Recurrence In Early Breast Cancer Research Articles

The correlation between Ki 67 and Oncotype Dx on HR+, HER2- early breast cancer management: Insights of molecular testing.

e12546 Background: Elevated Ki-67 expression serves as an indicator of tumoral proliferation in breast cancer (BC) and is used in Ecuador for survival estimation, recurrence risk assessment, and guiding chemotherapy decisions. The Oncotype DX Breast Recurrence Score (ODX RS) is a validated 21-gene assay for hormone receptor-positive, HER2-negative invasive BC. It predicts chemotherapy benefits and the risk of distant recurrence over 10 years and is a mortality indicator. ODX RS has the potential to reduce the need for chemotherapy, alleviate financial burdens, and enhance clinical outcomes. Despite conflicting evidence on the significance of Ki-67 in the ODX RS, there is a lack of exploration within Latin populations. This study aims to compare the correlation of immunohistochemical (IHC) measured Ki-67 to the ODX RS in the Ecuadorian population. Methods: A retrospective analysis included women with early BC who underwent ODX RS testing in Ecuador from May 2020 to January 2023. Inclusion criteria: early BC (T1-T3/N0-N1a); IHC estrogen receptor (ER) positive; HER2 negative; and availability of tumor size, grade, lymph node status, and Ki67 proliferation index data. Exclusion criteria: patients with recurrent BC, incomplete pathology, or lacking IHC data. Patients were categorized into low (≤5%), intermediate (6%–29%), and high Ki67 expression groups (≥30%). Using the statistical software SPSS, the correlation between ODX scores and Ki-67 expression was analyzed using Pearson’s correlation coefficient. For risk stratification groups, Spearman's correlation was employed. Results: Among 77 patients undergoing Oncotype DX testing, 64 (with a mean age of 55) met the inclusion criteria. Eighty-six percent of cases were invasive ductal carcinomas (IDC). Seventeen percent exhibited low Ki-67 expression, 61% intermediate, and 20% high. No statistically significant correlation was found between IHC Ki-67 expression and ODX RS (r=0.051; p=0.69), neither when stratified by categories (r=0.086; p=0.50). A subanalysis based on risk categories showed 82% correspondence in the low Ki-67 group, 18% in the intermediate group, and 31% in the high Ki-67 group. No significant correlation was observed when stratified by histological types (invasive ductal carcinoma and invasive lobular carcinoma), nor by sample origin (core biopsy, excisional biopsy). Conclusions: There was no correlation between IHC Ki-67 expression and ODX risk scores in this study involving Ecuadorian patients. Our findings emphasize that IHC Ki-67 expression should not be the sole determinant for guiding therapeutic decisions and predicting recurrence in early breast cancer.[Table: see text]

Artificial intelligence algorithms for recurrence risk score prediction in early-stage breast cancer: A multicenter study of 437 cases.

545 Background: In non-developed and developing countries, the 21 gene assay (Oncotype DX) test is expensive and not covered by private and social health insurance, which limits its use. However, clinicians need this test for treatment prediction in early stage breast cancer. Therefore, we aimed to predict the risk of recurrence in patients using artificial intelligence (AI) algorithms. Methods: This study was conducted with 437 early-stage breast cancer patients whose recurrence risk scores were determined by 21 Oncotype DX and were followed in 14 oncology centers in Turkey between 2012 and 2022. The optimum cut-off for the 21 gene assay risk score (RS) was found by ROC analysis using the patients' recurrence information (scale of RS ≥17: high risk, <17: low risk). In artificial intelligence prediction models, patients with a 21 gene assay risk score ≥17 were considered high risk. Additionally, algorithm predictions were made within other cut-offs recommended in the literature (<10, 11-25, >25). Python programming language was used in the analyses. The Random Forest (RF), Logistic regression (LG) and K-Nearest Neighbors (KNN) were used as AI prediction algorithms. Results: The study analyzed 437 women with an average age of 49.49±10.30. During the follow-up period from 2012 to 2022, 7.1% of the patients experienced a recurrence. AI prediction algorithms which were RF, LG, and KNN generated confusion matrices for two classes, with a threshold of 17 and 25. The algorithms were then applied to the dataset with risk score thresholds of 1-10, 11-25, and greater than 25, resulting in three classes. The dataset was analyzed using recall, precision, and F1 score values. The results showed that RF had the most accurate predictions for RS = 17 (Table). Conclusions: The use of artificial intelligence algorithms in predicting the risk of recurrence in early stage breast cancer is promising in determining treatment decisions for clinicians who cannot access genetic results. [Table: see text]

Can early post-operative MRI describe a predictor model for the likelihood of early breast cancer recurrence after conservative surgery?

Can early post-operative MRI describe a predictor model for the likelihood of early breast cancer recurrence after conservative surgery?

