Cancer Cases Research Articles

Longitudinal tracking of circulating rare events in the liquid biopsy of stage III–IV non-small cell lung cancer patients

In the United States, lung cancer is the second most common type of cancer with non-small cell lung cancer (NSCLC) encompassing around 85% of total lung cancer cases. Late-stage patients with metastatic disease have worsening prognosis, highlighting the importance of longitudinal disease monitoring. Liquid biopsy (LBx) represents a way for physicians to non-invasively track tumor analytes, such as circulating tumor cells (CTCs), and understand tumor progression in real-time through analyzing longitudinal blood samples. CTCs have been shown to be effective predictive biomarkers in measuring treatment efficacy and survival outcomes. We used the third-generation High-Definition Single Cell Assay (HDSCA3.0) workflow to analyze circulating rare events longitudinally during treatment in a cohort of 10 late-stage NSCLC patients, identifying rare events including circulating cancer cells (i.e., CTCs), and oncosomes. Here, we show (1) that there is a cancer specific LBx profile, (2) there is considerable heterogeneity of rare cells and oncosomes, and (3) that LBx data elements correlated with patient survival outcomes. Additional studies are warranted to understand the biological significance of the rare events detected, and the clinical potential of the LBx to monitor and predict response to treatment in NSCLC patient care.

Epigenome-wide association study of lung cancer among never smokers in two prospective cohorts in Shanghai, China

BackgroundThe aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic...

Global burden and economic impact of vaccine-preventable cancer mortality

Background Infections are responsible for approximately 13% of cancer cases worldwide and many of these infections can be prevented by vaccination. Human papillomavirus (HPV) and hepatitis B virus (HBV) are among the most common infections that cause cancer deaths globally, despite effective prophylactic vaccines being available. This analysis aims to estimate the global burden and economic impact of vaccine-preventable cancer mortality across World Health Organization (WHO) regions. Methods The number of deaths and years of life lost (YLL) due to five different vaccine-preventable cancer forms (oral cavity, liver, laryngeal, cervical and oropharyngeal cancer) in each of the WHO regions (African, Eastern Mediterranean, European, the Americas, South-East Asia Pacific and Western Pacific) were obtained from the Institute for Health Metrics Evaluation global burden of disease dataset. Vaccine-preventable mortality was estimated considering the fraction attributable to infection, to estimate the number of deaths and YLL potentially preventable through vaccination. Data from the World Bank on GDP per capita were used to estimate the value of YLL (VYLL). The robustness of these results was explored with sensitivity analysis. Given that several Epstein-Barr virus (EBV) vaccines are in development, but not yet available, the impact of a potential vaccine for EBV was evaluated in a scenario analysis. Results In 2019, there were 465,740 potentially vaccine-preventable cancer deaths and 14,171,397 YLL across all WHO regions. The estimated economic impact due to this mortality was $106.3 billion globally. The sensitivity analysis calculated a range of 403,025-582,773 deaths and a range in productivity cost of $78.8-129.0 billion. In the scenario analysis EBV-related cancer mortality increased the global burden by 159,723 deaths and $32.4 billion. Conclusion Overall, the findings from this analysis illustrated high economic impact of premature cancer mortality that could be potentially preventable by vaccination which may assist decision-makers in allocating limited resources among competing priorities. Improved implementation and increased vaccination coverage of HPV and HBV should be prioritized to decrease this burden.

A clinicopathological-imaging nomogram for the prediction of pathological complete response in breast cancer cases administered neoadjuvant therapy

ObjectiveTo construct a user-friendly nomogram with MRI and clinicopathological parameters for the prediction of pathological complete response (pCR) after neoadjuvant therapy (NAT) in patients with breast cancer (BC). MethodsWe retrospectively enrolled consecutive female patients pathologically confirmed with breast cancer who received NAT followed by surgery between January 2018 and December 2022 as the development cohort. Additionally, we prospectively collected eligible candidates between January 2023 and December 2023 as an external validation group at our institution. Pretreatment MRI features and clinicopathological variables were collected, and the pre- and post-treatment background parenchymal enhancement (BPE) and the changes in BPE on two MRIs were compared between patients who achieved pCR and those who did not. Multivariable logistic regression analysis was used to identify independent variables associated with pCR in the development cohort. These independent variables were combined into a predictive nomogram for which performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, decision curve analysis, and external validation. ResultsIn the development cohort, there were a total of 276 female patients with a mean age of 48.3 ± 8.7 years, while in the validation cohort, there were 87 female patients with a mean age of 49.0 ± 9.5 years. Independent prognostic factors of pCR included small tumor size, HER2(+), high Ki-67 index,high signal enhancement ratio (SER), low minimum value of apparent diffusion coefficient (ADCmin), and significantly decreased BPE after NAT(change of BPE). The nomogram, which incorporates the above parameters, demonstrated excellent predictive performance in both the development and external validation cohorts, with AUC values of 0.900 and 0.850, respectively. Additionally, the nomogram showed excellent calibration capacities, as indicated by Hosmer-Lemeshow test p values of 0.508 and 0.423 in the two cohorts. Furthermore, the nomogram provided greater net benefits compared to the default simple schemes in both cohorts. ConclusionA nomogram constructed using tumor size, HER2 status, Ki-67 index, SER, ADCmin, and changes in pre- and post-NAT BPE demonstrated strong predictive performance, calibration ability, and greater net benefits for predicting pCR in patients with BC after NAT. This suggests that the user-friendly nomogram could be a valuable imaging biomarker for identifying suitable candidates for NAT.

