Low Oncotype DX Recurrence Scores Research Articles

Correlation ofKi-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 - areview of137 cases.

Theuse ofchemotherapy in breast cancer management has significantly contributed to thedecrease in its mortality. Currently, theprognosis is determined by molecular biomarkers, such as oestrogen receptors, and human epidermal growth factor receptor 2. However, theincreasing use ofadvanced molecular technologies, including oncotype DX recurrence score (ODX-RS), has provided theability to estimate therisk ofrecurrence. Research has demonstrated that theODX-RS helps to predict recurrence risk and thepotential benefit ofchemotherapy in breast cancer. As aresult, it can assist clinicians in making decisions regarding using thechemotherapy. Thegoal ofwork is to explore thecorrelation between theODX-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 thehigh Ki-67-PI group: low ODX-RS in 12%, intermediate ODX-RS in 48%, and high ODX-RS in 40%. In conclusion, theresults show no significant correlation between theODX-RS and Ki-67-PI (r = 0.511, p-value < 0.9).

Treatment pattern of early-stage premenopausal breast cancer patients with low Oncotype DX score: Single center experience.

e12510 Background: The predictive value of Oncotype DX in early-stage node negative breast cancer had been previously well established. As per TAILORx, patients with a low Oncotype DX Recurrence Score RS (0–25) did not benefit from chemotherapy. Premenopausal patients are a crucial subgroup for which recommendations based on Oncotype DX are imprecise. Those with Oncotype DX RS 16-25 are thought to have a small benefit from chemotherapy. Our goal was to study the treatment pattern for this group of patients managed at our institution. Methods: We conducted a retrospective analysis to assess premenopausal patients with early-stage breast cancer who had Oncotype DX testing done. All eligible patients were compared based on whether chemotherapy was given or not. The primary endpoint evaluated was the rate of local recurrence. Univariate comparisons were assessed using t-tests or ANOVA for continuous variable &amp; chi-square for categorical variable. Results: A total of 506 patients younger than 50 years diagnosed between 01/2018 and 12/2020 who had an Oncotype DX available were identified. Of these, 344 were White, 137 were Black and 23 identified as another race. The average age of patients was 42.7 ± 5.5 years. Patients treated with chemotherapy were found to be on average younger than those who did not receive chemotherapy (42 years old vs 43.6 years old, P &lt; 0.0001). The average tumor size for patients who got chemotherapy was 3.26 cm compared to an average size of 2.78 cm for patients who avoided chemotherapy. 72.1% of patients with stage 2 disease had received chemotherapy compared to 38.1 % of patient with stage 1. There were 462 patients with RS &lt; 16, 28 patients with RS 16-25, and 16 patients with RS &gt; 25 as illustrated. Patients were followed from a range of 1.8 months to 30.7 months. There were 6 patients who had local recurrences identified, all of which had RS scores &lt; 16. Conclusions: In our study, 91.3% had RS &lt; 16 and generally should have avoided chemotherapy, however 35% of these patients continued to receive chemotherapy. Only 5.5% of our population had RS 16-25, a quarter of which (n = 7) received chemotherapy. Of those 7 patients, 3 had positive lymph node disease. None of these patients had disease recurrence to date. Patients with RS &gt;25 made up 3.2% of the population and would generally benefit from chemotherapy, however 12.5% of these patients did not end up receiving it. Using Oncotype DX in early-stage breast cancer helps avoid chemotherapy safely in majority of patients. [Table: see text]

Estrogen receptor positive breast cancer in an Afro-Caribbean cohort.

e12550 Background: Estrogen receptor-positive breast cancer (EBC) accounts for 78% of breast cancer (BC) cases in the United States, and with better prognosis compared to other BC subtypes. There is limited information on the incidence, presentation, and outcomes of BC in black women from the Caribbean. We describe the clinicopathologic features and treatment outcomes of EBC in this underrepresented immigrant patient population. Methods: This is a retrospective study conducted at Kings County Hospital, a public hospital in a Brooklyn, New York neighborhood with the second highest population of Afro-Caribbeans in the United States. Demographics and clinicopathological data of patients diagnosed with BC from 2015-2018 were collected from the hospital’s tumor registry. Descriptive statistics and Chi-square testing were used to analyze the data. Results: Of the 299 women with a BC diagnosis, 185 (62%) had EBC, with median age of 61, and median BMI of 29.9. Stratification by menopausal status revealed 75% of these patients were post-menopausal. 37% of pre-menopausal and 28% of post-menopausal women presented with lymph node involvement (LNI). At diagnosis, 61% of patients had localized disease, 30% regional LNI, and 9% distant metastases. Sub-analysis revealed 25%, 22%, 28%, 16% and 9% with stages 0, I, II, III and IV respectively. 39% of patients presented with Nottingham Grade 3, 50% with Grade 2, and 11% with Grade 1 disease. 25% of patients without LNI had Oncotype Dx testing. 22% of these had Recurrence Score (RS) less than 11, 50% RS 11-25, and 28% RS 26 or higher. Of the 27 patients who received neoadjuvant treatment, 22% had complete pathologic response, 37% had partial response, and 33% had disease progression. 81% of patients self-identified as Afro-Caribbean, 27% reported first- or second-degree relatives with a BC diagnosis and 22% first-degree relatives with non-breast malignancy. At time of data analysis, at median of 6 years, 75% of all patients were relapse and progression-free. Lasting response was correlated with cancer stage (p &lt; 0.01) but independent of tumor grade and Oncotype Dx RS (p = 0.18 and p = 0.29, respectively). Conclusions: In our study, Afro-Caribbean women with EBC presented with high-grade tumors and high incidence of regional LNI. Pre-menopausal women had a higher incidence of nodal involvement. Notable was a strong family history of cancer implying inherited or familial cancer syndromes. Progression-free survival was lower than expected and correlates with disease stage, but not with low Oncotype Dx RS. Further research is warranted to investigate better prognostic tools for this population.

