Giridhar, Karthik V.

Abstract Background: Multi-cancer early detection (MCED) tests are being established as a novel approach to screen for multiple cancer types with one test. A blood-based MCED test using cell-free DNA targeted methylation patterns to detect a shared cancer signal and predict a cancer signal origin (CSO) has demonstrated feasibility. An initial return of results study (PATHFINDER; NCT04241796) reported performance of a refined version of the MCED test, including a 43.1% positive predictive value (PPV), 98.5% negative predictive value (NPV), 99.5% specificity, and 88.0% CSO accuracy. To build on this work, the PATHFINDER 2 study (NCT05155605) will evaluate safety and performance of the MCED test in larger, more diverse populations. Methods: PATHFINDER 2 is a prospective, multicenter, interventional study. Participants ≥50 years of age will be enrolled, with specific targets to improve diversity (age, sex, race/ethnicity) and few exclusions due to comorbid conditions. Exclusion criteria include current clinical suspicion of cancer or recent cancer/treatment (within 3 years). Participants will undergo blood draw for MCED testing, followed by return of results (cancer signal detection and CSO) to the investigator and diagnostic evaluations if a cancer signal is detected. A confirmatory PET-CT scan will be performed when CSO-directed workups do not result in a cancer diagnosis. Participants will be followed for approximately 3 years. Primary endpoints include 1) MCED test safety in terms of diagnostic testing triggered by a positive result (number/type of procedures and adverse events) and 2) test performance (PPV, NPV, specificity, sensitivity, CSO accuracy, cancer detection rate and number needed to screen). Secondary endpoints include participant reported outcomes (eg, anxiety), utilization of guideline-recommended cancer screening, and cancer detection rate of confirmatory PET-CT, amongst others. The study plans to enroll approximately 35,000 participants across North America. Sites were selected based on geographic location, catchment area demographics, and practice setting (academic vs non-academic). Enrollment targets for age, sex and race/ethnicity (White [non-Hispanic] 72%; Hispanic or Latino 11%; African American or Black 11%; Asian, Native Hawaiian or Other Pacific Islander 6%; American Indian/Alaska Native 1%) were derived from US Census data. Strategies to promote diverse recruitment include translation of participant-facing documents across multiple languages, participant and healthcare provider educational material, and site-led community outreach campaigns. MCED testing is an emerging, potentially paradigm-changing strategy in cancer screening, and PATHFINDER 2 is designed to characterize the safety, performance, and clinical implementation of the MCED test as a screening tool in a broad and representative population. Citation Format: Karthik V. Giridhar, Michael J. Demeure, Raymond H. Kim, Justin A. Chen, Shirish Gadgeel, Dax Kurbegov, Margarita Lopatin, Roland Matthews, Marc Matrana, Charles McDonnell, Donald Richards, Benjamin Rybicki, Gretchen Stipec, Nima Nabavizadeh. PATHFINDER 2: A prospective study to evaluate safety and performance of a multi-cancer early detection test in a population setting [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 4784.

Abstract Purpose A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used. Materials and Methods A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 ­olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%. Results A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist. Conclusion This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081).

12114 Background: A retrospective study suggested a potential benefit from rose geranium in sesame oil nasal spray for alleviating nasal vestibulitis symptoms in patients (pts) undergoing chemotherapy. Methods: Pts undergoing active chemotherapy who reported moderate or worse nasal symptoms were randomized 1:1 to receive a rose geranium in sesame oil nasal spray (RG) or an isotonic saline nasal spray (IS), administered twice daily for two weeks. Consenting pts completed nasal symptom questionnaires at baseline and then weekly while on treatment. The number and percentage of pts experiencing improvements in their nasal symptoms 2 weeks after initiating the nasal spray, defined as symptoms moderately (2) or very much (3) better on a 7-point global impression of change score (ranging from scores of -3: very much worse, to 3: very much better), was estimated within and then between each randomized arm, using Fisher’s exact test (5% significance level). The estimated odds ratio was determined (95% confidence interval). After 2 weeks, pts initially randomized to IS were allowed to cross-over to RG and completed weekly surveys. Results: 106 pts consented to this study; 43 pts in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Pts had a mean age of 57.8 (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. The most prominent baseline nasal symptoms were dryness (36%) and bleeding (35%). Of the 43 evaluable pts who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the 41 pts who received IS (p=0.009; Table). On the global impression of change score, pts who received RG had a mean score of 1.93 (SD 1.16), compared to a mean score of 0.98 (SD 1.41) among pts who received IS. Adjusting for potential confounding factors, pts who received RG had a 4.56 odds of responding to the nasal spray, compared with those who received IS (p=0.005). There were no significant differences between pt responses based upon type of nasal symptoms, age, allergies, or gender. Adverse events were sparse and did not differ between arms. 34 pts crossed over to RG after week 2. Among the 29 pts who completed final surveys, 37% reported a response on IS, 79% reported a response on RG. Conclusions: Rose geranium in sesame oil nasal spray significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy. Clinical trial information: NCT04620369 . [Table: see text]

