Clinical Pathological Features Research Articles

Treatment of renal leiomyosarcoma with right atrial tumor embolus without cardiopulmonary bypass: a case report

ObjectiveTo investigate the clinical manifestations, imaging and pathological features, treatment methods and prognosis of primary leiomyosarcoma of kidney, and the choice of treatment with tumor thrombus.MethodsThe clinical data of a patient with primary renal leiomyosarcoma complicated with inferior vena cava and right atrial tumor thrombus were retrospectively analyzed. Radical resection of right kidney without cardiopulmonary bypass and removal of inferior vena cava and right atrial tumor thrombus were performed. Adjuvant intravenous chemotherapy was given according to the results, and follow-up observation was made.ResultsPostoperative pathological findings were: leiomyosarcoma (right renal tumor), the size of the mass was about 12.1 cm, and no cancer was found at the incision end of the right ureter.ConclusionPrimary leiomyosarcoma of kidney is rare in clinical practice, and complication of right atrial tumor embolus is even rarer. The disease has high malignant degree and poor prognosis. The clinical manifestations and imaging examinations were non-specific, and pathological diagnosis was the gold standard. Radical surgical resection is the main treatment method at present, and it provides experience for the treatment of grade IV tumor thrombus without cardiopulmonary bypass.

Risk factors for acute kidney injury and kidney relapse in patients with lupus podocytopathy

Abstract Background Patients with lupus podocytopathy show a high incidence of acute kidney injury (AKI) and relapse, but the risk factors and mechanisms were unclear. This study analyzed the clinical-pathological features, and risk factors for AKI and relapse in lupus podocytopathy patients. Methods The cohort of lupus podocytopathy was generated by screening the biopsies of patients with lupus nephritis (LN) from 2002 to 2022, and was divided into the mild glomerular lesion (MGL) and FSGS groups based on glomerular morphological characteristics. The acute (ATI) and chronic (CTI) tubulointerstitial lesions were semi-quantitatively scored. Logistic and Cox regression was employed to identify the risk factors for AKI and relapse, respectively. Results Among 6 052 LN cases, 98 (1.6%) were diagnosed as lupus podocytopathy, with 71 in the MGL group and 27 in the FSGS group. All patients presented with nephrotic syndrome, and 33 (34.7%) of them had AKI. Seventy-seven (78.6%) patients achieved complete renal response (CRR) within 12 weeks of induction treatment, in which there was no difference in CRR rate between glucocorticoid monotherapy and combination therapy with glucocorticoids plus immunosuppressants. Compared to the MGL group, patients in the FSGS group had significantly higher incidences of hypertension and hematuria; in addition, they had higher SLEDAI-2 K, ATI and CTI scores, but a significantly lower CRR rate. Urinary protein ≥ 7.0 g/24 h and serum C3 ≤ 0.750 g/L were independent risk factors for AKI. During a median follow-up of 78 months, 57 cases (60.0%) had relapse, and none reached the kidney endpoint. Failure to achieve CRR within 12 weeks, maintenance with glucocorticoid monotherapy and AKI at onset were independent risk factors for the kidney relapse. Conclusions In this study, histological subtypes of lupus podocytopathy are found to be associated with clinical feature and treatment response;in addition, several risk factors associated with AKI occurrence and kidney relapse are identified.

Correlation between CEUS LI-RADS categorization of HCC < 20 mm and clinic-pathological features

ObjectiveTo retrospectively evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) LI-RADS in liver nodules < 20 mm at high risk of hepatocellular carcinoma (HCC) and their correlation with clinic-pathological features.MethodsA total of 432 pathologically proved liver nodules < 20 mm were included from January 2019 to June 2022. Each nodule was categorized as LI-RADS grade (LR)-1 to LR-5 through LR-M according to CEUS LI-RADS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of CEUS LI-RADS were evaluated using pathological reference standard. Correlations between clinic-pathological features and CEUS LI-RADS categorization, together with major CEUS features, were further explored.ResultsWith LR-5 to diagnose HCC, the sensitivity, specificity, PPV, NPV, and AUC were 50.3%, 70.0%, 91.2%, 18.5%, and 0.601, respectively. The proportion of LR-5 in primary HCCs was significantly higher than that in recurrent ones (p = 0.014). HCC 10–19 mm showed significantly more frequent arterial phase hyper-enhancement (APHE) and late washout (p < 0.05) and less no-washout (p = 0.003) compared with those in HCC < 10 mm. Well-differentiated HCCs showed more frequent non-APHE and no-washout than moderate- and poor-differentiated HCCs (p < 0.05). Upgrading “APHE without washout” LR-4 nodules 10–19 mm with HCC history and “APHE with late mild washout” LR-4 nodules < 10 mm to LR-5 could improve the diagnostic performance of LR-5. The corresponding sensitivity, specificity, PPV, NPV, and AUC are 60.2%, 70.0%, 92.6%, 22.1%, and 0.651, respectively.ConclusionsCEUS LI-RADS is valuable in the diagnosis of HCC < 20 mm and performance can be improved with the combination of clinic-pathological features.Critical relevance statementCEUS LI-RADS was valuable in the diagnosis of HCC < 20 mm and its diagnostic performance can be improved by combining clinic-pathological features. Further research is needed to define its value in this set of lesions.Key PointsContrast-enhanced ultrasound can detect small liver lesions where LI-RADS accuracy is uncertain.Many LI-RADS Grade-4 nodules were upgraded to Grade-5 by combining imaging with clinic-pathological factors.The reclassification of LI-RADS Grade-5 can improve sensitivity without decreasing positive predictive value.Graphical

Abstract PO1-02-02: Update of RSClin with extended TAILORx follow-up and development and validation of a new tool for risk of late distant recurrence

Abstract Background: RSClin® (Sparano et al J Clin Oncol 2020, PMID 33306425) is an educational tool that estimates the 10-year risk of distant recurrence (DR) and the absolute benefit of chemotherapy in HR-positive, HER2-negative, node-negative early breast cancer. The RSClin tool integrates the Recurrence Score® (RS) result with the clinical-pathological features tumor grade, tumor size and patient age using patient-specific meta-analysis (PSMA) applied to the NSABP B-14, TAILORx and NSABP B-20 studies. Approximately 3 years of additional follow-up data have accumulated in the TAILORx study since the RSClin tool was developed, including 50% more DR events in the RS 11-25 group (375 vs. 250), and 46% more DR events in the overall population (561 vs. 384). Methods: The RSClin tool estimates were updated to include the extended follow-up data from TAILORx. As before, the PSMA included 10,004 women with hormone-receptor positive, HER2-negative, node-negative breast cancer from the NSABP B-14 (n=577) trial receiving endocrine therapy (ET) alone and the TAILORx trial receiving ET alone (n=4854) or chemotherapy (CT) plus ET (n=4573). The baseline risk estimate used TAILORx event rates with ET alone. Since there was evidence of differing hazard ratios in years 0-5 versus 5+, models using time-varying effects were used. A patient-specific estimator of absolute CT benefit was computed by combining a PSMA estimate of the individualized relative CT effect from the TAILORx and NSABP B-20 (n=550 HER2-negative) trials with risk estimates for ET alone. Similar methods were used to develop and validate a new tool for assessing the risk of late DR (from year 5 to 10) in patients who survive DR-free for 5 years on ET alone after surgery. External validation of DR risk estimation was performed in an independent cohort of 1098 women enrolled in the Clalit Health Service registry. Results: With the updated data, the model integrating RS result with clinical-pathological features was more informative for DR risk than either RS result alone or the clinical-pathological features alone, both for 10-year DR risk and for late DR risk (likelihood ratio tests, each p≤.001). The updated 10-year RSClin risk estimates are similar to the existing RSClin tool risk estimates with slightly lower risk estimates for very high RS results and more precise estimates for mid-range RS results. The updated chemotherapy effect estimates are slightly lower than for the existing RSClin. The updated RSClin tool 10-year risk estimates were strongly associated with DR risk in the independent Clalit registry (Cox regression p&amp;lt; .001) and closely approximated the observed DR risk (Lin concordance 0.87). The new tool’s late DR risk estimates beyond 5 years were strongly associated with late DR risk in the Clalit registry (Cox regression p=.002) and closely approximated the observed late DR risk (Lin concordance 0.92). Conclusions: The RSClin tool 10-year DR risk estimates have been updated to incorporate extended follow-up data from the TAILORx study. A new tool for assessing late DR risk has been developed and validated that provides more prognostic information than either clinical-pathological features or genomic risk used individually. Citation Format: Joseph Sparano, Michael Crager, Robert Gray, Gong Tang, Jess Hoag, Frederick Baehner, Charles Geyer, Steven Shak, Norman Wolmark, Salomon Stemmer. Update of RSClin with extended TAILORx follow-up and development and validation of a new tool for risk of late distant recurrence [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 PO1-02-02.

