HER2-negative Primary Breast Cancer Research Articles

Abstract RF01-01: SERENA-3: A randomized pre-surgical window of opportunity study assessing dose and duration of camizestrant treatment in post-menopausal women with ER-positive, HER2-negative primary breast cancer

Abstract Background Camizestrant, a next-generation oral selective estrogen receptor (ER) degrader (SERD) and pure ER antagonist, has demonstrated statistically significant and clinically meaningful progression-free survival (PFS) benefit over fulvestrant at both 75 and 150 mg once-daily doses in the Phase 2 SERENA-2 (NCT04214288) study in post-menopausal women with ER+ HER2- advanced breast cancer. SERENA-3 (NCT04588298) was established to explore the biological effects of three camizestrant dose levels in post-menopausal women with ER+ HER2- primary breast cancer. Methods Post-menopausal women with ER+ HER2- primary breast cancer scheduled to undergo curative intent surgery were randomly assigned in Stages 1 and 2 to pre-surgical treatment with camizestrant at 75, 150 or 300 mg once daily for 5 to 7 days or, in a sequential Stage 3, randomly assigned to camizestrant at 75 or 150 mg once daily for 12 to 15 days. Image-guided tumor biopsies were accessed as pre-treatment samples, while on-treatment ultrasound-guided tumor biopsies were obtained on the last day of camizestrant treatment. The primary objective was to explore the effect of camizestrant on ER expression by comparison of pre-treatment and on-treatment biopsies as assessed by immunohistochemistry (IHC) H-score. Secondary objectives included assessment of Ki67 and progesterone receptor (PgR) expression, and also of safety and tolerability, with exploratory pharmacodynamic (PD) assessment using other transcriptomic and proteomic technologies. The study was undertaken in 17 centers across 3 countries (Georgia, Mexico and the United Kingdom). Results 135 patients were randomized and received treatment. 76 patients received camizestrant for 5 to 7 days at doses of 75 mg (n=30), 150 mg (n=33), and 300 mg (n=13); 59 received camizestrant for 12 to 15 days at doses of 75 mg (n=30) and 150 mg (n=29). Baseline disease characteristics, and ER, Ki67 and PgR levels were well balanced across arms and stages. Pharmacokinetic (PK) observations in all stages were commensurate with steady-state predictions derived from previous studies. PD data for ER and Ki67 are shown in Table 1. Camizestrant reduced ER H-score by approximately 65% irrespective of dose or duration. While the 75 mg dose reduced Ki67 score to a lesser degree than 150 mg and 300mg after 5–7 days exposure, after 12–15 days exposure 75 and 150 mg reduced Ki76 score to a similar substantial degree (82% reduction). PD results assessed by additional transcriptomics and proteomics assays were concordant with the IHC analyses. No serious adverse events were reported. All treatment-emergent adverse events were grade 1, apart from one patient with a grade 2 visual impairment, and one patient with grade 3 diarrhea. Conclusions SERENA-3 is the first study investigating the effect of multiple dose levels of camizestrant with different treatment durations on ER, Ki67 and PgR expression in post-menopausal women with primary ER+ HER2˗ breast cancer. SERENA-3 demonstrated that the 75 mg dose of camizestrant achieves maximal levels of ER degradation and Ki67 suppression. Together with SERENA-2, this provides strong evidence supporting 75 mg as the optimal dose of camizestrant, including for the early disease setting, and highlights the additive value of a specifically designed multi-dose pre-surgical PD study for optimal dose selection. Table 1 Citation Format: John Robertson, Teimuraz Gogitidze, Zaza Katashvili, Juan Enrique Bargallo Rocha, Ekaterine Arkania, Iain Moppett, Kwok-Leung Cheung, Gia Nemsadze, Maxine Ajimi, Itziar Irurzun-Arana, Justin Lindemann, Teresa Klinowska, Alastair Mathewson, Christopher Morrow, Myria Nikolaou, Giorgi Dzagnidze. SERENA-3: A randomized pre-surgical window of opportunity study assessing dose and duration of camizestrant treatment in post-menopausal women with ER-positive, HER2-negative primary 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 RF01-01.

Performance of a novel spectroscopy-based tool for adjuvant therapy decision-making in hormone receptor-positive breast cancer: a validation study

PurposeDigistain Index (DI), measured using an inexpensive mid-infrared spectrometer, reflects the level of aneuploidy in unstained tissue sections and correlates with tumor grade. We investigated whether incorporating DI with other clinicopathological variables could predict outcomes in patients with early breast cancer.MethodsDI was calculated in 801 patients with hormone receptor-positive, HER2-negative primary breast cancer and ≤ 3 positive lymph nodes. All patients were treated with systemic endocrine therapy and no chemotherapy. Multivariable proportional hazards modeling was used to incorporate DI with clinicopathological variables to generate the Digistain Prognostic Score (DPS). DPS was assessed for prediction of 5- and 10-year outcomes (recurrence, recurrence-free survival [RFS] and overall survival [OS]) using receiver operating characteristics and Cox proportional hazards regression models. Kaplan–Meier analysis evaluated the ability of DPS to stratify risk.ResultsDPS was consistently highly accurate and had negative predictive values for all three outcomes, ranging from 0.96 to 0.99 at 5 years and 0.84 to 0.95 at 10 years. DPS demonstrated statistically significant prognostic ability with significant hazard ratios (95% CI) for low- versus high-risk classification for RFS, recurrence and OS (1.80 [CI 1.31–2.48], 1.83 [1.32–2.52] and 1.77 [1.28–2.43], respectively; all P < 0.001).ConclusionDPS showed high accuracy and predictive performance, was able to stratify patients into low or high-risk, and considering its cost and rapidity, has the potential to offer clinical utility.

