Rates of Pathologic Complete Response and Overall Survival in Patients with Inflammatory Breast Cancer: A National Cancer Database Study.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have worse survival compared with stage III non-IBC matched cohorts; however, the prognostic significance of achieving pathologic complete response (pCR) in the setting of IBC is not well described. We evaluated overall survival (OS) between IBC patients and non-IBC patients who achieved pCR. METHODS: Adult females diagnosed in 2010-2018 with clinical prognostic stage III unilateral invasive breast cancer treated with neoadjuvant chemotherapy (NAC) followed by surgery were selected from the National Cancer Database. Unadjusted OS from surgery was estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Cox proportional hazard models were used to estimate the association of study groups with OS after adjustment for available covariates. RESULTS: The study included 38,390 patients; n = 4600 (12.0%) IBC and n = 33,790 (88.0%) non-IBC. Overall pCR rates were lower for IBC compared with non-IBC (20.7% vs. 23.3%; p < 0.001). Among those achieving pCR, 5-year mortality was higher for IBC patients (16.4%, 95% confidence interval [CI] 13.9-19.1%) versus non-IBC patients (9.1%, 95% CI 8.4-9.8%; log-rank p < 0.001). Among all patients achieving pCR, IBC remained associated with worse OS compared with non-IBC (hazard ratio 1.48, 95% CI 1.19-1.85; p < 0.001). CONCLUSION: We found a lower pCR rate and worse OS in IBC patients compared with non-IBC stage III patients. Despite effective systemic therapies, achieving a pCR for IBC patients may not carry the same prognostic impact compared with non-IBC stage III patients.

Self-Reported Management of Inflammatory Breast Cancer Among the American Society of Breast Surgeons Membership: Consensus and Opportunities.

BACKGROUND: Inflammatory breast cancer (IBC) is rare and biologically aggressive. We sought to assess diagnostic and management strategies among the American Society of Breast Surgeons (ASBrS) membership. PATIENTS AND METHODS: An anonymous survey was distributed to ASBrS members from March to May 2023. The survey included questions about respondents' demographics and information related to stage III and IV IBC management. Agreement was defined as a shared response by >80% of respondents. In areas of disagreement, responses were stratified by years in practice, fellowship training, and annual IBC patient volume. RESULTS: The survey was administered to 2337 members with 399 (17.1%) completing all questions and defining the study cohort. Distribution of years in practice was 26.0% 0-10 years, 26.6% 11-20 years and 47.4% > 20 years. Overall, 51.2% reported surgical oncology or breast fellowship training, 69.2% maintain a breast-only practice, and 73.5% treat < 5 IBC cases/year. Agreement was identified in diagnostic imaging, trimodal therapy, and mastectomy with wide skin excision for stage III IBC. Lack of agreement was identified in surgical management of the axilla; respondents with < 10 years in practice or fellowship training were more likely to perform axillary dissection for cN0-N2 stage III IBC. Locoregional management of stage IV IBC was variable. CONCLUSIONS: Among ASBrS members, there is consensus in diagnostic evaluation, treatment sequencing and surgical approach to the breast in stage III IBC. Differences exist in surgical management of the cN0-2 axilla with uptake of de-escalation strategies. Clinical trials are needed to evaluate oncologic safety of de-escalation in this high-risk population.

Racial disparities in treatment and outcomes between non-Hispanic Black and non-Hispanic White women with nonmetastatic inflammatory breast cancer.

