Early BC Research Articles

Abstract PO2-19-07: PROOFS – Pre-/perimenopausal patients with HR+/HER2- EBC with intermediate to high clinical and low genomic risk, treated by endocrine treatment (ET) plus ovarian function suppression (OFS) or chemotherapy followed by ET

Abstract Background During the past years, clinical routine has shifted away from relying solely on clinicopathologic factors toward increasing use of multigene expression assays in guiding treatment decisions regarding adjuvant chemotherapy (CT) for hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer (EBC) with 0 to 3 positive lymph nodes. In case of a low genomic risk, there is strong consensus in favor of endocrine treatment (ET) alone for postmenopausal patients, regardless of clinical risk (supported by data from planB, ADAPT, RxPonder, TailorX, MINDACT). However, there is still uncertainty regarding optimal therapy for pre- and perimenopausal patients with a similar clinical/genomic risk profile. Since the observed benefit of CT in this patient group may be partly attributable to CT-induced ovarian function suppression (OFS), some of these patients could be spared CT by adding OFS to endocrine therapy. The West German Study Group (WSG) initiated the PROOFS-registry to create a real-world database on how to optimally treat these patients. Eligibility Criteria PROOFS (NCT05792150) aims at the long-term follow up of pre- or perimenopausal patients with HR+/HER2- EBC with an intermediate to high clinical risk of recurrence and low genomic risk measured by MammaPrint(R). Additional endocrine response assessment (Ki67) after a short preoperative endocrine therapy is encouraged. Up to 25% of the study population may have node-positive disease. Participants undergo standard-of-care treatment at physician´s discretion and according to clinical routine, which may include CT neoadjuvant or adjuvant + ET, ET + OFS in premenopausal, or ET +/- OFS in perimenopausal women. Specific Aims PROOFS aims to give insights in the real-world use of OFS and to confirm an excellent outcome in pre-/perimenopausal women with HR+/HER2- early BC with an intermediate to high clinical risk of recurrence and low genomic risk treated by ET +/- OFS alone (without CT). In addition, quality of life is captured. Statistical Methods The primary objective is to demonstrate the 5-year distant recurrence-free interval (dRFI) in patients treated by ET +/- OFS alone. The null hypothesis H(0) is: 5-year dRFI < 92%. Secondary endpoints for all patients are 5- and 10-year dRFI, distant disease-free survival (dDFS), overall survival (OS), breast cancer-free interval (BCFI), quality of life (QLQ BR23 and QLQ-C30) and therapy adherence. Cox regression models, Kaplan-Meier method and log-rank tests will be applied for survival analysis. Linear mixed models will be utilized to quantitatively describe the course of quality of life-scores as well as therapy adherence, and to conduct group comparisons. Present and Target Accrual The study is open for recruitment of 1500 patients (approximately 20% receiving CT and 80% receiving ET +/- OFS) at up to 100 centers in Germany (June 2023: 24 open for recruitment). Funding AGENDIA N.V., Amsterdam Contact Information rachel.wuerstlein@med.uni-muenchen.de Citation Format: Rachel Wuerstlein, Lotta Ada Fischer, Nadia Harbeck, Monika Graeser, Ulrike Nitz, Matthias Christgen, Sherko Kuemmel, Christine zu Eulenburg, Matthias Warm, Oleg Gluz. PROOFS – Pre-/perimenopausal patients with HR+/HER2- EBC with intermediate to high clinical and low genomic risk, treated by endocrine treatment (ET) plus ovarian function suppression (OFS) or chemotherapy followed by ET [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 PO2-19-07.

Abstract PO1-16-11: Real-world features and outcomes of young advanced breast cancer (ABC) patients (pts) from RegistEM (GEICAM/2014-03) study

Abstract Background: BC is the most incident cancer worldwide in < 40 years old (y) women. Increasing body mass index and changes in reproductive history contribute to the growing incidence of premenopausal BC. A higher proportion of luminal B-like and estrogen receptor negative (ER─) tumors, an increased risk of early relapse, and more unfavorable longer-term outcomes for young women with ER+ tumors when compared to older women, have been reported. In this analysis, we focus on age-specific BC characterization from a real-world population-based perspective. Methods: Pts were enrolled in the non-interventional and ambispective RegistEM study in ABC diagnosed between 2016 and 2019. We describe the features and outcomes of < 50 y pts at their initial BC diagnosis according to their BC subtype. BC subtypes were based on the most recent tumor tissue sample (distant metastasis, and in its absence, primary BC). Comparisons between < 40 and ≥ 50 y groups were performed. Results: Pts < 50 y represent 39% (n=685) of total pts with available data (n=1739, any age group) in the registry. By age, 12% (n=212) were < 40y, and 27% (n=473) 40-49y. At first BC diagnosis, 75% and 25% pts had early BC (EBC) and de novo metastatic BC (MBC), respectively. In EBC pts, stage II (50%) and III (28%) were the most frequent at diagnosis; invasive non-special type carcinoma was the predominant morphology, and grade 2 was the most common histological grade, but grade 3 was predominant in TN pts and HER2+ < 40y pts. The median time to recurrence was < 2y in TN pts, 3y in HER2+ pts, and 6y in luminal HER2─ pts. At ABC diagnosis, the median age was 47y, all pts were female but one, 98% white, and 60% premenopausal (94% were premenopausal at EBC diagnosis). A family history of BC and/or ovarian cancer was reported in 34% pts, and a hereditary-risk genetic test was performed in 39% (254 of 652) pts; 12% (n=30) had BRCA1/2 mutations, with a proportion higher in TN pts (9 of 33, 27%) vs. luminal HER2─ (21 of 183, 12%) and HER2+ (0 of 38) pts. Visceral disease was the most frequent in all subgroups, highlighting statistical differences (p=0.022) between age groups ( < 40y 55% vs. ≥50y 71%) only in TN pts. 60% had ≤ 2 locations involved, similarly in all subgroups. The presence of >2 metastatic locations was statistically higher in HER2+ pts ≥50y (54%) vs both < 40y (32%) and 40-49y (48%). Brain disease was more present at ABC diagnosis in TN (9%) and HER2+ (7%) than in luminal HER2─ (3%). Median no. of treatment lines (L) was 3 (range 0-11), and median follow-up 44 mo (95% CI: 41-44). 99% pts received 1L, the distribution of treatments by BC subtype within each age subgroup was similar; median duration of 1L was 21 months (mo) in luminal HER2─, 17 mo in HER2+, and 5 mo in TN pts. 68% of pts who received 1L, reached 2L. Duration of 2L dropped dramatically: 8 mo in luminal HER2─, 6 mo in HER2+, and 2 mo in TN pts. No differences between ≥50y and the rest of pts were observed in PFS for any treatment line. 49% pts had died at the database cut-off date (05-April-23), with no differences between age groups, but TN pts had the highest death rate (80%). Additional data according to BC subtypes and age groups are in the table. Conclusions: Luminal HER2─ was the predominant BC subtype in all age subgroups. Visceral disease was more prevalent in young TN pts compared to older pts. TNBC pts experienced a shorter median time to recurrence and the highest mortality rate regardless of age, compared to HER2+ and luminal HER2- pts, indicating the need for targeted interventions in this subgroup. Citation Format: Sara López-Tarruella, Angel Guerrero, Isabel Álvarez, Silvia Antolin Novoa, Ariadna Tibau, Josefina Cruz, César A Rodríguez, Purificación Martínez, J. Ignacio Chacón, María Hernández, Mireia Margelí, Encarna Adrover, Catalina Falo, Iria González, Álvaro Rodríguez-Lescure, María Marín, César Gómez, Juan de la Haba-Rodríguez, J. José Illaramendi, Raquel Andrés, Andrea Blasco, Mª José Escudero, Susana Bezares, Federico Rojo. Real-world features and outcomes of young advanced breast cancer (ABC) patients (pts) from RegistEM (GEICAM/2014-03) 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 PO1-16-11.

