Mastectomy Research Articles

Abstract PO2-08-01: Universal Multi-Gene Panel Testing of Newly Diagnosed Breast Cancer Patients in a Community Healthcare System

Abstract Introduction Multi-gene panel, germline genetic testing has emerged over the last decade as a useful tool in the assessment of hereditary cancer syndromes. As barriers to genetic testing are reduced, offering universal genetic testing to all cancer patients is a practice gaining traction. We present outcomes data specific to the offering of universal, multi-gene panel testing to newly diagnosed breast cancer patients in a community hospital setting. Methods A retrospective chart review was performed for all newly diagnosed breast cancer patients (n=1005) at a community hospital between 8/5/2019 and 8/5/2022. Uptake and outcomes of genetic counseling and genetic testing were assessed. All patients were offered genetic counseling, and those who consented to genetic testing were offered a multi-gene panel (37-93 genes). The National Comprehensive Cancer Network (NCCN) Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic (2020) guidelines were utilized to distinguish which patients met traditional genetic testing criteria. Results Of all newly diagnosed breast cancer patients, 915 (91.1%) patients underwent genetic counseling and 871 (86.7%) patients elected for genetic testing. Of those who declined genetic testing (n=134), 39 (29.1%) reported previous genetic testing. Of patients tested, 489 (56.1%) met NCCN criteria. Overall, 114 (13.1%) of tested patients received results with likely pathogenic/pathogenic (LP/P) variants. Of those, 86 (75.4%) had a clinically significant variant, a high-risk, moderate-risk or another dominantly inherited gene variant, while 28 (24.6%) were identified as genetic carriers; Table 1 summarizes genes with LP/P variants in this cohort, with 10 patients receiving results for 2 variants. Of the patients with clinically significant genetic results, 58 (67.4%) met NCCN criteria. Furthermore, 65 patients (75.6%) reported a family history of cancer relevant to the identified LP/P variant. The average age of the total population, and of those with a positive result, was 62 years. While nearly 19% of all patients tested were under age 50, patients under 50 comprised only 14.0% (n=12) of patients with a clinically significant result. Breast cancer management changes, including addition of a PARP inhibitor to chemotherapy regimen and/or elected bilateral mastectomies in the setting of unilateral disease, were noted in 71.4% (n=20) of patients with high-risk genetic findings and 20.6% (n=7) of patients with moderate-risk genetic findings. Conclusion The 86.7% uptake of genetic testing suggests implementation of universal testing in a community setting is feasible and favored by patients. Clinically significant genetic results would have gone undetected in 32.6% of patients if NCCN criteria was strictly utilized to offer testing. In addition to the 62 patients with high and moderate risk genetic results, utilization of expanded panel testing provided benefit for an additional 24 patients found to have an actionable variant in a gene that would not have been detected on traditional breast cancer panels. Our data supports the offering of genetic testing to all newly diagnosed breast cancer patients, regardless of age, family history, or other criterion, to inform precise breast cancer management and overall, lifetime cancer risks. Genetic Findings of Universal Multi-Gene Panels in a Community Setting Citation Format: Natalie Johns, Jody Wallace, Darbey Raible, Jordan Brady, Grace Miller, Brooke Phillips. Universal Multi-Gene Panel Testing of Newly Diagnosed Breast Cancer Patients in a Community Healthcare 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 PO2-08-01.

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 PO5-20-07: A Case of Metastatic Breast Cancer to Soft Tissue of the Thigh

