Diagnosis Of Inflammatory Breast Cancer Research Articles

Abstract PO3-06-05: Association of tumor-derived extracellular vesicles with circulating tumor DNA alterations in metastatic breast cancer patients: exploring differences in inflammatory breast cancer

Abstract Background: Liquid biopsy provides a real-time assessment of metastatic breast cancer (MBC). Recently, the complementary prognostic value of tumor-derived extracellular vesicles (tdEVs) and circulating tumor cells (CTCs) has been reported. We have previously confirmed the strong prognostic significance of CTCs and tdEVs in inflammatory breast cancer (IBC). While previous studies have reported the association of CTCs with circulating tumor DNA (ctDNA) alterations in MBC, no evidence is available for tdEVs. This study aimed to analyze the association of tdEVs with ctDNA alterations, to investigate the molecular pathways underlying their presence. Moreover, we explored potential differences of this association in patients (pts) with IBC to provide a comprehensive liquid biopsy-based portrait of this aggressive subtype of BC. Methods: Blood samples were collected from 355 pts with MBC before starting a new line of therapy at Northwestern University (Chicago, IL) between 2016 and 2021 (NU16B06 trial). For CTCs and tdEVs analysis, 7.5 mL of blood was processed with the CellSearch® system. The ACCEPT software was applied to CellSearch® images to automatically enumerate CTCs and tdEVs. Positivity cutoff was ≥5 for CTCs, while tdEV cutoff points were < 20 (low), 20-79 (intermediate), and ≥80 (high). For ctDNA analysis, matched plasma samples (± 1 month) were analyzed with the Guardant360™ NGS platform for the detection of somatic single nucleotide variants (SNVs) and copy number variations (CNVs), which were classified into oncogenic pathways based on defined profiles generated on the Cancer Genome Atlas database (p53, PI3K, ER, RTK, RAS, RAF, WNT, MYC, cell cycle, notch). Associations between ctDNA pathways alterations and tdEVs were tested in the overall population by multinomial logistic regression and corrected for significant clinical characteristics. Differences in liquid biopsy features between IBC and non-IBC subgroups were analyzed through Fisher's exact test. Results: Of the 355 MBC pts, 210 (62%) had HR+ BC, 61 (17%) had HER2+ BC, and 68 (20%) had triple-negative BC. Eighty-three (23%) had a diagnosis of IBC and had a numerically lower tdEV count. Also, lower tdEVs were detected in HER2+ BC as compared with HR+. Significantly higher tdEVs were observed among pts with lobular histology, liver, and bone metastases. CTC count was significantly associated with tdEV number. A matched plasma sample for ctDNA analysis was available for 175 pts (62 IBC and 113 non-IBC). In the overall population, SNVs in ER pathway were associated with intermediated/high levels of tdEVs (p=0.004 and 0.008). A similar association was observed for CNVs in the cell cycle pathway (p=0.008 and 0.007). Moreover, associations with ≥80 tdEVs were observed for PI3K SNVs and CNVs (p=0.039 and 0.004, respectively), RTK CNVs (p=0.023), and MYC CNVs (p=0.001). In multivariable analysis, clinical characteristics associated with higher tdEVs were lobular histology (p=0.014 for 20-79 and < 0.001 for ≥80) and bone metastases (p=0.019 for 20-79 and 0.002 for ≥80). When considering clinical variables of interest, only ER SNVs and MYC CNVs were significantly associated with intermediate (p=0.031) and high (p=0.022) tdEV counts, respectively. While the association with ER SNVs and cell cycle CNVs was significant both in the IBC and non-IBC subgroups, others were specific for a certain subgroup: higher tdEVs were significantly associated with PI3K SNVs only in non-IBC pts whereas the significant association with CNVs in PI3K and MYC pathways was observed only in pts with IBC. Conclusion: Detection of tdEVs was associated with particular genomic profiles. These alterations seem to be different in IBC further underlying a different biology of this BC subtype. Additional studies are needed to explore how to integrate different liquid-biopsy based biomarkers in the management of pts with MBC. Citation Format: Eleonora Nicolò, Lorenzo Gerratana, Lorenzo Foffano, Laura Munoz Arcos, Mara Serena Serafini, Maroua Manai, Letizia Pontolillo, Nadia Bayou, Elisabetta Molteni, Amanda Kaylan Strickland, Youbin Zhang, Paolo D’Amico, Andrew Davis, Jeannine Donahue, Huiping liu, William Gradishar, Ami Shah, Giuseppe Curigliano, Carolina Reduzzi, Massimo Cristofanilli. Association of tumor-derived extracellular vesicles with circulating tumor DNA alterations in metastatic breast cancer patients: exploring differences in inflammatory breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-05.