Abstract P6-01-27: Utilization of the Oncotype Dx Assay for Young Patients with Early Stage, Hormone-Receptor Positive, HER2-Negative Breast Cancer in an Integrated Health System

Abstract Background: Oncotype Dx (ODX) is one of the most widely used prognostic multigene expression assays for early-stage, hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer. Previous studies demonstrated reduction in chemotherapy in patients with a low ODX Recurrence Score (RS). Over recent years, utilization of this tool has increased in young breast cancer (YBC) patients (age≤40 years), a population often underrepresented in randomized clinical trials. The purpose of this retrospective study was to assess the utilization of this assay over time in an integrated health system and whether ODX RS results altered clinical practice. Methods: YBC patients with T1-T2N0 HR+HER2- breast cancer were retrospectively evaluated. Descriptive analysis examined the association between tumor characteristics, year of diagnosis, ODX testing, treatment, and recurrence outcomes. ODX risk categories were defined as: low risk 0-15; intermediate risk 16-25; high risk &amp;gt; 25. Recurrence was determined by the date of confirmation on pathology or imaging. Bivariate analysis compared characteristics between groups using Fisher exact tests for categorical variables and t-tests and nonparametric tests for continuous variables. Results: From 2008-2018, 1,436 Stage I-III YBC patients were diagnosed with invasive breast cancer, and 455 met eligibility criteria for ODX testing. Median follow-time (interquartile range, IQR) was 4.9 (2.8, 7.9) years for the 255 women who were tested and 5.7 (3.5, 8.7) years for the 200 women who were not tested (p&amp;lt; 0.05). Prior to 2018, 52.1% of patients were tested; after 2017, ODX testing rate increased to 88%. Overall, there were 255 patients who underwent ODX testing (55.9%). The median age (IQR) of patients who had an ODX test was 38.0 (35.0, 39.0). Of 225 tested patients, 42.0% (n=107) were White, 6.3% (n=16) Black, 33.7% (n=86) Asian/Pacific Islander, 15.7% (n=40) Hispanic, and 2.3% (n=6) identified as Other. There was no overall difference in testing based on ethnicity (p=0.42). More patients with grade 1 versus grade 3 disease were tested, 61.5% vs 45.2% (p=0.02 from overall Fisher exact test). Adjuvant chemotherapy was administered to 61.0% (122/200) patients who were not tested, whereas 38.4% (98/255) of those tested received chemotherapy (p&amp;lt; 0.001). In tested patients, 6% of low-risk (RS 0-15), 37% of intermediate risk (RS 16-25), and 92% of high risk (RS &amp;gt;25) patient received adjuvant chemotherapy. Among patients with T2 lesions, a higher proportion not tested (90.8% [59/65]) received adjuvant chemotherapy compared with those not tested (57.1% [40/70]). There were no differences in recurrence based on ODX testing, 11.0% (22/200) not tested vs. 9.4% (24/255) tested (p=0.26). Conclusions: Utilization of ODX testing increased after 2017. A significantly lower proportion of women who underwent ODX testing received chemotherapy, compared with women not tested for ODX. A higher percent of women with T2 cancer received chemotherapy if testing was not completed, which may reflect a greater fear of recurrence in younger patients. Further investigation is needed to better understand this potential risk of overtreatment in the YBC population. Citation Format: Ashley Aller, Jeanne A. Darbinian, Raymond Liu, Gillian Kuehner, Alison Savitz, Patience Odele, Laurel Habel, Brooke Vuong. Utilization of the Oncotype Dx Assay for Young Patients with Early Stage, Hormone-Receptor Positive, HER2-Negative Breast Cancer in an Integrated Health System [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 P6-01-27.

