High-risk Early Breast Cancer Research Articles

Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: a plain language summary of the monarchE study.

This article summarizes the most recent results of the monarchE study. This study was completed in participants with a type of breast cancer called HR+, HER2-, node-positive, high-risk early breast cancer. In this study, abemaciclib, a non-chemotherapy treatment, was administered with standard of care endocrine therapy after curative surgery. Most participants had received prior chemotherapy and/or radiotherapy. The study investigated if abemaciclib helped participants live longer without their cancer returning compared with participants who only received standard of care endocrine therapy. The study participants were assigned to 1 of 2 treatment groups. Participants in Group A were assigned to receive standard of care endocrine therapy with abemaciclib for 2years, followed by endocrine therapy for a total of at least 5years. Participants in Group B were assigned to receive standard of care endocrine therapy only for at least 5years. The effect of treatment was compared between these 2 groups. Overall, the results showed that the cancer was 34% less likely to come back after surgery in the participants in Group A (abemaciclib plus endocrine therapy) compared with those in Group B (endocrine therapy only). At 4years since the start of the study treatment, more participants who received the combination of abemaciclib plus endocrine therapy remained free of cancer compared with participants who received endocrine therapy alone (86% versus 79%). Participants who received abemaciclib plus endocrine therapy had more side effects than those who received endocrine therapy alone, but most of these effects were mild to moderate and reversible upon the end of therapy. The most common side effects in the abemaciclib group were diarrhea, infections, low number of white blood cells, and tiredness. This study found that administering abemaciclib in combination with standard endocrine therapy after curative breast surgery helped lower the risk of cancer returning in people with HR+, HER2-, node-positive, high-risk early breast cancer. Abemaciclib is a new treatment option for people with this diagnosis. People with high-risk early breast cancer should always talk to their doctors and nurses before making any decisions about their treatment.Clinical Trial Registration: NCT03155997 (monarchE study).

Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Although dose-dense adjuvant chemotherapy administered once every 2 weeks leads to superior outcomes compared with standard regimens once every 3 weeks, the observed improvement is largely limited to studies using the suboptimal paclitaxel schedule once every 3 weeks as control. PANTHER is an international phase III trial which compared sequential epirubicin/cyclophosphamide and docetaxel administered either once every 2 or once every 3 weeks, with tailored dosing at the dose-dense schedule according to hematologic toxicity. In this end-of-study analysis, the median follow-up was 10.3 years. Compared with standard adjuvant chemotherapy, dose-dense treatment improved breast cancer recurrence-free survival (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.98]; P = .030), event-free survival (HR, 0.78 [95% CI, 0.65 to 0.94]; P = .009), and distant disease-free survival (HR, 0.79 [95% CI, 0.64 to 0.98]; P = .030) while the improvement in overall survival was not statistically significant (HR, 0.82 [95% CI, 0.65 to 1.04]; P = .109). To our knowledge, this is the first trial that confirms the benefit of a dose-dense regimen over a control regimen containing docetaxel once every 3 weeks.

Prognostic utility of ctDNA detection in the monarchE trial of adjuvant abemaciclib plus endocrine therapy (ET) in HR+, HER2-, node-positive, high-risk early breast cancer (EBC).

LBA507 Background: In monarchE (NCT03155997), 2 years of adjuvant abemaciclib + ET resulted in sustained improvement in invasive disease-free survival (IDFS; HR=0.680, 7.6% absolute benefit at 5 years) in patients (pts) with HR+, HER2-, node-positive, high-risk EBC. Here, we investigate the prognostic value of ctDNA detection and dynamics in pts from monarchE. Methods: Samples were analyzed from a selected pt subset (n=1397; abemaciclib + ET arm, n=685; ET arm, n=712), enriched for overall IDFS events compared to the total monarchE study population (IDFS event rate: 31% [433/1397] vs 18% [992/5637]). Pts had blood collected pre-study treatment (baseline) and at 3, 6, or 24 months. ctDNA detection was performed using the personalized, tumor informed Signatera ctDNA assay (Natera, Inc) and whole exome sequencing (WES) of matched primary tumor and normal required for assay design was performed. Results: Among 1397 pts, 65% (n=910) had sufficient plasma samples and WES performed, and all 910 had successful ctDNA assay testing. Among these 910 pts, the IDFS event rate was 27% (abemaciclib + ET, 23% [101/438]; ET alone, 31% [146/472]). Rates of ctDNA positivity (at baseline and any change from baseline) and associated IDFS events are shown in Table. Among pts with ctDNA positivity, 87% had an IDFS event in comparison to 15% with persistent ctDNA negative (-) status during the study. Conclusions: In a pt subset from monarchE enriched for IDFS events, ctDNA detection was relatively infrequent (<20%); however, its detection at any time during the 24 months of study therapy was adversely prognostic. As compared to pts who had remaining ctDNA positive (+), pts who had clearance of ctDNA on therapy had lower risk of IDFS events, but the event risk still remained clinically meaningful in these pts. Clinical trial information: NCT03155997 . [Table: see text]

Emerging drugs in breast cancer: a focus on antibody–drug conjugates and novel treatment options in luminal disease

SummaryRecent years have seen the introduction of several new drugs and novel treatment approaches in early and advanced-stage breast cancer, leading to relevant improvements in outcome. Still, further reduction of recurrence risk in high-risk early breast cancer is required as is further improvement of disease control in metastatic disease, preferentially with parallel improvement of tolerability. Several antibody–drug conjugates are currently under clinical development, among them drugs targeting HER2, HER3 and TROP2; in addition, bispecific HER2-directed antibodies are a promising class of drugs. In hormone receptor-positive disease, optimizing treatment options in patients progressing on prior CDK4/6-inhibitor-based therapies is a focus of clinical research and recent developments encompass small molecule growth-factor pathway inhibitors such as the AKT inhibitor capivasertib, novel PIK3Ca inhibitors such as inavolisib as well as selective oestrogen receptor degraders and modulators. This article is intended as a short review of promising novel drugs in later clinical development in the field of breast cancer.

