Adjuvant Endocrine Therapy In Patients Research Articles

Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14–13/PrE0109)

BackgroundBidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC).MethodsPALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression’s value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models.ResultsFrom the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 – 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS.ConclusionsIn this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes.

Adherence to adjuvant hormone therapy in hormone-sensitive breast cancer: Insights from the Medical Oncology Department at Hassan II University Hospital, Morocco.

e12505 Background: Adjuvant endocrine therapy (AET) improves long-term survival for hormone-sensitive breast cancer; However, suboptimal adherence is prevalent, with many women failing to follow prescribed dosage and frequency. Long-term adherence patterns to AET are poorly understood. Additionally, there is a lack of data regarding the adherence to AET among Moroccan women and the factors that may influence it. Objectives: The primary objective of the study was to assess the adherence rate to AET in patients with HR-positive early breast cancer being treated at Hassan II University Hospital of Fez, Morocco. Secondary objectives included determining factors associated with poor adherence and assessing the adverse events associated with AET and their prevalence. Methods: We conducted a cross-sectional study involving 335 breast cancer patients undergoing AET. Eligible patients, who had received at least one dispensing of AET, participated in the study through a direct questionnaire survey after providing signed consent. The questionnaire comprised sections covering patient demographics, clinical data (stage, type of AET, duration of therapy), side effects or symptoms related to AET, other factors that may impact adherence. Adherence to AET was assessed at three points of measurement: 1 year, 3 years, and ≥ 5 years after the initiation of therapy. The study was carried out with respect to the Moroccan regulation in effect. Results: The study included 335 cases with an average age of 54 years. Participants were predominantly illiterate (62%) and post-menopausal (50.7%). Most were classified as stage II UICC (53.5%). Mastectomy was performed in the majority (74%). Neo(adjuvant) CMT was given to 79.4%, and adjuvant radiotherapy to 86.9%. Tamoxifen was administered to 55.4%, and aromatase inhibitors to 44.6%. Medical castration was associated with 12.5%, and 35 patients switched AET over time. Only 12.8% exceeded 5 years of AET during recruitment. Adherence assessment revealed an overall adherence rate of 53.4%. Notably, 67.2% claimed never to forget their medication, and about 20% temporarily stopped it, primarily due to lack of information. Most participants used a reminder strategy, notably alarms (43.3%). Treatment tolerance varied, with hot flushes and arthralgia being predominant side effects. Statistical analyses found a significant link between treatment lasting over 5 years and non-adherence (p = 0.003). However, the use of an alarm as a reminder strategy strengthened adherence (p = 0.021). No statistically significant differences were noted in other variables. Conclusions: Despite the benefits, ensuring adjuvant hormone therapy adherence is challenging. Our analysis, estimating a 53.4% global adherence, found that only treatment duration and recall strategy significantly correlated with adherence.

Abstract PO1-27-11: Survival Benefit of Adjuvant Endocrine Therapy in Patients with Estrogen Receptor Low-Positive Breast Cancer

Abstract Background: Estrogen receptor (ER) low-positive (1–10%) breast cancer is a very rare subtype that accounts for only 2–5% of all breast cancer cases and was introduced as a new category in the 2020 American Society of Clinical Oncology/College of American Pathologist Guidelines. There are limited data on the overall benefit of endocrine therapy for patients with ER low-positive cancers. The objective of this study was to analyze the clinicopathological characteristics and treatment patterns in patients with ER low-positive breast cancer and to compare disease-free survival (DFS) between patients who received and did not receive endocrine therapy. Methods: A retrospective search of the prospectively maintained database of our institution identified consecutive women with ER low-positive (1–10%) primary invasive breast cancer who underwent curative surgery at Seoul National University Hospital (Seoul, Korea) between January 2010 and April 2021. Standard immunohistochemical staining techniques were used to assess the level of ER, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, and semiquantitative scores (0–100%) were reported for ER and PR. DFS was defined as the time from surgery to the development of any recurrence and was compared between women who received and did not receive adjuvant endocrine therapy using univariable and multivariable Cox proportional hazards regression. Results: A total of 721 women (median age, 51 years; range, 24–83 years) with ER low-positive cancer were included in the analysis. Overall, 28% (203/721) had AJCC stage I, 42% (304/721) had stage II, and 30% (214/721) had stage III. PR expression was negative (&amp;lt; 1%) in 79% (571/721), low-positive (1–10%) in 12% (90/721), and high-positive ( &amp;gt;10%) in 8% (60/721). HER2 expression was negative in 54% (390/721) and positive in 46% (331/721). Most women (88% [634/721]) received adjuvant endocrine therapy, including all women with PR expression &amp;gt;10%. Of the 661 women with PR expression ≤10%, 87 (13%) did not receive adjuvant endocrine therapy. HER2-targeted therapy was performed in 81% (268/331) of women with HER2-positive cancer. During a median follow-up of 5.7 years, 98 (14%) had recurrence (25 locoregional/contralateral and 73 distant metastases). AJCC stage III (HR, 3.6; 95% CI: 2.4, 5.4; P &amp;lt; .001) and receiving total mastectomy (HR, 1.8; 95% CI: 1.2, 2.8; P = .004) were associated with worse DFS. Receiving adjuvant endocrine therapy was independently associated with better DFS in the entire cohort (HR, 0.46; 95% CI: 0.28, 0.76; P = .002) and in the HER2-negative subgroup (HR, 0.40; 95% CI: 0.22, 0.75; P = .004). In the HER2-positive subgroup, receiving adjuvant endocrine therapy was not significantly associated with better DFS (HR, 0.55; 95% CI: 0.23, 1.32; P = .18). Conclusion: In this large cohort of women with ER low-positive breast cancers, adjuvant endocrine therapy was administered in the majority of cases, including those with PR &amp;gt;10% expression. Receiving adjuvant endocrine therapy was associated with better DFS, especially when HER2 expression was negative. Citation Format: Su Hyun Lee, Han Suk Ryu, Myoung-jin Jang, Kyung-Hun Lee, Han-Byoel Lee. Survival Benefit of Adjuvant Endocrine Therapy in Patients with Estrogen Receptor Low-Positive Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-27-11.