Impact of estrogen receptor expression level on response to neoadjuvant chemotherapy and prognosis in HER2-negative breast cancers

BackgroundBreast cancers with 1–10% cell staining for estrogen receptor (ER) present particular clinical features. The clinical data of estrogen receptor expression level and treatment effect are limited, particularly regarding chemotherapy benefit. We evaluated the pathologic response to neoadjuvant chemotherapy (NAC) in ER low positive tumors (ER staining 1-10%) and compared it with ER > 10% positive tumors (ER staining > 10%) and ER-negative tumors. We further explored the differences in recurrence and survival with respect to the ER expression level.MethodPatients with stages II and III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery were categorized according to their ER percentages into three groups: ER-negative, ER low positive, and ER > 10% positive. Logistic regression models were used to assess the association between each variable and pathologic complete response (pCR). Kaplan‒Meier analysis was used to estimate survival outcomes. Cox models were used to adjust for patient and tumor characteristics.ResultsA total of 241 patients were analyzed. Of all patients included, 22 (9.1%) had ER low positive tumors, 159 (66.0%) had ER > 10% positive tumors, and 60 (24.9%) were ER-negative. Low ER positivity was significantly associated with a higher pCR rate than ER > 10% positivity (OR, 0.249; 95% CI, 0.067–0.923; P = 0.038). After a median follow-up time of 32 months, the disease-free survival (DFS) and overall survival (OS) of the patients with ER low positive tumors were significantly worse than those of the patients with ER > 10% positive tumors but similar to those with ER-negative tumors. After adjustment for covariates, ER low positive tumors were significantly associated with worse DFS than ER > 10% positive tumors.ConclusionOur results indicated that ER low positive breast cancer presents a better response to neoadjuvant chemotherapy and significantly worse prognosis for patients than those with ER > 10% positive tumors, but similar to the ER-negative group. These data support that this category of patients behaves clinically like patients with ER-negative breast cancer and should be treated differently from patients with ER > 10% positive tumors. Further prospective study is needed.

Validation of a novel and rapid reagent free assay to predict outcomes for adjuvant therapy decision making in hormone receptor-positive breast cancer.

545 Background: Digistain is a mid-infrared imaging technology that assesses aneuploidy by measuring the nuclear-to-cytoplasmic chemical ratio in the cellular content of tissues to generate the Digistain Index (DI). DI correlates with tumor grade and shows promise for risk stratification. Here we investigated whether DI could predict clinical outcomes in patients with early breast cancer to guide decision making regarding subsequent adjuvant chemotherapy. Methods: Infrared spectrometry was performed on existing tissue microarrays to determine the DI of 801 patients with hormone receptor-positive, HER 2-negative primary breast cancer with ≤3 positive lymph nodes who had received systemic endocrine therapy only. Multivariate logistic modelling incorporated the DI with pathological features to generate the Digistain Prognostic Score (DPS). Receiver operator characteristics curves were used to assess the ability of DPS to predict 5- and 10-year progression-free survival (PFS), recurrence and overall survival (OS). Results: In a Cox-regression analysis, the hazard ratio (HR) of DI to predict OS was 4.49 (95% CI 1.08–18.67; P=0.039) compared with HRs in the range of 1.04–1.81 (all P &lt; 0.001) for age, tumor grade, tumor size and lymph node stage. In multivariate modelling analysis, DPS was consistently highly accurate and had negative predictive values for PFS, recurrence, and OS at 5 and 10 years that were similar, if not superior, to existing genomic-based tests. Using the DPS, the HRs for Kaplan-Meier curves for low- vs. high-risk classification were statistically significant (P&lt;0.001) for PFS, recurrence and OS (1.80, 1.83 and 2.49, respectively). Conclusions: In patients with early breast cancer, DPS showed high accuracy and predictive performance, and was able to stratify patients into low or high risk. Considering its low cost and ability to provide almost immediate prognostic information, DPS has the potential to offer clinical utility to reduce the use of unnecessary chemotherapy.

Abstract P5-09-01: Neoadjuvant hormonal therapy plus palbociclib versus hormonal therapy plus placebo in women with operable, hormone sensitive and HER2-negative primary breast cancer

Abstract Background: Early biologic response to endocrine therapy, such as changes in Ki67 labeling index (LI), has been suggested to predict long-term outcomes in hormone sensitive breast cancer. The addition of a CDK4/6 inhibitor to endocrine therapy has been shown to augment biological response in breast cancer. Pre-operative Endocrine Prognostic Index (PEPI) scores, generated based on post-treatment Ki67 LI, have been shown to predict patient outcomes. EndoPredict® is a multigene assay that predicts the risk of distant recurrence in patients with operable estrogen receptor (ER)-positive HER2-negative breast cancer. This study was conducted to evaluate the efficacy of the neoadjuvant endocrine therapy plus palbociclib versus neoadjuvant endocrine therapy plus placebo. Patients and Methods: This is a phase III randomized, double-blind study of neoadjuvant hormonal therapy plus palbociclib versus neoadjuvant hormonal therapy plus placebo in untreated pre/peri- and post-menopausal women with operable, hormone receptor-positive (ER and/or progesterone receptor), HER2-negative breast cancer. The other major inclusion criteria included tumor size ≥ 15mm, T1c-3N0-1, Ki67 LI ≥14% by central assessment, and no previous history of radiotherapy or systemic therapy for breast cancer. Patients were randomly assigned 1:1 to receive 16 weeks of hormonal therapy plus palbociclib or hormonal therapy plus placebo. Hormonal therapy consisted of letrozole for post-menopausal patients and tamoxifen plus LH-RH agonist for pre/peri-menopausal patients. The co-primary endpoints included PEPI score and EPclin Risk Score, a score combining EndoPredict® molecular score with clinical factors. These scores were sequentially analyzed on a modified intent-to-treat basis according to the gatekeeping procedure: if statistical significance was detected on the PEPI score, the statistical significance of EPclin Risk Score would be assessed. The sample size was 100 patients in each arm, which was calculated with &amp;lt; 5% type I error rate (two sided) and 80% power. Results: Between 16 July 2019 – 7 July 2021, 141 eligible patients were randomized from 25 participating institutes in Japan, Korea, Taiwan, Hong Kong and Australia. One hundred twenty-six patients completed the treatment duration and surgical samples were collected to evaluate endpoints. All randomized patients were evaluable for safety assessment. Randomization was well-balanced in terms of age, menopausal status and cancer stage. The proportion of patients who had a low, moderate, or high PEPI score was 15.2%, 50.0% and 34.8% in the hormonal therapy plus palbociclib arm and 13.3%, 55.0% and 31.7% in the hormonal therapy plus placebo arm, respectively. There was no statistically significant difference in PEPI score between two arms (one-sided p-value=0.563). The proportion of patients who had a high risk EPclin Risk Score seemed lower in the palbociclib arm than in the placebo arm (62.1% vs 68.3%) although hypothesis testing was not performed on EPclin Risk Score because statistical significance was not detected on the PEPI score. No new safety signals were found in the study. Permanent discontinuation from the study in association with adverse events was reported for 7 (9.7%) patients in the hormonal therapy plus palbociclib arm and for 0 patients in the hormonal therapy plus placebo arm. Conclusions: The addition of palbociclib to neoadjuvant hormonal therapy did not improve efficacy measured by PEPI score. In palbociclib arm, the rate of patients who had a high risk EPclin Risk Score after treatment was lower than in placebo arm. Translational researches are ongoing to analyze molecular changes by treatments. The role of chemotherapy after neoadjuvant therapy is under investigation. Clinical trial identification: NCT03969121 Funding: Pfizer Inc. Citation Format: Takayuki Ueno, Louis W.C. Chow, Wonshik Han, Chiun Sheng Huang, G Bruce Mann, Satoshi Morita, Hironori Haga, Elham Fakhrejahani, Takayuki Kobayashi, Kenichi Inoue, Mariko Tokiwa, Hirofumi Suwa, Tomoyuki Aruga, Sachiko Minamiguchi, Yosuke Yamada, Yuko Tanabe, Masahiro Takada, Toshinari Yamashita, Hiroji Iwata, Chi-Feng Chung, Sachiko Takahara, Eriko Tokunaga, Shigeru Imoto, Eun Sook Lee, Yasuaki Sagara, Jee Hyun Kim, Richard H DeBoer, Hyun-Ah Kim, Hung Wen Lai, Ming-Feng Hou, Michelle White, Yoshiko Umeyama. Neoadjuvant hormonal therapy plus palbociclib versus hormonal therapy plus placebo in women with operable, hormone sensitive and HER2-negative primary breast cancer [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 P5-09-01.

