Inflammatory breast cancer (IBC) is a rare and aggressive subtype of locally advanced breast cancer (LABC). Its diagnosis is primarily clinical; however, a pathological confirmation of invasive cancer is required. Historically, IBC was a uniformly fatal disease. A major advance in the last three decades has been the introduction of a multidisciplinary approach to the management of this aggressive disease, incorporating pre-operative chemotherapy, surgery, and radiation therapy; this approach has significantly improved survival. Our review focuses on the progress made in the field of IBC research over the last decade, with particular attention to advances in the areas of epidemiology, molecular biology, and clinical management.
A Multidisciplinary Approach to IBC: A Major Advance
Perhaps the most important progress made in the field of IBC has been the adoption of a multidisciplinary approach to its diagnosis and management. The use of improved diagnostic and staging modalities followed by a sequential treatment management approach in the form of pre-operative chemotherapy followed by surgery and radiation therapy has significantly improved the prognostic outcomes associated with this aggressive disease.
Advances in imaging
The past 2 decades have seen a significant improvement in the imaging techniques used in IBC. These improved techniques have played key roles in tumor characterization, thereby facilitating image-guided biopsy, defining the extent of loco-regional disease, diagnosing distant metastases, and playing an important role in the evaluation of response to pre-operative chemotherapy.
The introduction of digital mammography with enhanced contrast resolution has allowed for improved detection of associated IBC-related abnormalities, including skin thickening, trabecular and stromal thickening, and diffuse increased breast density—which are all changes that reflect dermal lymphatic invasion. High-resolution ultrasonagraphy allows for the identification of any focal mass lesion, thereby facilitating image-guided biopsy for assessment of the involvement of loco-regional lymph nodes, which ultimately helps in the planning of locoregional treatment. MRI, when used in the diagnosis of IBC, has been found to have a high sensitivity for detection of the primary breast parenchymal lesion, as well as for global skin abnormalities; MRI can thus help guide high-yield skin punch biopsies. PET/CT has also been investigated as a tool that can potentially help in the diagnosis and staging of IBC. In a large retrospective study of 41 women with IBC that looked at the role of PET/CT as an initial staging tool, Carkaci et al reported hypermetabolic uptake in 98% of the patients. The investigators also noted that PET/CT detected the presence of ipsilateral axillary lymph nodes in 90% of women. Interestingly, 20 patients in this study were found to have distant metastatic disease, 7 of whom were not known to have metastases before they underwent PET/CT. Wang et al looked at the roles of all three imaging modalities in women with IBC. They concluded that breast MRI was the most accurate for detecting primary breast parenchymal lesions, that ultrasonography was useful for detecting the extent of loco-regional lymph node involvement, and that PET/CT was useful for providing additional information on the presence or absence of distant metastatic disease.
The optimal pre-operative regimen for the management of IBC has yet to be fully delineated due to the fact that information from large prospective clinical trials is not available. Much of the information that is available has been extrapolated from data on patients with non-IBC and from retrospective data on IBC patients. The Early Breast Cancer Trialists’ Collaborative Group’s 15-year update revealed that 6 months of an anthracycline-based polychemotherapy regimen reduced the annual breast cancer death rate by 38% among women younger than 50 years of age and by 20% among women aged 50 to 69 years. One of the first and largest studies to look at the question of anthracyline use in women with IBC comes from the University of Texas M.D. Anderson Cancer Center. The investigators pooled information on 178 women with IBC who were enrolled prospectively in 4 clinical trials; all women received a pre-operative anthracyline-based regimen followed by definitive local treatment. The investigators reported a median overall survival of 40 months, with an impressive 28% of patients being alive and disease-free at 15 years. In a more recent study by Baldini et al, the investigators looked at 68 women with IBC who were enrolled in 2 prospective trials. All women received an anthracycline-based pre-operative regimen followed by definitive local treatment and additional adjuvant chemotherapy. The investigators on this study reported 5- and 10-year overall survival rates of 44% and 32%, respectively.
Taxanes form an integral part of treatment of women with node-positive non-IBC. The role of taxanes has been investigated in women with IBC as well. Cristofanilli et al retrospectively looked at 240 women with IBC enrolled in 6 prospective clinical trials; they specifically looked at the question of whether adding taxanes to an anthracycline-based pre-operative regimen provided benefit. The authors reported that the addition of taxanes resulted in improved median, overall, and progression-free survival; the improvements reached statistical significance, specifically among women with estrogen receptor–negative disease (median overall survival, 54 months vs 32 months in patients who did not receive taxanes; median progression-free survival, 27 months vs 18 months in patients who did not receive taxanes). The incorporation of both anthracylines and taxanes into the pre-operative regimen is now considered standard of care for women with IBC.
An important component of the use of pre-operative chemotherapy is the assessment of response to treatment, with pCR considered to be an intermediate surrogate marker for improved survival. The question of whether pCR is a prognostic marker in IBC has also been investigated. Hennessy et al demonstrated that among women with IBC who had cytologically confirmed axillary lymph node metastases, 5-year recurrence-free and overall survival rates in the group of patients who attained pCR in the axillary lymph nodes (82.5% and 78.6%, respectively) were higher than the rates in those who had evidence of residual disease (37.1% and 25.4%, respectively). Ueno et al reported 15-year survival rates in women with IBC receiving pre-operative chemotherapy of 44%, 31%, and 7% in those patients who achieved a complete response, a partial response, and a less than partial response, respectively. Thus, from the available data it appears that among women with IBC, response to pre-operative chemotherapy plays a similar prognostic role to that observed among women with non-IBC.
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