Abstract P6-01-30: PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit

Abstract AIM: The majority of invasive lobular carcinomas (ILC) of the breast are luminal A tumors of good prognosis, having a low or intermediate OncotypeDX Recurrence Score (RS). They are usually treated with hormonal therapy only and some have doubted the relevance of the RS for patients with ILC. However, in a number of ILC cases a high RS can be found, indicating chemotherapy benefit. The aim of the present analysis was to explore in our database of lobular carcinomas analyzed with OncotypeDX, the percentage of tumors with a RS &amp;gt;25 and test the hypothesis if Progesterone Receptor (PgR) and/or Ki-67 expression could be an indicator to have patients evaluated with OncotypeDX. PATIENTS AND METHODS: Among 2.946 patients analyzed with Oncotype DX, we found 397 patients with pure lobular carcinomas (13.47%). Ki-67 expression was obtained from 315 patients and 13 of them (4%) had a high Ki-67 value of &amp;gt;30%. PgR expression was negative in 56 out of 397 patients (14%). We analyzed the possible relationship of RS values with PgR levels and Ki-67 expression. RESULTS: Overall, 94% of patients with ILC had a Recurrence Score ≤25 and only 6% (24/397) had a RS ≥26. There was a wide distribution of RS among patients with different values of PgR; however, there was a negative trend of Recurrence Score values and PgR expression levels. This trend was more obvious in the 56 patients with negative PgR expression. Although there were high RS values across all levels of Ki-67 expression, there was a trend towards high RS with higher Ki-67 expression; 5 out of 13 patients (38%) with ki-67 &amp;gt;30% had a RS ≥26. CONCLUSION: Our analysis shows that the majority of lobular carcinomas of the breast have a low OncotypeDX RS, suggesting that can be treated only with hormonal therapy. However, negative or low PgR levels and high Ki-67 expression might predict a high RS and thus chemotherapy benefit and those two parameters could be used as indicators for OncotypeDX evaluation of lobular carcinomas of the breast. Citation Format: Christos Markopoulos, Mahi Sariyanni, Asimina Karamargiou, Zoi Antonopoulou, Nikolaos Tsoulos. PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit [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 P6-01-30.

The effect of non-oncology drugs on clinical and genomic risk in early luminal breast cancer

An effect of non-oncology medications on cancer outcome has been proposed. In this study, we aimed to systematically examine the impact of commonly prescribed non-oncology drugs on clinical risk and on the genomic risk [based on the Oncotype DX recurrence score (RS)] in early breast cancer (BC). We collected data on clinical risk (stage and grade), genomic risk (Oncotype DX RS), and on non-oncology medications administered to 1423 patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative BC during the month of their surgery. The influence of various medications on clinical and genomic risks was evaluated by statistical analysis. Out of the multiple drugs we examined, levothyroxine was significantly associated with a high Oncotype DX RS (mean 24.78; P < 0.0001) and metformin with a low Oncotype DX RS (mean 14.87; P < 0.01) compared with patients not receiving other non-oncology drugs (mean 18.7). By contrast, there were no differences in the clinical risk between patients receiving metformin, levothyroxine, or no other non-oncology drugs. Notably, there was no association between the consumption of levothyroxine and metformin and proliferation marker (Ki67) levels, but both drugs were significantly associated with progesterone-related features, suggesting that they influence genomic risk through estrogen-dependent signaling. The results of this study indicate a significant impact of metformin and levothyroxine on clinical decisions in luminal BC, with potential impact on the clinical course of these patients.

The Role of Post-Mastectomy Radiation Therapy in Patients with pT3N0 Breast Cancer and Low Genomic Recurrence Score

<h3>Purpose/Objective(s)</h3> The role of post-mastectomy radiotherapy (PMRT) in patients with pT3 pN0 breast cancer remains controversial. We previously showed a correlation between PMRT and improved overall survival (OS) in pT3N0 patients who do not receive chemotherapy. However, it is unknown whether this correlation extends to patients with low genomic recurrence score (RS). In this analysis, we used the National Cancer Database (NCDB) to investigate the benefit of PMRT in pT3N0 patients with low RS. <h3>Materials/Methods</h3> We performed an analysis of NCDB patients with pT3N0 breast cancer who had low Oncotype DX RS (ORS) (< 25) and did not receive systemic chemotherapy. Patients were matched for baseline patient, tumor, and treatment characteristics using inverse probability of treatment weighting to minimize the impact of potential confounding variables. We stratified patients based on receipt of PMRT and compared OS using Kaplan-Meier estimates. Univariate and doubly-robust multivariable analyses were used to correlate PMRT and various baseline characteristics with OS. <h3>Results</h3> We identified 444 patients with pT3N0 breast cancer who had undergone mastectomy and had low-risk genomic assay scores who did not receive systemic chemotherapy. After IPTW matching, there were no significant differences in baseline patient characteristics. In the PMRT group, 44% received treatment to the chest-wall only, and 66% patients received chest wall and regional nodal irradiation. PMRT was associated with improved overall survival on both the univariate (HR=0.201; 95% CI=0.05-0.78; p=0.021) and doubly-robust multivariable analyses (HR=0.128; 95% CI=0.02-0.66; p=0.014). Receipt of endocrine therapy was also found to significantly improve overall survival (p=0.02). We attempted to repeat the analysis in patients with RS >25 who received chemotherapy, but we only identified a total of 78 such patients and could not perform a robust analysis. <h3>Conclusion</h3> This cohort analysis shows a strong correlation between PMRT and improved OS in pT3N0 patients with low ORS who do not receive chemotherapy. It is possible that with the de-escalation of chemotherapy and axillary surgery in this patient population in the modern era, the benefit of locoregional treatment with radiotherapy is magnified. Our analysis suggests that prospective data are needed before de-escalation of radiotherapy for these patients based on ORS.

