Low Recurrence Score Research Articles

Treatments and clinical outcomes in stage II colon cancer (CC) patients (pts) with 12-gene Oncotype DX Colon Recurrence Score assay-guided therapy: Real-world data.

3620 Background: The role of adjuvant chemotherapy (CT) in stage II CC is debated. The validated 12-gene Oncotype DX Colon Recurrence Score test provides a Recurrence Score (RS) result (range, 0-100) which estimates recurrence risk (RR) in stage II/III pts. We studied treatment and clinical outcomes in CC pts in whom treatment decisions incorporated the RS result. Methods: This prospectively designed cohort study included all stage II, MMR-P, CC pts who underwent the 12-gene Oncotype DX testing through Clalit between 1/2011 and 12/2016 and had available data with minimum 3-yr follow-up. Kaplan-Meier (KM) estimates and log-rank tests were used to compare RR and CC specific mortality (CCSM) between RS categories. Multivariable analysis (MVA) identified variables associated with RR/CCSM. Results: The analysis included 938 pts. Median age, 68 (IQR, 60-76) yrs; 96% had T3 tumors, and 89% had ≥12 nodes examined. Median RS was 26 (IQR, 19-33). The 3 RS categories (0-29, 30-40, and 41-100) included 65%, 24%, and 11% of pts, respectively. The overall CT use rate was 24%, with a significant difference between the 3 categories (14%, 36%, and 60%, respectively, P< .0001). Pts with very low RS (0-15) comprised 14% of the cohort (CT use rate, 11%). Younger pts, and those with invasion/perforation/obstruction were more likely to receive CT. Clinical outcomes with a median follow up of 6.9 (IQR, 5.5-8.6) yrs are presented (Table). Among untreated pts, KM estimates for RR and CCSM differed significantly between the 3 RS categories ( P< .0001). Outcome of untreated RS 0-15 pts was excellent. In an MVA model, male sex, presence of invasion/perforation/obstruction and higher RS category (RS 41-100 vs 0-29 and vs 30-40, but not RS 30-40 vs 0-29) were associated with increased RR. For CCSM, the results were similar, but this time age ≥70 yrs replaced sex as a significant prognostic variable. Clinical outcomes within each RS group did not differ significantly between treated and untreated pts, but were numerically better with CT in the RS 41-100 group. Conclusions: This real-world analysis showed that the RS results provide independent prognostic information in stage II CC. Further studies are needed to investigate the potential role of the RS result as a predictor of CT benefit, but the data suggest that this benefit may be limited to pts with high RS results. [Table: see text]

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 & 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 < 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 < 16, 28 patients with RS 16-25, and 16 patients with RS > 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 < 16. Conclusions: In our study, 91.3% had RS < 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 >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]

Correlation between Magee score and recurrence score in Indian patients with breast cancer.

e12555 Background: Recurrence score (RS) from Oncotype Dx (ODx) test predict chemotherapy benefit in estrogen receptor (ER) positive, and HER2-negative patients with breast cancer. ODx is an expensive test in an Indian practice setting - cost of adjuvant chemotherapy is one-sixth of the cost of the test. Magee equations use histopathological variables, and semiquantitative results from ER, PR and Ki-67, to calculate Magee score (MS) and provide a cost-effective surrogate mechanism for predicting RS. We aimed to assess the correlation between MS and RS in an Indian setting. Methods: Pathology reports were obtained from oncologists in India. Immunohistochemistry for ER and PR were reported using the Allred system. Therefore, two methods were identified to estimate H-scores - using a calculated method (A), and using an expert-approximated (B) method. MS were calculated by a single investigator blinded to the RS. MS and RS were then assessed for correlation via the Pearson correlation method. MS were arbitrarily stratified into ≤ 15, 15 - 30, and ≥ 30, and their overall agreement (OA) or concordance with RS risk categories, ≤ 15, 15 - 30, and ≥ 30, were assessed. The OA was assessed by determining the proportion of patients in similar risk categories across low, intermediate and high-risk RS and MS. Results: Among 34 patients included in the study, 38% (13) had an RS ≤ 15, 38% (13) had an RS between 15 and 30, and 23% (8) had an RS ≥ 30. Correlation coefficient between MS and RS was 0.78 for both methods of estimation (p<0.0001). The OA between MS-A and RS, and MS-B and RS were 59% (20/34) and 47% (16/34) respectively. The concordance between low-risk MS-A and RS is 78% (n=9) and between low-risk MS-B and RS is 50% (n=20). The concordance between high-risk MS-A and RS is 100% (n=2) and high-risk MS-B and RS is 100% (n=2). Conclusions: Although there is good correlation between RS and MS, the concordance between the two in similar risk categories is not optimal. Of the two methods to estimate H-score from Allred score, the calculated method seems to be more optimal. Our pilot study shows good correlation between MS and RS. We recommend that pathologists incorporate H-score as part of the reporting of ER and PR. A larger prospective study will be useful to test our hypothesis for the use of MS as a predictive tool for adjuvant chemotherapy in breast cancer.