Abstract P2-03-23: Retrospective evaluation of outcomes in a real-world, prospective cohort using EndoPredict: Results from the Charité registry

Abstract Background: EndoPredict is a prognostic and predictive gene expression assay that provides an EPclin risk score, which can be used to identify individuals with low enough risk of distant breast cancer recurrence that they may forgo chemotherapy. In clinical studies, EndoPredict has been validated to predict risk of distant recurrence up to 15 years and chemotherapy benefit. To date, real-world studies evaluating patient outcomes after prospective EndoPredict testing have been limited. Here, we report on outcomes collected via survey from patients enrolled in a registry created to generate real-world evidence from over 800 patients routinely tested with EndoPredict at Charité University Hospital Berlin. Methods: Female patients with hormone receptor positive, HER2 negative primary breast cancer with up to three positive lymph nodes who received prospective EndoPredict testing at Charité University Hospital Institute of Pathology between 2011 and 2016 were contacted to complete a survey for participation in this study. Surveys included questions on treatment and recurrence history. Patient demographics, clinical characteristics of the cancer, and EndoPredict results were retrieved from Charité records. All patients received EndoPredict test results before decision making on systemic treatment. After testing, treatment included either adjuvant endocrine therapy or adjuvant endocrine therapy plus adjuvant chemotherapy, and may have included radiotherapy. Cox proportional hazards models were fit with binary EPclin risk category (high, low) or continuous EPclin risk score predicting 5-year distant recurrence or recurrence of any kind. Analyses were performed across all survey responses, and in subsets of patients stratified by adjuvant chemotherapy treatment. Kaplan-Meier estimates of 5-year risk of recurrence were also calculated. Results: 842 patient survey responses were returned with informed consent and met study inclusion criteria. The median age at diagnosis was 54 years (IQR 49, 63), and across survey responses, 63.5% (N=535/842) of patients were lymph node negative, 60.9% (N=513/842) were T1, and 43.9% (N=370/842) were treated with adjuvant chemotherapy. Among included patients, 49.5% (N=417/842) were classified as EPclin low-risk and 50.5% (N=425/842) were high-risk. The concordance between EPclin risk category and chemotherapy status was 0.89 with 5.5% (N=23/417) of EPclin low-risk and 81.6% (N=347/425) of EPclin high-risk patients receiving treatment with chemotherapy. In the subset of patients not treated with adjuvant chemotherapy (N=472/842, 55.7%), continuous EPclin score was a significant predictor of distant recurrence (N=469; HR: 4.34, 95% CI 1.75-9.58); p = 2.4 × 10-3), and recurrence of any kind (N=468; HR: 3.39, 95% CI 1.61-6.58); p = 1.9 × 10-3). In EPclin low-risk patients treated with endocrine therapy alone, there was a low risk of 5-year distant recurrence (1.6%, 95% CI 0.7%-3.4%). In EPclin high-risk patients the risk of distant recurrence at 5 years was 6.8% (95% CI 2.6%-17.4%) in patients without chemotherapy and 3.6% (95% CI 2.1%-6.3%) in patients treated with chemotherapy. In an exploratory subgroup analysis in patients with node negative and node positive disease, risk of 5-year distant recurrence in EPclin low-risk patients without chemotherapy was 1.3% (95% CI 0.5%-3.5%) and 2.4% (95% CI 0.6%-9.2%), respectively. Conclusion: In this real-world cohort of patients with prospective routine testing with EndoPredict, EPclin scores were a significant predictor for patient-reported outcomes. Patients with EPclin low-risk scores had a low risk of 5-year distant recurrence even in the absence of chemotherapy treatment. This real-world result supports previous clinical studies demonstrating that patients with EPclin low-risk scores can safely forgo chemotherapy. Citation Format: Wolfgang D. Schmitt, Paul Jank, Inga Hoffmann, Berit M. Pfitzner, Lauren Lenz, Wyatt Clegg, Elke Keil, Sarah Ratzel, Elizabeth S. Cogan, Jens-Uwe Blohmer, Pauline Wimberger, Ralf Kronenwett, David Horst, Carsten Denkert. Retrospective evaluation of outcomes in a real-world, prospective cohort using EndoPredict: Results from the Charité registry [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 P2-03-23.

Discordance of HER2-Low between Primary Tumors and Matched Distant Metastases in Breast Cancer.