Abstract PO5-17-04: Tolerability of pertuzumab in older adults with HER2 positive breast cancer: A single institution experience

Abstract Background: Tumor HER2 over-expression occurs in 10 to 15% of older adults with breast cancer (BC). Combination HER2-directed therapy (pertuzumab and trastuzumab) with chemotherapy (CT) is the standard treatment for early and advanced HER2-positive bc. However, a study of more than 1,300 Medicare beneficiaries showed that about half of patients (pts) aged 65 or older with stage I to III HER2 positive bc did not receive trastuzumab-based therapy. This is likely due to concern for tolerability as older women remain underrepresented in clinical trials of breast cancer making it difficult to extrapolate tolerability of these agents in these patients. In the Neosphere and TRYPHAENA studies, the mean age of pts were 49.8 and 50.6 years, respectively. We examined the real-world tolerability of pertuzumab in combination with trastuzumab and systemic ct in women over the age of 65 with HER2 positive bc. Methods: An IRB approved retrospective review of medical records was conducted evaluating pts over the age of 65 with early or advanced HER2 positive bc treated at The Ohio State University Comprehensive Cancer center from January 1, 2015 to May,1 2020. Descriptive statistics (means, standard deviations, medians and ranges for continuous variables and frequencies and percents for categorical variables) were used to summarize disease and patient characteristics for pts enrolled in this study and treated with pertuzumab. The total number of planned and completed cycles of treatment as well as the number of treatment delays and dose reductions were also summarized using frequencies and percentages. The same descriptive statistics were used to summarize the number of grade II or IV toxicities and pathologic complete response (pCR) in the neoadjuvant setting. Results: A total of 71 pts met inclusion criteria. Mean age was 76 years (SD 4.1). Of these pts, 62 had stage I-III disease and 9 had metastatic disease. Additionally, 68% (48/71) had estrogen positive (ER) disease whereas 32% (23/71) had ER negative disease. Neoadjuvant systemic therapy was provided to 81% (50/62) of non-metastatic pts and 19% (12/62) received adjuvant therapy. The median number of completed neoadjuvant cycles (ct plus trastuzumab and pertuzumab) was 5.4 (SD 1.5). Among those who received pertuzumab with systemic ct in the neoadjuvant setting, 46% (23/50) of pts achieved a pCR (56% for ER negative disease and 41% for ER positive disease) The median number of completed adjuvant cycles (ct plus trastuzumab and pertuzumab) was 4.9 (SD 2.0). Pts with stage I to III disease completed a mean of 8.6 (SD 5.0) targeted therapy cycles (pertuzumab/trastuzumab). Pts with metastatic disease had a median of 5.7 (SD 1.0) cycles of ct plus trastuzumab and pertuzumab and received a mean of 34.4 (SD 36.0) cycles of maintenance pertuzumab. Treatment delay by 7 or more days occurred in 11% (8/71) of pts whereas 25% (18/71) of pts discontinued pertuzumab early. Pertuzumab termination occurred due to toxicity in 44% (8/18), metastasis in 11% (2/18), and other causes in 44% (8/18) of cases. For toxicities, 2% (1/51) of patients reported grade 3 pain, 25% (2/8) reported grade 3 fatigue, and 12% reported grade 4 diarrhea (1/8) (Table 1). Conclusions: Our study showed that pertuzumab was well tolerated in older pts with bc in the real-world setting. However, 25 % of pts still discontinued pertuzumab early which illustrates the importance of identifying pts who are at higher risk for toxicities prior to starting treatment. Table 1 Reported adverse events in patients age 65 and older receiving pertuzumab Citation Format: Nicole Williams, Austin Warmbier, Dureti Doto, Marilly Palettas, Julie Stephens, Dionisia Quiroga, Kai Johnson, Ashley Pariser, Mathew Cherian, Sagar Sardesai, Daniel Stover, Margaret Gatti-Mays, Robert Wesolowski, Bhuvana Ramaswamy. Tolerability of pertuzumab in older adults with HER2 positive breast cancer: A single institution experience [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 PO5-17-04.

Abstract PO1-27-09: TRIPTORELIN (11.25MG) vs TRIPTORELIN (3.75MG) IN PREMENOPAUSAL WOMEN WITH HIGH-RISK EARLY STAGE BREAST CANCER RH(+) and HER2(-) REAL WORLD EXPERIENCE. TRIPTO3 RESULTS