Clinicopathological and molecular pathological characteristics in tamoxifen‑related endometrial cancer.

Tamoxifen (TAM), a selective estrogen receptor modulator, is often used for long-term adjuvant endocrine therapy in patients with hormone receptor-positive breast cancer. TAM is known to increase the risk of endometrial cancer (EC); however, the mechanism has not yet been fully elucidated. Therefore, molecular genetic analysis of EC following TAM administration (TAM-related EC) was conducted. A total of 10 samples of TAM-related EC and 20 sporadic EC samples (as controls) were analyzed. Copy number variation analysis was conducted, microsatellite instability (MSI) status was assessed, and mismatch repair (MMR) protein expression was examined immunohistochemically. Copy number variation analysis revealed that KDR, NOTCH1, NTRK1, NTRK3 and PDGFRB were more frequently amplified in TAM-related EC (P=0.039, P<0.001, P=0.011, P=0.006 and P=0.035, respectively). In MSI analysis, 4 cases were classified as MSI-high (40%), which is a higher frequency compared with that among patients with sporadic EC (~10% in Japanese women). Loss of MMR proteins was confirmed in all MSI-high cases. In 1 MSI-high case, a benign lesion of hyperplasia prior to EC development was also MSI-high with loss of some MMR protein expression. Several genes were specifically amplified in TAM-related ECs. Furthermore, TAM-related ECs were frequently MSI-high. Further studies are required to be conclusive; however, the present findings may lead to a reduction of unnecessary gynaecological testing in clinical practice and also encourage the testing for MSI status for optimal individualized treatment.

The impact of 4R Care Delivery Model on timing and sequence of bone density screening among patients with breast cancer.

553 Background: Bone loss is common in patients with breast cancer and can impact treatment decisions related to endocrine therapy. Hence, bone density assessment prior to starting endocrine therapy is highly important, especially because endocrine therapy is the first line adjuvant treatment for patients with ER+ breast cancer. Implementing timely bone density assessment is challenging, particularly in the early care trajectory when there are many tests and procedures taking place. We conducted a care delivery optimization in a large health system to implement bone density testing and referral for bone health consultation prior to endocrine therapy. The optimization was conducted as part of implementing the 4R Oncology model (Right Info, Right Care, Right Patient, at the Right Time), a novel approach to improving patient-facing care planning, team-based delivery and patient self-management. Here we describe the impact of this intervention. Methods: A cohort of 278 women with breast cancer who were in the 4R intervention (the 4R cohort) was compared to a historical control cohort of 201 women who received care pre-4R. Demographic, bone health history, and oncologic care data were abstracted from chart review and clinical databases. The prevalence of bone loss and timing of bone density consultation request was compared between the 4R and historical control cohorts. Results: The age, race/ethnicity and rate of ER+ cancer were similar between cohorts. Patients in the 4R cohort were significantly more likely to have received a consultation for bone density screening prior to the start of endocrine therapy (see Table). They were also more likely to receive a bone density test result during their care (Table). These findings remained significant when data were restricted to those ≥ 50 years (as a proxy for postmenopausal status) and those with ER-positive breast cancer. The rates of osteopenia and osteoporosis were similar between the cohorts: control 47%, 24%; 4R cohort: 46%, 23% respectively (data not shown). Conclusions: Care optimization using the 4R Oncology Model was associated with a significant improvement in the timing of bone density testing before initiation of endocrine therapy. The 4R Oncology Model can lead to more informed decision making in adjuvant endocrine therapy for patients with breast cancer. Additional optimizations to improve the rates of bone density tests and referrals will be beneficial.[Table: see text]