Abstract PO2-01-11: Demographic, Lifestyle, and Clinical Factors Associated with Early vs. Late Recurrence among Women with Early-Stage Estrogen Receptor-Positive Breast Cancer in the Prospective Pathways Study

Abstract Background: Although women diagnosed with early-stage estrogen receptor (ER)-positive breast cancer generally have a favorable prognosis, they face a lingering risk of late recurrence that can occur years to decades after diagnosis. Relatively little is known about the demographic, lifestyle, or clinical factors associated with the risk of late recurrence, or whether the associations differ between early vs. late recurrence. Methods: We performed a comprehensive analysis of factors related to early vs. late recurrence in early-stage ER-positive breast cancer in the Pathways Study, an established prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California (KPNC) between 2006 and 2013. Recurrences were identified through monthly searches of the KPNC Cancer Registry, follow-up interviews with participants, and confirmation with electronic medical records. For this analysis, 2,473 women with stage I-IIB, ER-positive breast cancer were included, with ascertainment of recurrence and death through December 31, 2021. Univariate analysis and multivariable Cox regression models were used to examine the factors associated with early (< 5 years since diagnosis) and late (≥ 5 years since diagnosis) recurrence. Results: The median age of diagnosis was 57 (± 10) years, with 35% diagnosed before menopause. While 64% of patients self-reported as White, 16% identified as Asian, 6% Black, 12% Hispanic, and 2% other ethnicity. After a median 13.3 (range: 0.6-16.8) years of follow up, a total of 341 (13.8%) recurrences occurred, with 158 before and 181 at or after 5 years from diagnosis. Approximately a third of recurrences were local or regional and the other two thirds were distant. In univariate analysis, increasing stage and tumor grade were associated with higher risk of both early and late recurrence (p< 0.05). Progesterone receptor (PR) negativity was associated with only early (hazard ratio [HR]=1.49, 95% confidence interval [CI] 1.06-2.09) but not late recurrence (HR=0.90, 95% CI 0.63-1.28). In unadjusted models, receiving lumpectomy (vs. mastectomy), chemotherapy, radiation therapy, or endocrine therapy were associated with lower risk of both early and late recurrence. Among the demographic and lifestyle factors examined, postmenopausal status at diagnosis was associated with lower risk of early (HR=0.69, 95% CI 0.51-0.96) but not late recurrence (HR=1.00, 95% CI 0.73-1.36). No association was found with body mass index, socioeconomic measures (education, income, employment, marital status), smoking, alcohol intake, or physical activity assessed at the time close to diagnosis. Notably, minoritized racial/ethnic groups all had higher risk of early recurrence than White women (Asian: HR=1.76, 95% CI 1.16-2.66; Black: HR=2.33, 95% CI 1.38-3.93; Hispanic: HR=1.80, 95% CI 1.15-2.82), but no association was found with late recurrence (Asian: HR=0.99, 95% CI 0.65-1.51; Black: HR=0.80, 95% CI 0.41-1.58; Hispanic: HR=0.80, 95% CI 0.48-1.33). In multivariable Cox models adjusted for age, cancer stage, grade, PR status, surgery, radiation therapy, chemotherapy, and endocrine therapy, the trend of higher risk of early recurrence among minoritized racial/ethnic groups remained, although the association remained significant only in Black women (HR=1.89, 95% CI 1.08-3.31). Conclusion: Most histopathological features and cancer treatment modality had similar impact on early vs. late recurrence among women with early-stage ER-positive breast cancer, although PR negativity might be an adverse risk factor for early recurrence only. The findings of higher risk of early but not late recurrence among Asian, Black, and Hispanic relative to White women provide some novel data on the racial/ethnic disparities of prognosis for ER-positive breast cancer and may warrant further investigation. Citation Format: Alfredo Chua, Haiyang Sheng, Shipra Gandhi, Marilyn Kwan, Isaac Ergas, Janise Roh, Cecile Laurant, Thaer Khoury, Scarlett Gomez, Christine Ambrosone, Lawrence Kushi, Song Yao. Demographic, Lifestyle, and Clinical Factors Associated with Early vs. Late Recurrence among Women with Early-Stage Estrogen Receptor-Positive Breast Cancer in the Prospective Pathways Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-11.

Multimodality Imaging of Postmastectomy Breast Reconstruction Techniques, Complications, and Tumor Recurrence.

For women undergoing mastectomy, breast reconstruction can be performed by using implants or autologous tissue flaps. Mastectomy options include skin- and nipple-sparing techniques. Implant-based reconstruction can be performed with saline or silicone implants. Various autologous pedicled or free tissue flap reconstruction methods based on different tissue donor sites are available. The aesthetic outcomes of implant- and flap-based reconstructions can be improved with oncoplastic surgery, including autologous fat graft placement and nipple-areolar complex reconstruction. The authors provide an update on recent advances in implant reconstruction techniques and contemporary expanded options for autologous tissue flap reconstruction as it relates to imaging modalities. As breast cancer screening is not routinely performed in this clinical setting, tumor recurrence after mastectomy and reconstruction is often detected by palpation at physical examination. Most local recurrences occur within the skin and subcutaneous tissue. Diagnostic breast imaging continues to have a critical role in confirmation of disease recurrence. Knowledge of the spectrum of benign and abnormal imaging appearances in the reconstructed breast is important for postoperative evaluation of patients, including recognition of early and late postsurgical complications and breast cancer recurrence. The authors provide an overview of multimodality imaging of the postmastectomy reconstructed breast, as well as an update on screening guidelines and recommendations for this unique patient population. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Abstract 7653: Role of ITGB2 in patients with luminal B1 breast cancer