Abstract Background. Premenopausal women with high risk early stage BC HR+/Her2- present as a complex disease and generally have worse survival outcomes compared to postmenopausal women with the same disease. There are pathological clinical factors and genomic platforms that help us in therapeutic decisions. The use of triptorelin 3.75mg associated with AI promotes favorable results in terms of survival for premenopausal women with high-risk Early stage BC. TEXT/SOFT trial. TRIPTO3 study evaluates the use of Triptorelin 11.25mg vs. Triptorelin 3.75mg in this specific patient population. Methods: We reviewed medical records of premenopausal female patients with high-risk early stage breast cancer who have been treated and received triptorelin 3.75mg and triptorelin 11.25mg as part of their treatment. All patients were treated at a private Oncology Center between 2013 and 2020. The primary objective was disease-free survival. Results: 52 patients were found who met the inclusion criteria. 28(53.8%) patients received triptorelin 11.25mg and 24(46.2%) patients received triptorelin 3.75mg respectively. The median follow-up was 63 months and the disease-free survival for the Triptorelin 11.25mg group was 91.2% and for the Triptorelin 3.75mg group was 86.8% respectively (Hazard Ratio of disease-free survival was 1.2; 95% IC (0.2-7.2). Disease-free survival for both groups regardless of triptorelin dose was 89% at 5 years. The median disease-free survival was not reached in both groups. Conclusions: Our findings show that triptorelin 11.25 mg is similar to the use of triptorelin 3.75 mg in terms of disease-free survival for premenopausal women with high-risk early stage breast cancer. Citation Format: Ronald Limon, Mariano Lopez-Pereyra, Mario Gianella, Neysa Espinoza, Denize Ramirez, Carlos Antelo, Claudia Sitic, Wara Cortez, Oscar Niño De Guzman, Silvia Neciosup, Natalia Valdivieso. TRIPTORELIN (11.25MG) vs TRIPTORELIN (3.75MG) IN PREMENOPAUSAL WOMEN WITH HIGH-RISK EARLY STAGE BREAST CANCER RH(+) and HER2(-) REAL WORLD EXPERIENCE. TRIPTO3 RESULTS [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 PO1-27-09.

Abstract PO1-09-12: Cancer health disparities among patients with early-stage estrogen receptor-positive (ER+) breast cancer treated in public or private practices in Brazil

Abstract Background Cancer registries in Brazil are deficient and data about patients’ profiles and cancer treatment patterns are scarce in the country. Moreover, while 30% of population has access to private insurance, almost 70% of population uses publicly health services. The objective of this work was to describe the sociodemographic and clinicopathological characteristics of women with early-stage ER+ breast cancer on adjuvant ET in different regions of Brazil, and to describe treatment patterns for this disease according public and private institutions. Methodology: We performed a real-world data analysis in different institution regions of Brazil. Women with a history of early-stage ER+ invasive carcinoma of the breast on adjuvant endocrine therapy for at least 6 months were invited to participate of this study in 12 centers in four different regions in Brazil. Demographic and clinicopathologic information was retrieved from medical records. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured. High education level was defined by completed high school. Data collection was done with RedCap software. Qualitative variables were compared between groups using the Chi-square or exact Chi-square test and for quantitative variables the non-parametric Mann-Whitney test was used. P < 0.05 was considered significant. Analyzes were performed in SAS 9.4; Results: From June 2021 to May 2023, a total of 461 women with ER+, early BC, were included in this analysis. A total of 233 (50.6%) came from private institutions, the mean age was 56.02 years (range 22-93), 47.69% were non-white, 61.3% were post-menopause, 61.7% lived with a partner, and 76.2% were highly educated and 66.81% had comorbidities. Tumor staging at diagnosis was classified as III, II and I respectively in 21.26%, 43.17% and 35.57% of all cases. Regarding treatment received, 62.4% of patients underwent lumpectomy, 32.2% had axillary dissection, 67.6% received (neo)adjuvant chemotherapy, 45.2% were on aromatase inhibitors and 14.19% were on ovarian function suppression plus ET . Median duration of ET use was 2.78 years (range 6 months- 9.61 years). Publicly health insurance was associated significantly associated with younger age at diagnosis (< 60 yo), premenopausal status, to live alone, lower educational level, more advanced tumors, prior mastectomy, prior axillary dissection, prior neo-adjuvant chemotherapy, prior radiotherapy, lower use of aromatase inhibitors, ovarian function suppression plus ET, and CDK4/6 inhibitors, while higher use of concomitant medications. Conclusion: The study shows significant health disparities among women with early-stage ER+ breast cancer treated in private versus public institutions in Brazil. Importantly, despite having more advanced tumors, women in public institution had less access to ovarian suppression, CDK4/6 inhibitors and were treated with more aggressive surgical procedures. A deep discussion involving government, lawmakers, health care providers and patients should be conducted to try to decrease the described disparities. Patient’s characteristic and patterns of treatment among patients with estrogen receptor-positive breast cancer on adjuvant therapy according to health insurance in Brazil ALND: axillary lymph node dissection; CDK4/6i: CDK4/6 inhibitors; ET: endocrine therapy; OS: ovary suppression. Citation Format: Romualdo Barroso-Sousa, Daniele Assad-Suzuki, Danielle Santos, Fernanda Moura, Sulene Oliveira, Anna Luiza Galvão, Bruno Souza, Amanda Castro, Monalisa Andrade, Andrea Shimada, Yuri Beckedorff, Maria Cristina Magalhães, Cristiano Souza, Carlos Paiva, Heloísa Resende, Daniela Pereira, Angelica Rodrigues, Daniela Rosa. Cancer health disparities among patients with early-stage estrogen receptor-positive (ER+) breast cancer treated in public or private practices in Brazil [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 PO1-09-12.

Abstract PO3-20-01: ASTEFANIA: a Phase III study of ado-trastuzumab emtansine plus atezolizumab or placebo as adjuvant therapy in patients with residual invasive breast cancer after neoadjuvant HER2-targeted therapy and chemotherapy