Abstract PO5-09-10: Inflammatory Breast Cancer Patient Profile in a Population of Puerto Rican Women

Abstract Background: Breast cancer (BC) is the most frequently diagnosed cancer type, as well as the leading cause of cancer death among women in Puerto Rico (PR). Moreover, inflammatory breast cancer (IBC) is a highly aggressive BC subtype. The current study aimed to describe the patient profile and the clinicopathological characteristics of IBC tumors in Hispanic women living in Puerto Rico. Methods: This is a retrospective, population-based study using the Puerto Rico Central Cancer Registry (PRCCR) database and the Health Insurance Linkage Database (PRCCR-HILD) to identify and describe the patient profile of Puerto Rican women diagnosed with IBC from 2008 to 2018. Variables such as age at diagnosis, staging variables, tumor receptor subtypes, treatment received, and overall survival (OS) were studied. Statistical analysis methods were employed to describe the population, estimate survival curves and examine the risk of dying. Results: We identified a total of 51 patients. The mean age at diagnosis of IBC in the current study was 59 years old, which is older than the mean age at diagnosis of IBC for women in the mainland US, but younger than the mean age of women that are diagnosed with BC in PR (63 years old). A total of 62.8% of patients had no metastases at diagnosis and 64.7% were diagnosed with stage III disease. Most tumors presented with ER+/PR+/Her2- (21.6%), or a triple-negative (ER-/PR-/Her2-, 15.7%) tumor concordance. The OS during the 12 months post-diagnosis was 66%, whereas at 36 months, OS decreased to 39%. The triple-negative subtype had the worst survival at 36 months (36%). Women with stage IV disease and those with ER-/PR- tumor subtype had a higher risk of dying. Conclusions: This is the first research to describe the patient profile and characteristics of women diagnosed with IBC in Puerto Rico. Our results suggest that the Puerto Rican IBC patient population presents unique characteristics. This research increases awareness about this lethal disease in PR. Citation Format: Luz Arroyo-Cruz, Michelle Martinez-Montemayor. Inflammatory Breast Cancer Patient Profile in a Population of Puerto Rican Women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-10.

Abstract PO5-10-04: Rare to Care: Assessing Awareness and Health Disparity Factors Related to Inflammatory Breast Cancer in the Primary Care Setting

Abstract Background: The diagnosis of inflammatory breast cancer (IBC) is life-changing as it is a rare, highly aggressive breast cancer variant designated by NIH as a cancer health disparity. Given the unique presentation of diffuse tumor cell spread in the absence of a solid mass, which is not easily detected by self-breast exams or mammograms, IBC patients often face delays in diagnosis and treatment. Therefore, an individualized and a multifaceted approach that addresses the unique needs of the patient with input from both providers and the community is an unmet need. To address this, we are investigating the current knowledge and perspectives of providers and public related to rare cancers like IBC in primary care practices. Methods: Researchers and advanced practice providers collaboratively drafted and piloted the initial surveys with guidance from a Community Advisory Board, comprising of members from academic institutions, primary care practices in urban and rural setting, topical experts, and patient advocates, in order to assess primary care providers (PCPs) and general public knowledge, attitudes and health seeking practices related to rare cancer like IBC. Results: The surveys are currently being administered statewide specific to PCPs or public via cognitive interviews and/or using an online survey tool within North Carolina as a model of a large state (100 counties) with a range of population densities, race, ethnicities, and environmental burdens. Challenges elaborated at the PCP level include communicating rare cancer information, gaps in confidence in diagnosing IBC, timely follow-up with patients, and accessing specialty care and an unmet need for developing PCP educational modules to improve guideline-concordant care. Public data analyzed to date is from a Duke Outpatient Clinic, an urban ambulatory care teaching practice serving primarily low-income, medically complex patients in Durham (n=14) included 69% Black, 93% female, with 68% in households earning under $50,000 annually). 71% had not heard of IBC; 64% did not identify high BMI as a risk factor; 36% did not know there is differential race-related incidence; 74% did not recognize IBC-specific symptoms. 50% noted lack of insurance, transportation, religious reasons, or difficulty or fear of talking to a physician contributed in general delay in seeking health care. Most importantly, 93% expressed feeling comfortable sharing information about IBC with others. Majority expressed that adding visual aids and providing educational materials about IBC at the time of survey would be helpful. Conclusions: The results highlight the role of PCPs, including physicians, physician assistants, and nurse practitioners, who are often the first point of contact when patients begin to notice signs or symptoms. The general public and the patients with common breast cancer subtypes can provide valuable insight into their own health care experiences, what works for them and what barriers they face in their communities, which can be used to compare with experience of patients with IBC and other rare cancers. Overall, the lessons from this study inform the development of effective tools to educate PCPs and patients for this understudied cancer that contributes to disparities in clinical and survival outcomes in minoritized and marginalized populations. Support in part from the Duke Cancer Institute pilot as part of the P30 Cancer Center Support Grant (P30CA014236) and Duke School of Medicine Behavioral Health and Survey Research Core Facility Award (GRD, ANT); Duke Advanced Practice Provider Leadership Institute scholarship (VK, GRD), Department of Surgery (GRD); Duke Ahead Education grant; NIH/NCI RO1CA264529-01 (GRD); ACS Mission Boost grant MBG-20-141-01-MBG (GRD), Nakayama Public Service Scholar Award (AB). Citation Format: Gayathri R Devi, Lawrence Greenblatt, Rashmi Saincher, Valerie Keck, Beau Blass, Sarah Weaver, Alexandra Bennion, Anh Tran. Rare to Care: Assessing Awareness and Health Disparity Factors Related to Inflammatory Breast Cancer in the Primary Care Setting [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-10-04.