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 PO3-09-12: Exploring Gender-Specific Patterns of Breast Cancer in Brazil: A Comparative Epidemiological Study

Abstract Introduction: Male breast cancer constitutes approximately 1% of all breast cancer cases, and limited studies have focused on this population, resulting in a lack of understanding of the disease in men. This study aims to describe the epidemiological profile of male breast cancer in Brazil and compare it with female breast cancer. Methods: A comprehensive observational cross-sectional study was conducted using retrospective data from the DATASUS database (SISCAN/Cancer Information System) spanning the period from 2017 to 2021. Male and female patients diagnosed with breast cancer (ICD C50) during this period were included. Statistical analysis involved absolute values, percentages, and a 95% confidence interval (p < 0.05). Results: Analysis of the study period revealed 4,326 cases (1.8%) of male breast cancer and 236,597 cases (98.2%) of female breast cancer in Brazil. The southeast region had the highest concentration of cases for both sexes, while the northeast region showed a higher prevalence in males (p < 0.0004). Noteworthy findings include a higher mean age among males (59.5 years) compared to females (55.7 years) and a higher prevalence of advanced stages at diagnosis in males (72.8% vs. 59.3%). Diagnostic approaches, subtype distribution, and treatment modalities also differed between the genders. Conclusions: Male breast cancer presents with more advanced stages at diagnosis compared to females, necessitating more aggressive surgical interventions. However, males benefit from earlier initiation of treatment. These findings contribute to a better understanding of male breast cancer, enabling the development of tailored management strategies for this unique patient population. Comparison between male and female MC XX XX Source: Panel-Oncology Brazil (accessed 15/04/2023) Citation Format: Marcelo Antonini, Gabriel Pannain, Steffi Buttenbender, Andre Mattar, Reginaldo Coelho Lopes, Odair Ferraro. Exploring Gender-Specific Patterns of Breast Cancer in Brazil: A Comparative Epidemiological Study [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 PO3-09-12.

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 PO5-20-08: 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 PO4-14-11: Findings of clinically significant variants (Tier IA) with OmniSeq INSIGHT ® in a breast cancer cohort of 987 patients

Abstract Background: There were an estimated 2.3 million new breast cancer cases worldwide in 2020, with breast cancer now the most diagnosed type of cancer representing 25% of cancer cases and 17% of cancer deaths (1). The GLOBOCAN Cancer Tomorrow prediction tool estimates that incidence will increase by > 45% by 2040 (2). Optimal treatment for breast cancer is increasingly dependent upon knowing a patient’s somatic and germline genomic alteration status. To highlight the importance of these genomic alterations, we provide an overview of the genomic findings in 987 consecutive breast cancer patients tested in the course of routine clinical care. Methods: Comprehensive Genomic and Immune Profiling (CGIP) was performed on 987 qualified breast cancer samples at a CAP/CLIA and NYS CLEP certified reference laboratory with the OmniSeq INSIGHT ® test (3). OmniSeq INSIGHT ® is a next generation sequencing-based laboratory developed test for the detection of genomic variants, signatures, HLA Class I genotypes, and immune gene expression in formalin-fixed paraffin-embedded (FFPE) tumor tissue. DNA is sequenced to detect small variants in the full exonic coding region of 523 genes, copy number alterations in 59 genes (gains and losses), as well as analysis of microsatellite instability (MSI) and tumor mutational burden (TMB). RNA is sequenced to detect fusions and splice variants in 55 genes, in addition to mRNA expression in 64 immune genes. The resultant information, along with PD-L1 protein expression by immunohistochemistry (IHC), is intended for use by qualified health care professionals in accordance with professional guidelines in oncology for management of patients with solid neoplasms. Tier IA variants include variants with strong clinical significance as per AMP–ASCO–CAP recommendations (4). Results: There were 384 Tier IA variants detected in 370 of 987 breast cancer patients (~37.5%) with 251 in PIK3CA (65.3%), 60 in ERBB2 (15.6%), 46 in BRCA2 (11.9%), 19 in BRCA1 (4.9%), 4 in NTRK3 (1.0%), 1 in NTRK1 (0.26%) and 1 in PALB2 (0.26%) including copy number variations (CNV), gene fusion and single nucleotide variants (SNV). At the individual gene level for Tier IA variants, PIK3CA had 251 SNVs detected, ERBB2 had 55 CNVs, 1 gene fusion and 4 SNVs detected, BRCA2 had 39 SNVs and 8 CNVs detected, BRCA1 had 19 SNVs, NTRK3 had 4 gene fusions, NTRK1 had 1 gene fusion and PALB2 had 1 SNV detected. At the variant class level, there were 63 CNVs, 6 gene fusions and 315 SNVs observed. Conclusions: CGIP for breast cancer patients identified one or more clinically significant Tier IA genomic alterations that directs targeted therapy in ~ 37.5% of patients in a cohort of real world patients tested during the standard course of clinical care. This highlights the need for comprehensive genomic testing in breast cancer patients to drive therapeutic decision making.