Abstract PS09-06: Tumor infiltrating lymphocytes as a predictor of pathologic complete response to neoadjuvant therapy in HER2 positive breast cancer

Abstract Background The presence of tumor infiltrating lymphocytes (TILs) has shown positive prognostic relevance for certain subtypes of breast cancer, although its value as a predictive biomarker is still uncertain. The purpose of this study was to study the association between TILs expression with the pathologic complete response (pCR) following neoadjuvant therapy in Mexican patients with HER2+ breast cancer. Methods Retrospective cohort of patients with stage I-III HER2+ breast cancer who received neoadjuvant therapy between 2017 and 2020 at Instituto Nacional de Cancerología (INCan). We collected demographic and clinico-pathological characteristics. Stage was assigned using AJCC 7th criteria; hormone receptor (HR) and HER2 status were determined according to ASCO-CAP guidelines. Quantification of TILs was made by microscopy and stained with hematoxylin-eosin. TIL levels were defined as low (1-10%) intermediate (11-40%) and high ( &amp;gt;40%). Complete pathologic response was defined as the absence of invasive disease in breast and axilla (ypT0/is N0). pCR rates were compared using X2 and Fisher's exact tests according to demographic and clinicopathologic characteristics. Univariate logistic regression analysis was performed to estimate the probability of pCR according to relevant characteristics. Those parameters with p ≤0.10 on univariate analysis were included in a multivariate logistic regression model. A p&amp;lt; 0.05 was considered as statistically significant. Results We included 164 patients (mean age 51.0 years, SD 11.4). 86 patients (54.1%) were postmenopausal, 75 patients (47.2%) had T3-T4 tumors, 129 patients (81.1%) had positive lymph nodes, 133 patients (83.6%) presented Ki67 ≥30%, 59 patients (37.1%) had negative hormone receptors, 136 patients (85.5%) were treated with anthracyclines and 20 patients (12.6%) received dual anti-HER2 therapy with trastuzumab/pertuzumab. TIL expression was low in 84 patients (52.8%), intermediate in 47 (29.6%), and high in 28 patients (17.6%). The pathologic complete response (pCR) rate in the overall population was 50.9%. pCR rates according to the demographic and clinico-pathological features are listed in Table 1. In patients with intermediate-high TILs, pCR rates were 73.1% with trastuzumab, and 75.0% with dual HER2 blockade (p=0.91). Among patients with low TILs, pCR rates were 23.6% and 75.0%, respectively (p &amp;lt; 0.001). On univariate analysis, intermediate TILs (OR 3.59; 95% C.I 1.70-7.59; p= &amp;lt; 0.001), high TILs (OR 29.00; 95% C.I 6.40-131.37; p= &amp;lt; 0.001), Ki67 ≥30% (OR 2.73, 95% C.I 1.11-6.73; p=0.02), and dual anti-HER2 therapy (OR 3.31; 95% C.I 1.14-9.63 p= 0.021) were associated with a higher probability of pCR. T3/T4 tumor size (OR 0.43; 95% C.I 0.22-0.81; p = 0.009) was associated with a lower probability of pCR. Positive lymph nodes, HR status , and use of anthracyclines were not significantly associated. On multivariate analysis, intermediate TILs (OR 3.28; 95% C.I 1.46-7.32 p=.004), high TILs (OR 32.37; 95% C.I 6.84-153.04 p= &amp;lt; 0.001), and dual anti-HER2 therapy (OR 6.58; 95% CI 2.01-21.47 p= .002) remained significantly associated with pCR. Conclusions Intermediate/high TIL expression was significantly associated with pCR. Our results suggest that TIL expression could help select patients with locally advanced HER2+ breast cancer for treatment intensification with dual HER2 blockade in resource-limited settings. However, these findings require confirmation in larger, prospective studies before implementation into routine practice. TABLE 1. Pathologic complete response (pCR) rates according to demographic and clinical pathological features (n=164). Citation Format: Alberto Monroy Chargoy, Haydee Cristina Verduzco-Aguirre, Javier Monroy Chargoy, Jose Rodrigo Espinosa-Fernandez, Jesus Antonio Martinez Ojeda, Paula Cabrera-Galeana. Tumor infiltrating lymphocytes as a predictor of pathologic complete response to neoadjuvant therapy in HER2 positive 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 PS09-06.

Abstract PO1-15-06: Serum thymidine kinase activity as a “real-time” clinical biomarker of tumor response to CDK4/6 inhibition in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer

Abstract Background: CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) are standard first-line (1L) treatment for hormone receptor positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC). Despite general improvements in long-term outcome, not all patients benefit equally from these drugs. The average duration of 1L CDK4/6i therapy is ~2 years. However, 10-15% of patients will progress within 6 months of therapy initiation, while others will derive durable clinical benefit of years. Differences in treatment efficacy cannot be easily explained by clinical-pathological features. No predictive biomarkers are currently available to determine tumor sensitivity to CDK4/6i. There is an unmet need for a complementary diagnostic to identify patients that will or will not respond to these treatments in order to better inform therapy management. Thymidine kinase (TK) is an E2F-regulated enzyme that plays a key role in DNA replication during cell division. The expression and activity of TK is strongly linked to the cell cycle. TK is first expressed in late G1, peaks during S-phase, and then is degraded during mitosis. Because of the restricted expression of TK (only during S phase of the cell cycle) combined with the mechanism of action of CDK4/6i, the measurement of TK activity (TKa) may serve as an ideal pharmacodynamic biomarker to assess a tumor’s response to CDK4/6i-based therapy. DiviTum® TKa is an FDA cleared assay that can quantitate TKa from human serum (sTKa) and is intended to be used as a disease progression monitoring tool for patients with HR+, HER2- MBC. TK IMPACT is a prospective, single arm trial designed to assess the impact of incorporation of DiviTum® TKa on the physician’s decision regarding subsequent timing of routine disease monitoring modalities in patients with advanced HR+, HER2- MBC receiving 1L ET plus CDK 4/6i (NCT04968964). As a part of this ongoing study, DiviTum® TKa values are serially assessed relative to imaging findings and other circulating tumor biomarkers, such as CA15-3 and ctDNA. The primary endpoint is any physician-reported intended change in imaging testing interval post TKa by study cohort, within the first 48-week period of study participation, assessments for which are ongoing. Here we report real-world data and examples of the clinical utility of sTKa as a companion diagnostic from patients treated at Washington University Siteman Cancer Center, St. Louis, MO. Methods: Patients with HR+, HER2- MBC receiving 1L ET + any FDA-approved CDK 4/6i (palbociclib, ribociclib, or abemaciclib) had blood serum samples collected at baseline, weeks 2, 4, 6, 8, every 4 weeks up to week 24, and then every 12 weeks thereafter until disease progression. Samples were analyzed for TKa levels in real-time using the DiviTum® TKa assay. Optional repeat TKa within 2-4 wks (+/- 3 days) is permitted in case of rising TKa. Other standard monitoring assessments were carried out according to institutional guidelines and/or treating clinician discretion. Results: Pre-treatment and early on-therapy TKa levels predicted response to CDK4/6i therapy more accurately than a patient’s clinical characteristics. Rising TKa levels also identified patients with clinically occult disease progression ahead of imaging, and in some cases where radiographic interpretation and serum tumor markers such as CA15-3 were ambiguous. Measurement of TKa levels following CDK4/6i dose reduction was able to confirm continued optimal therapy response at the lower dose. A rise in TKa levels aligned with the re-emergence of ESR1 mutation as identified by ctDNA in one patient and may herald molecular progression. Conclusion: sTKa was able to predict tumor sensitivity and resistance (both intrinsic and acquired) to CDK4/6i + ET therapy in patients with HR+, HER2- MBC. We believe these findings help support the role of sTKa as a non-invasive pharmacodynamic biomarker that can assess in real-time a tumor’s response to CDK4/6i based therapy. Citation Format: Nusayba Bagegni, Amy Williams, Isabella Grigsby, Mattias Bergqvist, Katherine Clifton, Cynthia Ma. Serum thymidine kinase activity as a “real-time” clinical biomarker of tumor response to CDK4/6 inhibition in hormone receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-06.

Abstract PO4-03-07: The impact of chemotherapy relative dose intensity on pathological complete response in patients with triple negative breast cancer treated with neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NACT) is the preferred treatment approach for early-stage triple negative breast cancer (TNBC). Achieving pathologic complete response (pCR) after NACT is associated with improved event-free survival and overall survival in patients with TNBC. Major research efforts have been deployed to identify predictive biomarkers for pCR in TNBC. However, the values of chemotherapy (CT) relative dose intensity (RDI) in predicting pCR remain unclear. Methods: A retrospective analysis was conducted among 96 consecutive patients with early stage TNBC who received NACT between February 2018 and January 2023 at the University of Naples Federico II (Naples, Italy). Patients’ demographics, clinical-pathological features, and type of CT schedules were retrieved from electronic medical records. pCR was defined as the absence of residual invasive or in situ carcinoma in primary tumor and/or lymph nodes, upon chemotherapy administration. RDI was calculated as the ratio of delivered to planned CT dose intensity. RDI was defined as low if &amp;lt; 85% or high if ≥85%, respectively. Univariate and multivariate logistic regression were used to evaluate the association between age, tumor stage, RDI, CT regimen dose type, and pCR. Results: All patients were included in the analysis. Median age at diagnosis was 51 years (range 28-75). Sixty-five (68%) and 31 (32%) patients were diagnosed with stage II and stage III TNBC, respectively. Nineteen (19%) patients received a sequential schedule of anthracycline plus cyclophosphamide (AC) and a taxane (T). Sixty-one (64%) patients received AC followed by concurrent carboplatin-paclitaxel (CaP). Sixteen (17%) patients received the anti-PD1 pembrolizumab in addition to ACCaP chemotherapy backbone (ACCaP-Pem). Fifty-four (56%) patients received a dose-dense AC-based CT. A pCR was achieved in 59 (61%) patients. Interestingly, patients who received a dose-dense AC based neoadjuvant CT had higher chance to achieve a pCR compared with those treated with a non dose-dense AC based CT (70% vs 46%, p = 0.03). Overall, 79 (82%) and 17 (18%) patients received a RDI high and RDI low CT, respectively. No difference in terms of age, body mass index, performance status, tumor stage, type of chemotherapy was observed between the two groups (Table 1). At univariate analysis RDI high (OR 5.18, 95%CI: 1.65-16.31, p=0.005) and dose dense AC-based CT (OR 2.42, 95%CI: 0.18-0.97, p=0.04) were significantly associated with pCR. In a multivariate model including RDI, age, tumor stage, and AC regimen dose type, RDI was the only variable independently associated with pCR (OR 4.60, 95% CI: 1.40-15.06, p = 0.01). Conclusion: A chemotherapy RDI≥ 85% independently predicts pCR in early stage TNBC patients treated with standard NACT. In our cohort, one in five patients received a suboptimal chemotherapy dose intensity affecting at least in part tumor response. Studies with larger TNBC patient populations are warranted to confirm the impact of RDI on pCR and long-term outcomes. Table 1 Citation Format: Roberto Buonaiuto, Giuseppe Neola, Aldo Caltavituro, Paola Trasacco, Federica Pia Mangiacotti, Giovanna Pecoraro, Matteo Lambertini, Erica Pietroluongo, Pietro De Placido, Sabino De Placido, Valeria Forestieri, Mario Giuliano, Grazia Arpino, Carmine De Angelis. The impact of chemotherapy relative dose intensity on pathological complete response in patients with triple negative breast cancer treated with neoadjuvant chemotherapy [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 PO4-03-07.

Abstract PO5-03-10: The prognostic role of androgen receptor status in patients with triple negative breast cancer with an associated ductal carcinoma in situ

