Recurrence risk in early breast cancer as defined by clinicopathologic features.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18581-e18581
Author(s):  
Kristin M. Sheffield ◽  
Jessica R. Peachey ◽  
Michael W. Method ◽  
Brenda R. Grimes ◽  
Jacqueline Brown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Tumor Size ◽  
Disease Recurrence ◽  
Invasive Disease ◽  
Clinicopathologic Features ◽  
Ki 67 ◽  
Free Survival ◽  
Grade 3

e18581 Background: While most patients (pts) with HR+, HER2- early breast cancer (EBC) do not experience disease recurrence, those with high risk clinicopathologic features may have recurrence within the first few years on adjuvant endocrine therapy (AET). This study estimates risk of recurrence in pts with EBC based on clinicopathologic features and evaluates the medical need for more efficacious treatments using US oncology practice data. Methods: This retrospective study used the nationwide Flatiron Health electronic health record derived deidentified database. The cohort included pts with HR+, HER2- stage I-III breast cancer, diagnosed Jan 2011-Mar 2020, who received surgery and AET. Clinicopathologic features were used to identify a ‘high risk (HiR) group’ (≥ 4 positive axillary lymph nodes (LN), or 1-3 positive axillary LN and ≥ 1 of the following: Grade 3, tumor size ≥ 5 cm, or Ki-67 ≥ 20%) and ‘low risk (LoR) group’ (pts who do not meet above criteria, including a subset with node negative (N0) disease). Cox proportional hazards regression models compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) from AET initiation between groups according to a sequential gatekeeping strategy and stepwise analysis: first compare HiR group to N0 pts; if significant then compare HiR to LoR group. Results: 557 (13.8%) pts were in the HiR group and 3,471 (86.2%) in the LoR group (including 2,867 N0 pts). The study population (median age 64 yrs) was predominantly female (99.2%), white (69.4%) and postmenopausal (75.6%) with median follow-up of 39.6 months. Pts in the HiR group were younger and more likely premenopausal, have a BRCA mutation, invasive lobular carcinoma and less likely to have received an Oncotype DX test compared to LoR pts. Of the 557 HiR pts, 231 (41.5%) had ≥ 4 positive LN and 326 (58.5%) had 1-3 positive axillary LN with additional risk factor(s): tumor size ≥ 5 cm (11.7%), histologic grade 3 (32.0%), and/or Ki-67 ≥ 20% (31.6%). Most HiR pts received radiotherapy (82.4%) and chemotherapy (68.1%). Significant differences in IDFS and DRFS were observed between HiR group and N0 and LoR groups (logrank test p < .0001 for all). The 2-year IDFS rate was 88.1% in the HiR group, compared to 97.4% in N0 pts and 97.1% in the LoR group; 2-year DRFS rates were 89.0% compared to 97.9% and 97.7%, respectively. Pts in the HiR group had significantly higher hazard of invasive disease recurrence or death compared to N0 (HR = 3.42, 95% CI: 2.69-4.34, p < .0001) and LoR group (HR = 3.07, 95% CI: 2.46-3.84, p < .0001). Similar results observed for DRFS (HiR vs N0: HR = 3.46, 95% CI: 2.70-4.44, p < .0001; HiR vs LoR HR = 3.16, 95% CI: 2.50-3.98, p < .0001). Conclusions: Approximately 12% of pts with EBC and high risk clinicopathologic features experienced invasive disease recurrence or death within 2 years of initiating AET. Optimal use of standard therapies and novel treatment options are needed to prevent early recurrence and metastases in these pts.

Abemaciclib combined with adjuvant endocrine therapy in patients with high risk early breast cancer who received neoadjuvant chemotherapy (NAC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 517-517
Author(s):  
Miguel Martin ◽  
Roberto Hegg ◽  
Sung-Bae Kim ◽  
Michael Schenker ◽  
Daniela Grecea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Safety Profile ◽  
Tumor Size ◽  
Ki 67 ◽  
Treatment Benefit ◽  
Free Survival ◽  
Prior Chemotherapy