Abstract PO2-24-11: Hedgehog signaling influences tumor immunogenicity by the modulation of T cell populations in triple-negative breast cancer

Abstract Breast cancer is becoming more prevalent as it now makes up 30% of all new cancer cases yearly for U.S. women. Additionally, highly aggressive triple-negative breast cancer (TNBC) presents as immunologically “cold” tumors characterized by limited infiltration of anti-tumorigenic lymphocytes and the promotion of immunosuppressive cell populations. Therefore, it is essential to consider possible combinational therapies in treating primary tumors and in preventing metastases and recurrence. In the breast tumor microenvironment (TME), the presence and activity of regulatory T cells (Tregs) have been associated with poorer prognoses in breast cancer due to their ability to promote the progression of tumor growth and metastasis. Our group has extensively studied how the Hedgehog (Hh) signaling pathway can modulate the aggressiveness and the immune portfolio of the mammary TME, and we have recently reported the role of this pathway in regulating Treg activity and abundance. We have discovered that Hh inhibition can influence Treg-to-Th17 plasticity, promoting Tregs into a pro-inflammatory Th17-like phenotype (Tr17). As Tregs are highly influential to other immune populations of the TME, it is imperative to determine what phenotypic changes are induced in other T cell populations after systemic Hh inhibition in the mammary TME. We hypothesize that systemic Hh inhibition reshapes the tumor-immune microenvironment to be tumor-eradicating by influencing key immune populations of the mammary TME. Therefore, we further investigated how CD4+ and CD8+ T cells are influenced by systemic Hh blockade in a mammary carcinoma mouse model using single-cell RNA-Sequencing (scRNA-Seq) and R programming for data analyses and visualization. We sought to assess transcriptomic changes in tumoral T cells and to interpret how these elicited changes may be influencing the immunogenicity of the primary tumor. In these investigations, we found that systemic Hh inhibition modified the abundance and activation profile of CD4+ and CD8+ T cell populations within the primary tumor. As the infiltration and persistence of certain T cell subsets within the TME can influence tumor growth, dictate tumor recurrence, and contribute to immunotherapy responsiveness, it is essential to determine the mechanisms that modulates tumoral CD4+ and CD8+ T cells in the mammary TME. These studies will expand on the mechanism by which Hh signaling modulates mammary tumorigenesis systemically. This comprehensive work will also contribute to understanding the role of Hh signaling in modulating T cell subsets and inform future studies for innovative combinational therapeutic strategies to treat highly aggressive TNBC. Citation Format: Courtney Swain, Dominique Hinshaw, Heba Alsheikh, Brandon Metge, Lalita Shevde-Samant. Hedgehog signaling influences tumor immunogenicity by the modulation of T cell populations in triple-negative 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 PO2-24-11.

Abstract PO5-26-01: Assessing the effect of multimodal therapy in massive fungating breast cancers without distant metastasis

Abstract Background: Massive fungating breast cancers (MFBCs), which comprise exudative, foul-smelling tumors, the size of a child’s head or involve extensive ulceration are classified as locally advanced breast cancers. The National Comprehensive Cancer Network guidelines recommend preoperative neoadjuvant chemotherapy in patients with locally advanced breast cancer without distant metastases. However, limited evidence is available regarding the successful treatment of fungating breast cancers. In clinical practice, many fungating breast cancer cases are treated as stage IV tumors. This study aimed to investigate whether multimodal therapy, including surgery for giant breast cancers, can improve survival rates and whether the survival rates are comparable to those of other stage III breast cancers. Subjects and methods: Out of 1480 cases of primary breast cancer diagnosed at our hospital between June 2012 and March 2020, 123 patients with clinical stages IIIA–IIIC were chosen for analysis. Furthermore, 29 of these patients with MFBC were selected. During multimodal therapy for selected patients with fungating breast cancer, difficulties were encountered in some patients with single-stage skin suturing and closure after standard neoadjuvant chemotherapy. These patients underwent surgery with an additional skin flap or skin grafting. Furthermore, radiation therapy was added as needed. We compared the survival rates of these patients with those of patients who received drug therapy only according to the therapeutic protocol for Stage IV. Survival rates of patients with MFBC and other stage III breast cancers were also compared. Statistical analyses were conducted using the Kaplan–Meier curve and the log-rank test. Results: Of the 29 patients with MFBC, 22 (75.9%) and seven (24.1%) were treated with multimodal and palliative therapies, respectively. The median age and follow-up period of the multimodal therapy group were 62 (range: 43–94) years and 67 (range, 32–131) months, respectively. The corresponding values for the palliative therapy group were 79 (range: 42–88) years and 31 (range: 2–96) months. All patients in the palliative treatment group were hormone receptor positive and HER2 negative, and treatment with hormone therapy was initiated. The 7-year survival rate was significantly higher in the multimodal therapy group than in the palliative treatment group (92.3% vs. 68.6%, p = 0.0317). Furthermore, the 5-year distant recurrence-free rate was higher in the multimodal treatment group (79.3% vs. 63.5%). Local recurrence did not occur in any patient in the multimodal treatment group. There was no significant difference in the 7-year survival rates between patients with MFBC and those with other stage III breast cancers (86.8% vs. 75.3%; p = 0.239). Triple-negative breast cancer accounted for 20.8% (20 96) of the other stage III breast cancers, but none of these were MFBCs. Conclusions: Clinically, MFBCs are often palliatively treated as stage IV tumors, even in the absence of distant metastasis. However, the survival rate was significantly higher in the multimodal therapy group than in the palliative treatment group. Furthermore, the survival and distant recurrence-free rates for MFBC were higher than those for other stage III breast cancers. Therefore, patients with MFBCs should be actively treated using curative treatments. Citation Format: Tamaki Tamanuki, Maki Namura, Tomoyoshi Aoyagi, Haruhito Sakata, Mika Iwai, Shinichirou Shimizu, Hiroshi Matsuzaki. Assessing the effect of multimodal therapy in massive fungating breast cancers without distant 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 PO5-26-01.