Abstract Abstract Background Triple negative breast cancer (TNBC) is defined by the lack of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Prognostic immunohistochemical biomarkers in TNBC have been studied in recent years such as the androgen receptor (AR) which is expressed in 10-40% of TNBC. However the prognostic value of AR expression is not clear. Here, we studied the prognostic significance of AR expression in combination with the presence of a ductal carcinoma in situ (DCIS). Considering DCIS is a precursor of invasive ductal carcinoma, we hypothesize that TNBC with co-existing DCIS and presence of AR expression is less aggressive and patients are older at diagnosis. Methods We analyzed data retrospectively from all patients with stage 1-3 TNBC who underwent primary surgery and adjuvant chemotherapy in the University hospitals Leuven, between 01-01-2000 and 31-12-2017. Patient and tumor related characteristics were compared between two subgroups, one with co-existing DCIS and one with pure invasive carcinoma, without co-existing DCIS. AR expression was assessed by immunohistochemistry (IHC). We used AR expression in ≥1% and ≥10% of cells as cut-off scores. The prognostic role of the expression of AR in combination with a co-existing DCIS was analyzed, using the distant metastasis rate as primary endpoint. Results are presented as hazard ratios (HR) with 95% confidence intervals (CI). Secondary endpoints were associations of AR expression with clinical-pathological characteristics, time between diagnosis and metastasis, and disease specific mortality. Results In the 426 included patients with TNBC, co-existing DCIS was present in 66.7%; AR expression was expressed ≥1% in 29.3% and ≥10% in 21.4% of cases. Median age at diagnosis was 51 years (range: 22-85y). Age at diagnosis was independent of DCIS, dependent of AR expression; in DCIS positive cases, median age was 49 years if AR negative (IHC &amp;lt; 1%), 53 years if AR positive (IHC ≥1%), and 56 years if AR positive (IHC ≥10%) (p=0.006). In contrast in DCIS negative cases, median age was 51 years if AR negative (IHC &amp;lt; 1%), 51 if AR positive (IHC ≥1%), and 51 years if AR positive (IHC ≥10%) (p=0.895). AR expression was DCIS dependent and was ≥1% in 34.9% and ≥10% in 25.0% of patients in the DCIS group compared to 18.3% and 14.1% in the non-DCIS group (p=0.001 and p&amp;lt; 0.001 respectively). In both subgroups there was no significant difference for AR positive versus AR negative cases in lymph node involvement, tumor grade, tumor size and Nottingham Prognostic Index. Patients with a coexisting DCIS and AR expression did not have a different incidence of distant relapse compared to AR negative cases (AR ≥1%: p=0.2803 and AR ≥10%: p=0.5527). Of patients with coexisting DCIS, 12.0% (95% CI: 7.8; 17.1) in the AR negative group, 8.2% (95% CI: 3.8; 14.6) in the AR ≥ 1% group and 7.1% (95% CI: 2.6; 14.7) in the AR ≥ 10% group, had distant relapse within 2 years. Conclusion In patients with TNBC, AR expression is associated with older age in case of co-existing DCIS and patients with co-existing DCIS are more frequently AR positive. In patients with co-existing DCIS, there was no significant difference in distant relapse between AR negative and AR positive cases. Citation Format: Micaëlle Merckx. The prognostic role of androgen receptor status in patients with triple negative breast cancer with an associated ductal carcinoma in situ [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 PO5-03-10.

Abstract PO5-09-04: Oncotype DX Breast Recurrence Score® analysis in early-stage breast cancer associated with CHEK2, ATM and PALB2 germline pathogenic variants

Abstract Background: The 21-gene assay (Oncotype DX Recurrence Score, RS) is the only clinically validated assay to determine the prognosis in hormone-positive, HER2-negative breast cancer (BC) patients treated with endocrine therapy alone by predicting locoregional and distant recurrence. Outcomes of Oncotype RS in BRCA-associated BC has been studied previously, but the results of RS analysis in BC patients with the other BC susceptibility genes have not been documented. This study evaluates the clinical and pathological characteristics of BC patients with ATM, CHEK2 and PALB2 germline pathogenic variants (PV). Methods: Patients with invasive hormone-positive, HER2-negative BC who have had Oncotype DX Breast Recurrence Score® testing and who underwent genetic testing in the Breast Medical Oncology and the Breast Clinical Cancer Genetics Clinic at the University of Texas MD Anderson Cancer Center (MDACC) were identified from the prospectively maintained research database. Clinical and tumor characteristics were analyzed using descriptive statistics. Results: Between 1996 and June 2023, 5652 patients with Oncotype RS were included in this analysis. Amongst those 828 BC patients had genetic testing and 81 patients were found to have a pathogenic variant: 17 patients with a CHEK2 mutation, 10 patients with an ATM mutation, and 18 patients with a PALB2 mutation. Among patients with CHEK2 PV, median Oncotype RS was 17 (5–32) overall, 21 (13–32) for patients age &amp;lt; 50, and 14.5 (5–28) for patients age ≥50 (p= 0.2). Among patients with ATM PV, median RS was 16.5 (3–54) overall, 25 (10–54) for patients age &amp;lt; 50, and 14.5 (3–29) for patients age ≥50 (p= 0.19). Among patients with PALB2 PV, median RS was 26.5 (15–40) overall, 20 (15–40) for patients age &amp;lt; 50, and 31 (26–37) for patients age ≥50 (p= 0.012). Further patient and tumor characteristics are shown in Table 1. Conclusion: This is a single-institutional cohort of hormone-positive, HER2-negative BC patients who had Oncotype RS and who underwent genetic testing. Further analysis on clinical and tumor pathological characteristics and long-term outcome is ongoing. Table1. Patient and tumor characteristics Citation Format: Fatma Akkoc Mustafayev, Angelica Gutierrez Barrera, Diane Liu, Banu Arun. Oncotype DX Breast Recurrence Score® analysis in early-stage breast cancer associated with CHEK2, ATM and PALB2 germline pathogenic variants [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-04.

[Analysis of clinical characteristic of children with progressive familial intrahepatic cholestasis type 3].

Objective: To analyze the clinical manifestations, pathology, and gene variant characteristics in children with progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods: This retrospective study assessed the clinical manifestations, pathological features, gene variants, and prognosis data of 11 children with PFIC3 hospitalized in the Department of Hepatology, Fifth Medical Center, PLA General Hospital, from January 2015 to December 2022. Panel or whole exome sequencing was performed on the probands, followed by Sanger sequencing for verification within the family. Detected pathogenic variants were compared with known disease databases. Additionally, the new variants were predicted the deleteriousness and protein structure using relevant software to evaluate their pathogenicity. Results: Among the 11 PFIC3 children, 8 were boys and 3 were girls. The age of onset was 3.1 (0.2, 15.6) years. The main complaint of onset was different in the 11 patients;5 of them were abnormal liver function, 3 of them were liver and spleen enlargement, 2 of them were abdominal distension, and 1 of them was jaundice. Alanine aminotransferase, asparate aminotransferase and γ-glutamyltransferase increased in all the patients, which were(113±40), (150±44) and (270±156) U/L respectively. Moreover, direct bilirubin increased in 9 patients, and cholestasis was showed in 8 patients. All patients showed liver fibrosis on imaging, and 8 patients had cirrhosis. The pathological features of 8 cases by liver biopsy were as follows: 8 cases of fibrosis in the portal area, 7 cases of small bile duct hyperplasia, 4 cases of positive copper staining, and 5 cases of cirrhosis. A total of 17 ABCB4 gene variants were detected, including 9 new variants: c.589C>T(p.Q197X), c.1230+1G>A(Splicing), c.2914G>A(P.D972N), c.1058G>A(p.C353Y), c.956G>T(p.G319V), c.473T>A(p.L158Q), c.164T>C(p.L55S), c.2493G>C(p.R831S), and c.1150G>C(p.G384R). All 11 patients were treated with ursodeoxycholic acid and followed up for 5.1(0.6, 7.4) years. Among them, 4 cases of cirrhosis progressed continuously, 3 cases had liver transplantations, and the remaining 4 cases were stable after medical treatment. Conclusions: Children with PFIC3 have early onset, diverse clinical manifestations, rapid progression of fibrotic and cholestasis, as well as poor prognosis. Genetic testing helps to confirm the diagnosis.