517 Background: monarchE, a phase 3, open-label, randomized study evaluating abemaciclib combined with adjuvant endocrine therapy (ET) compared to ET alone in patients with HR+, HER2-, high risk early breast cancer (EBC), resulted in a statistically significant improvement in invasive disease-free survival (IDFS) (HR = 0.713; 95% CI: 0.583, 0.871). NAC is used in patients with HR+, HER2- EBC at higher risk of recurrence despite often limited response, suggesting a need for enhanced adjuvant ET. Methods: Patients with ≥4 positive notes (LNS), or 1-3 LNS and either Grade 3 disease, tumor size ≥5 cm, or central Ki-67 ≥20% were eligible. Prior chemotherapy (NAC, adjuvant, none) was one of the stratifications factors. Prior therapy and tumor characteristics prior to study entry were collected. Here, we present the results of the prespecified subgroup of patients who received NAC. Results: Out of 5,637 randomized patients, 2056 (36.5%) received NAC. For 84.8%, the chosen regimen included anthracycline + cyclophosphamide + taxane, for 4.4%, it included anthracycline + taxane. A total of 1044 (50.8%) patients who received NAC had a radiologic tumor size between 2-5 cm and 599 (29.1%) had tumors ≥5 cm at diagnosis. 6.2%, 49.4% and 36.7% of patients had tumors with histologic Grade 1, 2, 3 respectively. 55.2% of patients had LNS ≥4+ and 44.4% had 1-3+ LNS. Central Ki-67 prior to NAC was ≥20% in 64.8% of patients with available Ki-67 results (664 (32.3%) patients had missing Ki-67 results). Evaluation of clinical and pathological measures of response will be presented. A multivariate cox regression analysis of IDFS in the intent-to-treat (ITT) population, identified prior chemotherapy as prognostic, suggesting patients who received NAC were at risk of a worse outcome. Primary outcome efficacy data for patients who received NAC are shown in the table below. Abemaciclib + ET demonstrated treatment benefit in terms of IDFS vs ET alone (HR: 0.614 95% CI: 0.473, 0.797) with 2-year IDFS rates of 87.2% vs 80.6%, respectively. The addition of abemaciclib to ET resulted in an improvement in distant relapse-free survival (DRFS) (HR: 0.609, 95% CI: 0.459, 0.809), with 2-year DRFS rates of 89.5% and 82.8%, respectively. Safety profile was similar to the overall safety population. Conclusions: Patients with HR+, HER2- EBC who received NAC were noted to be at a higher risk of recurrence. In this subgroup, abemaciclib combined with ET demonstrated a clinically meaningful treatment benefit in IDFS and DRFS, which was numerically greater than in the ITT population. Safety data were consistent with abemaciclib safety profile. Clinical trial information: NCT03155997. [Table: see text]

scholarly journals Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 423-430 ◽  
Author(s):  
Alberto Zambelli ◽  
Giovanni Pappagallo ◽  
Paolo Marchetti
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Disease Free

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

Phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of adagloxad simolenin (OBI-822) and OBI-821 treatment in patients with early-stage triple-negative breast cancer (TNBC) at high risk for recurrence.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS599-TPS599
Author(s):  
Hope S. Rugo ◽  
Louis W. C. Chow ◽  
Javier Cortes ◽  
Peter A. Fasching ◽  
Pei Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
High Risk ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Invasive Disease ◽  
Free Survival ◽  
Disease Free

TPS599 Background: Adagloxad simolenin (AS) is a therapeutic vaccine comprising the tumor-associated antigen Globo H linked to the carrier protein keyhole limpet hemocyanin (KLH). The KLH provides antigenic immune recognition and T-cell responses. AS is co-administered with a saponin-based adjuvant OBI-821 to induce a humoral response. A phase 2 trial showed that AS/OBI-821 exhibited a trend for superior progression-free survival vs placebo in patients whose breast cancers have higher Globo H expression. Methods: Patients with TNBC (ER/PR < 5%, and HER2-negative) with nonmetastatic disease and either 1) residual invasive disease of ≥1 cm in the breast or ≥1 positive axillary node following neoadjuvant chemotherapy or 2) ≥4 axillary lymph nodes with invasive carcinoma treated with adjuvant chemotherapy are included. Patients are prescreened for Globo H expression using a validated IHC assay (H-score of ≥15). Patients will receive either AS (30 μg) with OBI-821 (100 μg) or volume-matched placebo (1:1), administered as SC injections. Up to 21 SC injections of study treatment (or placebo), will be administered over 100 weeks, given on the following schedule: weekly for 4 doses; every 2 weeks for 4 doses; every 4 weeks for 4 doses; and then every 8 weeks for 9 doses. Patients may terminate treatment due to disease recurrence or unacceptable toxicity, withdrawal of consent, protocol violation, loss to follow-up or death. The primary objective is to determine the effect of AS/OBI-821 treatment on invasive disease-free survival in patients with TNBC at high risk for recurrence. Secondary objectives are to determine the impact of AS/OBI-821 treatment on overall survival, quality of life (QoL), breast cancer-free interval, distant disease-free survival, safety, and tolerability. Imaging and clinical examination will be performed regularly for 5 years. QoL will be assessed using the EORTC Core Quality of Life Questionnaire (QLQ)-C30 plus the EORTC Breast Cancer-specific QLQ-BR23 questionnaire and the European Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire. Adverse events will be graded/recorded as per National Cancer Institute CTCAE v5.0. An estimated 668 subjects will be enrolled, treated for up to 2 years and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last subject randomized. Survival follow-up is for 5 years from randomization of last subject. Clinical trial information: NTC03562637 .

