Non-metastatic Inflammatory Breast Cancer Research Articles

Abstract B048: Disparities in treatment course and outcomes in females diagnosed with non-metastatic inflammatory breast cancer

Abstract Background: Inflammatory breast cancer (IBC) is an uncommon, aggressive disease with a poor prognosis. National treatment guidelines recommend neoadjuvant chemotherapy followed by modified radical mastectomy (MRM) and radiation. Disparities in treatment may contribute to survival differences, and few studies have assessed factors contributing to such variation. We aimed to identify demographic and facility differences in treatment and survival among females with non-metastatic IBC. Methods: Secondary analysis of the National Cancer Database (2012-2016) on females diagnosed with non-metastatic IBC was performed. Demographics, treatment, and facility data were collected. Statistical analysis was performed with SAS. Results: A total of 5,438 patients met the inclusion criteria. Receiving surgical intervention was associated with age (p<0.0001), race (p<0.0001), and facility (p=0.03), with increased odds of surgery for younger, white, and comprehensive community cancer program patients. Receiving radiation therapy was associated with age (p <0.0001) and race (p<0.0001), with decreased odds of radiation for older, Black, and Hispanic patients. Receiving chemotherapy was associated with age (p <0.0001), with increased odds of chemotherapy for younger patients. Days from diagnosis to treatment initiation was associated with race (p<0.0001) and facility (p=0.0089), with increased time for Black, Hispanic, and academic facility patients. Survival time was associated with age (p<0.0001), race (p<0.0001), facility (p=0.0002), Charlson-Deyo (CD) score (p<0.0001), and surgery (p<0.0001), with decreased survival for older, Black, non-academic facility, higher CD score, and non-surgery patients. Conclusions: Treatment trends and survival of IBC patients are impacted by sociodemographic and facility-level variation, which, when addressed, may help to improve patient outcomes. Citation Format: Kirsten Lung, Young Sheng, Brandon George, Alliric Willis, Melissa Lazar. Disparities in treatment course and outcomes in females diagnosed with non-metastatic inflammatory breast cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B048.

Systematic Review and Meta-Analysis of Treatment Effects on Survival in Patients with Inflammatory Breast Cancer.

The objective of this study was to determine the survival rate and the effects of different treatments on patients with inflammatory breast cancer (IBC). The study employed a systematic approach that included a search strategy across four databases: Embase, Web of Sciences, PubMed, and Scopus. The results obtained were screened initially by titles and abstracts, followed by full-texts in EndNote 8 software. The next stage involved data extraction and qualitative evaluation, where the Metan command was used to estimate the pooled survival rate. A total of 28 studies with a sample size of 63,796 were finally analyzed. The overall 3- and 5-year survival rates (OS) for IBC patients were found to be 52% (95% CI; 46-58%, I2: 99.42%) and 61% (95% CI; 53-69%, I2: 93.63%), respectively. The 5-year OS rates in patients with non-metastatic and metastatic IBC were 59% (95% CI; 54-63%, I2: 98.31%) and 30% (95% CI; 26-35%, I2: 50.84%), respectively. The 5-year OS rate in non-metastatic patients who underwent BCS surgery was 60% (CI 95%; 26-94%, I2: 95.13%). The overall 5- and 3-year OS rates for patients with IBC were lower than those for all types of breast cancer, and the rates were even lower in patients with metastasis. Therefore, it is recommended that healthcare workers and women at risk should be vigilant of early symptoms of IBC to prevent metastasis by seeking medical attention on time.

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

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. 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. 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). 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.