6557 Background: Trials that inadequately include underrepresented minority (URM) populations widen inequities in cancer care. We assessed reporting patterns, representation, and trends of URM representation in breast cancer (BC) trials. Methods: We analyzed all phase 2/3 trials for age disparity and trials recruiting from the US for racial/ethnic disparity amongst BC RCTs (1990-2021). Enrollment-incidence ratios (EIR), which compare trial proportions (TP) from age subgroups against global estimates of incidence in the corresponding age group (from Global Burden of Disease) and racial/ethnic subgroups against US-population-based incidence in the corresponding racial/ethnic group (from SEER 22), were calculated. Individual-trial EIRs were pooled using random-effects meta-analyses. EIRs of <0.80 indicated meaningful underrepresentation, while EIRs >1.20 indicated meaningful overrepresentation. Meta-regression was used to explore associations between key trial characteristics and EIR, and trends in EIR over the last three decades. Results: Of 842 global trials with 490,657 participants, 232 (27.6%) reported the number of participants in specific age strata and 144 (17.1%) reported outcomes by age. Only 60 trials recruited exclusively from the US. Of these, 41 (68.3%) reported race and 24 (40.0%) reported ethnicity, and 2 (3.3%) analyzed outcomes by race. Older adults aged ≥65 years (TP: 24.3%; EIR: 0.53 [95% CI: 0.47-0.60]) and Hispanic women (TP: 5.3%; 0.54; 0.40-0.75) were underrepresented across global trials and US-only trials respectively. Black women were significantly underrepresented in trials that led to FDA approval (0.38; 0.25-0.58) but not in US-only trials. Stratified analysis by BC subtype (with subtype-specific population incidence) showed underrepresentation of Black women in US-only trials for HER2+ BC (0.66; 0.47-0.93), Hispanic women in ER+ BC (0.42; 0.20-0.90), Asians in triple-negative BC (0.24; 0.11-0.53), and older women in HER2+ BC (0.35; 0.31-0.40) and triple-negative BC (0.36; 0.29-0.45). From 1990-2021, the representation of older women declined significantly (meta-regression coefficient for EIR: -0.4 per 10 years), while Black and Hispanic representation showed no significant change. Black (p = 0.02) and Hispanic representation (p = 0.05) worsened significantly in larger trials. Conclusions: Published reports of BC trials do not consistently report the inclusion of URM. Older and Hispanic women were consistently underrepresented, whereas Black women were underrepresented in large, practice-changing trials. [Table: see text]

Abstract Purpose: Strategies to implement estrogen therapy for advanced estrogen receptor–positive (ER+) breast cancer are underdeveloped. Preclinical data suggest that cycling treatment with 17β-estradiol followed by estrogen deprivation can control tumor growth long-term. Patients and Methods: Postmenopausal women with advanced ER+/HER2− breast cancer with recurrence or progression on ≥ 1 antiestrogen or aromatase inhibitor (AI)-based therapy were eligible. Patients received 17β-estradiol (2 mg orally, three times a day) for 8 weeks followed by AI (physician's choice) for 16 weeks, alternating treatments on an 8-week/16-week schedule until disease progression. Patients then optionally received continuous single-agent treatment until a second instance of disease progression. Endpoints included 24-week clinical benefit and objective response per RECIST, and tumor genetic alterations. Results: Of 19 evaluable patients, clinical benefit rate was 42.1% [95% confidence interval (CI), 23.1%–63.9%] and objective response rate (ORR) was 15.8% (95% CI, 5.7%–37.9%). One patient experienced a grade 3 adverse event related to 17β-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5 of 12 (41.7%) cases. Tumor ER (ESR1) mutations were found by whole-exome profiling in 4 of 7 (57.1%) versus 2 of 9 (22.2%) patients who did versus did not experience clinical benefit from alternating 17β-estradiol/AI therapy. The only two patients to experience objective responses to initial 17β-estradiol had tumor ESR1 mutations. Conclusions: Alternating 17β-estradiol/AI therapy may be a promising treatment for endocrine-refractory ER+ breast cancer, including following progression on CDK4/6 inhibitors or everolimus. Further study is warranted to determine whether the antitumor activity of 17β-estradiol differs according to ESR1 mutation status.