Abstract PO2-29-01: POSITIVE PREDICTIVE VALUE FOR THE MALIGNANCY OF MAMMOGRAPHIC ABNORMALITIS IN A ONE-STOP CLINIC MODEL FOR BREAST CANCER IN COLOMBI

Abstract Breast cancer (BC) is the most prevalent malignancy among women in Colombia, with the greatest incidence rate among malignancies. According to available data through the year 2020, the Colombian female population has officially documented 52,025 cases of breast cancer. This variety of cancer has emerged as the leading cause of cancer-related mortality among Colombian women. Currently, it is essential to emphasize the significance of the BI-RADS (Breast Imaging Reporting and Data System) classification as a means of categorizing patients’ risk levels based on criteria for subsequent breast pathology evaluation and diagnosis. We aimed to assess the positive predictive value of BIRADS IV and V in predicting the risk of breast cancer in the Colombian population. From September 2018 to December 2022, consecutive patients referred for breast mammography and suspected of having breast cancer underwent triple assessment of breast tumor and were included in this retrospective study. 27.937 patients were included with breast imaging report and BIRADS classification system 4 and 5. Patients with a previously diagnosed case of breast cancer and a BIRADS score of 1,2 or 3 were excluded. The positive predictive value of categories 4 and 5 was determined using histopathologic results of ultrasound- or stereotactically-guided biopsies as the gold standard. 46% of 21,442 patients had BACAF biopsies, 39% TRUCUT, and 15% stereotactic. Category 4A was found in 12,865 patients (60%) with a 7% positivity rate, 4B in 8,362 (25%) with 20%, and 4C and 5 in 3,216 (15%) with 75%. BIRADS 4 and 5 had a 20% positive predictive value, with 4,371 positive participants (31% under 49 and 69% over 50). Categories 4 - 5 were found to be beneficial for predicting the likelihood of malignancy, with categories 4C and 5 yielding the highest rates of positive results. Comparable to previous research, the PPV for malignancy in the present investigation was comparable. Citation Format: Kelly Corredor, Sara Gil, Carlos Agudelo, Clara Piedrahita, Melissa Naranjo. POSITIVE PREDICTIVE VALUE FOR THE MALIGNANCY OF MAMMOGRAPHIC ABNORMALITIS IN A ONE-STOP CLINIC MODEL FOR BREAST CANCER IN COLOMBI [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 PO2-29-01.

Abstract PO5-03-02: Ductal carcinoma in situ: An excess regard of the axilla?

