Rosai-Dorfman Disease of the Breast With Variable IgG4+ Plasma Cells: A Diagnostic Mimicker of Other Malignant and Reactive Entities.

Rosai-Dorfman disease (RDD) is an uncommon disorder, characterized by an atypical expansion of histiocytes which classically shows emperipolesis and immunoreactivity with S-100 protein. RDD affects the lymph nodes as well as extranodal sites; however, RDD of the breast is exceptionally rare. Herein, we describe the histopathologic features of 22 cases of RDD occurring in the breast, with an emphasis on the differential diagnosis. All cases were notable for an exuberant lymphocytic infiltrate with and without germinal center formation, and the majority (19/22) showed numerous plasma cells: 5 to 132/high-power field (HPF). IgG and IgG4 immunohistochemical stains were available for 13 cases; in no instance were criteria for IgG4-related sclerosing disease met, though in a single case the IgG4/IgG ratio was increased to 25%. Sclerosis was present in the majority of cases (18/22), and was frequently prominent. RDD cells showing emperipolesis were present in all cases (22/22), and ranged from rare (<1/50 HPF) to numerous (>50/50 HPF). Two of the cases in our series were initially misdiagnosed as inflammatory myofibroblastic tumor and plasma cell mastitis with granulomatous inflammation. As emperipolesis can be indistinct, the presence of stromal fibrosis and a prominent lymphoplasmacytic inflammatory infiltrate should prompt a careful search for the characteristic histiocytes, which can be aided by the use of S-100 immunohistochemistry.

Characterization of inflammatory breast cancer: a vibrational microspectroscopy and imaging approach at the cellular and tissue level.

Inflammatory breast cancer (IBC) has a poor prognosis because of the lack of specific biomarkers and its late diagnosis. An accurate and rapid diagnosis implemented early enough can significantly improve the disease outcome. Vibrational spectroscopy has proven to be useful for cell and tissue characterization based on the intrinsic molecular information. Here, we have applied infrared and Raman microspectroscopy and imaging to differentiate between non-IBC and IBC at both cell and tissue levels. Two human breast cancer cell lines (MDA-MB-231 and SUM-149), 20 breast cancer patients (10 non-IBC and 10 IBC), and 4 healthy volunteer biopsies were investigated. Fixed cells and tissues were analyzed by FTIR microspectroscopy and imaging, while live cells were studied by Raman microspectroscopy. Spectra were analyzed by hierarchical cluster analysis (HCA) and images by common k-means clustering algorithms. For both cell suspensions and single cells, FTIR spectroscopy showed sufficient high inter-group variability to delineate MDA-MB-231 and SUM-149 cell lines. Most significant differences were observed in the spectral regions of 1096-1108 and 1672-1692 cm-1. Analysis of live cells by Raman microspectroscopy gave also a good discrimination of these cell types. The most discriminant regions were 688-992, 1019-1114, 1217-1375 and 1516-1625 cm-1. Finally, k-means cluster analysis of FTIR images allowed delineating non-IBC from IBC tissues. This study demonstrates the potential of vibrational spectroscopy and imaging to discriminate between non-IBC and IBC at both cell and tissue levels.

MARCKS protein overexpression in inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of locally-advanced breast cancer. Identification of new therapeutic targets is crucial. We previously reported MARCKS mRNA overexpression in IBC in the largest transcriptomics study reported to date. Here, we compared MARCKS protein expression in IBC and non-IBC samples, and searched for correlations between protein expression and clinicopathological features. RESULTS: Tumor samples showed heterogeneity with respect to MARCKS staining: 18% were scored as MARCKS-positive (stained cells ≥ 1%) and 82% as MARCKS-negative. MARCKS expression was more frequent in IBC (36%) than in non-IBC (11%; p = 1.4E-09), independently from molecular subtypes and other clinicopathological variables. We found a positive correlation between protein and mRNA expression in the 148/502 samples previously analyzed for MARCKS mRNA expression. MARCKS protein expression was associated with other poor-prognosis features in the whole series of samples such as clinical axillary lymph node or metastatic extension, high pathological grade, ER-negativity, PR-negativity, HER2-positivity, and triple-negative and HER2+ statutes. In IBC, MARCKS expression was the sole tested variable associated with poor MFS. MATERIALS AND METHODS: We retrospectively analyzed MARCKS protein expression by immunohistochemistry in 502 tumors, including 133 IBC and 369 non-IBC, from Tunisian and French patients. All samples were pre-therapeutic clinical samples. We searched for correlations between MARCKS expression and clinicopathological features including the IBC versus non-IBC phenotype and metastasis-free survival (MFS). CONCLUSIONS: MARCKS overexpression might in part explain the poor prognosis of IBC. As an oncogene associated with poor MFS, MARCKS might represent a new potential therapeutic target in IBC.

