Breast Masses Research Articles

A case of diabetic mastopathy: An unusual breast lesion mimicking cancer in type 1 diabetes mellitus

Diabetic mastopathy is a rare fibroinflammatory disorder seen among middle aged and premenopausal age group. It is also called lymphocytic mastopathy or sclerosing lymphocytic mastitis. This is seen associated with type 1 diabetes mellitus and other autoimmune disorders specially related to endocrine disorders like thyroid. The definite diagnosis of diabetic mastopathy is truly based on biopsy and histopathological examination.A 33 year old female came to hospital with complaints of swelling in right breast since one month and pain since one week. She was a known case of type 1 diabetes mellitus since 10 years and on regular medications. Radiological Impression was possibilities of mastitis with abscess formation more likely to be considered. But infiltrating malignant neoplasm with areas of necrosis is also a differential diagnosis. Our histopathology laboratory, we received incision biopsy from right breast and microscopic examination from multiple tissue sections showed breast parenchyma with extensive fibrosis and periductal inflammatory infiltrate predominantly lymphocytes, plasma cells and a few neutrophils. Some of the ducts show epithelial proliferation forming bridges and micropapillae. Histopathological diagnosis was Lymphocytic Mastitis with features of Atypical Ductal Hyperplasia.: The diagnosis of Diabetic Mastopathy is based on clinical details, radiological evaluation and biopsy correlation. Sometimes it’s difficult to differentiate from carcinoma breast, so histopathological examination is indicated for a definitive diagnosis and management.

Advanced-stage breast cancer diagnosis and its determinants in Ethiopia: a systematic review and meta-analysis

IntroductionWorldwide, breast cancer is the primary cause of illness and death. Unless early detected and treated breast cancer is a life-threatening tumor. Advanced-stage presentation is greatly linked with short survival time and increased mortality rates. In Ethiopia nationally summarized evidence on the level of advanced-stage breast cancer diagnosis is scarce. Therefore, this systematic review and meta-analysis aimed to determine the pooled prevalence of advanced-stage breast cancer diagnosis and its determinants in Ethiopia.MethodBy following PRISMA guidelines, a systematic review and meta-analysis were carried out. To include relevant publications, a broad literature search was conducted in the African Online Journal, PubMed, Google Scholar, and Embase which are published until last search date; June 15, 2023. To prevent further duplication this review was registered in PROSPERO database with ID no of CRD42023435096. To determine the pooled prevalence, a weighted inverse variance random effect model was applied. I2 statistics and the Cochrane Q-test were computed to determine heterogeneity. To evaluate publication bias, a funnel plot, and Egger’s regression test were used.ResultA total of 924 articles were sought and finally 20 articles were included in this review. The pooled prevalence of advanced-stage breast cancer diagnosis in Ethiopia was 72.56% (95%CI; 68.46-76.65%). Use of traditional medicine as first choice (AOR = 1.32, 95% CI: (1.13–1.55)), delay of > 3 months in seeking care (AOR = 1.24, 95% CI: (1.09–1.41)), diagnosis or health system delay of > 2 months (AOR = 1.27, 95% CI: (1.11–1.46)), rural residence (AOR = 2.04, 95% CI: (1.42 − 2.92)), and chief complaint of a painless breast lump (AOR = 2.67, 95% CI: (1.76–4.06)) were significantly associated to advanced-stage diagnosis.ConclusionIn Ethiopia, more than two-thirds of breast cancer cases are diagnosed at an advanced stage. Use of traditional medicine before diagnostic confirmation, delay in seeking care, health system delay, rural residence, and chief complaint of painless breast lump were positively associated with an advanced-stage diagnosis. Policymakers and program designers give great focus to those delays so as to seek and access modern diagnosis and treatment as early as possible specifically focusing on those who are rurally residing.

BIA-ALCL and BIA-SCC: Updates on Clinical Features and Genetic Mutations for Latest Recommendations

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) and Breast Implant-Associated Squamous Cell Carcinoma (BIA-SCC) are emerging neoplastic complications related to breast implants. While BIA-ALCL is often linked to macrotextured implants, current evidence does not suggest an implant-type association for BIA-SCC. Chronic inflammation and genetics have been hypothesized as key pathogenetic players, although for both conditions, the exact mechanisms and specific risks related to breast implants are yet to be established. While the genetic alterations in BIA-SCC are still unknown, JAK-STAT pathway activation has been outlined as a dominant signature of BIA-ALCL. Recent genetic investigation has uncovered various molecular players, including MEK-ERK, PI3K/AKT, CDK4-6, and PDL1. The clinical presentation of BIA-ALCL and BIA-SCC overlaps, including most commonly late seroma and breast swelling, warranting ultrasound and cytological examinations, which are the first recommended steps as part of the diagnostic work-up. While the role of mammography is still limited, MRI and CT-PET are recommended according to the clinical presentation and for disease staging. To date, the mainstay of treatment for BIA-ALCL and BIA-SCC is implant removal with en-bloc capsulectomy. Chemotherapy and radiation therapy have also been used for advanced-stage BIA-ALCL and BIA-SCC. In-depth characterization of the tumor genetics is key for the development of novel therapeutic strategies, especially for advanced stage BIA-ALCL and BIA-SCC, which show a more aggressive course and poor prognosis.

Invasive Ductal Carcinoma Arising within a Fibroadenoma: A Case Report and Literature Review.

Background: Invasive ductal carcinoma (IDC) is the most common form of breast cancer, frequently presenting independently. Rarely, IDC arises within a fibroadenoma, a benign breast tumor typically associated with younger women. This case report and literature review aim to highlight the diagnostic challenges and clinical implications of finding IDC within a fibroadenoma. Case Presentation: A 36-year-old female patient presented with a dolent palpable mass in the right breast. Initial mammography described normal fibroglandular structures without significant findings. However, subsequent imaging ultrasound identified an 18x14 mm oval formation at the 9 o'clock position in the right breast, categorized as BI-RADS 3. Further histopathological evaluation after a biopsy confirmed the presence of a fibroadenoma with invasive ductal carcinoma, classified as Grade III with perivascular and neural infiltration. Discussion: The coexistence of IDC within a fibroadenoma poses significant diagnostic challenges due to the benign appearance of fibroadenomas on standard imaging modalities. This case emphasizes the need for a thorough evaluation and possible biopsy of fibroadenomas that exhibit atypical features or changes over time. Conclusion: This report underscores the importance of vigilance and comprehensive diagnostic strategies in cases of fibroadenomas, especially in patients with unusual or evolving lesions. The review of literature confirms that although rare, the occurrence of IDC within fibroadenomas can have significant implications for treatment and prognosis.

Abstract PO3-07-02: Radiomics Models for B-mode Breast Ultrasound and Strain Elastography to improve Breast Cancer Diagnosis (INSPiRED 005): An International, Multicenter Analysis