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 < 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.

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) <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 <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 <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 <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 <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 <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<0.001). (C) 29.0% (n=1,033) of patients with pN1mi and ODX <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<0.001). (D) A benefit in OS (p=0.017) was observed in cases with RS<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 <26 is unclear. Our large registry study found the addition of chemotherapy to endocrine therapy was associated with improved survival in cases with ODX<26 involving 1-3 lymph nodes, but not in node-negative or micro-metastatic disease. Prospective trials are needed to confirm these findings.

Abstract P1-04-09: Correlating Predicted Adjuvant Therapy Benefit and Risk of Recurrence between Breast Cancer Index (BCI) and 21-gene Oncotype DX Recurrence Score (RS)

Abstract Background: The 21-gene Recurrence Score (Oncotype DX) is a genomic assay that provides prognostic information for distant recurrence risk and is predictive of adjuvant chemotherapy benefit in hormone receptor (HR)-positive, HER-2 negative early-stage breast cancer (EBC). The Breast Cancer Index (BCI) is another molecular gene expression-based assay that evaluates the utility of extending adjuvant endocrine therapy (ET) from 5 to 10 years and predicts risk of distant recurrence. In January 2021, the National Comprehensive Cancer Network (NCCN) Guidelines added BCI to guide duration of adjuvant ET as a category 2A recommendation. The goal of this study was to evaluate the association between BCI and RS in terms of their predicted benefit for adjuvant therapy and risk of distant recurrence. We also assessed the association of various anatomic and biologic tumor features with BCI. Methods: We performed a retrospective chart review of all patients with HR-positive EBC who had a BCI and Oncotype DX performed between 2007-2021. Demographics, tumor characteristics and BCI and RS results were extracted from the electronic medical record. Patients were categorized by BCI predictive of extended ET (formerly BCI high) versus not (formerly BCI low) and RS of low (0-10), intermediate (11-25) and high (26-100). Numerical values for distant recurrence risk were recorded for both BCI and Oncotype DX tests. Multivariable regression models were used to assess the relationship between BCI and Oncotype DX as well as factors associated with each. Results: We identified 153 women with HR-positive EBC with both RS and BCI performed. The median age of the population was 57 years and 25% were premenopausal. 32% (n=49) had a BCI result predictive of benefit from extended adjuvant ET. When comparing patients with BCI predictive of extended ET versus those with BCI not predictive of extended ET, there was no association between BCI and RS based on multivariate logistic regression models, p=0.7. A similar distribution of RS was observed between patients who had a BCI result predictive of benefit from extended ET versus not predictive. Among 49 patients with a BCI predictive of extended ET, 35% had high RS, 63% intermediate RS and 2% low RS. Among 104 patients with a BCI not predictive of extended ET, 24%, 73% and 3% had high, intermediate, and low RS, respectively. Multivariate regression models revealed an association between poorly differentiated tumors and BCI result predictive of extended ET, p=0.002. No associations were observed between BCI and menopausal status, ER%, PR%, tumor size or lymph node positivity. Regarding risk of recurrence, there was an association between BCI and Oncotype DX in terms of their predicted numerical risk of recurrence, p< 0.001. Higher percentage of PR positivity, poorly differentiated tumors, and lymph node positivity were associated with a higher risk of recurrence on the BCI. Conclusions: In our patient population selected to have Oncotype DX and BCI performed, we found no association between the two genomic assays in terms of their predictive benefit. However, there was an association between Oncotype DX and BCI in terms of their prognostic ability. Given the increased use of BCI since its inclusion in national guidelines, it is important to understand its relationship with other genomic assays especially when used to guide clinical decisions and estimate prognosis. Citation Format: Rima Patel, Nicole Casasanta, Zhiqiang Li, Melanie Kier, Julia Blanter, Sophie Sohval, Malin Hovstadius, Catherine Wu, Marc Fink, Xiang Zhou, Brittney Zimmerman, Krystal Cascetta, Rong Chen, William Oh, Amy Tiersten. Correlating Predicted Adjuvant Therapy Benefit and Risk of Recurrence between Breast Cancer Index (BCI) and 21-gene Oncotype DX Recurrence Score (RS) [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 P1-04-09.

