Inflammatory Breast Cancer: A Complex Disease

The recognition of the existence of an aggressive, lethal subtype of breast cancer known as inflammatory breast cancer (IBC) dates back to 1924, when the first comprehensive assessment of IBC, based on a series of 28 patients, was presented by Lee and Tannenbaum.[1] However, the disease is rare, accounting for approximately 2.5% of all newly diagnosed breast cancers in the United States,[2] and its diagnosis is based mainly on a set of nonspecific clinical criteria. Both of these factors have contributed to the inability to accurately define prognostic and predictive markers as well as distinct molecular signatures of IBC that would distinguish it from non-IBC subtypes. In this issue of ONCOLOGY, Houchens and Merajver[3] have commendably attempted to summarize the results of existing research into the molecular determinants of this aggressive disease. The authors have focused specifically on classical prognostic and predictive markers, although these are not specific to the IBC breast tumor subtype. They have also critically examined data pertaining to the RhoC GTPase and WISP3 genes that have been found to be altered in most IBC tumors. A number of other issues surrounding IBC also deserve special attention to complement the story of this complex disease, including the prognostic impact of a multidisciplinary approach to management, the prognostic role of the HER2/neu gene, and the paradox surrounding the effect of race on survival. A Multidisciplinary Approach Perhaps one of the most striking elements of progress witnessed in the management of IBC has been the sequential incorporation of preoperative systemic chemotherapy, followed by surgery and radiation therapy. This multidisciplinary approach has essentially transformed IBC from being a once uniformly fatal disease to one where 15-year survival rates of 20% to 30% have been reported.[4,5] The use of preoperative chemotherapy afforded us the opportunity to observe patients who were able to attain a pathologic complete response (pCR)—a marker that has been shown to be a good surrogate for improved long-term survival outcomes.[6] The M.D. Anderson group has published one of the largest experiences of preoperative chemotherapy among women with IBC.[5] In this study, women with IBC exhibited 15-year disease-free survival rates of 44%, 31%, and 7% among those who had attained a complete, partial, and less than partial response, respectively,[5] indicating that even among women with IBC, response to treatment is an important surrogate for survival outcome. The HER2/neu Story nt out in their review, although a higher proportion of IBC tumors tend to overexpress HER2/neu compared to non–IBC tumors, this marker cannot distinguish between the two subtypes. However, HER2/neu may not confer the same prognostic significance among women with IBC tumors compared to those with non-IBC tumors. Our group recently reported on a cohort of 179 women with stage III IBC treated at the M.D. Anderson Cancer Center.[7] Among women with HER2/neu-positive disease, trastuzumab (Herceptin) was administered only upon recurrence and not in the adjuvant setting. Our results indicated that unlike findings in women with non-IBC tumors—where HER2/neu overexpression confers a poor prognosis—in the absence of the monoclonal antibody trastuzumab, HER2/neu overexpression did not affect recurrence-free survival. Furthermore, the administration of trastuzumab upon recurrence of disease among women with HER2/neu-positive tumors resulted in improved overall survival above and beyond those with HER2/ neu-negative tumors.