MRI Changes in Breast Skin Following Preoperative Therapy for Patients with Inflammatory Breast Cancer.

RATIONALE AND OBJECTIVES: Preoperative systemic therapy (PST) followed by mastectomy and radiation improves survival for patients with inflammatory breast cancer (IBC). Residual disease within the skin post-PST adversely impacts surgical outcome and risk of local-regional recurrence (LRR). We aimed to assess magnetic resonance imaging (MRI) breast skin changes post-PST with pathologic response and its impact on surgical resectability. MATERIALS AND METHODS: We retrospectively reviewed 152 baseline and post-PST breast MRIs of 76 patients with IBC. Using the ACR-BIRADS MRI lexicon, we correlated skin thickness, qualitative enhancement, and kinetic analysis with pathologic response in the skin at mastectomy. RESULTS: Baseline MRI showed skin thickening in all 76 patients, 75/76 (99%) showed skin enhancement, 54/75 (72%) had medium/fast initial kinetics, usually with persistent delayed kinetics in 49/54 (91%). Following PST, 66/76 (87%) had residual skin thickening with 64/76 (84%) showing a decrease; 33/76 (43%) had persistent enhancement. The median thickness post-PST was 4.7 mm with residual tumor in the skin, and 3.0 mm without residual tumor (p = 0.008). Regardless of pathologic response, the majority of patients had persistent skin thickening on MRI following PST (100% [14/14] with residual tumor and 84% [52/62] without residual tumor). There was no association between post-PST skin thickness on breast MRI and rate of LRR. CONCLUSION: Patients with IBC have skin thickening and enhancement on baseline breast MRI, with a statistically significant reduction in skin thickness following successful PST. Despite persistent skin changes on MRI, patients achieving a partial or complete parenchymal response to PST may proceed to mastectomy with low LRR rates.

Imaging Modalities in Inflammatory Breast Cancer (IBC) Diagnosis: A Computer-Aided Diagnosis System Using Bilateral Mammography Images.

Inflammatory breast cancer (IBC) is an aggressive type of breast cancer. It leads to a significantly shorter survival than other types of breast cancer in the U.S. The American Joint Committee on Cancer (AJCC) defines the diagnosis based on specific criteria. However, the clinical presentation of IBC in North Africa (Egypt, Morocco, and Tunisia) does not agree, in many cases, with the AJCC criteria. Healthcare providers with expertise in IBC diagnosis are limited because of the rare nature of the disease. This paper reviewed current imaging modalities for IBC diagnosis and proposed a computer-aided diagnosis system using bilateral mammograms for early and improved diagnosis. The National Institute of Cancer in Egypt provided the image dataset consisting of IBC and non-IBC cancer cases. Type 1 and Type 2 fuzzy logic classifiers use the IBC markers that the expert team identified and extracted carefully. As this research is a pioneering work in its field, we focused on breast skin thickening, its percentage, the level of nipple retraction, bilateral breast density asymmetry, and the ratio of the breast density of both breasts in bilateral digital mammogram images. Granulomatous mastitis cases are not included in the dataset. The system's performance is evaluated according to the accuracy, recall, precision, F1 score, and area under the curve. The system achieved accuracy in the range of 92.3-100%.

Baseline FDG PET-CT imaging is necessary for newly diagnosed inflammatory breast cancer patients: a narrative review.

OBJECTIVE: To review and discuss the rationale behind performing baseline 18-fluorodeoxyglucose positron emission tomography-computed tomography imaging for staging of inflammatory breast cancer patients. BACKGROUND: In the past three decades, the epidemiology of inflammatory breast cancer has resulted in separation of this entity from other breast cancer in staging and treatment. Advances in cancer imaging from 18-fluorodeoxyglucose positron emission tomography to 18-fluorodeoxyglucose positron emission tomography-computed tomography have now allowed for anatomic and functional correlation in evaluating extent of disease in cancer patients. Furthermore, studies throughout the past two decades have highlighted how 18-fluorodeoxyglucose positron emission tomography-computed tomography may play a role in staging inflammatory breast cancer patients given the uniqueness of this entity when compared to other breast cancers. METHODS: Narrative overview of the literature summarizing findings in the literature from searches in computerized databases and authoritative texts. The use of 18-fluorodeoxyglucose positron emission tomography-computed tomography with respect to regional nodal staging and distant metastasis detection in inflammatory breast cancer patients is reviewed. In addition, an overview of studies conducted to date comparing the sensitivity and specificity of 18-fluorodeoxyglucose positron emission tomography-computed tomography for baseline staging in inflammatory breast cancer patients is also provided. Therapeutic influences and effect on overall survival is discussed. CONCLUSIONS: Baseline 18-fluorodeoxyglucose positron emission tomography-computed tomography allows for more optimal nodal staging, which has implications in prognosis and treatment of inflammatory breast cancer patients. It also allows for improved detection of metastasis on baseline presentation allowing therapy to potentially target these additional sites of disease.