We examined differences in HER2 expression between primary tumors and distant metastases, particularly within the HER2-negative primary breast cancer cohort (HER2-low and HER2-zero). The retrospective study included 191 consecutive paired samples of primary breast cancer and distant metastases diagnosed between 1995 and 2019. HER2-negative samples were divided into HER2-zero (immunohistochemistry [IHC] score 0) and HER2-low (IHC score 1+ or 2+/in situ hybridization [ISH]-negative). The main objective was to analyze the discordance rate between matched primary and metastatic samples, focusing on the site of distant metastasis, molecular subtype, and de novo metastatic breast cancer. The relationship was determined by cross-tabulation and calculation of Cohen's Kappa coefficient. The final study cohort included 148 paired samples. The largest proportion in the HER2-negative cohort was HER2-low [primary tumor 61.4% (n = 78), metastatic samples 73.5% (n = 86)]. The discordance rate between the HER2 status of primary tumors and corresponding distant metastases was 49.6% (n = 63) (Kappa -0.003, 95%CI -0.15-0.15). Development of a HER2-low phenotype occurred most frequently (n = 52, 40.9%), mostly with a switch from HER2-zero to HER2-low (n = 34, 26.8%). Relevant HER2 discordance rates were observed between different metastatic sites and molecular subtypes. Primary metastatic breast cancer had a significantly lower HER2 discordance rate than secondary metastatic breast cancer [30.2% (Kappa 0.48, 95%CI 0.27-0.69) versus 50.5% (Kappa 0.14, 95% CI -0.03-0.32)]. This highlights the importance of evaluating potentially therapy-relevant discordance rates between a primary tumor and corresponding distant metastases.

Clinical Validation of EndoPredict in Pre-Menopausal Women with ER-Positive, HER2-Negative Primary Breast Cancer.

The EndoPredict prognostic assay is validated to predict distant recurrence and response to chemotherapy primarily in post-menopausal women with estrogen receptor-positive (ER+), HER2- breast cancer. This study evaluated the performance of EndoPredict in pre-menopausal women. Tumor samples from 385 pre-menopausal women with ER+, HER2- primary breast cancer (pT1-3, pN0-1) who did not receive chemotherapy in addition to endocrine therapy were tested with EndoPredict to produce a 12-gene EP molecular score and an integrated EPclin score that includes pathologic tumor size and nodal status. Associations of molecular and EPclin scores with 10-year distant recurrence-free survival (DRFS) were evaluated by Cox proportional hazards models and Kaplan-Meier analysis. After a median follow-up of 9.7 years, both the EP molecular score and the molecular-clinicopathologic EPclin score were associated with increased risk of distant recurrence [HR, 1.33; 95% confidence interval (CI), 1.18-1.50; P = 7.2 × 10-6; HR, 3.58; 95% CI, 2.26-5.66; P = 9.8 × 10-8, respectively]. Both scores remained significant after adjusting for clinical factors in multivariate analysis. Patients with low-risk EPclin scores (64.7%) had significantly improved DRFS compared with high-risk patients (HR, 4.61; 95% CI, 1.40-15.17; P = 4.2 × 10-3). At 10 years, patients with low-risk and high-risk EPclin scores had a DRFS of 97% (95% CI, 93%-99%) and 76% (95% CI, 67%-82%), respectively. The EPclin score is strongly associated with DRFS in pre-menopausal women who received adjuvant endocrine therapy alone. On the basis of these data, pre-menopausal women with EPclin low-risk breast cancer may be treated with endocrine therapy only and safely forgo adjuvant chemotherapy.

Annual Congress of the European Association of Nuclear Medicine 2021.

The radionuclide [99mTc]Tc-(HE)3-G3 is safe, well tolerated, and enables differentiation between HER2-positive and HER2-negative breast tumours, according to a first-in-human study presented by Olga Bragina (Tomsk National Research Medical Center, Tomsk, Russia). Patients with clinically confirmed HER2-positive or HER2-negative primary breast cancer were given [99mTc]Tc-(HE)3-G3 at a protein dose of 1000 μg (n=9), 2000 μg (n=10), or 3000 μg (n=9). No side-effects were noted during 7 days of post-injection observation. Visualisation of tumours using planar scintigraphy and single-photon-emission CT imaging was possible 2 h after injection, and the tumour-to-contralateral site ratio for HER2-positive breast tumours was significantly higher than the ratio for HER2-negative breast tumours (p<0·05).

The OncoMasTR Test Predicts Distant Recurrence in Estrogen Receptor-Positive, HER2-Negative Early-Stage Breast Cancer: A Validation Study in ABCSG Trial 8.

To validate the clinical performance of the OncoMasTR Risk Score in the biomarker cohort of Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 8. We evaluated the OncoMasTR test in 1,200 formalin-fixed, paraffin-embedded (FFPE) surgical specimens from postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer with 0 to 3 involved lymph nodes in the prospective, randomized ABCSG Trial 8. Time to distant recurrence (DR) was analyzed by Cox models. The OncoMasTR Risk Score categorized 850 of 1,087 (78.2%) evaluable patients as "low risk". At 10 years, the DR rate for patients in the low-risk group was 5.8% versus 21.1% for patients in the high-risk group (P < 0.0001, absolute risk reduction 15.3%). The OncoMasTR Risk Score was highly prognostic for prediction of DR in years 0 to 10 in all patients [HR 1.91, 95% confidence interval (CI) 1.62-2.26, P < 0.0001; C-index 0.73], in patients that were node negative (HR 1.79, 95% CI, 1.43-2.24, P < 0.0001; C-index 0.72), and in patients with 1 to 3 involved lymph nodes (HR 1.93, 95% CI, 1.44-2.58, P < 0.0001; C-index 0.71). The OncoMasTR Risk Score provided significant additional prognostic information beyond clinical parameters, Ki67, Nottingham Prognostic Index, and Clinical Treatment Score. OncoMasTR Risk Score is highly prognostic for DR in postmenopausal women with ER-positive, HER2-negative primary breast cancer with 0 to 3 involved lymph nodes. In combination with prior validation studies, this fully independent validation in ABCSG Trial 8 provides level 1B evidence for the prognostic capability of the OncoMasTR Risk Score.

Tumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti-PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast Cancer.