Abstract PO4-16-09: Enhancing Research on Inflammatory Breast Cancer through Count Me In: Assessing the Accuracy of Self-Reported Diagnoses

Abstract Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that relies on clinical identification of specific breast changes for diagnosis, in addition to pathological confirmation of invasive breast cancer. There is a clear need to increase participation of patients with IBC in research to better understand its clinical course and optimal treatment strategy. Count Me In (CMI) is a nonprofit research initiative that enables patients across the United States and Canada to accelerate cancer research by sharing their clinical data and biospecimens. The Metastatic Breast Cancer Project (MBCProject) was the first CMI initiative and is a prospective longitudinal cohort designed to capture these data from patients with metastatic breast cancer. Methods: We reviewed available medical records of patients participating in the MBCProject and who self-reported as having IBC. Records were reviewed by a study team member to identify documentation by a provider of an IBC diagnosis. For records without a documented IBC diagnosis, the clinical symptoms were assessed using a novel quantitative IBC scoring system (Mason G et al. BCRF 2022) currently being validated. Finally, records were also assessed by a physician for final determination of an IBC diagnosis. Records were classified as “concordant” or “not concordant”. Concordant is defined as “review of medical records confirms IBC using the unifying set of specific diagnostic criteria”. We desired the rate of concordant cases to be ≥90%; if ≤ 85% it would be considered as unacceptable to rely solely on patient self-report of IBC diagnosis in future research. Results: We reviewed records of 79 patients participating in the MBCProject who self-identified as having IBC and had medical records collected. Of these, 51 (64.5%) had IBC stated in providers’ notes. Of the remaining 28 patients, 6/28 met criteria for IBC using the new IBC diagnostic criteria, 17/28 didn’t have evidence of IBC based on the records available and 6/28 we were unable to make a final determination due to lack of records at the time of initial diagnosis. In total, 57/79 (72%; 95% CI 61-82%) patients had a concordant diagnosis. Conclusion: Patient self-report registries such as CMI are invaluable for the collection of clinical information and biospecimens for research of patients with rare diseases, however, a self-reported diagnosis of IBC may not be reliable. To improve the accurate identification of IBC, optimization of the questions asked to patients on these registries is warranted. This may include additional screening questions such as specific skin findings and timing of onset of symptoms. Focusing on patients with stage III IBC may also provide a better patient population to test this strategy. Citation Format: Elizabeth Troll, Sean Ryan, Virginia (Ginny) Mason, Mariesa D. Powell, Aditi Hazra, Nikhil Wagle, Mary McGillicuddy, Sara Tolaney, Meredith Regan, Filipa Lynce. Enhancing Research on Inflammatory Breast Cancer through Count Me In: Assessing the Accuracy of Self-Reported Diagnoses [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-09.

Abstract PO2-02-14: Development of a multi-institutional, photograph-rich clinical dataset to test and validate a novel inflammatory breast cancer (IBC) scoring system