Abstract BACKGROUND Ado-trastuzumab emtansine (T-DM1) is the standard of care for adjuvant treatment of patients (pts) with HER2-positive early breast cancer (eBC) who have invasive residual disease after preoperative treatment with taxane and HER2-targeted therapy. However, a high unmet need remains in some higher risk subgroups (e.g., inoperable or lymph node-positive, hormone receptor-negative disease) who have 3-year invasive disease-free survival (IDFS) rates of 76%. Exploratory analyses suggest that addition of the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab to T-DM1 results in longer progression-free survival compared with T-DM1 alone in pts with previously treated PD-L1-positive metastatic BC. PD-L1/programmed death-1 inhibitors may have a different effect in eBC, as they result in improved pathologic complete response in early triple-negative BC regardless of PD-L1 status. ASTEFANIA evaluates atezolizumab plus T-DM1 in PD-L1-unselected pts with higher risk residual invasive breast cancer after neoadjuvant treatment. TRIAL DESIGN ASTEFANIA is a Phase III, randomized, double-blind, multicenter, study in pts with centrally confirmed HER2-positive eBC with residual invasive disease at surgery after neoadjuvant chemotherapy and HER2-directed treatment including ≥9 weeks of taxane and ≥9 weeks of trastuzumab. Within 12 weeks of primary surgery, pts are randomized 1:1 to intravenous (IV) T-DM1 3.6 mg/kg every 3 weeks (q3w) plus atezolizumab 1200 mg IV q3w or T-DM1 3.6 mg/kg IV q3w plus placebo IV q3w for 14 cycles. Radiotherapy and/or endocrine therapy is administered per local standards. Randomization is stratified by clinical stage at presentation, hormone receptor status, preoperative HER2-directed therapy, and PD-L1 status. ELIGIBILITY CRITERIA Eligible pts have clinical stage cT4/any N/M0, any cT/N2–3/M0, or cT1–3/N0–1/M0 at presentation. Those with cT1–3/N0–1 disease must have pathologic evidence of residual invasive carcinoma in axillary lymph node(s) at surgery. Pts with cT1mi/T1a/T1b/N0 disease are not eligible. AIMS The primary endpoint is IDFS. Secondary endpoints include overall survival, safety, and patient-reported outcomes. STATISTICAL METHODS The log-rank test will be used to compare IDFS between the treatment arms, according to the protocol-defined stratification factors. The Cox proportional hazards model, stratified by the protocol-defined stratification factors, will be used to estimate the hazard ratio between the two treatment arms and its 95% confidence intervals. ACCRUAL As of Jun 28, 2023, 789 pts of the target of 1,700 have been enrolled. CONTACT INFORMATION For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only). Clinicaltrials.gov number NCT04873362. Originally presented at the ESMO Congress 2021, 202TiP, Peter Schmid et al. – Reused with permission. Further information is available in Future Oncology 2022; 18:3563–3572. Submitted with permission from Future Medicine & Future Science, part of the Future Science Group. Citation Format: Peter Schmid, Thomas Bachelot, Giampaolo Bianchini, Nadia Harbeck, Sherene Loi, Yeon Park, Aleix Prat, Leslie Gilham, Thomas Boulet, Nino Gochitashvili, Estefania Monturus, Chiara Lambertini, Beatrice Nyawira, Adam Knott, Sara Hurvitz. ASTEFANIA: a Phase III study of ado-trastuzumab emtansine plus atezolizumab or placebo as adjuvant therapy in patients with residual invasive breast cancer after neoadjuvant HER2-targeted therapy and 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 PO3-20-01.

Abstract PO2-19-08: INAVO121: Phase III study of inavolisib + fulvestrant vs alpelisib + fulvestrant in patients with hormone receptor-positive, HER2-negative, PIK3CA-mutated locally advanced or metastatic breast cancer

Abstract BACKGROUND Standard-of-care (SoC) endocrine therapy (ET) for patients (pts) with hormone receptor-positive, HER2-negative, PIK3CA-mutated locally advanced or metastatic breast cancer (HR+, HER2–, PIK3CA-mut LA/mBC) was transformed by combinations with cyclin-dependent kinase 4/6 inhibitors (CDK4/6is); a CDK4/6i-based combination is approved in high-risk early BC. However, in most pts, mechanisms of resistance that emerge during or after treatment with a CDK4/6i and ET combination lead to relapse/disease progression. Dysregulating mutations in PIK3CA, occurring in ~40% of HR+, HER2– BCs, represent a common mechanism of resistance to CDK4/6is and ET combinations. Alpelisib (ALP; a selective PI3Kα inhibitor; PI3Kαi) + fulvestrant (FUL) is approved for pts with HR+, HER2–, PIK3CA-mut LA/mBC, but its widespread implementation in clinical practice has been challenging. As such, there is a significant need to develop PI3Kαis with a better therapeutic index. Inavolisib (INAVO) is a highly potent and selective PI3Kαi that also facilitates the degradation of mutated PI3Kα isoform. INAVO has demonstrated manageable safety/tolerability, alone and in combination with SoC treatments in HR+, HER2–, PIK3CA-mut LA/mBC. Moreover, an ongoing Phase I trial showed that INAVO + FUL elicited encouraging preliminary antitumor activity in heavily pretreated pts, including a CDK4/6i-based regimen. TRIAL DESIGN INAVO121 is a Phase III, randomized, open-label study. Pts are randomized 1:1 to receive INAVO (9 mg oral daily; PO QD) + FUL (500 mg intramuscularly on Days [D] 1 and 15 of Cycle 1, then D1 of subsequent cycles), or ALP (300 mg PO QD) + FUL. Randomization is stratified by visceral disease (yes vs no) and prior CDK4/6i therapy (adjuvant vs metastatic setting). Pts will receive treatment until disease progression or unacceptable toxicity. ELIGIBILITY CRITERIA Pts have HR+, HER2–, PIK3CA-mut LA/mBC (confirmed by circulating-tumor DNA or tumor tissue), adequate hematologic and organ function, and disease progression after or during treatment with a CDK4/6i-based regimen. Up to two prior lines of systemic therapy in LA/mBC, including one line of chemotherapy, are allowed. AIMS The primary endpoint is progression-free survival (PFS) by blinded independent central review (BICR). Secondary endpoints include overall survival, BICR-objective response rate, BICR-best overall response, BICR-duration of response, BICR-clinical benefit rate, safety, tolerability, pt-reported outcomes, and pharmacokinetics. STATISTICAL METHODS A stratified log-rank test at an overall 0.05 significance level (two-sided) will be used for the primary endpoint analysis. Median PFS will be estimated using Kaplan–Meier methodology. An independent data monitoring committee will be in place for safety and efficacy. ACCRUAL The study is open for enrollment and has randomized four pts; the study is targeting 400 pts at ~200 sites globally. CONTACT INFORMATION For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only). Clinicaltrials.gov number NCT05646862. This abstract was originally presented at ASCO 2023 (TPS1123). Citation Format: Dejan Juric, Kevin Kalinsky, Seock-Ah Im, Eva Ciruelos, Giampaolo Bianchini, Carlos Barrios, William Jacot, Peter Schmid, Sherene Loi, Hope Rugo, Veronica Craine, Katherine Hutchinson, Aulde Flechais, Eirini Thanopoulou, Nadia Harbeck. INAVO121: Phase III study of inavolisib + fulvestrant vs alpelisib + fulvestrant in patients with hormone receptor-positive, HER2-negative, PIK3CA-mutated locally advanced or 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 PO2-19-08.