Abstract Background: Breast Elastography, a technique that quantifies tissue stiffness, has been evaluated to objectify and improve the performance of B-mode breast ultrasound. However, large prospective trials showed benefits in BI-RADS 4a breast masses only and a high operator dependency. Modern Artificial Intelligence techniques for automated image processing like radiomics, a technique where quantified features are extracted from images, may overcome these limitations. We aimed to develop and validate radiomics models based on B-mode and Strain Elastography (SE) images for patients with BI-RADS 3 or 4 breast masses and compare their performance to the respective human experts. Methods: This is a secondary analysis of an international, multicenter trial (NCT02638935), evaluating the performance of SE in women with BI-RADS 3 or 4 breast masses. Women were recruited at 12 institutions in 7 countries and underwent B-mode breast ultrasound as well as SE. B-mode images were saved and re-assed by three ultrasound readers ( >10 years of experience), resulting in three independent assessments and a final consensus assessment. SE was interpreted using the E-/B ratio. B-mode and strain images were manually segmented and quantitative radiomics features were extracted using pyradiomics. We used 10-fold cross-validation to build machine learning models (XGBoostTree, MARS) based on data of 11 of 12 study sites. The data of the 12th (largest) study site was used as external validation set. Performance metrics included sensitivity, specificity and area under the receiver operator characteristic curve (AUROC). Results: The study included a total of 1288 patients, 1206 with evaluable B-mode images and 1190 with evaluable Strain images. Mean age was 46.6 years (SD 16.02) and a total number of 29.0% (350 of 1206) and 28.9% (344 of 1190) breast masses were malignant in the B-mode and Strain cohort, respectively. Distribution of BI-RADS categories was 33.0%, 34.5%, 14.5%, and 18.0% for BI-RADS 3, 4a, 4b, and 4c, respectively. In the external validation set (n = 342), the B-mode radiomics model (XGBoostTree) achieved an AUROC of 0.86 (95% CI 0.82 to 0.90), with a sensitivity of 97.4% (95% CI 0.93 to 1.00, 113 of 116) and a specificity of 27.0% (95% CI 0.21 to 0.33, 61 of 226). The model showed equivalent performance compared to the three ultrasound readers (P = 0.133); see also Table 1. In the external validation set (n = 333), the Strain radiomics model (MARS) achieved an AUROC of 0.84 (95% CI 0.79 to 0.88), with a sensitivity of 100% (95% CI 47.0 to 58.0, 115 of 115) and a specificity of 25.5% (95% CI 0.22 to 0.34, 60 of 218). The model showed equivalent performance compared to the three ultrasound readers (P = 0.696) and performed significantly better compared to SE (P = 0.002); see also Table 1. Sensitivity of the strain model was descriptively higher (100% vs. 97.4%, see Table 1). Both models were well-calibrated. Conclusion: This is the largest development and validation study for radiomics models based on B-mode breast ultrasound and SE, to date. The radiomics models performed on par with human readers, with the strain radiomics model showing potential to identify initially missed carcinomas in BI-RADS 3 breast masses. Future implementation studies may evaluate the performance of these image analysis algorithms in clinical routine and their integration into the multi-modal breast cancer diagnostics process, including mammography and MRI. Table 1. Diagnostic performance metrics Citation Format: André Pfob, Tanja He, Lie Cai, Richard G. Barr, Volker Duda, Zaher Alwafai, Corinne Balleyguier, Dirk-André Clevert, Sarah Fastner, Christina Gomez, Manuela Goncalo, Ines Gruber, Markus Hahn, André Hennigs, Panagiotis Kapetas, Sheng-Chieh Lu, Juliane Nees, Ralf Ohlinger, Fabian Riedel, Matthieu Rutten, Benedikt Schaefgen, Anne Stieber, Riku Togawa, Mitsuhiro Tozaki, Sebastian Wojcinski, Cai Xu, Geraldine Rauch, Jörg Heil, Chris Sidey-Gibbons, Michael Golatta. Radiomics Models for B-mode Breast Ultrasound and Strain Elastography to improve Breast Cancer Diagnosis (INSPiRED 005): An International, Multicenter Analysis [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 PO3-07-02.

Abstract PO3-20-08: Case Studies on Detecting Ductal Carcinoma in Situ Using Contrast-Enhanced Spectral Mammography and Predictive Indicators for Underestimation

Abstract Purpose: To introduce clinical cases of ductal carcinoma in situ (DCIS) underestimation focusing on additional benefits of contrast-enhanced spectral mammography (CESM). Background: DCIS, a noninvasive breast cancer, is often underestimated during diagnosis. Predicting which cases will upgrade to invasive cancer is crucial. CESM offers superior diagnostic performance compared to mammography and mammography with targeted ultrasound (US). Its low-energy images improve microcalcification conspicuity, enable accurate tumor extent measurement, and provide information on enhancements associated with nonmass microcalcifications. Enhanced areas on CESM can be easily compared with mammographic microcalcifications, for they are obtained during the same session. Indicators heralding DCIS underestimation 1. Detectability: underestimated DCIS is more likely to be detected on CESM and mammogram than pure DICS, whereas detection rates do not statistically differ on US and MRI. 2. Lesion type: underestimated DCIS mostly presents as enhancing mass or nonmass lesions on CESM and calcifications on low-energy conventional mammography. 3. Disease extent: on CESM, pure DCIS show smaller tumor extent than the underestimated ones. 4. CESM gray value (CGV) of the lesion on recombined image: the pure DCIS types show lower mean, standard deviation, maximum, and difference values, whereas the underestimated types demonstrate lower minimum values, and vice versa. Case 1: Screen detected pure DCIS without postsurgical upgrade in an asymptomatic 44-year-old woman. US-guided core biopsy yielded DCIS, intermediate nuclear grade with necrosis. Postsurgical pathology confirmed a 1.5 cm pure ductal carcinoma in situ, intermediate nuclear grade with necrosis. (A) US shows a 1.3 cm irregular hypoechoic mass in the right breast. (B) Routine mammography demonstrates no definite abnormality in the right breast. (C) CESM shows a 1.2 cm irregular enhancing mass in the upper central portion of right breast and CGV was 2034 AU. (D) Contrast-enhanced MR images show a 2.1 cm irregular enhancing mass in 12 o’clock direction of the right breast. Case 2: Screen detected DCIS with postsurgical upgrade to microinvasive ductal carcinoma in a 64-year-old woman with nonspecific discomfort in her right breast. US-guided core biopsy yielded DCIS, high nuclear grade with necrosis. Postsurgical pathology confirmed a 2.8 cm sized microinvasive ductal carcinoma, high nuclear grade, histologic grade 3 with necrosis. (A) US demonstrates a 1.9 cm irregular hypoechoic mass with calcifications in 9 o’clock direction 2.1 cm from the nipple in the right breast. (B) Right magnification view shows a 2.5 cm-extent segmentally distributed fine pleomorphic calcifications in the right breast. (C) CESM shows a 3 cm irregular enhancing mass with calcifications in the right breast, and CGV was 2045 AU. (D) Contrast-enhanced MR images shows a 2.3 cm irregular enhancing mass in the right breast. Case 3: Screen detected DCIS with postsurgical upgrade to invasive ductal carcinoma with DCIS in a 47-year-old woman who had a family history of breast cancer. US-guided core biopsy yielded DCIS, intermediate nuclear grade with necrosis. Postsurgical pathology confirmed a 0.2 cm invasive ductal carcinoma with 2.4 cm DCIS. (A) US demonstrates a 2.3 cm irregular hypoechoic mass in the left breast. (B) Routine mammography shows asymmetry in the upper portion of the left breast. (C) CESM shows a 3 cm enhancing mass in the left breast, and CGV of the lesion on MLO-recombined image was 2072 AU. (D) Contrast-enhanced MR image shows a 6 cm irregular enhancing mass in the upper portion of the left breast. Conclusion: CESM provides added advantages over mammography and breast US in detecting underestimated DCIS, and it is comparable to breast MRI. Key indicators to consider include detectability, enhancing lesion, larger tumor extent, higher mean CGV on CESM. Citation Format: Minji Song, Hee Jung Shin. Case Studies on Detecting Ductal Carcinoma in Situ Using Contrast-Enhanced Spectral Mammography and Predictive Indicators for Underestimation [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 PO3-20-08.