Abstract Abstract: Ductal Carcinoma in Situ (DCIS) is a malignant proliferation of the epithelial inside the breast duct, which does not invade the myoepithelial layer and, therefore, does not have the capacity to generate metastases. [1]. However, an upstaging after surgery is possible, since there may be a concomitant invasive lesion that was not diagnosed in the pathological examination from biopsy, being discovered only after the surgical procedure [1]. In the pre-screening mammography era, DCIS was diagnosed. more commonly in symptomatic women presenting with a palpable nodule, papillary flow, or through an incidental finding on a breast biopsy [2], accounting for 1-2% of cancer cases. [3]. After the advent of mammographic screening, the incidence has considerably increased among asymptomatic women with mammographic changes such as calcifications. [4]. Nowadays the diagnosis of DCIS corresponds to 20-25% of biopsies secondary to screening mammographic changes. [1]. As we do know that the chance of axillary metastasis is potentially null, old series where axillary dissection (AD) was performed ipsilareral to the index tumor, axillary involvement was observed in less than 1% of cases [9]. Objectives: Our objective in this study was to describe in a single breast cancer reference center the surgical treatment of patients diagnosed with DCIS (mastectomy or breast conservative surgery – BCS). Methods: A retrospective analysis was made using the Pérola Byington Hospital’s database, from January 2011 to December 2019. During this period, 11,373 cases of breast cancer were treated int the institution and 812 (7.4%) were DCIS. Data was available and we could analyze 494 patients who underwent vacuum-guided biopsy guided by mammography or ultrasound and were diagnosed with DCIS and underwent surgical treatment at the Hospital. We grouped the patients into 3 age groups: under 40, 40-49, and 50 and over. In all groups, we had patients who underwent SNB using the patent blue technique or AD and were evaluated using the H&E method. It is not part of the Institutional protocol to perform IHC in axillary lymph nodes. We had also evaluated the type of surgery (BCS or mastectomy) in each age group. Results: DCIS was diagnosed through mammographic alterations in 62% of all cases and nuclear grade 2 was the most common, with 47%, followed by grade 3 and 1, 46% and 4%, respectively. In 2% of cases the data was missing. Comedoconecrosis was present in 78% of our specimens. BCS was the most frequently surgery performed (73% of cases), with the axillary approach being performed in 35% of these patients (32% for SNB and 3% for AD). While 27% of patients underwent radical surgery and in this group 92% were submitted to axillary approach (70% SNB and 22% AD). In the group of patients younger than 40 years, 74% of patients (17 out of 23 in total) underwent an axillary approach regardless of the type of surgery. When evaluating the predetermined age groups, we saw that most of our patients were 50 years or more (69%), followed by patients between 40-49 years (26%) and 5% in patients under 40 years. In 3% of cases (16 in 494) we reclassified the lesion as invasive carcinoma. None of them had a lymph node involved by malignant cells after surgery and that’s include the cases reclassified as invasive carcinoma. Conclusion: The results obtained in this analysis showing no axillary involvement will make us rethink the indications for the concomitant surgical approach of the breast and the axilla in cases with a diagnosis of DCIS as a way to reduce the axillary surgical overtreatment. It was not our goal to compare the costs and complications of each method of diagnosis and the prognostic factors after the treatment of DCIS. Citation Format: Andressa Amorim, Andre Mattar, Marcellus Ramos, Reginaldo Coelho Lopes, Luciana Damous, Luiz Henrique Gebrim. Ductal carcinoma in situ: An excess regard of the axilla? [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 PO5-03-02.

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 PO4-20-01: A PROSPECTIVE PILOT STUDY OF MAMMOGRAPHIC PREDICTION OF WOMEN’S RISK (M-POWER) IN NIGERIA

Abstract Background There have been no sustained efforts at stemming the rising incidence and mortality from breast cancer in sub-Saharan African countries like Nigeria. Mammography is the gold standard for breast cancer screening and is associated with improved survival particularly among women 50 to 69. Reports from various parts of Nigeria show very low mammography screening uptake. Causes include lack of geographical access, financial issues (less than 5% of the population is covered by the National Health Insurance Scheme), lack of awareness and the increasing expertise gap from the continued brain drain, despite the already low number of radiologists in the country. Given these obstacles, our long-term goal is to devise a rational basis for identifying mammographic risk categories so that this resource can be deployed cost-effectively. We propose to carry out a 5-year prospective mammographic study in Nigerian women and to use machine learning to develop a risk prediction algorithm, so that following a single screening mammogram, the appropriate frequency of subsequent mammograms can be determined. Our immediate goal is to examine the feasibility of performing such a study. To this end, we have initiated a cross-sectional pilot study that will recruit up to 2000 women in multiple urban centers in Nigeria. Objective: To explore feasibility of creating a digital mammography image database representative of the radiological features of the breast of Nigerian women. Objective: To explore feasibility of creating a database that can be used to inform a predictive mammographic risk model for breast cancer and identify the appropriate population that will benefit from breast cancer screening in Nigeria. Design This is a prospective, open-label, cross-sectional pilot study in 2000 eligible women in Nigeria and will include a single screening mammography examination. The mammography images will be read by the study radiologist. The Pilot phase will determine the feasibility and aid in the design of the of the Extension phase in which up to 20,000 participants will undergo yearly mammography examination for 5 years. Incident cases of breast cancer during the study period will permit the development of deep learning algorithms for predicting the risk of breast cancer in this population. Main Eligibility Criteria: Inclusion Criteria All consecutive women aged ≥40 years and < 65 years presenting for screening mammography at the participating institutions will be eligible. Signed study-specific written informed consent. Exclusion Criteria Complaint of a focal dominant lump or a bloody or clear nipple discharge. History of breast implants. Any woman who is pregnant or has reason to believe that she might be pregnant. Statistical Methods Analyses of continuous data will be summarized using descriptive statistics where the following parameters will be reported: Number of observations, Number of missing observations, Mean, Median, Standard deviation (SD), Minimum (Min), Maximum (Max) Categorical data will be presented with absolute and relative frequency (n and %). Present Accrual and Target accrual Two hundred ninety-six women have been enrolled and screening digital mammographic images using GE Digital mammography equipment have been obtained on all participants at 2 study sites in 2 cities in Southern Nigeria. The target accrual is 2000 participants over 12 months. Conclusion Our preliminary experience to date suggests the feasibility of proceeding with a larger prospective study to define mammographic risk groups in Nigerian women which will permit the rational allocation of resources for breast cancer prevention activities in this underserved population. Contact Information: Dr Toyin Shonukan at tshonukan@yemanjacancercare.org Citation Format: Oluwatoyin Shonukan, Hyelakumi Ibrahim, Esther Udoh, Wahab Egbeolu, Kanyinsola Oyeyinka, Jonas Haggstrom. A PROSPECTIVE PILOT STUDY OF MAMMOGRAPHIC PREDICTION OF WOMEN’S RISK (M-POWER) IN NIGERIA [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 PO4-20-01.