Preoperative Radiation Therapy for Chemorefractory Localized Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is a rare breast cancer subtype. Chemorefractory nonmetastatic IBC, defined by locoregional progression under neoadjuvant chemotherapy, is a rare situation with few therapeutic options. Owing to the rarity of this clinical presentation and the lack of specific data, no specific management guidelines exist. We evaluated whether preoperative radiation therapy/chemoradiotherapy could achieve locoregional control after first-line neoadjuvant chemotherapy in patients with IBC. Patients with chemorefractory disease receiving preoperative radiation therapy were identified from a retrospective multicenter cohort of consecutive patients with IBC diagnosed between 2010 and 2017 at 7 oncology centers in France. Overall, 18 patients among the 364 patients (5%) treated for IBC had progressive disease during neoadjuvant chemotherapy. These patients had aggressive tumors with lymph node involvement at diagnosis (n=17; 94.4%), triple-negative subtype (n=11; 61.1%), Scarff Bloom and Richardson grade 3 (n=10; 55.6%), and high Ki67 (median, 56.0%). After preoperative radiation therapy, all patients had a complete (n=1; 5.6%) or partial (n=17; 94.4%) locoregional response. One patient (5.6%) experienced acute grade 3 dermatitis. Twelve (66.7%) patients underwent surgery as planned. The estimated median follow-up was 31 months. The median overall survival, disease-free survival, distant metastases-free survival, and locoregional recurrence-free survival were 19 months, 4.5 months, 5 months, and 6 months, respectively. Ultimate locoregional control was obtained for 11 patients (61.1%), and 13 patients (72.2%) experienced metastatic progression. Triple-negative subtype (hazard ratio [HR], 15.54; P=.011) and surgery (HR, 0.23; P=.030) were significantly associated with overall survival in the univariate analysis. In multivariate analyses, the triple-negative subtype remained a significant prognostic factor (HR, 13.04; P=.021) for overall survival. Preoperative radiation therapy is a feasible approach with acceptable toxicities. It allowed surgery and ultimate locoregional control in a majority of patients. The lack of translation into better survival has been a challenge, in part owing to the metastatic propensity of patients with chemorefractory IBC, especially in the overrepresented triple-negative population in this series.

Complete response in the axilla and the non-triple negative subtype are favourable prognostic factors for survival outcomes in inflammatory breast cancer.

To assess real-world outcomes and prognostic factors of non-metastatic inflammatory breast cancer according to immunohistochemistry (IHC)-based subtype and treatment regimen. An institutional retrospective analysis of patients treated with neoadjuvant systemic treatment (NAST) for stage III inflammatory breast cancer diagnosed between 2001 and 2018 was performed. The survival outcomes in relation to patient characteristics, tumour characteristics, treatment modality and response to NAST were analyzed. 225 patients fulfilled the inclusion criteria, 90% of patients were node-positive. IHC-based subtypes: 39.1% were HR+/HER2-, 19.1% HR+/HER2+, 23.1% HR-/HER2+ and 18.7% HR-/HER2-. Treatment was multimodal: NAST (100%), surgery (94.2%) and radiotherapy (94.2%). 53.3% of patients received adjuvant endocrine therapy, 34.3% (neo)adjuvant trastuzumab. Tri-modality therapy was applied in 89.3% of patients. Following NAST, a pathologic complete remission (pCR) in the breast was found in 16.9%, in the axilla in 29.7% and in both the breast and axilla in 10.3% of patients. The axillary pCR rate was significantly higher in HR- subtypes. Median overall survival (OS) was 8.9, 7.2, 5.8 and 2.3 years (p<0.001) for HR+/HER2-, HR+/HER2+, HR-/HER2+ and HR-/HER2- subtype, respectively. On multivariate analysis, IHC-based subtype, age and axillary pCR were found as independent prognostic factors for RFS and OS. pCR rate and median OS improved over time, 5.8% vs 14.7% and 4.7 vs 10.0 years (2001-2009 vs. 2010-2018), respectively. Axillary pCR and the non-triple-negative IHC-based subtype are favourable prognostic factors for RFS and OS in inflammatory breast cancer. Introduction of taxanes and antiHER2 drugs contributed to improved pCR rate and OS.