Prospective study of AI-assisted prediction of breast malignancies in physical health examinations: role of off-the-shelf AI software and comparison to radiologist performance

ObjectiveIn physical health examinations, breast sonography is a commonly used imaging method, but it can lead to repeated exams and unnecessary biopsy due to discrepancies among radiologists and health centers. This study explores the role of off-the-shelf artificial intelligence (AI) software in assisting radiologists to classify incidentally found breast masses in two health centers.MethodsFemale patients undergoing breast ultrasound examinations with incidentally discovered breast masses were categorized according to the 5th edition of the Breast Imaging Reporting and Data System (BI-RADS), with categories 3 to 5 included in this study. The examinations were conducted at two municipal health centers from May 2021 to May 2023.The final pathological results from surgical resection or biopsy served as the gold standard for comparison. Ultrasonographic images were obtained in longitudinal and transverse sections, and two junior radiologists and one senior radiologist independently assessed the images without knowing the pathological findings. The BI-RADS classification was adjusted following AI assistance, and diagnostic performance was compared using receiver operating characteristic curves.ResultsA total of 196 patients with 202 breast masses were included in the study, with pathological results confirming 107 benign and 95 malignant masses. The receiver operating characteristic curve showed that experienced breast radiologists had higher diagnostic performance in BI-RADS classification than junior radiologists, similar to AI classification (AUC = 0.936, 0.806, 0.896, and 0.950, p < 0.05). The AI software improved the accuracy, sensitivity, and negative predictive value of the adjusted BI-RADS classification for the junior radiologists’ group (p< 0.05), while no difference was observed in the senior radiologist group. Furthermore, AI increased the negative predictive value for BI-RADS 4a masses and the positive predictive value for 4b masses among radiologists (p < 0.05). AI enhances the sensitivity of invasive breast cancer detection more effectively than ductal carcinoma in situ and rare subtypes of breast cancer.ConclusionsThe AI software enhances diagnostic efficiency for breast masses, reducing the performance gap between junior and senior radiologists, particularly for BI-RADS 4a and 4b masses. This improvement reduces unnecessary repeat examinations and biopsies, optimizing medical resource utilization and enhancing overall diagnostic effectiveness.

Abstract PO2-20-08: Metastatic Lung Cancer Masquerading as Metaplastic Breast Cancer

Abstract Background Metaplastic breast carcinoma (MBC) is an unusual malignancy that presents a diagnostic challenge due to the presence of varying cytomorphologies that can be seen in benign and malignant tumors. We posit that metastatic disease to the breast, itself an uncommon entity, should be considered in the differential diagnosis of MBC. We report a unique case of metastatic non-small cell lung cancer (NSCLC) with an actionable driver mutation that presented as a symptomatic breast mass and was initially considered to represent MBC. Report A 74-year-old woman with a 22-pack-year smoking history presented to the breast clinic complaining of a palpable left breast mass that had grown rapidly over the previous month. Ultrasound-guided biopsy of the breast mass revealed high-grade poorly differentiated carcinoma. On immunohistochemical (IHC) evaluation, tumor cells were strongly positive for epithelial markers CAM5.2 and keratin AE1/AE3, weakly positive for breast cancer (BC) marker TRPS1, and negative for BC marker GATA3, squamous cell carcinoma markers p63 and CK5, and melanoma marker SOX10. Metaplastic triple-negative BC was diagnosed. However, concern remained for metastasis from a non-breast primary tumor due to the patient’s constitutional symptoms such as fatigue, night sweats, and 60-pound unintentional weight loss over the previous year, as well as interval development of a suspicious nodular rash on her right upper extremity. An FDG-PET-CT was obtained and demonstrated a hypermetabolic left lung consolidation (maximum SUV 33.3) measuring 7.2 cm, pulmonary nodules, and extensive thoracic lymphadenopathy. Due to rising suspicion for a primary lung tumor, additional IHC staining on the original breast biopsy was requested. Tumor cells were positive for TTF-1, consistent with metastatic lung adenocarcinoma. Tissue next-generation sequencing (NGS) identified a MET exon 14 skipping mutation, making the patient eligible for treatment with capmatinib, a first-line kinase inhibitor targeted therapy for metastatic NSCLC. At the time of this report, the patient has completed a course of palliative stereotactic body radiation therapy to the left lung and started capmatinib 400 mg BID, which she is tolerating well. Her first restaging scans after treatment initiation will be obtained one week after the time of this report. Conclusion In the absence of heightened suspicion for a non-breast primary tumor, our patient had initially received a diagnosis of triple-negative MBC. This diagnosis would have exposed her to increased treatment-related toxicities from cytotoxic chemotherapy and poor prognosis from MBC without survival benefit from targeted therapy for NSCLC. We advocate for the use of supplemental body imaging, expert and comprehensive IHC evaluation, and multidisciplinary discussion in cases of MBC and undifferentiated breast malignancy to facilitate accurate diagnosis and treatment. Citation Format: Tanmayi Pai, Marte Wasserman, Jason Lewis, Miglena Komforti, James Jakub, Augustine Lee, Yanyan Lou, Pooja Advani, Rohit Rao. Metastatic Lung Cancer Masquerading as Metaplastic 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 PO2-20-08.

Abstract PO5-20-08: A Case of Multifocal Ductal Breast Carcinoma with Extension into Lobules and Concurrent Primary Colon Adenocarcinoma

Abstract Background Multifocal (MF) multicentric breast cancer is a form of breast cancer that consists of disease independently developing at various locations due to a tumor clone spreading within the ductal complex. Multifocal breast cancer is associated with increased local recurrence. Our case highlights an example of multifocal breast cancer and addresses treatment challenges. Case presentation The patient is a 52-year-old African American female with a history of HCV cirrhosis, diabetes mellitus, and hypertension who presented with a palpable 4 cm right breast mass, without adenopathy, clinically Stage II, T2N0. Mammogram revealed a 2.5 cm right breast mass and three right level 1 axillary nodes with biopsy confirming invasive ductal carcinoma with extension into the lobules, ER positive (3%)/PR-/HER2-, Ki-67 95%. Neoadjuvant paclitaxel, carboplatin, and pembrolizumab was initiated but she incurred complications of decompensated liver cirrhosis after the second cycle and treatment was held. After 2 cycles her tumor was not palpable, and surgery was recommended, but due to COVID infection and concurrent decompensated liver failure surgery management was delayed. She underwent staged surgery with partial mastectomy without lymph node exploration. Histopathology showed DCIS grade 3 with extension into lobules and invasive ductal carcinoma with no lymphovascular invasion and all margins were negative, pathological stage ypT3NxM0. Immunohistochemistry demonstrated partial ER+ (50%)/PR-/HER2-, Ki-67 80%. She was given 4 cycles of adjuvant cyclophosphamide, adriamycin, pembrolizumab and continued on maintenance pembrolizumab. The patient was found with anemia out of proportion to chemotherapy and underwent colonoscopy that showed a colonic mass. Biopsy showed a primary moderately differentiated colonic adenocarcinoma. Her re-excision with new margins for partial mastectomy had negative margins, and 2 negative sentinel lymph nodes for ypN0. Genetic testing was negative. She continued on adjuvant immunotherapy with pembrolizumab for breast cancer. She is planned to start on adjuvant anastrozole. Patient has completed adjuvant radiation treatment and has no new complaints. She is pending curative intent completion colectomy for colon cancer. Discussion This case of MF breast cancer is significant, as one foci was ER negative, which responded to neoadjuvant chemoimmunotherapy and other ER positive that did not respond to treatment and was surgically excised. The pathology report from the surgical specimen revealed DCIS with extension into the lobules. Due to her tenuous clinical condition, she had staged surgeries for breast cancer, and now colon cancer. Genetic testing is negative. Currently, there is insufficient data to suggest which surgical approach is preferred in MF breast cancer. Based on the literature, breast conservation therapy (BCT) is a feasible option and is oncologically safe. Due to the patients’ medical condition and infections, it was felt a less invasive surgery could offer cure and minimize complications. Our patient underwent neoadjuvant chemoimmunotherapy, followed by partial mastectomy, adjuvant chemoimmunotherapy, second staged completion breast surgery, radiation therapy, and anti-estrogen therapy. MF breast cancer is associated with increased lymph node involvement. A 2022 meta-analysis found that multifocal and multicentric breast cancer has a slightly increased risk of death as compared to unifocal tumors. Lastly, our patient is African American, and multifocal tumors occur with a higher incidence in African Americans (43.4%) and Asian patients (37%) as compared to whites (28.9%). This case of breast cancer highlights treatment challenges in a case of multifocal multicentric breast cancer occurring concurrently with a secondary primary colonic cancer. Citation Format: Rabab Jafry, Hina Khan, Jessica Jones. A Case of Multifocal Ductal Breast Carcinoma with Extension into Lobules and Concurrent Primary Colon Adenocarcinoma [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 PO5-20-08.