PURPOSE: The incidence rate of inflammatory breast cancer (IBC) is higher among non-Hispanic Black (NHB) than non-Hispanic White (NHW) women. We examined the differences in treatment and outcomes between NHB and NHW women with IBC, accounting for demographic, clinicopathological, and socioeconomic factors. METHODS: We collected data from the Surveillance, Epidemiology, and End Results database for NHB and NHW women with IBC diagnosed between 2010-2016. We analyzed the odds of receiving chemotherapy, radiation, and surgery between NHB and NHW women. We evaluated overall survival (OS) with Kaplan-Meier methods and Cox proportional hazards methods. Competing risk analysis was used to compare the risk of breast cancer death between NHB and NHW women. We also evaluated the magnitude of survival disparities within the strata of demographic, socioeconomic, and treatment factors. RESULTS: Among 1,652 NHW and 371 NHB women with IBC, the odds of receiving chemotherapy, surgery, and radiation were similar for NHB and NHW. After 39-month follow-up, the median OS was 40 and 81 months for NHB and NHW, respectively (p < 0.0001). The risk of breast cancer death was higher for NHB than NHW women (5-year risk of breast cancer death, 51% vs. 35%, p < 0.0001). CONCLUSION: After adjustment for demographic, clinicopathological, and socioeconomic factors; NHB women with IBC had similar odds of receiving surgery, chemotherapy, and radiation therapy, but were more likely to die of the disease compared to their NHW counterparts. Our findings suggest the presence of masked tumor biology, treatment, or socioeconomic factors associated with race that can lead to worse IBC outcomes.

Low Rates of Local-Regional Recurrence Among Inflammatory Breast Cancer Patients After Contemporary Trimodal Therapy.

BACKGROUND: Inflammatory breast cancer (IBC) represents a rare (2-3 %) but aggressive subset of breast cancer with a historically reported 5-year overall survival rate of 50 % and a 3-year local-regional recurrence (LRR) rate of 20 %. This study aimed to evaluate long-term LRR in a contemporary cohort of non-metastatic IBC patients undergoing trimodal therapy at a single institution and identify factors associated with local and distant failure. METHODS: The study identified 262 patients with non-metastatic IBC who received trimodal therapy (neoadjuvant chemotherapy, modified radical mastectomy, adjuvant radiation) from an institutional prospective database (2007-2019). Long-term outcomes of local-regional and distant metastasis were reported. Survival outcomes were analyzed using the Cox proportional hazards regression model. RESULTS: The median age at diagnosis was 52 years, and the median follow-up period was 5.1 years. In this cohort, 82 (31.3 %) patients achieved a pathologic complete response (pCR) in the breast and axilla. Local-regional recurrence was observed in 18 (6.9 %) patients (11 isolated to the chest wall, 4 isolated to regional nodes, and 3 involving chest wall and ipsilateral axillary nodes). Distant metastasis was observed in 92 (35.1 %) patients. During the follow-up period, 90 deaths occurred. In the multivariate analysis, pCR was associated with improved disease-free survival (hazard ratio [HR], 0.26; 95 % confidence interval [CI], 0.13-0.51; p = 0.001) and overall survival (HR, 0.31; 95 % CI, 0.15-0.65; p = 002). CONCLUSIONS: During a median follow-up period longer than 5 years, the local-regional relapse rate for the IBC patients treated with contemporary trimodal therapy was 6.9%, similar to that for the non-IBC patients. After chemotherapy, surgical resection with modified radical mastectomy to negative margins and postmastectomy radiation therapy resulted in excellent long-term local-regional control.

Tailoring Treatment for Patients with Inflammatory Breast Cancer.

OPINION STATEMENT: Inflammatory breast cancer (IBC) is a rare but aggressive subtype of breast cancer that has a propensity for locoregional recurrence and distant metastasis and is associated with a disproportionately high percentage of breast cancer deaths. IBC is not resectable at initial diagnosis and trimodality therapy is considered the standard treatment for IBC. This includes systemic therapy upfront, followed by modified radical mastectomy and comprehensive chest wall and regional node radiation. Despite this aggressive multi-modal treatment strategy, the prognosis remains worse in IBC when compared with non-inflammatory locally advanced breast cancers. For patients presenting with de novo stage IV IBC, treatment recommendations vary depending on tumor burden, cancer subtype, and presence of comorbidities. Efforts to improve outcomes in IBC are currently underway; however, progress has been affected by the low incidence of disease and limited number of dedicated studies in this population. Improvements in systemic therapies in breast cancer in general are likely to lead to improvements in IBC as well. More dedicated trials are needed to identify additional treatment strategies that may help to improve prognosis for these patients. Additionally, better frameworks for diagnosis, risk stratification based upon factors such as molecular subtype and response to neoadjuvant therapy, will be important to make further progress in IBC.