Abstract Purpose: Luminal-type breast cancers are the most commonly diagnosed in women. Among them, the luminal B1 subtype exhibits higher proliferation rates and a worse prognosis compared to the luminal A subtype. Despite significant advancements in detection and therapies, recurrence still occurs after primary treatment. In this study, our aim is to identify genomic alterations in early recurrent luminal B1 breast cancer. Experimental Design: In this VGHTPE cohort, we recruited a total of 42 patients diagnosed with stage I-III luminal B1 breast cancer, comprising 15 subjects who experienced recurrence within five years and 27 subjects who did not. Genomic DNA was extracted from formalin-fixed paraffin-embedded samples and subjected to targeted next-generation sequencing. We assessed cell aggressiveness through in vitro transwell migration, invasion, and sphere assays. Results: Luminal B1 breast cancer patients with advanced stage and poorly differentiated tumors were associated with recurrence within five years. Driver gene mutation analysis revealed that TP53 mutations were present in 46.7% of patients who experienced recurrence within five years, compared to 29.6% in the non-recurrence group. In the analysis of copy number variations, the most common amplifications/gains observed in luminal B1 breast cancer patients were in MCL1, MYC, and KLF6. Remarkably, patients who experienced recurrence within five years showed a higher occurrence of gain in ITGB2, the gene encoding the integrin β chain, compared to those who remained recurrence-free. Patients with ITGB2 amplifications/gains had a shorter 5-year recurrence-free survival compared to those with a neutral status. In vitro studies revealed that the knockdown of ITGB2 suppressed cell migration, invasion, and sphere formation in estrogen receptor-positive HER2-negative breast cancer cells. Conclusion: Our study has identified ITGB2 amplifications/gains as a potential biomarker for early recurrence in luminal B1 breast cancer. Citation Format: Chun-Yu Liu, Ji-Lin Chen, Yi-Fang Tsai, Ta-Chung Chao, Wan-Lun Wang, Pei-Ju Lien, Chih-Yi Hsu, Jiun-I Lai, Chi-Cheng Huang, Jen-Hwey Chiu, Ling-Ming Tseng. Role of ITGB2 in patients with luminal B1 breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7653.

Matrix Metalloproteinase as Predictors of Local Recurrence in Early-Stage Breast Cancer After Mastectomy and Chemotherapy A Cross-Sectional Study in Single Centre

Introduction: The prognosis for early-stage breast cancer is generally favourable. However, in cases when a recurrence manifests after therapy, the prognosis becomes significantly poor. To determine early breast cancer recurrence risk, a marker is needed. Currently, previous tumour markers are used to predict general breast cancer, lacking specificity in the context of early breast cancer. Matrix Metalloproteinase1 (MMP1) is already acquainted with the local recurrence process of invasive ductal carcinoma (IDC). MMP1 expression may better predict early recurrence in early-stage IDC than other approaches. This research examined the potential predictive value of MMP1 expression in early-stage IDC for early local recurrence and its correlation with clinicopathological factors. Methods: This study was a cross-sectional analysis of a single center's medical records. The sample size was 25 subjects for the group without recurrence and 25 subjects with recurrence. Mastectomy and chemotherapy were performed from January 2014 through December 2019. Using immunohistochemistry, paraffin blocks of surgical specimens were examined for MMP1. The data processing was done utilising the trial version of IBM SPSS 25. and Openepi 3.0 programs and analysed using Bivariate, which is performed using the Chi-square test or Fisher's exact test. Result: The statistic test showed a significant difference (p < 0.000) in the average expression of MMP1 for non-recurrence cases (3,95±5,36) compared to recurrence cases (14,95±5,36). We also found a statistically significant correlation between recurrence and high expression of MMP1 (odd ratio [OR]= 60.38, 95% confidence interval [CI]=10.01-364.3, p<0.001). Clinicopathological variables and MMP1 expression did not have a significant correlation. Conclusions: In early-stage IDC, MMP1 expression had the potential to predict and could be an independent prognostic factor for early recurrence.

Predictive factors of axillary lymph node involvement in Tunisian women with early breast cancer

Background: Axillary lymph node involvement (ALNI) is associated with an increased risk of local recurrence and poor prognosis in early breast cancer. The determination of the risk of positive axillary lymph node contributes to therapeutic decisions.Objectives: The aim of this study was to identify clinicopathological predictive factors of axillary lymph node metastases in patients with early breast cancer.Methods: We included patients with clinical T0, T1 andT2 invasive breast carcinoma who underwent resection of the primary tumor and axillary staging by sentinel lymph node biopsy and/or axillar lymph node dissection between 2012 and 2018.Results: Of the 135patients included, 41.5% had ALNI. Regarding univariate analysis, clinical factors correlated with positive ALNM were clinical tumour size>30mm, clinical tumour stage, clinical number of tumours, clinical axillary nodal status and nodal status on ultrasound. Pathologic factors associated with nodal involvement were pathologic tumour stage, tumour grade SBR, number of foci, lymphovascular invasion, perineural invasion and Ki67>20%.In multivariate logistic regression, clinical axillary nodal status, pathologic tumour stage and lymphovascular invasion (LVI) remained as independent predictors of ALNI.Conclusions: Based on these results, we suggest that clinical axillary nodal status, pathologic tumour stage and LVI are predictive factors for ALNM in Tunisian women with early breast cancer.