Abstract PO5-20-11: Synchronous Breast Cancer and Pheochromocytoma: A Case Series

Abstract Background: Pheochromocytomas are rare, although literature suggests a rising incidence due to the widespread use of sensitive imaging modalities. Synchronous presentation of breast cancer with a pheochromocytoma is exceedingly rare with only one case documented in the literature. We present two cases of malignancy in the breast in which pheochromocytomas were incidentally detected during workup and management with vastly different presentations. Case Presentation: Two patients presented with breast cancer and were secondarily diagnosed with pheochromocytoma. Patient 1 is a 48-year-old postmenopausal female with a history of intraductal papilloma four years prior, who presented with right breast nipple discharge. Diagnostic mammogram showed a right breast mass and biopsy confirmed an intraductal papilloma with intermediate-grade DCIS, ER+/PR-. She had no family history of cancer or PGL/PPC. During a scheduled lumpectomy, she developed hypoxia, hypotension, and flash pulmonary edema requiring intubation and ECMO with prolonged ICU stay and long recovery with tracheostomy for four months. Contrast-enhanced CT of her abdomen showed a 9 cm right adrenal mass. Serum and urine metanephrines were markedly elevated, and it was determined that she had an adrenal crisis secondary to undiagnosed pheochromocytoma. She completed treatment for DCIS with lumpectomy and radiation and is currently on adjuvant anastrozole. She additionally had an adrenalectomy for pheochromocytoma, which was found to be stage PASS 2. Subsequent genetic testing confirmed the absence of germline mutations associated with hereditary PGL/PPC or breast cancer. Patient 2 is a 57-year-old female presenting with a history of left breast mass she first noted a year ago, with newly found nipple retraction and skin changes. Biopsy showed invasive ductal carcinoma of the breast, G3, Stage IIIA, pT3N2aM0, ER 95%/PR-/Her2- (IHC 0). Staging PET scan showed a 3.4 cm hypermetabolic left adrenal mass in addition to the breast mass and left axillary adenopathy. Serum and urine metanephrines were elevated, and pheochromocytoma was diagnosed. Family history was positive only for pancreatic cancer in a maternal aunt. Comprehensive genotype testing was negative for hereditary breast cancer and PGL/PCC syndromes. She was concomitantly treated with a radical mastectomy for breast cancer and a left adrenalectomy and tolerated the procedure well as she received perioperative alpha-adrenergic blockade with doxazosin. She has received chemotherapy and radiation for breast cancer treatment and is currently on adjuvant anastrozole. The adrenal mass was confirmed to be a pheochromocytoma PASS 2-3. Discussion: We present two unique cases of breast cancer and pheochromocytomas discovered in tandem with variable clinical manifestations. It is extremely uncommon to have a presentation of primary breast malignancy concomitantly with pheochromocytoma, and we demonstrate two cases that occurred within months of one another at our facility. During the first case, metastatic workup was not indicated for DCIS. However, during the seemingly benign lumpectomy procedure, the patient experienced significant complications, leading to intense ICU management, intubation, and tracheostomy. In the second case, a metastatic workup was completed due to locally advanced breast cancer where the adrenal mass was detected and a pheochromocytoma was diagnosed prior to surgery. This allowed both cancers to be resected simultaneously and safely. This series demonstrates the importance of keeping pheochromocytomas in the differential during the workup of adrenal masses prior to surgical interventions. Additionally, they demonstrate how the usual workup and management of breast cancer does not take into account these rare but significant diagnoses, and that can result in fatal consequences. Citation Format: Nikita Dahake, Abhimanyu Tushir, Aruna Padmanabhan. Synchronous Breast Cancer and Pheochromocytoma: A Case Series [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 PO5-20-11.

Abstract PO2-20-10: Exceptional long-term disease control on pembrolizumab monotherapy in a patient with TMB-high PMS2-mutated MMR-deficient triple negative breast cancer brain metastasis

Abstract Introduction The brain is among the most common sites of breast cancer (BC) spread. Prognosis of BC brain metastasis (BCBM) differs by receptor subtype, with poorest median overall survival (OS) for triple-negative (TN) BCBM at under 5 months. Though treatment guidelines have evolved in recent years, most strategies have focused on local therapies including surgery and stereotactic radiotherapy (SRT), rather than on systemic agents. The 2020 FDA approval of pembrolizumab (pembro) for patients (pts) with metastatic high-tumor mutational burden (TMB-h, ≥ 10 mutations/megabase) solid tumors, agnostic of primary site, combined with clinical trials in melanoma reporting efficacy of immune checkpoint inhibitors (ICI) against BM, suggest a potential use of ICI for pts with TMB-h BCBM. Results of the TAPUR study supported modest therapeutic benefit of pembro for 28 pts with metastatic BC selected for TMB-h, with median OS of 30.6 weeks, but did not include pts with active BCBM. TMB-h is uncommon in BC, and further genomic signatures remain to be elucidated to identify pts with BCBM responsive to ICI. We present a remarkable case of a pt with Lynch Syndrome (LS) due to a germline PMS2 mutation, who developed TMB-h, mismatch repair (MMR)-deficient TN BCBM, and has maintained stable disease for over 6 years on pembro monotherapy. Case description A 62-y.o. woman underwent screening mammography that identified a right breast mass. Pt has a family history of a mother with uterine and pancreatic cancer, and father with bladder cancer. Biopsy confirmed invasive ductal carcinoma (IDC), grade 1 (G1), ER/PR-positive, HER2 score 0. She underwent partial mastectomy, axillary dissection, radiation, and received adjuvant anastrozole. Three years later, while still on anastrozole, she presented with a 6 cm right breast mass. Mastectomy disclosed G3, ER/PR-negative, HER2-positive (3+, Her2:CEP17 ratio 5.6) IDC. She received adjuvant chemotherapy (AC-T) and 1 year of trastuzumab. Seven years later, pt presented with headaches and word finding difficulties. MRI identified a 3.6 cm frontal mass, which biopsy revealed as TN BCBM. Systemic imaging ruled out distant metastases. Pt proceeded with SRT and exemestane (despite receptor staining ER- in case of a possible false negative result). Despite radiotherapy, pt had BCBM progression within the same year with the largest mass diameter grown to 4.8 cm. Resection (followed by SRT) identified the dominant histology as G3 TNBC. Following transition of care to our institution, germline testing revealed a pathogenic mutation in PMS2 (c943C >T). Tumor sequencing of the resected brain metastasis showed TMB of 48 and MMR deficiency. Therefore, systemic therapy with pembro monotherapy was initiated and maintained with good tolerability. Two years later, concern for progression from rising tumor markers led to addition of concurrent carboplatin/gemcitabine for 5 cycles. Imaging and tumor markers stabilized, and pt returned to pembro monotherapy. Today, 3 years later, and over 6.5 years after initial TN BCBM diagnosis, pt continues to have stable disease on pembro with an excellent performance status (ECOG 0) and no evidence of intracranial or extracranial progression. Discussion We document an exceptional case of prolonged benefit to pembro in a pt with TMB-h PMS2-mutated MMR-deficient TN BCBM. This case highlights two major pragmatic points to clinical practice; (i) the significance of germline testing in all pts with metastatic BC, and (ii) the impact of molecular testing of tumor tissue to identify rare alterations which may have dramatic effects on pt outcomes. Altogether, this case is a remarkable addition to growing evidence that TMB could be a biomarker for predicting response to ICI therapy and provides an example of ICI efficacy in the setting of BCBM. Further research on additional genomic, clinical, and pathologic features associated with ICI responsiveness is warranted for greater precision in BCBM management. Citation Format: Jaeyoon Cha, Albert Grinshpun, Lauren Buckley, Brian Alexander, Sara Tolaney, Nancy Lin. Exceptional long-term disease control on pembrolizumab monotherapy in a patient with TMB-high PMS2-mutated MMR-deficient triple negative breast cancer brain metastasis [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 PO2-20-10.

