In ER-Positive, HER2-Negative Breast Cancers, HER2 mRNA Levels Correlate Better with Clinicopathologic Features and Oncotype DX Recurrence Score than HER2 Immunohistochemistry.

With the approval of trastuzumab deruxtecan for treating advanced human epidermal growth factor receptor-2 (HER2) low breast cancer (BC), it has become increasingly important to develop more accurate and reliable methods to identify HER2-low BC. In addition, HER2 immunohistochemistry (IHC) has limitations for quantification of HER2. We explored the relationship between HER2 IHC and mRNA levels and evaluated whether HER2 IHC scores and mRNA levels are associated with clinicopathologic features and Oncotype DX Recurrence Score (RS) in estrogen receptor (ER)-positive, HER2-negative BCs. A total of 750 BCs sent for Oncotype DX (ODX) testing were included in this study, and 559 with HER2 mRNA levels were available. There were no statistically significant differences between HER2 0 and HER2-low BC in clinicopathologic variables or ODX RS using HER2 IHC. There was a significant difference in median HER2 mRNA values between HER2 0 and HER2-low (8.7 vs 9.3, P < .001); however, the HER2 mRNA distribution had substantial overlap between these 2 groups with a suboptimal area under the receiver operating characteristic curve (area under the receiver operating characteristic curve = 0.68). A HER2 mRNA value of 9.2 was generated as the optimal cutoff for distinguishing HER2 0 and HER2-low BC. Comparing ER+ BCs with HER2 mRNA high (>9.2) and low (≤9.2) revealed a statistically significant difference in most clinicopathologic variables and ODX RS. From this large cohort of ER-positive, HER2-negative BC, our results demonstrated that HER2 mRNA levels correlated better with clinicopathologic features and recurrence risk as assessed by ODX RS than HER2 IHC scores. Our findings suggest that HER2 mRNA-detecting methods could potentially serve as a quantitative and reliable method for identifying a biologically meaningful group of HER2-low BC. Further study is needed to determine whether HER2 mRNA levels could be more reliable than IHC for identifying which patients will be most likely to benefit from trastuzumab deruxtecan.

Real-world use of multigene signatures in early breast cancer: differences to clinical trials.

PURPOSE: In Italy, Lombardy was the first region to reimburse multigene assays (MGAs) for patients otherwise candidates for chemotherapy. This is a real-world experience of MGAs usage in six referral cancer centers in Lombardy. METHODS: Among MGAs, Oncotype DX (RS) was used in 97% of cases. Consecutive patients tested with Oncotype DX from July 2020 to July 2022 were selected. The distribution of clinicopathologic features by RS groups (low RS: 0-25, high RS: 26-100) was assessed using chi-square and compared with those of the TAILORx and RxPONDER trials. RESULTS: Out of 1,098 patients identified, 73% had low RS. Grade and Ki67 were associated with RS (p < 0.001). In patients with both G3 and Ki67 > 30%, 39% had low RS, while in patients with both G1 and Ki67 < 20%, 7% had high RS. The proportion of low RS in node-positive patients was similar to that in RxPONDER (82% vs 83%), while node-negative patients with low RS were significantly less than in TAILORx (66% vs 86%, p < 0.001). The distribution of Grade was different from registration trials, with more G3 and fewer G1 (38% and 3%) than in TAILORx (18% and 27%) and RxPONDER (10% and 24%) (p < 0.001). Patients ≤ 50 years were overrepresented in this series (41%) than in TAILORx and RxPONDER (31% and 24%, respectively) (p < 0.001) and, among them, 42% were node positive. CONCLUSIONS: In this real-world series, Oncotype DX was the test almost exclusively used. Despite reimbursement being linked to pre-test chemotherapy recommendation, almost 3/4 patients resulted in the low-RS group. The significant proportion of node-positive patients ≤ 50 years tested indicates that oncologists considered Oncotype DX informative also in this population.

Defining the Biology of Estrogen Receptor-Low-Positive Breast Cancer.