The Oncotype DX recurrence score impact on the management of ER-positive, HER2-negative, node-negative breast cancer

Introduction: Oncotype DX recurrence score is used to categorize estrogen-receptor-positive, human epidermal growth factor receptor-2 negative, lymph-node negative early breast cancer in high- or low-recurrence risk groups. It has a guiding significance for whether post-operative chemotherapy or only hormonal manipulation is selected as an adjuvant treatment. Aims: Assess the impact of the Oncotype DX recurrence score on adjuvant chemotherapy-related management decision-making in the cases of ER+ve, HER2–ve, LN–ve early breast cancer in our local unit. Material and methods: A cohort of 76 patients with early breast cancer were included, two had bilateral disease. All were operated for estrogen-receptor-positive, human epidermal growth factor receptor-2 negative, lymph-node negative early breast cancer. Tumor grade, Ki67 proliferative index, PREDICT and Oncotype DX recurrence score results were obtained in addition to the offered treatment information for each case. Results: After the primary tumor surgery and an Oncotype DX recurrence score assessment, 18 patients (24%) were eligible for adjuvant chemotherapy; out of them, 10 patients (56%) had a chemotherapy absolute survival benefit of &gt; 15% at 10 years, where 5 patients (30%) had a chemotherapy relative survival benefit of ~ 6.5%, 3 patients (17%) had a chemotherapy relative survival benefit of ~1.6%. In this cohort, 10 patients (13%) had a low Oncotype DX recurrence score; however, they received adjuvant chemotherapy based on other clinico-biological parameters. The other 48 patients (63%) with a low recurrence risk were spared potential adverse events related to the systemic therapy. Based on the menopausal status, every patient had received suitable hormonal manipulation therapy. The data also revealed the absence of a relationship between the Ki67 proliferative index and the Oncotype DX recurrence score (p = 0.06); moreover, the size of the tumor did not correlate with the Oncotype DX recurrence score (p = 0.5). Conclusion: The Oncotype DX recurrence score provides a credible prediction of distant disease recurrence risk in early breast cancer; however, it does not correlate with other prognostic markers, such as the Ki67 proliferative index as well as the tumor size. In this cohort, the use of the Oncotype DX recurrence score led to a 24% rate of treatment recommendations in the direction of adjuvant chemotherapy in addition to anti-hormonal therapy for estrogen-receptor-positive, human epidermal growth factor receptor-2 negative, lymph-node negative early breast cancer.

Effect of Radiation Therapy following Breast Conserving Surgery (BCS) in Women with Early Stage Breast Cancer and Low Oncotype DX Recurrence Scores (RS)TM

Effect of Radiation Therapy following Breast Conserving Surgery (BCS) in Women with Early Stage Breast Cancer and Low Oncotype DX Recurrence Scores (RS)TM

Abstract 3298: Oncotype DX recurrence score: Implications for disparities in receipt of chemotherapy and breast cancer-specific mortality in Georgia