Abstract Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

AbstractObjectiveElevated serum chromogranin A (CGA) is associated with intrinsic or treatment‐related neuroendocrine differentiation (NED) in men with metastatic castration‐resistant prostate cancer (mCRPC). Fluctuations in serum CGA during treatment of mCRPC have had conflicting results. We analyzed the impact of (i) rising serum CGA and (ii) baseline CGA/PSA ratio during treatment to identify associations with abiraterone acetate (AA) therapy.MethodsBetween June 2013 and August 2015, 92 men with mCRPC were enrolled in a prospective trial with uniform serum CGA processing performed before initiating abiraterone acetate/prednisone (AA/P) and serially after 12 weeks of AA/P treatments. Serum CGA was measured using a homogenous automated immunofluorescent assay. Patients receiving proton pump inhibitors or with abnormal renal function were excluded due to possible false elevations of serum CGA (n = 21 excluded), therefore 71 patients were analyzed. All patients underwent a composite response assessment at 12‐weeks. Kaplan–Meier estimates and Cox Regression models were used to calculate the association with time‐to‐treatment failure analyses and overall survival.ResultsAn increase in chromogranin was associated with a lower risk of treatment failure (hazard ratio [HR]: 0.52, p = 0.0181). The median CGA/PSA ratio was 7.8 (2.6–16.0) and an elevated pretreatment CGA/PSA ratio above the median was associated with a lower risk of treatment failure (HR: 0.54 p value = 0.0185). An increase in CGA was not found to be associated with OS (HR: 0.71, 95% CI: 0.42–1.21, p = 0.207). An elevated baseline CGA/PSA ratio was not associated with OS (HR: 0.62, 95% CI: 0.37–1.03, p = 0.062). An increase in PSA after 12 weeks of treatment was associated with an increased risk of treatment failure (HR: 4.14, CI: 2.21–7.73, p = < 0.0001) and worse OS (HR: 2.93, CI: 1.57–4.45, p = < 0.0001).ConclusionsWe show that an increasing chromogranin on AA/P and an elevated baseline CGA/PSA in patients with mCRPC were associated with a favorable response to AA/P with no changes in survival. There may be limited clinical utility in serum CGA testing to evaluate for lethal NED as AA/P did not induce lethal NED in this cohort. This highlights that not all patients with an increasing CGA have a worse OS.