Abstract P3-05-20: Low 21-Gene Recurrence Score Is Not Associated with a High Axillary Nodal Burden in Post-Menopausal Women Presenting with a Clinically Negative Axilla

Abstract Background: The predictive and prognostic value of the 21-gene recurrence score (RS) has emphasized the importance of tumor biology and minimized the credence of a limited (1-3 positive) nodal burden. The practice changing results of RxPonder demonstrated that post-menopausal women with 1-3 positive lymph nodes (pN1) and a RS of ≤25 did not necessarily benefit from adjuvant chemotherapy. Given that RS influences adjuvant therapy decision-making more significantly than nodal status, it is unclear whether axillary staging with sentinel lymph node biopsy (SLNB) has a continued role in the surgical care of post-menopausal patients otherwise presenting with early stage, clinically node negative (cN0) hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer. In this context, the de-escalation of axillary staging, especially in the presence of a low RS, is an area of active investigation. To help elucidate this further, we sought to estimate the association of RS with pathologic nodal stage. Methods: Using the 2004-2019 National Cancer Database (NCDB) Patient User File (2022 release), we evaluated the association of RS with the incidence of pN0, pN1 and pN2-3 disease. Only female patients diagnosed who were age 50 and older with HR+/HER2- invasive breast cancer were eligible, and only those presenting with cT1-T2N0 who underwent upfront surgery with a SLNB comprised our study population. Those with Oncotype DX testing performed with an available RS were included. Given the limitations within the dataset, age 50 and over was selected as a surrogate for post-menopausal status. Categorical variables were compared between RS groups (≤25 vs. >25) using chi-square tests and continuous variables were compared using t-tests. A logistic regression analysis was performed to estimate the association between RS (≤25 vs. >25) and nodal burden (pN2-3 vs pN0-1). Results: There were 151,447 patients with an invasive breast cancer diagnosis between 2015 and 2019 who met inclusion criteria. The average age at diagnosis was 64.1 (IQR 58-69) and almost 75% of tumors displayed ductal histology. There were 130,568 (86.2%) patients with a RS≤25 and 20,879 (13.8%) with a RS >25. On final pathology, 85.2% were pN0 and 14.8% were pN1-3. For those with a RS ≤25, 84.9% were pN0, 14.8% were pN1 and 0.3% were pN2-3. For those with a RS >25, 86.8% were pN0, 12.9% were pN1 and 0.3% were pN2-3. Overall, 14.5% demonstrated pN1 disease, of which 12.3% yielded a RS >25. Of the 461 patients with pN2-3 disease for whom RS was available, 12.4% (57 patients) had RS >25. After adjustment, RS >25 was associated with reduced incidence of pN2-3 compared to pN0-1 (OR=0.64, 95% CI 0.47-0.87, p=0.004). Conclusion: In this population of post-menopausal patients with cT1-T2N0, HR+/HER2- invasive breast cancer and an available RS, almost 86% displayed pN0 or pN1 disease in conjunction with a RS ≤25. Based on the current available literature, less than 5% of cT1-2N0 patients are thought to harbor >pN1 disease. These data add further support, suggesting that this patient population is unlikely to harbor a higher than limited nodal burden given a clinically negative axilla. Though less than 0.5% of the studied patient population demonstrated pN2-3 disease, an important caveat to make is that these patients would not have met criteria for RS, and it’s likely this low number reflects the absence of testing. Given that RS has not been validated for this higher nodal stage, we cannot make recommendations to omit axillary surgery in this cohort of patients. The data presented here provides further rationale for the two large prospective studies addressing whether SLNB could be eliminated in patients with otherwise small HR+/HER2- tumors which are currently ongoing. Table 1: Pathologic Nodal Staging Based on Recurrence Score Citation Format: Astrid Botty van den Bruele, Morgan Paul, Samantha M. Thomas, Sarah L. Sammons, Maggie L. DiNome, Jennifer K. Plichta, Akiko Chiba, Laura H. Rosenberger, E Shelley Hwang. Low 21-Gene Recurrence Score Is Not Associated with a High Axillary Nodal Burden in Post-Menopausal Women Presenting with a Clinically Negative Axilla [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 P3-05-20.