Relevance of timing intake of everolimus (EVE) combined with adjuvant endocrine therapy (ET) in patients (pts) with high-risk early breast cancer: Results of a sub-study of the UCBG-UNIRAD trial.

542 Background: We reported the benefit of taking evening tamoxifen compared to morning/afternoon as adjuvant treatment for high-risk breast cancers in the UNIRAD phase III trial (NCT01805271) (1). Here, we examine the relevance of EVE timing intake in this trial. Methods: 1,277 pts with high-risk HR+/ HER2- primary BC were randomly assigned to adjuvant ET with placebo or EVE (1). Patients prospectively reported in a diary the daily timing for ET and EVE intake among four 6-h slots (06:00 to 11:59 (morning), 12:00 to 17:59 (afternoon), 18:00 to 23:59 (evening), or 24:00 to 05:59 (night). The association between EVE, ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial. Results: EVE timing was recorded by 513 of 632 patients (81.2%). Patients declaring EVE intake in the morning (n= 248, 48 %) or in the afternoon (n=52, 10%) were older than those declaring evening (n=207, 40 %) or night (n=6,1%) intakes ( p<0.001). They were more likely to be postmenopausal (p=0.001) and to take AI rather than tamoxifen (p = 0.03). Only 17 patients (3%) changed EVE intake timing throughout the study. EVE intake dialy times were binned into 2 categories for analyses: morning/afternoon group (n=300) and evening/night group (n = 213). The patients who took morning/afternoon EVE chose another timing for ET in 38% of the cases compared to 17.1% in evening/Night EVE group (p<0.01). The timing of EVE intake was not significantly associated with definitive EVE withdrawal ( p=0.62) in the whole population. Time to EVE withdrawal was significantly longer in the patients taking tamoxifen rather than AI (17.2 vs 10.9 months, p = 0.0047). Prolonged duration of EVE treatment was associated with evening/night intakes of both EVE and tamoxifen, compared to other drug timing modalities (p = 0.04). With a median follow-up of 85months, 15 patients relapsed locally (3%), 55 developed metastases (11%), 36 patients died (7%). Overall, EVE intake timing was not associated with DFS (HR=0.84 [95% CI, 0.53 - 1.35], p=0.4). There was a significant interaction between EVE timing intake and ET type ( P interaction= 0.001). Patients on evening/night EVE combined with tamoxifen had a reduced likelihood of relapse compared to those taking morning/afternoon EVE (HR = 0.17 [0.05- 0.59], p = 0.005). In contrast, no significant EVE effect was found in the AI group (HR = 1.56 [0.92 2.64], p = 0.1). Evening/Night intake of EVE plus tamoxifen was independently associated with DFS (HR 0.13 [0.03-0.6], p = 0.002) after adjustment for age, nodal status, tumor size, ET timing intake, and EVE dose (2.5, 5 or 10 mg). Conclusions: These exploratory results are consistent with a role of circadian rhythm in the efficacy of EVE when given with tamoxifen in pts with high risk early breast cancer. 1. S. Giacchetti et al, Abst 546, ASCO 2023. Clinical trial information: NCT01805271 .

Dose-dense adjuvant chemotherapy in patients with HER2-low early breast cancer: An exploratory analysis of the GIM2 trial.

532 Background: Dose-dense (DD) adjuvant chemotherapy represents the standard treatment for patients with node-positive early-stage HER2-negative breast cancer, but its role in HER2-low disease is unknown. In this exploratory analysis of the Gruppo Italiano Mammella 2 (GIM2) trial, we investigated efficacy of DD chemotherapy among patients affected by HER2-negative breast cancer according to HER2 immunohistochemistry (IHC) score (low vs. zero). Methods: Patients with node-positive early breast cancer were randomly assigned to receive either DD or standard schedule anthracycline- and taxane-based chemotherapy. HER2 status was assessed locally. Tumours with HER2 score 0 were classified as HER2-zero, while those with a HER2 score 1+ or 2+ without fluorescence in situ hybridization (FISH) amplification were defined as HER2-low. Some tumours were classified as HER2-negative with unknown IHC score. Survival outcomes were compared between patients with HER2-zero vs HER2-low tumours. Results: Among 2003 patients enrolled in the GIM2 trial, 1243 subjects were eligible for this analysis. Median age was 52 years (interquartile range [IQR] 44-59) and 604 patients (48.6%) were pre-menopausal. Hormone receptor status was positive in 87.9% of cancers. 475 tumours were classified as HER2-zero (38.2%), 446 (35.9%) were defined HER2-low and 322 (25.9%) were HER2-negative with unknown IHC score. No significant differences were found in terms of baseline characteristics between these three subgroups. At a median follow-up of 14.9 years (IQR 8.4-16.2), no significant interaction was observed between treatment effect and HER2 status in invasive disease-free survival (iDFS) (p for interaction=0.46) nor in overall survival (OS) (p for interaction=0.43). Comparing patients with HER2-zero breast cancer with those affected by HER2-low tumours, no significant differences in iDFS were observed (15yr iDFS were 61% vs. 54%, respectively, p=0.25), nor OS differences (15yr OS were 75% vs. 72%, respectively, p=0.19). When investigating DD schedule efficacy among patients with HER2-zero tumours, hazard ratio (HR) for iDFS was 0.64 (95% confidence interval [CI] 0.46-0.87) and HR for OS was 0.57 (95%CI 0.38-0.88). Similarly, within patients affected by HER2-low breast cancer, HR was 0.83 (95%CI 0.62-1.11) for iDFS and 0.83 (95%CI 0.57-1.22) for OS. These results were consistent with the findings of efficacy of DD chemotherapy in the overall population included in this analysis (HR for iDFS 0.73 [95%CI 0.61-0.89]; HR for OS 0.69 [95%CI 0.54-0.88]). Conclusions: In this exploratory analysis of a large phase III adjuvant trial, HER2 status (i.e. HER2-zero vs HER2low) did not show prognostic value. In patients with high-risk early breast cancer, the benefit of DD chemotherapy was observed irrespective of HER2 status. Clinical trial information: NCT00433420 .