Immunotherapies targeting PD-1/L1 enhance pathologic complete response (pCR) rates when added to standard neoadjuvant chemotherapy (NAC) regimens in early-stage triple-negative, and possibly high-risk estrogen receptor-positive breast cancer. However, immunotherapy has been associated with significant toxicity, and most patients treated with NAC do not require immunotherapy to achieve pCR. Biomarkers discerning patients benefitting from the addition of immunotherapy from those who would achieve pCR to NAC alone are clearly needed. In this study, we tested the ability of MHC-II expression on tumor cells, to predict immunotherapy-specific benefit in the neoadjuvant breast cancer setting. This was a retrospective tissue-based analysis of 3 cohorts of patients with breast cancer: (i) primary nonimmunotherapy-treated breast cancers (n = 381), (ii) triple-negative breast cancers (TNBC) treated with durvalumab and standard NAC (n = 48), and (iii) HER2-negative patients treated with standard NAC (n = 87) or NAC and pembrolizumab (n = 66). HLA-DR positivity on ≥5% of tumor cells, defined a priori, was observed in 10% and 15% of primary non-immunotherapy-treated hormone receptor-positive and triple-negative breast cancers, respectively. Quantitative assessment of MHC-II on tumor cells was predictive of durvalumab + NAC and pembrolizumab + NAC (ROC AUC, 0.71; P = 0.01 and AUC, 0.73; P = 0.001, respectively), but not NAC alone (AUC, 0.5; P = 0.99). Tumor-specific MHC-II has a strong candidacy as a specific biomarker of anti-PD-1/L1 immunotherapy benefit when added to standard NAC in HER2-negative breast cancer. Combined with previous studies in melanoma, MHC-II has the potential to be a pan-cancer biomarker. Validation is warranted in existing and future phase II/III clinical trials in this setting.

The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers

The biology of breast cancer response to neoadjuvant therapy is underrepresented in the literature and provides a window-of-opportunity to explore the genomic and microenvironment modulation of tumours exposed to therapy. Here, we characterised the mutational, gene expression, pathway enrichment and tumour-infiltrating lymphocytes (TILs) dynamics across different timepoints of 35 HER2-negative primary breast cancer patients receiving neoadjuvant eribulin therapy (SOLTI-1007 NEOERIBULIN-NCT01669252). Whole-exome data (N = 88 samples) generated mutational profiles and candidate neoantigens and were analysed along with RNA-Nanostring 545-gene expression (N = 96 samples) and stromal TILs (N = 105 samples). Tumour mutation burden varied across patients at baseline but not across the sampling timepoints for each patient. Mutational signatures were not always conserved across tumours. There was a trend towards higher odds of response and less hazard to relapse when the percentage of subclonal mutations was low, suggesting that more homogenous tumours might have better responses to neoadjuvant therapy. Few driver mutations (5.1%) generated putative neoantigens. Mutation and neoantigen load were positively correlated (R2 = 0.94, p = <0.001); neoantigen load was weakly correlated with stromal TILs (R2 = 0.16, p = 0.02). An enrichment in pathways linked to immune infiltration and reduced programmed cell death expression were seen after 12 weeks of eribulin in good responders. VEGF was downregulated over time in the good responder group and FABP5, an inductor of epithelial mesenchymal transition (EMT), was upregulated in cases that recurred (p < 0.05). Mutational heterogeneity, subclonal architecture and the improvement of immune microenvironment along with remodelling of hypoxia and EMT may influence the response to neoadjuvant treatment.

A New PET Probe for Imaging Chimeric Antigen Receptor T Cells.

HomeRadiology: Imaging CancerVol. 3, No. 2 PreviousNext Research HighlightsFree AccessA New PET Probe for Imaging Chimeric Antigen Receptor T CellsGary D. LukerGary D. LukerGary D. LukerPublished Online:Mar 26 2021https://doi.org/10.1148/rycan.2021219004MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major Focus: To investigate the feasibility of imaging chimeric antigen receptor (CAR) T cells with a zirconium 89–labeled antibody targeted to inducible T-cell costimulator (ICOS or CD278).■ Key Result: ImmunoPET imaging of ICOS enabled the visualization of activated CAR T cells without affecting persistence or function of these cells in a mouse model of B-cell lymphoma.■ Impact: ImmunoPET with antibody detection of the endogenous activation marker ICOS provides a potentially general approach to image any CAR T-cell therapy.CAR T cells are a type of cancer therapy based on engineering a patient’s own T cells with a receptor for a specific protein target on cancer cells. After expansion of the cells in a laboratory, a patient receives an infusion of the engineered CAR T cells. For efficacy, the cells must migrate to tumors, proliferate, as well as become and remain activated to kill target cancer cells. CAR T cells have shown impressive successes in some blood cancers, such as B-cell malignancies, but efficacy remains limited in solid tumors. A major challenge in understanding successes and failures of CAR T-cell therapy is the ability to monitor these cells in vivo. Current methods rely on measuring numbers of cells in the circulation, but this approach does not reliably reflect actual migration of CAR T cells into a tumor.Simonetta and colleagues analyzed human and mouse CAR T cells and identified ICOS as a promising marker of activation to an antitumor state. The team labeled an antibody to ICOS with zirconium 89, providing a probe for PET imaging of CAR T cells in a mouse model of B-cell lymphoma. PET imaging showed greater accumulation of the immunoPET probe to ICOS in mouse bone marrow sites of lymphoma. Tracer doses of the immunoPET antibody did not affect persistence or function of CAR T cells as cancer immunotherapeutics. While the current study investigated therapy in mice, the study suggests that immunoPET imaging of ICOS could become a clinically translatable, general approach to monitor cancer therapy with a wide range of CAR T cells.Highlighted ArticleSimonetta F, Alam IS, Lohmeyer JK, et al. Molecular imaging of chimeric antigen receptor T cells by ICOS-ImmunoPET. Clin Cancer Res 2021;27:1058–1068. doi: https://doi.org/10.1158/1078-0432.CCR-20-2770Highlighted ArticleSimonetta F, Alam IS, Lohmeyer JK, et al. Molecular imaging of chimeric antigen receptor T cells by ICOS-ImmunoPET. Clin Cancer Res 2021;27:1058–1068. doi: https://doi.org/10.1158/1078-0432.CCR-20-2770 Crossref, Medline, Google ScholarArticle HistoryPublished online: Mar 26 2021 FiguresReferencesRelatedDetailsRecommended Articles CD38-targeted Immuno-PET of Multiple Myeloma: From Xenograft Models to First-in-Human ImagingRadiology2020Volume: 295Issue: 3pp. 606-615Nanotechnology for Cancer Imaging: Advances, Challenges, and Clinical OpportunitiesRadiology: Imaging Cancer2021Volume: 3Issue: 318F FDG PET/CT and Novel Molecular Imaging for Directing Immunotherapy in CancerRadiology2022Volume: 304Issue: 2pp. 246-264Identification of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer by Using HER2-targeted 89Zr-Pertuzumab PET/CTRadiology2020Volume: 296Issue: 2pp. 370-378Radiotheranostics in Cancer Diagnosis and ManagementRadiology2018Volume: 286Issue: 2pp. 388-400See More RSNA Education Exhibits Immune Effector Cell Therapy for Solid Tumors: Opportunities for Interventional RadiologyDigital Posters2019When Things Go Wrong, Characteristic PET CT Patterns of Triple and Double-Hit Lymphoma; A Pictorial ReviewDigital Posters2018Imaging Biomarkers in Targeted Therapies: From Quantitative Imaging to RadiomicsDigital Posters2019 RSNA Case Collection Benign bone marrow stimulation RSNA Case Collection2020Primary Calvarial Lymphoma RSNA Case Collection2021Primary Bone LymphomaRSNA Case Collection2020 Vol. 3, No. 2 Metrics Altmetric Score PDF download

