Managing Recurrent Metastatic ER+ Breast Cancer

Gretchen G. Kimmick, MD, MS:In March of 2015, I met a 52-year-old woman who was referred for multidisciplinary assessment. She was diagnosed with breast cancer, which had been found during a screening mammogram. A breast MRI showed a 55-mm lesion in her left breast, which is quite large. She had a family history of breast cancer. Her aunt was age 50 when she was diagnosed. Genetic testing was negative.

She had a lumpectomy and axillary staging. She had a high-grade tumor—grade 3, invasive ductal carcinoma. The hormone receptor status was positive. She was estrogen receptor-positive and progesterone receptor-negative. Her tumor was HER2 [human epidermal growth factor receptor 2]-negative with an immunohistochemistry score of 1+. We also did an Oncotype DX score, which was in the high-risk range, 35.

She was staged as T3N0. There was no clinical evidence of metastasis. She had an excellent performance status, except that she had just had surgery. The decision was made to give her chemotherapy. She received standard chemotherapy with Adriamycin [doxorubicin] and Cytoxan [cyclophosphamide], followed by Taxol [paclitaxel]. Then, since her cancer had been hormone receptor-positive, she was started on endocrine therapy, with letrozole as adjuvant treatment.

In April of 2017, she had a CT scan with contrast. The scan showed a 4-mm nodule in her left lung. A biopsy was done, and it confirmed metastatic breast cancer to the lungs, which was, again, estrogen receptor-positive and HER2-negative. Endocrine therapy with letrozole was stopped and next-line endocrine therapy with fulvestrant was started. That was continued for 3 months. Then, we did restaging scans to monitor for response. Again, the cancer had grown.

Treatment with endocrine therapy was stopped and chemotherapy, with an oral agent called capecitabine, was started. Scans at 3 and 6 months after starting capecitabine revealed that there was a partial response. She came back for scans in April of 2018. She was tired and had pain when she breathed deeply. Again, we did scans. We checked the CT angiogram. There was no pulmonary embolism, but the lesions in the lungs were worse. And, at that point, she had new liver metastasis.

The oral agent was stopped, and she started intravenous chemotherapy with eribulin at a standard dose of 1.4 mg/m²every week, for 2 weeks in a row. Then, she had 1 week off.

To start off with, when she was diagnosed, she had a fairly large tumor. It was hormone receptor-positive and HER2-negative. The tumor was found through a mammogram, which means she probably didn’t do breast exams because it was fairly large. The risk of it coming back was high enough that I may have considered not even doing an Oncotype DX test. I would want to give her the benefit of treatment, with a high-grade tumor that was progesterone receptor-negative.

The Oncotype DX score confirmed that the risk was high. A note should be made about the management of people who have hormone receptor-positive cancers that are HER2-negative. The TAILORx data from the 2018 ASCO [American Society of Clinical Oncology] Annual Meeting, that was published on as well, showed that women who had hormone receptor-positive, HER2-negative, node-negative breast cancers and an intermediate Oncotype DX recurrence score, and negative lymph nodes, probably don’t benefit enough from chemotherapy to make it worth doing. At the ASCO Annual Meeting, that was a practice-changing presentation.

The fact that her cancer actually returned within a few years is concerning, which kind of goes along with having a high-risk Oncotype DX score that shows up later. She did not respond to initial endocrine therapy for metastatic disease. That puts you in a situation where you’re managing a patient who has hormone receptor-positive, HER2-negative cancer that is not responsive to endocrine therapy. So, she was started on chemotherapy.

Prognostically, with recurrent cancer, the Oncotype DX score doesn’t have much to do with how things go after the cancer recurs. We know that recurrent breast cancer is not curable. So, she’ll be treated with chemotherapy, or some type of treatment to control the disease for the rest of her life.

I usually tell patients that when their cancer recurs, the point is to keep them vertical instead of horizontal. You’re giving them treatment that actually makes their life better and can help them live longer. They can tolerate the treatment and keep the cancer under control so that they can go about what they want to do with their life, each day at a time.

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