A phase II trial comparing dalpiciclib in combination with letrozole versus standard chemotherapy as neoadjuvant therapy in patients with high-risk HR- positive HER-2 negative breast cancer: DARLING-02.

TPS626 Background: Dalpiciclib is a CDK4/6 inhibitor that has shown promising efficacy and safety when in combination with endocrine in the treatment of advanced HR+ HER2- breast cancer. Building on preliminary findings from our previous study (Geng, 2023SABCS PO2-02-05), we aim to evaluate the efficacy and safety of dalpiciclib combined with letrozole versus standard chemotherapy as neoadjuvant treatment in patients with high-risk early breast cancer (EBC). Methods: This is a prospective, multicenter, randomized phase II non-inferiority trial. Main eligibility criteria include: female patients ≥18 years, ECOG performance status of 0-1, histologically confirmed invasive breast cancer, clinical stage T1c-T2, cN1–2 or T3-4, cN0-2, ER≥50%, HER2-negative, and Ki67 ≤ 20%. Participants are randomized 1:1 to receive either 24-week experimental intervention (oral dalpiciclib 150mg once daily for 3 weeks on, 1 week off and oral letrozole 2.5 mg/day) or 24-week standard intervention (intravenous epirubicin 100 mg/m² and intravenous cyclophosphamide 500 mg/m² on day 1 for three 3-week cycles, followed by intravenous docetaxel 100 mg/m2 on day 1 for three 3-week cycles). The primary endpoint is the objective response rate (ORR) assessed by RECIST v1.1. Secondary endpoints include patient-reported outcomes (EORTC QLQ-C30, EORTC QLQ-BR23), residual cancer burden 0–I rate, preoperative endocrine prognostic index score 0 rate, pathological complete response rate , 2-year invasive disease-free survival rate, and safety. Exploratory endpoints include biomarker analysis. The hypothesis is that the experimental group will not be inferior to control group. Assuming an ORR of 70% for both groups, a sample size of 65 patients per group is required to achieve 80% power to detect a non-inferiority margin of up to 20% at a two-sided significance level of 5%. A total of 130 patients are needed (65 per group). Considering a dropout rate of 10% per group, the total sample size is approximately 144 patients. The trial was registered at ClinicalTrials.gov (NCT06107673) and is actively recruiting. Clinical trial information: NCT06107673 .

PARPi eligibility amongst women with newly diagnosed invasive breast cancer enrolled in the GREAT universal genetic testing study.

531 Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of BRCA-associated metastatic and high-risk early breast cancer. Recent guidelines have endorsed the use of BRCA1/2 testing for all patients with breast cancer who may be eligible for PARPi therapy, however it is unclear what proportion of patients are impacted by these recommendations. Methods: We sought to evaluate pre-test and post-test eligibility for PARPi in women aged >18 years old with a first diagnosis of stage I-IV invasive breast cancer who enrolled in a prospective, multicentered universal genetic testing study between 2019-2022. All enrolled patients underwent pre-test counselling and an obligatory primary panel of BRCA1, BRCA2, and PALB2 at the time of diagnosis. Candidacy for PARPi was determined by biologic subtype, clinical stage, pathologic stage, and/or response to neoadjuvant chemotherapy. Results: Of 1017 patients referred for the study, 805 were eligible and 729 (90.6%) consented to participate. The median age at diagnosis was 53 years (IQR, 45-62 years) and 96.2% had stage I-III disease. Overall, 32 (4.4%) patients had a germline pathogenic variant (GPV) in BRCA1/2, and 7 (1.0%) had a GPV in PALB2. Of 112 (15.4%) patients with triple negative breast cancer (TNBC), 19.6% had a GPV in BRCA1/2 or PALB2, whereas in 487 (66.8%) with ER+HER2- disease, 2.9% had a GPV (p<0.001). Among the 112 patients with TNBC, 64 (57%) were candidates for PARPi pre-genetic testing, and 12 (10.7%) remained eligible due to a GPV in BRCA1/2. Among the 487 patients with ER+HER2- breast cancer, 37 (5.1%) were candidates for PARPi pre-genetic testing, and 1 (0.2%) remained eligible due to a BRCA1 GPV identified on testing. All patients who were PARPi eligible were <65 years of age or >65 years with TNBC. Conclusions: In women with newly diagnosed invasive breast cancer, approximately 14% are candidates for PARPi prior to genetic testing, and 1.8% remain PARPi eligible due to a confirmed pathogenic variant in BRCA1/2. Consequently, genetic testing impacts systemic therapy decisions for PARPi in 10% of TNBC patients and fewer than 1% of women with ER+HER2- breast cancer. [Table: see text]

Incidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial.