Abstract Purpose: Susan G. Komen, The Inflammatory Breast Cancer (IBC) Research Foundation, and the Milburn Foundation convened a collaborative of patient advocates, clinicians, and researchers and proposed a novel quantitative scoring system for IBC diagnosis. The score includes timing of symptoms, extent of skin edema and erythema/other discoloration, breast and nipple asymmetry, lympho-vascular space invasion, nodal stage, and diffuse extent disease in the breast on breast imaging. Total scores were categorized (< 14 Not IBC, 14-24 Weak Possibility of IBC, 25-41 Strong Possibility of IBC, > 41 Definitely IBC). Herein, we developed a multi-institutional clinical dataset to retrospectively test and validate the proposed scoring system. Methods: IBC (N= 988) and non-IBC (N=322) cases were identified at two institutions with dedicated multi-disciplinary IBC programs, UT MD Anderson Cancer Center (MDA) and Dana-Farber Cancer Institute (DFCI). The DFCI cohort was diagnosed from 1986-2021 and the MDA cohort was diagnosed from 2010-2020. The non-IBC cohorts were identified as consecutive T4b and T4c cases in existing retrospective databases. Photographs were reviewed for available cases. All scoring variables were reviewed with data extractors and standard operating procedures (SOPs) developed for all ambiguous findings and language. A subset of scores were reviewed by IBC clinicians (FL, WW) and discrepancies discussed to inform the SOPs. Missing data imputation using three methods was examined. Area under the curve (AUC) - Receiver operator characteristic (ROC) curves and values, and sensitivity and specificity for the proposed score cut offs were examined. Results: Of 1320 patients currently in the analysis, 421 (31.9%) have missing data on > 1 characteristics and 47 (3.6%) are missing data on > 4. The rubric characteristic most commonly missing was “nipple abnormalities” accounting for 21.0% and 19.3% for IBC and non-IBC cohorts respectively. Unavailable bilateral breast photograph was the primary source of missing data. The highest scoring finding was present in the following percentage of IBC and non-IBC cases, respectively: timing of symptom onset < 3 months (74.1% vs 38.6%), any peau d’orange (61.2% vs 30.1%), clinically apparent enlargement or new asymmetry of breast size (87.8% vs 90.1%), complete or near complete involvement of the breast skin by erythema or discoloration (55.6% vs 25.6%), new nipple inversion (24.6% vs 9.0%), dermal lymphovascular emboli present (17.9% vs 1.8%), diffuse involvement of the breast parenchyma by imaging (72% vs 77.7%). True IBC cases were categorized as Definitely IBC, Strong Possibility, Weak Possibility, not IBC and unknown 19.7%, 49.1%, 0.4%, 0.1%, and 30.7%. True non-IBC were 0.6%, 51.8%, 9.9%, 2.1%, and 35.5%. Random imputation, lowest value imputation, and median value imputation were compared to impute missing data. AUC-ROC values for each method were similar, 0.80 - 0.84. Conclusion: We describe the development of the largest multi-institutional IBC clinical database to date. SOPs for the rubric characteristics were developed. The importance of bilateral photography to assess the score retrospectively is highlighted. The score is associated with a good AUC-ROC but still leaves much overlap among cases between 25 and 42. Further optimization of the current scoring system and association with outcomes are in progress. Citation Format: Filipa Lynce, Samuel Niman, Megumi Kai, Sean Ryan, Elizabeth Troll, Li Li, Kathy Miller, Reshma Jagsi, Ginny Mason, Beth Overmoyer, H. T. Carisa Le-Petross, Faina Nakhlis, Savitri Krishnamurthy, Beth Harrison, Susie X. Sun, Eren Yeh, Jennifer Bellon, Laura Warren, Michael Stauder, Meredith Regan, Wendy Woodward. Development of a multi-institutional, photograph-rich clinical dataset to test and validate a novel inflammatory breast cancer (IBC) scoring system [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-14.

Delayed Diagnosis of Inflammatory Breast Cancer Presenting as Acute Mastitis in a Patient One Month Postpartum.

Inflammatory breast cancer (IBC) is a rare yet aggressive form of invasive ductal carcinoma, with a poor prognosis and decreased 5-year survival rates. Characteristic findings for IBC include rapid onset of breast edema, peau d'orange appearance, and involvement of the breast skin. Additionally, diagnosis is confirmed with a skin punch biopsy. With such nonspecific features, IBC can be mistaken for benign etiologies, causing delays in diagnosis and treatment. This patient is a 44-year-old woman presenting with left breast swelling while concurrently breastfeeding. Following antibiotic treatment but no symptom resolution, the patient was referred out for further follow-up. Despite multiple imaging studies, suggesting benign findings, clinical suspicion prompted continued evaluation and finally diagnosis of triple-negative inflammatory breast cancer with distant metastases. Further awareness of the presentation of IBC and its mimicking of other disease processes such as mastitis is paramount to earlier detection and improved outcomes in future patients.

Inflammatory Breast Cancer with Diffuse Breast Erythema and Swelling as Symptoms

<p>臨床上，乳房紅腫常會讓人聯想為乳房發炎性疾病。本案例是一位44歲女性，因右側乳房瀰漫性紅腫約四週未改善就醫，後診斷為右側乳癌第三期，並行右側乳房根除性手術，術後三週，住院計畫做化療，發現白血球升高、右胸壁及右腋下多處復發。考量疾病進展迅速，回溯過去病史、治療過程及病理報告，最後診斷為發炎性乳癌（Inflammatory Breast Cancer, IBC），予以多模式治療後，腫瘤消除。發炎性乳癌相當罕見，沒有特定組織學，易與乳房發炎性疾病及其它局部嚴重晚期乳癌（Locally Advanced Breast Cancer, LABC）混淆。建議臨床同仁，如果乳房有發炎現象，使用抗生素兩週無效時，須將發炎性乳癌列為鑑別診斷並將其特徵謹記於心，以免延誤治療和危害病人生命。</p> <p> </p><p>In clinical practice, breast erythema is often linked to breast inflammatory diseases. The case of this study is a 44-year-old female, who went to the hospital due to diffuse erythema with swelling on the right breast for four weeks. She was initially diagnosed with stage III breast cancer and received a right-side radical mastectomy. When she was admitted for chemotherapy three weeks after the sur-gery, she was found to have leukocytosis and multiple metastasis over the right chest wall and right axillary. Therefore, cancer recurrence was suspected. Considering the rapid progression of the disease and reviewing past medical history, medical treatment procedures, and pathological report, the final diagnosis of inflammatory breast cancer (IBC) was made. After multimodal treatments, the tumors were eliminated. Given that IBC is easily confused with inflammatory diseases and other locally advanced breast cancer (LABC), if the breast is inflamed and antibiotic treatments are not effective for two weeks inflammatory breast cancer (IBC) must be included in the differential diagnosis. The healthcare provider must keep IBC’s characteristics in mind to avoid delay treatment which might en-danger the patient’s life.</p> <p> </p>