Incidence, characteristics, and management of central nervous system metastases in patients with inflammatory breast cancer.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have a high risk of central nervous system metastasis (mCNS). The purpose of this study was to quantify the incidence of and identify risk factors for mCNS in patients with IBC. METHODS: The authors retrospectively reviewed patients diagnosed with IBC between 1997 and 2019. mCNS-free survival time was defined as the date from the diagnosis of IBC to the date of diagnosis of mCNS or the date of death, whichever occurred first. A competing risks hazard model was used to evaluate risk factors for mCNS. RESULTS: A total of 531 patients were identified; 372 patients with stage III and 159 patients with de novo stage IV disease. During the study, there were a total of 124 patients who had mCNS. The 1-, 2-, and 5-year incidence of mCNS was 5%, 9%, and 18% in stage III patients (median follow-up: 5.6 years) and 17%, 30%, and 42% in stage IV patients (1.8 years). Multivariate analysis identified triple-negative tumor subtype as a significant risk factor for mCNS for stage III patients. For patients diagnosed with metastatic disease, visceral metastasis as first metastatic site, triple-negative subtype, and younger age at diagnosis of metastases were risk factors for mCNS. CONCLUSIONS: Patients with IBC, particularly those with triple-negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing mCNS. Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted.

Inflammatory breast cancer defined: proposed common diagnostic criteria to guide treatment and research.

PURPOSE: Inflammatory breast cancer is a deadly and aggressive type of breast cancer. A key challenge relates to the need for a more detailed, formal, objective definition of IBC, the lack of which compromises clinical care, hampers the conduct of clinical trials, and hinders the search for IBC-specific biomarkers and treatments because of the heterogeneity of patients considered to have IBC. METHODS: Susan G. Komen, the Inflammatory Breast Cancer Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to review the state of IBC and to propose initiatives to advance the field. After literature review of the defining clinical, pathologic, and imaging characteristics of IBC, the experts developed a novel quantitative scoring system for diagnosis. RESULTS: The experts identified through consensus several "defining characteristics" of IBC, including factors related to timing of onset and specific symptoms. These reflect common pathophysiologic changes, sometimes detectable on biopsy in the form of dermal lymphovascular tumor emboli and often reflected in imaging findings. Based on the importance and extent of these characteristics, the experts developed a scoring scale that yields a continuous score from 0 to 48 and proposed cut-points for categorization that can be tested in subsequent validation studies. CONCLUSION: To move beyond subjective 'clinical diagnosis' of IBC, we propose a quantitative scoring system to define IBC, based on clinical, pathologic, and imaging features. This system is intended to predict outcome and biology, guide treatment decisions and inclusion in clinical trials, and increase diagnostic accuracy to aid basic research; future validation studies are necessary to evaluate its performance.

Guideline-Consistent Treatment for Inflammatory Breast Cancer Provides Associated Survival Benefit Independent of Age.

BACKGROUND: Guideline-consistent treatment (GCT) for inflammatory breast cancer (IBC) includes neoadjuvant chemotherapy (NAC), modified radical mastectomy (MRM), and radiation. We hypothesized that younger patients more frequently receive GCT, resulting in survival differences. METHODS: Using the National Cancer Database (2004-2018), female patients with unilateral IBC (by histology code and clinical stage T4d) were stratified by age (< 50, 50-65, > 65 years). Factors associated with NAC, MRM, radiation, and "GCT" (defined as all three treatments) were identified using multivariable logistic regression. Multivariable Cox proportional hazards regression identified predictors of overall survival. RESULTS: Of 3278 IBC patients, 30% were younger than 50 years, 44% were 50-65 years of age, and 26% were older than 65 years. The youngest group comprised the greatest proportion of non-White patients ([35%] vs. [29%] age 50-65 years and [23%] age > 65 years, p < 0.001) and was most often treated at academic facilities ([33%] vs. [28%] age 50-65 years; and [23%] age > 65, p < 0.001). Patients older than 65 years received NAC, MRM, and radiation less frequently, and only 35% underwent GCT (vs. [57%] age 50-65 years and [52%] age < 50 years; p < 0.001). On multivariable logistic regression, age older than 65 years independently predicted omission of NAC (odds ratio [OR], 0.36), MRM (OR, 0.56), and radiation (OR, 0.56) (all p < 0.001), and patients older than 65 years also were less likely to undergo GCT than patients 50-65 years of age (OR, 0.65; p = 0.001). GCT was associated with superior overall survival in all three age groups ([hazard ratio {HR}, 0.61] age < 50 years, [HR, 0.62] age 50-65 years, [HR, 0.53] age > 65 years; all p < 0.001). CONCLUSION: Advanced age alone should not limit receipt of GCT for IBC. Multimodal care should be performed for IBC patients of all ages to improve oncologic outcomes for this aggressive breast cancer subtype.