201 Background: Previous studies have evaluated peripheral whole blood mRNA to identify prognostic biomarkers in metastatic prostate cancer, with no consistent genes of prognostic significance between studies and sample collection done at various points of therapy. We aim to identify the prognostic value of 20 previously identified genes in patients mCRPC from a prospective clinical trial. Methods: Between June 2013 and August 2015, whole blood was prospectively collected in PAXgene RNA tubes from 92 men with mCRPC (NCT01953640). Gene expression from samples with RIN > 4.0 were quantified using a customized NanoString CodeSet of 20 candidate genes (C1QA, MCM2, STOM, GABARAPL2, R10K3, HMBS, TFDP1, CDKN1A, ITGAL, TMCC2, TERF2IP, MMP9, SNCA, TIMP1, SLC4A1, SELENBP1, TMEM66, SEMA4D, PROS1, CD22). The raw data from the nCounter Analysis system were normalized to the positive controls and log2 transformed. Univariable Cox proportional hazards models were performed on each target gene sufficiently above negative control (5 times the maximum value of the negative control) to evaluate associations with overall survival (OS). For each gene we considered a linear, quadratic, or categorical model with quantile cutpoints. Categorical models with cutpoints at the 25th percentile for the genes CD22, GABARAPL2, R10K3, and STOM were used as there was a nonlinear relationship between gene expression and death hazard. The remaining genes were modeled with a linear model. Findings were considered statistically significant based on p-values adjusted using the Holm-Bonferroni correction. Results: 18/20 genes were identified and passed quality control (QC) measures, which excluded C1QA and MCM2. 72/92 men had an evaluable pretreatment specimen that passed QC. The median age was 72 years. The study cohort was evenly balanced in terms of Gleason score ( < = 7 v. > 7) and 60% had high volume disease. The median follow-up time was 5.73 years (IQR: 5.39, 6.49) and 58 patients had died. Of the 18 genes evaluated, STOM (Stomatin) [hazard ratio (HR) 3.00, adjusted p = 0.007] and GABARAPL2 (GABA Type A Receptor Associated Protein Like 2) [HR 2.62, adjusted p = 0.033] were significantly associated with overall survival in univariate analysis. In multivariate analysis, after adjusting for volume of metastatic disease and Gleason score, STOM [HR 2.89, adjusted p = 0.014] was significantly associated with overall survival. Conclusions: Elevated whole blood mRNA expression of STOM is adversely associated with OS in mCRPC. Further studies investigating elucidating the molecular significance of STOM in mCRPC are planned. Clinical trial information: NCT01953640 .

ImportanceAurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. The safety and preliminary efficacy of alisertib was demonstrated in early-phase trials; however, its activity in CDK 4/6i–resistant MBC is unknown.ObjectiveTo assess the effect of adding fulvestrant to alisertib on objective tumor response rates (ORRs) in endocrine-resistant MBC.Design, Setting, and ParticipantsThis phase 2 randomized clinical trial was conducted through the Translational Breast Cancer Research Consortium, which enrolled participants from July 2017 to November 2019. Postmenopausal women with endocrine-resistant, ERBB2 (formerly HER2)–negative MBC who were previously treated with fulvestrant were eligible. Stratification factors included prior treatment with CDK 4/6i, baseline metastatic tumor ERα level measurement (&amp;lt;10%, ≥10%), and primary or secondary endocrine resistance. Among 114 preregistered patients, 96 (84.2%) registered and 91 (79.8%) were evaluable for the primary end point. Data analysis began after January 10, 2022.InterventionsAlisertib, 50 mg, oral, daily on days 1 to 3, 8 to 10, and 15 to 17 of a 28-day cycle (arm 1) or alisertib same dose/schedule with standard-dose fulvestrant (arm 2).Main Outcomes and MeasuresImprovement in ORR in arm 2 of at least 20% greater than arm 1 when the expected ORR for arm 1 was 20%.ResultsAll 91 evaluable patients (mean [SD] age, 58.5 [11.3] years; 1 American Indian/Alaskan Native [1.1%], 2 Asian [2.2%], 6 Black/African American [6.6%], 5 Hispanic [5.5%], and 79 [86.8%] White individuals; arm 1, 46 [50.5%]; arm 2, 45 [49.5%]) had received prior treatment with CDK 4/6i. The ORR was 19.6%; (90% CI, 10.6%-31.7%) for arm 1 and 20.0% (90% CI, 10.9%-32.3%) for arm 2. In arm 1, the 24-week clinical benefit rate and median progression-free survival time were 41.3% (90% CI, 29.0%-54.5%) and 5.6 months (95% CI, 3.9-10.0), respectively, and in arm 2 they were 28.9% (90% CI, 18.0%-42.0%) and 5.4 months (95% CI, 3.9-7.8), respectively. The most common grade 3 or higher adverse events attributed to alisertib were neutropenia (41.8%) and anemia (13.2%). Reasons for discontinuing treatment were disease progression (arm 1, 38 [82.6%]; arm 2, 31 [68.9%]) and toxic effects or refusal (arm 1, 5 [10.9%]; arm 2, 12 [26.7%]).Conclusions and RelevanceThis randomized clinical trial found that adding fulvestrant to treatment with alisertib did not increase ORR or PFS; however, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and CDK 4/6i–resistant MBC. The overall safety profile was tolerable.Trial RegistrationClinicalTrials.gov Identifier: NCT02860000