Abstract PO5-20-09: LOCOREGIONAL MANAGEMENT OF DE NOVO STAGE IV HORMONE-POSITIVE BREAST CARCINOMA AFTER CDK 4/6 INHIBITOR TREATMENT

Abstract Systemic therapy remains the backbone for treatment of metastatic breast carcinoma. Locoregional treatment of the primary tumor remains controversial. While it has an established role in the palliative setting, its survival benefit remains unclear. The rationale behind locoregional approach is the reduction of tumor burden and the removal of cancer stem cells which may propagate the disease. In previous literature, hormone-positive breast cancer seems to be the best candidate for locoregional treatment in the presence of synchronous metastases. We present a case of a 43 year-old, female, with no known comorbidities, who sought consult due to note of a hard lump on her right breast. Core needle biopsy of the right breast mass was performed which showed invasive breast carcinoma, no special type, Nottingham histologic grade 2. On immunohistochemistry, tumor was ER +8, PR +8, Ki 67 90%, Her-2 neu negative. Baseline positron emission tomography/CT (PET/CT) scan showed hypermetabolic, heterogeneously-enhancing lobulated right breast mass, 3 × 6.7 × 7.7 cm, with smaller hypermetabolic adjacent nodules. There was also note of multiple enhancing, hypermetabolic lung and pleural nodules, and lymphadenopathies in the mediastinal, right axillary, right cardiophrenic and perigastric areas. Well-defined, hypermetabolic heterogeneously hypoenhancing masses were also seen in segments II and VII of the liver. There was also note of right-sided pleural effusion. Ultrasound-guided thoracentesis was done which turned positive for malignant cells on pleural fluid analysis. She underwent 4 cycles of chemotherapy with Doxorubicin and Paclitaxel. Reevaluation PET-CT scan revealed partial response. Patient was then started on Ribociclib plus Letrozole with ovarian function suppression for 18 months. On latest reevaluation PET/CT scan, there was no evidence of hypermetabolic metastatic disease, with demonstration of hypermetabolic activity only in the right breast. The patient then underwent right total mastectomy, with histopathologic findings of residual invasive carcinoma, Nottingham histologic grade 3, residual tumor size of 3.5 cm, with 95% tumor cellularity and lymphovascular invasion identified, ypT2. All surgical margins were negative for tumor. Currently, the patient has no evidence of disease, with ribociclib and letrozole continued until disease progression or unacceptable toxicity. In this case, surgery of the primary tumor was performed in the presence of a responsive metastatic disease, with the primary tumor being the only evidence of disease. With the advent of newer therapy options like cyclin-dependent kinase 4/6 inhibitors offering outstanding survival benefit for metastatic disease, a more aggressive and synergistic approach with locoregional therapy may be done to eradicate the tumor burden, translating to better long-term survival. Locoregional management of the primary tumor should be discussed in the context of a multidisciplinary team approach and should be individualized based on the individual patient’s need. Citation Format: Raye Angeli Abella, Rubi Li. LOCOREGIONAL MANAGEMENT OF DE NOVO STAGE IV HORMONE-POSITIVE BREAST CARCINOMA AFTER CDK 4/6 INHIBITOR TREATMENT [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 PO5-20-09.

Abstract PO3-10-11: Mujeres Avanzando a la Sobrevida (MAS: women going forward in survival): Breast Cancer Characteristics and Delays in Care in Honduras

Abstract Introduction: Low and middle-income countries have exceedingly high breast cancer mortality rates primarily due to delays to diagnosis and treatment. The Breast Health Global Initiative (BHGI) recommends a diagnostic interval (time from initial provider visit to receiving a diagnosis) of < 60 days. Honduras is one of the poorest countries in the western hemisphere and has a paucity of published breast cancer research. Our objective was to understand delays in breast cancer diagnosis and treatment in Honduras. Methods: We initiated a prospective cohort study (Mujeres Avanzando a la Sobrevida (MAS: Women Going Forward in Survival)) in 2021 at two hospitals in two major cities in Honduras. All patients with newly diagnosed breast cancer were invited to participate. We prospectively collected demographic, cancer, and treatment data through patient interviews and surveys. We also determined several time intervals including: onset of symptoms to initial provider visit (patient interval), initial provider visit to biopsy (diagnostic interval), and biopsy to first treatment (treatment interval). Patients also completed the Unger-Saldana Delay Survey to assess their perceptions of any delays in cancer care and reasons for these delays. Results: We enrolled 95 patients with an average age of 54 years. 73% of patients reported an income of < 1 minimum wage (< 8,448 lempiras/month). 93% were housewives, and 35% were married. The majority of patients had an elementary school education or no education (61%). The most common first symptom was a breast lump (81%). The majority of patients had advanced stage disease (Stage III and IV: 64%). The mean patient interval was 185 days. The mean diagnostic interval was 153 days, and the mean treatment interval was 139 days. Most patients (61%) thought their symptoms were slightly serious or not serious at all, and 78% did not think their symptoms were due to cancer. Most patients (60%) thought they were able to see a physician immediately or soon after symptoms developed (63%). Patient stated reasons for not seeking care earlier included believing their symptoms would self-improve, being unsure which health service to go to, lack of money, and fear. Similarly, most patients (67%) thought the time between seeing their first provider and visiting the cancer hospital was immediate or soon but not immediately. Reasons for this delay included lack of information, lack of money, wait times to appointment or tests, incorrect initial diagnosis, and fear. Conclusion: In this prospective cohort study, nearly two-thirds of patients in Honduras were diagnosed with stage III/IV breast cancer. We found marked delays in patient, diagnostic, and treatment intervals, even though patients perceived their care to be immediate. Importantly, the diagnostic interval far exceeded 60 days, as recommended by the BHGI. This study provides initial insight into delays in breast cancer care in Honduras and provides an opportunity to target obstacles to early diagnosis and treatment and to improve breast cancer survival. Citation Format: Saranya Prathibha, Alejandra Molina, Jorge Siryi, Kristhel Gaitán, Mildred Raudales, Manuel Maldonado, Todd Tuttle, Suyapa Bejarano. Mujeres Avanzando a la Sobrevida (MAS: women going forward in survival): Breast Cancer Characteristics and Delays in Care in Honduras [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 PO3-10-11.