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer

PurposeMammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain.MethodsWe evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided.ResultsAdjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32–0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39–0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33).ConclusionsThe prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.

Toremifene, an Alternative Adjuvant Endocrine Therapy, Is Better Than Tamoxifen in Breast Cancer Patients with CYP2D6*10 Mutant Genotypes.

Tamoxifen showed individual differences in efficacy under different CYP2D6*10 genotypes. Our study evaluated the prognosis of tamoxifen or toremifene in hormone receptor (HR)-positive breast cancer patients under different genotypes. CYP2D6*10 genotypes of HR-positive breast cancer patients were determined by Sanger sequencing, and all the patients were divided into tamoxifen group or toremifene group. A total of 268 patients with HR-positive breast cancer were studied. The median follow-up time was 72.0 months (range, 5.0 to 88.0 months). Of these, 88 (32.9%), 114 (42.5%), and 66 (24.6%) patients had C/C, C/T, and T/T genotypes, respectively. Among patients who received tamoxifen (n=176), the 5-year disease-free survival (DFS) rate in patients with C/C and C/T genotype was better than that in patients with T/T genotype, and the difference was statistically significant (p < 0.001 and p=0.030, respectively). In patients receiving toremifene, CYP2D6*10 genotype was not significantly associated with DFS (p=0.325). Regardless of genotypes, the 5-year DFS rate was higher in patients treated with toremifene than in patients with tamoxifen (91.3% vs. 80.0%, p=0.011). Compared with tamoxifen, toremifene remained an independent prognostic marker of DFS in multivariate analysis (hazard ratio, 0.422; p=0.021). For all the 180 patients with CYP2D6*10 C/T and T/T genotypes, the 5-year DFS rate was significantly higher in the toremifene group than in the tamoxifen group (90.8% vs. 70.1%, p=0.003). Toremifene may be an alternative adjuvant endocrine therapy for patients with CYP2D6*10 mutant genotypes.

Tailoring the optimal duration of the extended adjuvant endocrine therapy in patients with early-stage breast cancer. A systematic review and meta-analysis of randomized clinical trials.

Controversy exists regarding the optimal duration of the extended adjuvant endocrine treatment (ET) in patients with early-stage breast-cancer (eBC). We performed a systematic review and trial-level meta-analysis of all randomized clinical trials (RCTs) comparing a "limited-extended" adjuvant ET (defined as more than 5 but less than 7.5 years of treatment overall) versus a "full-extended" adjuvant ET (defined as more than 7.5 years of treatment overall) in eBC. To be eligible, RCTs had to i) compare a "limited-extended" adjuvant ET versus a "full-extended" adjuvant ET in patients with eBC; and ii) report disease-free survival (DFS) hazard ratio (HR) according to the disease nodal-status [i.e., nodal-negative (N-ve) versus nodal-positive (N+ve)]. The primary endpoint was to assess the difference in efficacy of full-versus limited-extended ET, measured in terms of the difference in DFS log-HR, according to the disease nodal-status. Secondary endpoint was the difference in efficacy of full-versus limited-extended ET according to tumor size (i.e., pT1 vs pT2/3/4), histological grade (i.e., G1/G2 vs G3), patients' age (i.e., ≤60 vs>60 years) and previous type of ET (i.e., aromatase inhibitors vs tamoxifen vs switch strategy). Three phase III RCTs fulfilled the inclusion criteria. A total of 6689 patients were included in the analysis, of which 3506 (53%) had N+ve disease. The full-extended ET provided no DFS-benefit as compared with the limited-extended ET in patients with N-ve disease (pooled DFS-HR=1.04, 95%CI: 0.89 to 1.22; I2=18%). Conversely, in patients with N+ve disease the full-extended ET significantly improved DFS, with a pooled DFS-HR of 0.85 (95%CI: 0.74 to 0.97; I2=0%). There was a significant interaction between the disease nodal-status and the efficacy of the full-versus limited-extended ET (p-heterogeneity=0.048). The full-extended ET provided no significant DFS-benefit as compared with the limited-extended ET in all the other subgroups analyzed. Patients with eBC and N+ve disease can obtain a significant DFS-benefit from the full-extended as compared with the limited-extended adjuvant ET.