Identification of barriers at the primary care provider level to improve inflammatory breast cancer diagnosis and management

The purpose of this study, based in the United States, was to evaluate knowledge gaps and barriers related to diagnosis and care of inflammatory breast cancer (IBC), a rare but lethal breast cancer subtype, amongst Primary Care Providers (PCP) as they are often the first point of contact when patients notice initial symptoms. PCP participants in the Duke University Health System, federally qualified health center, corporate employee health and community practices, nearby academic medical center, Duke physician assistant and advanced practice nurse leadership program alumni were first selected in a convenience sample and for semi-structured interviews (n = 11). Based on these data, an online survey tool was developed and disseminated (n = 78) to assess salient measures of IBC diagnosis, health disparity factors, referral and care coordination practices, COVID-19 impact, and continuing medical education (CME). PCP reported access to care and knowledge gaps in symptom recognition (mean = 3.3, range 1–7) as major barriers. Only 31 % reported ever suspecting IBC in a patient. PCP (n = 49) responded being challenged with referral delays in diagnostic imaging. Additionally, since the COVID-19 pandemic started, 63 % reported breast cancer referral delays, and 33 % reported diagnosing less breast cancer. PCP stated interest in CME in their practice for improved diagnosis and patient care, which included online (53 %), lunch time or other in-service training (33 %), patient and provider-facing websites (32 %). Challenges communicating rare cancer information, gaps in confidence in diagnosing IBC, and timely follow-up with patients and specialists underscores the need for developing PCP educational modules to improve guideline-concordant care.

Time to treatment in inflammatory breast cancer: Experience from a single institution.

e13530 Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that accounts for nearly 10% of breast cancer caused mortality. With an annual rate between 1-4% per year and 3-year overall survival (OS) of about 65%, timely completion of trimodal treatment including systemic therapy, surgery, and radiation therapy is essential. Prior studies have demonstrated impact of time to treatment on OS of non-IBC patients. The aim of this study was to examine the relationship between the time from diagnosis to treatment and outcomes for patients with IBC. Methods: Categorically matched patients who underwent treatment of inflammatory and non-inflammatory locally advanced breast cancer at an NCI-Designated Comprehensive Cancer Center from 2006-2016 were analyzed. Clinicopathologic factors were compared using Chi-square and Wilcoxon Rank Sum tests. Overall survival was assessed using Kaplan-Meier methods and log-rank tests. Results: Of 217 patients who underwent excision for breast cancer, 99 had an IBC diagnosis. All patients were female, 85% (n=84) white, and 98% (n=97) had single-sided breast disease. Thirty-one percent (n=31) of patients had clinically node positive (N1) disease, the majority were ER negative (53%), and 38% were HER2 positive. There was no difference in time from first abnormal mammogram to diagnosis between IBC vs non-IBC patients. Ninety-one percent (n=90) of IBC patients underwent neoadjuvant chemotherapy compared to 52% (n=61) of non-IBC patients (p<0.001). Only 27% (n=27) of IBC had a pathological complete response. IBC patients tended to present earlier with symptoms (p=0.054), begin chemotherapy sooner after diagnosis (median days: 10.5 vs 17.0, respectively; p=0.002), and were more likely to receive radiation earlier after surgery (p<0.001). However, IBC patients were also more likely to undergo surgery later (191 vs 153 days; p<0.001) and have a worse OS (p=0.006). While not statistically significant, there was a trend toward worse OS for IBC patients with delayed chemotherapy initiation (p=0.459). Conclusions: IBC is an aggressive form of breast cancer associated with poor OS. Patients with this diagnosis are more likely to receive trimodal therapy sooner, but this may not significantly improve their OS. Further studies are necessary to evaluate effect of time from presentation of initial symptoms to treatment initiation on outcomes.

SP33. Optimizing Patient Selection for Lympha in Patients with Inflammatory Breast Cancer