Abstract Background: Among women diagnosed with stage I-IIIa, node negative or positive (1-3), hormone receptor positive (HR+) and HER2 negative breast cancer (BC), the Oncotype DX recurrence score is used to guide chemotherapy treatment decisions. There is limited evidence on differences in the distribution of recurrence scores among non-Hispanic Black women (NHB), and whether this could contribute to the well-documented racial disparities in BC-specific mortality. The objective of this study was to evaluate the role of Oncotype DX recurrence score on racial disparities in BC-specific mortality between black and white women in Georgia. Methods: In this study, patients were identified from the Georgia Cancer Registry. We included 4562 non-Hispanic White (NHW) and 1353 NHB women with an initial diagnosis of stage I-III HR+ breast cancer in Georgia (2010-2014), with a corresponding Oncotype DX recurrence score from Genomic Health, Inc. Logistic regression was used to estimate the odds of chemotherapy receipt between NHB and NHW women by Oncotype DX recurrence score (low [&amp;lt;18], medium [18-30], and high [≥31]). Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) comparing BC-specific mortality rates by both race and recurrence score. Results: Compared with NHW breast cancer patients, NHB women were more likely to be classified with a high recurrence score (11% vs. 7%), and less likely to be classified with a low risk of recurrence (53% vs. 59%). In the age-adjusted models, NHB women with a high recurrence score were less likely to receive chemotherapy (OR=0.60, 95%CI 0.35, 1.04), however there was no difference in receipt of chemotherapy between NHB and NHW women with low or medium recurrence risk scores. After adjusting for age, we observed that NHB women with a low recurrence score had 3.05 times the hazard of BC-specifc mortality (95%CI 1.29, 7.04) compared to NHW women. Among women with a medium or high recurrence score we did not observe a racial disparity in BC mortality (HRhigh vs. low=1.49, 95%CI 0.51, 4.37). Conclusion: Our results indicate variation in receipt of chemotherapy by race, particularly among NHB women with a high Oncotype DX score. However, we observed the most pronounced racial disparity in BC-specific mortality among women with low Oncotype Dx recurrence scores. These findings should be replicated in larger studies with robust numbers of NHB women. Additional research is needed to understand differences in chemotherapy treatment decisions and validation of the Oncotype DX recurrence score cut points in diverse populations. Citation Format: Lindsay J. Collin, Brittany Crawford, Ming Yan, Renjian Jiang, Kevin Ward, Mylin Torres, Keerthi Gogineni, Preeti Subhedar, Lauren E. McCullough. Oncotype DX recurrence score: Implications for disparities in receipt of chemotherapy and breast cancer-specific mortality in Georgia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3298.

Abstract P4-08-12: Comparative analyses of the prognostic value of oncotype and mammaprint using the National Cancer Database

Abstract INTRODUCTION: Majority of the approximately 40,610 deaths from metastatic breast cancer in the US each year occur in women with hormone receptor positive breast cancer who recur after treatment for early stage disease. Genomic analysis is increasingly used to personalize breast cancer treatment for women with early breast cancer resulting in AJCC 8 modification of TNM staging. The 70-gene Mammaprint was developed using both ER- and ER+ breast tissue samples, while the 21-gene Oncotype DX (ODX) assay was developed using only ER+ breast tissue. Previous studies found that the two genomic assays gave discordant testing results. OBJECTIVE: To compare the performance of Mammaprint and Oncotype DX in assigning prognosis in early stage hormone receptor positive breast cancer. METHOD: A retrospective cohort of women diagnosed with early stage, hormone receptor positive breast cancer who received ODX or Mammaprint was established using the National Cancer Data Base (NCDB), 2010-2014. Using the propensity score matching method, we defined two groups of patients with similar clinical and demographic characteristics; one group received ODX and another received Mammaprint. The groups were matched by clinicopathologic and demographic factors. We examined the association between ODX or Mammaprint and overall survival using Log-rank test and Cox models in the two groups separately. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated as strength of association. The prognostic values were evaluated using c-index (i.e. area under ROC curve). RESULTS: Of 320,276 eligible patients with breast cancer, 41.5% received ODX and 1.3% received Mammaprint testing. The use of ODX increased from 34.3% in 2010 to 45.2% in 2014, while the use of Mammaprint increased from 0.5% in 2010 to 2.0% in 2014. After propensity score matching, we identified 3319 patients who received ODX and matched to 3319 patients who received Mammaprint. Compared to patients with a low risk Mammaprint score (n=1915), patients with a high risk Mammaprint score (n=1404) had 4.53-fold increased risk of dying (95% CI 2.79-7.36). The c-index for Mammaprint was 0.683. Relative to patients with a low ODX recurrence score (n=1927), the HR for intermediate ODX score was 1.23 (95% CI 0.76-1.98) and the HR for high ODX score was 3.62 (95% CI 2.21-5.94). The c-index for ODX was 0.601. In patients with ODX testing, 28.2% received chemotherapy. In patients with Mammaprint testing, 42.4% received chemotherapy. Based on MINDACT's modification of Adjuvant!Online, 49.2% patients were assigned to the clinical high risk group, including 22.3% to the clinical high risk/genomic low risk (C-high/G-low) subgroup and 26.9% to the C-high/G-high subgroup. The percentage of patients receiving chemotherapy with C-low/G-low, C-low/G-high, C-high/G-low, and C-high/G-high were 4.3%, 70.4%, 32.2%, and 84.9%, respectively. CONCLUSION: The findings from our preliminary study suggest that Mammaprint may achieve better separation of high risk from low risk patients. However, it is possible that having more genes in multigene assays would better capture the heterogeneity of hormone receptor positive breast cancer and guide choice of optimal systemic therapy to reduce risk of metastases. Citation Format: Ibraheem AF, Olopade O, Huo D. Comparative analyses of the prognostic value of oncotype and mammaprint using the National Cancer Database [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-12.

Introduction of a New Staging System of Breast Cancer for Radiologists: An Emphasis on the Prognostic Stage.