The impact of 4R Care Delivery Model on timing and sequence of bone density screening among breast cancer patients.

e24061 Background: Bone loss is common in patients with breast cancer and can impact treatment decisions related to endocrine therapy. Hence, bone density assessment prior to start of endocrine therapy is highly important, especially because endocrine therapy is recommended as the first line of adjuvant treatment in patients with ER+ breast cancer. However, implementing bone density assessment in a timely manner is challenging, particularly early in the care trajectory, which involves many specialties and includes many other tests and procedures. We conducted a care delivery optimization in a large health system to implement bone density testing and referral for bone health consultation prior to endocrine therapy. The optimization was conducted as part of implementing the 4R Oncology model (Right Info, Right Care, Right, Right Patient, at the Right Time), a novel approach to optimizing patient-facing care planning, team-based delivery and patient self-management. Here we describe the impact of this optimization. Methods: A cohort of 278 women with breast cancer who were in the 4R intervention (the 4R cohort) was compared to a historical control cohort of 201 women who received care pre-4R. Demographic, bone health history, and oncologic care data were abstracted from chart review and clinical databases. The prevalence of bone loss and timing of bone density consultation request was compared between the 4R and historical control cohorts. Results: The age, race/ethnicity and rate of ER+ cancer were similar between the cohorts. Patients in the 4R cohort were significantly more likely than those in the control cohort to have received a consultation for bone density screening prior to the start of endocrine therapy. They were also more likely to receive a bone density test result during their care. These findings remained significant when data were restricted to those ≥ 50 years (as a proxy for postmenopausal status) and those with ER-positive breast cancer. The rates of osteopenia and osteoporosis were similar between the cohorts: control 47%, 24%; 4R cohort: 46%, 23% respectively (data not shown). Conclusions: Care optimization using the 4R Oncology Model was associated with a significant improvement in the timing of bone density test before initiation of endocrine therapy. The 4R Oncology Model can lead to more informed decision making in adjuvant endocrine therapy for patients with breast cancer. Additional optimizations to improve the rates of bone density tests and referrals will be beneficial. [Table: see text]

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

538 Background: Adjuvant endocrine therapy (ET) is the standard of care for Estrogen Receptor (ER)-positive early-stage breast cancer. However, many patients suffer from adverse events associated with ET. The prognosis of patients with T1a/bN0 breast cancer with ER-positive and human epidermal growth factor 2 (HER2)-negative is excellent, and it is not clear whether adjuvant ET should be recommended. Here we evaluate the effect of adjuvant ET for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Methods: This study was a multicenter, retrospective cohort study that evaluated adjuvant ET for patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Patients who underwent surgery between 2008 and 2012 in 47 institutions of the Japan Clinical Oncology Group (JCOG) breast cancer group were eligible. We analyzed the cumulative incidence of distant metastasis as primary endpoint using the Gray test model and time to event endpoints (distant disease free survival and overall survival) using log-rank test between patients treated with and without adjuvant ET. We also used Gray test model for the analysis of the cumulative incidence of ipsilateral and contralateral breast cancer. Predictive factors were assessed using the Fine-Gray model and the Cox proportional hazards model. Results: The median follow-up period was 9.2 years. Of 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%] diseases), 3991 (83.9%) received adjuvant ET. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In the multivariate analysis, the independent risk factors of distant metastasis were no ET, mastectomy, high grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% (HR, 0.54; 95% CI, 0.38-0.77). Adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs 6.9%; sHR, 0.17; 95% CI 0.11-0.28, and 1.9% vs 5.2%; sHR, 0.33; 95% CI, 0.22-0.49). Conclusions: Adjuvant endocrine therapy significantly reduces distant metastases, however the absolute difference is small for ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, it reduced ipsilateral and contralateral breast cancer as well. Shared decision making regarding the omission of adjuvant endocrine therapy is crucial, especially in patients with low risk of distant metastasis.

Optimum duration of extended adjuvant endocrine therapy in patients with hormone receptor-positive breast cancer: protocol for a network meta-analysis of randomised controlled trials

IntroductionThe type of extended adjuvant endocrine therapy is not clear, nor is the optimum duration of extended adjuvant endocrine therapy for patients with early breast cancer. Our study aims to...