Efficacy and safety analysis of Chinese patients in monarchE: Abemaciclib combined with adjuvant endocrine therapy for high risk HR+, HER2- early breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 522-522
Author(s):  
Shao Zhimin ◽  
Qingyuan Zhang ◽  
Chuan-gui Song ◽  
Quchang Ouyang ◽  
Zhenzhen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Safety Analysis ◽  
Invasive Disease ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Free Survival ◽  
To Receive

522 Background: In monarchE, abemaciclib (oral CDK4&6 inhibitor) plus endocrine therapy (ET) as adjuvant treatment for HR+, HER2- high risk early breast cancer (EBC), demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) compared to ET alone. Here we present the efficacy and safety analysis of Chinese patients from monarchE. Methods: The overall study design was reported previously. Eligible patients were randomized to receive abemaciclib (150 mg BID for 2 years) combined with standard adjuvant ET or ET alone. The primary endpoint was IDFS per STEEP criteria. Secondary endpoints included distant relapse-free survival (DRFS), overall survival, and safety. Exploratory subgroup analyses were conducted among Chinese patients enrolled from Mainland China, Hong Kong, and Taiwan in the intent-to-treat (ITT) population. Results: A total of 501 Chinese patients were randomized to receive abemaciclib plus ET (259 patients) or ET alone (242 patients). At the time of data cutoff (July 8, 2020), 356 (71.1%) patients were still in the 2-year treatment period. A total of 26 IDFS events were observed (11 and 15 events in abemaciclib plus ET and ET arm, respectively). Comparing to ET alone, abemaciclib combined with ET reduced the risk of developing invasive disease or death by 34.3% (HR: 0.657, 95% CI: 0.301, 1.435) for Chinese patients, together with a clinically meaningful improvement in the 2-year IDFS rate (95.6% vs 92.1%). The addition of abemaciclib to ET also resulted in an improvement in DRFS (HR: 0.601, 95% CI: 0.245, 1.477) for Chinese patients, with the 2-year DRFS rate at 96.7% (ET alone: 93.4%). In the abemaciclib arm, the most frequent treatment-emergent adverse events (TEAEs) and grade ≥3 TEAEs: diarrhea (90.3% and 5.0%), leukopenia (76.8% and 21.2%), and neutropenia (76.4% and 23.9%), respectively. Conclusions: Abemaciclib combined with adjuvant ET demonstrated clinically meaningful IDFS and DRFS benefits among Chinese patients with HR+, HER2-, high risk EBC, which was consistent with the ITT population as reported previously. The safety profile of abemaciclib in Chinese EBC patients was consistent with global population and also with that observed in Chinese metastatic breast cancer patients. Clinical trial information: NCT03155997.

eMonarcHER: A phase 3 study of abemaciclib plus standard adjuvant endocrine therapy in patients with HR+, HER2+, node-positive, high-risk early breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS596-TPS596
Author(s):  
Sara M. Tolaney ◽  
Lesley Fallowfield ◽  
Peter A. Kaufman ◽  
Eva M. Ciruelos ◽  
Mary Corona Gainford ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Primary Breast Tumor ◽  
Phase 3 ◽  
Free Survival ◽  
Node Positive ◽  
High Risk Disease ◽  
Definitive Surgery

