Cancer

Inflammatory breast cancer (IBC) is a form of locally advanced breast cancer that has been difficult to diagnose. With the application of the Poussée Évolutive and American Joint Committee on Cancer classifications for IBC, IBC trends have significantly shifted in Tunisia. The authors reviewed the historical data of IBC cases in Tunisia and discovered a decreasing trend to <10% IBC cases.

The authors attempted to extrapolate the approximate incidence of new cases of inflammatory breast cancer (IBC) in Italy, where IBC represents 0.6% to 2.0% of all breast cancers diagnosed every year, by taking into account the difference in incidence observed in areas that are covered or are not covered by organized screening programs. The results indicated that the clinical and biologic characteristics of IBC in Italy are quite similar to those of IBC in the United States and have the same behavior

Retroviral sequences with high homology to the mouse mammary tumor virus have been found in 40% of the sporadic breast cancers of American women. The authors report that inflammatory breast cancer in American women shows a higher incidence of viral sequences (71%) than sporadic breast cancer. Similar incidence has also been found in inflammatory breast cancers from Tunisia.

The Tumor Registry rule for recording inflammatory breast cancer (IBC) cases has changed. Results of searches using the International Classification for Oncology histology code for IBC will no longer include clinically diagnosed cases.

Histomorphometric and molecular studies indicate that inflammatory breast carcinoma has more active ongoing angiogenesis than other types of breast cancer. The growth pattern of inflammatory breast carcinoma, with numerous and large intravascular tumor emboli and scattered foci of tumor within the breast, supports the self-metastasis model and can explain the rapid local expansion of this type of breast cancer.

Advances in imaging techniques such as mammography, sonography, magnetic resonance imaging, and positron emission tomography/computed tomography (PET/CT) have improved the diagnosis and staging of inflammatory breast cancer (IBC). Data regarding PET/CT in IBC are still preliminary and will require additional studies for confirmation.

The authors presented their results from a literature review of series on targeted therapy in inflammatory breast cancer. Guided by the knowledge gained from their review, the authors currently are investigating the role of epidermal growth factor receptor as a potential therapeutic target in inflammatory breast cancer.

The pan-histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA; vorinostat) blocked self-renewal and homotypic aggregation of inflammatory breast cancer (IBC) tumor spheroids, leading to loss of the integrity of these 3 dimensional structures. Although SAHA did not alter the total amount of E-cadherin protein, it induced a change in location from the plasma membrane to the cytoplasm. SAHA is the first agent shown to be capable of altering the structure and functions of IBC tumor spheroids, which serve as in vitro surrogates of IBC tumor emboli that are the classic pathological signatures of IBC. These studies suggest that SAHA warrants further evaluation for its therapeutic effects in IBC, the most aggressive form of locally advanced breast cancer.

The 2 closely related small GTPases, RHOC and RHOA, are involved in mammary gland carcinogenesis. By selectively knocking down these proteins, we have been able to show that RHOC, and not RHOA, modulates surface expression and colocalization of α2 and β1 integrins in MDA-MB-231 on collagen I, suggesting that RHOC and RHOA play different roles in cell-matrix adhesion, motility, and invasion of MDA-MB-231. Neither RHOC or RHOA affected integrin expression in the inflammatory breast cancer cell line SUM149, further highlighting the different regulation of adhesion and motility in inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer, and its molecular basis is poorly elucidated. New high-throughput gene expression profiling technologies have been applied recently to small and heterogeneous series of clinical samples and have revealed the great transcriptional heterogeneity of IBC; the existence of molecular subtypes similar to non-IBC; differences in gene expression levels between IBC and non-IBC variables across studies; and, to date, no gene overlap across the reported signatures. In the future, larger series of IBC samples that are selected using homogeneous criteria must be profiled, and the current results call for urgent international collaborations.

Evidence from cell lines, animal models, and human samples suggests that stem cells are involved in the biology of inflammatory breast cancer (IBC). Concise analyses of gene and microRNA expression profiles of human IBC samples corroborate this hypothesis and pinpoint involved signaling pathways.

Results from studies of pharmacologic agonists, antagonists, and short-hairpin RNA indicated for the first time that the prostanoid receptor 3 (EP3) and EP4 differentially regulate vasculogenic mimicry and invasion exhibited by inflammatory breast cancer cells.

In this retrospective review of patients with inflammatory breast disease, achieving a pathologic complete response to treatment improved recurrence-free survival but had no impact on overall survival. Patients who had metastatic disease at the outset tended to do much worse, and positive estrogen receptor status conferred a better outlook.

The addition of anthracyclines and taxanes to neoadjuvant chemotherapy regimens for inflammatory breast cancer (IBC) has improved survival compared with historical controls. Vascular endothelial growth factor, a promoter of angiogenesis, is highly expressed in IBC, making the angiogenesis pathway an attractive therapeutic target.

Since 1995, innovative systemic therapies have been assessed in France in multicentric trials, initially centered on high-dose chemotherapy (HDC) with hematopoietic stem cell transplantation (3 studies, closed), and, more recently, on targeted therapies (2 studies, ongoing). More than 380 patients have been included. Anti-ERBB2 and antiangiogenic drugs are being tested and should improve survival. Because of the rarity and the heterogeneity of disease, well-designed, large-scale, collaborative studies are mandatory.

Inflammatory breast cancer is an aggressive form of locally advanced breast cancer characterized by rapid disease onset. Targeting key molecular markers, such as HER2, with novel therapeutic agents (trastuzumab and lapatinib) may improve prognosis.

The clinical-pathological features of inflammatory breast cancer include enrichment of factors that have been previously associated with radioresistant disease, including negative hormone receptor status and a phenotype enriched for relatively radioresistant breast cancer stem/progenitor cells. The prevalent basal phenotype of inflammatory breast cancer makes it an ideal clinical model to examine stem cell hypotheses, which the authors believe can help guide future trials to continue making incremental progress against this aggressive disease.