Abstract Breast cancer is the most diagnosed cancer in women worldwide. The predominant cause of breast cancer mortality is metastatic disease with bone, lung, liver and brain being most common sites of metastasis. After melanoma, breast cancer is the most common cancer to have cutaneous metastatic disease and this presentation represents half of all cutaneous metastases. We are presenting a case of a 70-year-old female with distant recurrence of breast cancer to the left thigh. A 70-year-old female presented to clinic with a palpable left breast mass noted July 2022. Her medical history was notable for right sided upper lobe stage IIIB squamous cell lung cancer diagnosed in 2013 treated with chemotherapy and chest radiation (RT), menopause at 25 years old following TAH/BSO for fibroids. Family history included prostate cancer and genetic testing was negative for pathogenic mutation. Diagnostic mammogram showed a lesion in the left breast at 9:00 of 1.4 cm x 1.2 cm x1.4 cm, and biopsy showed grade 3 triple negative invasive ductal carcinoma (IDC). Her nodes were clinically and radiologically negative. She opted for breast conservation. In September of 2020 the patient had a left lumpectomy with sentinel lymph node biopsy. Final pathology (path) was pT1cN0 with two foci of IDC, grade 3, measuring 1.9 × 1.9 × 1.1 cm and 0.4 × 0.2 × 0.2 cm with negative margins. Two sentinel lymph nodes were negative for carcinoma. She received 4 cycles of doxorubicin and cyclophosphamide and started paclitaxel, but only completed 5/12 planned cycles. During these treatment cycles she was admitted twice for shortness of breath and found to have an exudative pleural effusion, repeat cytology was negative for malignancy at which point fluid did not recur. There was no CT evidence of lung nodules or plural thickening. Echocardiogram showed normal ejection fraction of 45%. PET scan was negative. Chemotherapy was stopped in February of 2021. Initial pre-operative discussion with radiation oncology indicated no contraindication to adjuvant RT. However, after simulation, it was deemed by radiation oncology that the patient was no longer a candidate for RT as during her lung cancer treatment, she had received RT of 69.4 Gy including the area of the current lumpectomy cavity. She then opted for bilateral mastectomy with immediate reconstruction in June 2021. Final path from both breasts showed no carcinoma. In November of 2021 she was admitted for shortness of breath and on CT scan was noted to have a left sided lung nodule. The patient declined biopsy and underwent a left wedge resection in January of 2022. Final path showed a 2.2. cm carcinoma consistent with breast primary that was ER 0, PR 0, and Her 2 neu 1+. She was started on capecitabine with plan for 6 months of treatment but stopped taking this after one month due to severe pain in her hands and feet. In November 2022 the patient noted a left thigh mass. Exam showed a firm, palpable thigh mass without overlying skin changes and core needle biopsy showed adenocarcinoma, favoring breast primary, ER 0, PR 0, HER 2 neu 2+ and FISH negative. PET scan showed no uptake in the chest abdomen or pelvis, however a 2.6 × 2.3 × 3.1 cm round mass in the left thigh was seen with SUV max of 8.6. She was started on traztuzumab-deruxtecan by medical oncology in December of 2022. The thigh tumor shrank significantly, however, patient discontinued after two infusions, citing intolerable hand weakness. She then received RT to the thigh. She was treated using 3D technique and 6 MV photons for a total dose of 5400 cGY, from February to March of 2023. Repeat PET June 2023 showed no avid uptake in the thigh. She has declined any additional systemic therapy. Soft tissue metastasis in distant recurrent breast cancer is uncommon and little guidance exists on clinical management. In cases of metastatic disease to the skin, hormone positive lesions can be managed with hormonal therapy. Early detection and biopsy for receptor studies may help guide therapy in cases of distant soft tissue recurrence. Citation Format: Rangel Melissa, Julia Alexieva, Alison Coogan, Lily Hussein, Elizabeth Marcus, Julie Wecsler. A Case of Metastatic Breast Cancer to Soft Tissue of the Thigh [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 PO5-20-07.

Abstract PO5-08-04: Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center

Abstract Background: Pathogenic variants (PVs) in ATM are associated with an increased risk of breast, pancreas, and other cancers. The clinical and pathological characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing between December 2012 and May 2023 and were identified to harbor ATM PVs were included in the study. We analyzed demographics, germline findings, histopathology, genomic recurrence score, and management of ATM PV carriers with breast cancer. Results: A total of 222 individuals were identified to have PVs in ATM, of whom 184 (83%) were female. The majority were Caucasian (n = 179, 81%) and of those, 22 (12%) had Ashkenazi Jewish ancestry. The median age at genetic testing was 52y, with a range of 20-90y. A total of 111 patients (50%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 70; 63%). The median age at breast cancer diagnosis was 53y, with a range of 25-84y. The most common histopathology was invasive ductal carcinoma (74%), followed by DCIS (21%), and invasive lobular carcinoma (5%). The majority of patients had breast tumors with stage 2 or 3 (78%), grade 2 or 3 (92%), ER and/or PR positive (92%) and HER2 negative (70%). One patient had triple-negative breast cancer. Forty-four percent of breast cancers were less than two centimeters, 23% were lymph node-positive, and 29% had lymphovascular invasion. Thirty-eight percent of patients underwent bilateral mastectomy, 54% received radiation therapy, 40% received adjuvant chemotherapy, 24% received neoadjuvant chemotherapy, and 70% received hormonal therapy. Of the 15 breast cancers with known 21-gene recurrence scores, 47% were intermediate (11-26), 33% were high (>=26) and 20% were low (< =10). Other notable cancers observed were pancreas (n = 9), colorectal (n = 6), prostate (n = 5), uterine (n = 4), melanoma (n = 4), and thyroid (n = 4). Conclusion: Our study outlines the clinical and pathological characteristics of ATM-associated breast cancer in a large academic center. The majority of breast cancers were invasive ductal type, early stage, intermediate or high grade, and hormone receptor-positive with an intermediate or high recurrence score. Despite the early stage, a significant proportion of patients underwent bilateral mastectomy. Further studies are needed to better elucidate the unique characteristics of breast cancer in ATM PV carriers in order to provide tailored management guidelines for this population. Citation Format: Ujjwal Karki, Tara Rangarajan, Dana Zakalik. Characteristics of breast cancer in carriers of pathogenic variant in ATM in a large academic health center [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 PO5-08-04.