Abstract PO1-16-12: The McPeak-Sirois Group Breast Metastases Registry

Abstract Background: In 2020, the McPeak-Sirois Group (MPSG), a Quebec-based breast cancer trials consortium, launched a feasibility pilot project to register prospectively cases of metastatic breast cancer (MBC). This Breast Metastases Registry (BMR) had the following objectives: a) to measure real-world progression-free and overall survival; b) to capture real-world evidence in efficacy of novel therapeutic approaches and c) to facilitate the development of clinical research projects in MBC. Methods: The pilot phase was initiated in three major academic hospitals with the intention of testing the feasibility of building a BMR and to assess barriers before extension to other hospitals in the province of Quebec. Funding was obtained through non-profit organizations and the pharmaceutical industry. The project was approved by a research ethics board and informed consent was obtained from each patient. The main inclusion criteria was a MBC diagnosis at the time of enrolment. Metastatic diseases were considered de novo if the metastatic condition was detected at the same time of the primary disease diagnosis or within the following 4 months. The information in the BMR relates to participants’ health status, including but not limited to hospitalizations, diagnoses, medications, medical procedures and imaging, pathology, genetic and laboratory results. In addition to the prospective data, the registry also captures information retrospective to the date of enrollment. Results: Between July 30, 2021 and April 22, 2023, a total of 427 patients were approached by a research nurse and 423 patients enrolled and 4 refused (99.2% participation rate). Approximately one third of the cohort was diagnosed between 2021-2023 (30.3%) while 69.7% were in 2002-2020 timeframe. The majority was either HR+/HER2- (55.3%) or HER2+ (26.9%). The median age at the time of MBC diagnosis was 57 years (Q1-Q3 range: 47-67 years). We observed that 57.9% of patients had a relapsed MBC while de novo MBC comprised 42.1% of the cohort with the highest percentage in the HER2+ group (59.6%). The median time between primary cancer and metastatic disease in those with relapsed MBC is shorter in triple negative breast cancer (28.9 months) compared to 71.4 months in HR+ disease. Among all lines of treatment for metastatic disease, independently of age at time of MBC diagnosis, 21% of patients participated in a clinical trial. Discussion: The pilot project demonstrated the acceptability and feasibility of building a MBC provincial registry as illustrated by the high participation rate (more than 99%). The next step is to expand the registry to other hospital sites in Quebec, however, the main difficulty is having the necessary manpower (oncology registrars) to ensure data entry. Over one third of the MBC patients presented as de novo disease (and more than half of these with HER2+ disease). This proportion of de novo MBC is unusually high and is likely due to a recruitment bias during the pilot phase as data entry was prioritised for de novo diagnoses over MBC at time of recurrence and patients were recruited at any time in their MBC trajectory and not only at the time of their MBC diagnosis. Clinical trial participation was higher in our cohort compared to the usually reported 5% participation rate. This may be due to recruitment bias but needs to be evaluated further. Conclusion: We have found that recruiting patients in a metastatic cancer registry and collecting their real-world data is not only feasible but well received by patients. The limiting factor for expansion to other hospitals is lack of oncology registrars. At maturity, the BMR will be a unique and powerful resource for breast cancer research and will allow researchers and their collaborators to unite their efforts to better understand how stage IV breast cancer is treated and how management of the disease can be improved. The BMR could also have the potential to improve participation in clinical trials and to stimulate clinical research. Citation Format: Julie Lemieux, Danielle Charpentier, Dominique Johnson, Nathalie Bolduc, Caty Blanchette, Claude Nadon, Sarkis Meterissian. The McPeak-Sirois Group Breast Metastases Registry [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 PO1-16-12.

Abstract PO4-16-01: EZH2 is Overexpressed in Invasive Carcinoma and DCIS in both BRCA1 and BRCA2 Mutation Carriers