Abstract PO1-20-12: CD8+ Tumor Infiltrating Lymphocytes Turn a Cold Tumor Hot in Metastatic Breast Cancer

Abstract Introduction: Turning “cold” tumors “hot” is considered essential for immune-oncology therapies to be effective. Bria-IMT is an allogenic human cancer cell line with antigen presenting cell activity (SV-BR-1-GM) designed to overcome the immune-suppressive tumor microenvironment. However, until now there has not been proof that “cold” tumors can become “hot” with this therapy. Using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α and developed for CD8 ImmunoPET, we image before and after Bria-IMT therapy administration to assess the baseline status as well as changes in CD8 cell presence after initiation of therapy. Here we present the first evidence that cold tumors can become hot on treatment with Bria-IMT combined with an anti-PD-1 checkpoint inhibitor (CPI), showing CD8+ cells increased over baseline using CD8 ImmunoPET. Case: After informed consent, a 61 year-old Hispanic female, enrolled in the ongoing randomized phase 2 Bria-IMT trial in advanced heavily pretreated metastatic breast cancer (MBC) (NCT03328026). Her history included MBC in May 2020, ductal type, grade 3, triple negative breast cancer (TNBC) with 6 prior lines of therapy including a Trop-2-directed antibody-drug conjugate and 6 lines of chemotherapy. Precision medicine testing identified no actionable targets. All prior therapies had progressive disease as their best response. The subject was randomized to start the CPI after 2 cycles of Bria-IMT to “train” the host immune system before proceeding with combination immune-oncology therapy. Baseline testing revealed the subject to be anergic to candida and SV-BR-1-GM inoculation. However, by cycle 3 delayed-type hypersensitivity to SV-BR-1GM developed. Interestingly the subject matched SV-BR-1-GM at 2 HLA loci: DRB3*02:02 and DRB1*11:04 which in previous publications is associated with greater clinical benefit. Tumor markers were stable or decreased slightly including CEA (25% decrease) and CA 15-3 (43% decrease). Circulating Tumor Cells (CTCs) and Cancer Associated Macrophage Like cells (CAMLs) also improved. Standard imaging at baseline showed 3 main sites of disease including a large right breast mass, multiple right axillary lymph nodes and a right lower lobe mass with CD8 ImmunoPET uptake in these areas similar to the blood pool. On the follow-up CT imaging, all of these lesions increased in size with newly appreciated pulmonary nodules. The right lower lobe mass showed increased CD8 ImmunoPET accumulation with an SUV of 5.8 (close to the liver background) as compared to an SUV of 2.2 at baseline. The lesions in the right breast and right axilla remained at blood pool levels. There was an increase in CD8 ImmunoPET uptake in bilateral inguinal lymph nodes reaching an SUV of 4.8 as compared to SUV 2.2 at baseline. In addition, there were non-enlarged lymph nodes in bilateral axillary regions that also showed increased radio-tracer accumulation reaching an SUV of 9.5 as compared to SUV 4.9 at baseline. Conclusion: This subject demonstrated a mixed response of metastatic lesions on CD8 ImmunoPET with encouraging changes in peripheral blood tumor markers and CTCs. The nonspecific nodal localization of CD8 ImmunoPET may indicate a systemic activation of CD8 positive lymphoid cells. This shows the value of CD8 ImmunoPET in identifying lesions that are progressing on treatment versus pseudo progression. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites as well as an increase in lymphoid organs. This advance may aid in triaging patients, adjudicating pseudo-progression and predicting clinical benefit of immune based therapies. Citation Format: Russ Kuker, Frances Valdes-Albini, Giuseppe Del Priore, Aazim Arif, Kristin Schmiedehausen, Carmen Calfa. CD8+ Tumor Infiltrating Lymphocytes Turn a Cold Tumor Hot in Metastatic 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 PO1-20-12.

Abstract PO4-25-08: Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population

Abstract Secretory breast carcinoma (SBC) is a rare and distinct disease, comprising approximately 0.01% of all breast carcinomas. This is a case of an 8-year-old boy who presented with a 1.5-year history of a non-tender, slowly enlarging left subareolar mass, not associated with nipple discharge. Serologic workup revealed minimally elevated prolactin with normal-range FSH, LH, estradiol and testosterone, as well as normal-range beta-hCG, LDH and AFP. Ultrasound showed a circumscribed solid hypoechoic lesion with internal arterial vascularity, favoured to represent a sebaceous cyst. Excisional biopsy was performed, and histologic examination revealed the classic intra- and extracellular secretory material typically seen in SBC. Immunohistochemical (IHC) stains for mammaglobin, S-100 and high molecular weight keratin (CK5) were positive. ER was positive, though not strong staining, and PR and HER2 were negative. A screen for NTRK fusions with pan-TRK IHC was positive. No skin, perineural or lymphovascular invasion was identified. RNA-based NGS demonstrated ETV6-NTRK3 fusion and confirmed the diagnosis of SBC. The patient underwent mastectomy and SLNB, which showed no residual tumor and no positive lymph nodes. A full metastatic work-up was not performed and the patient did not receive neoadjuvant therapy. First described as “juvenile breast carcinoma,” SBC has since been recognized to occur across a wide age range, with most cases occurring in adults. SBC in male pediatric patients is exceptionally rare, with fewer than 20 cases reported in the literature. In this demographic, SBC is usually detected clinically as a subareolar mass not associated with nipple discharge, and appears as a well-circumscribed mass on imaging, mimicking benign entities. SBC is usually detected at a low stage, treated surgically, and follows a clinically indolent course with excellent outcomes. Positive axillary nodes have been identified in a few male children, who subsequently underwent chemo- and/or radiotherapy, with no recorded recurrences in these cases. Distant metastases are an extremely uncommon feature of SBC and have not been reported in the pediatric male population; however, due to the rarity of this diagnosis, particularly in this demographic, robust long-term follow-up data are still lacking. The name “secretory” derives from the histologic appearance of the dense eosinophilic secretory material seen in tumor lumina and bubbly material in the cytoplasm of tumor cells. Similar to the cytologic characteristics of other translocation-driven neoplasms, SBC shows minimal pleomorphism. Mitoses are absent or rare. IHC stains are typically positive for S-100 and high molecular weight keratins and negative for ER, PR, and HER2. Despite the immunophenotypic similarities to triple negative/basal-like carcinomas (TNBC/BLC) the molecular relationship between SBC and TNBC/BLC is unclear. Though initially defined by its distinctive secretions on histology, SBC is now chiefly characterized by a balanced translocation, t(12;15)(p13;q25), resulting in oncogenic ETV6-NTRK3 fusion. Recent cases have demonstrated this using a variety of molecular techniques, including FISH, RT-PCR, and in our case, RNA-based NGS. This translocation also characterizes non-breast secretory carcinomas and has been identified in several other neoplasms, including pediatric mesenchymal tumours and adult acute myeloid leukemia. The rarity of SBC, particularly in the male pediatric population, underlines the necessity of this case report. Additionally, this case highlights the importance of considering SBC as a potential diagnosis in male children presenting with a breast mass, even in the presence of benign imaging characteristics. Table 1: Clinicoradiologic and pathomolecular characteristics of SBC in pediatric males AND, axillary node dissection; CT, chemotherapy; ER, estrogen receptor; FISH, fluorescence in situ hybridization; LE, local excision; MRM, modified radical mastectomy; nd, no data; NED, no evidence of disease; NGS, next-generation sequencing; NS, nodal sampling; PA, periareolar; PR, progesterone receptor; RA, retroareolar; RM, radical mastectomy; PCR, polymerase chain reaction; RT, radiotherapy; SA, subareolar; SLNB, sentinel lymph node biopsy; SM, simple mastectomy; WLE, wide local excision *Not reported as strong staining Table 2: Immunohistochemical phenotype of secretory breast carcinoma EMA, epithelial membrane antigen; ER, estrogen receptor; PR, progesterone receptor *Not reported as strong staining Table 3: Laboratory investigations AFP, alpha fetoprotein; FSH, follicle stimulating hormone; hCG, human chorionic gonadotropin; LDH, lactate dehydrogenase; LH, luteinizing hormone Citation Format: Rebecca Brassington, Svetlana Silverman, Ioana Bratu. Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population [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 PO4-25-08.