In 2017, the American Joint Committee on Cancer announced the 8th edition of its cancer staging system. For breast cancer, the most significant change in the staging system is the incorporation of biomarkers into the anatomic staging to create prognostic stages. Different prognostic stages are assigned to tumors with the same anatomic stages according to the tumor grade, hormone receptor (estrogen receptor; progesterone receptor) status, and HER2 status. A Clinical Prognostic Stage is assigned to all patients regardless of the type of therapy used; in contrast, a Pathologic Prognosis Stage is assigned to patients in whom surgery is the initial treatment. In a few situations, low Oncotype DX recurrence scores can change the prognostic stage. The radiologists need to understand the importance of the biologic factors that can influence cancer staging.

Evaluation of Prognosis in Hormone Receptor–Positive/HER2-Negative and Lymph Node–Negative Breast Cancer With Low Oncotype DX Recurrence Score

IntroductionHormone receptor–positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancers without lymph node metastasis have good prognosis. We compared the prognosis of hormone receptor–positive, HER2-negative, lymph node–negative cancers with Oncotype DX score ranges of 1 to 10 (1-10 group) and 11 to < 18 (11-18 group). Patients and MethodsA total of 107 cases in the 1-10 group and 225 cases in the 11-18 group were reviewed. All patients received surgery. The use of chemotherapy, radiotherapy, and endocrine therapy, and overall survival (OS), disease-free survival (DFS), and distant metastasis were compared between groups. ResultsThere were no statistical differences in the use of chemotherapy (5.05% vs. 6.05%, P = .724) or radiotherapy (52.53% vs. 59.07%, P = .276) between the 1-10 group and the 11-18 group, respectively. The median OS and DFS were 47 and 45 months, respectively, in the 1-10 group, and 49 and 48 months in the 11-18 group. No significant difference was seen in OS (P = .995), DFS (P = .148), or rates of metastasis (P = .998). The 11-18 group had more death events and distant metastasis (death, 5 events; recurrence, 2 events; metastasis, 2 events) than the 1-10 group (death, 0 events; recurrence, 4 events; metastasis, 0 events). The majority of recurrences seen in both groups were in young patients who failed to comply with their endocrine therapy regimen. ConclusionPatients in both the 1-10 group and the 11-18 group had good prognoses. Those who experienced recurrence were more likely to be premenopausal and to have failed to comply with the recommended endocrine therapy regimen. Endocrine therapy remains important in these patients.

Breast Cancer—Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual

Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible. The panel felt that, to maintain worldwide value, the tumor staging system should remain based on TNM anatomic factors. However, the recognition of the prognostic influence of grade, hormone receptor expression, and HER2 amplification mandated their inclusion into the staging system. The value of commercially available, gene-based assays was acknowledged and prognostic input added. Tumor biomarkers and low Oncotype DX recurrence scores can alter prognosis and stage. These updates are expected to provide additional precision and flexibility to the staging system and were based on the extent of published information and analysis of large, as yet unpublished databases. The eighth edition of the AJCC TNM staging system, thus, provides a flexible platform for prognostic classification based on traditional anatomic factors, which can be modified and enhanced using patient biomarkers and multifactorial prognostic panel data. The eighth edition remains the worldwide basis for breast cancer staging and will incorporate future online updates to remain timely and relevant. CA Cancer J Clin 2017;67:290-303. © 2017 American Cancer Society.

Clostridium septicum Aortitis with Synchronous Ascending Colon and Rectal Adenocarcinoma

Introduction: Sepsis secondary to C. septicum is associated with underlying occult colorectal malignancy and has a high mortality. Case Report: A 66-year-old Puerto Rican male with no significant PMH presented with three days of generalized abdominal pain and one episode of bright red blood mixed with stool. He reported subjective fevers with chills and constipation for one month. He denied nausea, vomiting, diarrhea, pruritus, weight loss, fatigue or jaundice. There was no family history of colon cancer. The patient had normal vital signs except for a temperature 101 F. Lab results were significant for leukocytosis and microcytic anemia. An abdominal ultrasound was suggestive of right colon mass and infrarenal aortitis, confirmed on the CT scan. (Image-1 and 2). Colonoscopy revealed a 2 cm mass in the proximal ascending colon and a 5 cm rectal mass (Image-3), both suspicious for malignancy. As resection of both masses at the time of aortic surgery seemed too high risk and the right colon mass was the more likely infectious culprit based on review of literature, resection of the rectal mass was thus deferred. The patient underwent transabdominal excision of infected infra-renal abdominal aorta, proximal bilateral common iliac arteries and proximal inferior mesenteric artery, followed by reconstruction with aorto-iliac cryopreserved homograft. An extended right hemi-colectomy and end ileostomy were performed as well. Cultures from blood and aorta grew C. septicum, sensitive to ampicillin-sulbactam. The right colon mass was adenocarcinoma on pathology. The patient improved clinically and completed six weeks of antibiotics. Follow up PET CT scan revealed non-specific findings. Three months later, patient underwent transanal intramural excision of rectal mass. It was adenocarcinoma on histology but was negative for C. septicum. Patient had a low oncotype DX recurrence score and was offered but declined adjuvant chemotherapy.Figure 1Figure 2Figure 3Conclusion: This is the first case of C septicum aortitis in the setting of synchronous colon and rectal adenocarcinomas. Antibiotics, aortic reconstruction and curative resection of underlying occult colon cancer (source of infection) are the cornerstone in the treatment of C. septicum aortitis. Right-sided colon cancer is the more common location of the source of infection in the setting of C. septicum aortitis.

