Adjuvant Therapy in ER+ Breast Cancer

Gretchen G. Kimmick, MD, MS:We give adjuvant therapy, which is preventive therapy, for breast cancer. We think it’s fairly easy to decide whether or not to give a pill. As endocrine therapy, the pill options include things like letrozole and tamoxifen, given once per day. The side effects that are seen are mostly menopausal types of side effects—hot flashes and some joint stiffness. The bigger decision is whether or not to give chemotherapy. Chemotherapy has higher short-term risks. The regimens cause hair loss, and there are some long-term risks for cardiotoxicity and neuropathy, and those kinds of thing. So, the big decision is whether or not to give chemotherapy in addition to endocrine therapy. That’s where the Oncotype DX score comes in—to help you make that decision.

We also look at the size of the cancer, the lymph node status, and the grade of the cancer when making decision as to whether or not to give chemotherapy. She had a fairly large hormone receptor-positive, HER2 [human epidermal growth factor receptor 2]-negative cancer. It was high risk, based on her Oncotype DX score. I would suggest an anthracycline/taxane chemotherapy regimen based on the fact that the cancer was so large. There is some debate, however, as to whether or not we should be using anthracyclines in that setting.

A trial that studied 6 cycles of Taxotere [docetaxel] with Cytoxan [cyclophosphamide], which is not necessarily a benign regimen, with standard anthracycline/taxane continuing regimens was done. In patients who had lymph nodes that had cancer in them, the anthracycline-containing regimens were better. So, in patients who are at high risk and have lymph nodes that are positive, in whom you’re debating whether to use an anthracycline, I would say to use the anthracycline. However, in patients with negative lymph nodes—a tumor of less than 5 cm, or 3 cm, or less—if you’re going to use chemotherapy, 4 or 6 cycles of Taxotere with Cytoxan may be adequate.

For the 5-cm cancer, I think there’s room for debate. Some people would suggest using the 6 cycles of the taxane-containing regimen based on her age, the high grade of the cancer, and the fact that the tumor was so large. I do think it was acceptable to use the taxane and anthracycline-containing regimen in her case.

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