Recent advances in the epidemiology of inflammatory breast cancer.

The survival after the diagnosis of inflammatory breast cancer (IBC) has been steadily improving for the past few decades. This has been due to advances in the knowledge of IBC in a number of fields, including epidemiology, molecular biology, and medical management. In this review we summarize some of the most important recent advances in these fields and suggest possible opportunities for continued improvement.

Inflammatory Breast Cancer: a Separate Entity.

PURPOSE OF REVIEW: Inflammatory breast cancer (IBC) is an uncommon but highly aggressive subtype of breast cancer that contributes significantly to breast cancer-related mortality. In this review, we provide an overview of the clinical and molecular characteristics of IBC, and highlight some areas of need for ongoing research. RECENT FINDINGS: The disease is characterized by florid tumor emboli that obstruct dermal lymphatics, leading to swelling and inflammation of the affected breast. Recent studies have focused on tumor cell intrinsic features, such as signaling through pathways involved in growth and stem-like behavior, as well as extrinsic features, such as the immune system, that can be leveraged to develop new potential therapies. Key efforts have led to an increase in awareness of the disease as well as new insights into IBC pathogenesis. However, there is a strong need for new therapies designed specifically for IBC, and many unanswered questions remain.

Rates of immune cell infiltration in patients with triple-negative breast cancer by molecular subtype.

In patients with triple-negative breast cancer (TNBC), tumor-infiltrating lymphocytes (TILs) are associated with improved survival. Lehmann et al. identified 4 molecular subtypes of TNBC [basal-like (BL) 1, BL2, mesenchymal (M), and luminal androgen receptor (LAR)], and an immunomodulatory (IM) gene expression signature indicates the presence of TILs and modifies these subtypes. The association between TNBC subtype and TILs is not known. Also, the association between inflammatory breast cancer (IBC) and the presence of TILs is not known. Therefore, we studied the IM subtype distribution among different TNBC subtypes. We retrospectively analyzed patients with TNBC from the World IBC Consortium dataset. The molecular subtype and the IM signature [positive (IM+) or negative (IM-)] were analyzed. Fisher's exact test was used to analyze the distribution of positivity for the IM signature according to the TNBC molecular subtype and IBC status. There were 88 patients with TNBC in the dataset, and among them 39 patients (44%) had IBC and 49 (56%) had non-IBC. The frequency of IM+ cases differed by TNBC subtype (p = 0.001). The frequency of IM+ cases by subtype was as follows: BL1, 48% (14/29); BL2, 30% (3/10); LAR, 18% (3/17); and M, 0% (0/21) (in 11 patients, the subtype could not be determined). The frequency of IM+ cases did not differ between patients with IBC and non-IBC (23% and 33%, respectively; p = 0.35). In conclusion, the IM signature representing the underlying molecular correlate of TILs in the tumor may differ by TNBC subtype but not by IBC status.

Clinicopathologic predictors of lymph node metastasis in breast cancer patients according to molecular subtype.

PURPOSE: We present a large institutional study to determine factors predictive of axillary lymph node (LN) metastasis in breast cancer according to molecular subtype. METHODS: We conducted a retrospective analysis of our prospectively maintained breast cancer database study using data from of women managed from January 2009 through December 2013. Clinicopathologic characteristics were correlated with lymph node status and outcome according to breast cancer molecular subtyping. RESULTS: LN metastases were detected in 464 (32.1%) of 1444 women with breast cancer. By multivariate analysis, independent factors predictive of LN involvement were: for the luminal A subtype (n=776): tumour size: OR=1.05 [95% CI: 1.03-1.07] P<0.0001; lymphovascular invasion: OR=3.06 [95% CI: 1.80-5.20] P<0.0001 and tumour grade: OR=1.65 [95% CI: 1.07-2.58] P=0.026. For luminal B subtype (n=441): age: OR=0.97 [95% CI: 0.95-0.99] P=0.004; tumour size: OR=1.03 [95% CI: 1.01-1.05] P=0.002; lymphovascular invasion: OR=3.21 [95% CI: 1.92-5.44] P<0.0001; inflammatory breast cancer: OR=12.36 [95% CI: 2.18-243.3] P=0.019. For the HER2 subtype (n=72): lymphovascular invasion: OR=7.87 [95% CI: 2.10-35.2] P=0.003. For the triple negative subtype (n=155): parity: OR=1.53 [95% CI: 1.10-2.25] P=0.02; tumour size: OR=1.03 [95% CI: 1.01-1.05] P=0.002 and lymphovascular invasion: OR=7.13 [95% CI: 2.46-22.8] P=0.00048. CONCLUSION: This retrospective study provides valuable insight into LN involvement of patients with primary breast cancer according to molecular subtyping.

Inflammatory breast cancer: a proposed conceptual shift in the UICC-AJCC TNM staging system.

In the absence of histological criteria that distinguish between inflammatory and non-inflammatory breast cancer, diagnosis of inflammatory breast cancer relies entirely on the existence of clinical criteria as outlined by the TNM classification. This classification restricts patients presenting with clinical criteria characteristic of inflammatory breast cancer to subcategory T4d, which immediately relegates all patients with non-metastatic inflammatory breast cancer to stage 3, regardless of tumour size or nodal spread. Patients who present with metastatic disease are consigned to stage 4, and the TNM classification does not distinguish patients on the basis of the presence of inflammatory criteria. Evidence by our group and others suggests that patients with inflammatory breast cancer have significantly reduced overall survival among those who present with distant metastasis at diagnosis (stage 4). In light of these results, this Personal View addresses whether the current TNM staging classification accurately represents a distinction between patients with inflammatory and those with non-inflammatory breast cancer.

Distinct outcomes in patients with different molecular subtypes of inflammatory breast cancer.

OBJECTIVES: To determine the outcome of patients with luminal A, luminal B, human epidermal growth factor receptor-2 (HER-2) positive, and triple negative molecular subtypes of inflammatory breast cancer (IBC) using a retrospective analysis. METHODS: This study was conducted between February 2004 and February 2010 in 3 different hospitals in China. The clinical outcomes, pathological features, and treatment strategies were analyzed in 67 cases of IBC without distant metastases. A chi-square test and one-way ANOVA were used to assess outcomes between different subtypes. Overall survival (OS) was analyzed using the Kaplan-Meier method and multivariate analysis was conducted using the Cox regression model. RESULTS: The 2-year OS rate was 55% for the entire cohort. Median OS time among patients with luminal A was 35 months, luminal B was 30 months, HER-2 positive was 24 months, and triple negative subtypes was 20 months, and were significantly different from each other (p=0.001). Using multivariate analysis, luminal A had 76% (p=0.037), luminal B had 54% (p=0.048), and HER-2 positive subtypes had 47% (p=0.032) decreased risk of death compared with the triple negative subtype.  Furthermore, elevated Ki-67 labeling was associated with increased risk of death, while the surgical treatment significantly improved patient survival. CONCLUSION: Breast cancer subtypes are associated with distinct outcomes in IBC patients. Patients that presented with triple negative IBC had poorer outcome than luminal A, luminal B, and HER-2 subtypes. These results indicate that IBC is a heterogeneous disease similar to the conventional breast cancer.