PURPOSE: Patients with inflammatory breast cancer (IBC) are at high risk for lymphedema due to their need for axillary lymph node dissection (ALND) and high-dose regional nodal radiation. LYMPHA (Lymphatic Microsurgical Preventive Healing Approach) is increasingly offered for prevention of upper extremity lymphedema after breast cancer treatment. Prior studies focus on intraoperative and postoperative lymphedema risk factors, some of which are unknown preoperatively when the decision to perform LYMPHA is made. This study aimed to identify preoperative lymphedema risk factors in the high-risk IBC population. METHODS: Retrospective review of our institution’s IBC program database was conducted. All patients with IBC who underwent neoadjuvant chemotherapy (NAC) and modified radical mastectomy (MRM) with adjuvant radiation were reviewed. The primary outcome was self-reported lymphedema development. Secondary endpoints were time from IBC diagnosis, mastectomy, or radiation completion to lymphedema diagnosis. Multivariable logistic regression analysis was used to identify preoperative lymphedema risk factors, while controlling for number of lymph nodes removed during ALND, number of positive lymph nodes, presence of residual disease on final pathology, and need for adjuvant systemic therapy. Additionally, the subset of patients who underwent breast reconstruction was reviewed and descriptive statistics of reconstructive techniques performed. RESULTS: Of 356 patients (86% Stage 3, 14% Stage 4) who underwent NAC, MRM and radiation, complete data on risk factors were available for 134 (37.6%). Mean age at diagnosis was 51 years (range 22-89 years). Forty-seven percent of patients developed lymphedema during treatment and 87% had ≥5 lymph nodes removed. Four percent developed lymphedema preoperatively (mean 138 days, median 149 days after IBC diagnosis), 14.6% developed lymphedema after surgery and before radiation (mean 51 days, median 45 days postoperatively), and 81.7% developed lymphedema after radiation (mean 470 days, median 271 days after radiation). Obesity (BMI > 30) (OR 2.7, CI 1.2-6.4, p = 0.02) and non-white race (OR 4.5, CI 1.2-23, p = 0.04) were preoperative risk factors for lymphedema. Reconstruction data was available for 91.3% of patients (n=325). Of these, 78.5% (n=255) did not receive reconstruction. Among those who underwent reconstruction (n=70, 21.5%), most patients were younger than 50 years (n=41, 58.6%). Most who underwent reconstruction were white (n=63, 90.0% versus n=2, 2.86% black and n=5, 7.14% other). Ethnicity data was available for 48 patients (68.6%). The majority of patients were non-Hispanic (n=46, 95.83%). BMI data was available for 48 patients and the majority had BMI <30 (n=29, 60.42%). CONCLUSION: Patients with IBC are at high risk of lymphedema, with 47% of patients in our study developing self-reported lymphedema. While need for NAC, ALND, and PMRT are known risk factors, we identified obesity and non-white race as additional lymphedema risk factors in this population. Given this high prevalence, LYMPHA should be considered for all patients with IBC. Larger, prospective studies are needed to further evaluate potential racial disparities in lymphedema development.

Abstract P1-14-02: Breast cancer in pregnancy: A retrospective clinical study in a single large tertiary cancer center in the United Arab Emirates

Abstract Introduction: Pregnancy associated breast cancer (PABC) is defined as any breast cancer (BC) diagnosed during pregnancy or one year postpartum. BC considered the most common type of malignancy in pregnant women, occurring approximately once in every 3000 pregnancies. In view of the fact that PABC is a relatively rare event surrounded by multiple variables, few studies address the best management and treatment options. Objectives: The aim of this study is to report the incidence, clinicopathological characteristics and treatment outcomes of PABC diagnosed over 20 years period treated in Tawam hospital. This will help clinician, researchers shed the light of the unmet needs for this entity of BC. Method: We reviewed all BC patients ≤ 40 years of age diagnosed between 2000 -2020 in Tawam hospital and identified those with PABC as the definition above. Information was obtained from the Tawam Cancer Registry and analyzed. A retrospective data analysis was conducted. The data analyzed using the SPSS software. The study was approved by the hospital Research Ethics Board. Results: a total of 67 patients were identified in the study with pregnancy associated BC among all BC patients age ≤ 40 years old which compromised 7.4% (67/911) from year 2000 till 2022. The clinical and the pathological characteristics of these patients are provided in table 1. Around 22 (32.8%) of the patients were diagnosed at the second trimester. Only 6 (8.6%) patients found to have inflammatory breast cancer diagnosis. 31(42%) patients had hereditary genetic testing done of which 5 (16.1%) patients found to have pathogenic genetic mutations. Pathogenic mutations identified including 3 (9.7%) patients with BRCA2 mutation, 1 patient had BRCA1 mutation, and 1 patient had TP53 mutation. Out of these 67 patients, 36 (65.5%) underwent modified radical mastectomy, 19 (34.5%) had lumpectomy, 37 (55.2%) had axillary lymph node dissection, 14 (20.8%) had sentinel lymph node biopsy, 13 (19.4%) had the surgery during the pregnancy and 45 (67.1%) had adjuvant radiation therapy post delivery. Regarding the chemotherapy, 29 (43.2%) patients received Neoadjuvant chemotherapy, 24 (35.8%) received Adjuvant chemotherapy, 11 (16.4%) were pregnant when they received chemotherapy. Only 7 (10.4%) patients had termination of their pregnancies, while 3 (4.4%) patients had spontaneous miscarriage. 47 (70.1%) patients delivered at our facility and 9 (13.4%) patients delivered at other facilities (unknown delivery details). In terms of delivery type, 24 (35.8%) patients had C-section surgery, and 23 (34.3%) patients had spontaneous vaginal delivery. All of the patients who had delivery in Tawam hospital, delivered healthy baby with no complications. Survival analysis and treatment outcome to be presented in the meeting. Conclusion: Our study showed that significant proportion of the patients with PABC diagnosed with HER2neu + disease, stage II-III disease, high grade tumors and nodal involvement on initial presentation. Patients were treated according to the standard of care with trend of favorable delivery outcomes. PABC is a unique entity of BC that requires careful planning and multidisciplinary approach with consideration of factors related to feral, pregnancy and maternal outcomes. Table 1: Clinical and Pathological Characteristics of Pregnancy Associated Breast Cancer (N=67) Citation Format: Mohammad Hourani, Rawan Bdair, Mawada Hussein, Ali Yousif, Lina Wahba, Abla AlAgha, Alaa Shoqeir, Fatima Alkindi, Aydah Alawadhi. Breast cancer in pregnancy: A retrospective clinical study in a single large tertiary cancer center in the United Arab Emirates [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 P1-14-02.