Abstract P2-03-06: Real world treatment of node negative low and intermediate recurrence score breast cancer

Abstract Introduction: Patients younger than 50 years old with node negative hormone receptor (HR) positive her2 negative breast cancer and oncotype Dx recurrence scores (RS) under 16 do not benefit from adjuvant chemotherapy. Those with a RS between 16-25 may have a marginal benefit from the addition of adjuvant chemotherapy, however a similar benefit may be achieved with adjuvant ovarian function suppression (OFS). The aim of this study is to describe real world treatment patterns and outcomes of premenopausal node negative patients with low and intermediate RS, with an emphasis on adjuvant OFS, endocrine therapy (ET), and menopausal status during adjuvant treatment. Methods: We retrospectively reviewed the records of all node negative patients under 50 years old who were sent for oncotype testing between 2008 and 2018. One hundred and sixty-five patients with low or intermediate RS were included in our analysis. Continuous variables were described using medians and interquartile range (IQR). Categorical variables were described as frequencies and percentages. Differences between categorical variables were analyzed with the chi squared test and survival was analyzed using the Kaplan-Meier method. The cox proportional hazards model was used to test the effect of multiple factors on survival. Breast cancer specific survival (bcss) was defined as the time to first breast cancer recurrence (local recurrence, second breast cancer, distant recurrence) and distant disease-free survival (ddfs) was defined as the time to any distant recurrence. Results: The median age was 44 (41-47) and median RS was 17 (14-20). Median follow-up time was 82 (61-108) months. One hundred and three (62.4%) patients had low clinical risk as defined in TailorX and 136 (82.4%) had intermediate RS. Fourteen (8.5%) patients with nodal micrometastases were also included. Only 5 (3%) patients received adjuvant chemotherapy and 74 (44.8%) received adjuvant OFS. Of the 91 (55%) of patients who did not received OFS, 21 (23%) went into menopause or underwent subsequent oopherectomy while on adjuvant ET. One hundred and three (62.4%) patients received adjuvant tamoxifen alone, 16 (9.7%) received an aromatase inhibitor alone, and 40 (24.2%) underwent an endocrine switch with all but 1 beginning treatment with tamoxifen. There were no significant differences in clinical risk or RS risk group between patients that received and did not receive OFS. There were 22 (13.3%) bcss recurrences. Twelve (7.2%) patients had a local recurrence, 5 (3%) patients had second breast cancers, and 5 (3%) had a distant recurrence as their first recurrence. Overall, only 6 (3.6%) patients had a distant recurrence. Both OFS and ET type were not significantly associated with bcss or ddfs. On univariate analysis menopause during ET was significantly associated with improved bcss (HR= 0.2, 95% CI 0.05-0.85), however on multivariate analysis it was no longer significant. Conclusion: With only 6 (3.6%) distant recurrences over a median follow-up of over 6.5 years node negative premenopausal women with low or intermediate RS treated in our institution show an excellent prognosis regardless of treatment type. Our results support the evidence that most of these patients do not need chemotherapy and suggests that most patients do not require OFS as well. Additional data examining the relationship between gene expression profiles and OFS benefit are needed to help guide OFS treatment in premenopausal patients who do not require chemotherapy. Citation Format: Opher Globus, Keren Levanon, Einav Nili-Gal Yam. Real world treatment of node negative low and intermediate recurrence score breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-06.