Abstract P4-03-01: Persistence with adjuvant endocrine therapy in patients with early breast cancer at high risk of recurrence: a US-based real-world study

Abstract Background: Previous studies have highlighted concerns regarding treatment persistence (TP) of patients with early breast cancer (EBC) taking adjuvant endocrine therapy (ET) but these data have not been analyzed based on patient’s risk of recurrence. The aim of this study is to evaluate the TP of patients at high risk of recurrence based on clinicopathologic criteria used in the monarchE trial. Methods: This observational retrospective cohort study used nationwide Flatiron Health electronic health record (EHR)-derived de-identified database of US patients diagnosed with EBC from Jan 2011 to Sept 2020. Overall, 4028 patients were selected based on the following criteria: adult female or male with diagnosis of HR+, HER2– EBC (stage IA-IIIC) with no evidence of distant metastasis who received surgical resection and adjuvant endocrine therapy. Patients were divided into 2 groups; GroupA: patients with clinicopathologic features suggestive of high risk of recurrence: ≥4 positive(+) axillary lymph nodes (ALN), OR 1-3+ ALN and either Grade3 disease, or tumor size ≥ 5 cm, or Ki-67 ≥ 20%. GroupB: patients with stage IA-IIIC disease who did not meet those high risk criteria. TP (time from start to discontinuation of adjuvant ET) was compared between the 2 groups. Patients who had a gap of &amp;gt;90 days after their last date of ET, as documented in the EHR, were considered to have discontinued ET. Patients whose last ET was ≤90 days from Sept 2020 were censored. Cumulative incidence functions of nonpersistence were estimated, treating recurrences or deaths occurring during ET as competing risks. Results: While gender and race distributions were similar between groups, patients in GroupA (n=557) were younger and more likely to be premenopausal, have an ECOG PS score of 1 or 2+, and have received mastectomy, radiation and chemotherapy compared to GroupB (n=3471). Estimates of the cumulative incidence functions of nonpersistence were statistically different between the groups (p &amp;lt;.001). The Table shows the cumulative incidence (standard error) of nonpersistence at years 1-5 after initiating ET. Conclusions: This study suggests that patients at high risk of recurrence have higher ET-TP than those at lower risk. The separation was most pronounced at 5 years. The steep increase in 5-year nonpersistence in lower risk group could be due to a perception of less need to continue ET for longer periods of time in lower risk disease. The greater persistence in patients at high risk is noteworthy, but interventions to improve patient’s TP are still warranted. Table 1: Cumulative incidence of nonpersistence after initiating ET Citation Format: Kristin M. Sheffield, Alexandra S. Vitko, Jacqueline Brown. Persistence with adjuvant endocrine therapy in patients with early breast cancer at high risk of recurrence: a US-based real-world study [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 P4-03-01.

Abstract P1-01-05: Adjuvant S-1 plus endocrine therapy for estrogen receptor-positive, HER2-negative, primary breast cancer: updated overall survival analysis from the POTENT trial

Abstract Background: The Phase III POTENT trial demonstrated an improvement in invasive disease-free survival (IDFS) by the addition of S-1, an oral fluoropyrimidine, to adjuvant endocrine therapy in patients with ER-positive/HER2-negative early breast cancer. Because the trial was terminated at the interim analysis as the primary endpoint was met, the result of the overall survival (OS) remains immature. Methods: This multicenter observational study aimed to investigate the survival outcomes of patients who participated in the POTENT trial, in which patients with stage I to IIIB ER-positive, HER2-negative breast cancer without protocol-defined low-risk features received adjuvant endocrine therapy alone or with S-1 for 1 year. Of the full analysis set (FAS) of the POTENT trial (N=1930), patients who withdrew the consent or whose institutions terminated the contract were excluded from this study. The primary endpoint was OS. Secondary endpoints were IDFS and distant recurrence-free survival (DRFS). Results: A total of 337 patients (17%) in the POTENT study were excluded from this analysis (eight patients withdrew consent and 329 patients for institutions whose contract had been terminated). A total of 1593 patients were included in this study (803 in the endocrine therapy alone group and 790 in the endocrine therapy plus S-1 group). The median follow-up was 77.5 months (IQR: 68.8–86.0). The median duration of endocrine therapy was 71 and 69 months in the endocrine therapy alone and endocrine therapy plus S-1 groups, respectively. The patient characteristics were well balanced between the treatment groups, except for the number of lymph nodes involved. The endocrine therapy alone group included more patients with four or more positive nodes than the endocrine therapy plus S-1 group (12% vs. 9%, P=0.01). 58 (7%) patients in the endocrine therapy alone group and 51 (6%) in the endocrine therapy plus S-1 group died (HR 0.89, 95%CI: 0.61–1.30, P=0.54). The 5-year overall survival estimate was 94.7% (95%CI: 92.9–96.1%) in the endocrine therapy alone group and 95.6% (95%CI: 93.8–96.8%) in the endocrine therapy plus S-1 group. IDFS events were observed in 166 patients (21%) in the endocrine therapy alone group and in 135 patients (17%) in the endocrine therapy plus S-1 group (HR 0.80, 95%CI: 0.64–1.01). DRFS events occurred in 123 patients (15%) in the endocrine therapy alone group and in 91 patients (12%) in the endocrine therapy plus S-1 group (HR 0.74, 95%CI: 0.56–0.97). Conclusions: In this observational study, data from 337 patients (17%) were missing from the FAS of the POTENT trial. Both the endocrine therapy alone group and endocrine therapy plus S-1 groups showed favorable OS, and OS was similar between the treatment groups. The benefit of IDFS and DRFS by the addition of S-1 to endocrine therapy were maintained. Citation Format: Masahiro Takada, Shigehira Saji, Takayuki Ueno, Norikazu Masuda, Hiroshi Ishiguro, Takanori Ishida, Toshiaki Saeki, Shigeru Imoto, Shinji Ohno, Hiroji Iwata, Tomoharu Sugie, Kenjiro Aogi, Hirofumi Mukai, Shin Takayama, Nobuaki Sato, Yuichiro Kai, Masahiro Kitada, Rikiya Nakamura, Yutaka Matsuyama, Masakazu Toi. Adjuvant S-1 plus endocrine therapy for estrogen receptor-positive, HER2-negative, primary breast cancer: updated overall survival analysis from the POTENT trial [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 P1-01-05.