Abstract PS9-52: A randomized phase II trial of interventions with frozen groves and compression stockings to prevent nab-paclitaxel induced chemotherapy-induced peripheral neuropathy (SPOT trial)

Abstract Background: Nab-paclitaxel(nab-PTX) is improved taxane in terms of solubility, alcohol-free and reduced incidence of anaphylaxis. On the other hand, chemotherapy-induced peripheral neuropathy (PN) is known as a major adverse event which was failed to suppress by many medications. Recently, some reports describe about cooling and compression of extremities of patients treated by taxane can reduce the incidence and severity of PN. The efficacies of interventions with frozen groves and compression stockings to prevent nab-PTX-induced PN was examined.Methods: The patients with HER2 negative primary breast cancers treated by four cycles of nab-PTX pre-/post- operative chemotherapies were randomized to two groups (interventions with frozen groves (FG) and compression stockings (CS), and with standard care (SD)). Primary endpoint was frequency and time to onset of &amp;gt;Grade 2 PN by CTCAE ver.4.0, and secondary endpoints are frequency of &amp;gt;Grade2 PN at the end of four cycles of nab-PTX, HRQOL, recovery of PN for 5 years from the end of nab-PTX and safety. Also, we requested to keep diary with several questions for patient reported outcomes (PRO).Results: Of the 124pts enrolled, 123(62 FG/CS, 61 SD) were included in the intent-to-treat analysis. There were no significant differences in clinicopathological findings between two groups. As a primary endpoint, frequency and time to onset of &amp;gt;Grade 2 motor-PN /sensory-NP of hands comparing FG and SD showed p=0.162/0.599, and of foots comparing CS and SD showed p=0.525/0.933 (Log-rank test with one sided significant level of 10%). Conversely, the worst Grade of sensory-PN is statistically significant difference at Cycle 2 (p=0.021; Mann-Whitney’s U-test with two-sided significant level of 5%), &amp;gt;Grade3 of motor-PN was statistically significant low in all cycles (p=0.022; Log-rank test with one sided significant level of 10%), &amp;gt;Grade1 of sensory-PN was statistically significant low (p=0.022; Log-rank test with one sided significant level of 10%), and &amp;gt;Grade3 of sensory-PN was statistically significant low in all cycles (p=0.072; Log-rank test with one sided significant level of 10%) with FG in detail. In addition, Grade3 of motor-PN was statistically significant low in all cycles (p=0.022; Log-rank test with one sided significant level of 10%), &amp;gt;Grade1 of sensory-PN was statistically significant low (p=0.015; Log-rank test with one sided significant level of 10%), and &amp;gt;Grade3 of sensory-PN was statistically significant low in all cycles (p=0.089; Log-rank test with one sided significant level of 10%)in all cycles (p=0.022; Log-rank test with one sided significant level of 10%) with CS in detail. Moreover, PRO indicated by patients’ diary showed interesting patterns of increase and decrease in sense of pain and paralyzed which might be corresponding to efficacy of interventions with FG and CS.Conclusion: Although primary endpoints were not met by the interventions with FG and CS, this trial revealed the detail of PN caused by nab-PTX, and these interventions might delay beginning of sensory and motor PN and reduce the worst grade of PN. The adverse events grading according to CTCAE and PRO indicated by patients’ diary seems to be not completely matched, the usefulness of FG and CS are investigating with more questionnaire. (UMIN: UMIN000016902) Citation Format: Masahiro Kashiwaba, Takahiro Nakayama, Takafumi Sangai, Takashi Morimoto, Hiroyuki Yasojima, Yutaka Yamamoto, Shinji Ohno, Norikazu Masuda. A randomized phase II trial of interventions with frozen groves and compression stockings to prevent nab-paclitaxel induced chemotherapy-induced peripheral neuropathy (SPOT trial) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-52.

Abstract OT-09-05: A randomized, pre-surgical study to investigate the biological effects of AZD9833 doses in women with ER-positive HER2-negative primary breast cancer (SERENA-3)