Contralateral Axillary Metastasis in Patients with Inflammatory Breast Cancer.

BACKGROUND: Nearly one-third of patients with inflammatory breast cancer (IBC) present with de novo stage IV disease. There are limited data on frequency and clinical outcomes of contralateral axillary metastasis (CAM) in IBC with no consensus diagnostic and treatment guidelines. PATIENTS AND METHODS: Frequency of synchronous CAM was calculated in unilateral IBC patients at a single center (10/2004-6/2019). Clinicopathologic variables, diagnostic evaluation, treatment received, and overall survival (OS) were assessed and compared. RESULTS: Of 588 unilateral IBC patients, 49 (8.3%) had synchronous CAM. Of these, 32 (65.3%) also presented with metastatic disease at another distant site. CAM was not associated with age, tumor laterality, breast cancer subtype, grade, or cN stage (p > 0.05). The sensitivity/specificity to detect CAM was as follows: mammography (18.2%/99.2%), ultrasound (92.3%/95.5%), PET (90.1/99.1%), and MRI (76.0%/98.6%). Following systemic therapy, 22 patients had contralateral axillary surgery, and 18 received adjuvant contralateral nodal radiation. On multivariable analysis including tumor receptor subtypes, patients with stage IV-isolated CAM has statistically similar survival to stage III patients (HR 1.37, 95% CI 0.70-2.69, p = 0.36). Patients with Stage IV non-CAM (HR 2.18, 95% CI 1.66-2.85, p < 0.001) and stage IV-CAM plus other distant metastasis (HR 2.57, 95% CI 1.59-4.16, p < 0.001) had higher risk of death (reference: stage III disease). CONCLUSIONS: CAM in IBC was diagnosed in 8.3% of patients at presentation and was best identified by ultrasound and PET. We recommend routine contralateral axillary ultrasound as part of staging for all IBC patients. Diagnosis of CAM is a key first step toward much-needed prospective clinical trials evaluating management and outcomes of CAM in IBC.

A novel CD74-ROS1 gene fusion in a patient with inflammatory breast cancer: a case report.

BACKGROUND: CD74-ROS1 fusion genes have been detected in non-small cell lung carcinomas (NSCLC), but not in inflammatory breast cancer. CASE PRESENTATION: Herein, we report a CD74-ROS1 fusion gene identified in a 64-year-old Chinese woman with inflammatory breast cancer (IBC). The patient initially presented with a rapidly growing mass in the left breast with diffuse erythema developing over a period of 2 months. Diagnosis of invasive breast carcinoma was made by core needle biopsy. Positron emission tomography-computed tomography (PET/CT) demonstrated multiple organ metastases. Genomic DNA was extracted from tumor tissue and analyzed using next-generation sequencing (NGS). The CD74-ROS1 fusion gene was detected in the genomic DNA. The patient refused crizotinib treatment, and could not tolerate the side effects of palliative chemotherapy. Unfortunately, the patient died 4 months after diagnosis. CONCLUSION: We report the case of a CD74-ROS1 fusion gene in a patient with IBC. This may reveal, for the first time, a possible association between CD74-ROS1 gene fusion and rapid progression of inflammatory breast cancer. Multigene panel testing can be performed when rapidly progressive breast cancer occurs and could reveal potential therapeutic strategies.

New Treatment Strategies for the Inflammatory Breast Cancer.

OPINION STATEMENT: Inflammatory breast cancer (IBC) remains the most aggressive type of breast cancer. During the past decade, enormous progress has been made to refine diagnostic criteria and establish multimodality treatment strategies as keys for the improvement of survival outcomes. Multiple genomic studies enabled a better understanding of underlying tumor biology, which is responsible for the complex and aggressive nature of IBC. Despite these important achievements, outcomes for this subgroup of patients remain unsatisfactory compared to locally advanced non-IBC counterparts. Global efforts are now focused on identifying novel strategies that will improve treatment response, prolong survival for metastatic patients, achieve superior local control, and possibly increase the cure rate for locally advanced disease. Genomic technologies constitute the most important tool that will support future clinical progress. Gene-expressing profiling of the tumor tissue and liquid biopsy are important parts of the everyday clinical practice aiming to guide treatment decisions by providing information on tumor molecular drivers or primary and acquired resistance to treatment. The International IBC expert panel and IBC International Consortium made a tremendous effort to define IBC as a distinct entity of BC, and they will continue to lead and support the research for this rare and very aggressive disease. Finally, a uniform platform is now required to develop and lead large, multi-arm, proof-of-concept clinical trials that perform rapid, focused, and cost-effective evaluations of potential novel therapeutics in IBC.