BACKGROUND: We sought to better define estrogen receptor-low-positive (ER-low+) breast cancer biology and determine the utility of the Oncotype DX Breast Recurrence Score® (RS) assay in this population. METHODS: Patients with information regarding percentage ER positivity and PAM50 subtype were identified in The Cancer Genome Atlas (TCGA) and subtype distribution was determined. Next, patients with ER-low+ (ER 1-10%), HER2- breast cancer undergoing upfront surgery with known RS result were identified in the National Cancer Database (NCDB) and our institutional Dana-Farber Brigham Cancer Center (DF/BCC) database; RS distribution was examined. Finally, patients with ER-low+, HER2- breast cancer treated at DF/BCC from 2011 to 2020 without prior RS results and in whom tissue was available to perform the assay were identified. RS results, treatment, recurrence and breast cancer-specific survival (BCSS) were determined. RESULTS: Of 1033 patients in TCGA, ER percentage and PAM50 subtype were available for 342 (33.1%) patients. Forty-six (13.5%) had ER-low+/HER2- tumors, among whom 82.6% were basal and 4.3% were luminal A. Among 3423 patients with ER-low+/HER2- disease in the NCDB, RS results were available for 689 (20.1%) patients; 67% had an RS ≥26. In our institutional database, only two patients with ER-low+/HER2- disease and an RS were identified, both with RS ≥26. Among 37 patients in our institutional cohort without prior RS, 35 (97.4%) had an RS ≥26, determined with testing. After a median follow-up of 40 months (range 3-106), three patients, all treated with chemotherapy, recurred. Three-year BCSS was 97.0% (95% confidence interval 96.9-97.1%). CONCLUSIONS: Most ER-low+/HER2- breast cancers are basal-like, with RS ≥26 suggesting these tumors are similar to triple-negative disease.

Young Age as a Predictor of Chemotherapy Recommendation and Treatment in Breast Cancer: A National Cancer Database Study.

INTRODUCTION: Breast cancer, although the second most common malignancy in women in the United States, is rare in patients under the age of 40 y. However, this young patient population has high recurrence and mortality rates, with chemotherapy frequently used as adjuvant treatment. We aimed to determine whether age is an independent predictor of chemotherapy recommendation and subsequent treatment and the relationship to Oncotype Dx (ODX) recurrence score (RS). METHODS: The National Cancer Database was retrospectively reviewed from 2010-2016 to identify women with early-stage (pT1-pT3, pN0-pN1mic, M0), hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer who underwent ODX RS testing. RESULTS: Of 95,382 patients who met the inclusion criteria, risk groups using the traditional ODX RS cutoffs were 59% low, 33% intermediate, and 8% high. Using Trial Assigning Individualized Options for Treatment RS cutoffs, risk groups were 23% low, 62% intermediate, and 15% high. Chemotherapy recommendation decreased as age at diagnosis increased (P < 0.001). Increasing age was associated with decreased odds of chemotherapy recommendation in univariate models both continuously (odds ratio: 0.98, 95% confidence interval 0.97-0.98; P < 0.001) and categorically by decade (P < 0.001). Age by decade remained an independent prognosticator of chemotherapy recommendation (P < 0.001), adjusted for risk groups. CONCLUSIONS: Chemotherapy recommendation and treatment differs by age among patients with early-stage hormone receptor positive breast cancer who undergo ODX testing. While molecular profiling has been shown to accurately predict the benefit of chemotherapy, younger age at diagnosis is a risk factor for discordant use of ODX RS for treatment strategies in breast cancer; with patients aged 18-39 disproportionately affected.

Correlation of Ki-67 proliferative index with oncotype DX recurrence score in hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer with low-burden axillary nodal disease - a review of 137 cases.

The use of chemotherapy in breast cancer management has significantly contributed to the decrease in its mortality. Currently, the prognosis is determined by molecular biomarkers, such as oestrogen receptors, and human epidermal growth factor receptor 2. However, the increasing use of advanced molecular technologies, including oncotype DX recurrence score (ODX-RS), has provided the ability to estimate the risk of recurrence. Research has demonstrated that the ODX-RS helps to predict recurrence risk and the potential benefit of chemotherapy in breast cancer. As a result, it can assist clinicians in making decisions regarding using the chemotherapy. The goal of work is to explore the correlation between the ODX-RS and Ki-67 proliferative index (Ki-67-PI). This study included 137 patients with oestrogen positive, human epidermal growth factor receptor 2-negative early breast cancer, and had non- or early axillary disease. Patients with low Ki-67-PI were as follows: low ODX-RS in 17%, intermediate ODX-RS in 80%, and high ODX-RS in 2%. In the high Ki-67-PI group: low ODX-RS in 12%, intermediate ODX-RS in 48%, and high ODX-RS in 40%. In conclusion, the results show no significant correlation between the ODX-RS and Ki-67-PI (r = 0.511, p-value < 0.9).