Abstract P2-14-05: Patient rather than tumor factors predict contralateral prophylactic mastectomy for inflammatory breast cancer

Abstract Introduction: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer with best outcomes result-ing from trimodality therapy: neoadjuvant chemotherapy (NAC), modified radical mastectomy (MRM), and radiation (PMRT). Contralateral prophylactic mastectomy (CPM) is generally discour-aged at the time of MRM due to poor prognosis. Our aim was to identify factors associated with CPM for IBC and determine its relationship with overall survival (OS). Methods: The National Cancer Database was used to identify female patients with AJCC stage IIIC unilateral IBC (cT4d and inflammatory histology code) treated 2004-2018. Patients were stratified by mastec-tomy type: unilateral mastectomy (UM) was defined as MRM or simple mastectomy, and CPM was defined as UM + CPM. Logistic regression identified factors associated with mastectomy type, and multivariable proportional Cox hazards regression identified factors associated with OS. A subset analysis of patients receiving NAC compared complete pathologic response (pCR) between mastec-tomy groups. Results: Of the 2,837 patients with non-metastatic IBC, 2,013 (70.2%) underwent UM and 855 (29.8%) had CPM. The CPM group was significantly younger than the UM group (mean age 52 vs. 56.6 years, p=0.028), more frequently identified as Non-Hispanic White (79.7% vs. 70.1%, p&amp;lt; 0.001), and had private insurance (66.9% vs. 55.6%, p&amp;lt; 0.001). Nearly all patients received chemotherapy and over 80% were treated with NAC. Receipt of PMRT did not differ by mastectomy type (80% for UM and CPM). On multivariable logistic regression, patients age &amp;lt; 40 were more likely to undergo CPM than UM (OR 3.7, 95% CI 1.61-8.5, p&amp;lt; 0.002). Patients with age &amp;gt;70, Hispanic ethnicity, and public insur-ance were significantly less likely to receive CPM (all p≤0.002). On multivariable Cox regression ad-justed for patient, tumor, and treatment factors, CPM was not associated with OS benefit (HR 0.86, 95% CI 0.73-1.02, p=0.08). Higher histologic grade, node-positive disease, and greater co-morbidity were associated with poorer OS, while receipt of chemotherapy and PMRT improved OS. In the subset of NAC patients, overall pCR did not differ significantly by mastectomy type (CPM 22.3%, UM 19.4%, p=0.26). When included in multivariable models, pCR rates were not predictive of CPM de-spite being associated with improved OS. Conclusion: Nearly 30% of IBC patients undergo CPM despite discouragement by guidelines. Demographic char-acteristics – particularly age &amp;lt; 40 – predicted CPM, suggesting patient preferences and access to care affect surgical decisions. As expected, trimodality therapy and favorable NAC response im-proved oncologic outcomes, but CPM had no association with OS. While CPM may be chosen for risk reduction and symmetry, patients should be counseled that it does not improve survival for IBC. Citation Format: Lauren M. Drapalik, Amanda L. Amin, Ashley Simpson, Lisa Rock, Mary Freyvogel, Robert Shenk, Megan E. Miller. Patient rather than tumor factors predict contralateral prophylactic mastectomy for inflammatory breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-05.

Aspirin Use Is Associated With Improved Outcomes in Inflammatory Breast Cancer Patients.

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and has a high propensity for distant metastases. Our previous data suggested that aspirin (acetylsalicylic acid, ASA) use may be associated with reduced risk of distant metastases in aggressive breast cancer; however, there are no reported studies on the potential benefit of ASA use in patients with IBC. Data from patients with non-metastatic IBC treated between 2000-2017 at two institutions, were reviewed. Overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were performed using Kaplan-Meier analysis. Univariate and multivariable logistic regression models were used to identify significant associated factors. Of 59 patients meeting the criteria for analysis and available for review, 14 ASA users were identified. ASA users demonstrated increased OS (p = 0.03) and DMFS (p = 0.02), with 5-year OS and DMFS of 92% (p = 0.01) and 85% (p = 0.01) compared to 51% and 43%, respectively, for non-ASA users. In univariate analysis, pT stage, pN stage, and ASA use were significantly correlated (p < 0.05) with OS and DFS. On multivariable analysis, ASA use (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.01-0.8) and lymph node stage (HR, 5.9; 95% CI, 1.4-25.9) remained significant for OS and DFS ASA use (HR, 0.13; 95% CI, 0.03-0.56) and lymph node stage (HR, 5.6; 95% CI, 1.9-16.4). ASA use during remission was associated with significantly improved OS and DMFS in patients with IBC. These results suggest that ASA may provide survival benefits to patients with IBC. Prospective clinical trials of ASA use in patients with high-risk IBC in remission should be considered.