584 Background: I-SPY2 was the first randomized trial to demonstrate an improvement in pCR and EFS when Immune Checkpoint Inhibitors (ICI) were added to standard neoadjuvant chemotherapy. This finding was validated in the phase 3 KEYNOTE 522 trial for triple-negative breast cancer, leading to approval of pembrolizumab (pembro) in this setting. ICIs add the risk of immune-related adverse events (irAEs); while most irAEs are reversible, endocrinopathies appear to persist. Higher rates of adrenal insufficiency (AI), either from primary adrenalitis or hypophysitis, have been reported with ICI-based therapy (tx) in early breast cancer (EBC) compared to advanced disease. Here we describe the incidence and time of onset of AI with ICI-based tx in I-SPY2. Methods: I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within biomarker subtypes defined by hormone receptor, HER2, and MammaPrint status to evaluate novel agents in the neoadjuvant setting in patients (pts) with high-risk EBC. Treatment included weekly paclitaxel (T) plus ICI-based tx x 4 cycles, followed by doxorubicin/cyclophosphamide (AC) every 2-3 weeks x 4. 6 completed investigational arms included ICIs: T+pembro x 4, T+pembro x 8 (+/- AC), T+pembro+SD101 (TLR9 agonist), T+durvalumab+olaparib, T+cemiplimab (cemi), and T+cemi+REGN3767 (anti-LAG-3). AI diagnoses were made by treating providers with review from two board certified endocrinologists. AI was defined as AM serum cortisol level < 3 mcg/dl in absence of recent glucocorticoid treatment. If ACTH was low or normal, pt was dx with hypophysitis; if ACTH was elevated, pt was dx with primary AI. Results: 442 pts in I-SPY2 received ICI-based tx; 11.8% (n=52) developed AI (primary+hypophysitis). Mean age of pts who developed AI was 47.3 vs 48.6 yrs in those who did not (p=0.44). Incidence of AI was highest in arms with dual immune modulation (18.1%) as compared to single ICI tx (8.5%). Median time to onset varied by arm, ranging from 92-204 days from first ICI dose. While some cases occurred during ICI tx (13.5%), the majority occurred between 12-24 wks after tx initiation, with 21.2% diagnosed after completion of all tx. The majority (94.2%) of pts with AI were symptomatic; the most common presenting symptoms included fatigue (59.6%), nausea (48.1%), and vomiting (34.6%). All pts with AI remain on glucocorticoid replacement tx. Conclusions: The incidence of AI in EBC is higher than has previously been reported in advanced disease, with higher rates observed in those tx with dual immune modulation. No correlation was observed with age; correlation of AI with response predictive subtype and other clinicopathologic features is ongoing and will be presented. Given the high incidence of AI in EBC, close monitoring in the peri/postoperative setting and education of pts and providers is critical, as risk persists even after completion of tx. Work to identify risk factors for AI is ongoing. Clinical trial information: NCT01042379 .

Real-world immune-related adverse events in patients with early triple negative breast cancer who received pembrolizumab.

1099 Background: The addition of pembrolizumab to chemotherapy (KEYNOTE-522 regimen) in high risk early triple negative breast cancer (TNBC) has improved clinical outcomes. However, this treatment can result in immune-related adverse events (irAEs) involving any organ and in some cases, life-long toxicities or even death. This retrospective study describes real-world patterns of irAEs in patients (pts) with early TNBC who received pembrolizumab at two academic centers. Methods: We evaluated irAEs in pts with stage II-III TNBC from MD Anderson Cancer Center and Lyndon B Johnson diagnosed between January 2018 and May 2023 who received neoadjuvant pembrolizumab plus chemotherapy. We excluded those enrolled on clinical trials. We utilized ASCO irAE and CTCAE v5 guidelines for toxicity grading. Logistic regression assessed the effect of clinical variables on irAEs, adjusting for covariates. Results: We identified 233 pts with a median age of 51 ± 12 years; 62% with stage II and 35% with stage III TNBC; 25% were Hispanic/Latino, 21% non-Hispanic Black and 42% were non-Hispanic White. In total, 80 pts (34%) developed 100 separate irAEs (94 with definite and 6 with possible/probable attribution). The most common irAEs were endocrine (52%) followed by gastrointestinal (23%). Grade ≥ 3 irAE occurred in 26 instances, with the most common being gastrointestinal (13 instances). A fatal irAE occurred in 2 pts where both were colitis. A total of 26 irAEs resulted in hospitalization, 45 required systemic steroids, and 15 required additional immunosuppressive therapy. Most (66) irAEs were unresolved at last follow up, although the majority had improved to grade 1 (37/66) and 32 patients discontinued pembrolizumab early due to irAEs. No clinical factor (race, stage, tumor grade, age, body mass index) was associated with development of an irAE. Conclusions: In this real-world diverse population, we identified a similar rate and severity of irAEs as reported in the KEYNOTE-522 trial. Hospitalizations occurred in 26% of irAEs while most developed persistent immune toxicity. Gastrointestinal irAEs were more common compared to KEYNOTE-522 reported data. Research is needed to better predict and mitigate the burden of irAEs and to improve the long-term survivorship care of pts with early TNBC pts who receive pembrolizumab. [Table: see text]

Real life comparison between doxorubicin and cyclophosphamide (AC) dose-dense (dd) and conventional dose AC in patients with triple negative breast cancer (TNBC) under neoadjuvant treatment.