New Approaches in Breast Cancer Radiotherapy.

Breast cancer stands as the most prevalent malignancy, necessitating a well-established approach to its management due to its sustained prevalence over decades. The implementation of intensive treatments, combining various modalities, has yielded excellent survival outcomes. Consequently, the optimization of quality of life and the mitigation of long-term side effects emerge as critical considerations for clinicians. As a result, discussions regarding treatment de-intensification strategies have been initiated for all treatment modalities, including surgery, radiotherapy (RT), and chemotherapy. RT plays a crucial role in adjuvant therapy. The efficacy of RT in disease control and overall survival across all stages of breast cancer has been demonstrated in numerous clinical trials and meta-analyses utilizing extensive datasets. However, advancements in genetic tumor profiling and improved identification of disease subgroups have prompted a reevaluation of RT omission in low-risk groups as a strategy for treatment de-intensification. Conversely, technological improvements and shortened total treatment times with hypofractionation make RT a secure and feasible option for enhancing local control and survival with minimal impact on the quality of life.

The added value of ultrasound imaging biomarkers to clinicopathological factors for the prediction of high-risk Oncotype DX recurrence scores in patients with breast cancer.

Background: The Oncotype DX (ODX) recurrence score (RS), a 21-gene assay, has been proven to recognize patients at high risk of recurrence (RS ≥26) who would benefit from chemotherapy. However, it has limited availability and high costs. Our study thus aimed to identify ultrasound (US) imaging biomarkers and develop a prediction model for identifying patients with a high ODX RS. Methods: In this retrospective study, consecutive patients with T1-3N0-1M0 breast cancer who were hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative who had an available ODX RS were reviewed. Patients treated from May 2012 and December 2015 were placed into a training cohort, and those treated from January 2016 to January 2017 were placed in a validation cohort. Clinicopathologic data were collected, and preoperative US scans were analyzed. Univariable and multivariable regression analyses were performed to evaluate the independent predictors for a high-risk of breast cancer in the training cohort, and a nomogram was developed and evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: A total of 363 patients were in the training cohort and 160 in the validation cohort, with the proportion with a high RS (RS 26-100) being 14% and 13.1%, respectively. Echogenic halo, enhanced posterior echo, low level of progesterone receptor (PR), and high Ki-67 index were identified as independent risk factors for high RS (all P values <0.05). The nomogram was constructed based on the combined model, which showed a better discrimination ability than did the clinicopathological model [combined model: AUC =0.95, 95% confidence interval (CI): 0.93-0.97; clinicopathological model: AUC =0.89, 95% CI: 0.86-0.92; P=0.001] and greater clinical benefit according to DCA. Furthermore, the nomogram was found to be effective in the validation cohort (AUC =0.90, 95% CI: 0.84-0.94), especially in patients with stage T1N0M0 disease (AUC =0.91, 95% CI: 0.84-0.95). Conclusions: US features may serve as valuable imaging biomarkers for the prediction of high recurrence risk in patients with T1-3N0-1M0 breast cancer and hormone receptor (HR)-positive and HER2-negative status. A nomogram incorporating PR status, Ki-67 index, and US imaging biomarkers showed a good discrimination ability in the early selection of patients at high risk of recurrence, especially in those with stage T1N0M0 disease.

Development of a nomogram to predict recurrence scores obtained using Oncotype DX in Japanese patients with breast cancer.