Abstract PO1-19-11: Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for HER2+ Metastatic Breast Cancer (HER2CLIMB-05, Trial in Progress)

Abstract Background The current first-line (1L) standard of care (SOC) for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is trastuzumab (T) plus pertuzumab (P) and a taxane. Despite advances in 1L SOC, most patients progress during maintenance therapy with T+P. Tucatinib is a tyrosine kinase inhibitor (TKI) approved in combination with T and capecitabine for adults with HER2+ MBC, with and without brain metastases (BM). In HER2CLIMB, addition of tucatinib significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with HER2+ MBC and was well tolerated. Adding tucatinib also reduced the risk of disease progression or death in patients with untreated and/or active BM (Murthy et al. NEJM 2020, Curigliano et al. Ann Oncol 2022). HER2CLIMB-05 investigates whether adding tucatinib to 1L SOC as maintenance therapy will extend PFS while maintaining quality of life (QOL). Methods HER2CLIMB-05 (NCT05132582) is a phase 3, randomized, double-blind study evaluating tucatinib plus T+P as maintenance therapy for HER2+ MBC. Approximately 650 patients will be enrolled. Eligible patients will have advanced HER2+ disease, no progression on 4–8 cycles of prior 1L SOC, Eastern Cooperative Oncology Group Performance Status of 0 or 1, and no or asymptomatic BM. Exclusion criteria include prior treatment with anti-HER2 and/or anti-epidermal growth factor receptor TKI (prior SOC for early BC is permitted) or inability to undergo contrast magnetic resonance imaging of the brain. Patients will be randomized 1:1 to receive either tucatinib or placebo twice daily, with T+P once every 21 days. Patients with hormone receptor-positive disease may receive endocrine therapy. The primary endpoint is investigator-assessed PFS. Secondary endpoints include OS, time to deterioration of health-related QOL, central nervous system PFS, safety, and pharmacokinetic (PK) parameters. PFS and OS will be compared using a two-sided stratified log-rank test between treatment groups. Time-to-event endpoints will be summarized using the Kaplan–Meier method. PK and safety data will be summarized using descriptive statistics. Enrollment is ongoing in Austria, Chile, Greece, Italy, Japan, Poland, Portugal, Spain, the US, and several other European, APAC, and LATAM countries. This abstract was previously presented at ESMO-BC 2022, FPN (Final Publication Number): 415, by Veronique Dieras (reused with permission). Citation Format: Erika Hamilton, Junji Tsurutani, Giuseppe Curigliano, Miguel Martín, Ciara O'Sullivan, Joo Hyuk Sohn, Konstantinos Tryfonidis, Libero Santarpia, Shan Yang, Véronique Diéras. Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for HER2+ Metastatic Breast Cancer (HER2CLIMB-05, Trial in Progress) [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 PO1-19-11.

Abstract PS16-02: Efficacy and safety of first-line atezolizumab + bevacizumab + paclitaxel in patients with advanced triple-negative breast cancer: the ATRACTIB phase 2 trial

Abstract BACKGROUND Triple-negative breast cancer (TNBC) is an aggressive tumor characterized by poor outcomes and new treatment strategies are urgently required. The programmed cell death-ligand 1 (PD-L1) antibody (Ab) atezolizumab (ATZ) combined with first-line (1L) nab-paclitaxel (nab-PTX) is approved in multiple countries for the treatment of PD-L1-positive patients (pts) with advanced TNBC (aTNBC) based on a significant improvement in progression-free survival (PFS) and a numerically higher and clinically meaningful median overall survival (OS). A synergism between antiangiogenic therapy and immunotherapy (IO)-based strategies has been observed preclinically and in different tumor types, but data in aTNBC is lacking. METHODS ATRACTIB (NCT04408118) is an international, open-label, single-arm, phase 2 trial evaluating the efficacy and safety of 1L ATZ + BVZ + PTX for pts with aTNBC, regardless of their tumors’ PD-L1 status. Adult pts with untreated, unresectable locally advanced/metastatic TNBC were included. Pts who had received (neo)adjuvant taxane-based chemotherapy (CT) and/or IO and/or an antiangiogenic agent had to have had a relapse with a disease-free interval beyond 12 months (mo). Pts received intravenous ATZ 840 mg + BVZ 10 mg/kg on days (D)1 and D15 + PTX 90 mg/m2 on D1, 8, and 15 of every 28-day cycle until disease progression, intolerable toxicity, death, or patient withdrawal. Tumor assessments were performed every 8 weeks for the first 12 mo and every 12 weeks thereafter. Baseline PD-L1 expression was centrally assessed using 22C3 (combined positive score [CPS]) and SP142 (expression on tumor-infiltrating immune cells [ICs]) Abs. The primary endpoint was investigator-assessed PFS by RECIST v.1.1. Key secondary endpoints included OS, objective response rate (ORR), clinical benefit rate (CBR), duration of response (DoR), and safety. Median PFS was analyzed with exponential maximum likelihood estimation (H0: ≤7.0 mo; HA: ≥9.5 mo). We estimated that enrolling 100 pts would provide 80% power at one-sided α nominal level of 5%, assuming a 10% drop-out rate. RESULTS Between October 2020 and May 2022, 100 female pts from 28 centers across 5 European countries were included. Median age was 55.0 years (32.0 - 84.0), 57.0% of pts had visceral disease, 46.0% had ≥3 metastatic sites, and 70.0% had received prior treatment for early BC (taxane-based CT in 87.1% of them). A total of 82 and 85 tumor samples out of 100 pts were available for PD-L1 assessment using 22C3 and SP142 assays, respectively. Most pts had PD-L1-negative tumors (87.8% with 22C3 [CPS < 10] and 97.6% with SP142 [expression on < 1% positive of ICs]). At data cutoff (15th September 2023), 23 pts were still on therapy. With a median follow-up of 16.7 mo (1.1 - 34.1), median PFS was 11.0 mo (95% CI, 9.0 - 13.2). OS data were immature at data cutoff, with 30 events. Estimated 18-month OS was 69.4% (95% CI, 58.4% - 78.1%). ORR was 63.0% (95% CI, 52.8% - 72.4%), CBR was 79.0% (95% CI, 69.7% - 86.5%), and median DoR was 10.0 mo (95% CI, 7.2 - 13.8). Regarding safety, the most common treatment-emergent adverse events (TEAEs) were peripheral neuropathy (68.0%) and fatigue (62.0%). Grade (G) 3/4 treatment-related TEAEs occurred in 47.0% of pts, mainly peripheral neuropathy (13.0%) and neutropenia (12.0%). Any-grade immune-related TEAEs, thrombosis or embolism, and bleeding occurred in 13.0% (5.0%; G≥3), 4.0% (1.0%; G≥3), and 10.0% (0.0%; G≥3) of pts, respectively. There were no drug-related deaths. CONCLUSIONS 1L ATZ + BVZ + PTX demonstrated encouraging anti-tumor activity in aTNBC pts, most of them presenting with PD-L1-negative tumors. Median PFS seems to be much higher compared with that previously reported with other IO-based regimens in a similar patient population. The safety profile was consistent with the known safety data of ATZ and BVZ combined with CT, without significant added toxicity. These results merit further research of this combination for PD-L1-negative aTNBC. Citation Format: Maria Gion, Patricia Cortez-Castedo, Isabel Blancas, Alfonso Cortés, Frederik Marmé, Salvador Blanch, Serafin Morales Murillo, Nieves Díaz, Isabel Calvo-Plaza, Sabela Recalde, Alejandro Martínez-Bueno, Manuel Ruiz-Borrego, Elisenda Llabres, María Teresa Taberner, Michelino de Laurentiis, José Ángel García-Sáenz, Jana Repkova, Antonio Antón, Joseph Gligorov, Susana de la Cruz, Oliver Hoffmann, Jacques Medioni, Melissa Phillips, Miguel Sampayo-Cordero, Daniel Alcalá-López, José Manuel Pérez-García, Antonio Llombart-Cussac, Javier Cortés. Efficacy and safety of first-line atezolizumab + bevacizumab + paclitaxel in patients with advanced triple-negative breast cancer: the ATRACTIB phase 2 trial [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 PS16-02.