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence.

Abemaciclib [Verzenio® (USA) or Verzenios® (EU)] is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with adjuvant endocrine therapy for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive, early breast cancer with a high risk of recurrence. In a phase III trial, abemaciclib plus endocrine therapy reduced the risk of recurrence of breast cancer compared with endocrine therapy alone, including in patients who had previously received neoadjuvant chemotherapy, in patients with high- and low-scoring Ki-67 tumours, and in both premenopausal and postmenopausal patients. The tolerability profile of abemaciclib plus endocrine therapy was acceptable and manageable, with diarrhoea, infections and neutropenia being the most common adverse events. Thus, abemaciclib in combination with standard endocrine therapy is a valuable additional treatment option for patients with HR+, HER2-, node-positive early breast cancer with a high risk of recurrence.

Adjuvant endocrine therapy in patients with estrogen receptor-low positive breast cancer: A prospective cohort study

BackgroundLittle is known about the benefits of adjuvant endocrine therapy (ET) in low ER-positive breast cancer (1%–10%) patients. We analyzed the association between ET and breast cancer-specific survival (BCSS) in these patients with respect to the regimen and the duration of ET. MethodsPatients were classified into three groups based on the regimen and duration of ET. The regimens included aromatase inhibitor (AI) monotherapy or sequential tamoxifen followed by an AI (AI/T + AI), or only tamoxifen and no ET. The duration of ET included 2–3 years and >3 years. Multivariate Cox regression analysis was employed to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs). ResultsOf the 10,696 patients diagnosed with breast cancer between 2010 and 2020, 407 women were identified with ER-low positive disease and met the inclusion criteria. During a median follow-up of 5.2 years, patients who received ET improved BCSS. Of them, those with AI/T + AI had increased BCSS compared to patients without ET, after adjusting for demographics and tumor characteristics, especially in ER-low/HER-2-positive breast cancer. After additional adjustment for treatment mode, the association maintained a similar trend. Patients who received >3 years of ET was associated with a better DFS. There was no significant difference in BCSS between patients with 2–3 years and >3 years of ET. ConclusionFor ER-low patients, findings suggest that ET with AI/T + AI may be a reasonable treatment alternative. This effect should be assessed in randomized studies.

Factors influencing the initiation of adjuvant endocrine therapy in patients with estrogen receptor-positive ductal carcinoma in situ: a single institution experience