Predicting early breast cancer recurrence from histopathological images in the Carolina Breast Cancer Study

Approaches for rapidly identifying patients at high risk of early breast cancer recurrence are needed. Image-based methods for prescreening hematoxylin and eosin (H&E) stained tumor slides could offer temporal and financial efficiency. We evaluated a data set of 704 1-mm tumor core H&E images (2–4 cores per case), corresponding to 202 participants (101 who recurred; 101 non-recurrent matched on age and follow-up time) from breast cancers diagnosed between 2008–2012 in the Carolina Breast Cancer Study. We leveraged deep learning to extract image information and trained a model to identify recurrence. Cross-validation accuracy for predicting recurrence was 62.4% [95% CI: 55.7, 69.1], similar to grade (65.8% [95% CI: 59.3, 72.3]) and ER status (66.3% [95% CI: 59.8, 72.8]). Interestingly, 70% (19/27) of early-recurrent low-intermediate grade tumors were identified by our image model. Relative to existing markers, image-based analyses provide complementary information for predicting early recurrence.

Estimating the overall survival benefit of adjuvant chemo-endocrine therapy in women over age 50 with pT1-2N0 early stage breast cancer and 21-gene recurrence score ≥26: A National Cancer Database analysis.

Validation studies of the 21-gene recurrence score (RS) previously demonstrated that adjuvant chemotherapy plus endocrine therapy (CET) was associated with a significant survival benefit in women with node negative breast cancer (BC) and RS >31. However, the TAILORx trial, did not quantify the benefit of adjuvant CET in older women with node negative hormone receptor positive (HR+) BC with RS ≥26. We hypothesized that CET would be associated with improved overall survival (OS) compared to endocrine therapy (ET) in women >50 with HR+/HER2-node negative BC and RS ≥26. The National Cancer Database (NCDB) was queried to identify women >50 with RS ≥26 ER+/HER2-BC pT1-2N0M0. Chi-square and logistic regression analysis determined the difference between ET and CET. OS was analyzed using a multivariable Cox model. We included 16,745 women-4740 (28.3%) received ET and 12,005 (71.7%) received CET. Women who received CET had: moderately (OR = 1.853, p < 0.001) or poorly/undifferentiated tumors (OR = 3.875, p < 0.001), pT2 (OR = 1.356, p < 0.001), or lymph-vascular invasion (OR = 1.206, p = 0.001). After accounting for demographic and oncologic factors, 5-year OS rates were significantly superior in women receiving CET vs. ET alone (95.4% vs. 92.0%, Hazard Ratio = 0.680, p < 0.001). We observed that CET was associated with a clinically and statistically significant higher OS compared to ET alone in women >50 years of age with RS ≥26 pT1 and pT2 N0M0 HR+/HER2-breast cancer, and which suggests that cytotoxic chemotherapy has an impact on reducing mortality that is independent of induction of premature ovarian failure.

Expert UK consensus on the definition of high risk of recurrence in HER2-negative early breast cancer: A modified Delphi panel

BackgroundThere is currently no standardised definition for patients at high risk of recurrence of human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC; stages 1–3) after surgery. This modified Delphi panel aimed to establish expert UK consensus on this definition, separately considering hormone receptor (HR)-positive and triple-negative (TN) patients. MethodsOver three consecutive rounds, results were collected from 29, 24 and 22 UK senior breast cancer oncologists and surgeons, respectively. The first round aimed to determine key risk factors in each patient subgroup; subsequent rounds aimed to establish appropriate risk thresholds. Consensus was pre-defined as ≥70% of respondents. ResultsExpert consensus was achieved on need to assess age, tumour size, tumour grade, number of positive lymph nodes, inflammatory breast cancer and risk prediction tools in all HER2-negative patients. There was additional agreement on use of tumour profiling tests and biomarkers in HR-positive patients, and pathologic complete response (pCR) status in TN patients. Thresholds for high recurrence risk were subsequently agreed. In HR-positive patients, these included age <35 years, tumour size >5 cm (as independent risk factors); tumour grade 3 (independently and combined with other high-risk factors); number of positive nodes ≥4 (independently) and ≥1 (combined). For TN patients, the following thresholds reached consensus, both independently and in combination with other factors: tumour size >2 cm, tumour grade 3, number of positive nodes ≥1. ConclusionsThe results may be a valuable reference point to guide recurrence risk assessment and decision-making after surgery in the HER2-negative eBC population.