[A Case of HER2-Positive Inflammatory Breast Cancer for Which Preoperative Chemotherapy with Pertuzumab Resulted in a Pathological Complete Response].

A 52-year-old woman presented with redness and swelling with a peau d'orange appearance in the whole right breast. Ultrasound revealed elevated subcutaneus fat density and a diffuse hypoechoic area. She was diagnosed with inflammatory breast cancer(T4dN2M0, Stage III B of the HER2 subtype). After 4 courses of EC treatment as primary systemic therapy, the hypoechoic area was still present. Subsequent chemotherapy with pertuzumab, trastuzumab, and docetaxel was effective, as hypoechoic area was not observed on ultrasound. She underwent mastectomy and axillary dissection, and pathological examination revealed pCR. At present, 2 years after surgery, the patient is alive with no reccurence.

Inflammatory Breast Cancer: Patterns of Failure and the Case for Aggressive Locoregional Management.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive subtype. This study analyzes the patterns of failure in patients with IBC treated at our institution. METHODS: We retrospectively analyzed the records of 227 women with IBC presenting between 1997 and 2011. Survival analysis was used to calculate overall survival (OS) and disease-free survival. Competing risk analysis was used to calculate locoregional recurrence (LRR). RESULTS: A total of 173 patients had locoregional-only disease at presentation (non-MET). Median follow-up in the surviving patients was 3.3 years. Overall, 132 (76.3 %) patients received trimodality therapy with chemotherapy, surgery, and radiotherapy. Three-year OS was 73.1 % [95 % confidence interval (CI) 64.9-82.4]. Cumulative LRR was 10.1, 16.9, and 21.3 % at 1, 2, and 3 years, respectively. No variable was significantly associated with LRR. Fifty-four patients had metastatic disease at presentation (MET). Median follow-up in the surviving patients was 2.6 years. Three-year OS was 44.3 % (95 % CI 31.4-62.5). Twenty-four (44.4 %) patients received non-palliative local therapy (radiotherapy and/or surgery). For these patients, median OS after local therapy was 2 years. Excluding six patients who received local therapy for symptom palliation, the crude incidence of locoregional progression or recurrence (LRPR) was 17 % (4/24) for those who received local therapy compared with 57 % (13/23) for those who did not. CONCLUSIONS: For non-MET patients, LRR remains a problem despite trimodality therapy. More aggressive treatment is warranted. For MET patients, nearly 60 % have LRPR with systemic therapy alone. Local therapy should be considered in the setting of metastatic disease to prevent potential morbidity of progressive local disease.

Molecular subtypes in patients with inflammatory breast cancer; a single center experience.

PURPOSE: The purpose of this study was to investigate the frequency and prognosis of inflammatory breast cancer (IBC) according to molecular subtypes. METHODS: Demographic data were examined for 78 patients diagnosed with IBC among breast cancer patients monitored in our clinic. Patients were staged according to the 2010 AJCC guidelines. Physical examination and radiographic findings classified on the basis of Response Evaluation Criteria in Solid Tumors (RECIST) guidelines were employed in the evaluation of clinical response to systemic therapy. Subtype analysis was performed in patients with IBC and subtypes were compared. Patients were divided on the basis of metastatic or non metastatic status and survival analysis was performed on the basis of molecular subtypes. RESULTS: Distribution analysis of molecular subtypes revealed a lower incidence of luminal A and a higher incidence of both HER 2 (+) and triple negative breast cancer in IBC. Molecular subtypes had no effect on survival in the non metastatic (p=0.61) and metastatic patient group (p=0.08). CONCLUSION: This study showed that IBC frequency is higher in HER2 overexpressing and triple negative subtypes. No survival differences were noticed in relation to molecular subtypes in IBC patients.