Long-term Oncologic Outcomes in Patients with Inflammatory Breast Cancer with Supraclavicular Nodal Involvement.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer characterized by rapid progression and early metastasis, often with advanced nodal locations, including the supraclavicular (SCV) nodal basin. Previously considered M1 disease, ipsilateral clinical supraclavicular node involvement (N3c) disease is now considered locally advanced disease and warrants treatment with intent to cure. The objective of this study was to evaluate the long-term outcomes of patients with IBC and N3c disease. PATIENTS AND METHODS: This study was conducted using a prospectively collected database of all patients with IBC treated at a dedicated cancer center from 2007 to 2019. Surgical patients with SCV nodal involvement and complete follow-up were identified. Our primary outcome was 5-year overall survival (OS). Multivariate Cox proportional hazards models were used to determine predictors for survival. Event-free survival (EFS) and OS were calculated using the Kaplan-Meier method. RESULTS: There were 70 patients who met inclusion criteria. All patients underwent comprehensive trimodality therapy. The majority of patients had complete (66.2%) radiologic response in the SCV nodal basins following neoadjuvant therapy. Six patients (8.6%) had a locoregional recurrence, with two (2.9%) occurring in the supraclavicular fossa. The 5-year OS was 60.2% [95% confidence interval (CI) 47.7-72.7%]. Increasing age (hazard ratio 2.7; p = 0.03) and triple-negative subtype (hazard ratio 4.9; p = 0.03) were associated with poor OS. The 5-year EFS was 56.1% (95% CI 40.9-68.8%). The presence of more than ten positive axillary nodes on final surgical pathology (hazard ratio 5.5; p = 0.01) predicted poor EFS. CONCLUSIONS: With comprehensive trimodality therapy and multidisciplinary team approach, patients with IBC with supraclavicular nodal involvement experience excellent locoregional control and favorable survival.

Lymphedema in Inflammatory Breast Cancer Patients Following Trimodal Treatment.

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a debilitating sequela of breast cancer treatment and is becoming a greater concern in light of improved long-term survival. Inflammatory breast cancer (IBC) is a rare and aggressive malignancy for which systemic therapy, surgery, and radiotherapy remain the standard of care, thereby making IBC patients highly susceptible to developing BCRL. This study evaluated BCRL in IBC following trimodal therapy. METHODS: IBC patients treated from 2016 to 2019 were identified from an institutional database. Patients were excluded if they presented with recurrent disease, underwent bilateral axillary surgery, did not complete trimodal therapy, or were lost to follow-up. Demographic, clinicopathologic factors, oncologic outcomes, and perometer measurements were recorded. BCRL was defined by clinician diagnosis and/or objective perometer measurements when available. Time to development of BCRL and treatment received were captured. RESULTS: Eighty-three patients were included. Median follow-up was 33 months. The incidence of BCRL was 50.6% (n = 42). Mean time to BCRL from surgery was 13 (range 2-24) months. Demographic and clinicopathologic features were similar between patients with and without BCRL with exception of higher proportion receiving delayed reconstruction in the BCRL group (38.1% vs. 14.6%, p = 0.03). Forty patients (95.2%) underwent BCRL treatment, which included physical therapy (n = 39), compression (n = 38), therapeutic lymphovenous bypass (n = 13), and/or vascularized lymph node transfer (n = 12). CONCLUSIONS: IBC patients are at high-risk for BCRL after treatment, impacting 51% of patients in this cohort. Strategies to reduce or prevent BCRL and improve real-time diagnosis should be implemented to better direct early management in this patient population.

The Role of Mastectomy in De Novo Stage IV Inflammatory Breast Cancer.