Evaluation of Breast Edema Findings at T2-weighted Breast MRI Is Useful for Diagnosing Occult Inflammatory Breast Cancer and Can Predict Prognosis after Neoadjuvant Chemotherapy.

Background Prediction of occult inflammatory breast cancer (IBC) and breast cancer prognosis based on breast edema findings on T2-weighted MRI scans, even for patients without clinical signs of IBC, would be useful in both pretreatment planning and prognosis and may elucidate the underlying biologic mechanisms. Purpose To evaluate whether classification of breast edema on T2-weighted MRI scans is useful for predicting the prognosis of patients with breast cancer treated with neoadjuvant chemotherapy (NAC). Materials and Methods A retrospective evaluation was performed of women with breast cancer who underwent breast MRI and were treated with NAC between January 2011 and December 2018. Breast edema on T2-weighted images was scored on a scale of 1 to 4, as follows: (a) breast edema score (BES) 1, no edema; (b) BES 2, peritumoral edema; (c) BES 3, prepectoral edema; and (d) BES 4, subcutaneous edema (suspicious for occult IBC). Clinically evident IBC was classified as BES 5 (without MRI). The log-rank test was performed, and hazard ratios were calculated using the Cox hazard model to evaluate associations between BES and progression-free survival (PFS) and overall survival (OS). PFS rate at 100 months after initiation of therapy was also evaluated. Results Of 408 patients (median age, 53 years; range, 28-80 years), 65 (16%) had a recurrence and 27 (7%) died. The log-rank test revealed differences in PFS for BES 4 versus 1, BES 5 versus 1, BES 5 versus 2, and BES 5 versus 3 (adjusted P < .05 for all). PFS rates for BES 1-5 were 0.92, 0.85, 0.80, 0.62, and 0.58, respectively, and the corresponding OS rates at 100 months were 0.98, 0.91, 0.92, 0.77, 0.86, respectively. Conclusion Classification of breast edema findings on T2-weighted MRI scans using a breast edema score was related to the prognosis of patients after neoadjuvant chemotherapy. © RSNA, 2021 Online supplemental material is available for this article.

[18F]FDG PET/CT in the staging of inflammatory breast cancer: A systematic review.

Up to 78 % of patients with inflammatory breast cancer (IBC) present with axillary lymph node involvement and up to 40 % with distant metastases. Previous studies indicate that 2-deoxy-2-(18F)fluoro-d-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) might be used for initial staging in patients with inflammatory breast cancer (IBC). In other cancer types, [18F]FDG PET/CT has been demonstrated to be a sensitive technique, providing complementary information on locoregional and distant disease to conventional imaging modalities. This systematic review showed that 18F]FDG PET/CT detects additional locoregional lymph node metastases and distant metastases in 10.3 % of patients, that were not detected with standard staging imaging. Compared with conventional imaging procedures, [18F]FDG PET/CT had better diagnostic performance for detection of locoregional and distant metastases and should standardly be used in the diagnostic work-up of IBC patients.

Discrepancy between FDG-PET/CT and contrast-enhanced CT in the staging of patients with inflammatory breast cancer: implications for treatment planning.

PURPOSE: Optimizing treatment strategies for patients with inflammatory breast cancer (IBC) relies on accurate initial staging. This study compared contrast-enhanced computed tomography (ce-CT) and FDG-PET/CT for initial staging of IBC to determine the frequency of discordance between the two imaging modalities and potential impact on management. METHODS: 81 patients with IBC underwent FDG-PET/CT and ce-CT prior to starting treatment. FDG-PET/CT and ce-CT scans were independently reviewed for locoregional and distant metastases and findings recorded by anatomic site as negative, equivocal, or positive for breast cancer involvement. Each paired ce-CT and FDG-PET/CT case was classified as concordant or discordant for findings. Discordant findings were subclassified as (a) related to the presence or absence of distant metastases; (b) affecting the locoregional radiation therapy plan; or (c) due to incidental findings not related to IBC. RESULTS: There were 47 discordant findings between ce-CT and FDG-PET/CT in 41 of 81 patients (50.6%). Thirty (63.8%) were related to the presence or absence of distant metastases; most commonly disease detection on FDG-PET/CT but not ce-CT (n = 12). FDG-PET/CT suggested alterations of the locoregional radiation therapy plan designed by CT alone in 15 patients. FDG-PET/CT correctly characterized 5 of 7 findings equivocal for metastatic IBC on ce-CT. CONCLUSIONS: This study demonstrates differences between ce-CT and FDG-PET/CT for initial staging of IBC and how these differences potentially affect patient management. Preliminary data suggest that FDG-PET/CT may be the imaging modality of choice for initial staging of IBC. Prospective trials testing initial staging with FDG-PET/CT versus important clinical end-points in IBC are warranted.