Abstract PO2-20-09: Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- breast cancer

Abstract INTRODUCTION: Metastatic breast cancer is an infamously heterogeneous disease—characterized by a range of clinical presentations and treatment responses. In light of this heterogeneity, ASCO guidelines recommend patients with new, accessible metastatic tumors undergo a biopsy to inform treatment decisions. Here, we present a patient with HR+/HER2- disease with a long history of unusually heterogeneous responses—and a repeat metastatic biopsy that provided an answer. CASE: A 55-year-old woman presented for consultation of treatment-refractory metastatic breast cancer. She was originally diagnosed with a right-sided Stage III HR+/HER2- invasive ductal carcinoma (IDC) at the age of 33. Upon staging, she was incidentally found to have a right lower-lobe lung carcinoid tumor that was removed by lobectomy. She underwent a partial mastectomy, axillary lymph node dissection, followed by adjuvant chemo- and radiation therapy. She tolerated one week of tamoxifen which was discontinued due to adverse effects. Fifteen years later, screening mammography revealed a suspicious lesion in the right breast—biopsy consistent with a new IDC. She underwent bilateral mastectomies which showed a pT1cNxM0 G2 IDC with associated DCIS (ER+/PR+/HER2 IHC 2+, FISH-negative, Oncotype RS 12). Genetic testing was negative. The patient trialed adjuvant tamoxifen, which was discontinued due to repeat adverse effects. Two years later, rising tumor markers prompted restaging scans that demonstrated an enlarging liver lesion. Liver biopsy was consistent with metastatic adenocarcinoma of the breast (ER+/PR+/HER2 IHC 0), GATA3 positive. Patient was started on letrozole with lupron and palbociclib with disease control for two years until progression in the bone, prompting a switch of letrozole to fulvestrant with continued palbociclib. Her disease was stable for two additional years until progression of multiple liver lesions. She was then started on single-agent paclitaxel. At this point, she was seen in our office for consultation and next-line therapy options. Repeat staging scans showed heterogeneous response in the liver with overall progression. ctDNA testing revealed a mutation in MEN1 (p.Q354*, 2.8% VAF) without other actionable alterations. Patient opted to enroll into a clinical trial of an experimental ER-antagonist but experienced progression of her liver lesions on first staging scans. A second liver biopsy was performed on a progressive lesion which showed ER-/PR-/HER2- disease. She opted to enroll into a Phase 1b/2 trial with sacituzumab govitecan-hziy in combination with a PARPi. Staging scans again showed a mixed response in the liver. Given a history of mixed responses and discordant receptor staining, the differential diagnosis included loss of hormone receptor expression in the breast carcinoma versus metastases from an occult neoplasm. Additional immunohistochemical studies were performed on a subsequent liver biopsy showing positivity for chromogranin, synaptophysin, and INSM1, and negative results for ER, PR, GATA3, and TRPS1. Next-generation sequencing of the progressive lesion revealed a MEN1 SNV (p.Q354*, VAF 82%) as well as loss of 11q (MEN1 locus) suggestive of biallelic loss of MEN1—providing molecular evidence of a metastatic carcinoid tumor. A history of mixed response in the liver was concluded to be two coexisting neoplasms—a metastatic HR+/HER2- breast cancer as well as a late recurrence of a right-lower lobe carcinoid tumor from 22 years prior. DISCUSSION: The unanticipated discovery of an occult, coexisting neoplasm in the setting of a metastatic HR+/HER2- breast cancer illustrates the value of meticulous pathological review, repeat molecular testing and the use of next-generation diagnostic tools such as tumor sequencing in the advanced setting—particularly when a clinical story defies conventional expectations—to personalize care and optimize oncologic management in the face of complex biology. Citation Format: Nolan Priedigkeit, Jane Brock, Olivia Cunningham, Molly Skeffington, Melissa Hughes, Nancy Lin, Susan Lester, Heather Parsons. Hiding in plain sight: A heterogeneous response in a patient with metastatic HR+/HER2- 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 PO2-20-09.