Breast Cancer Recurrence Prediction Using Data Mining

Today, the Healthcare sector is generating a vast amount of meticulously detailed information on individuals and their medical issues. Medical data may be investigated for hidden patterns or connections using data mining techniques. The spread and return of the illness are the main causes of breast cancer fatalities. One of the most important areas of study in the field of medicine is the early diagnosis of breast cancer. Healthcare businesses can benefit from data mining by forecasting patient illnesses and behaviour trends. This is performed by analyzing data from many angles and by using data mining to find hidden patterns and associations between seemingly unrelated bits of information. Months after the original diagnosis and breast cancer therapy, a metastatic recurrence of the disease may happen. Only a few number of techniques have been researched in the state of the art due to the challenges associated with early breast cancer recurrence prediction during its medication. The aim of the research is to review the work done by different researchers in this field and to compare the various traditional data mining classifiers (Logistic Regression, Naïve Bayes, K-Nearest Neighbours, Decision Tree, Support Vector Machines, and Random Forest) applied to Breast Cancer Data Set from UCI Machine Learning Repository. Out of these, the best results were given by Random Forest Algorithm with 98.4% accuracy.

Outcomes in Premenopausal Patients with HR+/HER2- Breast Cancer and Lymph Node Micrometastasis Based on the 21-Gene Recurrence Score.

Postmenopausal patients with hormone receptor positive, HER2-negative (HR+/HER2-) early breast cancer (EBC) and 21-gene OncotypeDX (ODX) recurrence scores (RS) <26 do not benefit from chemoendocrine therapy ("CET") compared to endocrine monotherapy ("E"), regardless of nodal status. In premenopausal patients, nodal status is significant in interpretation of RS. However, guidelines are not explicit in recommendations for patients with micrometastasis ("pN1mi" staging). A cohort of patients aged <50 years with HR+/HER2- EBC who underwent ODX testing was identified within the National Cancer Database 2004-2019 dataset. We confirmed the prognostic value of ODX in pN1mi disease with multivariate Cox regression for overall survival (OS). We explored how patterns of practice differed by nodal status in cases of low RS (<26) with chi-squared testing. Finally, we performed Kaplan-Meier models comparing OS for those with RS <26 receiving E versus CET, controlling for nodal status. Of 72 068 patients aged <50 years with HR+/HER2- EBC, 6.1% (n = 4402) had micrometastasis. Multivariate Cox regression confirmed prognostic value of ODX in this pN1mi cohort (P < .001). In the context of RS <26, CET was used most commonly in patients with 1-3 involved lymph nodes ("pN1a-c" disease), less frequently in pN1mi disease, and least in node-negative ("pN0") disease. A benefit in OS was observed in cases with RS <26 and pN1a-c receiving CET vs. E (P = .017), but not in pN1mi (P = .49) or pN0 (P = .57) disease. Our large registry analysis found CET was associated with improved OS in pN1a-c, but not in pN1mi or pN0 disease.

Outcomes in premenopausal patients with HR+/HER2- breast cancer and lymph node micro-metastasis based on the 21-gene recurrence score.

571 Background: Postmenopausal patients with hormone receptor positive, HER2-negative (HR+/HER2-) early breast cancer (EBC) and 21-gene OncotypeDX (ODX) recurrence scores (RS) &lt;26 do not benefit from chemoendocrine therapy (‘CET’) compared to endocrine monotherapy (‘E’). The TAILORx and RxPONDER trials demonstrated this was consistent in node-negative and node-positive disease, respectively. In premenopausal patients, however, guidelines for those with low RS diverge between disease involving 0 (pN0) vs. 1-3 (pN1a-c) lymph nodes. Additionally, treatment decisions are less clear for patients with micro-metastasis (pN1mi), who comprised only about 10% of patients in RxPONDER. This study used the National Cancer Database (NCDB) to assess treatment patterns and survival outcomes in premenopausal patients with EBC and lymph node micro-metastasis. Methods: A cohort of patients aged &lt;50, diagnosed between 2004-2019 with HR+/HER2- EBC and who underwent ODX testing, was recruited from the NCDB. (A) Firstly, we described demographic and clinical characteristics of a sub-cohort with micro-metastasis using univariate statistics. (B) We confirmed the prognostic value of ODX in this sub-cohort with multivariate Cox regression analysis of overall survival (OS). (C) We explored patterns of practice amongst the total cohort with ODX &lt;26 with chi-squared testing for differences in CET use by nodal status. (D) To elucidate the predictive value of this assay, we performed Kaplan-Meier models comparing OS for those with RS &lt;26 receiving E vs. CET, controlling granularly for nodal status: (i) pN1a-c, (ii) pN1mi, and (iii) pN0. Results: Of n=72,068 patients aged &lt;50 with HR+/HER2- EBC and ODX data, 6.1% (n=4,402) had micro-metastasis. (A) The median age of this subgroup was 45 (IQR 41-47) years. Most tumors were grade II (n=2,472, 57.7%) with ductal histology (n=3,500, 80.3%). 73.4% of pN1mi cases had RS &lt;26, while 26.6% had RS ≥26. (B) Multivariate Cox regression – adjusting for comorbidity, race and chemotherapy use – confirmed significance in this pN1mi cohort of RS ≥26 prognosticating poorer OS compared to RS 0-15 (HR 4.42, 95% CI 2.35-8.31, p&lt;0.001). (C) 29.0% (n=1,033) of patients with pN1mi and ODX &lt;26 underwent CET, greater than 15.2% (n=6,568) with pN0 and less than 47.3% (n=2,884) with pN1a-c staging (p&lt;0.001). (D) A benefit in OS (p=0.017) was observed in cases with RS&lt;26 and pN1a-c using CET (5-year OS: 99%) vs. E (5-year OS: 97.5%), but not in pN1mi (p=0.49) or pN0 (p=0.57) disease. Conclusions: The management of premenopausal patients with HR+/HER2- EBC, isolated micro-metastasis, and ODX &lt;26 is unclear. Our large registry study found the addition of chemotherapy to endocrine therapy was associated with improved survival in cases with ODX&lt;26 involving 1-3 lymph nodes, but not in node-negative or micro-metastatic disease. Prospective trials are needed to confirm these findings.