Contemporary Trends in Breast Reconstruction Use and Impact on Survival Among Women with Inflammatory Breast Cancer.

Breast reconstruction is generally discouraged in women with inflammatory breast cancer (IBC). Nevertheless, reconstruction rates are increasing in this population. We aimed to determine contemporary trends and predictors of breast reconstruction use and its impact on mortality among IBC patients. Demographic, clinicopathologic, and follow-up data for women with non-metastatic IBC having mastectomy between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Rates and predictors of immediate breast reconstruction, along with survival outcomes between the breast reconstruction and no reconstruction groups were calculated. To account for selection bias, a propensity score analysis matching one reconstruction patient to three no reconstruction patients was performed. A total of 4076 women with non-metastatic IBC who underwent mastectomy (388 [9.5%] with breast reconstruction and 3688 [90.5%] without) were included. The proportion of women undergoing breast reconstruction and contralateral prophylactic mastectomy increased from 6.2 to 15.3% and 12.9 to 29.6%, respectively, between 2004 and 2015. Younger age, higher annual income, metropolitan residence, and bilateral mastectomy predicted breast reconstruction use. The 10-year breast cancer-specific survival was 62.9% for women having breast reconstruction and 47.6% for women not having breast reconstruction. After propensity-matched analysis, 10-year cancer-specific survival was similar between the reconstruction (56.6%) and no reconstruction (62.2%) groups (adjusted hazard ratio 0.96, 95% confidence interval 0.79-1.16; p=0.65). Breast reconstruction rates continue to rise among IBC patients, particularly young women and women with access to reconstruction. Breast reconstruction is not associated with inferior breast cancer-specific survival and can be an option for select patients.

Nivolumab with chemotherapy as neoadjuvant treatment for inflammatory breast cancer.

e12633 Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer with poor prognosis and is often resistant to neoadjuvant systemic therapy with early recurrence and metastases. PD-L1 expression in IBC is moderate to high, and blockade of the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a promising treatment to enhance clinical response. We examined the efficacy of neoadjuvant nivolumab (anti-PD-1 antibody) with chemotherapy in IBC. Methods: This is an open-label multicohort multicenter study of nivolumab with neoadjuvant chemotherapy in patients with newly diagnosed non-metastatic IBC (n=52). All breast cancer subtypes (ER/PR/HER2) were allowed. Patients received nivolumab 360 mg on day 1 (21-day cycle) x 4 cycles with standard chemotherapy. Cohort 1 (HER2-negative) received nivolumab with paclitaxel (80 mg/m2)x12 weeks followed by doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) (AC) x 4 cycles. Cohort 2 (HER2-positive) received nivolumab with taxane (paclitaxel 80 mg/m2, docetaxel 75 mg/m2, or nab-paclitaxel 100 mg/m2), trastuzumab (8 mg/kg then 6 mg/kg), and pertuzumab (840 mg then 420 mg) x 4 cycles followed by AC x 4 cycles. All patients underwent modified radical mastectomy (MRM) followed by radiation and adjuvant therapy per institutional standard of care. Primary objective was pathologic complete response (pCR) (ypT0/Tis ypN0). Residual Cancer Burden (RCB) was assessed. Secondary objectives were safety/tolerability and invasive recurrence-free interval at 2 years. Breast biopsies, residual tumor tissue, and peripheral blood samples were collected for correlative biomarker testing. PD-L1 expression in tumor tissue will be assessed as a predictive marker. Study was closed after 8 patients were enrolled due to slow accrual. Results: 8 patients were enrolled from June 2019-December 2020. All completed neoadjuvant systemic therapy with nivolumab and none had disease progression. They underwent MRM between January 2020-June 2021. Mean age was 57 years (range 43-74). 4 were HER2-positive, 3 were TNBC, and 1 was HR-positive/HER2-negative. 3 were Caucasian, 2 were Latino, 2 were Black, and 1 was Asian. There was no grade 4 toxicity. Most common grade 3 toxicity was neutropenia (n=3). Immune-related events were diarrhea/colitis (n=2) and elevated liver transaminases (n=1). At time of MRM, 4 patients had pCR, 1 had RCB-I, 2 had RCB-II, and 1 had RCB-III. They remain with no evidence of disease and are in follow-up. Tumor biological correlatives are being performed. Conclusions: Addition of nivolumab to neoadjuvant therapy was tolerable and safe and demonstrated anti-tumor activity in IBC with high pCR rate in this pilot study. This supports further investigation of the role of checkpoint inhibitors in treatment of IBC. Clinical trial information: NCT03742986. [Table: see text]