e12662 Background: High-risk early triple-negative breast cancer (TNBC) is frequently associated with early recurrence and high mortality. Studies suggest a sustained clinical benefit in patients with TNBC who have a pathological complete response (PCR) after neoadjuvant chemotherapy (NACT). The dose-dense (dd) regimen demonstrated improved survival regardless of hormone receptor expression or HER2 status. The doxorubicin and cyclophosphamide (AC) regimen can be performed in (dd), therefore it must include granulocyte growth factors, which may increase costs and toxicities. The object of the study was to evaluate their clinical characteristics and treatment, patients with TNBC, stage I-III who received ACdd in neoadjuvant treatment versus patients who received AC dose conventional (dc). Methods: We performed a retrospective observational cohort study of patients with early TNBC, stage I-III who received neoadjuvant treatment with chemotherapy based on doxorubicin, cyclophosphamide, paclitaxel and carboplatin associated with pembrolizumab. Results: All 82 patients were women 57.3% received ACdd, 30.4% received AC dc. In group ACdd 59.5% had intercurrence related with chemotherapy, in which 17.8% were neutropenic fever and 21.4% had developed different types of infections (ex: diarrhea, pneumonia and others). In these 2 groups all of them had received antibiotic. About 50% of the patients had developed intercurrence because of treatment toxicity and just 3.5% had disease progression. The other group that we evaluated is composed by patients who ACdc, dose Regarding to these group 48% developed any intercurrence during the neoadjuvant treatment, in which 8.3% had neutropenic fever and 25% had different types of infections. All of them earned antibiotic. About clinical and pathological response, the group that earned ACdd 61.7% got complete clinical response and 8.5% had a disease progression during the treatment. In the other arm 68% got complete clinical response and 4% had a progression. Conclusions: AC dd was more prevalent in our series, despite the additional use of granulocyte growth factor, there were more complications in this group and it did not demonstrate better results than those who received conventional dose AC.

The SURVIVE study: Liquid biopsy guided surveillance after intermediate- to high-risk early breast cancer.

TPS620 Background: Current guidelines limit routine breast cancer (BC) follow-up to clinical examinations and breast imaging. This is based on the results of two large cohort studies conducted in the 1980s that showed no improvement in overall survival (OS) by an intensified screening for distant metastases. Thus, imaging for distant metastases should currently only be performed in patients with specific symptoms. To detect distant relapse in a pre-symptomatic stage, we suggest the evaluation of a liquid biopsy-guided intensified surveillance, analyzing tumor markers (CA 27.29, CA 125 and CEA), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Methods: Funded by the German Federal Ministry of Education and Research, the SURVIVE study is the first large, randomized BC surveillance trial to investigate the potential survival benefit of a liquid biopsy guided follow-up care in intermediate- to high-risk early breast cancer patients. The trial is a German multicenter, controlled phase 3 superiority study, in which 3500 patients are randomized in a 1:1 ratio to standard vs. liquid biopsy guided intensified follow-up care. Eligible patients are adults with confirmed primary invasive intermediate to high-risk early BC, defined as an indication for (neo-)adjuvant chemotherapy, and/or large tumor size (> 50 mm), and/or positive lymph nodes (≥ pN1mi), and/or high grade (≥ G3). Primary anti-tumor therapy (surgery, adjuvant chemo- or radiotherapy) must have been completed previously. Patient enrollment during adjuvant endocrine, antibody- or targeted therapy is allowed. The total study duration is 144 months. Stratification factors are study site as well as HR-, HER2- and nodal status at surgery.Both study arms receive standard follow-up according to national guidelines, and the intensified surveillance arm will be tested for standard tumor markers, CTCs and ctDNA via tumor-informed approach (RaDaR assay). Pre-specified abnormal findings of any of the liquid biopsy markers indicative of minimal residual disease trigger complete staging. In the event of confirmed disease recurrence, guideline-based treatment follows, otherwise, liquid biopsy testing continues. If applicable, study participants may enter interventional trials. Statistics:The two primary objectives are to determine whether intensified, liquid biopsy-guided surveillance leads to better OS or an overall lead-time effect, compared to standard surveillance. OS will be analyzed in the ITT population using Kaplan Meier methods and cox regression models, the overall lead time effect is a purely descriptive composite measure. Secondary objectives include IDFS, DDFS, DRFS, BCSS and quality of life (QoL). Aims: We propose a liquid biopsy guided follow-up method, with high sensitivity and specificity for the earlier detection of distant (oligo-)metastases, to enable earlier initiation of therapy. Clinical trial information: NCT05658172 .

Predicting epirubicin response in Danish patients with breast cancer.

539 Background: Anthracyclines are highly effective chemotherapy drugs. However, they are toxic and feared for their cardiotoxicity. There is a need for improved personalized prediction of treatment benefit. For example, state-of-the-art guidelines (NCCN Guidelines Version 1.2024 and meta-analysis PMID: 37061269) mark anthracyclines as optional adjuvant treatment of estrogen receptor (ER) positive, HER2 negative early high-risk breast cancer. A biomarker to predict whether a patient will benefit from anthracycline treatment could potentially lead to increased cure rate and overall reduced toxicity. However, no such test exists. Here we introduce a clinically validated, predictive test based on clinical tumor transcriptome data and the cell line panel NCI60 that can forecast epirubicin response in breast cancer patients with high accuracy. Methods: Microarray gene expression levels and growth inhibition levels (GI50) from the NCI60 cell line panel were acquired from NCBI to build a prediction algorithm. A tumor-specific variance-based filter based on >6.000 patient tumors was applied to select the most relevant genes. AUC (Area Under Curve) was used to evaluate the performance of numerous configurations and combinations of parameters that led to different gene-signature sets. Response scores based on the gene expression level of all genes in each signature were generated for each sample in a published cohort (PMID: 23340299) and a final signature with 141 genes was the best-performing signature (Progressive Disease versus Response AUC 0.81 and ANOVA-test p-value < 0.01). The model was validated on a cohort of Danish breast cancer patients treated with epirubicin in the metastatic setting (n=153), with time-to-progression (TTP) as endpoint (PMID: 31654283, PMID: 30099635). Finally, we used an established method (PMID: 30289602) to test if the gene signature was correlated between microarray- and RNA sequencing-based datasets. Results: The hazard ratio (HR) for the best-performing signature was 0.31 when comparing patients with a difference of at least 50 in response score (two-sided p-value = 0.012, 95% confidence interval 0.12-0.77, endpoint TTP, continuous scoring). This was consistent in a multivariate model including ER and HER2. Using the data and method provided by Pedersen et al (PMID: 30289602), we also saw a high correlation between matching microarray and RNA sequencing datasets for the genes in our model (mean Pearson’s r = 0.87). Conclusions: Here is presented a development and clinical validation of an accurate epirubicin response signature for breast cancer patients. The expression of the genes in the signature is highly correlated between microarray- and RNA sequencing data. Moving forward, we will seek to validate the model independently on RNA sequencing data. Our aim is that these models will be accepted for prospective clinical tests at local hospitals in Denmark in early 2025.

Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial

Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271). 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus. Patients prospectively reported in a diary the daily timing of ET intake among four 6-h slots (06:00-11:59 (morning), 12:00-17:59 (afternoon), 18:00-23:59 (evening), or 24:00-05:59 (nighttime). The association between ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial and the results of this observational study are reported here. ET timing was recorded by 855 patients (67.2%). Patients declaring morning (n=465, 54.4%) or afternoon (n=45, 5.4%) ET intake were older than those declaring evening (n=339, 39.6%) or nighttime (n=5, 0.6%) intake. With a median follow-up of 46.7 months, 118 patients had a local (n=30) or metastasis relapse (n=84), and 41 patients died. ET intake timing was not associated with DFS in the whole population (HR=0.77, 95% CI [0.53-1.12]). The association between ET intake timing and DFS according to the stratification factors revealed interactions with ET agent (tamoxifen versus Aromatase inhibitors (AI) with an increased DFS in the group of evening/nighttime versus morning/afternoon tamoxifen intake (HR=0.43, 95% CI [0.22-0.85]), while no association was found for AI intake (HR=1.07, 95% CI [0.68-1.69]). The interaction between ET intake timing and ET agent remained in multivariable analysis (HR=0.38 [0.16-0.91]). Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies. UNIRAD was Supported by a grant from the French Ministry of Health PHRC 2012 and received funding from La Ligue contre le Cancer, Cancer Research-UK, Myriad Genetics, and Novartis.

Abstract GS03-06: Genomic and transcriptomic profiling of primary tumors from patients with HR+, HER2-, node-positive, high-risk early breast cancer in the monarchE trial

Abstract Background Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in significant and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in patients (pts) with HR+, HER2-, node-positive, high-risk early breast cancer in the monarchE trial (NCT03155997). Abemaciclib benefit was sustained beyond the completion of treatment (tx) with deepening magnitude of absolute benefit in IDFS and DRFS at 5 years. Here, we evaluate comprehensive molecular profiling of archived primary tumor tissue and association with clinical outcomes. Methods For biomarker analysis, a proportionally stratified random sampling case-cohort design was utilized to include all patients who experienced an IDFS event at a pre-specified interim analysis with a median follow up of 54 months. A cohort of 895 pts (189 with IDFS event) in the abemaciclib + ET arm was matched 1:1 with 903 pts (270 with IDFS event) in the ET arm. Baseline primary tumor samples underwent exome-capture RNA sequencing (RNAseq; n=1324, 23% intent-to-treat (ITT) population) and paired tumor-normal (germline blood samples) whole-exome sequencing (WES; n=1234, 22% ITT population). Expression-based intrinsic subtypes (i.e., luminal A (LumA), luminal B (LumB), HER2-enriched (HER2E), basal- and normal-like) were characterized using the Absolute Intrinsic Molecular Subtyping model. The 21-gene expression signature score (Oncotype DX test) was inferred from RNAseq; samples were categorized into lower (0-25) and high (26-100) risk groups. To investigate associations of biomarkers with abemaciclib benefit, WES genomic events including oncogenic and hotspot mutations by OncoKB, and copy number events, of incidence >9% were pre-selected. Results The biomarker subset of monarchE was reflective of the ITT population. A total of 1190 tumors (abemaciclib+ET n= 605; ET alone n=585) yielded adequate RNAseq results. Intrinsic subtype distribution was consistent across tx arms (Table A). Low tumor purity limited assessment of the normal-like subtype. The 4-year IDFS benefit of abemaciclib was consistent across all subtypes. LumA cancers had the lowest risk of recurrence while HER2E and basal-like subtypes had the highest. Inferred 21-gene expression signature score showed similar benefits from abemaciclib in both lower and high-risk groups (Table B). A total of 1173 tumors yielded adequate WES results (abemaciclib+ET n=580; ET alone n=593). Consistent abemaciclib benefit was observed across the most frequently altered genes (Table C). In exploratory analysis, lower benefit from abemaciclib was seen in the subset of focal-high level MYC amplified tumors (n=176, HR 1.30, 95% CI, 0.77, 2.20) compared to MYC non-amplified tumors (n=997, HR 0.62, 95% CI, 0.47, 0.80, nominal interaction p=0.014). The treatment benefit of abemaciclib was observed across all subpopulations of altered genes based on gene expression data. Conclusions Adjuvant abemaciclib+ET maintained IDFS benefit compared to ET alone across all molecular subtypes as measured by RNAseq. Benefit was consistent across most altered genes assessed by WES, except for the subset of tumors with MYC amplification. Additional research is necessary to confirm these findings. Table. Citation Format: Nicholas Turner, Jorge Reis-Filho, Matthew Goetz, Christine Desmedt, Sarat Chandarlapaty, Hironobu Sasano, Carlos Arteaga, Sherene Loi, Stephanie Graff, Deli Liu, Vanessa Rodrik-Outmezguine, Anthony Sireci, Cynthia Sandoval Rubenstein, Helen Won, Lacey M. Litchfield, Maria Munoz, Stephen Johnston. Genomic and transcriptomic profiling of primary tumors from patients with HR+, HER2-, node-positive, high-risk early breast cancer in the monarchE 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 GS03-06.