Adherence to adjuvant tamoxifen and associated factors in breast cancer survivors

Adjuvant endocrine therapy reduces the recurrence and mortality of early hormone receptor-positive breast cancer in both pre- and postmenopausal women. The aim of this study was to investigate adjuvant tamoxifen adherence and associated factors in breast cancer survivors. This descriptive, prospective study was conducted in 2019-2020 with the participation of 531 women who survived breast cancer and were under follow-up at the Senology Institute of a hospital in Istanbul. Inclusion criteria were having completed treatment for early hormone receptor-positive breast cancer, being prescribed tamoxifen, and being 18years or older. Data were collected using a patient information form and the Morisky Medication Adherence Scale-8 (MMAS-8). The mean age of the participants was 44.9 ± 6.5years, and the mean duration of tamoxifen use was 834.4 ± 685.7days. The women's mean MMAS-8 score was 6.86 ± 1.39. Medication adherence was significantly positively correlated with current age (p = 0.006) and age at diagnosis (p = 0.002). There was a statistically significant difference between tamoxifen adherence according to participants' employment status (p = 0.028), chronic disease status (p = 0.018), loss of libido (p = 0.012), treatment-related changes in mood changes (p = 0.004), and having negative effects affecting daily life (p < 0.001). Overall, breast cancer survivors in this study reported moderate adherence to tamoxifen. The women's individual characteristics and the adverse effects of treatment influenced medication adherence. Healthcare professionals can help increase adherence to this treatment, which reduces the risk of mortality, by explaining the importance of the medication, identifying and eliminating barriers to adherence, and informing women about evidence-based interventions to increase medication compliance.

P088 The evaluation of the 21-gene Breast Recurrence Score assay as a prognostic factor for locoregional recurrence in early breast cancer treated by lumpectomy and intraoperative radiotherapy only

P088 The evaluation of the 21-gene Breast Recurrence Score assay as a prognostic factor for locoregional recurrence in early breast cancer treated by lumpectomy and intraoperative radiotherapy only

Abstract P3-05-39: Expert consensus on the definition of high risk of recurrence in HER2-negative early breast cancer: a modified Delphi panel

Abstract PURPOSE: There is currently no standardised definition for patients at high risk of recurrence of HER2-negative early breast cancer (eBC, stages 1–3) after surgery. Recognising that the assessment of high risk is often multifactorial, the aim of this modified Delphi panel was to establish expert UK consensus on this definition, separately considering HR-positive and triple-negative (TN) patients. METHODS: A total of 45 UK-based clinicians, including breast cancer oncologists and surgeons, were invited to participate. The number of respondents in each of three rounds was 29, 24 and 22 respectively. Statements were developed using the results from a targeted literature review and the guidance of a lead clinician, and comprised free-text, single-choice or numerical formats. The first round aimed to determine which factors are currently used in clinical practice to assess risk of recurrence in the populations of interest. In the subsequent rounds, the objective was to establish thresholds indicative of high risk in a 10-year timeframe for each of the factors retained in Round 1. Between each round, statements were refined, considering the distribution of responses and free-text notes provided by participants. Consensus for single-choice questions was set at a pre-defined threshold of ≥70% of respondents. RESULTS: Consensus was achieved on the need to assess age, tumour size, tumour grade, number of positive nodes, presence of inflammatory breast cancer and one or more risk prediction tools to define high risk of recurrence in all HER2-negative patients. In HR-positive patients, there was agreement on the use of one or more tumour profiling tests and biomarkers to define high risk of recurrence. However, there was no consensus on biomarker use in TN patients, and support for specific biomarkers (such as Ki-67) was conflicting for both sub-populations based on the analysis of free-text notes. Similarly, while there was consensus on the use of pCR status/residual disease to indicate high risk in TN patients, this factor failed to reach consensus for the HR-positive sub-population. Germline BRCA status and menopausal status were not considered to be key factors for risk of recurrence in either biological subtype. In the second and third rounds, thresholds indicative of high recurrence risk were agreed; it should be noted that the free-text responses provided by the participants frequently highlighted that many of the factors should be considered along a continuous scale when assessing the risk of individual patients. In HR-positive patients, these thresholds included: age &amp;lt; 35 years, tumour size &amp;gt;5 cm (each when considered independently from other risk factors); tumour grade 3 (independently or in combination with other factors); number of positive lymph nodes ≥4 when considered independently or ≥1 in combination with other factors. For patients with TN tumours, the following thresholds reached consensus, whether considered independently or in combination with other factors: tumour size &amp;gt;2 cm, tumour grade 3, number of positive lymph nodes ≥1. In several cases, however, no consensus could be reached on the appropriate threshold indicating high risk of recurrence. In the HR-positive sub-population, these included thresholds for age and tumour size, when considered in combination with other factors. In the TN sub-population, this included age, whether independently or in combination with other factors. CONCLUSIONS: The expert consensus reached in this panel highlights that an integrated model is important in assessing recurrence risk in eBC and that definitions of high risk differ according to biological subtype. The results may serve as a valuable reference point for clinicians to use in assessing risk of disease recurrence and in making treatment decisions after surgery in the HER2-negative eBC population. FUNDING: AstraZeneca UK Ltd. Writing support: Costello Medical. Citation Format: Ellen R. Copson, Jean E. Abraham, Jeremy P. Braybrooke, Stuart A. McIntosh, Caroline O. Michie, Carlo Palmieri, Rebecca Roylance, Saiqa Spensley. Expert consensus on the definition of high risk of recurrence in HER2-negative early breast cancer: a modified Delphi panel [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 P3-05-39.