BACKGROUND: Chemotherapy is crucial for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and its survival benefits may outweigh adverse events. Oncotype DX (ODX) assesses this balance; however, it is expensive. Using nomograms to identify cases requiring ODX may be economically beneficial. We aimed to identify clinicopathological variables that correlated with the recurrence score (RS) and develop a nomogram that predicted the RS. METHODS: We included 457 patients with estrogen receptor-positive, HER2-negative breast cancer with metastases in fewer than four axillary lymph nodes who underwent surgery and ODX at our hospital between 2007 and 2023. We developed nomograms and internally validated them in 310 patients who underwent surgery between 2007 and 2021 and validated the model's performance in 147 patients who underwent surgery between 2022 and 2023. RESULTS: Logistic regression analysis revealed that progesterone receptor (PgR) level, histological grade (HG), and Ki67 index independently predicted the RS. A nomogram was developed using these variables to predict the RS (area under the curve [AUC], 0.870; 95% confidence interval [CI], 0.82-0.92). The nomogram was applied to the model validation group (AUC, 0.877; 95% CI, 0.80-0.95). When the sensitivity of the nomogram was 90%, the model was able to identify 52.3% low-RS and 41.2% high-RS cases not requiring ODX. CONCLUSIONS: This was the first nomogram model developed based on data from a cohort of Japanese women. It may help determine the indications for ODX and the use of nomogram to identify cases requiring ODX may be economically beneficial.

Is Oncotype DX testing informative for breast cancers with low ER expression? A retrospective review from a biomarker testing referral center.

PURPOSE: It remains unclear whether patients with HER2-negative, low-estrogen receptor (ER-low)-positive early breast cancer (BC) benefit from Oncotype DX® (ODX) testing. METHODS: We conducted a retrospective review of cases referred for ODX testing over a seven-year period from a breast biomarker testing referral center (n = 854). For each case, we recorded the ODX Recurrence Score (RS) along with percentage of ER nuclear positivity and staining intensity on immunohistochemistry. Our criteria for ER-low was defined as ≤10% cells with nuclear positivity and/or weak intensity of staining. Slides from all ER-low cases were reviewed and the reported ODX ER gene scores were recorded. We randomly selected a comparator group of 56 patients with ER > 10% positivity and non-weak staining intensity (ER-high). RESULTS: We identified 27 cases (3.2%) that met our criteria for ER-low. Of these, 92.6% had a high RS (>25), and 7.4% had a RS of 25. All cases with ≤10% ER nuclear positivity had a high RS. Most ER-low cases (85.2%) had ODX quantitative ER gene scores in the negative range, whereas all (100%) ER-high cases had positive ER gene scores. CONCLUSION: ODX does not appear to add significant additional information to inform treatment decisions for most patients with ER-low BC. Incorporating weak ER staining intensity in addition to low percentage of nuclear positivity identifies about twice as many ER-low patients, although with reduced specificity for high RS. Our study supports the contention that most ER-low early BC should be regarded similarly to ER-negative BC.

Cost-Effectiveness Analysis of the Oncotype DX Breast Recurrence Score® Test from a US Societal Perspective.

Background and Objectives: The 21-gene assay (the Oncotype DX Breast Recurrence Score® test) estimates the 10-year risk of distant recurrence in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer to inform adjuvant chemotherapy decisions. The cost-effectiveness of the 21-gene assay compared against standard clinical-pathological risk tools alone for HR+/HER2- early-stage breast cancer was assessed using an economic model informed by evidence from randomized controlled trials. Materials and Methods: A cost-effectiveness model consisted of a decision-tree to stratify patients according to their Recurrence Score (RS) results and the use of adjuvant chemotherapy, followed by a Markov component to estimate the long-term costs and outcomes of the chosen treatment. Distributions of patients and distant recurrence probabilities were derived from the TAILORx (N0) and RxPONDER (N1) trials. The model was evaluated from a healthcare payer and societal perspective. Endocrine therapy and chemotherapy use were informed using clinical expert opinion to reflect US clinical practice and were combined with Medicare drug costs (2021) to estimate the cost of treatment. Societal costs included lost productivity and patient out-of-pocket costs obtained from literature. Results: The Oncotype DX test generated more quality-adjusted life-years (QALYs) (N0: 0.25; N1: 0.08) at a lower cost (N0: -$13,395; N1: -$2526) compared to clinical-pathological risk alone from a societal cost perspective. The overall conclusions from the model did not change when considering a payer perspective. The main cost drivers were avoidance of distant recurrence for N0 (-$12,578), and the cost of adjuvant chemotherapy for N1 (-$2133). Lost productivity had a major impact in the societal perspective analysis (N0: -$4607; N1: -$1586). Conclusion: Adjuvant chemotherapy decisions based on the RS result led to more life year gains and lower healthcare costs (dominant) compared to using clinical-pathological risk factors alone among patients with HR+/HER2- N0 and N1 early-stage breast cancer.