TPS596 Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) with high-risk characteristics has a high risk of disease recurrence. Novel therapeutic options for this population are urgently needed. Abemaciclib is an oral, selective, and potent CDK4 & 6 inhibitor administered on a continuous schedule which is approved for HR+, HER2- advanced BC (ABC) as monotherapy and in combination with endocrine therapy (ET). Abemaciclib combined with ET demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) in participants (pt) with HR+, HER2-, node-positive, high risk early breast cancer (EBC) and also clinical activity in HR+, HER2+ ABC. The eMonarcHER trial investigates whether abemaciclib plus ET will improve IDFS in pts with HR+, HER2+, node-positive, high risk EBC. Methods: eMonarcHER is a phase 3 global, randomized, double-blinded, placebo (PB)-controlled trial in participants with HR+, HER2+, node-positive, high risk EBC who have completed adjuvant HER2-targeted therapy (tx). Eligible participants are randomized 1:1 to receive either abemaciclib 150 mg twice daily or PB, plus standard ET. Study intervention period will be ≤26 cycles (approximately 2 years) followed by ≤8 years of ET as medically indicated. Participants must have undergone definitive surgery of the primary breast tumor and have high-risk disease. High-risk disease is defined as (i) detection of residual axillary nodal disease at the time of definitive surgery in participants with prior neoadjuvant (neoadj) tx; or (ii) in patients not receiving neoadj tx, must have either ≥4 pathologically positive axillary lymph nodes (pALNs), or 1-3 pathological pALNs and either: histologic Grade 2-3 and/or primary invasive tumor size ≥5 cm. Participants must have received either adjuvant pertuzumab plus trastuzumab with chemotherapy or adjuvant T-DM1. Stratification factors include treatment with neoadj tx, menopausal status, and region. The study is powered at approximately 80% to detect the superiority of abemaciclib plus ET over PB plus ET in terms of IDFS (as defined by the STEEP system) at a 1-sided α =.025 using a log-rank test. Assuming a hazard ratio of 0.73, this requires approximately 324 events at final IDFS analysis. Key secondary objectives include overall survival, distant relapse free survival, safety, pharmacokinetics, and patient-reported outcomes. The study is planned to start in March 2021. Approximately 525 centers in 23 countries plan to enroll ̃2450 participants. Clinical trial information: NCT04752332.

Abstract PD2-01: High Ki-67 as a biomarker for identifying patients with high risk early breast cancer treated in monarchE

2021 ◽  
Author(s):  
Nadia Harbeck ◽  
Stephen Johnston ◽  
Peter Fasching ◽  
Miguel Martin ◽  
Masakazu Toi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Ki 67

scholarly journals Does Mode of Surgical Intervention Based on Oncotype DX Score Influence Disease Recurrence in Early Breast Cancer?

2020 ◽  
Vol 06 (02) ◽  
pp. e135-e138
Author(s):  
T. M. Aherne ◽  
M. R. Boland ◽  
D. Catargiu ◽  
K. Bashar ◽  
T. P. McVeigh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Local Excision ◽  
Wide Local Excision ◽  
Surgical Intervention ◽  
Disease Recurrence ◽  
Low Risk ◽  
Oncotype Dx ◽  
Significant Difference

Abstract Introduction Routine utilization of multigene assays to inform operative decision-making in early breast cancer (EBC) treatment is yet to be established. In this pilot study, we sought to establish the potential benefits of surgical intervention in EBC based on recurrence risk quantification using the Oncotype DX (ODX) assay. Materials and Methods Consecutive ODX tests performed over a 9-year period from October 2007 to May 2016 were evaluated. Oncotype scores were classified into high (≥31), medium (18–30), or low-risk (0–17) groups. The primary outcome was breast cancer recurrence. Subgroup analysis offered assessment of the recurrence effect of mode of surgical intervention for patient groups as defined by the oncotype score. Results In total 361 patients underwent ODX testing. The mean age and follow-up were 55.25 (± 10.58) years and 38.59 (± 29.1) months, respectively. The majority of patients underwent wide local excision (86.7%) with 8.9 and 4.4% patients having a mastectomy or wide local excision with completion mastectomy, respectively. Fifty-one percent of patients fell into the low risk ODX category with a further 40.2 and 8.5% deemed to be of intermediate and high risk. Five patients (1.38%) had disease recurrence. Comparative analysis of operative groups in each oncotype group revealed no difference in recurrence scores in the low- (p = 0.84) and high-risk groups (p = 0.92) with a statistically significant difference identified in the intermediate risk group (p = 0.002). Conclusion To date we have been unable to definitively identify a role for ODX in guiding surgical approach in EBC. There is, however, a need for larger studies to examine this hypothesis.

scholarly journals Effect of Estrogen Receptor Expression Level and Hormonal Therapy on Prognosis of Early Breast Cancer

2021 ◽  
Author(s):  
Kyung-Hwak Yoon ◽  
Yeshong Park ◽  
Eunyoung Kang ◽  
Eun-Kyu Kim ◽  
Jee Hyun Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Hormonal Therapy ◽  
Large Scale ◽  
Receptor Expression ◽  
Recurrence Free Survival ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Free Survival ◽  
Er Expression

Abstract PurposeEstrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1-10%) of ER expression have been separately defined as ER Low Positive (ERlow). It is suggested that ERlow tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh).MethodsRetrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ERlow, and ER-negative (ER-)).ResultsA total of 2162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1654 (76.5%) were ERhigh, 54 (2.5%) were ERlow, and 454 (21.0%) were ER- patients. ERlow cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2 (HER2), negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER- tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ERlow group (P = 0.418).ConclusionERlow breast cancer showed distinct clinicopathological features. ERlow tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ERlow breast cancer.

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