Abstract PO1-16-02: Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC)

Abstract Background: Circulating Tumor Cells (CTC) can be isolated in 40-80% of patients with metastatic breast cancer (MBC). High levels of CTC, defined as ≥5/7.5 ml of blood are associated with shorter progression-free survival and overall survival. CTC can be tested for clinically relevant biomarkers, such as ER, and HER2 status, and have the potential to guide therapy as well as help with disease monitoring. We investigated CTC detection rate, its correlation with clinical characteristics, pathological characteristics, and response to treatment in patients with any type of metastatic breast cancer who progressed on at least one line of therapy. Methods: Eligible patients with MBC were enrolled in the IMAGE-II study (Individualized Molecular Analyses Guide Efforts in Breast Cancer) NCT02965755, in which we obtained archival tissue as part of the standard of care, and prospectively collected serial blood samples for CTC analysis. We compared CTC levels and biomarker status with clinical factors, tissue-based pathology, and molecular biomarkers. We assessed whether changes in CTC count correlated with treatment response. Blood samples were collected at baseline (Day 1), after 1-2 weeks of therapy, after 8-12 weeks, and at subsequent restaging (every 8-12 weeks). Medical records were reviewed every 3 months for ongoing treatment response, and death. Samples were processed at the Biocept CLIA-certified Laboratory. CTC were enumerated by the presence of CD45- and DAPI+ cells. Further CTC characterization was performed by antibody staining of specific protein biomarkers (ER, HER2). Fisher’s exact test was used to evaluate the association between baseline CTC &amp;lt; 5 and ≥5/7.5ml with patient characteristics. McNemar’s test was used to assess discordance between tissue-based and CTC-defined markers. Results: Between 1/26/2018 and 12/31/22 baseline samples were collected from 70 women with a median age of 56 (36-82) who were enrolled at four study sites. CTC was detected in 59 (84%) of participants. Baseline CTC counts were &amp;lt; 5/7.5 ml in 37/59 (63%) and ≥5/7.5 ml in 22/59 (37%) of participants. Differences between breast cancer subtype and CTC-receptor status were observed (Table 1). Among the 41 patients who were ER-positive, 31 (76%) were CTC ER-negative(p&amp;lt; 0.001). Among 29 patients who were ER-negative, 4 (14%) were CTC ER-Positive (P&amp;lt; 0.001). Among the 7 patients who were HER2 positive, 2(29%) were HER2 positive on CTC. Among 63 patients who were HER2 negative, 7(11%) had HER2 expression on their CTC. The discordance in the classification of HER2 wasn't statistically significant (p=0.77). Elevated CTC at baseline was more frequently detected in younger participants (&amp;lt; 50 years old) (55% vs 27%; P=0.22), in Black women compared to White (60 % vs 29 %, P=0.27), and in participants with visceral vs non-visceral metastasis (52% vs 28 %, P=0.40). Patients with CTC ≥5 vs &amp;lt; 5/7.5mL at baseline had a shorter duration of anti-HER2-based therapy (61.5 vs 836 days, p=0.04). There were no statistically significant differences among participants who received chemotherapy agents (316.5 vs 365.5 days, P=0.88), endocrine therapy (376 vs 490 days, P=0.89), or overall therapy (272 vs 390 days, P=0.21). Conclusions: We observed significant differences in the expression of ER between tumor tissue and CTC, which can be partly due to tumor evolution over time. Additionally, participants who are young, Black, and those who have visceral metastasis may have higher CTC counts. Higher CTC counts were associated with a shorter duration of anti-HER2 therapy. Although it didn’t meet statistical significance, a similar trend was observed in patients who received chemotherapy and endocrine therapy. Table 1: MBC Tissue-Based Subtype and CTC-receptor status at baseline Citation Format: Asnakech Bayable, Tingchang Wang, Amanda Blackford, Jessica Tao, Jenna Canzoniero, Seoho Lee, Faith Too, Barbara Blouw, Mary Wilkinson, Rima Couzi, Antonio Wolff, Christie Hiton, Ben Park, Vered Stearns, Cesar Santa-Maria. Correlation of Circulating Tumor Cells (CTC) with Clinical Characteristics, Pathological Factors, and Treatment Response in Patients with Metastatic Breast Cancer (MBC) [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 PO1-16-02.

Abstract PO5-04-01: Inetetamab combined with sirolimus and chemotherapy in HER2 positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR pathway after trastuzumab treatment

Abstract Objective: To explore the efficacy and safety of Inetetamab Combined with Sirolimus and Chemotherapy in the treatment of human epidermal factor receptor 2 (HER2) positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR (PAM) pathway after Trastuzumab treatment. Methods: This prospective multicenter clinical study enrolled HER2 positive metastatic breast cancer patients at the National Cancer Center in China from July 2021 to September 2022 with PAM pathway mutation confirmed by histology or peripheral blood genetic testing. The inclusion criteria included: 1) Recurrent and metastatic breast cancer patients with HER2 positive confirmed histologically; 2) ECOG PS score ≤ 2; 3) Patients who have progressed after previous treatment with Trastuzumab; 4) Patients with PAM pathway mutation confirmed by Genetic testing; 5) Patients' cardiac, pulmonary, liver and bone marrow functions are basically normal; 6) Patients voluntarily sign informed consent forms. The exclusion criteria included: 1) Patients previously treated with mTOR inhibitors or pyrotinib; 2) Patients who have used chronic Corticosteroid for more than 3 months or used Immunosuppressive drug within 4 weeks; 3) Patients with symptomatic central nervous system metastasis; 4) Patients with left ventricular Ejection fraction&amp;lt; 50% or clinical manifestations of obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency, and severe valvular disease; 5)Diagnosed with other malignant tumors within five years. Patients were randomly divided into trial group and control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, and control group received pyrotinib and chemotherapy. RECISTv1.1 standard was used to evaluate the efficacy of patients. Descriptive statistics are used to summarize clinical pathological features. Kaplan Meier method was used to draw survival curves. Log-rank test was used to compare progression free survival (PFS) differences between groups. P&amp;lt; 0.05 was considered statistically significant. Results:A total of 59 HER2 positive metastatic breast cancer patients with abnormal activation of PAM pathway were included, of which 37 patients received the treatment of inetetamab group and 22 patients received the treatment of pyrotinib group. The median follow-up time was 5.33 months. In the intent-to-treat set, the median PFS of patients in the inetetamab group was 4.64 months, which was shorter than 5.69 months in the pyrotinib group. There was no statistically significant difference between the two groups (P=0.51; HR=0.41; 95% CI, 0.12-1.45). The objective response rate (ORR) of the inetetamab group and the pyrotinib group were 28.1% and 29.4%, respectively. In terms of safety, the incidence of adverse events (AE) in the experimental group was (33/37) 89.1%, while (16/21) 76.2% in the control group. The incidence of AE above level 3 in the inetetamab group and pyrotinib group were (13/37) 35.1% and (3/21) 14.3%, respectively. Conclusion:For the metastatic HER2 positive breast cancer patients with abnormal activation of PAM pathway treated with trastuzumab previously, the combination of inetetamab with sirolimus and chemotherapy regimen are equivalent to the combination of pyrotinib and chemotherapy regimen. It demonstrated that combination of inetetamab with sirolimus and chemotherapy could be one of the treatment options for the metastatic HER2 positive breast cancer patients. Citation Format: Qiao Li, Dan Lv, Xiaoying Sun, Mengyuan Wang, Li Cai, Feng Liu, Chenghui Li, Jiuda Zhao, Jing Sun, Yehui Shi, Fei Ma. Inetetamab combined with sirolimus and chemotherapy in HER2 positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR pathway after trastuzumab treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-01.

