Malgorzata Banys-Paluchowski

Circulating tumor cells in breast cancer—current status and perspectives

The phenomenon of tumor cell dissemination through the blood stream has been known since the 19th century. Circulating tumor cells (CTCs) may be detected in peripheral blood of patients with breast cancer and may serve as a surrogate marker for minimal residual disease. Prognostic relevance of CTCs has already been demonstrated in early and metastatic breast cancer and commercially available detection systems are currently employed in various clinical trials. Since peripheral blood is an easily accessible compartment, serial reevaluation of CTCs is possible and may contribute to better therapy monitoring. Another potential of CTCs lies in the characterization of tumor cells. Expression profiles may differ between CTCs and primary tumor, which may result in different responses to treatment. Assessment of molecular features of CTCs may be an important step for the optimization of adjuvant and metastatic systemic therapy.

Potential Role of Circulating Tumor Cell Detection and Monitoring in Breast Cancer: A Review of Current Evidence

The phenomenon of hematogenous tumor cell dissemination in patients with solid tumors has been extensively explored over the last decades. Breast cancer research investigated at first disseminated tumor cells in the bone marrow; however, the focus soon moved to circulating tumor cells (CTCs) in the peripheral blood as blood is easily accessible without an invasive procedure. The prognostic significance of CTC presence has been shown in large studies both in adjuvant and metastatic setting and commercially available detection assays have been evaluated for monitoring in clinical trials. Beyond detection and enumeration of CTCs, the characterization of single tumor cells may enhance our knowledge on disease progression and thus optimize treatment choices.

Liquid Biopsy in Metastasized Breast Cancer as Basis for Treatment Decisions.

According to current guidelines, the additional biopsy of breast cancer metastases to analyze the receptor status for phenotype assessment is recommended. However, due to clinical difficulties in performing biopsies of metastatic lesions, the phenotype of the primary tumor most often determines the treatment decisions in metastatic breast cancer. Liquid biopsy allows the analysis of several circulating biomarkers like circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) in peripheral blood samples of cancer patients. Thus, it is an elegant and easily practicable technique that delivers information on the current disease status. Determination of the CTC phenotype regarding the hormone receptor and human epidermal growth factor receptor 2 (HER2) status might replace additional tissue biopsy for planning further therapy strategies. Liquid biopsy is a crucial step towards a more individualized cancer therapy. In contrast to the conventional concept of tissue biopsy, it offers an easy, less invasive acquisition of biomaterial. In addition, it allows multiple repetitions and real-time monitoring of metastasized disease in the clinical routine. However, the clinical utility of liquid biopsy still needs to be evaluated.

Evaluation of serum epidermal growth factor receptor (EGFR) in correlation to circulating tumor cells in patients with metastatic breast cancer

Overexpression of epidermal growth factor receptor in breast cancer is associated with estrogen receptor negativity, higher histological grade and larger tumors. The aim of the present study was to evaluate the clinical significance of serum EGFR (sEGFR) in relation to circulating tumor cells (CTCs) in metastatic breast cancer. 252 patients were enrolled in this prospective multicentre study. Blood was drawn before start of a new line of therapy. sEGFR was determined using a sandwich-type ELISA. CTCs were detected using CellSearch. sEGFR was determined in 48 healthy controls and 252 patients, with no significant differences between the two groups. Clinical-pathological parameters did not correlate with sEGFR, irrespective of the cutoff chosen. Patients with sEGFR levels above the 50th and 75th percentile were more likely to present with <5 CTCs per 7.5 ml blood (p = 0.007; p = 0.003). Patients with sEGFR ≥73 ng/ml had significantly longer overall survival than those with sEGFR <73 ng/ml (19.7 vs. 15.2 months; p = 0.007). In the multivariate analysis, presence of ≥5 CTCs, higher grading and higher line of therapy remained independent predictors of shorter OS, while only higher line of therapy and presence of ≥5 CTCs were independent predictors of shorter PFS.