Abstract B045: Assessing knowledge and barriers at the primary care provider level that contribute to disparities in inflammatory breast cancer diagnosis and treatment

Abstract Background: Although recognized as the most lethal breast cancer, inflammatory breast cancer (IBC), a NCI designated rare cancer and a cancer health disparity, is severely understudied. Given the unique presentation of diffuse tumor spread without a solid mass, not easily detected by self-breast exams or mammograms, IBC patients often face delays in diagnosis and treatment leading to poor outcomes. Moreover, reproductive risk factors in IBC and high incidence in younger women, minoritized and marginalized populations highlight the significance of primary care providers (PCP) who are often the first point of contact when patients begin to notice symptoms. Methods: In this study, we evaluated the knowledge gaps and barriers amongst PCP (physicians, physician assistants, nurse practitioners) in their ability to recognize the signs and coordinate care effectively for IBC. To assess PCP experiences with IBC in their practices and overall breast cancer care during COVID, we first conducted semi-structured interviews (n=11) with providers selected from a convenience sample at Duke University and in the local clinics. Based on data from these interviews and additional cognitive interviews, we developed and disseminated a comprehensive online survey (n=78). Results: In this study, access to care was identified as the single most important barrier to treating rare cancers. Furthermore, majority of the PCPs in this cohort identified only a moderate ability to recognize IBC in patients (mean = 3.3, range 1-7), thereby limiting early diagnosis. From the semi-structured interviews, PCPs recognized that IBC is not likely to be part of typical differential diagnosis when patients present with mastitis or breast changes, and most had not seen IBC in their practice. Only 31% (n=78) reported ever suspecting IBC in a patient. Delays in referrals to specialized large clinical centers were also reported as a major barrier. In particular, 62.8% (n=49) reported some delay in referrals for diagnostic imaging. In addition, since the COVID-19 pandemic started, 33% reported diagnosing less breast cancer cases and 63% reported that they experienced breast cancer referral delays. When asked what methods providers would find most helpful to learn more about diagnosing and caring for patients with IBC, the top three modes of preferred education were online CME options (53%); lunchtime, or other in-service training (33%); and website for patients and providers (32%). Conclusions: We succeeded in developing a survey instrument and to our knowledge first mixed methods study to assess PCP knowledge gaps and barriers to timely diagnosis and care of IBC patients. Results underscore need to develop PCP training modules and care coordination tools to improve guideline-concordant care. This survey instrument also has the potential to serve as a blueprint to design, implement, and evaluate interventions for other rare cancers. Support: Duke Behavioral Health and Survey Research Core Award (GRD, ANT); Dept of Surgery (GRD); Duke Undergraduate Nakiyama Public Service Scholar (AB). Citation Format: Gayathri R. Devi, Laura J. Fish, Alexandra Bennion, Sarah Weaver, Gregory Sawin, Anh N. Tran. Assessing knowledge and barriers at the primary care provider level that contribute to disparities in inflammatory breast cancer diagnosis and treatment [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B045.

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%.

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

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. 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. 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. 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.

CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer.

Background Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtypes of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. Material and Methods. Two datasets from gene expression omnibus database (GEO) were selected. Enrichment analysis and protein-protein interaction (PPI) network for the DEGs were performed. We analyzed the prognostic values of hub genes in the Kaplan-Meier Plotter. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) was used to find candidate small molecules capable to reverse the gene status of IBC. Results 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. The KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A, and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24, and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cancer. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Conclusion Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC.

Cancer inflammatoire du sein : Aspects épidémiologiques, diagnostiques, thérapeutiques et évolutifs. A propos de 43 cas à l’Institut Joliot-Curie de Dakar

OBJECTIVE: To clarify the epidemiological, diagnostic and therapeutic features and to improve the prognosis of inflammatory breast cancer. MATERIALS AND METHODS: This is a retrospective study from January 1, 2018 to December 31, 2020 including patients with a diagnosis of inflammatory breast cancer. RESULTS: During the study, 1.730 cases of breast cancer were collected, of which 43 cases of inflammatory cancer (2.5%). The average age of the patients was 44.8 years. The average consultation time was 6.4 months. All patients had lymph node involvement. Non-specific infiltrating carcinoma was the histological type found in all cases. All patients received at least a first line of chemotherapy with a better clinical response to taxanes than to anthracyclines. Surgery was performed in 69.76% of cases. Forty percent of patients were alive at the end of the study. CONCLUSION: Inflammatory breast cancer is quite rare at the Joliot-Curie Institute. The diagnosis is late. Early diagnostic and therapeutic management would improve the therapeutic outcome of inflammatory breast cancer. KEYWORDS: Inflammatory breast cancer; Epidemiology; Prognosis.