INTRODUCTION: The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population. METHODS: Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007-2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local-regional recurrence patterns were described and survival analyses were conducted. RESULTS: All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2-]: 31.1% vs. 44.2%; HR-negative [HR-]/HER2+: 24.4% vs. 15.4%; and HR-/HER2-: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p < 0.001). Of the 47 patients who completed trimodality therapy, 6 (12.8%) had a local-regional recurrence. Median overall survival (OS) was 19 months in the non-MRM group and 58 months in the MRM group (p < 0.001). On multivariable analysis, clinical N3 disease (hazard ratio 2.16, 95% confidence interval [CI] 1.07-4.37; p = 0.03) as well as tumor subtypes HR+/HER2- (hazard ratio 4.98, 95% CI 1.15-21.47; p = 0.03) and HR-/HER2- (hazard ratio 7.18, 95% CI 1.66-31.07; p = 0.008) were associated with decreased OS. Partial/complete response of distant disease to chemotherapy (hazard ratio 0.43, 95% CI 0.24-0.77; p = 0.005) and receipt of MRM (hazard ratio 0.52, 95% CI 0.29-0.93; p = 0.03) were independently associated with improved OS. CONCLUSIONS: In our retrospective study, MRM in de novo stage IV IBC patients is an independent factor associated with improved OS. Our findings strongly support the need for prospective randomized trials evaluating possible survival benefits of MRM in de novo stage IV IBC patients.

Inflammatory Breast Cancer at the Extremes of Age.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare breast malignancy with poor outcomes compared with non-IBC. Age-related differences in tumor biology, treatment, and clinical outcomes have been described in non-IBC. This study evaluated age-related differences in IBC. METHODS: From an institutional prospective database, patients with an IBC diagnosed from 2010 to 2019 were identified. Age was categorized as 40 years or younger, 41 to 64 years, and 65 years or older. Demographics, clinicopathologic features, and treatment received were compared. Recurrence and survival outcomes were analyzed using the log-rank test and the Cox proportional hazards model. RESULTS: Of 523 IBC patients, 113 (21.6%) were age 40 years or younger, and 72 (13.8%) were age 65 years or older. The groups did not differ statistically by race/ethnicity, N stage, clinical stage, or tumor subtype. The younger patients included a higher proportion of Hispanic and Asian patients, triple-negative breast cancer (TNBC), and clinical N2/N3. Trimodality therapy was received by 92% of the stage 3 patients, with no difference in pathologic complete response (pCR) by age (23.3% vs 28.6%; p = 0.46). During a median follow-up period of 40 months, 17% of the patients experienced locoregional recurrence and 42.8% had distant metastasis. No difference in 3-year recurrence-free survival (57.9% vs 42.6% vs 54%; p = 0.42, log rank) or overall survival (OS) (75.6% vs 77.1% vs 64.4%; p = 0.31, log rank) by age was observed, and no difference in OS by age in de novo stage 4 disease was observed. In the multivariate analysis, worse OS was associated with TNBC (hazard ratio [HR], 1.99, 95% confidence interval [CI], 1.31-3.05) and no pCR (HR, 4.45; 95% CI, 2.16-9.18). CONCLUSION: No significant differences were observed in demographics, treatment patterns, or clinical outcomes for IBC patients age 40 years or younger compared with those age 65 years or older treated by a specialized multidisciplinary team. These findings do not support age-related treatment de-escalation in IBC.

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.

Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis.

BACKGROUND: Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. METHODS: Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. RESULTS: Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR-/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR-/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR-/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216-0.902; P = 0.025) and HR-/HER2- cohort (HR = 1.738; 95% CI: 1.192-2.534; P = 0.004). CONCLUSIONS: Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR-/HER2+ subtype is associated with a better outcome, and HR-/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

Inflammatory breast cancer: early recognition and diagnosis is critical.

