Pregnancy-associated breast cancer (PABC) is commonly defined as a breast cancer occurring during pregnancy, throughout 1 year postpartum, or during lactation. Despite being a rare circumstance, PABC is one of the most common types of malignancies occurring during pregnancy and lactation, with growing incidence in developed countries, due both to decreasing age at onset of breast cancer and to increasing maternal age. Diagnosis and management of malignancy in the prenatal and postnatal settings are challenging for practitioners, as the structural and functional changes that the breast undergoes may be misleading for both the radiologist and the clinician. Furthermore, safety concerns for the mother and child, as well as psychological aspects in this unique and delicate condition, need to be constantly considered. In this comprehensive review, clinical, diagnostic, and therapeutic aspects of PABC (including surgery, chemotherapy and other systemic treatments, and radiotherapy) are presented and fully discussed, based on medical literature, current international clinical guidelines, and systematic practice.

Background: Several studies have raised the issue of the inadequacy of CellSearch^® to detect the entire pool of circulating tumor cells (CTCs) from blood of cancer patients, suggesting that cells expressing low levels of epithelial cell adhesion molecule (EpCAM) are not recognized by the capture reagent. In this exploratory study, we aimed to evaluate the status of EpCAM in CTCs isolated from a group of metastatic colorectal cancer patients, in 40% of whom, CTC had been found to be undetected by the CellSearch^® system. Methods: CTCs were analyzed using both a microfiltration method (ScreenCell) and CellSearch^® in parallel. Furthermore, since EpCAM exists in 2 different variants, we investigated the presence of both its intracellular domain (EpICD) and extracellular domain (EpEX) through immunofluorescence staining of CTCs on filters. Results: Results from immunofluorescence experiments demonstrated that, overall, EpICD and/or EpEX was expressed in 176 CTCs detected by ScreenCell, while the CellSearch^® system was able to capture only 10 CTCs. Conclusions: This is the first demonstration that the low sensitivity of CellSearch^® to detect CTCs in colorectal cancer patients is not due to the lack of EpCAM.

Circulating tumor cells (CTCs) detach from a primary tumor or its metastases and circulate in the bloodstream. The vast majority of CTCs are deemed to die into the bloodstream, with only few cells representing viable metastatic precursors. Particularly, single epithelial CTCs do not survive long in the circulation due to the loss of adhesion-dependent survival signals. In metastatic colorectal cancer, the generation of large CTC clusters is a very frequent occurrence, able to increase the aptitude of CTCs to survive in the bloodstream. Although a deepened analysis of large-sized CTC clusters might certainly offer new insights into the complexity of the metastatic cascade, most CTC isolation techniques are unfortunately not compatible with large-sized CTC clusters isolation. The inappropriateness of standard CTC isolation devices for large clusters isolation and the scarce availability of detection methods able to specifically isolate and characterize both single CTCs and CTC clusters finally prevented in-depth studies on the prognostic and predictive value of clusters in clinical practice, unlike that which has been described for single CTCs. In the present study, we validated a new sequential filtration method for the simultaneous isolation of large CTC clusters and single CTCs in patients with metastatic colorectal cancer at failure of first-line treatments. The new method might allow differential downstream analyses for single and clustered CTCs starting from a single blood draw, opening new scenarios for an ever more precise characterization of colorectal cancer metastatic cascade.

Molecular alterations are not randomly distributed in colorectal cancer (CRC), but rather clustered on the basis of primary tumor location underlying the importance of colorectal cancer sidedness. We aimed to investigate whether circulating tumor cells (CTC) characterization might help clarify how different the patterns of dissemination might be relative to the behavior of left- (LCC) compared to right-sided (RCC) cancers. We retrospectively analyzed patients with metastatic CRC who had undergone standard baseline CTC evaluation before starting any first-line systemic treatment. Enumeration of CTC in left- and right-sided tumors were compared. The highest prognostic impact was exerted by CTC in left-sided primary cancer patients, even though the lowest median number of cells was detected in this subgroup of patients. CTC exhibit phenotypic heterogeneity, with a predominant mesenchymal phenotype found in CTC from distal compared to proximal primary tumors. Most CTC in RCC patients exhibited an apoptotic pattern. CTC in left-sided colon cancer patients exhibit a predominant mesenchymal phenotype. This might imply a substantial difference in the biology of proximal and distal cancers, associated with different patterns of tumor cells dissemination. The poor prognosis of right-sided CRC is not determined by the hematogenous dissemination of tumor cells, which appears to be predominantly a passive shedding of non-viable cells. Conversely, the subgroup of poor-prognosis left-sided CRC is reliably identified by the presence of mesenchymal CTC.