Abstract Background AZD9833 is an orally bioavailable selective estrogen receptor (ER) antagonist and degrader (SERD) that has shown anti-tumor efficacy in a range of preclinical breast cancer models. SERENA-1, an ongoing first-in-human study assessing AZD9833 as a monotherapy and in combination with palbociclib, established dose-dependent tolerability in pre- and post-menopausal women at doses of 25-450 mg once daily (QD), with clinical benefit and target engagement at all dose levels. Two randomized, open-label Phase 2 trials are also ongoing in women with ER+ HER2- breast cancer. SERENA-2 compares the efficacy of AZD9833 with fulvestrant in post-menopausal women with advanced breast cancer following treatment with ≤1 endocrine therapy. SERENA-3 will examine the biological effects of different doses of AZD9833 in treatment-naïve women with primary breast cancer. Methods SERENA-3 is a randomized, open-label, parallel-group, pre-surgical study to investigate the biological effects of different doses of AZD9833 in ER+, HER2- primary breast cancer. Eligible patients will be post-menopausal (and potentially pre-menopausal) women awaiting curative-intent surgery for newly diagnosed, ER+ HER2- primary breast cancer. The study is designed in two stages. In Stage 1, 24 post-menopausal women will be randomized 1:1 to receive either 75 mg or 150 mg oral AZD9833 QD for 5-7 days, followed by a minimum 5-day pre-surgery washout period; Stage 2 gives provision for additional groups depending on emerging data from Stage 1. The primary objective of this study is to explore the effect of AZD9833 on ER expression in pre- and on-treatment tumor samples from women with primary breast cancer, as assessed by immunohistochemistry and H-score. Safety and tolerability will be assessed as secondary endpoints, along with the pharmacokinetic and pharmacodynamic effects of AZD9833 on other biomarkers. Blood will be collected at screening, on the day of biopsy and the day of surgery to assess circulating tumor DNA and exploratory biomarkers. Primary endpoint analysis will be performed on the pharmacodynamic analysis set. The study will be conducted in 20 centers across 3 countries. For more information please contact Professor John Robertson at: john.robertson@nottingham.ac.uk. Citation Format: John FR Robertson, Iain Moppett, Juan Enrique Bargalló Rocha, Giorgi Dzagnidze, Joanna Harding, Teresa Klinowska, Richard Mather, Alastair Mathewson, Rhiannon Maudsley, Christopher J Morrow, Andrew Saunders, Andy Sykes, Li Zhang, Justin PO Lindemann. A randomized, pre-surgical study to investigate the biological effects of AZD9833 doses in women with ER-positive HER2-negative primary breast cancer (SERENA-3) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-09-05.

Gene expression comparison between primary estrogen receptor‐positive and triple‐negative breast cancer with paired axillary lymph node metastasis

The aim of this study is to characterize and compare changes in gene expression patterns of paired axillary lymph node (ALN) metastases from estrogen receptor (ER)-positive and triple-negative (TNBC) primary breast cancer (PBC). Patients with stage 2-3 PBC with macrometastasis to an ALN were selected. Gene expression of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Changes in gene expression between ER/PR-positive, HER2-negative PBC, and their paired ALN metastases were compared with TNBC and their paired ALN metastases. Fourteen pairs of ER-positive and paired ALN metastasis were analyzed. Compared with the PBC, ALN metastasis had 673 significant differentially expressed genes, including 348 upregulated genes and 325 downregulated genes. Seventeen pairs of TNBC and paired ALN metastasis were analyzed. ALN metastasis had 257 significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. When gene expression of the ALN for ER-positive PBC was compared to that of TNBC, 97 genes were upregulated in both, and 115 genes were similarly downregulated. Common upregulated genes were associated with cell death, necrosis, and homeostasis. Common downregulated genes were those of migration, degradation of extracellular matrix, and invasion. Although ER-positive PBC and TNBC have a distinct gene expression profiles and distinct changes from PBC to ALN metastases, a significant number of genes are similarly up- or downregulated. Understanding the role of these common genomic changes may provide clues to understanding the metastatic process itself.

Identification of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer by Using HER2-targeted 89Zr-Pertuzumab PET/CT.

Background Human epidermal growth factor receptor 2 (HER2)-targeted therapies are successful in patients with HER2-positive malignancies; however, spatial and temporal heterogeneity of HER2 expression may prevent identification of optimal patients for these therapies. Purpose To determine whether imaging with the HER2-targeted PET tracer zirconium 89 (89Zr)-pertuzumab can depict HER2-positive metastases in women with HER2-negative primary breast cancer. Materials and Methods From January to June 2019, women with biopsy-proven HER2-negative primary breast cancer and biopsy-proven metastatic disease were enrolled in a prospective clinical trial (ClinicalTrials.gov NCT02286843) and underwent 89Zr-pertuzumab PET/CT for noninvasive whole-biopsy evaluation of potential HER2-positive metastases. 89Zr-pertuzumab-avid foci that were suspicious for HER2-positive metastases were tissue sampled and examined by pathologic analysis to document HER2 status. Results Twenty-four women (mean age, 55 years ± 11 [standard deviation]) with HER2-negative primary breast cancer were enrolled. Six women demonstrated foci at 89Zr-pertuzumab PET/CT that were suspicious for HER2-positive disease. Of these six women, three had biopsy-proven HER2-positive metastases, two had pathologic findings that demonstrated HER2-negative disease, and one had a fine-needle aspirate with inconclusive results. Conclusion Human epidermal growth factor receptor 2 (HER2)-targeted imaging with zirconium 89-pertuzumab PET/CT was successful in detecting HER2-positive metastases in women with HER2-negative primary breast cancer. This demonstrates the ability of targeted imaging to identify patients for targeted therapies that might not otherwise be considered. © RSNA, 2020 Online supplemental material is available for this article. See the editorial by Mankoff and Pantel in this issue.

A randomized study comparing docetaxel/cyclophosphamide (TC), 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by TC, and TC followed by FEC for patients with hormone receptor-positive HER2-negative primary breast cancer

PurposeOur primary objective was to determine the benefit/risk of anthracycline-free regimens by comparing docetaxel + cyclophosphamide (TC) alone, fluorouracil + epirubicin + cyclophosphamide (FEC) followed by TC, or TC followed by FEC as a primary treatment for patients with HR-positive, HER2-negative BC.MethodsWe randomized patients with stage I–III HR-positive HER2-negative, operable BC to receive either six cycles of TC (TC6), three cycles of FEC followed by three cycles of TC (FEC-TC), or three cycles of TC followed by three cycles of FEC (TC-FEC). The primary endpoint was the pathological response. Secondary endpoints included clinical response, type of surgical procedure, recurrence, death, and adverse events (by NCI-Common Terminology Criteria for Adverse Events v.3.0). We conducted all statistical analyses using SAS Version 9.2.ResultsWe enrolled 195 patients and analyzed data from 193 as the intention-to-treat population. Pathological complete response rates were numerically higher in the TC6 group than in the other groups (p = 0.321). The breast conservation rate was significantly higher in the TC6 group (73%) than in the other groups (FEC-TC 51%, TC-FEC 45%, p = 0.007). Adverse events with grade > 3 were not common in the treatment groups (p = 0.569). The overall and distant disease-free survivals were similar among the groups with median follow-up of 5.80 years.ConclusionsDespite similar long-term efficacy and safety profile, the higher breast conservation rate in the TC6 group suggests that preoperative chemotherapy without an anthracycline may benefit patients with HR-positive HER2-negative BC.Trial registrationUMIN000003283 https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003873.

