re newly diagnosed with metastatic disease—it is more perplexing to decide what to do in practice. The reason for that is because CDK4/6 inhibitors are more toxic than endocrine therapy, alone. And, they’re more expensive.

So, when we’re trying to decide what to do as first-line treatment in a patient who isn’t on an adjuvant aromatase inhibitor, we’re thinking about an aromatase inhibitor plus or minus this other drug. We always talk to the patient about the fact that the data that we have available right now says that the CDK4/6 inhibitor improves, or lengthens time to progression, versus the endocrine agent, alone. I’ve been in practice for a long time, and I’ve seen patients who have been on endocrine agents, by themselves. They have lived for many years with a good quality of life. The endocrine agent controls the cancer. They don’t have to deal with the expense of the CDK4/6 inhibitor and the costs of the side effects when adding that therapy. They just stay on the endocrine agent for 10 years.

Right now, the problem is that the studies compared endocrine agents with endocrine agents plus the CKD4/6 inhibitor. They showed a better response, but they don’t have a marker. There was no study done to declare who needs to get that CDK4/6 inhibitor. Right now, we don’t know who needs to get it and who is going to have the better survival with it versus without it. I do know that some women don’t need to get a CDK4/6 inhibitor. Some will do well on it for decades—on the aromatase inhibitor in the setting of new metastatic disease that’s hormone receptor-positive and HER2 [human epidermal growth factor receptor 2]-negative; or, someone who had cancer 20 years ago and had endocrine therapy. Fifteen years ago, they stopped it and now they have a recurrence.

So, the pace of the disease makes a difference. If the patient was diagnosed 20 years ago and they now have a recurrence, that’s not a fast-growing disease. Symptoms also make a difference, in terms of treatment choice. Then, we have to think about the costs of all of these things.

Transcript edited for clarity.

A 52-Year-Old Woman with MetastaticER+ Breast Cancer

March 2015

• A 52-year-old postmenopausal woman was referred for multidisciplinary assessment after being diagnosed with breast cancer, found incidentally on routine screening mammogram
  • Breast MRI revealed a 55-mm lesion in her left breast
  • FH includes a great aunt on her mother’s side who died of breast cancer at age 50
  • gBRCA1/2negative
• She underwent lumpectomy with axillary staging
• Biopsy findings:
  • Histology: invasive ductal carcinoma, grade 3
  • Hormone receptor status: ER+/ PR (-)
  • HER2,IHC 1+
  • OncotypeDx RS-high (27)
• Staging, T3BN0M0
• ECOG 1
• She completed 4 cycles of dose-dense doxorubicin/cyclophosphamide followed by 4 cycles of paclitaxel; she was then started on adjuvant letrozole

April 2017

• On routine follow-up, chest CT with contrast showed 4 small nodules in the left lung; biopsy confirmed metastatic breast cancer
  • Letrozole was changed to fulvestrant; imaging at 3 months showed progressive disease
  • She was subsequently started on treatment with capecitabine; imaging at 3 and 6 months showed a partial response
  • She was scanned for pulmonary embolism

April 2018

• On routine follow-up:
  • The patient complained of fatigue and new onset chest pain with deep breathing
  • FDG PET/CT showed 2 new liver lesions and progression in the lung lesions
  • ECOG 1
  • The patient was started on eribulin IV, with a dosing schedule of days 1 and 8, every 21 days