Abstract P1-24-05: Breast conserving surgery for non-metastatic inflammatory breast cancer: A National Cancer Database (NCDB) study

Abstract Background: Single center studies have suggested breast conserving surgery (BCS) as treatment for inflammatory breast cancer (IBC). Given its infrequency, a multi-hospital database study is useful. This study reports the characteristics, outcomes, and prognostic factors of women with non-metastatic IBC who underwent BCS. Methods: The National Cancer Database (NCDB) was queried for women ≥18 years old with cT4dN0-3M0. Outcomes were compared between treatment groups. A Cox proportional hazards model assessed the relationship of variables and the overall survival (OS). Results: A total of 12,223 women were treated as follows: no surgery (12.8%), BCS (3.3%), and mastectomy (83.9%). BCS was significantly more common in academic/research institutions, South and North-East hospitals, no special type histology, triple negative breast cancer, single quadrant tumors, and node-negative tumors. Most patients who underwent BCS received chemotherapy (86.2%) and radiation therapy (61.9%), while hormonal therapy was infrequent (37.1%). Mortality was higher with BCS than mastectomy at 30 (1.3% versus 0.3%, p&amp;lt;0.001) and 90 (6.8% versus 1.5%, p&amp;lt;0.001) days post-surgery. Three- and five-year OS post-BCS was lower compared to mastectomy but higher than no surgery. Prognostic factors of OS for patients who underwent surgery included academic/research institutions, income ≥$63,000, hormone positive tumors, and receipt of chemotherapy and radiation therapy. Conclusion: BCS is offered to select women with non-metastatic IBC across NCDB participating hospitals. Caution is necessary while studying if surgery can be de-escalated in IBC. Standardized multidisciplinary care along with mastectomy remains the norm for patients with non-metastatic IBC. Citation Format: Fernando A. Angarita, Stephen B. Edge, Kristopher Attwood, Kazuaki Takabe, Jessica Young. Breast conserving surgery for non-metastatic inflammatory breast cancer: A National Cancer Database (NCDB) study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-24-05.

Trends in Sentinel Lymph Node Biopsies in Patients With Inflammatory Breast Cancer in the US

The standard of care for inflammatory breast cancer (IBC) is neoadjuvant chemotherapy, total mastectomy with axillary lymph node dissection (ALND), and postmastectomy radiation therapy. Existing studies suggest that sentinel lymph node biopsy (SLNB) may not be reliable in IBC. The use and frequency of SLNB in women with IBC is not well characterized. To determine the frequency and temporal trend of SLNB in patients with IBC. This retrospective cohort study used the National Cancer Database, a nationwide hospital-based cancer registry, and included women who were diagnosed with nonmetastatic IBC and underwent axillary surgery from 2012 to 2017. Data were analyzed from January 2021 to May 2021. Any SLNB, including SLNB alone and SLNB followed by ALND, and ALND alone. Scatterplot fit with a linear regression model were used to evaluate the yearly increase of any SLNB use. Multivariable logistic regression models to evaluate the association of study variables with the outcome of any SLNB. This study included a total of 1096 women (mean [SD] age, 56.1 [12.9] years) who were 18 years or older with nonmetastatic IBC diagnosed between 2012 and 2017. Of the 186 of 1096 women (17%) who received any SLNB, 137 (73.7%) were White individuals; and of the 910 of 1096 women (83%) who received an ALND only, 676 (74.3%) were White individuals. Among women undergoing any SLNB, 119 of 186 (64%) did not undergo a completion ALND. There was a statistically significant increasing trend in the use of SLNB from 2012 to 2017 (22 of 205 patients [11%] vs 32 of 148 patients [22%]; P = .004). In multivariable analysis, the use of SLNB was associated with diagnosis year (2017 vs 2012; odds ratio [OR], 2.26; 95% CI, 1.26-4.20), clinical nodal status (cN3 vs 0; OR, 0.39; 95% CI, 0.22-0.67), and receipt of reconstructive surgery (OR, 1.80; 95% CI, 1.09-2.96). The findings of this cohort study suggest that there is frequent and increasing use of SLNB in patients with IBC that is not evidence-based or supported by current treatment guidelines.

Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients

Inflammatory breast cancer (IBC) is an aggressive BC subtype with poor outcomes. A targetable somatic PIK3CA mutation is reported in 30% of IBC, allowing for treatment by PI3Kα-specific inhibitors, such as alpelisib. The aim of this study was to evaluate the detection rate of circulating PIK3CA mutation in locally-advanced IBC (LAIBC) patients harbouring a PIK3CA mutation on initial biopsy. This monocentric retrospective study was based on available stored plasma samples and tumour biopsies at diagnosis from all LAIBC patients treated with neo-adjuvant chemotherapy (NCT) between 2008 and 2018 at the Centre Henri Becquerel. PIK3CA mutations (E542K, E545K, H1047R/L) were assessed by droplet digital PCR (ddPCR) in plasma samples and tumoral tissue at diagnosis. A total of 55 patients were included. Overall, 14/55 patients (25%) had a PIK3CA mutation identified on baseline biopsy (H1047R = 8; H1047L = 3; E545K = 2; E542K = 1). Among them, 11 (79%) patients had enough DNA for circulating DNA analyses, and corresponding circulating PIK3CA mutations were found in 6/11 (55%). Among the 41 patients without PIK3CA mutations on biopsy, 32 (78%) had enough DNA for circulating DNA analysis, and no circulating PIK3CA mutation was identified. Our results revealed no prognostic or predictive value of PIK3CA mutations at the diagnosis of non-metastatic IBC but highlighted the prognostic value of the cfDNA rate at diagnosis. Our study showed that a corresponding circulating PIK3CA mutation was identified in 55% of LAIBC patients with PIK3CA-mutated tumours, while no circulating mutation was found among patients with PI3KCA wild-type tumours.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of outcomes in inflammatory breast cancer.

Background: Inflammatory breast cancer (IBC) is uncommon, aggressive and associated with poor survival outcomes. The lack of prognostic biomarkers and therapeutic targets specific to IBC is an added challenge for clinical practice and research. Inflammatory biomarkers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (NLR and PLR) demonstrated independent prognostic impact for survival in breast cancer. In our study, these biomarkers were investigated in a cohort of patients with nonmetastatic IBC. Methods: A retrospective cohort of 102 IBC patients with nonmetastatic disease was conducted at the Mohammed VI University Hospital (Oujda, Morocco) between January 2010 and December 2014. NLR and PLR were obtained from blood cell count at baseline before neoadjuvant chemotherapy (NACT) from patients' medical records. The receiver operating characteristic was used to find the optimal cut-off. Correlation between these blood-based biomarkers and response to NACT was analyzed by Chi-squared and Fisher's exact test. Their prognostic value for predicting disease-free survival (DFS) and overall survival (OS) was performed based on Cox regression models. Results: Totally, 102 patients with IBC were included in the analysis. Pathologic complete response (pCR) after NACT, defined by the absence of an invasive tumor in the breast tissues and nodes after surgery (ypT0 ypN0), was observed in eight patients (7.8%). NACT response was found to be associated with menopausal status (p=0.039) and nodal status (p<0.001). Patients with a low NLR had a higher pCR rate as compared with the high-NLR group (p=0.043). However, the pCR rate was not significantly associated with age (p=0.122), tumor side (p=0.403), BMI (p=0.615), histological grade (p=0.059), hormone receptors status(p=0.206), HER2 (p=0.491) and PLR (p=0.096). Pre-treatment blood-based NLR of 2.28 was used as the cut-off value to discriminate between high and low NLR according to the receiver operating characteristic curves. Similarly, a value of 178 was used as the cut off for PLR. Patients with low-NLR had a significantly better 5-year DFS (p<0.001) and OS (p<0.001) than the high-NLR group. Moreover, low-PLR was significantly associated with higher DFS (p=0.001) and OS (p=0.003). The NLR showed a significant prognostic impact for DFS (HR: 2.57; 95% CI: 1.43-4.61; p=0.01) and for OS (HR: 2.92; 95% CI: 1.70-5.02; p<0.001). Similarly, a meaningful association between PLR and 5-year DFS (HR: 1.95; 95% CI: 1.10-3.46; p=0.021) and OS (HR: 1.82; 95% CI: 1.06-3.14; p=0.03) was noticed. Conclusions: High NLR and PLR were found associated with reduced DFS and OS in nonmetastatic IBC. Further studies are awaited to confirm these findings.

