Over the past decade, inflammatory breast cancer (IBC), a rare and aggressive subtype of locally advanced breast cancer (LABC), has received much attention at the level of public awareness as well as at the level of research. The diagnosis of IBC is primarily clinical, although a pathological confirmation of invasive cancer is required. The most widely used definition of IBC is that which has been put forward by the American Joint Committee on Cancer; this definition states in part that IBC is “a clinicopathologic entity characterized by diffuse erythema and edema of the breast, often without an underlying palpable mass.” The incidence of IBC varies across different geographic locations but typically accounts for approximately 1% to 5% of all newly diagnosed breast cancers in the United States. The rarity of the disease makes large prospective clinical trials difficult, with the result that much of the information we have on IBC is based on retrospective studies. Furthermore, the subjective nature of the clinical diagnostic criteria has led to wide variability in clinical reports at both the epidemiological and molecular levels.
Historically, IBC was a uniformly fatal disease, with a 5-year actuarial overall survival of less than 5%, a median survival of only 15 months, and local recurrence rates as high as 50% when treated with surgery alone or in combination with radiation therapy.[4,5] A major advance of the last three decades has been the introduction of a multidisciplinary approach to the management of this aggressive disease that incorporates pre-operative chemotherapy, surgery, and radiation therapy. As a result, survival outcomes have improved significantly, with 15-year survival rates of 20% to 30% reported.[6,7] However, despite this progress, most women in whom IBC is diagnosed eventually experience a recurrence and die from the disease—highlighting the need for further research.
Specifically, current research is focused on the following objectives:
• Refining the clinical diagnostic parameters to decrease subjectivity.
• Delineating diagnostic markers to enhance diagnostic accuracy.
• Developing predictive and prognostic markers to aid in treatment planning.
• Characterizing IBC at the molecular level.
• Developing targeted therapies based on an enhanced understanding of the biology of IBC, with the hope that such an approach will positively impact prognostic outcomes.
High-throughput molecular analysis has provided great insight into the understanding and characterization of non-IBC breast tumors. This has perhaps been one of the biggest advances in the field of breast cancer. Such technology has rarely been used in the realm of IBC, in part because of IBC's comparative infrequency and thus the small number of diagnostic samples. However, the last decade has seen an upsurge in the understanding of IBC at both a clinical and a molecular level.
Epidemiology and Risk Factors
Epidemiological research on IBC has not enjoyed the kind of progress seen with other subtypes of breast cancer. This lag in progress is primarily due to the rarity of the disease, which has resulted in small numbers of patients with IBC being available to any single institution; it is also due to the lack of an agreed upon case definition for IBC, which has made it difficult for institutions to collaborate. Nonetheless, data have emerged from large population-based studies. One important observation that has been made is that, unlike with non-IBC breast tumors and despite the overall low incidence of IBC (it accounts for only 1% to 5% of all newly diagnosed breast cancer cases), the incidence of IBC in the United States appears to be increasing. This may in part be the result of increased awareness among both patients and oncologists.
It is interesting to note that there is striking geographic variation in the incidence of IBC, with the lowest incidence reported in North America and a higher incidence reported in North African countries—especially Morocco, Algeria, Tunisia, and Egypt, where the incidence of IBC has been reported to be between 10% and 15%. However, it is uncertain in these countries whether case registration is complete and whether strict definitions are used for IBC detection.
Variations in incidence have also been reported among different ethnic groups in the United States. In a large population-based study of 3,626 women with IBC diagnosed between 1994 and 1998, Wingo et al reported an IBC rate of 1.3 per 100,000 for all races combined, with African Amer-ican women having the highest risk (1.6 per 100,000) and Asian and Pacific Islander women having the lowest risk (0.7 per 100,000). Other key observations concerning women in whom IBC has been diagnosed include their younger age at presentation compared with women with non-IBC, their lower median survival compared with patients with LABC (2.9 years vs 6.4 years), and the significantly in-creased odds of IBC developing in women with a high body mass index. Currently, the mammary tumor virus is being investigated as a potential risk factor for IBC based on the observation that in North America a higher incidence of the viral sequence (71%) has been observed in women with IBC than in women with sporadic breast cancers; a similar incidence has also been observed in IBC tumor samples from Tunisia.
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