Dentistry in Ancient Egypt

Dentistry, dated in Ancient Egypt as an independent profession since the early 3rd millennium BC, was the first specialty recorded in a document in ancient Egypt, but nothing proves teeth interventions in mummies. The mouth and dental preservation was very important in rituals and theology because, as a source of exterior speech, it allowed man to express his spiritual feelings. The emphasis put on the mouth, lips, tongue, palate and teeth, was connected with the soul, the expression, and articulation of words. In the ‘Opening of the mouth’ ceremony, the dead jaws were freed to rebirth, give a voice and utter the words and names of power. Thus the white and healthy child Horus’ teeth allow to make up the undamaged mouth (PT 79 a) and five onions, their symbolic representation, were given the dead as a sacred offering. The emphasis put on the mouth, lips, tongue, palate and teeth, was connected with the soul, the expression, and articulation of words. As source of exterior speech, they allow man to express his spiritual feelings. In the Memphite theology the intellectual God Creator Ptah have generated the world pronouncing their names. Teeth and lips represent the magical verbal action and the tongue means speech, the _logos_. Dental problems were well known and some indications of doctor’s different diagnosis and treatments were found in medical papyri. The most common dental diseases were: attrition, frequent until pulp exposure, receding gums, caries and the destruction of enamel, chronic suppurative periodontitis that causes mobility, dental abscess and sepsis, loose teeth, ulcerative stomatitis, alveolar diseases and heavy deposits of calculus. Egyptian paleopathology and molecular biology provide new medical information and had revolutionized all aspects of dentistry, changing previous beliefs. However Egyptians were creative or witty and had devised many treatments for the various affections, both chirurgical and medicinal in nature, using different drugs. By studying a critical scrutiny of the development of dentistry profession in ancient times, it has been possible an exploration of dental problems, diseases and treatments and establishing guidelines and difficulties.

Problems of Dating Spread on Radiocarbon Calibration Curve Plateaus: The 1620–1540 BC Example and the Dating of the Therasia Olive Shrub Samples and Thera Volcanic Eruption

AbstractDetermining calendar ages for radiocarbon dates, or ordered sequences of radiocarbon dates, that intersect with a plateau on the radiocarbon calibration curve can be problematic since, without additional prior constraints, the calendar age ranges determined will tend to spread across the plateau, yielding wide and less than useful calendar age probability densities and age ranges. Where possible, modeling analysis should seek to identify informative priors that act to restrict the otherwise poorly controlled spread of probability across plateaus. Such additional information may be available, among other sources, from the stratigraphy, the context, or the samples themselves. The recent dating of ordered sequences of radiocarbon dates on sections of branches of the same olive (Olea europaea) shrub from Therasia (southern Aegean) associated with the Minoan eruption of the Thera (Santorini) volcano (Pearson et al. 2023), which intersect with the plateau in the radiocarbon calibration curve ca. 1620–1540 BC, offers an example of the problem. A re-analysis adding some plausible informative priors offers a substantially better defined likely dating range and different conclusions. Instead of finding an inconclusive probability range “encompassing the late 17th and entire 16th century BC” followed by arguments for “indications of increased probabilities for a mid-16th century BC date for the eruption,” a re-analysis incorporating appropriate informative priors identifies the likely date range as falling between the late 17th to early 16th centuries BC.

New Light on the Land of Sūḫu

Abstract In this review article, Philippe Clancier’s recent monograph on the history of the overlooked Late Bronze and Early Iron-age polity of Sūḫu lying on the Middle Euphrates is examined. It is demonstrated that the central contention of two identically named polities of Sūḫu (“Eastern” and “Western Sūḫu” respectively), ruled by two competing dynasties with differing political relationships to Assyria, is not supported by the textual record. As a corrective, a new comprehensive political history of Sūḫu in the early first millennium BC is presented here, as a basis for future research.

Abstract 812: Association of obesity with the early onset and diagnosis of triple negative breast cancer in black women

Abstract Breast cancer (BC) continues to be the most common cancer and the second leading cause of cancer-related death in American women. Furthermore, it affects Black women more adversely than their White counterparts, who experience an early disease onset, diagnosed more often with aggressive triple-negative breast cancer (TNBC) molecular subtype, and face greater mortality. The reasons for these disparities; however, are largely unknown. Here, using a retrospective dataset, we examined the association of body mass index (BMI) with BC early onset and diagnosis with specific molecular subtype in race-based distributions. Study cohort included 1085 BC patients, who visited University of South Alabama Health clinics between October, 2017 and March, 2022. Patients were divided into three BMI [(normal weight, NW (<24.9), overweight, OW (25-29.9), and obese, Ob (>30.0)], three age (<45 years, 45-65 years, >65 years), and four molecular subtypes [Luminal A (HR+, HER2-), Luminal B (HR+, HER2+), HER2 enriched (HR-, HER2+), and TNBC (HR-, HER2-) categories. The data show a higher prevalence of BC in Ob women (46%) than OW (27%) and NW (27%) women of all age groups and its incidence was much greater in Ob Black women (61%) than Ob White women (39%). Further, Black women had nearly twice higher diagnosis at an early age than White women. Moreover, Ob Black women had over 7- and 1.5-folds higher incidence of early onset BC than NW and OW Black women, respectively, whereas, early onset BC did not exhibit a correlative pattern in White women. Luminal A and TNBC subtypes were the most common in women with early onset BC and Black women exhibited more than twice incidence of TNBC (32%) compared to the White women (14%) of all ages. In contrast, incidence of luminal A subtype was less prevalent in Black (57.4%) than in White (72.6%) women. Interestingly, both luminal A and TNBC subtypes were also more prevalent in Ob women; however, the risk of being diagnosed with TNBC increased dramatically in Ob Black women compared to Ob White women. Together, these findings establish obesity as a major underlying cause of early onset BC and TNBC diagnosis in Black women, which could be targeted to diminish the BC disparity gaps. Citation Format: Sarabjeet Kour Sudan, Amod Sharma, Kunwar Somesh Vikramdeo, Wade Davis, Cindy Nelson, Karan Singh, Ajay Pratap Singh, Seema Singh. Association of obesity with the early onset and diagnosis of triple negative breast cancer in black women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 812.