Trends, survival outcomes, and predictors of nonadherence to mastectomy guidelines for nonmetastatic inflammatory breast cancer.

The Current National Comprehensive Cancer Network guidelines recommend modified radical mastectomy (MRM) as the surgical treatment of choice for nonmetastatic inflammatory breast cancer (IBC). Limited studies have looked into the outcomes of breast conserving surgery (BCS) vs. MRM for IBC. National Cancer Database (NCDB) data from 2004 to 2014 were retrospectively analyzed. Patients' demographics, tumor characteristics, and overall survival (OS) trends were compared for BCS and MRM cases of nonmetastatic IBC. Univariate and multivariate analyses were performed. A total of 413 (3.89%) BCS and 10,197 (96.11%) MRM cases were identified. Median follow-up was 58.45months. Compared to MRM, BCS patients were more likely to be older, be African American, have Medicare/Medicaid or be uninsured, live in lower education ZIP codes, and live in a metropolitan area (all p<0.05). BCS rates significantly decreased from 5.84% in 2004 to 3.19% in 2014 (p<0.001). BCS patients also were more likely to have less than 50% of the breast involved (51.57% vs. 43.88%; p=0.0081) and were less likely to receive trimodal therapy (50.85% vs. 74.62%; p=<0.0001). The OS was significantly higher in the mastectomy group over 9years at 62.02% vs. 54.47% in the BCS group. Additionally, in the adjusted multivariate model, BCS cases were associated with 23% higher hazards of overall mortality (p=0.0091). BCS was performed in a limited number of cases, which decreased over the study period. The analysis identified both demographic predictors of receiving BCS and significantly lower OS for IBC patients undergoing a BCS.

Immediate Breast Reconstruction for Inflammatory Breast Cancer: Trends in Use and Clinical Outcomes 2004-2016.

National guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR. Using the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan-Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes. 6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P < 0.001). Median follow-up was 43 and 45 months for IBR and non-reconstructed patients, respectively (P = 0.29). On Cox multivariable analysis, IBR was associated with improved OS (HR 0.63, 95% CI 0.44-0.90, P = 0.01), but this association was not significant on IPW analysis (P = 0.06). In PSM cohorts, this association remained significant (HR 0.60, 95% CI 0.40-0.92, P = 0.02). Margin status, time to PMRT, 30-day readmission, and 30-/90-day mortality did not differ between groups (all P > 0.05). Although not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety.

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

BackgroundPrevious 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.MethodsSurveillance, 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.ResultsOut 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).ConclusionsPatients 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.

Aspirin Use is Associated with Improvement in Overall Survival and Recurrence Free Survival in Inflammatory Breast Cancer Patients