Utility of Oncotype DX Risk Assessment in Patients With Invasive Lobular Carcinoma

Introduction/BackgroundOncotype DX (Genomic Health, Redwood City, CA) uses reverse transcriptase polymerase chain reaction analysis to measure tumor gene expression for determining recurrence risk (RR) and guiding chemotherapy decisions for breast cancer patients. Invasive lobular carcinoma (ILC) is a histologic subtype that has not been the focus of prior studies validating Oncotype DX. The study purpose was to develop a model using histologic tumor characteristics to predict uniformly low Oncotype DX Recurrence Scores (RS) in ILC. Patients and MethodsILC cases in our pathology database with Oncotype DX testing were identified. Histologic tumor characteristics, immunohistochemical (IHC) of estrogen receptor (ER)/progesterone receptor (PgR) percent, HER2, E-cadherin expression, and Ki-67 levels were obtained for cases. Discriminant analysis was used to test the hypothesis that tumors classified as lower/higher risk based on Oncotype DX RS would differ significantly on a linear combination of variables. ResultsFrom 2006 – 2014, 158 cases of ILC having Oncotype DX testing were identified; 90 low risk (RS < 18), 66 intermediate risk (RS 18 – 30) and 2 high risk (RS > 30). Discriminant analysis showed that PgR% followed by Ki-67 provided the greatest contribution to discern low versus elevated RS. A subset of 57 cases (∼36%) with predicted probabilities > 86% for either low or high RS yielded 96.5% correct classification, 92.3% sensitivity, and 97.7% specificity. ConclusionOur analytical model may be useful in predicting lower RR in patients with ILC. If validated, this provides a faster and less expensive alternative to Oncotype DX testing in certain patients with ILC.

Use of modified Magee equations and histologic criteria to predict the Oncotype DX recurrence score

Oncotype DX (Genomic Health, Redwood City, CA, USA, current list price $4,350.00) is a multigene quantitative reverse transcription-polymerase chain reaction-based assay that estimates the risk of distant recurrence and predicts chemotherapy benefit for patients with estrogen receptor (ER)-positive breast cancers. Studies have suggested that standard histologic variables can provide similar information. Klein and Dabbs et al have shown that Oncotype DX recurrence scores can be estimated by incorporating standard histologic variables into equations (Magee equations). Using a simple modification of the Magee equation, we predict the Oncotype DX recurrence score in an independent set of 283 cases. The Pearson correlation coefficient (r) for the Oncotype DX and average modified Magee recurrence scores was 0.6644 (n=283; P<0.0001). 100% of cases with an average modified Magee recurrence score>30 (n=8) or an average modified Magee recurrence score<9 (with an available Ki-67, n=5) would have been correctly predicted to have a high or low Oncotype DX recurrence score, respectively. 86% (38/44) of cases with an average modified Magee recurrence score≤12, and 89% (34/38) of low grade tumors (NS<6) with an ER and PR≥150, and a Ki-67<10%, would have been correctly predicted to have a low Oncotype DX recurrence score. Using an algorithmic approach to eliminate high and low risk cases, between 5% and 23% of cases would potentially not have been sent by our institution for Oncotype DX testing, creating a potential cost savings between $56,550.00 and $282,750.00. The modified Magee recurrence score along with histologic criteria may be a cost-effective alternative to the Oncotype DX in risk stratifying certain breast cancer patients. The information needed is already generated by many pathology laboratories during the initial assessment of primary breast cancer, and the equations are free.

Utility of Oncotype DX risk assessment in patients with invasive lobular carcinoma (ILC).