Inflammatory breast cancer is a rare and aggressive malignancy that is often initially misdiagnosed because of its similar presentation to more benign breast pathologies such as mastitis, resulting in treatment delays. Presenting symptoms of inflammatory breast cancer include erythema, skin changes such as peau d' orange or nipple inversion, edema, and warmth of the affected breast. The average age at diagnosis is younger than in noninflammatory breast cancer cases. Known risk factors include African American race and obesity. Diagnostic criteria include erythema occupying at least one-third of the breast, edema, peau d' orange, and/or warmth, with or without an underlying mass; a rapid onset of <3 months; and pathologic confirmation of invasive carcinoma. Treatment of inflammatory breast cancer includes trimodal therapy with chemotherapy, surgery, and radiation. An aggressive surgical approach that includes a modified radical mastectomy enhances survival outcomes. Although the outcomes for patients with inflammatory breast cancer are poor compared with those of patients with noninflammatory breast cancer, patients with inflammatory breast cancer who complete trimodal therapy have a favorable locoregional control rate, underscoring the importance of a prompt diagnosis of this serious but treatable disease. Obstetrician-gynecologists and other primary care providers must recognize the signs and symptoms of inflammatory breast cancer to make a timely diagnosis and referral for specialized care.

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.

Biological subtype, treatment response and outcomes in inflammatory breast cancer using data from the National Cancer Database.

BACKGROUND: Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort. METHODS: Patients with non-metastatic IBC treated in 2010-2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), ER-/HER2- and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ2 tests were used to compare pCR rates, and Kaplan-Meier curves and Cox proportional hazards regression to analyse overall survival. RESULTS: Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2- in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER-/HER2- in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2- (6·2 per cent), HER2+ (38·8 per cent), ER-/HER2- (19·1 per cent) (P < 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2- 64·9 per cent, HER2+ 74·0 per cent, ER-/HER2- 44·0 per cent; P < 0·001) and by pCR within subtypes (all P < 0·001). In multivariable analysis, ER-/HER2- subtype (hazard ratio 2·89 versus HER2+ as reference; P < 0·001) and absence of total pCR (hazard ratio 3·23; P < 0·001) predicted worse survival. CONCLUSION: Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease.

ANTECEDENTES: En tanto que el cáncer inflamatorio de mama (inflammatory breast cancer, IBC) se ha postulado como una entidad biológica distinta, las guías de práctica clínica y datos previos sugieren que el tratamiento y los resultados están influenciados por aproximación al subtipo biológico estándar. El objetivo de este estudio fue la validación en una cohorte reciente de pacientes incluidas en una extensa Base de Datos Nacional de Cáncer (National Cancer Database, NCDB). MÉTODOS: A partir de la NCDB, se identificaron las pacientes con IBC no metastásico tratadas en con neoadyuvancia sistémica y cirugía durante el periodo 2010-2015. El subtipo biológico aproximado se categorizó como ER+/HER2-, ER-/HER2- y HER2+. La respuesta patológica completa total (pathologic complete response, pCR) se definió como ypT0/ypTis, ypN0. Se utilizaron pruebas de ji al cuadrado para comparar las tasas de pCR y las curvas de Kaplan-Meier y la regresión de riesgos proporcionales de Cox para analizar la supervivencia global (overall survival, OS). RESULTADOS: En las 4.068 pacientes con IBC (mediana de edad 56 años), el subtipo biológico aproximado fue ER+/HER2- en 1.575 (39%), HER2+ en 1.323 (33%) y ER-/HER2- en 1.170 (29%). Un total de 3.351 pacientes (84%) eran cN+ en el momento de la presentación, sin diferencias entre los subtipos. Las tasas totales de pCR variaron significativamente en función del subtipo: ER+/HER2- (6%), HER2+ (39%), ER-/HER2- (19%), P < 0,001, así como las tasas de pCR de la mama (10%, 45%, 25%) y las tasas de pCR de los ganglios linfáticos (17%, 57%, 33%). La OS a los 5 años varió significativamente según los subtipos (ER+/HER2- 65%, HER2+ 74%, ER-/HER2- 44%, P < 0,001) y según la pCR en cada uno de los subtipo (en cada uno P < 0,01). En el análisis multivariable, el subtipo ER-/HER2- (cociente de riesgos instantáneos, hazard ratio, HR 2,9, P < 0,001 versus HER2+) y la ausencia de pCR total (HR 3,2, P < 0,001) predijeron una peor supervivencia. CONCLUSIÓN: Tanto la respuesta al tratamiento del IBC y como la supervivencia variaron en función del subtipo biológico aproximado, tal como sucede en otros cánceres de mama invasivos. Estos datos apoyan la importancia de continuar ajustando el tratamiento sistémico al subtipo biológico aproximado y resaltan la mejoría reciente de los resultados en las pacientes HER2+.

Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes (sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort. PATIENTS AND METHODS: Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings. RESULTS: Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy (P = 0.01), had a hormone receptor-positive tumour (P = 0.001) and had lower cN stage at diagnosis (P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR (P = 0.002) and correlated with sTIL infiltration (P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27-0.81, P = 0.006) in a multivariate model. CONCLUSIONS: IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC.

Metastatic behavior and overall survival according to breast cancer subtypes in stage IV inflammatory breast cancer.

BACKGROUND: Distant metastatic disease is frequently observed in inflammatory breast cancer (IBC), with a poor prognosis as a consequence. The aim of this study was to analyze the association of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) based breast cancer subtypes in stage IV inflammatory breast cancer (IBC) with preferential site of distant metastases and overall survival (OS). METHODS: For patients with stage IV IBC, diagnosed in the Netherlands between 2005 and 2016, tumors were classified into four breast cancer subtypes: HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. Patient, tumor, and treatment characteristics and sites of metastases were compared. OS of the subtypes was compared using Kaplan-Meier curves and the log-rank test. Association between subtype and OS was assessed in multivariable models using logistic regression. RESULTS: In total, 744 eligible patients were included: 340 (45.7%) tumors were HR+/HER2-, 148 (19.9%) HR-/HER2+, 131 (17.6%) HR+/HER2+, and 125 (16.8%) HR-/HER2-. Bone was the most common metastatic site in all subtypes. A significant predominance of bone metastases was found in HR+/HER2- IBC (71.5%), and liver and lung metastases in the HR-/HER2+ (41.2%) and HR-/HER2- (40.8%) subtypes, respectively. In multivariable analysis, the HR-/HER2- subtype was associated with significantly worse OS as compared to the other subtypes. CONCLUSION: Breast cancer subtypes in stage IV IBC are associated with distinct patterns of metastatic spread and display notable differences in OS. The use of breast cancer subtypes can guide a more patient-tailored staging directed to metastatic site and extend of disease.

Marital status is an independent prognostic factor in inflammatory breast cancer patients: an analysis of the surveillance, epidemiology, and end results database.

OBJECTIVES: The aim of this analysis was to study the impact of marital status on inflammatory breast cancer (IBC) patients, as the prognostic impact is yet to be studied in detail. METHODS: Data of IBC patients from 2004 to 2010 were sorted out from the database of surveillance, epidemiology, and end results (SEER), and overall survival (OS) rates and breast cancer-specific survival (CSS) rates were compared between a group of married and unmarried patients. The comparison was performed by Kaplan-Meier method with log-rank test, and multivariate survival analysis of CSS and OS was performed using the Cox proportional hazard model. RESULTS: Data of 1342 patients were collected from the SEER database, on an average 52% of married patients (n = 698, 52.01%) and 48% of unmarried patients (n = 644, 47.99%) for this analysis. Married patients were more likely to be more younger (aged ≤ 56) (52.44% vs. 43.94%), white ethnicity (83.24% vs. 71.58%), HoR positive (48.28% vs. 41.61%), more patients received surgery (78.51% vs. 64.60%), chemotherapy (90.69% vs. 80.12%) and radiotherapy (53.44% vs. 44.41%) compared to unmarried group, and less likely to be AJCC stage IV (26.22% vs. 35.40%) (All P ˂ 0.05). Married patients had better 5-year CSS (74.90% vs. 65.55%, P < 0.0001) and OS rates (45.43% vs. 33.11%, P < 0.0001). The multivariate analysis revealed that marital status is an independent prognostic factor, whereas the data of unmarried patients showed worse CSS (HR 1.188; 95% CI 1.033-1.367; P = 0.016) and OS rates (HR 1.245; 95% CI 1.090-1.421; P = 0.001).The subgroup analysis further revealed that the OS and CSS rates in the married group were better than the unmarried group, regardless of different AJCC stages. CONCLUSION: Marital status was an independent prognostic indicator in IBC patients. As the study reveals, the CSS and OS rates of the married patients were better than those of the unmarried patients.