Abstract PO3-20-09: METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA

Abstract Metaplastic breast carcinoma is a rare histologic subtype of breast carcinoma, accounting for only 0.2 to 2% of all breast cancers. It is comprised of a heterogeneous histology involving mesenchymal and epithelial components. Metaplastic breast carcinoma usually harbors a triple-negative phenotype, but carries a worse prognosis compared to other breast cancer subtypes. Due to its unique histopathological and molecular characteristics, there has been limited data on the optimal management of metaplastic breast carcinoma. Moreover, the presence of a secondary breast neoplasm in the background of a prior ovarian carcinoma represents a diagnostic and therapeutic challenge. We report a case of a 55-year-old female with a previous history of serous ovarian carcinoma six years ago, who presented with an enlarging right breast mass. Digital mammography showed a right retro-areolar mass, 5.7 x 4.8 x 5.4 cm, BIRADS 4C. Initial biopsy done showed presence of atypical cells in a background of cystic change. The patient underwent modified radical mastectomy with incision biopsy and frozen section. Final histopathologic diagnosis was consistent with metaplastic breast carcinoma, mixed epithelial and mesenchymal type, Nottingham grade 2, with no lymphovascular invasion identified, pT2N0. Tumor was ER negative, PR negative, Her 2 neu negative, with Ki-67 of 10% on immunohistochemistry. She then underwent adjuvant treatment with 6 cycles of paclitaxel and carboplatin. Six years prior, the patient was likewise diagnosed with high-grade serous ovarian carcinoma. She had total abdominal hysterectomy with bilateral salpingo-oophorectomy and adjuvant chemotherapy with 6 cycles of Paclitaxel and Carboplatin was given. She had recurrence in the paraaortic lymph node after 3 years and underwent cytoreductive surgery with excision of nodule and hyperthermic intraperitoneal chemotherapy with cisplatin. Currently, the patient has no evidence of disease in the recent positron emission tomography scan, with normal serum CA-125 level. The current standard of care for metaplastic breast carcinoma follows that of triple-negative breast cancer. However, previous literature has shown that metaplastic breast carcinoma is more chemo-refractory compared to triple-negative breast cancer, with more response seen with taxane-based chemotherapy. Due to poor response rates to neoadjuvant chemotherapy, surgical management for early-stage disease is warranted. Targeting molecular alterations is necessary to improve the prognosis of this subtype. Genomic features of homologous recombination deficiency were also found to be more prevalent in metaplastic breast cancer, thus genomic testing is warranted, especially in the setting of a prior history of ovarian carcinoma. Citation Format: Raye Angeli Abella, Carlos Dy. METACHRONOUS METAPLASTIC BREAST CARCINOMA IN A 55-YEAR-OLD PATIENT WITH SEROUS OVARIAN CARCINOMA [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 PO3-20-09.

Abstract PO4-20-07: Dense Breast Tissue in a High-Risk African-American Woman with DCIS and Nodal Metastasis of Intra-ductal Carcinoma: A Case Report and Discussion on the Current USPSTF Draft Recommendation

Abstract Introduction and objectives: The incidence of breast cancer (BC) in younger women has increased in recent years, raising the discussion on adjustments to screening recommendations. This past May, a new draft recommendation to the USPSTF guidelines for BC screening adjusted the age of screening from 50 to 40. However, there is still insufficient evidence to recommend adjusted screening guidelines for patients at increased risk including ethnic minorities with higher mortality and women with dense breasts. The paucity of trials and reviews for many of these at-risk groups may be leading to later diagnosis and poorer outcomes. This case highlights the importance of clinical judgment when screening patients whose presentation lies outside the guidelines. Clinical Case: A 29-year-old AAW with past medical history of bipolar disorder presents to her primary care physician in April 2023 with concern for left breast mass. Patient was previously on risperidone and Depakote for her bipolar disorder one year prior which resulted in drug-induced amenorrhea and breast tenderness with evidence of elevated prolactin. She was taken off her medication with return of her menses, but breast tenderness persisted for three months. During this time, she noticed a palpable breast mass. Family history is not significant for breast cancer. Breast ultrasound and mammography revealed “extremely dense” breast tissue bilaterally. Imaging significant for 7.6 × 6.2 × 6.3 cm irregular mass in the lower inner quadrant of the left breast with pleomorphic calcifications. Biopsy subsequently performed with breast pathology significant for ER+/PR- ductal carcinoma in situ. However, lymph node pathology showed evidence of invasive ductal carcinoma raising question of diagnosis of possible occult breast cancer versus breast cancer with axillary metastasis. PET CT did not show evidence of metastatic disease. She was started on neoadjuvant chemotherapy. Discussion and Conclusion: It is well known that African American women (AAW) are at increased risk for mortality due to BC, aggressive secondary BC, and for high-risk tumor biology. Additionally, AAW generally have more dense breast tissue, another risk factor for BC. Dense breast tissue can make it more difficult to characterize high-risk lesions on screening modalities. In regard to this patient, her dense breast tissue may obfuscate characterization of areas of possible primary cancer being the cause of her nodal metastasis. Current guidelines do not take these well-known associations and risk factors into account. A separate treatment algorithm may be required to work up a patient from high-risk groups such as this patient case. It is crucial that future guidelines on screening should incorporate specific risk factors which would help detect BC earlier in vulnerable populations. Citation Format: Vinita Akula, Jessica Jones. Dense Breast Tissue in a High-Risk African-American Woman with DCIS and Nodal Metastasis of Intra-ductal Carcinoma: A Case Report and Discussion on the Current USPSTF Draft Recommendation [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 PO4-20-07.

Abstract PO5-20-12: A Case of Bilateral Breast Cancer in a patient on Ocrelizumab

Abstract Background: Ocrelizumab is an anti-CD20 B cell depleting monoclonal antibodies that was FDA approved in 2017 for Relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis based on two large phase III trials (OPERA I and ORATORIO)1. In these trials, patients being treated with Ocrelizumab developed more malignancies compared to placebo. Among these cancers, breast cancer was prominent occurring in about 0.5-0.8% of the patients in the Ocrelizumab group as opposed to 0% in the placebo group. Here we present a case of bilateral breast cancer in a patient with Multiple Sclerosis (MS) treated with Ocrelizumab. Case Presentation A 66-year-old woman with a long-standing history of relapsing-remitting multiple sclerosis (MS) presented to us with concerns of bilateral masses on a screening mammogram. She was diagnosed with MS 30 years prior to presentation and was initially treated with multiple immunomodulators. However, she had progression of disease and was started on Ocrelizumab two years prior to presentation. She was up to date with her screening mammograms which had been unrevealing till now. Family history was significant for breast cancer in her grandmother in her 70s. Her annual mammogram screening showed bilateral irregular masses. A subsequent right breast ultrasound showed three breast masses(1cm, 0.5cm and 0.5cm respectively) and her left breast showed a 0.5 cm mass. Biopsy from the right breast showed invasive ductal and lobular carcinoma(ER+, PR+, HER2-) and that from the left breast showed invasive lobular carcinoma(ER+, PR+, HER2-).She underwent bilateral mastectomies and sentinel lymph node biopsies. The surgical margins and lymph nodes were negative for malignancy hence radiation was not warranted. Genetic testing revealed one pathogenic variant in MSH3 but was negative for BRCA1 and 2. Since her Oncotype dx score was low, adjuvant chemotherapy was not offered. She was started on aromatase inhibitor and her Ocrelizumab was permanently discontinued. Discussion Ocrelizumab is one of the immunomodulator drugs for MS with a probable mechanism being B-cell depletion. The mechanism of how it causes breast cancer is unknown. However, suggested theory is that B cell inhibitors can increase the risk of breast cancer by inhibiting the potentially protective role of the B cells. The B cells are thought to play a role in the tumor micro-environments as antigen presenting cells and activators of natural killer and cytolytic T cells targeted toward lysis of tumors. Also, B cell presence, specifically CD20 B cells, is linked to a better prognosis in breast cancer. One study has also pointed out the importance of timing of anti-b cell therapy in relation to cancer morbidity. Treatment of mice with Anti-CD20 therapy prior to tumor challenge did not result in cancer metastasis. Whereas post tumor challenge, there was increased tumor cell survival and metastasis. Our patient although had a family history of breast cancer, did not have a genetic mutation that could have contributed to her breast cancer. Her breast cancer developed after her therapy with Ocrelizumab hence raising suspicion for causation. With rise in the use of immunosuppressive therapies, further data is needed to delineate pathogenesis. Women with MS have lower all-cause survival after breast cancer diagnosis than women without MS. Hence it is important to identify any risk factors or therapies that might be associated with increased risk of cancer. Citation Format: Kriti Mehra, Mohamad Hejazi. A Case of Bilateral Breast Cancer in a patient on Ocrelizumab [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 PO5-20-12.

