Abstract
The presence of micrometastatic disease will ultimately determine the breast cancer-specific mortality of patients treated according to current guidelines. Minimal residual disease (i.e., occult tumor, not detected by conventional tests) may exist in two forms: a dormant form of only micrometastasis and a more aggressive “awakened” form where CTCs (circulating tumor cells) are actively disseminating. The hypothesis is that patients with CTCs have a more advanced or aggressive disease (that the cancer has “awoken” and there is active dissemination), whereas those patients with only micrometastasis have “dormant” disease and, although at risk of future relapse, may not do so for many years. This case study shows how determining the presence of both CTCs and bone marrow micrometastasis could be used to monitor disease activity and determine treatment changes before the appearance of metastatic disease.Presented is the case of a 53-year-old postmenopausal woman who presented with a T2N1M0 invasive ductal breast cancer. She had been treated with partial mastectomy, axillary dissection, local radiotherapy, and adjuvant chemotherapy. As the cancer was estrogen receptor-positive, she was taking tamoxifen. Two years into treatment, she was assessed for minimal residual disease and was found to be positive for CTCs and bone marrow micrometastasis. Her treatment was changed to letrozole and differing bisphosphonates. The minimal residual disease was finally eliminated, and at 16 years post-initial treatment, there was no evidence of relapse.The detection of minimal residual disease can be used to monitor treatment effect and change therapy in order to maintain the asymptomatic status of the patient and prevent disease progression.
Highlights
The presence of micrometastatic disease will determine the breast cancer-specific mortality of patients treated according to current guidelines
In the disease process, tumor cells disseminate into the circulation, with an estimated 106 circulating tumor cells (CTCs) per gram of primary tumor entering the circulation on a daily basis
This minimal residual disease, i.e., occult tumor not detected by conventional tests, may exist in two forms: a dormant form of only micrometastasis and a more aggressive “awakened” form where CTCs are actively disseminating
Summary
The presence of micrometastatic disease will determine the breast cancer-specific mortality of patients treated according to current guidelines. This case study shows that determining the presence of both CTCs and bone marrow micrometastasis in a patient treated for breast cancer could be used to monitor disease activity and determine treatment changes before the appearance of metastatic disease. The slides were processed in the same way as for CTCs. The initial evaluation for minimal residual disease showed that the patient was positive for CTCs, with 5 cells/blood sample detected (Figure 1) and positive for bone marrow micrometastasis (Figure 2). The follow-up evaluation in 2005 showed limited numbers of mammaglobin-positive cells in the bone marrow, but the patient remained negative for CTCs. There was no evidence of metastatic relapse on bone scan, CT scanning, or mammography. The changes in treatment appeared to eradicate both circulating tumor cells and bone marrow micrometastasis
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