Inflammatory breast cancer: A review from our experience.

INTRODUCTION: Inflammatory Breast Cancer (IBC) is a distinct and rare type of breast cancer accounting for up to 6% of all breast cancer cases in Europe. The aim of this study was to investigate diagnostic methods, treatments, and outcome after IBC in patients treated at a single institution in Denmark. METHOD: All patients treated for IBC at Aarhus University Hospital between 2000 and 2014 were identified and included in the cohort. Survival was assessed using Kaplan-Meier curves and log-rank statistics. RESULTS: A total of 89 patients were identified with a median follow up of 3.6 years. The overall survival at 5 and 10 years were 41% and 18%, respectively. The disease free survival at 5 and 10 years were 47% and 27%, respectively. Thirty-four percent had distant metastasis at time of diagnosis. Patients with ER positive tumors had a significantly better overall survival than patients with ER negative tumors (p = 0.01). CONCLUSION: Despite a more aggressive systemic and loco-regional treatment today, IBC is still a very serious disease with a high mortality.

Clinico-pathologic and mammographic characteristics of inflammatory and non-inflammatory breast cancer at six centers in North Africa.

PURPOSE: We describe the clinico-pathologic and mammographic characteristics of inflammatory breast cancer (IBC) and non-IBC cases enrolled in a case-control study. Because IBC is a clinico-pathologic entity with rapid appearance of erythema and other signs, its diagnosis is based on clinical observation and thus, by necessity, subjective. Therefore, we evaluate our cases by photographic review by outside expert clinicians and by degree of adherence to the two most recent definitions of IBC: the international expert panel consensus statement and American Joint Committee on Cancer (AJCC) 8th edition (we used the slightly less restrictive 7th edition definition for our study). METHODS: We enrolled 267 IBC and 274 age- and geographically matched non-IBC cases at 6 sites in Egypt, Tunisia, and Morocco in a case-control study of IBC conducted between 2009 and 2015. We collected clinico-pathologic and mammographic data and standardized medical photographs of the breast. RESULTS: We identified many differences between IBC and non-IBC cases: 54.5% versus 68.8% were estrogen receptor-positive, 39.9% versus 14.8% human epidermal growth factor receptor 2-positive, 91% versus 4% exhibited erythema, 63% versus 97% had a mass, and 57% versus 10% had mammographic evidence of skin thickening. Seventy-six percent of IBC cases adhered to the expert panel consensus statement and 36% to the AJCC definition; 86 percent were confirmed as IBC by either photographic review or adherence to the consensus statement. CONCLUSIONS: We successfully identified distinct groups of IBC and non-IBC cases. The reliability of IBC diagnosis would benefit from expert review of standardized medical photographs and associated clinical information.

Metabolic Characterization of Inflammatory Breast Cancer With Baseline FDG-PET/CT: Relationship With Pathologic Response After Neoadjuvant Chemotherapy, Receptor Status, and Tumor Grade.

BACKGROUND: The aim of this study was to determine if, in inflammatory breast cancer (IBC), baseline metabolic activity (maximum standardized uptake value [SUVmax]) of primary tumor and involved regional lymph nodes (IRLN) are prognostic markers of response after neoadjuvant systemic therapy (NAS). PATIENTS AND METHODS: Baseline 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography scans were retrospectively reviewed among 61 women with IBC who received NAS, had mastectomy, and had available pathology reports. Primary tumor and IRLN SUVmax were compared between patients with a pathologic complete response (pCR) versus those with residual disease after NAS. A multivariate Cox model was fit to evaluate the effects of SUVmax on overall survival, adjusting for pCR and stratified by receptor status and disease stage. RESULTS: SUVmax in primary IBC tumors tended to increase with tumor grade (trend test P = .06) and was lower for stage III, non-triple-negative (TN) versus stage III, TN and stage IV, non-TN disease (P = .04). Neither primary tumor nor IRLN SUVmax was significantly different comparing pCR versus residual disease after NAS. Adjusting for pathology response in the overall survival model stratified by stage and receptor status, baseline SUVmax in primary IBC tumor was associated with an estimated hazard ratio of 1.10 (95% confidence interval, 0.97-1.25; P = .15) for patients with stage III, TN and stage IV, non-TN disease. This hazard ratio corresponded to a 1.74-fold risk of death with 1 standard deviation (SD = 5.9) increase in baseline SUVmax in primary IBC tumor. CONCLUSION: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography provides prognostic information for newly diagnosed IBC. Larger studies are needed to confirm these findings and assess how such early information could affect treatment choices for IBC in the neoadjuvant setting.