Attempt to Substitute the Oncotype DX Breast Recurrence Score® Test by Histopathological Factors and MUC1 Protein Expression.

Background/Aim: Oncotype DX Breast Recurrence Score® test (ODx) is a gene profiling assay predicting the benefit of adjuvant chemotherapy for early-stage hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Meanwhile, to avoid unnecessary financial burden on the patient, many studies have attempted to establish alternatives to ODx using conventional clinicopathological factors, but these have not yet been successful. Thus, we retrospectively investigated clinicopathological factors to establish alternatives to ODx. Patients and Methods: Data from 114 Japanese women who underwent ODx were retrospectively examined to investigate the relationship between ODx recurrence score (RS) and clinicopathological features, including MUC1 staining patterns on immunohistochemical assessment. An RS of 0-25 was defined as low, and 26-100 as high. Results: Ninety patients (79%) had low RS and 24 patients (21%) had high RS. Univariate analysis revealed that low tumor grade, high progesterone receptor (PgR) expression, and low Ki67 labeling index (LI) were significantly associated with low RS (p=0.025, p<0.001, and p<0.001, respectively). Tumors with an apical pattern of MUC1 staining also frequently had a low RS (p=0.024). In multivariate analysis, PgR expression and Ki67 LI were independent factors associated with RS (p<0.001, for both). When the ODx results were categorized with a combination of these two factors, only 2% of the PgR-high and Ki67-low group (one in 51 cases) had a high RS. Conclusion: PgR expression and Ki67 LI were independent factors correlated with RS. MUC1 staining pattern also has the potential to be a useful marker. We believe that it is crucial to continue attempts to identify patients who are unlikely to benefit from ODx.

Does Pre-Emptive Availability of PREDICT 2.1 Results Change Ordering Practices for Oncotype DX? A Multi-Center Prospective Cohort Study.

For early-stage hormone receptor (HR)-positive and HER2-negative breast cancer, tools to estimate treatment benefit include free and publicly available algorithms (e.g., PREDICT 2.1) and expensive molecular assays (e.g., Oncotype DX). There remains a need to identify patients who de-rive the most benefit from molecular assays and where this test may be of poor value. In this multicenter prospective cohort study, we evaluated whether use of PREDICT 2.1 would impact physician decision making. For the first 6 months of the study, data on physician use of both PREDICT 2.1 and Oncotype DX ordering were collected on all newly diagnosed patients eligible for molecular testing. After 6 months, an educational intervention was undertaken to see if providing physicians with PREDICT 2.1 results affects the frequency of Oncotype DX requests. A total of 602 patients across six cancer centers in Ontario, Canada were recruited between March 2020 and November 2021. Providing PREDICT 2.1 results and an educational intervention did not alter the ordering of an Oncotype DX. For patients with low clinical risk, either by clinico-pathologic features or by PREDICT 2.1, the probability of obtaining a high Oncotype DX recurrence score was substantially lower compared to patients with high-clinical-risk disease. The introduction of an educational intervention had no impact on molecular assay requests. However, routine ordering of molecular assays for patients with low-clinical-risk disease is of poor value.

Oncotype DX in Breast Cancer Management: Insights and Outcomes From the United Arab Emirates.

Introduction Breast cancer remains the most significant cancer affecting women worldwide, with an increasing incidence, especially in developing regions. The introduction of genomic tests like Oncotype DX has revolutionized personalized treatment, allowing for more tailored approaches to therapy. This study focuses on the United Arab Emirates (UAE), where breast cancer is the leading cause of cancer-related deaths among women, aiming to assess the predictive accuracy of the Oncotype DX test in categorizing patients based on recurrence risk. Materials and methods A retrospective cohort study was conducted on 95 breast cancer patients diagnosed at Tawam Hospital between 2013 and 2017 who underwent Oncotype DX testing. Data on patient demographics, tumor characteristics, treatment details, and Oncotype DX scores were collected. Survival analysis was performed using the Kaplan-Meier method, with the chi-square goodness of fit test assessing the model's adequacy. Results The cohort's age range was 27-71 years, with a mean age of 50, indicating a significant concentration of cases in the early post-menopausal period. The Oncotype DX analysis classified 55 patients (57.9%) as low risk, 29 (30.5%) as medium risk, and 11 (11.6%) as high risk of recurrence. The majority, 73 patients (76.8%), did not receive chemotherapy, highlighting the test's impact on treatment decisions. The survival analysis revealed no statistically significant difference in recurrence rates across the Oncotype DX risk categories (p = 0.268231). Conclusion The Oncotype DX test provides a valuable genomic approach to categorizing breast cancer patients by recurrence risk in the UAE. While the test influences treatment decisions, particularly the use of chemotherapy, this study did not find a significant correlation between Oncotype DX risk categories and actual recurrence events. These findings underscore the need for further research to optimize the use of genomic testing in the UAE's diverse patient population and enhance personalized treatment strategies in breast cancer management.

