Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBC's unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy. CA Cancer J Clin 2010;60:351-375.© 2010 American Cancer Society, Inc.To earn free CME credit or nursing contact hours for successfully completing the online quiz based on this article, go to http://CME.AmCancerSoc.org.Inflammatory breast cancer (IBC) is a clinicopathological entity characterized by rapid progression and aggressive behavior from onset of disease. Historically, its prognosis has been very grim. Especially before the introduction of systemic chemotherapy, attempts to control IBC with either surgery alone or surgery combined with radiation therapy resulted in median survival times of less than 15 months and local recurrence rates as high as 50%. 1 Although survival times have increased with multimodal therapy, they are still around 35% to 40% and much lower than those for other breast cancers. Because IBC is rare, clinicians are less familiar with it than with the more common types of noninflammatory breast cancers (non-IBC). The purpose of this review is to describe the clinical diagnosis, epidemiology, imaging, biology, and multidisciplinary treatment of IBC. We summarize both current practice and novel concepts under investigation.

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We conclude that, in the adjuvant setting, c-erbB-2 status should not be used to determine whether a woman should receive adjuvant systemic therapy (weak prognostic factor). In addition, c-erbB-2 status should not be used to determine whether a patient should receive endocrine therapy. When adjuvant chemotherapy is recommended, anthracycline-based therapy should be the preferred regimen for c-erbB-2-positive patients. However, when anthracyclines are contraindicated, alkylating agent-based therapy should not be withheld. To determine the true predictive role and strength of the marker for response to each therapy, prospective randomized clinical trials or formal meta-analyses are required.

Purpose. We review the current status of multidisciplinary care for patients with inflammatory breast cancer (IBC) and discuss what further research is needed to advance the care of patients with this disease.Design. We performed a comprehensive review of the English-language literature on IBC through computerized literature searches.Results. Significant advances in imaging, including digital mammography, high-resolution ultrasonography with Doppler capabilities, magnetic resonance imaging, and positron emission tomography-computed tomography, have improved the diagnosis and staging of IBC. There are currently no established molecular criteria for distinguishing IBC from noninflammatory breast cancer. Such criteria would be helpful for the diagnosis and development of novel targeted therapies. Combinations of neoadjuvant systemic chemotherapy, surgery, and radiation therapy have led to an improved prognosis; however, the overall 5-year survival rate for patients with IBC remains very low (ϳ30%). Sentinel lymph node biopsy and skin-sparing mastectomy are not recommended for patients with IBC.Conclusion. Optimal management of IBC requires close coordination among medical, surgical, and radiation oncologists, as well as radiologists and pathologists. There is a need to identify molecular changes that define the pathogenesis of IBC to enable eradication of IBC with the use of IBC-specific targeted therapies. The Oncologist 2012;17: 891-899

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Triple-negative breast cancer (TNBC) often grows rapidly and has poor outcomes, with a high recurrence rate and a short interval between recurrence and death. New molecular-targeted therapies are being developed, but cannot be used at present. Other strategies for the management of TNBC are needed. TNBC is characterized by an expanding growth pattern without extensive intraductal spread and is a good candidate for breast-conserving therapy (BCT) with sufficient margins. The local recurrence rate after BCT is not high as those of other subtypes of breast cancer. In contrast, the regional recurrence rate is higher in TNBC than in other subtypes. Sentinel node biopsy and axillary resection should therefore be performed with the upmost caution. Radiation therapy has been shown to be useful for the management of TNBC. Radiation therapy of the chest wall after mastectomy and the regional area as well as the breast after breast-conserving surgery should be considered. Chemotherapy is the only systemic treatment available for TNBC. In our hospital, a combination of cyclophosphamide, epirubicin, and 5-fluorouracil (FEC) followed by docetaxel (DTX) or DTX followed by FEC has been used to treat tumors more than 2 cm in diameter or node-positive breast cancer. Neoadjuvant chemotherapy with these regimens has produced pathological complete response (pCR) rates higher than 20% in patients with TNBC, regardless of the specific order of agents. Tumors tend to shrink towards their center and can be a good indication for BCT. After 3 years, a pCR is associated with good outcomes, whereas a non-pCR sometimes results in distant recurrence, even when residual tumor is minimal. Patients should be closely observed during neoadjuvant chemotherapy. If there is any evidence of tumor progression, the chemotherapeutic regimen should be modified or surgery performed, without losing the opportunity to administer potentially effective treatment. Several studies indicate that neoadjuvant chemotherapy with platinum-based regimens is effective for TNBC and is thus an important treatment option. We have used regimens combining epirubicin and cyclophosphamide (EC) to treat tumors 1-2 cm in diameter without node metastasis, and 2 of 21 patients presented with distant metastases (disease-free interval, 2 and 5 years). We have not used systemic therapy to treat tumors 1 cm or less in diameter without node metastasis, and all 8 patients are alive without recurrence for more than 4 years. After distant recurrence in patients with TNBC, the same chemotherapeutic agents as those used for other subtypes of breast cancer are recommended, but the response is often disappointing, leading to poor outcomes. TNBC presents with different clinical features from other subtypes. The treatment strategy should be selected according to the characteristics of the specific subtype of breast cancer.

Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT.

Purpose Inflammatory breast cancer (IBC) is a unique clinical entity characterized by rapid onset of erythema and swelling of the breast often without an obvious breast mass. Many studies have examined and compared gene expression between IBC and non-IBC (nIBC), repeatedly finding clusters associated with receptor subtype, but no consistent gene signature associated with IBC has been validated. Here we compared microdissected IBC tumor cells to microdissected nIBC tumor cells matched based on estrogen and HER-2/neu receptor status. Methods Gene expression analysis and comparative genomic hybridization were performed. An IBC gene set and genomic set were identified using a training set and validated on the remaining data. The IBC gene set was further tested using data from IBC consortium samples and publically available data. Results Receptor driven clusters were identified in IBC; however no IBC-specific gene signature was identified. Fifteen genes were correlated between increased genomic copy number and gene overexpression data. An expression-guided gene set upregulated in the IBC training set clustered the validation set into two clusters independent of receptor subtype but segregated only 75% of samples in each group into IBC or nIBC. In a larger consortium cohort and in published data the gene set failed to optimally enrich for IBC samples. However, this gene set had a high negative predictive value for excluding the diagnosis of IBC in publically available data (100%). An IBC enriched genomic data set accurately identified 10/16 cases in the validation data set. Conclusions Even with microdissection, no IBC-specific gene signature distinguishes IBC from nIBC. Using microdissected data, a validated gene set was identified that is associated with IBC tumor cells. IBC comparative genomic hybridization data are presented, but a validated genomic data set that identifies IBC is not demonstrated.