28 Background: Oncotype DX (Genomic Health, Redwood City, CA) is a breast cancer assay that uses reverse transcriptase polymerase chain reaction (RT-PCR) to measure gene expression in paraffin-embedded tumor tissue, which correlates with recurrence risk. This test is used to guide chemotherapy decisions in patients with estrogen receptor-positive breast cancer. Invasive lobular carcinoma (ILC) is a distinct histologic subtype, inherently estrogen receptor rich, that has not been the unique focus of prior studies validating Oncotype DX. The study purpose was to determine if there are certain features of ILC that predict uniformly low Oncotype DX Recurrence Scores (RS) such that Oncotype DX testing may be unnecessary, saving patients time and financial resources. Methods: A search was conducted of all ILC cases having Oncotype DX testing in our hospital pathology database. The Oncotype DX RS, histologic tumor characteristics (including subtype and grade), immunohistochemical (IHC) analyses of estrogen receptor (ER)/progesterone receptor (PR) percent (by image analysis), E-cadherin expression, and Ki-67 levels were obtained for each case. Discriminant analysis was used to test the hypothesis that tumors classified as low or high risk based on the Oncotype DX RS would differ significantly on a linear combination of selected variables. Results: From 2006 to 2013, 158 cases of ILC having Oncotype DX testing were identified; 90 low risk (RS &lt;18), 66 intermediate risk (RS 18 – 30) and 2 high risk (RS &gt; 30). Discriminant analysis showed that PR% followed by Ki-67 provided the greatest contribution to discriminating between low versus high RS. A subset of 57 cases (~ 36%) with predicted probabilities &gt; 86% for either low or high RS yielded 96.5% correct classification, 92.3% sensitivity, and 97.7% specificity. Conclusions: Our analytical model may be useful in predicting high versus low recurrence risk in some patients with ILC. If validated, this provides a faster and less expensive alternative to Oncotype DX testing in certain patients with ILC.

Reply to E.J. Moylan et al

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-38 study was designed to determine whether gemcitabine (G) added to dose-dense paclitaxel (P) following dose-dense doxorubicin and cyclophosphamide (dose-dense AC followed by PG) would improve outcomes in women with node-positive breast cancer relative to both dose-dense AC followed by P and docetaxel (T) AC (TAC).1 Dose-dense AC followed by P had been defined as an optimal adjuvant chemotherapy regimen with a toxicity profile that allowed for the addition of G and represented the conventional control arm for B-38. However, it was recognized that if dose-dense AC followed by PG improved outcomes over dose-dense AC followed by P, questions about the activity of the regimen relative to an optimal T-based regimen would persist, so B-38 included TAC as a second control arm. Inclusion of what were perceived as two optimal adjuvant chemotherapy regimens as controls also provided the opportunity for direct comparison of the two regimens in a large phase III trial. Results showed no benefit with the addition of G and no statistical differences in efficacy between the control regimens. However, toxicity profiles differed; thus, physicians and patients can now choose an anthracycline and taxane regimen based on considerations of schedule and toxicity, not relative efficacy. As Moylan et al2 point out, there was no statistically significant difference between dose-dense therapy and TAC in the estrogen receptor (ER) –positive cohort, which supports our statement regarding these findings. The results from B-38 were analyzed and submitted for publication before results from the referenced Southwest Oncology Group (SWOG) study were reported. Clearly, the use of weekly paclitaxel is an acceptable alternative to the dose-dense schedule of four cycles of paclitaxel, but it may be associated with more neurotoxicity. The meta-analysis by Bonilla et al is not based on data from trials but from a literature review. In fact, the authors stated in the conclusion, “However, additional data from randomized controlled trials are needed before dose-dense therapy can be considered as the standard of care.”3 NSABP B-38 is one such trial, with almost 5,000 patients randomly assigned. Moylan et al express “grave concerns” about the characterization in our study of the control regimens with equivalent efficacy as optimal, inferring that we were advocating for indiscriminant use of these regimens in all patients with node-positive, ER-positive breast cancer. This was clearly not the theme of our discussion. B-38 was designed in 2002, was activated in 2004, and completed accrual in 2007. Perou et al4 first described their intrinsic breast cancer types by unsupervised hierarchical clustering analysis in 2000. The apparent utility of the Oncotype DX recurrence score assay to identify subgroups of patients with ER-positive breast cancer who did not derive benefit from chemotherapy was reported in 2006 by the NSABP in node-negative patients5,6 and by SWOG in 2009 in node-positive patients.7 As a result of these and other studies, it has been increasingly recognized that the degree of benefit a patient receives from chemotherapy depends on the molecular subtype of the tumor. As stated in our discussion, biology must be the most important consideration for the development of future trials. The era of large adjuvant trials that do not consider molecular subtypes has run its course. We agree that many patients with node-positive, ER-positive breast cancer may not require a third-generation adjuvant regimen or need chemotherapy at all. Trials such as RxSPONDER ({type:clinical-trial,attrs:{text:NCT01272037,term_id:NCT01272037}}NCT01272037), which is evaluating the role of chemotherapy in node-positive patients with low Oncotype DX recurrence scores, are needed to determine whether promising predictive markers will be able to define groups of ER-positive patients who will not benefit from chemotherapy. Conversely, we should be recruiting patients with high-risk ER-positive tumors to trials such as SWOG 1207/NSABP B-53 ({type:clinical-trial,attrs:{text:NCT01674140,term_id:NCT01674140}}NCT01674140), which is evaluating the addition of a mammalian target of rapamycin inhibitor to endocrine therapy, rather than continuing to address nuances of chemotherapy.