Abstract PO1-25-04: PTN-positive luminal progenitors induce angiogenesis and metastasis in inflammatory breast cancer

Abstract Background Inflammatory breast cancer (IBC) is a lethal subtype of breast cancer characterized by rapidly arising diffuse erythema and edema of the overlying skin that was thought to contribute to rapid metastasis. Dissecting the intricate cellular ecosystems within tumors and affected skin and their complex interplay may be pivotal in unraveling the aggressive nature of IBC. Methods Integrative analysis containing single-cell RNA sequencing, bulk RNA sequencing, and whole exome sequencing, was performed on paired tumor and skin samples from 17 treatment-naive IBC patients and 5 non-IBC patients from multiple centers. Meanwhile, paraffin sections and serum specimens from two centers were conducted to validate the omics results. Additionally, public single-cell transcriptomic data of non-IBC tumors and normal mammary glands, RNA microarray data from IBC cases, and the Cancer Genome Atlas (TCGA) database were utilized to validate the characteristics of IBC microenvironment. The regulatory mechanism was verified by in vitro experiments. Results We delineated the landscapes of IBC tumor and affected skin microenvironment at the single-cell level and demonstrated that the luminal progenitors (LP) cells highly expressing pleiotrophin (PTN) were most significantly enriched in IBC tumors compared to non-IBC tumors and normal mammary glands, in two independent cohorts. Moreover, the serum concentrations of PTN were significantly higher in IBC patients compared with non-IBC patients. Notably, PTN secreted by PTN+ LP cells interacted with Neuropilin 1(NRP1) receptor on endothelial tip cells in both tumor and affected skin of IBC. Moreover, in vitro assay demonstrated knocking down the expression of NRP1 on human umbilical vein endothelial cells significantly blocked PTN-induced migration, tube formation and sprouting, which might be independent of VEGFA. In addition, two immature phenotypes of PVL_MMP9 and PVL_CCL19 cells recruited by endothelial tip cells via PDGFB/PDGFRB axis were accumulated in affected skin of IBC, which might be associated with promotion of malignant cell metastasis. Finally, we revealed that malignant cells in affected skin of IBC had a higher ability of epithelial-mesenchymal transition than IBC intratumoral malignant cells and identified enhanced crosstalk between immature PVL cells and malignant cells in the skin affected with IBC , through TNFSF12-TNFRSF12A, TGFB-TGFBR1/TGFBR2, MDK-SDC1/4/NCL/(ITGA6+ITGB1). Conclusion We identified a unique, non-malignant epithelial cell subpopulation PTN+ LP cells, which induce massive angiogenesis via the PTN-NRP1 axis, recruit the immature phenotype PVL cells accumulated in affected skin of IBC thus promoting tumor progression. Our findings offer comprehensive insights into the pathogenesis of IBC and uncover a previously unknown, promising therapeutic target. Patient of discovery cohort details Clinical and pathology details for inflammatory breast cancer(IBC) and non-IBC patients analysed by single-cell RNA sequencing(scRNA-seq), bulk RNA sequencing(bulk RNA-seq) and whole exome sequencing(WES) in this study. Clinicalpathological feature of validation cohort Citation Format: Mengmeng Zhang, Kaiwen Zhou, Ting Liu, Filipa Lynce, Filipa Lynce, Wendy Chen, Qianjun Chen, Xiaoping Li, Zhongyu Yuan, Juan Xu, Zhenhai Cai, Jianping Guo, Nan Shao, Ying Lin. PTN-positive luminal progenitors induce angiogenesis and metastasis in inflammatory breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-25-04.

Abstract PO5-02-14: Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients

Abstract Introduction: The long-term severe adverse events associated with anthracyclines, including irreversible cardiotoxicity, myelodysplastic syndromes, and therapy-related leukemias, led researchers to question the risk-benefit of anthracycline-based chemotherapy regimens, especially for patients without axillary lymph node involvement, leading to an increasing trend to omit anthracyclines in adjuvant treatment. Docetaxel plus cyclophosphamide (TC) has replaced doxorubicin plus cyclophosphamide (AC) for lower-risk patients that need adjuvant chemotherapy. However, the optimal number of cycles of adjuvant in patients with node-positive or node-negative breast cancer is currently unknown. Methods: We performed a retrospective cohort study of patients with HER2-negative breast cancer, stage I to III, that received adjuvant docetaxel and cyclophosphamide (TC) for four or six cycles, treated from January 2010 to December 2021. Patients were included from four cancer institutions, both private and public, located in the South, Southeast, and Northeast of Brazil. Objectives: To investigate the clinical-pathological characteristics and survival of earlystage HER2-negative breast cancer patients who received four (TC4) or six cycles (TC6) of adjuvant docetaxel and cyclophosphamide (TC). Results: We collected data from six hundred and ninety-eight patients, 98.7% were female with an average age of 52 years, 51.9% were postmenopausal, 14.6% BRCA gene mutation, 66% had some comorbidity, and only 8.4% were not candidates for anthracyclines. Two hundred and twenty-five patients had public and 473 private health insurance. About 13.2% of the patients were hormone receptor negative (HR-) and 86.8% hormone receptor positive (HR+), 57.4% breast-conserving surgery and 77.7% sentinel lymph node (SL). Five hundred sixty-four (80.8%) patients received TC4 and 134 (19.2%) TC6. We observed that patients who received TC 6 had unfavorable prognostic factors such as: (TC4 vs TC6) previous breast cancer (8.7% vs 16.3%) (p=0.002), invasive ductal carcinoma (IDC) (73.4 vs 86.7%) (p=0.009), histological grade 3 (HG3) (34.9 vs 42.9%) (p= 0,085) conservative surgery (59.4% vs 53%) (p=0144), SL (80.9% vs 62.2%) (p =0.001), Lymph node positive (15% vs 42.3%) (p=0.001), pathological stage II (37.5% vs 50%) (p=0.001).Treatment completion rates were 96.5% and 84.3% for TC4 and TC6, respectively (p=0,02). The incidence of grade 3 or higher toxicity with TC6 (14% vs 21.1%; p= 0,043). Febrile neutropenia was observed in 6.7% of both groups. Grade 3 or higher neuropathy was most common with TC6 (2.2% vs 10.3%; p=0,163). Permanent treatment discontinuation was more frequent in the TC6 group (3.4% vs. 9.8%; p=0,004), as well as late toxicity (3.4% vs. 9.2%; p=0,004). Ninety-four percent of the patients completed the proposed cycles of chemotherapy, 72% received adjuvant radiotherapy and 85.4% received adjuvant hormone therapy, with 42% of these receiving an aromatase inhibitor for 5 years. The median follow-up of the entire cohort was 61 months. There was no difference in the 5-year DFS (77.5% vs. 64.7%; p=0.159) or the 5-year OS (89.5% vs. 70.5%; p= 0,06) between patients treated with TC4 and TC6. Conclusion: TC6 was commonly used for patients with unfavorable prognostic factors as history of previous breast cancer, (IDC), HG III, lymph node positive and stage II. Patients who received TC6 had less chance of completing the treatment and more severe toxicity, especially late peripheral neuropathy. There was no difference in DFS or OS. Citation Format: Mila Kraychete, Marcelle Cesca, Guilherme Almeida, Leonardo Santana, Luciana Leite, Solange M. Sanches, Vladmir Cordeiro de Lima, Rafaela Pirolli, Rafael Manea, Felipe Kaneta, Jean Coutinho, Lucas Vian, Waires Zeviani, Marcio Reis, Luciana Landeiro, Clarissa Mathias, Geila Nunez, Tamara Santana, Monique Tavares. Clinical-pathological determinant factors to choose between four or six cycles of adjuvant chemotherapy with docetaxel/cyclophosphamide (TC) in a retrospective real-world cohort of HER2-negative breast cancer patients [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 PO5-02-14.