Immediate DIEP Breast Reconstruction in a Trans Woman with Breast Cancer

Summary: Breast cancer is a leading cause of cancer among cisgender women worldwide, with an incidence that continues to rise. Breast reconstruction is increasingly recognized as an integral part of breast cancer management. In tandem, the population of trans women is also increasing. However, few studies have focused on the management of breast cancer in this population, given that estrogen therapy has the potential to increase the risk of breast cancer. We present the case of a 51-year-old trans woman diagnosed with right breast cancer following a 32-year history of estrogen therapy. She presented to our clinic for consultation and immediate breast reconstruction. She opted for bilateral skin-sparing mastectomies, sentinel lymph node biopsies, and immediate breast reconstruction using deep inferior epigastric perforator free flaps. There were no postoperative flap complications. Final pathology revealed invasive mucinous carcinoma, devoid of lymph node involvement. The patient was satisfied with her reconstruction and is currently planning for nipple reconstruction. To the authors’ knowledge, this is the first reported case in the literature of bilateral deep inferior epigastric perforator free flap reconstruction in the trans female population after breast cancer diagnosis. This case underscores the need for a holistic treatment approach and heightened vigilance among trans women on estrogen therapy. It also highlights that breast reconstruction should be considered and offered to this patient population.

Efficacy of Erector Spinae Plane (ESP) Block for Non-cardiac Thoracic and Upper Abdominal Surgery: A Single Institute Comparative Retrospective Case Series.

Introduction Erector spinae plane (ESP) block was first introduced for the management of thoracic pain but has become increasingly popular for the treatment of abdominal surgical pain. Previous studies have shown the ESP block can be easily adapted to abdominal procedures at the corresponding dermatome level and provide postoperative analgesia. Though the versatility, simplicity, and safety of the ESP block have been demonstrated, there is a gap in the literature regarding its comparison between thoracic and abdominal surgeries. This study aims to evaluate the efficacy of the ESP block in treating acute postoperative pain in patients undergoing thoracic and abdominal surgeries. Methods This retrospective study included 50 patients in the non-cardiac thoracic surgery group (bilateral breast mastectomy with reconstruction) and 50 patients in the abdominal surgery group (robotic or laparoscopic sleeve gastrectomy). Data was obtained via the acute pain service records at a tertiary care center from 2018 to 2022.All patients received bilateral ESP blocks, performed under ultrasound guidance. Various parameters were evaluated including oral morphine equivalents (OMEs) and visual analog scale (VAS) scores during post-anesthesia care unit (PACU), 6, 12, and 24 hours postop. The use of abortive antiemetic medications within 24 hours was also measured to evaluate the incidence of nausea and vomiting. The results were analyzed and compared. No control group is included, as all patients at our institution receive a peripheral nerve block as a part of the institution's enhanced recovery pathway (ERP). Results This retrospective study included 50 patients in the non-cardiac thoracic surgery group (bilateral breast mastectomy with reconstruction) and 50 patients in the abdominal surgery group (robotic or laparoscopic sleeve gastrectomy). Compared to the thoracic group, the abdominal group had a statistically higher VAS score in PACU with mean difference (MD)1.3 VAS, 95% confidence interval (CI) 0.03-2.56, p-value 0.0443, statistically higher OME consumption in the PACU (difference 13.35 OME, 95% CI 4.97-21.73, p-value 0.0003), and requiredsignificantly more antiemetic pharmacotherapy (mean 1.4 antiemeticsadministered, 95% CI 0.84-2.04, p-value <0.0001). Despite the abdominal group having more OME utilization in the PACU, there was no difference in cumulative OME use in the first 24hours (95% CI-9.745-24.10, p-value 0.4021). Conclusion In this study, we demonstrated that ESP blocks are an effective regional anesthesia technique to reduce postoperative pain and opioid consumption. The ESP block can serve as a useful and safe alternative to either thoracic epidural or paravertebral blocktechniques in thoracic and upper abdominal surgeries for perioperative pain management.

Timing of genetic testing in BRCA1/2 and PALB2-Associated breast cancer: Preoperative result disclosure increases uptake of risk-reducing mastectomy and reduces unnecessary exposure to radiotherapy

IntroductionThe impact of timing of genetic testing on uptake of risk reducing mastectomy (RRM) in affected female BRCA1/2 or PALB2 carriers remains an area of evolving interest, particularly with the introduction of mainstream genetic testing initiatives. MethodsWomen with stage I-III breast cancer and a confirmed germline pathogenic variant in BRCA1/2 or PALB2 between 2000 and 2023 were identified from an institutional genetics database. Uptake of RRM was evaluated according to disclosure of genetic testing results before or after index surgery for a first diagnosis of breast cancer. ResultsThe cohort included 287 female BRCA1/2 or PALB2 carriers with a median age of 44 years (IQR, 36–52). Overall, 155 (54 %) carriers received genetic testing results before and 132 (46 %) after index breast surgery. Receipt of genetic testing results before surgery was associated with a higher rate of index bilateral mastectomy (58.7 % vs. 7.6 %, p < 0.001) and a commensurate decrease in adjuvant radiation (41.9 % vs. 74.2 %, p < 0.001). At a median follow up of 4.4 years after genetic testing, 219 (76.3 %) affected carriers had undergone bilateral RRM, including 83.9 % with preoperative knowledge and 67.4 % of patients with postoperative knowledge of their germline pathogenic variant (log rank, p < 0.001). On multivariate regression, disclosure of genetic testing results before index breast surgery was independently associated with long-term uptake of bilateral mastectomy (HR 1.69, 95 % CI 1.21–2.38). ConclusionGenetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making.