Outcomes After Multidisciplinary Treatment of Inflammatory Breast Cancer in the Era of Neoadjuvant HER2-directed Therapy.

OBJECTIVES: We previously reported survival trends among patients with inflammatory breast cancer (IBC) over a 30-year period before 2005. Here we evaluated survival outcomes for women with IBC diagnosed before or after October 2006, in the era of HER2-directed therapy and after opening a dedicated multidisciplinary IBC clinic. METHODS: We retrospectively identified and reviewed 260 patients with newly diagnosed IBC without distant metastasis, 168 treated before October 2006 and 92 treated afterward. Most patients received anthracycline and taxane-based neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Survival outcomes were compared between the 2 groups. RESULTS: Median follow-up time was 29 months for the entire cohort (39 and 24 mo for patients treated before and after October 2006). Patients treated more recently were more likely to have received neoadjuvant HER2-directed therapy for HER2-positive tumors (100% vs. 54%, P=0.001). No differences were found in receipt of hormone therapy. Three-year overall survival rates were 63% for those treated before and 82% for those treated after October 2006 (log-rank P=0.02). Univariate Cox analysis demonstrated better overall survival among patients treated after October 2006 than among those treated beforehand (hazard ratio [HR] 0.5; 95% confidence interval [CI], 0.34-0.94); a trend toward improved survival was noted in the multivariate analysis (HR=0.47; 95% CI, 0.19-1.16; P=0.10). Significant factors in the multivariate model included HER2-directed therapy (HR=0.38; 95% CI, 0.17-0.84; P=0.02) and estrogen receptor positivity (HR=0.32; 95% CI, 0.14-0.74; P=0.01). CONCLUSIONS: Survival improved in the context of the IBC clinic and prompt initiation of neoadjuvant HER2-directed therapeutics.

EZH2 expression correlates with locoregional recurrence after radiation in inflammatory breast cancer.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2), a member of the polycomb group proteins, has been shown to promote cancer progression and breast cancer stem cell (CSC) expansion. Breast CSCs are associated with resistance to radiation in inflammatory breast cancer (IBC), a rare but aggressive variant of breast cancer. In this retrospective study, we examined the clinical role of EZH2 in locoregional recurrence (LRR) of IBC patients treated with radiation. PATIENTS AND METHODS: 62 IBC patients who received radiation (7 pre-operative, 55 post-operative) and had adequate follow up to assess LRR were the subject of this study. Positive EZH2 status was defined as nuclear immunohistochemical staining in at least 10% of invasive cancer cells. Association of EZH2 expression with clinicopathologic features were evaluated using the Chi-square statistic and actuarial LRR free survival (LRFS) was determined using the Kaplan-Meier method. RESULTS: The median follow-up for this cohort was 33.7 months, and the 5-year overall LRFS rate was 69%. Of the 62 patients, 16 (25.8%) had LRR, and 15 out of 16 LRR occurred in EZH2 expressing cases. Univariate analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year locoregional free survival (LRFS) rate than patients who had EZH2-negative IBC (93.3% vs. 59.1%; P = 0.01). Positive EZH2 expression was associated significantly with negative ER status (97.1% in ER- vs 48.1% in ER+; P < 0.0001) and triple-negative receptor status (P = 0.0001) and all triple-negative tumors were EZH2-positive. In multivariate analysis, only triple negative status remained an independent predictor of worse LRFS (hazard ratio 5.64, 95% CI 2.19 - 14.49, P < 0.0001). CONCLUSIONS: EZH2 correlates with locoregional recurrence in IBC patients who received radiation treatment. EZH2 expression status may be used in addition to receptor status to identify a subset of patients with IBC who recur locally in spite of radiation and may benefit from enrollment in clinical trials testing radiosensitizers.

Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties.

Although there is a growing literature describing the role of macrophages in breast cancer, the role of macrophages in inflammatory breast cancer (IBC) is unclear. The aim of present study was to isolate and characterize tumor associated macrophages of IBC and non-IBC patients and define their role in IBC. Tumor infiltrating monocytes/macrophages (CD14+ and CD68+) were measured by immunohistochemistry using specific monoclonal antibodies. Blood drained from axillary vein tributaries was collected during breast cancer surgery and the percentage of CD14+ in the total isolated leukocytes was assessed by flow cytometric analysis. CD14+ cells were separated from total leukocytes by immuno-magnetic beads technique and were cultured overnight. Media conditioned by CD14+ were collected and subjected to cytokine profiling using cytokine antibody array. Wound healing and invasion assays were used to test whether cytokines highly secreted by tumor drained macrophages induce motility and invasion of breast cancer cells. We found that macrophages highly infiltrate into carcinoma tissues of IBC patients. In addition blood collected from axillary tributaries of IBC patients is highly enriched with CD14+ cells as compared to blood collected from non-IBC patients. Cytokine profiling of CD14+ cells isolated from IBC patients revealed a significant increase in secretion of tumor necrosis factor-α; monocyte chemoattractant protein-1/CC-chemokine ligand 2; interleukin-8 and interleukin-10 as compared to CD14+ cells isolated from non-IBC patients. Tumor necrosis factor-α, interleukin-8 and interleukin-10 significantly increased motility and invasion of IBC cells in vitro. In conclusion, macrophages isolated from the tumor microenvironment of IBC patients secrete chemotactic cytokines that may augment dissemination and metastasis of IBC carcinoma cells.

Risk factors for inflammatory breast cancer and other invasive breast cancers.

BACKGROUND: We investigated risk factors for inflammatory breast cancer (IBC), a rare, aggressive, and poorly understood breast cancer that is characterized by diffuse breast skin erythema and edema. METHODS: We included 617 IBC case subjects in a nested case-control study from the Breast Cancer Surveillance Consortium database (1994-2009). We also included 1151 noninflammatory, locally advanced, invasive breast cancers with chest wall/breast skin involvement (LABC), 7600 noninflammatory invasive case subjects without chest wall/breast skin involvement (BC), and 93 654 control subjects matched to case subjects on age and year at diagnosis and mammography registry. We present estimates of rate ratios (RRs) and 95% confidence intervals (CI) from conditional logistic regression analyses for each case group vs control subjects based on multiply imputed datasets. RESULTS: First-degree family history of breast cancer and high mammographic breast density increased risk of IBC, LABC, and BC. High body mass index (BMI) increased IBC risk irrespective of menopausal status and estrogen receptor (ER) expression; rate ratios for BMI 30 and greater vs BMI less than 25 were 3.90 (95% CI = 1.50 to 10.14) in premenopausal women and 3.70 (95% CI = 1.98 to 6.94) in peri/postmenopausal women not currently using hormones. BMI 30 and greater slightly increased risk of ER-positive BC (RR = 1.40; 95% CI = 1.11 to 1.76). Statistically significant reductions in risk of ER-negative IBC with older age at first birth and of ER-positive IBC with higher education were not seen for LABC and BC of the same ER status. CONCLUSIONS: Different associations with BMI, age at first birth, and education between IBC and/or LABC and BC suggest a distinct etiology for IBC.

Modern outcomes of inflammatory breast cancer.