Abstract PO3-20-10: Case Series: Invasive Secretory Carcinoma

Abstract Secretory variant invasive ductal carcinoma is not well described in the literature but is defined by its unique histopathology. These tumors stain positive for S100 and are typically triple negative hormonal cancers with an overall good prognosis. There is speculation that secretory carcinoma in adults is more aggressive with a greater likelihood for tumor recurrence. We present two case studies of this rare histopathologic diagnosis. First, a 76-year-old female with a recurrent secretory variant, invasive ductal carcinoma of the left breast. Second, a 68-year-old male who presented with invasive and in situ secretory carcinoma. A thorough chart review of all available institutional and outside institution records was performed from initial diagnosis to current treatment. Background information and de-identified patient information was summarized for this case series. This is a 76-year-old female who presented to her physician in 2011 with a palpable left breast and axillary mass. Her workup demonstrated ER+/PR+/HER2- invasive ductal carcinoma with lobular features of the left breast measuring 2.3 cm, along with a 1.5 cm malignant axillary lymph node. She underwent a left breast lumpectomy with axillary dissection. She underwent adjuvant whole breast radiation, axillary nodal radiation, and was placed on anastrozole therapy for 5 years. Seven years later a recurrence was noted in the superior aspect of the left breast. MRI guided biopsy revealed recurrent left breast cancer with pathology of invasive ductal carcinoma, secretory variant. She elected to undergo lumpectomy alone. Final pathology demonstrated invasive ductal carcinoma, secretory variant, ER negative (0%), PR negative (0%), HER2 negative (0%), pT1bNx. She underwent accelerated adjuvant partial breast radiation. Follow up and surveillance with bilateral breast MRI two years later demonstrated a new left breast mass, found to be triple negative, recurrent secretory variant invasive ductal carcinoma. She underwent definitive treatment with a left skin sparing mastectomy, right sentinel lymph node biopsy, and a latissimus dorsi flap with implant placement. Final pathology demonstrated multifocal recurrent secretory carcinoma, two foci measuring 6 and 11 mm. Our second patient was a 68-year-old male who initially presented to the clinic for evaluation of a ventral incisional hernia. During his initial assessment, a palpable retro-areolar nodule was noted on physical exam. Subsequent mammography demonstrated a hypoechoic mass with irregular margins measuring 2.8 x 2.3 x 1.7 cm along with increased vascularity and calcifications. An ultrasound guided biopsy demonstrated invasive secretory carcinoma. Initial pathologic testing of the tumor demonstrated ER positive (5%), PR positive (1%), and HER2 negative. The patient was taken to the operating room for a total mastectomy with sentinel lymph node biopsy. His postoperative pathology demonstrated negative margins, and invasive secretory carcinoma with lymph nodes negative for metastatic disease. Secretory variant of invasive ductal carcinoma is rare and is determined by its unique immunohistochemical features. We present two cases of secretory carcinoma at our institution. Data suggests that local recurrence is common in patients with secretory breast cancer, occurring in 33-44% of cases. Ki-67 index has been used as a prognostic indicator for metastases and recurrence of disease. Current treatment regimens are diverse; however, surgery is favored as the primary method. This report shows that although indolent, multifocality and recurrence is plausible. Given the limited data on this subset of carcinoma, more investigation is warranted to describe the effectiveness of adjuvant treatment options. Case 1 –insert figure image– Histopathologic examination at 200x shows invasive carcinoma with dense eosinophilic secretory material. By immunohistochemistry, the cells are negative for ER (0%) and PR (0%) with a HER2Neu score of 0, supporting the diagnosis of invasive secretory carcinoma. Case 2 –insert figure image– Histopathologic examination at 200x shows invasive carcinoma with dense eosinophilic secretory material. The tumor cells are positive for CK5/6 (patchy), CD117, ER (focal and weakly), and S100; negative for p63 and calponin, supporting the diagnosis of invasive secretory carcinoma. NTRK3 gene rearrangement was detected on fluorescence in situ hybridization (FISH). Citation Format: Lauren Geisel, Hemanth Venkatesh, Alyssa Obermiller, Quyen Chu, Jessica Gielow, Danielle Henry. Case Series: Invasive Secretory Carcinoma [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 PO3-20-10.

Abstract PO3-20-12: A Case Report on the Management of a Patient with Local Breast Cancer, BIA-ALCL and Radiation Induced Metastatic Angiosarcoma: A Multidisciplinary Approach

Abstract A Case Report on the Management of a Patient with Local Breast Cancer, BIA-ALCL and Radiation-Induced Metastatic Angiosarcoma: A Multidisciplinary Approach  Abstract: Breast cancer recurrence presents a complex challenge in clinical practice. We present the case of a 60-year-old female with a history of stage 2A right breast cancer diagnosed on 12/1/2013. The patient underwent bilateral mastectomy and adjuvant chemotherapy, followed by breast reconstruction. The patient subsequently developed asymmetric right breast swelling, which was biopsied and was positive for T lymphocyte markers CD30, CD43, CD45, CD4 and she was diagnosed with anaplastic large cell lymphoma in 12/14/2018, which was thought to be associated with her breast implants. In May 2022, a right chest wall mass was detected, which demonstrated growth and increased vascularity on imaging. A biopsy on 5/5/22 confirmed poorly differentiated carcinoma initially thought to be a secondary intraductal carcinoma of the breast, invading the chest wall by metastasis or direct extension, negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Further workup confirmed this mass to be angiosarcoma, most likely associated with the patient’s prior radiation therapy. The patient was started on neoadjuvant carboplatin/paclitaxel/pembrolizumab on 6/9/2022, and continued with Doxorubicin/Cyclophosphamide and pembrolizumab, which was completed on 11 November 2022. Imaging studies post-treatment showed a slightly smaller mass in the right mastectomy bed, indicating a partial response to treatment. However, a subsequent PET scan revealed a recurrence of breast cancer in the right chest wall. Considering the patient's history of prior radiation therapy and the inability to administer further radiation, the treatment plan was revised. She underwent reconstructive chest wall surgery on 1/4/2023, with complete resection and negative margins. She started on adjuvant pembrolizumab planned for one year, but the patient presented on 3/3/2023 with the growth of a chest wall mass and bleeding, consistent with progression. Liquid Tempus testing was obtained but negative for an actionable target. Options such as hyperthermia, enrollment to clinical trial, and re-irradiation were discussed, and the patient was restarted on weekly paclitaxel on 3/31/2023 due to a previous response. The patient had further local disease progression on 5/26/2023, and this regimen was stopped. The patient is planning to get Tempus testing on tumor tissue and start the next line palliative regimen with either doxorubicin or gentamicin and repeat re-irradiation if no response to these regimens. This case report highlights the challenges in managing breast cancer therapy-induced adverse conditions with two secondary tumors, both associated with the patient’s prior therapy. The importance of a multidisciplinary approach, including medical oncology, surgical oncology, radiation oncology, and sarcoma specialists, is emphasized. The use of molecular testing and consideration of clinical trials may provide additional treatment options. Further research and clinical trials are warranted to optimize the management of recurrent breast cancer with transformation to rare histological subtypes such as angiosarcoma. Citation Format: Liubou Varanitskaya, Serhan Unlu, Christina Clemow. A Case Report on the Management of a Patient with Local Breast Cancer, BIA-ALCL and Radiation Induced Metastatic Angiosarcoma: A Multidisciplinary Approach [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 PO3-20-12.