TP53-associated early breast cancer: new observations from a large cohort.

A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features. This multicenter cohort study included women with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic breast cancer diagnosed between 2002 and 2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were used to summarize proportions, and differences were assessed using χ2 or Wilcoxon rank sum tests. Metachronous contralateral breast cancer risk, radiation-induced sarcoma risk, and recurrence-free survival were analyzed using the Kaplan-Meier methodology. Among 227 women who met study criteria, the median age of first breast cancer diagnosis was 37 years (range = 21-71), 11.9% presented with bilateral synchronous breast cancer, and 18.1% had ductal carcinoma in situ only. In total, 166 (73.1%) patients underwent mastectomies, including 67 bilateral mastectomies as first breast cancer surgery. Among those patients with retained breast tissue, the contralateral breast cancer rate was 25.3% at 5 years. Among 186 invasive tumors, 72.1% were stages I to II, 48.9% were node negative, and the most common subtypes were hormone receptor-positive/HER2-negative (40.9%) and hormone receptor positive/HER2 positive (34.4%). At a median follow-up of 69.9 months (interquartile range = 32.6-125.9), invasive hormone receptor-positive/HER2-negative disease had the highest recurrence risk among the subtypes (5-year recurrence-free survival = 61.1%, P = .001). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. We observed high rates of ductal carcinoma in situ, hormone receptor-positive, and HER2-positive breast cancers, with a worse outcome in the hormone receptor-positive/HER2-negative luminal tumors, despite appropriate treatment. Confirmation of these findings in further studies could have implications for breast cancer care in those with Li-Fraumeni syndrome.

The Impact of Radiation on Nipple Symmetry After Bilateral Nipple-Sparing Mastectomy and Implant-Based Reconstruction: An Objective Analysis.

Radiation therapy can adversely affect outcomes of implant-based breast reconstruction, potentially complicating procedures like nipple-sparing mastectomy (NSM), which is increasingly popular in breast cancer management. This study aims to evaluate the impact of radiation on nipple symmetry in patients undergoing bilateral NSM with implant-based reconstruction. We conducted a retrospective analysis using data from an Emory University review board-approved database. This encompassed bilateral NSMs coupled with immediate implant-based reconstructions. The BCCT.core software was employed to objectively measure nipple asymmetry preoperatively and postoperatively. Metrics, such as Breast Retraction Assessment values, upper nipple retraction, lower breast contour, and nipple to midline (NML) discrepancies were quantified. The study included 80 patients with a minimum of 1 year of follow-up; among them, 15 received radiation therapy (RT) while 65 did not. The reconstructions were divided into tissue expander, used in 39 cases (48.8%), and direct-to-implant (DTI), employed in 41 cases (51.2%). The DTIs were further categorized based on the location of the implant: 22 subpectoral and 19 prepectoral. Radiation was applied to 15 breasts, distributed among prepectoral DTI (4), subpectoral DTI (6), and tissue expander (5). Breast Retraction Assessment scores significantly differed between the nonirradiated and irradiated groups (1.49 vs 2.64, P < 0.0004). Nipple to midline differences and Upper Nipple Retraction also significantly varied postradiation, especially when comparing subpectoral and prepectoral implant placements. Radiation therapy has a detrimental effect on nipple symmetry after bilateral NSM and implant-based reconstruction, with variations seen regardless of the implant's placement or the reconstructive technique utilized. Specifically, subpectoral reconstructions irradiated were prone to lateral nipple displacement, likely related to radiation-induced pectoralis muscle changes, while prepectoral irradiated reconstructions tended to have increased vertical displacement. These insights are crucial for patient education and surgical planning in the context of radiation and breast reconstruction.

Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico.

Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer-associated germline PV carriers in Mexico. Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges. Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership (P = .04) and believing GCRA was useful (P < .001). Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.

Clinical value of KiSS-1 and MMP-2 expression levels in breast cancer tissue in evaluating prognosis of elderly breast cancer patients after modified radical mastectomy.