Budget Impact of the Oncotype DX Breast Recurrence Score® Test in Patients with Early Primary Hormone-Receptor-Positive, HER2-Negative, Node-Positive Breast Cancer in Germany.

Background: Gene expression tests can inform decisions on whether to recommend or omit chemotherapy for patients with early HR+, HER2- breast cancer. The benefit of these tests is well established and fully reimbursed by sickness funds for lymph node-negative (pN0) patients in Germany. A budget impact model was built to evaluate the effect of using the Oncotype DX Breast Recurrence Score® test also for node-positive (pN1: 1-3 positive lymph nodes) patients. Methods: The prospective randomized clinical trial, RxPONDER, defined conditions (Recurrence Score result 0-25 for postmenopausal patients with 1-3 positive lymph nodes) under which omitting chemotherapy does not significantly impact invasive disease-free survival with results currently reported for 5-year follow-up. The present budget impact model calculates average total cost per node-positive patient versus no testing from a sickness funds perspective, taking into account not only the budgetary impact of avoiding chemotherapy and associated side effects, but also the costs of treating those patients who develop distant metastasis. The stability of the results was investigated by probabilistic multivariate sensitivity analysis. Results: After deducting testing cost, applying the Oncotype DX Breast Recurrence Score test yielded an average savings per node-positive patient of EUR 4,272. Without the test costs, the greatest savings resulted from reductions in direct treatment costs and costs arising from the treatment of chemotherapy-related side effects, which together averaged EUR 6,677. The targeted use of chemotherapy after testing also resulted in slightly lower costs for treatment of distant metastasis, if it did occur. The multivariate sensitivity analysis also almost exclusively resulted in cost savings. Conclusion: Analogous to the pN0 situation, this budget impact model demonstrates that the Oncotype DX Breast Recurrence Score test can also reduce healthcare costs in Germany in treatment of node-positive (pN1: 1-3 positive lymph nodes) patients by minimizing both unnecessary chemotherapy and undertreatment. Additional benefits to patients would include reduced morbidity and improved quality of life for those patients who can safely avoid chemotherapy or undertreatment.

Application of a 21-Gene Recurrence Score in a Swiss Single-Center Breast Cancer Population: A Comparative Analysis of Treatment Administration before and after TAILORx.

In patients with hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2-) negative breast cancer (BC), the TAILORx study showed the benefit of adding chemotherapy (CHT) to endocrine therapy (ET) in a subgroup of patients under 50 years with an intermediate Oncotype DX recurrence score (RS 11-25). The aim of the present study was to determine if the TAILORx findings, including the changes in the RS categories, impacted CHT use in the intermediate RS (11-25) group in daily practice, as well as to identify the main factors for CHT decisions. We conducted a retrospective study on 326 BC patients (59% node-negative), of which 165 had a BC diagnosis before TAILORx (Cohort A) and 161 after TAILORx publication (Cohort B). Changes in the RS categories led to shifts in patient population distribution, thereby leading to a 40% drop in the low RS (from 60% to 20%), which represented a doubling in the intermediate RS (from 30% to 60%) and an increase of 5% in the high RS (from 8-10% to 15%). The overall CHT recommendation and application did not differ significantly between cohort B when compared with A (19% vs. 22%, resp., p = 0.763). In the intermediate RS (11-25), CHT use decreased by 5%, while in the high-risk RS category (>25), there was an increase of 13%. The tumor board recommended CHT for 90% of the patients according to the new RS guidelines in cohort A and for 85% in cohort B. The decision for CHT recommendation was based on age (OR 0.93, 95% CI 0.08-0.97, p = 0.001), nodal stage (OR 4.77, 95% CI 2.03-11.22, p < 0.001), and RS categories (RS 11-25 vs. RS 0-10: OR 0.06 (95% CI 0.02-0.17), p < 0.001; RS > 26 vs. RS 11-25: OR 618.18 95% CI 91.64-4169.91, p < 0.001), but did not depend on the cohort. In conclusion, while the tumor board recommendation for CHT decreased in the intermediate RS category, there was an increase being reported in the high RS category, thus leading to overall minor changes in CHT application. As expected, among the younger women with intermediate RS and unfavorable histopathological factors, CHT use increased.