Abstract Background The transcriptional repressor EZH2 (Polycomb Group Protein Enhancer of Zeste Homologue 2) is overexpressed in multiple neoplasms including breast cancer where it associates with high proliferation, aggressive features and poor prognosis and is of interest as a potential therapeutic target. EZH2 nuclear expression in breast cancer has been shown to correlate specifically with high tumor grade and basal-like histologic features but has not been well studied in cancers from BRCA carriers. Here we evaluate the expression of EZH2 protein in BRCA-associated invasive breast carcinomas and precursor lesions. Methods Eighteen cases of invasive breast cancer in consented BRCA carriers (8 BRCA1 and 10 BRCA2) treated at Dana Farber Cancer Institute from 2001-2019 were reviewed by two pathologists (TAD and RBPP). Histopathologic features (histologic subtype, nuclear grade, mitotic score) and presence of precursor lesions were recorded. Immunohistochemistry for EZH2 was performed on freshly cut formalin-fixed paraffin-embedded tissue sections (1-3 sections/case) using a monoclonal antibody against EZH2 (D2C9, Cell Signaling). Nuclear EZH2 expression was scored as negative (score=1, no staining); weak (score 2, < 25%); moderate (score=3, 25–75%); and strong (score=4, >75%), of any intensity following published criteria. EZH2 overexpression was defined as scores 3 and 4. Results The majority of the invasive carcinomas showed grade III histology (13/18, 72%), as expected. Of 8 BRCA1 cases, 6 were classified as grade III (75%), 1 as grade II, and 1 as grade I (7 cases of invasive ductal carcinoma and 1 case of invasive tubular carcinoma). Of 10 BRCA2 cases, 7 were classified as grade III (70%) and 3 as grade II (30%) (5 cases of invasive ductal carcinoma and 5 cases of invasive carcinoma with ductal and lobular features). The majority of cases (13 of 18, 72%) showed high expression of EZH2 in the invasive carcinoma (6 BRCA1 and 7 BRCA2 cases; 2 grade II and 11 grade III). Of 13 cases with EZH2 overexpression, 6 were ER+/PR+/HER2- and 7 were triple negative, with 9 invasive ductal carcinomas and 4 invasive carcinomas with ductal and lobular features. Of 5 cases with no/low EZH2 overexpression, 1 was ER+/PR+/HER2-, 3 were ER+/PR-/HER2- and 1 was triple negative, with 3 invasive ductal carcinomas, 1 invasive carcinoma with ductal and lobular features and 1 invasive tubular carcinoma. In all cases with adjacent ductal carcinoma in situ (DCIS) (n=14), the pattern of EZH2 expression in the DCIS was identical to that seen in the invasive carcinoma (11 high and 3 low expression). Overexpression of EZH2 was not observed in any other precursor lesions (LCIS, ADH, ALH) or in normal tissue. Conclusion EZH2 protein overexpression is seen in the majority of invasive carcinomas in BRCA carriers, both in BRCA1 and in BRCA2. In all cases, the associated DCIS shows the same pattern of expression as the invasive carcinoma, suggesting that overexpression occurs early in tumorigenesis, while tumor cells are still confined within the ducts. The high rate of overexpression of EZH2 in BRCA1- and BRCA2-associated tumors suggests a potential role for EZH2 as a target and/or a biomarker in these cancers. Citation Format: Tabata Alves Domingos, Roberto Bonfim Pimenta Peixoto, Rodrigo Fonseca Abreu, Ashka Patel, Krishan Taneja, McKenna Moore, Celina Kleer, Deborah Dillon. EZH2 is Overexpressed in Invasive Carcinoma and DCIS in both BRCA1 and BRCA2 Mutation Carriers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-01.

Spatial distribution of non-communicable diseases; a case of Ischaemic Heart Diseases, Cancer and Diabetes in Sri Lanka

The abstract provides a comprehensive overview of the global prevalence of non-communicable diseases (NCDs) and their impact on public health, emphasizing their leading role in morbidity and mortality worldwide. It highlights the specific burden of Ischaemic heart diseases, cancers, and diabetes, with a significant portion of premature deaths occurring in low- and middle-income countries. Transitioning to Sri Lanka, the abstract underscores the country's shift towards NCDs as the primary health concern, attributing over 80% of premature deaths to these diseases. The narrative emphasizes the influence of rapid lifestyle changes and socio-economic development on the rise of NCDs in Sri Lanka and emphasizes the urgent need for comprehensive research to understand trends, patterns, and contributing factors for effective preventive measures.

Abstract PO5-16-08: Breast cancer in men: 15 years of experience in an oncology reference center in northern Mexico

Abstract Background Breast cancer in men accounts for about 1% of all breast cancers. Classic risk factors include increasing age, a family history of cancer, and mutations in predisposing genes. The alteration of the estrogen-androgen ratio has been as involved in the genesis of this cancer due to its increased risk in conditions such as liver dysfunction, obesity, marijuana use, thyroid disease, Klinefelter’s syndrome, hormonal therapies, orchitis, cryptorchidism, and testicular damage. Purpose Hereby we aim to update the analysis of the published demographic, clinical and treatment-related characteristics of this disease in our center including the last 15 years, as well as newly identified relevant variables that will serve as the basis for awareness and screening programmes for our population. Methods We performed a retrospective observational analysis of the medical records of men diagnosed with breast cancer that were treated in “Centro Universitario Contra el Cáncer” between January 2007 and December 2022. A total of seventeen cases of male breast cancer were included in the analysis. The variables included are age at diagnosis, body mass index, comorbidities, cigarette and alcohol use, method of diagnosis, histological type/grade, clinical stage, estrogen, progesterone, and human epidermal growth factor receptor-2 (HER2) receptor status, and treatment received. We also looked at the dates of symptom onset, diagnosis, and treatment to determine the intervals between these events. SPSS v25 software was used for data analysis. The Shapiro-Wilk test was employed to determine the normality of the variables. Variables with a normal distribution were described with median and interquartile range for the 25th and 75th percentiles. Categorical variables were expressed as absolute numbers and percentages. Results Although we found some similarities between the characteristics of our population and those reported in the American and European series, there were many significant differences. Mean age at diagnosis was 62.9 (±11.7) years, 5.5 years earlier than the reported age of 68.4 years. In terms of risk factors, our population was twice as likely to report a family history of cancer as the American series (41% vs. 15-20%). Overweight and obesity together accounted for 76.5% followed by alcohol consumption in 70.6% and cigarette smoking in 47.1% of patients. Diabetes mellitus and systemic arterial hypertension were present in 70% of our population. These entities are known to alter the estrogen-androgen ratio. The initial symptom in 88.2% of patients was a retroareolar tumor. The mean time from symptom onset to cancer diagnosis was 14.4 months. Estrogen and/or progesterone receptor status was positive in 82.3%. HER2 overexpression was not found. 17.6% of the cancers were classified as triple negative in contrast to the 0.3% reported in other series. Regarding treatment, 88.3% underwent upfront surgery, of which 76% were modified radical mastectomies. Axillary node dissection was performed in 86.6% of the cases and sentinel node biopsy in the rest. Seventy-six percent of patients received chemotherapy and radiotherapy in the adjuvant setting. Tamoxifen was the most common drug of choice (87.5%) in the patients considered as candidates for hormonal therapy Conclusions This study updates the results previously reported from our center with additional information that enabled new important conclusions to be drawn about our population. These findings provide the basis for a better understanding of this disease, which is necessary to establish public policies and recommendations to reduce the negative impact of this type of cancer. Table. Demographic and Clinical Characteristics of the Patients Citation Format: Fernando Peña, Javier A. Martínez-Moyano, Francisco Alvarado-Villarreal, Carlos Salazar-Mejía, David Hernández-Barajas, Oscar Vidal-Gutiérrez. Breast cancer in men: 15 years of experience in an oncology reference center in northern Mexico [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 PO5-16-08.