We attempted to clarify clinical value of KiSS-1 and MMP-2 levels in breast cancer (BC) tissue in evaluating prognosis of elderly BC patients after modified radical mastectomy (MCM). The data of 192 elderly female BC patients receiving MCM in our hospital from January 2018 to December 2022 were collected. According to prognosis, patients received division into poor prognosis group (n = 43) and good prognosis group (n = 149). The serum CEA level and KiSS-1 and MMP-2 levels in BC tissue received measurement in both groups. The predictive value of KiSS-1 and MMP-2 alone and jointly in adverse prognosis of elderly BC patients after MCM received assessment. Results showed that No statistical significance was exhibited between both groups in general data (P > 0.05). The serum CEA level and MMP-2 expression in BC tissue in poor prognosis group exhibited elevation relative to those in good prognosis group, and KiSS-1 expression in BC tissue in poor prognosis group exhibited depletion relative to that in good prognosis group, indicating statistical significance (P < 0.05). The high-level KiSS-1 might be a protective element for adverse prognosis of elderly BC patients after MCM, and high-level CEA and MMP-2 might be an independent risk element for adverse prognosis of elderly BC patients after MCM (P < 0.05). KiSS-1 and MMP-2 alone and jointly predicted AUC of adverse prognosis in elderly BC patients after MCM were 0.93, 0.802 and 0.958, with certain predictive values; when cutoff values of KiSS-1 and MMP-2 were 6.15 and 2.26, the predictive value was the best. In conclusion, KiSS-1 and MMP-2 levels in BC tissue possess relation to adverse prognosis of MCM. KiSS-1 and MMP-2 levels in elderly BC patients before surgery may be detected in the future to assist in prognosis evaluation of elderly BC patients after MCM.

Abstract 1293: Uncovered: The breast cancer journey of a Black woman from advocacy to awareness to action

Abstract Background: There have been 3 significant life events guiding my journey from being a young, Black mother with stage 4 breast cancer and thyroid cancer to an engaged patient partner. The first was having a benign breast tumor removed at age 14. The second was my 2017 mBC diagnosis, including my bilateral mastectomy and the lack of images and information available for Black women concerning reconstruction and scar management. The third is exclusion from and the lack of diversity in clinical trials. Objective: In order to address the disparities in cancer and my unmet needs, I use my story and experiences as a catalyst for change primarily in three forms, which have evolved over time: advocacy, awareness, and action. Methods: Advocacy: To unburden myself from the shame about my breast health and the scar from my surgery at age 14, I vocalized my concerns and needs as an adult navigating my breast reconstruction options after my 2017 cancer diagnosis. Ongoing frustration that my needs were not being addressed led me to create Uncovered: A Breast Recognition Project, in collaboration with Rethink Breast Cancer. Uncovered, a digital and print resource, shines a light on the disparities and challenges that Black, Indigenous and people of color face in breast cancer care. Awareness: The 2020 edition started with my story and those of 7 Black women. After Uncovered launched, other racialized women reached out with similar experiences. The resource was expanded in 2021 to include stories and images of an Inuk woman, Black women, and women of color. This confirmed a systemic need to raise awareness and address racialized communities and inequities in breast cancer care. Action: As a result of the slow progress towards systemic change, I, along with the women of Uncovered, co-created the Wish List in 2021. The Uncovered Wish List is 6 accessible and actionable items that should be a priority for ending disparities in breast cancer care. Due to the complexity of my diagnosis, which limits my clinical trial options, and the historical underrepresentation of racialized communities in clinical trials, I now partner with cancer institutions and organizations that focus on research to address ongoing unmet needs with the goal to improve equity, diversity and inclusion. Results: Uncovered is a first-of-its-kind resource in Canada. To date, it has had a global reach of over 70 million through conferences, panels, podcasts, resource links, presentations, and various media. The recognition of my story, Uncovered, and the Wish List allows me to form collaborative connections, and become an engaged patient partner committed to systemic change. Conclusion: Despite systemic barriers, it is possible for Black women with breast cancer to advocate, raise awareness and take action towards change in meaningful ways. Citation Format: Michelle Audoin. Uncovered: The breast cancer journey of a Black woman from advocacy to awareness to action [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1293.