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer (BC), with high propensity for distant metastases. Previous data has suggested that aspirin use may be associated with improved risk of distant metastases in aggressive breast cancer, but there are no reported studies of potential benefit of aspirin use in IBC patients. Our goal was to determine whether there is an association of aspirin use with improvement in outcomes for patients with IBC. Patients with non-metastatic IBC treated from 2000-2017 at two institutions were reviewed (IRB protocol STU- 052012-019). Clinicopathologic data, including evidence of aspirin use in remission period (beginning within 2 years of diagnosis and lasting for a minimum of 60 days), was collected and analyzed. Overall survival (OS), disease free survival (DFS), and distant metastases free survival (DMFS) were obtained using Kaplan Meier analysis. Univariate and multivariate logistic regression models were constructed to identify significant factors. 59 patients meeting criteria for analysis were available for review, of which 14 aspirin users were identified. The aspirin and non-aspirin groups did not show any significant distribution differences in patient characteristics (e.g. ER/PR status, pathologic tumor (pT) stage, pathologic nodal (pN) stage, LVI, endocrine therapy use, chemotherapy use, triple negative status). Aspirin users demonstrated increased OS (p = .03) and DMFS (p = .02), with 4-year OS and DMFS of 92% (p = .01) and 85% (p = .01) compared to 56% and 43% respectively for non-aspirin users. On univariate analysis, pT stage, pN stage, and aspirin use, were significantly correlated (p<.05) with OS and DFS. On multivariate analysis, aspirin use (HR = .11, CI 0.01- 0.8) and lymph node stage (HR = 5.9, CI 1.4-25.9) remained significant for OS and DFS (aspirin use (HR = 0.13, CI 0.03-0.56) and lymph node stage (HR = 5.6, CI 1.9-16.4). Aspirin use initiated during remission period was associated with significantly improved OS and DMFS in IBC patients. These hypotheses-generating results suggests that aspirin use may provide survival benefit for IBC patients. Prospective clinical trial(s) of augmented ASA use in patients with high risk IBC in remission should be considered for development.

265P Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients

265P Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients

Abstract OT2-04-01: A prospective, multicentre, open-label, randomized phase II study of PEmbroLizumab in combination with neo-adjuvant (F)EC-paclitaxel regimen in HER2-negative Inflammatory breast CANcer

Abstract Background: Inflammatory breast cancer (IBC) represents a rare but aggressive form of locally advanced BC. In spite of multimodality therapy including neoadjuvant chemotherapy (NAC), radical surgery and radiotherapy, prognosis remains poor, notably in HER2-negative subtypes. Whole-genome and gene expression profiling studies in IBC have identified an immune-enriched signature predicting for pathological complete response (pCR), suggesting a critical role for T-cell cytotoxicity in reaching complete tumor cell elimination after NAC. In addition, overexpression of programmed cell death ligand 1 (PD-L1) mRNA in IBC is more frequent than in non-IBC and has significant correlation with pCR. Pembrolizumab (PEM), an anti- programmed cell death 1 (PD 1) receptor antibody, inhibiting its interaction with PD-L1, is registered or in development across a large range of malignancies. PEM may boost anti-tumor immunity, eradicating residual tumor cells and thus improving pCR and outcome in HER2-negative IBC. Trial design: PELICAN-IPC 2015-016 trial (NCT03515798), sponsored by Institut Paoli-Calmettes with financial support of MSD, is a multicenter, randomized phase II, non-comparative study evaluating the addition of PEM to anthracyclines/taxanes NAC in non-metastatic HER2-negative IBC. Patients will receive 4 cycles of Q3W FEC100 (5FU 500 mg/m², Epirubicin 100 mg/m², Cyclophosphamide 500 mg/m²; non-triple negative) or 4 cycles of Q2W EC (Epirubicin 90 mg/m², Cyclophosphamide 600 mg/m²; triple-negative) followed by Q1W paclitaxel 80 mg/m² x 12, with (arm B) or without (arm A) Q3W IV PEM 200 mg started with C2 FEC/EC. The primary endpoint will be pCR in the experimental arm. The study also includes a run-in safety phase. Secondary endpoints include tolerance, invasive disease-free, event-free and overall survivals in each arms and collection of pre- and post-treatment tissue and blood samples for pharmacodynamics measurements and biological correlates. Following Simon’s 2-stage optimal procedure a total of 54 patients in arm B is required to reject the null hypothesis of a truly ineffective experimental arm (H0: p&amp;lt;= 20%) with 5% error risk and 90% power assuming a true pCR rate of 40%. 27 additional patients will be enrolled in the control arm A. Since June 2018, 7 patients have been enrolled in a single center and 13 additional centers are expected to open before the end of 2019. Citation Format: Anthony Gonçalves. A prospective, multicentre, open-label, randomized phase II study of PEmbroLizumab in combination with neo-adjuvant (F)EC-paclitaxel regimen in HER2-negative Inflammatory breast CANcer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-04-01.

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

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. 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. 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. 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.