Abstract PO3-03-06: Real-world efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy in Brazilian patients with early-stage triple-negative breast cancer

Abstract Background: Early-stage triple-negative breast cancer (TNBC) is associated with high risk of early recurrence and disease-specific mortality. Studies suggest a sustained clinical benefit in patients with TNBC who have a pathological complete response (PCR) after neoadjuvant chemotherapy (NACT). In TNBC, the combination of immunotherapy based on immune checkpoint inhibitors (anti-PD-1/PD-L1) combined with chemotherapy has been shown to be effective both in the advanced and early. In the early-stage setting, the addition of pembrolizumab to platinum-containing NACT significantly increased pathological complete response (pCR). Methods: We performed a retrospective observational cohort study of patients diagnosed with TNBC, stage II-III, who received NACT with chemotherapy based on paclitaxel and carboplatin (TC) followed by doxorubicin plus cyclophosphamide (AC) associated with pembrolizumab, treated from June 2022 to July 2023, at AC Camargo Cancer Center, São Paulo, Brazil. Objectives: To investigate the real-world pCR rate and safety profile of early-stage TNBC treated with neoadjuvant chemotherapy (weekly TC, ddAC/AC) associated with pembrolizumab and to describe the clinical-pathological characteristics of this population. Results: Eighty patients received neoadjuvant pembrolizumab plus chemotherapy. Around 50.6% of patients were premenopausal, with a median age of 47 years old at diagnosis. About 18% carried a germline mutation in the BRCA1 (50%) .Regarding the pathological characteristics of the tumor, 90.9% were invasive ductal carcinoma (IDC), 80% had histological grade (HG) III, and average Tumor Infiltrating Lymphocytes (TILs) was 18%. In 94.8% of cases, Ki67 was expressed in more 20% of tumor cells. The expression of HER2 was low in 14%, and 5% were ER-low. Regarding the clinical stage of the primary tumor, (64.9%)cT2, (18%) cT3, (10%) cT1c, and (2.5%) cT4. Regarding regional lymph node staging, 48%, 33.7%, 10.3%, and 6.4% were classified as cN0, cN1, cN2a, and cN, respectively. Clinical stage was IIA (42.8%), IIB (24.6%), IIIA (14.2%), IIIB ( 9%), and IIIC (5%). Regarding chemotherapy, 57.1% received dose dense AC, 54% percent had chemotherapy-related toxicity, 35.7% had neutropenic fever, 32.4% required hospitalization, and 31% used antibiotics. 31% received eight cycles of neoadjuvant pembrolizumab and 53.2% of patients completed all NACT, among these patients, 61% had complete .A cutoff date, about 61% of patients have undergone surgery, and 66.6% achieved a complete pathological response (ypT0ypN0). Patients that received eight cycles of neoadjuvant pembrolizumab had a higher chance of pathological complete response rate (61% vs. 45.2%) p=0.073. Immune-related toxicities (IRT) were observed in 16.8% patients, being the most common endocrinologic and cutaneous, being G3 or higher in 46%. About 15.5% used corticosteroids. Fifty percent had already started or completed adjuvant therapy, from which 66.6% received only adjuvant pembrolizumab, 28% had adjuvant pembrolizumab plus capecitabine, 1.2% received adjuvant capecitabine, and 1.2% had adjuvant olaparib. Eight percent of our patients have already completed nine cycles of adjuvant pembrolizumab, 12.7% did not receive adjuvant pembrolizumab due to prior toxicity. In our cohort, we observed greater intercurrences related to ddAC versus conventional AC 61.4% versus 52.4%, p=0.492, therefore, it did not impact whether or not the chemotherapy was completed. Conclusion: Our cohort is composed mostly of pre-menopausal with stage IIA tumors. Most patients received ddAC, Fifty-four percent had chemotherapy-related toxicity. We observed a high rate of pCR (61%) on our patients have already undergone surgery, 66.6% achieved a complete pathological response.Of those who received 8 cycles of neoadjuvant pembrolizumab had a higher chance of pathological complete response rate (61% vs. 45.2%) p=0.073 Citation Format: isadora sousa, Ana Carolina M. Comini, Italo BORGES, Flavia C. Balint, Livia alexandre Martins, Debora G. Sousa, Solange M. Sanches, Marcelle G. Cesca, Vladmir Cordeiro de Lima, Monique Tavares. Real-world efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy in Brazilian patients with early-stage 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 PO3-03-06.

Abstract PO3-09-04: Identification of germline pathogenic variants to guide systemic therapy: Prevalence and spectrum of PVs among Mexican patients with metastatic breast cancer

Abstract BACKGROUND Currently, international genetic cancer risk assessment (GCRA) guidelines recommend genetic testing for the identification of germline pathogenic variants (PVs) in patients with metastatic breast cancer (MBC) to guide systemic therapy. Patients with PVs in BRCA genes are candidates to receive poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPi). The prevalence of PVs in patients with HER2-negative MBC has been reported to be 10%. The proportion of MBC in low- and middle-income countries (LMIC) is higher. However, access to genetic testing in LMIC is limited and contributes to the gap in genetic epidemiology knowledge. We aimed to describe the frequency of germline PVs in breast cancer associated genes and clinic-pathologic characteristics of Mexican women with MBC. METHODS This retrospective study included Mexican women from 7 centers in Mexico, who were diagnosed with MBC and had genetic testing. Pathogenic and likely pathogenic variants were reported. Demographic, histopathological characteristics, family history and access to treatment with PARPi, were obtained from chart review. RESULTS From August 2017 to May 2023, 114 Mexican women with MBC were included, median age at diagnosis was 47 years (range 24-80 y), 42% had de novo metastatic, and 58% recurrent disease. 86.8% had infiltrating ductal carcinoma, 51.3% had HR+HER2- (n=58), 4.4% HR+HER+ (n=5), 5.3% HR-HER2+ (n=6), and 38.6% triple negative tumors (n=44). Sites of metastatic disease were as follows: 61.4% non-regional nodes (n=70), 57% bone (n=65), 40.3% lung (n=46), 30.7% liver (n=35), 15.8% central nervous system (n=18) and 7% peritoneal carcinomatosis (n=8). The frequency of PVs was 22% (25/114); 84% of the PVs were heterozygous, mainly identified in BRCA genes (BRCA1 n=12, BRCA2 n=9), and in 4 patients in other genes (PALB2 n=2, PTEN n=1, MUTYH n=1). Among PARPi candidates, 40% (10/25) received Olaparib, the majority received it on the second or subsequent lines of treatment (7/10) with a median progression free survival of 6 months (3-13 m). BRCA carriers were younger at BC diagnosis (38.5 vs. 49 years, p=0.00694) and had a significant higher proportion of family history of ovarian cancer (p=0.00039), but not for breast (p=0.06), prostate (p=0.71) or pancreatic cancer (p=0.098), compared to non-carriers. CONCLUSION We found a high frequency of PVs in BRCA genes in Mexican women with MBC. Access to the genetic testing and targeted therapy should be improve in the Mexican population in order to decrease disparities in cancer care in the Mexican Population. In addition, genetic testing allows to identify other family members at risk with cascade testing and to recommend them risk reduction strategies. Citation Format: Jose Luis Rodriguez-Olivares, Maria Fernanda Esparza-Orozco, Jose Alfredo Ramirez-Gonzalez, Roberto Ivan Sanchez-Reyes, Enrique Isay Talamantes-Gamez, Gregorio Quintero-Beulo, Gilberto Lopez-Rosas, Karla Alicia Centelles-López, Brizio Moreno-Jaime, Daniela Vazquez-Juarez, Ana Maria Hernandez-Murillo, Ilana de la Puente Tawil, Jeffrey Weitzel, Cynthia Villareal Garza, Yanin Chavarri-Guerra. Identification of germline pathogenic variants to guide systemic therapy: Prevalence and spectrum of PVs among Mexican patients with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-04.