Abstract 1622: Characterization of the phylogenetic relationships in bilateral breast angiosarcoma

Abstract Background: Breast angiosarcoma represents around 20% of all angiosarcomas, and often spread to lung, liver, and bones. Driver mutations of angiosarcoma, specifically PTPRB, and PLCG1, are well-known as reported previously. Notably, contralateral breast is another metastatic site of the breast angiosarcoma, where an unusual location for other soft tissue sarcomas. However, it remains uncertain whether the contralateral disease originates from the primary tumor or emerges independently. Here, we present a 75-year-old woman with bilateral breast angiosarcomas to investigate the genetic relationship between the tumors. Methods: Irregular and heterogeneous masses were synchronously detected through breast sonography. Whole genome sequencing (WGS) was conducted at 60X coverage using bilateral total mastectomies, along with a matched normal blood sample (n=1). Single nucleotide variants (SNVs) and small indels were identified using Strelka2 and Varscan2. Subsequent filtering was performed using custom Python scripts to establish high-confidence variants. A phylogenetic tree was then reconstructed based on SNVs to trace clonal evolution and distinguish between de novo primary and metastasis. Following this, COSMIC mutational signatures were analyzed to characterize the genomic profile. Results: For the left breast angiosarcoma, we found 1,086 SNVs and 101 indels, while the right breast angiosarcoma had 921 SNVs and 92 indels. Despite their small size (&amp;lt;1.0 cm) and low FNCLCC grade (G1), these two cancers shared 600 SNVs and 135 indels as “truncal events”, indicating that one side metastasized from the other. According to the phylogenetic tree and the molecular clock of the two angiosarcomas, we estimated that the metastasis occurred during the middle stages of cancer evolution. Additionally, we identified 7 nonsynonymous SNVs (ADAMTS7, RPS15, CYP2A6, OR1S2, ARHGAP23, GNAQ, UGT2B7), five of which were shared. Remarkably, the GNAQ driver mutation exhibited a mutation at codon 209, a hotspot mutation not previously reported in breast angiosarcoma. The dominant Cosmic mutational signatures were SBS1/5 and ID1/2, all of which were associated with aging. Conclusion: Our findings demonstrate that bilateral breast angiosarcomas metastasized from one side to the other, as evidenced by the WGS data. This study underscores that the capability of WGS to distinguish between oligometastatic disease and multiple primary cancers, which has implications for predicting patients’ prognosis. Citation Format: Minju Kim, Jeonghwan Youk, Soyeon Kim, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Myung Geun Song, Jiwon Koh, Jeong Mo Bae, Hyeong-Gon Moon, Seock-Ah Im. Characterization of the phylogenetic relationships in bilateral breast angiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1622.

Impact of microporous polysaccharide haemostatic agent on patients undergoing mastectomy or axillary dissection on seroma formation and timing of drain removal

Background: Seroma formation is a known complication following mastectomy and axillary lymph node dissection (ALND) leading to morbidity and financial implications for patients. ARISTATM AH has been designed to prevent postoperative seromas formation in vitro. Methods: We performed a single institution, single surgeon retrospective study from January 2017 to December 2022 in patients undergoing mastectomy/axillary dissection to evaluate seroma formation rates and timing of drain removal. Results: A total of 72 cases were included in our retrospective review of electronic medical records. Of these, 40 patients underwent ipsilateral mastectomies with sentinel node biopsies, 8 patients underwent bilateral mastectomies, and 18 patients underwent axillary dissections without concurrent mastectomy. Our analysis showed a non-significant decrease in seroma formation when ARISTATM AH was used intra-operatively (10%) compared to standard care (24%), (p=0.14). The ARISTATM AH group had a statistically significantly longer mean drain removal time than the standard care group (12.9 vs 7.6 days, p=0.002). Conclusions: There was a trend towards lower seroma formation and a significantly longer requirement for drain placement after mastectomy in ARISTATM AH group. Further research including randomised controlled multi-centre study evaluating the benefit of topical haemostatic agents in reducing seroma formation in breast surgery is warranted.

Screening chest wall ultrasound in the mastectomy patient

BackgroundWhile there are clear guidelines regarding chest wall ultrasound in the symptomatic patient, there is conflicting evidence regarding the use of ultrasound in the screening of women post-mastectomy. ObjectiveTo assess the utility of screening chest wall ultrasound after mastectomy and to assess features of detected malignancies. MethodsThis IRB approved, retrospective study evaluates screening US examinations of the chest wall after mastectomy. Asymptomatic women presenting for screening chest wall ultrasound from January 2016 through May 2017 were included. Cases of known active malignancy were excluded. All patients had at least one year of clinical or imaging follow-up. 43 exams (8.5 %) were performed with a history of contralateral malignancy, 465 exams (91.3 %) were performed with a history of ipsilateral malignancy, and one exam (0.2 %) was performed in a patient with bilateral prophylactic mastectomy. ResultsDuring the 17-month period, there were 509 screening US in 389 mastectomy patients. 504 (99.0 %) exams were negative/benign. Five exams (1.0 %) were considered suspicious, with recommendation for biopsy, which was performed. Out of 509 exams, 3 (0.6 %) yielded benign results, while 2 (0.39 %) revealed recurrent malignancy, with a 95 % confidence interval (exact binomial) of 0.05 % to 1.41 % for screening ultrasound. Both patients who recurred had previously recurred, and both had initial cancer of lobular histology. ConclusionOf 509 chest wall screening US exams performed in mastectomy, 2 malignancies were detected, and each patient had history of invasive lobular carcinoma and at least one prior recurrence prior to this study, suggesting benefit of screening ultrasound in these populations.