Abstract 4854: Breast cancer incidence trends in Ukraine 2010-2019: Rising incidence at young ages

Abstract Background. BC commonly affects women of older age, however, in developing countries around 20-25% cases of BC presented in young woman. Age-specific clinical characteristics or outcomes data for young women are lacking. Most of the standard treatments used in this subpopulation currently are derived from older patients. Early onset BC is often defined aggressive in nature. Several research have attributed this to a hidden unique biology. However, findings remain controversial. Purpose: The aim of this study is to describe recent trends for BC incidence in Ukraine since 2010 by age groups and interpret them to seek clue for improvement. Methods: We analyzed records from the NCR on 143420 BC cases (C50, International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)) diagnosed in 2010-2019 in female Ukrainian population. The data were submitted on the beginning of 2022. We calculated annual age-standardized incidence rates (ASRWs) for three age groups. The estimated annual percent change (EAPC) of the rates was calculated using the generalized linear regression. The difference of the rates with its statistical significance was determined with the standardized rate ratio. Results: During 2010-2019, the proportion of BC in all cancers detected at the age of 20-44 increased from 21.7% to 25.9%, while the frequency of BC detection at the age of 45+ did not change and ranged 19.3-20.2%. During the study period, the BC incidence rate has increased significantly (≤0.01): the ASRW of females aged 0-85+ grew with EAPC=0.6% amounting to 42.4-45.7 per 100,000 population, the incidence rate of women aged 45+ grew with EAPC=0.3% ranging from 130.0 to 139.6 per 100,000 population, while the incidence rate of women aged 20-44 grew with EAPC=1.8% amounting to 22.8-27.8 per 100,000 population. In age group 20-44 years, EAPC of BC incidence (1.8%) significantly exceeds the EAPC of the incidence for all cancers combined (0.2%). The dynamics of stage distribution showed increasing proportion of BC cases detected in women aged 20-44 in stage 1 (by 4.1% from 2010 to 2019) and its decreasing for BC cases detected in stage 2 by 4.5%; the proportion of cases diagnosed in stage 4 decreased by 0.5% along with increase in number of cases with undefined stage by 0.6%. Conclusions: The obtained results indicate trends for increasing the incidence of Early Onset BC in Ukraine and justify need for the further research elucidating prognosis and validating novel biomarkers for customizing therapy for this patient group . Citation Format: Nataliia Verovkina, Olena Sumkina, Liubov Syvak, Wafik El-Diery. Breast cancer incidence trends in Ukraine 2010-2019: Rising incidence at young ages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4854.

Abstract 6991: Transcriptomic profiling of human and mouse models highlights YAP pathway hyperactivation as the underlying mechanism of the biological and clinical aggressiveness of Numb-defective bladder cancer

Abstract In this study, we identify a previously uncharacterized role for the tumor suppressor, Numb, in bladder tumorigenesis, defining new predictive biomarkers and potentially actionable targets for the treatment of non-muscle-invasive bladder cancers. We conducted a comprehensive IHC analysis of Numb expression leveraging two retrospective longitudinal cohorts comprising 356 post-cystectomy muscle-invasive bladder cancer (MIBC) patients and 77 high-grade non-muscle-invasive (NMIBC) patients with transurethral resections. We found that Numb expression is frequently deregulated in the tumor compared to the adjacent normal urothelium, with NumbLow status correlating with poorer prognosis both in MIBC, associated with advanced stage at diagnosis, vascular invasion, and worse overall survival, and in NMIBC, where a NumbLow status associates with a higher rate of progression to life-threatening MIBC disease. In a transgenic mouse model with targeted deletion of the Numb gene in the basal layer of the bladder mucosa, we observed that loss of Numb per se is sufficient to drive malignant transformation of the normal urothelium and accelerates tumorigenesis in carcinogen-induced models. Integrative transcriptomic analysis of human and mouse Numb-deficient BC models revealed consistent dysregulation of the YAP1/TAZ1 inhibitory Hippo pathway, identifying YAP1 transcriptional hyperactivation as the most distinguishing trait downstream of NUMB loss. Through genetic and pharmacological functional inhibition studies in relevant mouse and human BC cell line-based models, we provide proof-of-evidence that interfering with YAP pathway activation at multiple upstream levels of the Hippo cascade reverts the aggressive Numb loss-associated tumor phenotypes, in particular growth and invasive/migratory potential, thereby highlighting the YAP pathway as a potential therapeutical vulnerability for the treatment of clinically aggressive Numb-deficient human BC. We also identified a gene signature of early BC depending on loss of Numb that we extensively validated for its potential as a predictor of NMIBC to MIBC progression, arguing for its clinical application as a biomarker for NIMBC patient stratification for targeted anti-YAP signaling treatment to prevent MIBC transition. In summary, our study identifies a previously uncharacterized role of Numb in bladder cancer progression, highlighting its potential as a predictive biomarker of NMIBC to MIBC transition and response to targeted therapies, thereby advancing a framework for precision oncology for NMIBC patients at high risk of progression to life-threatening MIBC disease. Citation Format: Francesco Antonio Tucci, Rosa Pennisi, Maria Grazia Filippone, Roberta Bonfanti, Francesco Romeo, Damiano Rigiracciolo, Stefano Freddi, Francesca Sanguedolce, Giuseppe Renne, Giancarlo Pruneri, Gianluca Vago, Daniela Tosoni, Salvatore Pece. Transcriptomic profiling of human and mouse models highlights YAP pathway hyperactivation as the underlying mechanism of the biological and clinical aggressiveness of Numb-defective bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6991.