Abstract P6-01-16: Circulating Tumour DNA (ctDNA) Detection and Dynamics in Patients with Early Breast Cancer (EBC): Results of the Neoadjuvant TRACER cohort

Abstract Background: ctDNA dynamics are associated with treatment response, and ctDNA detection following treatment is associated with disease recurrence in early breast cancer (EBC). Highly sensitive assays may permit effective risk stratification and guide interventional strategies. RaDaR, a bespoke assay using deep sequencing of tumour-specific variants, has been shown to detect recurrence in the postoperative setting. We quantified ctDNA using RaDaR in serial samples from a large prospective cohort of EBC patients who received standard neoadjuvant chemo- (+/- HER2- targeted) therapy. Methods: Patients with EBC of all receptor subtypes receiving neoadjuvant therapy were enrolled in the TRACER cohort from 2015. Plasma samples (Streck) were collected at baseline, during treatment, perioperatively, and during follow-up. RaDaR was performed on all available timepoints for patients with tissue available for exome sequencing (assay requirement). Clinical and pathologic characteristics, treatment, and recurrence outcomes were collected. Results: 145 patients were recruited as of April 2021, and over 700 plasma samples were collected through December 2021 (patient characteristics, Table 1). 115 (79%) tissue samples were retrieved for assay design. Data are presented for the initial 43 patients and 265 samples analyzed, including 82 post-surgical time points. Median time since diagnosis was 3.5 years (range, 1.5-5.0). Exome sequencing and assay generation were successful in all patients (n=43), yielding assays targeting a median of 48 (range 22-50) variants. 88% (38/43 patients) had ctDNA detected at baseline, with median variant allele frequency (eVAF) in positive patients of 0.15% (range, 0.0019-4.9%). ctDNA levels fell rapidly with treatment: 19/37 (51.3%; median eVAF in positive patients: 0.0098%, range 0.001-0.156%) had ctDNA detected prior to cycle 2, and 4/32 (12.5%) had ctDNA detected at cycle 4 or 5 (mid treatment; median eVAF in positive patients: 0.001%, range, 0.0007-0.011%). In the perioperative period, 17/18 (94%) of patients with available pre-operative specimens and 27/28 (96%) of patients with available post-operative samples had clearance of ctDNA. In adjuvant follow up, ctDNA was detected in 4 of the 43 analyzed patients, with ctDNA clearance observed following planned switch of endocrine therapy in one. Clinical follow-up continues, and analysis of the remaining samples (72 patients and over 425 samples) is underway. Conclusion: RaDaR demonstrated high sensitivity for ctDNA prior to treatment in patients receiving neoadjuvant therapy for EBC, permitted dynamic monitoring of treatment effect, and identified patients with persistent ctDNA after curative-intent therapy, as well as ctDNA emergence prior to clinical recurrence. Full results for the TRACER cohort and analysis of clinical covariates will be presented at the meeting. ClinicalTrials.gov NCT03702309. Table 1. Patient Baseline Characteristics Citation Format: Mitchell J. Elliott, Zachary Veitch, Philippe Bedard, Eitan Amir, Aaron Dou, Jesus Fuentes Antras, Michelle Nadler, Nicholas Meti, Nancy Gregorio, Elizabeth Shah, Helen Chow, Nathan Campbell, Samantha Terrell, Charlene Knape, Karen Howarth, Lillian Siu, Hal Berman, David W. Cescon. Circulating Tumour DNA (ctDNA) Detection and Dynamics in Patients with Early Breast Cancer (EBC): Results of the Neoadjuvant TRACER cohort [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 P6-01-16.