Influencia del score de recurrencia Oncotype Dx en la decisión del tratamiento adyuvante del cáncer de mama / Influence of Oncotype Dx recurrence score in the decision of the adjuvant treatment of breast cancer

Objetivos El objetivo primario del presente estudio es analizar cómo la utilización del ensayo Oncotype Dx modifica y condiciona la elección del tratamiento adyuvante. En segundo lugar, nos propusimos evaluar la evolución de aquellas pacientes con score de recurrencia menor a 10, las cuales han sido clasificadas en el ensayo clínico TailorX como pacientes de bajo riesgo pasibles de ser tratadas solo con terapia hormonal adyuvante Por último, buscamos evaluar si existe correlación entre el valor de Ki 67, la invasión linfovascular (ILV) y el score del Oncotype Dx. Material y método Analizamos retrospectivamente 62 pacientes con cáncer de mama con receptores hormonales positivos, her2 Neu negativo y ganglios negativos, a las cuales se les solicitó el score de recurrencia Oncotype Dx, y comparamos con las indicaciones de terapia adyuvante surgidas previamente de factores de riesgo clínicos y anátomo-patológicos. Resultados Treinta pacientes (48,4%) presentaron score de bajo riesgo, 25 (40,3%) score de riesgo intermedio y las 7 restantes (11,3%) score de alto riesgo de recurrencia. Analizando el cambio de conducta, una vez obtenido el resultado del Oncotype Dx, encontramos un cambio de decisión en 16 pacientes (26%). Según la indicación de los factores de riesgo clínicos y anátomo-patológicos, de las 62 pacientes incluidas en este estudio, se había indicado adyuvancia con quimioterapia y hormonoterapia a 26 pacientes y hormonoterapia solamente a las 36 pacientes restantes. Posterior a la realización del Oncotype Dx, de las 26 pacientes a las cuales se les había indicado quimioterapia, en 12 se modificó el tratamiento a adyuvancia hormonal solamente (46,15% de reducción de la indicación en este grupo). Por otra parte, en aquellas 36 pacientes respecto de las cuales nuestra indicación previa había sido solamente adyuvancia hormonal, el resultado del Oncotype Dx determinó la realización de quimioterapia en 4 (11,1%). Cotejando la correlación entre Oncotype Dx y factores anátomo-patológicos, encontramos como dato interesante que todas aquellas pacientes con score de alto riesgo presentaban Ki 67 elevado, pero no a la inversa, mientras que no hallamos relación entre invasión linfovascular (ilv) presente y Oncotype Dx elevado. Conclusiones Consideramos que la utilización de plataformas genómicas como el Oncotype Dx es un elemento útil a la hora de tomar decisiones sobre el tratamiento adyuvante del carcinoma de mama Luminal con ganglios negativos, donde la indicación de la quimioterapia adyuvante debe ser cuidadosamente evaluada.