Abstract 6076: Mathematical oncology in the context of early breast cancer detection

Abstract Breast cancer (BC) is the most common cancer in women globally, with approximately 94% of patients initially diagnosed with early-stage disease. However, despite the initial lack of detectable metastases and administration of subsequent treatments, 40% of these patients will develop recurrence over their lifetime. The standard screening method for BC is mammography, with a tissue biopsy to confirm diagnosis. However, only ~60% of all cases are currently diagnosed via this pathway, primarily due to the limited (86.9%) sensitivity. To demonstrate the feasibility of a liquid biopsy (LBx) test for early BC detection and assessment, we employed the third-generation, High Definition Single Cell Assay (HDSCA3.0) to detect and characterize rare cells (e.g., circulating tumor cells [CTCs]) and acellular structures (e.g., oncosomes) in patient peripheral blood samples using immunofluorescent (IF) imaging. We have previously investigated this signal in a cohort of early-stage BC patients (n = 74), late-stage BC patients (n = 26), and age- and gender-matched controls (n = 30) and observed statistically significant differences in levels of total rare cells, CTCs, and oncosomes via a manual approach. For this study, we employed a hybrid methodology, that utilizes both automatic and manual techniques, to investigate the reproducibility of the signal in an expanded validation set. Within this modified approach, we employ an outlier detection algorithm to accelerate the rare event identification and curation process (minimizing the manual portion), a separate machine learning model to classify the events based on their IF expressions, and a suite of applications to enumerate and quantify the result. After implementation, we quantified the results of the fully manual and hybrid approaches to determine the signal loss associated with scale up. Utilizing the hybrid approach, we observed similar results as with the fully manual and were able to stratify the three cohorts with high accuracy. Namely, there was an increase in the total rare cell and CTC populations in late-stage BC patients, and an increase in the oncosome population for the early-stage BC patients. To note, these patients included a subset with invasive lobular carcinoma (ILC; n = 19), which manifests in ~5-15% of BC cases and is considered “mammogram silent” due to the biological development of the disease. Additionally, employing the hybrid approach allowed for analyzing patient samples in less time while minimizing overall signal loss. In summary, we have been able to detect reproducible patterns in the enumeration of rare cells and oncosomes with high accuracy. When utilized at the patient-level, these analytes can power prediction models that are capable of stratifying disease from non-disease. The results presented here demonstrate the utility of a LBx test as a companion to screening mammography in the detection of early-stage BC across various histologies. Citation Format: Jeremy Mason, Stephanie N. Shishido, George Courcoubetis, Dean Tessone, Emmett Liljegren, Amin Naghdloo, James Hicks, Jorge J. Nieva, Peter Kuhn. Mathematical oncology in the context of early breast cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6076.

Iron Age Connectivity Revealed by an Assemblage of Egyptian Faience in Central Iberia

Research concerning transactions in the early first millennium bc in the westernmost Mediterranean has tended to focus on colonial coastlands occupied by scattered Levantine outposts, whereas cross-cultural interactions in hinterland regions have remained ill-defined. This article presents an assemblage of Egyptian vitreous artefacts, namely beads, a Hathor amulet, and further items from the seventh-century bc rural village of Cerro de San Vicente (Salamanca) in the interior of Spain. Macroscopic and chemical analyses demonstrate their likely manufacture in Egypt during the Middle and New Kingdom (second millennium bc), attesting to a far-reaching Phoenician maritime network that connected both ends of the Mediterranean. The authors interpret the items as liturgical objects, rather than mere high-status trinkets, that formed part of a widely shared Mediterranean world view and associated ritual mores. They consider the impact of cultural syncretism, which reached even remote and allegedly isolated peripheral settings in Iberia.

Late prehistoric and early historic chronology of Myanmar: a four-millennia sequence from Halin

Myanmar is located within an important geographic corridor of prehistoric demographic and technological exchange, yet relatively few archaeological sites have been securely dated. Here, the authors present a new radiocarbon chronology for Halin, a UNESCO-listed complex in the north-central Sagaing Division of Myanmar, which contributes to the generation of nuanced regional chronologies and to improving the temporal resolution of Southeast Asia more generally. Discussion of 94 radiocarbon determinates, together with site stratigraphy and pottery traditions, provides a chronological sequence from the early third millennium BC to the early second millennium AD. Corroboration of the beginning of this sequence would place Halin as the oldest currently dated Neolithic site in Mainland Southeast Asia and would provide support for the two-layer model of Neolithic migration.

ФИНАНСИРОВАНИЕ ПРАЗДНИКОВ В АФИНАХ ВТОРОЙ ПОЛОВИНЫ V - НАЧАЛА IV В. ДО Н. Э. ПО ДАННЫМ ДОГОВОРОВ ОБ АРЕНДЕ ТЕМЕНОСОВ

The article deals with the issue of financing festive ceremonies in ancient Athens in the middle of the 5th – early 4th centuries BC Epigraphic material is used as the main source – inscriptions dedicated to the leasing of sacred land plots (temenos). In ancient Greece, there were a large number of holidays that were held pompously. Judging by the information of ancient authors, data from archeology and epigraphy, a large expenditure of funds was spent on their conduct, which came from various sources. The analysis of the content of the inscriptions on the leasing of temenos suggests how festivals were financed in ancient Attica during the leasing of sacred lands. The analysis of the epigraphic data shows that, in accordance with the terms of the temenos lease agreements, landlords (demes, phratries and religious communities) ordered tenants to transfer funds to finance public celebrations (Panathenaea, Apaturia, Dionisii), as well as for local holidays. In addition, part of the grown crops and livestock were sent to the solemn sacrifices that accompanied every Greek holiday. The receipt of those funds was monitored by officials of the Athens polis.

Plateletcrit is predictive of clinical outcome and prognosis for early-stage breast cancer: A retrospective cohort study based on propensity score matching.

Breast cancer (BC) is diagnosed as the most common cancer in women in 2022 according to the American Cancer Society. It is essential to detect early and treat early. Several studies have shown that some blood parameters have important predictive value for BC. In this study, we aim to explore whether some immune-associated blood parameters are relevant to disease-free survival (DFS) in early-stage BC. A single-center, regression cohort study of 1490 patients with early-stage BC in Shanghai Cancer Center was conducted from January 2008 to December 2016. The patients were matched according to the ratio of 1:1 based on Propensity Score Matching (PSM). All patients who experienced disease progression were matched successfully. Thus, 58 pairs of subjects were obtained. Matched blood parameters were evaluated by paired samples t-test or Wilcoxon signed-rank test. Factors with statistical difference were further evaluated by stratified COX regression model. Univariate analysis showed differences in platelet-related parameters (PLT, PCT, and PLR) and NLR between the two matched groups. However, stratified COX regression analysis, which ruled out the confounding effects of multiple factors, found that only PCT had prognostic value in early BC patients at baseline and study endpoint. Meanwhile, platelet-related parameters (PLT, MPV) and NLR were different in the progressive group by self before and after comparison. However, the multiple-factor analysis showed that only the NLR had prognostic value. ROC curve analysis indicated that the best sensitivity (65.45%) and specificity (78.18%) were obtained when the baseline PCT was 0.225. The optimal sensitivity (70.91%) and specificity (65.45%) were obtained when the PCT of disease progression was 0.215. The Kaplan-Meier curve was used to calculate the DFS rate based on the critical values of the two groups. Some blood parameters have value to predict DFS in early-stage BC patients, especially platelet-associated parameters.