Liposarcoma of the breast arising in a malignant phyllodes tumor: A case report and review of the literature

Liposarcoma of the breast is a very rare malignant tumor. It can clinically manifest as a palpable breast mass and mimic primary breast cancer. We report an unusual case of a 51-year-old female who presented with an asymptomatic right breast mass, which was histologically diagnosed as well differentiated liposarcoma arisen within malignant phyllodes tumor. The patient underwent breast conserving surgery, received no adjuvant treatment and is disease-free after 2 years. Radiological and histopathological features are presented and described in detail. Data from the literature are presented and therapy recommendations discussed.

The Value of Antiangiogenics in Breast Cancer Therapy

Tumor-induced angiogenesis supplies the tumor with nutrients and oxygen necessary to grow and provides tumor cells with a possibility to intravasate into blood vessels as first step of metastatic spread. In the last two decades, evidence has been accumulating that controlling tumor-associated angiogenesis might be a promising strategy against cancer growth. In breast cancer, a number of angiogenesis inhibitors have been investigated in clinical trials. The antibody against vascular endothelial growth factor (VEGF) bevacizumab has been approved for treatment of metastatic breast cancer in Europe. Although the mechanism of action is still under study, bevacizumab was also tested in other clinical settings of breast cancer treatment such as neoadjuvant and adjuvant therapy, as maintenance therapy, and in combination with both chemotherapy and other targeted agents. Other antiangiogenic agents, such as oral tyrosine kinase inhibitors sorafenib, sunitinib, and pazopanib, were tested and have not yielded as promising results. In this chapter, we will review the current evidence and clinical relevance of antiangiogenic treatment in early and metastatic

Male papillary breast cancer treated by wide resection and latissimus dorsi flap reconstruction: A case report and review of the literature

Breast cancer (BC) in men represents between 0.5% and 1% of all BC diagnosed each year. We report a case of advanced BC in a 62-year-old male treated at our interdisciplinary Breast Cancer Center. The patient presented with a newly diagnosed large, symptomatic mass in his left breast. Clinical examination showed a not movable mass of 16 cm diameter, deforming the whole breast; the overlying skin was livid and hypervascularized. Enlarged lymph nodes were palpable in the axillary pit. He had no concomitant diseases at time of presentation. He denied any first- or second degree family medical history of cancer of any type and he never received radiotherapy. Ultrasound guided minimal-invasive 14-gauge core biopsy revealed a moderately differentiated encapsulated papillary carcinoma with high expression of estrogen and progesterone receptors (both > 80%, IRS 12) and HER2-negative. Because of the tumor size a mastectomy with axillary dissection and chest wall reconstruction using a latissimus dorsi flap was performed. Histological analysis showed invasive growth besides typical (non-invasive) papillary carcinoma and was classified as invasive solid papillary carcinoma; pT3 (10 cm), pN0 (0/15), M0, R0; OncotypeDX Recurrence Score indicated low risk (RS: 2). After discussion in the interdisciplinary tumor board meeting, radiation therapy and tamoxifen were recommended. The patient had an uneventful recovery and is disease-free after two years of follow-up. Male BC is typically diagnosed at an advanced stage, most likely due to a lack of awareness that men can develop BC. Therefore, in case of a large tumor, a flap-based thoracic reconstruction may be required.

Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature

Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis.

Circulating Tumor Cells

Breast cancer (BC) therapy has fundamentally progressed in the last 30 years with the change from radical mastectomy to recent individualized local and systemic therapy regimens. By combining the modern treatment modalities, approximately 77 % of BC patients can be cured, still leaving potential for optimization in 23 % of cases, which will develop metastatic disease due to tumor cell dissemination despite optimal treatment. It has been known since the 19th century that most of the solid cancers shed circulating tumor cells (CTCs) into the blood circulation already at a very early stage. Based on this observation, CTCs are a surrogate marker for minimal residual disease (MRD) and precursors of metastatic disease (“seed”). Current research indicates that the phenotype and genotype differ between CTCs and primary tumor, which may result in different therapeutic responses. Therefore, characterization of CTCs may be an important step for the optimization of adjuvant and metastatic systemic treatment.