Abstract ED01-01: Optimizing endocrine therapy in premenopausal women

Abstract Premenopausal women with early-stage hormone receptor (HR)-positive breast cancer are candidates for adjuvant endocrine therapy and have several treatment options. The clinical team should assess an individual woman’s risk of recurrence, estimate benefits from specific endocrine manipulations, and consider co-morbidities, adverse event profile and host factors. Risk stratification strategies including clinic-pathologic features, genomic assays and composite scores can guide recommendations regarding type and duration of endocrine therapy, in particular in node-negative disease. Adjuvant tamoxifen for 5 to 10 years significantly reduces breast cancer recurrence and death. Premenopausal women who are at high risk of recurrence benefit from ovarian function suppression (OFS) with tamoxifen or an aromatase inhibitor for 5 years. Those include women with high-risk clinico-pathological features and younger age, and for whom chemotherapy is commonly recommended. There are currently no available data regarding the use of extended OFS beyond 5 years. Newer data support the addition of CDK 4/6 inhibitors to endocrine therapy in women with high-risk disease. Endocrine therpay is associated with frequent bothersome and few significant side effects that can negatively impact quality of life and adherence to treatment. Clinicians must carefully weigh the benefits associated with specific endocrine therapies, and possible short- and long-term side effects to individualize therapy, and to consider interventions to enhance adherence. Citation Format: V. Stearns. Optimizing endocrine therapy in premenopausal women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED01-01.

Cutaneous manifestations of adult-onset Still's disease: A comparative study between young-onset and elderly-onset groups.

We investigated the detailed characteristics and proportions of typical and atypical rashes in 28 patients with adult-onset Still's disease (AOSD) by retrospectively examining the clinical symptoms and pathological features. The patients consisted of six males and 22 females aged between 23 and 85 years. The skin rashes observed in the study population were as follows: (i) typical rash in six cases, (ii) atypical rash in 19, and (iii) both typical and atypical rash in three cases (in all three cases, typical rash preceded atypical rash). Furthermore, we classified atypical rashes into persistent pruritic papules and plaques (PPPP) and others. In 22 cases of atypical rashes, 10 cases had PPPP. In a comparison between young-onset (<65 years) (n = 16) and elderly-onset (≥65 years) (n = 12) AOSD cases, typical rashes were observed more frequently in the young-onset cases. Regarding atypical rashes, PPPP was significantly more common in the elderly-onset cases.

Machine learning for predicting liver and/or lung metastasis in colorectal cancer: A retrospective study based on the SEER database

ObjectiveThis study aims to establish a machine learning (ML) model for predicting the risk of liver and/or lung metastasis in colorectal cancer (CRC). MethodsUsing the National Institutes of Health (NIH)'s Surveillance, Epidemiology, and End Results (SEER) database, a total of 51265 patients with pathological diagnosis of colorectal cancer from 2010 to 2015 were extracted for model development. On this basis, We have established 7 machine learning algorithm models. Evaluate the model based on accuracy, and AUC of receiver operating characteristics (ROC) and explain the relationship between clinical pathological features and target variables based on the best model. We validated the model among 196 colorectal cancer patients in Beijing Electric Power Hospital of Capital Medical University of China to evaluate its performance and universality. Finally, we have developed a network-based calculator using the best model to predict the risk of liver and/or lung metastasis in colorectal cancer patients. Results51265 patients were enrolled in the study, of which 7864 (15.3 %) had distant liver and/or lung metastasis. RF had the best predictive ability, In the internal test set, with an accuracy of 0.895, AUC of 0.956, and AUPR of 0.896. In addition, the RF model was evaluated in the external validation set with an accuracy of 0.913, AUC of 0.912, and AUPR of 0.611. ConclusionIn this study, we constructed an RF algorithm mode to predict the risk of colorectal liver and/or lung metastasis, to assist doctors in making clinical decisions.

A Prognosis and Immunological Study of Cellular Aging Related lncRNAs in Lung Adenocarcinoma

Background: Recently, cellular senescence has been recognized as a novel hallmark of cancer. However, the mechanisms that control cellular senescence remain poorly understood. This study seeks to discover long non-coding RNAs (lncRNAs) that are linked to senescence and can predict outcomes in lung adenocarcinoma (LUAD) patients. Methods: Using RNA sequencing data from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) and senescence genes from the CellAge database, a group of lncRNAs related to senescence was initially identified. Subsequently, through univariate and multivariate Cox regression analyses, a senescence-related lncRNA signature (SenLncSig) linked to the prognosis of LUAD was developed. LUAD patients were categorized into high-risk and low-risk groups based on the median risk score of SenLncSig. Kaplan-Meier analysis was employed to assess differences in overall survival (OS) between these subgroups. Additionally, disparities in Gene Set Enrichment Analysis (GSEA), immune infiltration, scores from the tumor immune dysfunction and exclusion (TIDE) module, and choices of chemotherapy and targeted therapy were also evaluated between the high-risk and low-risk groups. Results: Based on univariate and multivariate Cox regression analyses, we established a prognostic model composed of seven senescence-related lncRNAs, named SenLncSig, which includes AL031775.2, AC026355.1, AL365181.2, AC090559.1, AL606489.1, AL513550.1, and C20orf197. This model divides patients into high-risk and low-risk groups, with the high-risk group showing significantly shorter overall survival compared to the low-risk group, with a hazard ratio (HR) of 1.326. The predictive accuracy of SenLncSig was validated through ROC curves and principal component analysis (PCA). Additionally, we developed an intuitive survival prediction tool that combines SenLncSig with clinical pathological features to assess patients' overall survival (OS). Enrichment analysis (GSEA) revealed that SenLncSig is involved in multiple pathways related to tumor immune modulation. Risk model analysis indicated significant differences between the high and low-risk groups in terms of immune status and responses to immunotherapy, chemotherapy, and targeted therapy. Conclusion: In this study, a lncRNA signature named as SenLncSig was developed that not only identifies the senescence phenotype and predicts prognosis but also has the capability to forecast the response of LUAD to immunotherapy.