PURPOSE: To report contemporary outcomes for inflammatory breast cancer (IBC) patients treated in the modern era of trastuzumab and taxane-based chemotherapy. METHODS AND MATERIALS: We retrospectively reviewed the charts of 104 patients with nonmetastatic IBC treated between January 2000 and December 2009. Patients who received chemotherapy, surgery, and radiation therapy were considered to have completed the intended therapy. Kaplan-Meier curves estimated locoregional control (LRC), distant metastases-free survival (DMFS), and overall survival. RESULTS: The median follow-up time was 34 months; 57 (55%) patients were estrogen receptor progesterone receptor (ER/PR) negative, 34 (33%) patients were human epidermal growth factor receptor 2 (her2)/neu amplified, and 78 (75%) received definitive postoperative radiation. Seventy-five (72%) patients completed all of the intended therapy, of whom 67 (89%) received a taxane and 18/28 (64%) of her2/neu-amplified patients received trastuzumab. For the entire cohort, the 5-year rates of overall survival, LRC, and DMFS were 46%, 83%, and 44%, respectively. The ER/PR-negative patients had a 5-year DMFS of 39% vs. 52% for ER/PR-positive patients (p = 0.03). The 5-year DMFS for patients who achieved a pathologic complete response compared with those who did not was 83% vs. 44% (p < 0.01). Those patients who received >60.4 Gy (n = 15) to the chest wall had a 5-year LRC rate of 100% vs. 83% for those who received 45 to 60.4 Gy (n = 49; p = 0.048). On univariate analysis, significant predictors of DMFS included achieving a complete response to neoadjuvant chemotherapy (hazard ratio [HR] = 5.8; 95% confidence interval [CI] = 1.4-24.4; p = 0.02) and pathologically negative lymph nodes (HR = 4.1; 95% CI = 1.4-11.9; p < 0.01), but no factor was significant on multivariate analysis. CONCLUSIONS: For IBC patients, the rate of distant metastases is still high despite excellent local control, particularly for patients who received >60.4 Gy to the chest wall. Despite the use of taxanes and trastuzumab, outcomes remain modest, particularly for those with ER/PR-negative disease and those without a pathologic complete response.

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas.

Oncotype DX is an RT-PCR-based 21-gene assay validated to provide prognostic and predictive information in the form of a Recurrence Score in patients with estrogen receptor-positive, lymph node-negative breast cancer. Although the Recurrence Score was shown to correlate with several histopathological tumor features, there is a significant proportion of cases showing an apparent discrepancy between Recurrence Score and risk estimates based on the traditional clinicopathological tumor features. In this study, we tested whether a proliferating, cellular stroma and/or admixed inflammatory cells may result in an artificially increased Recurrence Score in low-grade invasive breast cancers. We analyzed the histopathological features in 141 low-grade invasive breast carcinomas, including 41 special type (tubular, cribriform and mucinous) carcinomas, with available Recurrence Score. The tumor stroma was evaluated for increased cellularity and presence of inflammatory cells. Double immunohistochemical stains for pancytokeratin and Ki-67 was performed to assess the cell proliferation in tumor vs stromal/inflammatory cells. The clinicopathological features of tumors with Recurrence Score <18 (low risk) were compared with those with Recurrence Score ≥18 (intermediate/high risk). Carcinomas associated with Recurrence Score ≥18 showed lower progesterone receptor immunoreactivity, increased stromal cellularity and presence of inflammatory cells associated with the tumor. Double immunohistochemical stains showed significantly increased proliferation in stromal/inflammatory cells compared with carcinoma cells in cases associated with Recurrence Score ≥18. A Ki-67-positive stromal/tumor cells ratio of >1 predicted Recurrence Score ≥18 with an area under the curve of 0.8967 on receiver operator curve analysis (P<0.0001). Our results suggest that the presence of increased stromal cellularity and/or associated inflammatory cells in low-grade invasive breast carcinomas may contribute to an apparently increased risk of recurrence according to Oncotype DX Recurrence Score. Careful assessment and correlation with histopathological features in such cases may help in determining the appropriate patient management.

Triple-negative subtype predicts poor overall survival and high locoregional relapse in inflammatory breast cancer.

BACKGROUND: Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. METHODS: We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989-2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER(+) (ER(+)/PR(+) and HER-2-; n = 105), ER(+)HER-2(+) (ER(+)/PR(+) and HER-2(+); n = 37), HER-2(+) (ER(-)/PR(-) and HER-2(+); n = 83), or triple-negative (TN) (ER(-)PR(-)HER-2(-); n = 91). Kaplan-Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors. RESULTS: The median age was 50 years (range, 24-83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER(+) patients, 73.5% for ER(+)HER-2(+) patients, 54.0% for HER=2(+) patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001-.03). CONCLUSIONS: TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype.