Abstract P3-08-05: Impact of estrogen receptor levels on outcome in triple negative breast cancer patients treated with (neo)adjuvant chemotherapy

Abstract Background: Although 1% is recommended by guidelines as cut-off for estrogen receptor (ER) positivity, the 10% cut-off is often used in clinical practice based on studies showing that breast cancers with ER ≥1% &amp;&amp;lt;10% have biological characteristics and prognosis similar to those with ER &amp;lt;1%. Our aim was to compare disease-free survival (DFS) and overall survival (OS) according to ER level in a cohort of patients with HER2-negative, ER&amp;lt;10% and progesterone receptor &amp;lt;10% undergoing (neo)adjuvant chemotherapy. Methods: Clinicopathological data of patients with triple negative breast cancer (defined as ER and progesterone receptor &amp;lt;10% and HER2-negative) treated at our Institution with (neo)adjuvant chemotherapy between January 2000 and April 2019 were collected. Patients were categorized according to ER expression; &amp;lt;1% or ≥1%&amp;&amp;lt;10%. Pathologic complete response (pCR) was defined as ypT0/is and ypN0. DFS was calculated from date of diagnosis to date of relapse (locoregional or distant), death or last follow up. OS was calculated from the date of diagnosis to date of death or last follow up. Hazard ratios and 95% CI were calculated with the Cox proportional hazard regression model. Results: 406 patients were included: 364 with ER&amp;lt;1%, 42 with ER≥1%&amp;&amp;lt;10%. Main characteristics: median age 54 years (range 25-84), ductal histology 91% (N 367), grade 3 88% (N 350), median ki67 58%, stage at diagnosis: I 33% (N 134), II 52% (N 212), III 15% (N 59). There was no significant difference in clinicopathological characteristics according to ER level. However, ER≥1%&amp;&amp;lt;10% tumors had a numerically higher frequency of advanced disease stages (I 19% N=8, II 57% N=24, III 24% N=10, p=0.057).Almost half of the patients (41%, N=165) received neoadjuvant chemotherapy: 39% in the ER&amp;lt;1% and 57% in the ER≥1%&amp;&amp;lt;10% cohort (p=0.032). pCR was achieved by 63 patients (38%). pCR rate was similar in the two cohorts (38% in ER&amp;lt;1% cohort, 44% in ER≥1%&amp;&amp;lt;10% cohort, p=0.498). 274 patients (67%) received adjuvant chemotherapy (41 after previous neoadjuvant treatment): 69% in the ER&amp;lt;1% and 55% in the ER≥1%&amp;&amp;lt;10% cohort (p=0.092). With a median follow up of 54 months, 88 patients had relapsed and 64 died. No difference in DFS and OS was observed according to ER levels: 5-year DFS was 73.7% in ER&amp;lt;1% and 73.1% in ER≥1%&amp;&amp;lt;10% cohort (log-rank p=0.610); 5-year OS was 82.3% in ER&amp;lt;1% and 76.7% in ER≥1%&amp;&amp;lt;10% cohort (log-rank p=0.820). Disease stage at diagnosis was the only clinicopathological variable significantly associated with DFS and OS in the overall study cohort (data not shown). DFS and OS Hazard Ratios for ER≥1%&amp;&amp;lt;10% tumors as compared to ER&amp;lt;1% tumors at univariable analysis and after correction by stage are presented in the table. Conclusions: Early HER2-negative primary breast cancer with ER &amp;lt;10% behaves clinically like ER&amp;lt;1% breast cancer in terms of DFS and OS after (neo)adjuvant chemotherapy. Our results support the definition of TNBC as HER2-negative breast cancer with ER&amp;lt;10% and PgR&amp;lt;10%, rather than &amp;lt;1%. DFS and OS Hazard Ratios for ER≥1%&amp;&amp;lt;10% tumors as compared to ER&amp;lt;1% tumorsDFSHazard Ratio (95% CI)Hazard Ratio (95% CI) corrected by stagep-valueER&amp;lt;1%RefRef0.957ER≥1%&amp;&amp;lt;10%1.19 (0.61-2.30)0.98 (0.51-1.91)OSHazard Ratio (95% CI)Hazard Ratio (95% CI) corrected by stagep-valueER&amp;lt;1%RefRef0.805ER≥1%&amp;&amp;lt;10%1.10 (0.50-2.40)0.90 (0.41-2.00) Citation Format: Gaia Griguolo, Maria Vittoria Dieci, Michele Bottosso, Vassilena Tsvetkova, Carlo Alberto Giorgi, Silvia Angelini, Giulia Tasca, Enrico Cumerlato, Marcello Lo Mele, PierFranco Conte, Valentina Guarneri. Impact of estrogen receptor levels on outcome in triple negative breast cancer patients treated with (neo)adjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-05.

Retrospective cost-analysis of the EndoPredict test in patients with primary breast cancer in a German breast center

The objective of this article is the economic evaluation of the EndoPredict test in the assessment of the indication for chemotherapy in female breast cancer patients with intermediate risk of recurrence. A retrospective cost analysis based on patient files in a German breast center was conducted, including female estrogen receptor positive (ER+) and HER2-negative (HER2-) primary breast cancer patients. The EndoPredict test was performed retrospectively on archived tumor material. Direct medical costs (in- and outpatient treatment, drug prescriptions including chemotherapy and additional medications) were evaluated. Furthermore, hypothetical direct costs were calculated for a scenario where treatment decisions would have considered the results of the EndoPredict test. Eighty-two women [mean age 62 (37–77) years] met the inclusion criteria; half of them received chemotherapy. In total, using the information from the EndoPredict, chemotherapy could have been avoided in 16 patients. Average costs of outpatient chemotherapy were 14,835€/patient. Costs for the EndoPredict were 1811€/patient. Total costs in the hypothetical scenario amounted to 968,273€ (inpatient care: 447,524€; outpatient care including pharmaceuticals: 372,247€; EndoPredict: 148,502€). This retrospective analysis indicates potential cost savings with the application of the EndoPredict in the treatment decision in direct medical costs of about 10.5%, corresponding to 1.384€/test.