Abstract PS06-01: Results from a pilot study exploring ctDNA detection using a tumor-informed assay in the monarchE trial of adjuvant abemaciclib with endocrine therapy in HR+, HER2-, node-positive, high-risk early breast cancer

Abstract Background Two years of adjuvant abemaciclib + endocrine therapy (ET) resulted in significant and clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in patients (pts) with HR+, HER2-, node-positive, high-risk early breast cancer (EBC) in the monarchE trial (NCT03155997). The benefit of abemaciclib was sustained beyond completion of treatment and deepened in magnitude at 4 years for IDFS and DRFS. This pilot study investigated the technical feasibility of ctDNA detection beginning prior to study treatment, as well as rates of persistence and clearance in a subset of EBC pts from monarchE using the clinically validated SignateraTM ctDNA assay. Methods Samples were analyzed from a selected subset of pts (n=178; 84 from abemaciclib+ET arm; 94 ET alone) who had blood collected both before initiating protocol directed therapy, Visit 1 (V1; randomization + ≤ 3 days) and near completion of the 2-year treatment period, Visit 27 (V27; 24 months +/- 5 days from V1). This cohort of pts was enriched for overall IDFS events compared to the total monarchE study population, however pts with relapses occurring prior to V27 were excluded. Primary tumors from selected pts were subjected to whole exome sequencing (WES). Selected samples included those from pts with a range of tumor mutation burden. Cell-free DNA was extracted from 356 plasma samples. A Signatera ctDNA assay was developed for each pt based on up to 16 variants detected by WES from each baseline tumor sample. Results The IDFS event rate for the selected subset (n=178) was 39.3% (abemaciclib+ET 34.5% [29/84] and ET alone 43.6% [41/94]). Ten pts (5.6%) were initially ctDNA+ and 42 pts (23.6%) were persistently (7 pts, 3.9%) or became (35 pts, 19.7%) ctDNA+ at V27. Notably, 70% of pts who were initially ctDNA+ and 100% of pts who were either persistently ctDNA+ or became ctDNA+ experienced recurrence (see Table 1). In contrast, none of the 3 pts that cleared ctDNA+ developed recurrence. In pts persistently ctDNA negative (neg), 28 (21.1%) experienced recurrence. Overall, 10% (7/70) of pts with IDFS events were initially ctDNA+ and 50% (35/70) had detectable ctDNA at V27. Conclusions Detection of ctDNA soon after completing neoadjuvant chemotherapy was infrequent, but also associated with a high-risk of recurrence. ctDNA positivity was common at the end of the 2-year treatment period and was highly prognostic with all pts subsequently developing disease recurrence. Importantly, ~30% of pts with early ctDNA detection ultimately dropped below detection limits during the 2-year treatment period and none developed recurrence. Although some pts remained persistently ctDNA neg during this study and experienced recurrence, the delay in recurrence may indicate longitudinal benefit from remaining ctDNA neg. Future planned analysis of an expanded cohort reflective of the intent to treat population including additional timepoints within the 2-year treatment period will further define how ctDNA dynamics may identify pts at high-risk of recurrence. Table 1. Summary of Subset Positivity Rates. + positive; - negative; NA, not applicable. Citation Format: Sherene Loi, Stephen Johnston, Carlos Arteaga, Stephanie Graff, Sarat Chandarlapaty, Matthew Goetz, Christine Desmedt, Jorge Reis-Filho, Hironobu Sasano, Vanessa Rodrik-Outmezguine, Anthony Sireci, Cynthia Sandoval Rubenstein, Helen Won, Deli Liu, Lacey M. Litchfield, Nicholas Turner. Results from a pilot study exploring ctDNA detection using a tumor-informed assay in the monarchE trial of adjuvant abemaciclib with endocrine therapy in HR+, HER2-, node-positive, high-risk early 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 PS06-01.

Abemaciclib in the Adjuvant Setting for Breast Cancer: A Systematic Review

The combination of adjuvant Abemaciclib with endocrine therapy (ET) has emerged as a significant advancement in the management of HR+, HER2-, node-positive, high-risk early breast cancer, as demonstrated by the findings of the MonarchE trial. This innovative treatment approach yielded not only statistically significant but also clinically meaningful improvements in invasive disease-free survival. Moreover, the benefits of this treatment combination were sustained over time, with a median follow-up of 27 months revealing continued clinically meaningful advantages in both invasive disease-free survival and distant recurrence-free survival. Importantly, these benefits extended beyond the initial 2-year treatment period, highlighting the durable efficacy of Abemaciclib and ET in preventing disease progression and distant metastasis. Furthermore, the safety profile of the combination therapy was found to be manageable and tolerable. This aspect is crucial for ensuring patient adherence to treatment and minimizing the burden of adverse effects. Overall, these findings underscore the potential of adjuvant Abemaciclib with ET as a valuable therapeutic option for patients with high-risk early breast cancer, offering both efficacy and tolerability in the long-term management of the disease. More studies are required, especially in the elderly, in order to know how to counteract diarrhea and to make Abemaciclib more tolerated.