Abstract Background: Two poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) are currently FDA-approved for the treatment of HER2-negative metastatic breast cancer (MBC) in carriers of germline pathogenic variants (PVs) in BRCA1 or BRCA2 (BRCA1/2). This study explores the clinical outcomes of MBC patients treated with a PARPi. Methods: In this retrospective study, we included MBC patients treated with a PARPi between January 2017 and February 2022 at Mayo Clinic (Minnesota, Arizona, Florida, and Mayo Clinic Health Systems). We used the Kaplan Meier method to estimate the time-to-treatment-failure (TTF) and the log-rank test to compare different subsets. In addition, predictors of TTF were identified in a multivariate cox-proportional hazard regression model, including age at PARPi initiation, race, ethnicity, histology, estrogen receptor (ER), progesterone receptor (PR), and HER2 expression of the tumor, the number of prior therapies, type of PARPi, and PV carrier status (germline BRCA1/2 or PALB2 vs. somatic BRCA1/2 vs. other). Results: Sixty-five patients treated with PARPi (olaparib: 51; talazoparib: 14) were included in the final analysis. Fifty-five patients were carriers of germline PVs in BRCA1 (n=24, 37%), BRCA2 (n=27, 42%) or PALB2 (n=4, 6%), whereas ten patients (15%) had no germline PVs but the tumor had a somatic mutation in the homologous recombination-related (HRR) genes (7 in BRCA1/2, 2 in ATM, and 1 in CDKN2A and CDH1). At the data cutoff, 48 (74%) patients had discontinued PARPi due to progression or death. Fifteen (23%) patients required a dose reduction due to side effects. Occurrence of grade ≥ 3 side effects: anemia in 8, fatigue in 4, neutropenia in 2, and thrombocytopenia in 2 patients. Eight (15.7%) patients in the olaparib group and seven (50%) patients in the talazoparib group required a dose reduction for side effects. No patient on olaparib required drug discontinuation due to side effects, whereas two patients on talazoparib were switched to olaparib due to cytopenias and could tolerate olaparib. Median TTF in the overall population was 8 months (95% confidence interval [CI]: 6.4 – 9.6), and there was no difference (p=0.64) in TTF between the olaparib and talazoparib groups. Median TTF in the germline BRCA1, BRCA2, and PALB2 PV carriers were 7, 8, and 11 months, respectively (p=0.57). Among patients with somatic BRCA1/2 mutations, the median TTF was 4 months. Numerically, patients with HER2-positive tumors (n=8) had a shorter TTF compared to HER2-negative tumors (Median TTF: 4 vs. 8 months, p=0.098). No significant difference in TTF was observed by ER or PR status of the tumor, age at initiation of PARPi, the number of prior therapies, and prior use of platinum-based chemotherapy or CDK4/6 inhibitors. In multivariate analysis, HER2 positivity (hazard ratio [HR]: 8.0, 95% CI: 2.2 – 29.4, p=0.002), somatic BRCA1/2 mutations (HR: 7.6, 95% CI: 1.2 – 50.0, p=0.03) and somatic mutations in other HRR genes (HR: 19.1, 95% CI: 3.1 – 118.6, p=0.002) were associated with worse TTF. Conclusions: In the real world, PARPi were well-tolerated with promising time-to-treatment-failure (TTF) benefits comparable to data from clinical trials. Notably, relatively shorter TTF was observed in patients with somatic BRCA1/2 and other HRR gene mutations and HER2-positive MBC. These findings improve our understanding of the role of PARPi in MBC and will help to guide treatment decisions with PARPi in the clinical setting. Citation Format: Nusrat Jahan, Jodi Taraba, Karthik V. Giridhar, Roberto A. Leon-Ferre, Amye J. Tevaarwerk, Elizabeth Cathcart-Rake, Ciara C. O’Sullivan, Prema Peethambaram, Timothy J. Hobday, Kathryn Ruddy, Lida A. Mina, Pooja Advani, Felipe Batalini, Matthew P. Goetz, Tufia C. Haddad, Fergus J. Couch, Siddhartha Yadav. Clinical outcomes of metastatic breast cancer patients treated with poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi): the Mayo Clinic experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-22.