Decision-making for bilateral risk-reducing mastectomy for an increased lifetime breast cancer risk: A qualitative metasynthesis.

Previvor is a term applied to a person with an identified, elevated lifetime cancer risk but without an actual cancer diagnosis. Previvorship entails the selection of risk management strategies. For women with a genetic mutation that increases their predisposition for a breast cancer diagnosis, bilateral risk-reducing mastectomy (BRRM) is the most effective prevention strategy. However, BRRM can change a woman's breast appearance and function. The purpose of this qualitative metasynthesis (QMS) was to better understand the decision-making process for BRRM among previvors. A theory-generating QMS approach was used to analyze and synthesize qualitative findings. Research reports were considered for inclusion if: (1) women over 18years of age possessed a genetic mutation increasing lifetime breast cancer risk or a strong family history of breast cancer; (2) the sample was considering, or had completed, BRRM; (3) the results reported qualitative findings. Exclusion criteria were male gender, personal history of breast cancer, and research reports which did not separate findings based on cancer diagnosis and/or risk-reduction surgery. A theory and corresponding model emerged, comprised of seven themes addressing the decision-making process for or against BRRM. While some factors to decision-making were decisive for surgery, others were more indefinite and contributed to women changing, processing, or suspending their decision-making for a period of time. Regardless of the decision previvors make about BRRM, physical and psychosocial well-being should be considered and promoted through shared decision-making in the clinical setting.

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol

IntroductionCalcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is...

MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. Entrance into an MRI surveillance program. Cox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P < .001) for women with BRCA1 sequence variations and 0.87 (95% CI, 0.10-17.25; P = .93) for women with BRCA2 sequence variations. Results of this cohort study suggest that among women with a BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. Further studies of women with BRCA2 sequence variations are needed to ascertain these women obtain the same benefits associated with MRI surveillance.

A160 A CASE OF BREAST CANCER METASTASIS MASQUERADING AS SIGNET RING CELL ADENOCARCINOMA OF THE STOMACH

Abstract Background Gastric cancer has a poor prognosis, particularly at advanced stages. Endoscopic submucosal dissection (ESD) can be used to treat selected early-stage gastric cancers. This case study explores the challenge of diagnosing and managing patients when metastatic lesions mimic primary gastric cancer, as seen in this case of breast cancer metastasis resembling signet ring cell adenocarcinoma of the stomach. Aims The aim of this case report is to describe an unusual case of breast cancer metastasis to the stomach identified unexpectedly on random gastric biopsies, initially diagnosed as a primary gastric signet ring cell adenocarcinoma. Methods Clinical and pathological records of the described patient were reviewed retrospectively. Furthermore, a review of the relevant literature was also performed. Results A 68 year-old-woman underwent gastroscopy for nausea and vomiting. Her past medical history was remarkable for bilateral mastectomies ten years ago for invasive lobular carcinoma, with metastatic bone disease diagnosed by imaging five years prior. She had been well controlled on letrozole taken intermittently due to side effects. At endoscopy, while the stomach appeared grossly normal, random biopsies done for Helicobacter pylori identified a single focus of signet ring cell adenocarcinoma. Subsequent chromoendoscopy identified an area of subtle mucosal abnormality for which the patient declined surgery and was instead managed by ESD which surprisingly yielded no dysplasia. A follow up gastroscopy with random biopsies also failed to identify any areas of dysplasia, but random biopsies on a subsequent gastroscopy again identified a minute focus of adenocarcinoma with signet ring cell morphology. Given the unusual presentation of apparent signet ring cell adenocarcinoma in two distinct areas in the stomach without any visible endoscopic abnormality an in-depth pathological analysis was conducted. By immunohistochemistry the tumor cells stained positive for Estrogen Receptor, GATA3, and CK7 and negative for antibodies targeting CK20 and CDX2, which supported an interpretation of minute multifocal breast cancer metastases to the stomach from hematogenous spread. Conclusions In this case, repeated endoscopic investigations and immunohistochemical staining revealed minute multifocal breast cancer metastases to the stomach. Conventional tumor staging methods often cannot identify microscopic metastases, potentially impacting disease progression and patient care. A high level of suspicion for metastatic breast cancer and a detailed pathological analysis allowed for the correct diagnosis in this patient. Funding Agencies None