Abstract PO5-20-10: Treatment with CDK4/6 Inhibitor in a Patient with Metastatic Breast Cancer Causing Myelophthisis

Abstract Background: Symptomatic bone marrow metastasis causing myelophthisis is a rare manifestation of metastatic breast cancer, indicating a poor prognosis due to significant cytopenias. CDK4/6 inhibitors are first-line therapies for metastatic hormone-positive breast cancer but remain an unclear choice in breast cancer patients with significant cytopenias due to associated hematological adverse effects. We present a case of biopsy-proven hormone-positive breast cancer with bone marrow infiltration causing profound pancytopenia. CDK4/6 inhibitors were safely administered despite their cytopenic effects. Case Presentation: A 59-year-old female presented after an abnormal annual mammogram and biopsy showed calcifications stromal fibrosis, cyst formation, and usual ductal hyperplasia in the right upper outer quadrant. One month later, she presented to an outside hospital with gingival bleeding, epistaxis, progressive dyspnea on exertion, and generalized weakness. Labs showed severe anemia with a hemoglobin of 4.8 g/dL (baseline 12.1 g/dL), thrombocytopenia with platelets of 5 K/mm (baseline 215 K/mm), LDH of 879, reticulocyte count of 5%, and negative direct Coombs test. Peripheral smear showed no schistocytes, but showed nucleated RBCs, severely reduced platelets, and occasional giant platelets. The patient was treated for presumed ITP, and the presence of nucleated RBCs prompted bone marrow biopsy which confirmed metastatic invasive lobular carcinoma breast cancer (ER 90-95%, PR 90-95%, HER2 1+). She was discharged on letrozole 2.5 mg daily with close outpatient oncologic follow-up. One week later, she presented to our institution with persistent symptomatic anemia and thrombocytopenia. Inpatient systemic therapy was begun using dose-reduced Palbociclib (75mg) and letrozole with close CBC monitoring while also receiving packed red blood cells (goal >6.5) and platelet transfusions (goal >10). Repeat bone marrow biopsy showed extensive marrow fibrosis, but no significant hematopoietic elements. ADAMTS13 was 134%, ruling out TTP, and she was treated again for presumed ITP with dexamethasone and IVIG, Throughout the 4-week admission, her right breast mass decreased in size and she was discharged after completing 3 weeks of Palbociclib with biweekly outpatient transfusions. During follow-up, the patient’s hemoglobin and platelets slowly started to respond allowing her to become transfusion-independent and allowing dose escalation. Restaging scans 2 months after hospitalization showed an overall improvement of disease burden. The patient continued to do well for almost 18 months, however, later redeveloped visceral crisis and is responding to chemotherapy. Discussion: There is limited data on the management of breast cancer with bone marrow infiltration at presentation. A wide range of survival data in different case reports exists, ranging from 5 to 44 months. However, chemotherapy was used in these studies rather than CDK4/6 inhibitors. By far, cytopenias are the most concerning grade 3 and 4 side effect of Palbociclib. Data from the PALOMA-1 trial suggest that hematologic toxicities, specifically neutropenia, were different from those associated with cytotoxic chemotherapies and are more transient and reversible in nature. Studies have examined the in vitro mechanism of bone marrow suppression in Palbociclib versus cytotoxic chemotherapy, and its cytostatic effect on neutrophil precursors allows for hematological toxicities to be transient. With strong supportive care measures, patients in bone marrow visceral crisis can be safely treated with cytopenic CDK4/6 inhibitors. Citation Format: Nikita Dahake, Jordan Senchak, Jalil Nasibli, Jason Incorvati. Treatment with CDK4/6 Inhibitor in a Patient with Metastatic Breast Cancer Causing Myelophthisis [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 PO5-20-10.