PurposeThis study evaluates whether race, socioeconomic status, insurance type, oncological provider type, and prior cancer treatment are associated with the suggestion and acceptance of hormonal therapy in patients with estrogen receptor (ER)-positive Ductal carcinoma in situ (DCIS). This study also assesses whether disparities exist pertaining to prescription of such medications.MethodsThis single-center retrospective study included 111 patients diagnosed with DCIS between 2020 and 2021. Data collected included race, type of insurance, prescribing providers, and socioeconomic status. We used zip codes to identify the poverty levels in these areas as published in the United States Census Bureau and stratified the patients into quartiles accordingly. Chi-Square statistics were used to calculate significance levels.ResultsThere was no significant correlation between the intake of hormonal therapy and race (p = 0.60), insurance (p = 0.50), socioeconomic (p = 0.58), or providers (p = 0.99). 79.3% of women were offered endocrine therapy. Of those who were offered endocrine therapy, 70.8% accepted. Of patients not on hormonal therapy, 45.8% were not recommended the medications by their provider, and 54.2% declined treatment when offered.ConclusionIn this study, patients’ demographics and providers were not associated with adjuvant hormonal therapy initiation in DCIS. Our results show that abstaining from endocrine therapy in DCIS patients is both due to lack of provider recommendation and patient rejection of these medications. The wide variation in hormonal therapy treatment among ER-positive DCIS patients suggests a need for improved provider-patient communication regarding the risks and benefits of endocrine therapy in order to ensure a shared decision-making process.

Assessing the benefit of adjuvant endocrine therapy in patients following breast-conserving surgery with or without radiation stratified by a 7-gene predictive DCIS biosignature.

502 Background: Breast conserving surgery (BCS) followed by radiotherapy (RT) has been the mainstay for DCIS treatment. Adjuvant endocrine therapy (ET) has often been recommended based on multiple randomized clinical trials (RCT). However, these studies have failed to identify subsets of patients who did or did not benefit from adjuvant RT/ET therapy after BCS. We evaluated the association of a 7-gene predictive DCIS biosignature (PreludeDx, Laguna Hills, CA) to assess the impact of ET on 10-yr ipsilateral breast recurrence (IBR) risk after BCS alone or with RT. Methods: DCISionRT with integrated Residual Risk subtype (RRt) reported a decision score (DS) and three risk groups, a) Low Risk (DS≤2.8), b) Elevated Risk (DS &gt; 2.8 without RRt) and c) Residual Risk (DS &gt; 2.8 with RRt). DCISionRT/RRt was evaluated in 926 patients from 4 cohorts who were treated with BCS alone or with RT/ET. The three risk groups were assessed for 10-yr total (invasive and in situ) IBR risk by Kaplan Meier and Cox proportional hazards survival analysis. Results: DCISionRT/RRt classified 338 (37%) women as Low Risk, 399 (43%) as Elevated Risk, and 189 (20%) as Residual Risk. Overall, patients treated with ET had a significantly lower 10-yr IBR risk in multivariable analysis independent of RT (HR = 0.55, p = 0.033). In the Low Risk group treated with BCS without RT, the average 10-yr IBR risk was 5.6% (95% CI 2.5-12.1%, n = 124) and was not significantly different with vs without ET (p = 0.33). The 10-yr IBR risk after BCS alone was 22.6% in the Elevated Risk group and 50.3% in the Residual Risk group. Compared to BCS alone, the 10-year IBR risk tended to be lower in patients prescribed ET without RT in the Elevated (11.6%, 95% CI 3.9-32%) and Residual (15.4%, 95% CI 4.1-49%) Risk groups. 10-yr IBR risk was not significantly reduced by RT within the Low Risk group (p = 0.7) but was significantly reduced to 6.3% (95% CI 3.4-12%) by RT within the Elevated Risk (HR = 0.2, p &lt; 0.001) and to 12.5% (95% CI 6.4-23%) within the Residual Risk (HR = 0.2, p &lt; 0.001) groups. 10-yr IBR risk was significantly higher after RT in the Residual (HR = 2.5, p = 0.013) vs. Elevated Risk groups. After BCS and RT, there was no significant reduction in 10-yr IBR risk for those treated with vs without ET in the Elevated (p = 0.22) and Residual (p = 0.87) risk groups. Conclusions: The DCISionRT/RRt biosignature demonstrated prognostic and predictive RT response in Elevated and Residual Risk patients. Consistent with prior RCT data, ET was associated with lower 10-yr IBR risk overall, and within the DCISionRT Elevated and Residual Risk groups without RT. However, neither ET nor RT were asssociated with significant risk reduction in the Low Risk group. There was no added benefit of ET in the Elevated and Residual Risk groups after BCS+RT; the Residual Risk group patients still had a high IBR risk after RT.