Differentiating benign and malignant inflammatory breast lesions: Value of T2 weighted and diffusion weighted MR images.

OBJECTIVES: Benign and malignant inflammatory breast lesions demonstrate similar findings on both T2 weighted imaging (T2WI) and dynamic contrast enhanced (DCE) images. We hypothesized that benign inflammatory lesions might be differentiated form malignancies using a combination of apparent diffusion coefficient (ADC) values derived from diffusion weighted images (DWI) and T2WI. MATERIALS AND METHODS: We retrospectively reviewed 162 patients undergoing breast MRI (T2WI, DWI and DCE images) between 2008 and 2015 who had breast lesions with high T2WI signal intensity (High T2 SI) including 14 benign inflammatory lesions, 69 benign non-inflammatory lesions, 16 malignant inflammatory lesions and 63 malignant non-inflammatory lesions. On the High T2 SI and low T2WI signal intensity (Low T2 SI) areas in these breast lesions, we calculated ADC values from b values of 0 and 1000 s/mm2. RESULTS: The mean ADC values ±â€¯standard deviation (10-3 mm2/s) of the High T2 SI areas in benign inflammatory, benign non-inflammatory, malignant inflammatory and malignant non-inflammatory breast lesions were 0.75 ±â€¯0.18, 1.77 ±â€¯0.33, 2.06 ±â€¯0.32 and 1.88 ±â€¯0.41, respectively. Those of the Low T2 SI areas in benign inflammatory, benign non-inflammatory, malignant inflammatory and malignant non-inflammatory lesions were 0.89 ±â€¯0.15, 1.31 ±â€¯0.28, 0.87 ±â€¯0.20 and 0.94 ±â€¯0.27 respectively. ADC values of High T2 SI areas of the benign inflammatory lesions were significantly lower than those of benign non-inflammatory, malignant inflammatory, and malignant non-inflammatory lesions (p < 0.001). ADC values of Low T2 SI areas in benign inflammatory lesions were not significantly different from those of malignant inflammatory (p = 0.99) or malignant non-inflammatory lesions (p = 0.72). CONCLUSION: For breast lesions with High T2 SI, segmenting the High T2 SI for ADC mapping distinguishes benign from malignant inflammatory conditions. Using ADC mapping of the Low T2 SI areas will not result in this distinction.

Incidence of inflammatory breast cancer in patients with clinical inflammatory breast symptoms.

BACKGROUND: To describe a large cohort of women with non-puerperal inflammatory breast and to identify characteristics of inflammatory breast cancer. METHODS: All patients consulting for inflammatory breast syndrome in the breast unit of our tertiary University hospital between September 2013 and December 2015 were prospectively included. We excluded women who were pregnant or in the postpartum period. Patients underwent systematic clinical examination and imaging (breast ultrasonography and mammography). A biopsy was performed if the clinician suspected a malignant lesion of the breast. Clinicopathologic and radiologic data were registered. Statistics were performed using R (3.0.2 version) software. RESULTS: Among the 76 patients screened and included, 38 (50%) had a malignant lesion at final diagnosis, 21 (27.6%) were diagnosed with infectious disease and 17 (22.4%) with inflammatory disease of the breast. When compared to patients with benign disease, patients with a malignant lesion were significantly older (p = 0.022, CI95% 1.78-14.7), had a significantly bigger palpable mass (p<0.001, CI 95% 22.8-58.9), were more likely to have skin thickening (p = 0.05) and had more suspicious lymph nodes at clinical examination (p<0.001, CI 95% 2.72-65.3). Precise limits on ultrasonography were significantly associated with benign lesions. The presence of a mass (p = 0.04), micro calcifications (p = 0.04) or of focal asymmetry (p<0.001, CI95% 1.3-618) on mammography was significantly associated with malignant disease. CONCLUSION: Inflammatory breast cancer was common in our cohort of women consulting for inflammatory breast syndrome. Identifying these patients with high-risk malignancy is crucial in the management of an inflammatory breast.

Inflammatory breast disease: A pictorial essay with radiological-pathological correlation.

Inflammatory conditions of the breast are an important group of diseases that can mimic breast carcinoma on clinical and radiological grounds. This pictorial essay presents the radiological and pathological features of some of these entities.