Abstract P2-11-06: Plasma assay of methylated DNA markers (MDM) detects patients with metastatic breast cancer (MBC) compared to healthy controls and treated breast cancer patients with no evidence of disease

Abstract Objective: Aberrantly methylated DNA may be used to detect minimal residual disease or early recurrence in breast cancer. As a 1st step, we aimed to develop an MDM panel to delineate between healthy women, stage I-III breast cancer in remission with no evidence of disease (NED), and metastatic breast cancer (MBC). Methods: We prospectively enrolled patients into 3 groups: healthy controls (adult females with a normal mammogram in past 12 months with no history of breast cancer), NED [stage I-III breast cancer with no clinical evidence of recurrence 6 months - 3 years post-treatment (adjuvant endocrine therapy allowed)], and MBC (collected either at initial diagnosis of untreated metastatic disease or radiographic progression). DNA was extracted from 6 mL of plasma derived from blood collected in LBgard tubes (Exact Sciences Corp., San Diego CA), and was bisulfite-treated and assayed by target enrichment long-probe quantitative amplified signal (TELQASTM) method for a panel of 15 previously identified MDMs [Table], normalized by the control gene, B3GALT6. Areas under the receiver operating characteristic curve (AUC) were calculated for each MDM to assess discrimination of MBC from other groups. With 60 patients per group, we had greater than 80% power to detect a difference of 0.20 from the null AUC of 0.7. Results: We tested samples from 60 MBC (10 untreated, 50 recurrent), 60 NED, and 60 healthy women. The median age was 63 (IQR, 55-72) and was not different between groups. The NED group was all hormone-receptor (HR) positive, with 47 (78%) being human epidermal growth factor receptor 2 negative (HER2-) and 13 (22%) HER2+; 48 (80%) were stage I and 9 (15%) were N+. The MBC group had 35 (58%) patients with HR+/HER2- tumors, 11 (18%) HR+/HER2+, and 6 (10%) HR-/HER2-, 4 (7%) HR-/HER2+, with 4 (7%) unknown. Of the 41 MBC whose original stage and nodal status were known 9 (22%) were stage I and 22 (54%) were N+. The markers were able to discriminate between MBC and NED patient samples with AUCs from 0.97 to 0.72. AUCs for 10/15 MDMs (ITPRIPL1, EMX1, C17orf64, OSR2, TRIM67, CHST2, IFFO1, TRH, FAM59B, and MPZ) were &amp;gt;0.90. No difference in MDMs was observed between the healthy and NED groups. Conclusions: MDMs, assayed from plasma, appear highly discriminant for metastatic breast cancer cases in comparison to control patients with NED or healthy controls. Further clinical validation of this MDM panel in a larger cohort is warranted. Table 1. Plasma MDM discrimination of metastatic breast cancer (MBC) from healthy controls and previously treated breast cancer patients with no evidence of disease (NED) Citation Format: Karthik V. Giridhar, Fergus J. Couch, Jason P. Sinnwell, Seth W. Slettedahl, William R. Taylor, Douglas W. Mahoney, Patrick H. Foote, Maria C. O’Connell, Mariah J. Robran, Mary E. Devens, Anna M. Gonser, Nicole Larson, Karen A. Doering, Kelli N. Burger, Michael Kaiser, Hatim Allawi, Kathryn Ruddy, Janet Olson, John B. Kisiel. Plasma assay of methylated DNA markers (MDM) detects patients with metastatic breast cancer (MBC) compared to healthy controls and treated breast cancer patients with no evidence of disease [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 P2-11-06.

Do circulating neutrophil extracellular traps predict recurrence in early breast cancer?

Neutrophil extracellular traps (NETs), three-dimensional structures formed by neutrophil enzymes such as neutrophil elastase (NE) and nuclear components (DNA), have been associated with progression and metastasis in breast cancer (BC). Thus, the aim of this study was to evaluate the association of circulating NETs with clinicopathological characteristics and outcomes in early BC. A prospective cohort included women with newly diagnosed early BC. NETs were defined as the presence of NE-DNA complexes in plasma, measured by optical density. Levels of NETs were dichotomized according to the median, as low and high levels of circulating NETs. Fisher's exact test was used to evaluate associations between NETs and clinicopathological characteristics and outcomes. Survival was assessed using the Kaplan Meier method and log-rank test. Forty patients were included, 23 (57.5%) patients with low and 17 (42.5%) with high levels of circulating NETs. No associations were found between clinicopathological characteristics and circulating NETs levels. Recurrence (p = 0.99) and site of recurrence (p = 0.99) were not statistically associated with plasma NETs levels. Overall, recurrence-free survival was not statistically different between circulating levels of NETs. With a short follow-up and low number of events, our results suggest that circulating levels of NETs at diagnosis of early BC are not associated with more aggressive clinicopathological characteristics, recurrence, or site of recurrence.