Factors influencing the initiation of adjuvant endocrine therapy in patients with Estrogen receptor-positive ductal carcinoma in situ: A single institution experience.

e18569 Background: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal breast cancers. The aim of treatment in DCIS is to prevent local recurrence as almost half of recurrences can be invasive. Few studies have specifically addressed how provider recommendation and patient’s demographic factors contribute to medication initiation in women with DCIS. The objective of this study is to evaluate whether disparities exist pertaining to prescription of adjuvant hormonal therapies. Methods: This single-center retrospective study included 111 patients diagnosed with DCIS between 2020 and 2021. Data collected included race, type of insurance, prescribing providers, and socioeconomic status. We used zip codes to identify the poverty levels in these areas as published in the United States Census Bureau and stratified the patients into quartiles accordingly. Chi-Square statistics were used to calculate significance levels. Results: The average age was 62.8. 63 (56.8%) patients received adjuvant hormonal therapy, and 48 (43.2%) did not. White patients comprised 53.1% of the population, while African Americans were 45%. Among the white patients, 52.5% took hormonal therapy, while 62% of African Americans received hormonal treatment. Majority had Medicare insurance (49.5%), or a commercial insurance (42.3%). 62% of Medicare patients received hormonal therapy and 52.5% of commercial insurance users received adjuvant treatment. 34% lived in areas with the percentage below poverty line greater than 21.9%, 27% lived in areas with the percentage below poverty line between 16.4-21.9%, 38.7% % lived in areas with the percentage below poverty line between 10.6% and 16.4%, and 9% lived in areas with the percentage below poverty line was less than 10.6%. Providers were grouped into either breast oncologist or general oncologists. Breast oncologists prescribed hormonal treatment to 56.8% of their patients, and general oncologists to 56.7% of their patients. There was no statistical significant correlation between the intake of hormonal therapy and race (P = 0.6), insurance (P = 0.5), socioeconomic (P = 0.58) or providers (P = 0.99). Conclusions: In this single-center study, we didn’t find that patients’ demographics or providers influenced the decision to initiate adjuvant hormonal therapy in DCIS.

Cyclin dependent kinase 4/6 inhibitors in early breast cancer: what is the role of Ki-67?

Hormone receptor-positive and HER2-negative early breast cancer accounts for approximately 70% of all breast cancer diagnoses. In this setting, adjuvant endocrine therapy significantly improves survival outcomes, with selective use of neoadjuvant or adjuvant chemotherapy, as guided by clinical, pathological, and molecular recurrence risk assessments. To our knowledge, the monarchE study is the first randomised, clinical, phase 3 trial to show benefit, in terms of invasive disease-free survival, from the addition of the cyclin dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib to adjuvant endocrine therapy in patients with high-risk hormone receptor-positive, HER2-negative, and lymph node-positive early breast cancer. 1 Johnston SRD Harbeck N Hegg R et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020; 38: 3987-3998 Google Scholar , 2 Harbeck N Rastogi P Martin M et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021; 32: 1571-1581 Google Scholar These results led to the subsequent approval of abemaciclib by the US Food and Drug Administration (FDA) in October, 2021, restricted to patients who have tumours with immunohistochemical Ki-67 expression of 20% or higher, as measured by the companion diagnostic MIB-1 pharmDx assay (Dako Omnis, Agilent Technologies, Santa Clara, CA, USA).

De‐escalation of five‐year adjuvant endocrine therapy in patients with estrogen receptor‐low positive (immunohistochemistry staining 1%‐10%) breast cancer: Propensity‐matched analysis from a prospectively maintained cohort

BackgroundThe standard 5 years of endocrine therapy has demonstrated additional benefits compared with short‐term (2‐3 years) treatment in patients with estrogen receptor (ER)‐positive breast cancer; however, data specific to ER‐low positive breast cancer (1%‐10% by immunohistochemistry) are limited, and it is unclear whether long‐term treatment is still necessary for this subgroup.MethodsThe authors used the prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center for this propensity‐matched analysis. The primary end point was disease‐free survival. Multivariate Cox regression analysis and propensity score‐matching methods were used to minimize bias. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistics were 2‐sided.ResultsFrom 2012 to 2017, 22,768 consecutive women had pathologically confirmed, early stage breast cancer, and 1013 (4.45%) were identified with ER‐low positive disease. Among these, 634 patients met the inclusion criteria and were divided into 3 groups: those who received no endocrine therapy (n = 89), those who received 2 to 3 years of endocrine therapy (n = 185), and those who received approximately 5 years of endocrine therapy (n = 360). At a median follow‐up of 65 months, there was no significant difference in disease‐free survival between patients who received 2 to 3 years and 5 years of endocrine therapy (HR, 0.82; 95% CI, 0.51‐1.33; P = .43). The findings were consistent after multivariate Cox analysis of the propensity score‐matched samples (5 vs 2‐3 years of treatment: HR, 0.74; 95% CI, 0.41‐1.31; P = .30).ConclusionsShort‐term endocrine therapy for 2 to 3 years might be an alternative for patients who have ER‐low positive breast cancer instead of the standard 5 years of treatment.