Bilateral metachronous inflammatory breast cancer. A rare case of this biologically aggressive breast cancer subtype.

Background: Inflammatory Breast Cancer (IBC) is a rare and biologically aggressive form of breast cancer. In IBC, breast cancer cells directly invade and block the lymphatic channels of the overlying skin. We present a very rare case of a 59 year old postmenopausal lady with a bilateral metachronous IBC treated in our tertiary centre where her initial diagnosis of IBC was 3 years before her IBC diagnosis in the contralateral breast. Although both IBCs had lobular features, they carried completely different biological characteristics.

Characterization of Inflammatory Breast Cancer in Hispanic Women from Puerto Rico.

Background: Breast cancer (BC) is the most diagnosed cancer and the leading cause of cancer death among women in Puerto Rico (PR). Inflammatory breast cancer (IBC) is considered the most aggressive BC subtype. This study characterized the IBC population of Hispanic women living in Puerto Rico and aimed to estimate the IBC survival rate using data from the Puerto Rico Central Cancer Registry (PRCCR). Methods: This is a retrospective, population-based study using the PRCCR database and the Health Insurance Linkage Database (PRCCR-HILD). We analyzed data from patients that were diagnosed with IBC from January 1, 2008 to December 31, 2018. Patients were identified using the International Classification of Diseases for Oncology, 3rd edition (ICD-O-3) site codes C50.0-C50.9 and histology code 8530. Variables such as age at diagnosis, marital status, health insurance, geographic area of residence, staging variables, tumor receptor subtypes, treatment received, and overall survival (OS) were studied. Statistical analysis methods were employed to describe the population, estimate survival curves and examine the risk of dying. Results: The data of 51 patients were included. The mean age at diagnosis of IBC in the current study was 59 years old. A total of 62.8% of patients had no metastases at diagnosis and 64.7% were diagnosed with stage III disease. Most tumors presented with ER+/PR+/Her2- (21.6%), or a triple negative (ER-/PR-/Her2-, 15.7%) tumor concordance. The OS during the first year was 66% (90% CI: 0.54-0.76), whereas 36 months post-diagnosis was at a low 39% (90% CI: 0.27-0.59). The triple-negative subtype had the worst survival at 36 months (36% [90% CI: 0.11-0.62]). This study revealed through Cox regression analysis that women with stage IV disease and those with ER-/PR- tumor subtype have a higher risk of dying (HR 4.99; [90% CI: 2.30-10.83] and HR 4.74; [90% CI: 1.88-11.95]), respectively. Conclusions: Our results suggest that the Puerto Rican IBC patient population presents unique characteristics. This is the first research to describe the patient profile and characteristics of women diagnosed with IBC in PR. This research increases awareness about this lethal disease in PR.

Why diagnosing inflammatory breast cancer is hard and how to overcome the challenges: a narrative review.

The purpose of this narrative review is to summarize the contributors to misdiagnosis or delayed diagnosis of inflammatory breast cancer (IBC) and strategies for expedient diagnosis. Patients with IBC often report the disease as initially being misdiagnosed, most commonly as mastitis. We reviewed the literature on this challenging diagnosis by using sequential PubMed search criteria including IBC breast symptoms, IBC diagnosis, and IBC imaging modalities to augment the authors' knowledge of IBC. Other references were added from the manuscripts identified in the PubMed searches and from manuscript reviewers. Several factors contribute to the delayed diagnosis of IBC. One important factor is that IBC is uncommon, and many generalists may not be aware of it in the differential diagnosis of breast skin symptoms. Several features of IBC contribute to the low sensitivity of mammography for its detection, and so the diagnosis is based on clinical factors and is thereby subjective. The presentation can be highly varied; classic textbook images that do not capture the range of presenting signs and symptoms across skin tones may contribute to missed diagnoses in patients with atypical presentations. In fact, the staging system of the American Joint Committee on Cancer, which requires erythema of the breast skin for diagnosis, may exclude patients with obvious global breast skin findings that are not explicitly red. We present an adapted algorithm for working up the undiagnosed inflammatory breast to ensure the timely and accurate diagnosis of IBC. We assert that frank, non-erythematous global skin signs in an enlarged breast with diffuse breast malignancy are sufficient to diagnose IBC if the timing of these signs and findings on biopsy are consistent. We further provide images of atypical IBC identified by global breast skin signs, including peau d'orange, consistent with IBC in the absence of frank erythema.

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.