Abstract PO1-20-05: SURVIVE study – a multicenter, randomized, controlled phase 3 superiority trial, evaluating liquid biopsy guided intensified follow-up surveillance in women with intermediate-to high-risk early breast cancer

Abstract Background: Current guidelines limit routine breast cancer follow-up to clinical examinations and breast imaging. This is based on the results of two large cohort studies conducted in the 1980s that showed no improvement in overall survival (OS) by an intensified screening for distant metastases. Thus, imaging for distant metastases should currently only be performed in patients with specific symptoms. To detect distant relapse in a pre-symptomatic stage, we suggest the evaluation of a liquid biopsy-guided intensified surveillance, analyzing tumor markers (CA 27.29, CA 125 and CEA), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Trial design: Funded by the German Federal Ministry of Education and Research, the SURVIVE study is the first large, randomized breast cancer surveillance trial to investigate the potential survival benefit of a liquid biopsy guided follow-up care in intermediate- to high-risk early breast cancer patients. The trial is a German multicenter, controlled phase 3 superiority study, in which 3500 patients are randomized in a 1:1 ratio to standard vs. liquid biopsy guided intensified follow-up care. At the time of writing 150 patients have been enrolled since December 2022. The total study duration is 144 months. Stratification factors are study site as well as HR-, HER2- and nodal status at surgery. Both study arms receive standard follow-up according to national guidelines. Additional blood samples (year 1-3 every 3 months, year 4-5 every 6 months) and standardized Quality of Life (QoL) questionnaires (EORTC-QLQ-C30/PA-F12, every 6 months) will be collected. While the standard surveillance arm samples will only be stored in a biobank, samples collected in the intensive surveillance arm will be tested for standard tumor markers, CTCs and ctDNA. Pre-specified abnormal findings of any of the liquid biopsy markers indicative of minimal residual disease trigger complete staging. In the event of confirmed disease recurrence, guideline-based treatment follows, otherwise, liquid biopsy testing continues. If applicable, study participants may enter interventional trials. Eligibility criteria: Eligible patients are adult females or males with histologically confirmed primary invasive intermediate to high-risk early breast cancer, defined as an indication for (neo-)adjuvant chemotherapy, and/or large tumor size ( > 50 mm), and/or positive lymph nodes (≥ pN1mi), and/or high grade (≥ G3). Primary anti-tumor therapy (surgery, adjuvant chemo- or radiotherapy) must have been completed ≤ 24 months (≤ 60 months for luminal carcinoma) previously. Patient enrollment during adjuvant endocrine- or antibody-therapy, CDK4/6-/PARP- or PI3K-inhibitors and antibody-drug conjugates is allowed. Statistical methods: The two primary objectives are to determine whether intensified, liquid biopsy-guided surveillance leads to better OS or an overall lead-time effect, compared to standard surveillance. The primary endpoint OS will be analyzed in the ITT population using Kaplan Meier methods and cox regression models, the overall lead time effect is a purely descriptive composite measure. Secondary objectives include invasive disease-free survival (IDFS), distant disease-free survival (DDFS), distant recurrence free survival (DRFS), breast cancer-specific survival (BCSS) and quality of life (QoL). Specific aims: To improve OS and the QoL during breast cancer follow-up, we propose a liquid biopsy guided follow-up method, with high sensitivity and specificity for the earlier detection of distant (oligo-)metastases, to enable earlier initiation of therapy. Conclusion: The SURVIVE-study is a long-awaited trial in early breast cancer follow-up, based on promising liquid biopsy markers. If successful, the results will lead to a paradigm shift in current follow-up care of intermediate to high-risk early breast cancer survivors. Clinical trial information: NCT05658172 Citation Format: Franziska Mergel, Sophia Huesmann, Thomas Friedl, Kerstin Pfister, Tatjana Braun, Angelina Fink, Forca Mehmeti, Tanja Fehm, Volkmar Müller, Klaus Pantel, Andreas Hartkopf, Elisabeth Wiesmüller, Brigitte Rack, Wolfgang Janni. SURVIVE study – a multicenter, randomized, controlled phase 3 superiority trial, evaluating liquid biopsy guided intensified follow-up surveillance in women with intermediate-to high-risk early 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 PO1-20-05.

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 PO1-13-01: Safety profiles of Chinese breast cancer patients who received abemaciclib in MONARCH plus and monarchE study

Abstract Aim: Abemaciclib demonstrated efficacy with tolerable safety profile in Chinese patients (CN pts) with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) and high-risk early breast cancer (EBC). The overall safety profile of abemaciclib in Chinese ABC and EBC pts was consistent with overall population in the MONARCH plus and monarchE studies. To better understand the safety of abemaciclib in CN pts, beyond the previously reported most frequent adverse events (AEs), we report a comprehensive summary of other selected AEs in CN pts in the two trials. Methods: Study designs of MONARCH plus (NCT02763566) and monarchE (NCT03155997) studies were reported previously. To report detailed characteristics of a selected AE profile, including alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, fatigue, nausea, and vomiting, data were pooled across all CN pts from these two phase 3 studies. The safety population was defined as all randomized patients receiving at least 1 dose of Abemaciclib or endocrine therapy. Data cutoff time is May 18, 2020 and July 1, 2022, respectively. Results: Among 6052 participants in the overall safety population, 875 CN pts (14.5%) were included (512/3100 abemaciclib, 363/2952 placebo). CN pts treated with abemaciclib indicated consistent AE profiles in combination with different endocrine therapies (aromatase inhibitors or Fulvestrant). Detailed characteristics of selected AEs are summarized in table. No deaths due to the selected AEs were reported in CN pts. Conclusion: The selected AEs of abemaciclib group were in low severity with limited grade 3-4 events. Those AEs were tolerable and generally manageable in CN pts in the MONARCH plus and monarchE trials. Citation Format: Zhimin Shao, Qingyuan Zhang, Quchang Ouyang, Qiang Liu, Jifeng Feng, Hui-Ping Li, Xiaojia Wang, Ning Liao, Liu Yang, Qinyi Zhu, Chenxi Qian, Zefei Jiang. Safety profiles of Chinese breast cancer patients who received abemaciclib in MONARCH plus and monarchE 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 PO1-13-01.