Inflammatory breast cancer in north Africa: comparison of clinical and molecular epidemiologic characteristics of patients from Egypt, Tunisia, and Morocco.

Understanding molecular characteristics that distinguish inflammatory breast cancer (IBC) from non-IBC is crucial for elucidating breast cancer etiology and management. We included 3 sets of patients from Egypt (48 IBC and 64 non-IBC), Tunisia (24 IBC and 40 non-IBC), and Morocco (42 IBC and 41 non-IBC). Egyptian IBC patients had the highest combined erythema, edema, peau d'orange, and metastasis among the 3 IBC groups. Egyptian IBC tumors had the highest RhoC expression than Tunisians and Moroccan IBCs (87% vs. 50%, vs. 38.1, for the 3 countries, respectively). Tumor emboli were more frequent in Egyptian IBC than non-IBC (Mean ± SD: 14.1 ± 14.0 vs. 7.0 ± 12.9, respectively) (P < 0.001) and Tunisians (Mean ± SD: 3.4 ± 2.5 vs. 1.9 ± 2.0, respectively) (P < 0.01). There was no difference of emboli in Moroccan tumors (1.7 ± 1.2 vs. 1.8 ± 1.2 for IBC and non-IBC, respectively (P=0.66). This study illustrates that RhoC overexpression and tumor emboli are more frequent in IBC relative to non-IBC from Egypt and Tunisia. Tumors of Moroccans were significantly different from Egyptian and Tunisian tumors for RhoC expression and emboli. Future studies should focus on relating epidemiologic factors and clinical pictures to molecular features of IBC in these and other populations.

Phase II trial of combination of pegylated liposomal doxorubicin, cisplatin, and infusional 5-fluorouracil (CCF) plus trastuzumab as preoperative treatment for locally advanced and inflammatory breast cancer.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) was shown as active but less toxic compared to doxorubicin in advanced breast cancer. Given its low cardiotoxicity, the combination of PLD and trastuzumab appears most attractive in the treatment of human epidermal factor receptor 2 (HER2)-positive breast cancer. PATIENTS AND METHODS: We investigated the activity of 8 courses of PLD in combination with cisplatin and infusional 5-fluorouracil (CCF) plus 3-week trastuzumab in patients with primary or recurrent cT2-T4 a-d, N0-3, M0 any estrogen receptor (ER), HER2-positive breast cancer. Patients with ER and/or progesterone receptor (PgR) ≥ 10% tumors received also letrozole (plus triptorelin if premenopausal). The principal endpoint was clinical response rate; secondary endpoints were the pathologic complete response rate (pCR) and the cardiac safety of the combination. RESULTS: Thirty-two patients were enrolled in the study and all are evaluable for response and toxicity. Fifteen patients (47%) had ER-positive tumors, 15 patients and 2 patients had ER absent and ER poor tumors, respectively. Thirteen patients (41%) had inflammatory breast cancer (IBC) and 84% of patients had clinically positive nodes. A clinical response rate of 94% (95% CI, 79%-99%) and a pCR rate of 41% (95% CI, 24%-59%) were observed. Fifty-four percent of patients with IBC obtained a pCR. Eleven patients discontinued treatment before completing 8 courses as planned. No patient developed relevant cardiac toxicity. CONCLUSION: In this series of very locally advanced breast cancer, the combination of CCF and trastuzumab was very active obtaining an impressive rate of pCR, particularly in IBC, which merits further investigation in larger series.

Trimodal therapy for inflammatory breast cancer: a surgeon's perspective.

Inflammatory breast cancer (IBC) is a rare and most aggressive form of breast cancer. The onset and progression of disease are rapid; diagnosis must be made expediently to initiate treatment quickly. In this review, the clinical presentation, trimodal therapy, surgical principles and a brief summary of the Louisiana State University at Shreveport experience with IBC are presented. With this aggressive approach, 5-year survival of better than 40-50% can be expected. This represents a substantive improvement in clinical outcome for IBC patients compared with 30 years ago.