Objectives The primary objective is to analyze how the use of Oncotype Dx modifies and conditions the choice of adjuvant treatment. Second, to evaluate the evolution of those patients with score of recurrence <10 ­of low risk in TailorX Clinical Trial­, treatable with hormonal adjuvancy only. Finally, compare correlation between lymphovascular invasion (ilv), Ki 67 and Oncotype High Dx. Materials and method We retrospectively analyzed 62 breast cancer patients with hormone receptor positive, hers Neu negative and negative lymph nodes, who were asked for the Oncotype Dx recurrence score and compared with the indications for adjuvant therapy that had previously arisen from clinical and anatomic risk factors pathological. Results Thirty patients (48.4%) presented a low risk score, 25 patients (40.3%) intermediate risk and the remaining 7 patients (11.3%), a high risk score for recurrence. Once the Oncotype Dx result was obtained, we found a decision change in 16 patients (26%). According to the indication of the clinical and anatomopathological risk factors, of the 62 patients included in this study, adjuvancy had been indicated with chemotherapy and hormone therapy to 26 patients and only hormone therapy to the remaining 36 patients. After the Oncotype Dx, of the 26 patients to whom chemotherapy had been indicated, in 12 of them the treatment was modified to hormonal adjuvancy only (46.15% reduction of the indication in this group). On the other hand, in those 36 patients that our previous indication had been only hormonal adjuvancy, the result of the Oncotype Dx determined the accomplishment of chemotherapy in 4 of them (11.1%). Comparing the correlation between Oncotype Dx and anatomopathological factors, we found that all those patients with a high risk score had elevated Ki 67, but not inversely, whereas we did not find a relation between present lymphovascular invasion (ilv) and Oncotype High Dx. Conclusions We believe that the use of genomic platforms such as Oncotype Dx is a useful element when making decisions about the adjuvant treatment of Luminal breast cancer with negative ganglia, where the indication of adjuvant chemotherapy should be carefully evaluated.

Impacto del Score de Recurrencia de 21 genes en la indicación de tratamiento sistémico adyuvante: nuestra experiencia en el Hospital Italiano de Buenos Aires / Impact of the Recurrence Score on clinical decision-making about chemotherapy in the adjuvant setting: our experience at Hospital Italiano of Buenos Aires (Argentina)

Introducción Las plataformas genómicas han tomado gran relevancia como factores pronósticos y predictivos para definir tratamiento adyuvante en pacientes con cáncer de mama. Su uso permitiría discriminar un subgrupo de pacientes en quienes la indicación de quimioterapia podría ofrecer más morbilidad que verdadero beneficio. Objetivos Describir las características de las pacientes en quienes se utilizó la plataforma Oncotype DX® y evaluar el impacto del Score de Recurrencia (Recurrence Score) como herramienta de decisión para la indicación de adyuvancia. Material y método Se consideraron pacientes operadas entre 2013 y 2017 en el Hospital Italiano de Buenos Aires, Argentina, con diagnóstico de carcinoma invasor primario de mama de subtipo Luminal A o B, her2neu negativas. Se seleccionaron los casos en los que se solicitó Oncotype DX® y se describieron sus características clínicas e histológicas. Resultados Se utilizó Oncotype DX® en 47 pacientes con cáncer de mama invasor. En el 48,9% se obtuvo un Recurrence Score de riesgo bajo, en el 40,4% de riesgo intermedio y en el 10,6% de riesgo alto. En 22 casos (46,8%) consideramos que hubo un cambio de conducta en la indicación de adyuvancia. Conclusiones En nuestra experiencia, hemos visto que la plataforma genómica Oncotype DX® sería una herramienta útil para definir tratamiento adyuvante en tumores de tipo Luminal, her2neu negativo.

Introduction Over the past decade, gene expression assays have become relevant prognostic factors for guiding clinical decision-making in patients with breast cancer. Their use allows to discriminate which patients are most likely to benefit from chemotherapy in the adjuvant setting, avoiding unnecessary toxicity. Objectives To describe the clinical and pathologic characteristics of patients in whom Oncotype DX® was used as a prognostic factor and assess the impact of the Recurrence Score on clinical decision-making. Materials and method Patients who underwent surgery at the Hospital Italiano de Buenos Aires, Argentina, between 2013 and 2017 for Estrogen-Receptor positive (er+), her2neu negative primary breast cancer were considered eligible. We evaluated the cases in which Oncotype DX® was ordered and described the clinical and pathologic characteristics, as well as whether Recurrence Score (rs) modified the prescription of adjuvant therapy. Results Oncotype DX® was performed in 47 patients. The distribution of patients according to rs was as follows: low risk rs 48,9%, intermediate risk 40,4% and high risk 10,6%. We considered that adjuvant therapy decision was modified after rs in 22 patients (46,8%). Conclusions Oncotype DX® and its resulting Recurrence Score appear to be a clinically useful tool for decision-making in the adjuvant setting for patients with er+, her2neu negative breast cancer.