Body mass index mediates the prognostic significance of circulating tumor cells in inflammatory breast cancer.

BACKGROUND: Obesity (BMI≥30) may be an etiologic and prognostic factor in inflammatory breast cancer (IBC). We examined the relationship between BMI, pathologic complete response (pCR), and circulating-tumor-cell (CTC) levels in IBC. METHODS: Cohort included IBC patients diagnosed 2005-2015 who had neoadjuvant chemotherapy during a prospective trial on CTCs and pathologic review describing pCR. Chi-square, logistic regression, and Cox proportional hazards models were used to identify clinicopathologic associations with event-free survival (EFS). RESULTS: Of 73 patients, 61 (84%) had CTC values, 22 (30%) achieved a pCR, and 39 (53%) were obese. There was no difference between obese and non-obese patients for pCR rates (31% vs. 29%, p = 0.90) or presence of CTCs (23% vs. 26%, p = 0.80). Among non-obese patients, CTCs were associated with worse EFS (HR 11.69, p < 0.01), but among obese patients, there was no difference in EFS between those with and without CTCs. CONCLUSIONS: BMI mediates CTCs' prognostic significance in IBC.

Circulating Tumor Cells in Breast Cancer Patients.

Breast cancer is the most commonly diagnosed cancer among women, resulting in an estimated 40,000 deaths in 2014.1 Metastasis, a complex, multi-step process, remains the primary cause of death for these patients. Although the mechanisms involved in metastasis have not been fully elucidated, considerable evidence suggests that metastatic spread is mediated by rare cells within the heterogeneous primary tumor that acquire the ability to invade into the bloodstream. In the bloodstream, they can travel to distant sites, sometimes remaining undetected and in a quiescent state for an extended period of time before they establish distant metastases in the bone, lung, liver, or brain. These occult micrometastatic cells (circulating tumor cells, CTCs) are rare, yet their prognostic significance has been demonstrated in both metastatic and non-metastatic breast cancer patients. Because repeated tumor tissue collection is typically not feasible and peripheral blood draws are minimally invasive, serial CTC enumeration might provide "real-time liquid biopsy" snapshots that could be used to identify early-stage breast cancer patients with micrometastatic disease who are at risk for disease progression and monitor treatment response in patients with advanced disease. In addition, characterizing CTCs might aid in the development of novel, personalized therapies aimed at eliminating micrometastases. This review describes current CTC isolation, detection, and characterization strategies in operable breast cancer.

Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection in Nonmetastatic Breast Cancer Patients.

BACKGROUND: Circulating tumor cells (CTCs) can be identified in approximately 25% of nonmetastatic breast cancer patients, and data are emerging regarding their prognostic significance. We hypothesized that CTCs identified before resection of the primary tumor would predict worse outcomes in nonmetastatic breast cancer patients. STUDY DESIGN: We performed CTC enumerations on 509 patients with nonmetastatic breast cancer as part of an IRB-approved study. The CTCs (per 7.5 mL blood) were identified using the CellSearch System (Janssen). The presence of ≥1 CTC meeting morphologic criteria for malignancy was considered a positive result. Log-rank test and Cox regression analysis were applied to establish the association of CTCs with relapse-free and overall survival. RESULTS: Median follow-up was 48 months and mean age was 53 years. Fifty-nine percent of patients (299 of 509) had tumors larger than 2 cm, and 46% (234 of 509) had positive lymph nodes. One hundred sixty-six patients received neoadjuvant chemotherapy (NACT) before CTC assessment, and 343 patients were chemonaïve. One or more CTC was identified in 43 of 166 (26%) NACT treated patients, and in 81 of 343 (24%) chemonaïve patients. Circulating tumor cells were not associated with tumor size, grade, or lymph node status (p = NS). Detection of 1 or more CTCs predicted decreased relapse-free (log-rank p < 0.001, hazard ratio [HR] 2.72, 95% CI 1.57 to 4.72; p < 0.001) and overall survival (log-rank p = 0.02, HR 2.29, 95% CI 1.12 to 4.67; p = 0.03) at 48 months of follow-up. CONCLUSIONS: One or more CTCs identified before resection of the primary breast tumor predicted worse relapse-free and overall survival, irrespective of primary tumor size, grade, or lymph node positivity.