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 >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 >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 >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.

Abstract P2-23-11: Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma: an update in nearly one million cases

Abstract Background: Invasive ductal carcinoma (IDC) accounts for ~80% of all invasive breast carcinomas (IBC) with several histologic subtypes comprising the remainder of cases. Some histologic subtypes of IDC (such as tubular carcinoma) have been associated with better prognosis, while other subtypes (such as metaplastic and micropapillary) have been associated with poorer prognosis. Prior studies have shown patients with early stage, hormone-receptor positive IBC that have low Recurrence Score® (RS), as measured by the 21-gene Oncotype DX® (ODX) assay, have little benefit from chemotherapy. Here, we report our experience with the histologic subtypes of IDC and associated patterns of observed gene expression using ODX. Methods: All US samples submitted for IBC ODX between 2005 to 2021 were reviewed. Ductal carcinoma NOS (DC), tubular carcinoma (TC), cribriform carcinoma (CC), mucinous carcinoma (MUC), lobular carcinoma classic, solid or alveolar type (ILC), pleomorphic lobular carcinoma (PL), medullary/medullary-like carcinoma (MED), metaplastic carcinoma (MET), micropapillary carcinoma (MP), papillary carcinoma (PC) and solid papillary carcinoma (SPC) were included. Quantitative expression of 16 cancer-related genes was measured on a scale from 2 to 15 (relative to reference genes) where 1 unit increment is associated with ~2-fold change in expression. RS was calculated as published. Descriptive statistics for the RS, individual genes (ER, PR, HER2), and gene groups [invasion gene group (IGG) and proliferation gene group (PGG)] were obtained. Results: A total of 957,624 samples were included in this analysis with 85.4% DC, 9.7% ILC, 2.8% MUC, 0.5% TC, 0.4% PL, 0.4% PC, 0.3% MP, 0.2% CC, 0.2% MED, 0.1% SPC, and 0.02% MET. For all types, a wide continuous range of RS was noted. MET had the highest median RS, followed in decreasing order by MED, PL, DC & ILC, TC, MUC, MP, CC, SPC, and PC. ER and PR were highest among PC and SPC. ER and PR were lowest among MED and MET. HER2 was highest among PC and TC and lowest among MED and MET. IGG was highest in MET and lowest in SPC. PGG was lowest for TC and highest for MED and MET. ER+/PR-/HER2- phenotype occurred more often in MED and PL. ER-/PR+/HER2- phenotype rarely occurred, but was most frequent in MED and MET. ER+/PR+/HER2+ accounted for 0.4% of our total sample. Conclusions: Here, we demonstrate histologic subtypes of IDC have a wide continuous range of RS. ODX assay may be used to further stratify patients with IDC and its histologic subtypes; however, further studies are needed to better understand the predictive capability of ODX in the histologic subtypes. Table 1. Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma Table 2. Biomarker profile in histologic subtypes of invasive breast carcinoma Citation Format: Nhu Thuy Can, Cynthia A. Flannery, Jess Hoag, Alekhya Akkunuri, Helen Bailey, Frederick Baehner. Quantitative gene expression by RT-PCR in histologic subtypes of invasive breast carcinoma: an update in nearly one million cases [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 P2-23-11.

Abstract P2-11-31: FAVORABLE LOCOREGIONAL CONTROL IN CLINICALLY NODE-NEGATIVE HORMONE-RECEPTOR POSITIVE BREAST CANCER WITH LOW 21-GENE RECURRENCE SCORES: A SINGLE INSTITUTIONAL STUDY WITH 10-YEAR FOLLOW-UP

Abstract Background: Recent studies have shown a lower likelihood of locoregional recurrences in patients with low 21-gene recurrence score (RS). In this single institutional study, we investigated any associations between different cut-off values of 21-gene RS and histopathological factors and outcome in patients with long-term follow-up. Methods: Between February 2010 to February 2013, 61 patients with early stage clinically node-negative hormone receptor-positive and HER2-negative breast cancer tested for the 21-gene RS assay, were included into the study. The clinicopathological, treatment and outcome characteristics were analyzed. Results: Median age was 48 (range, 29-72). Of those, 53 patients were diagnosed with Stage 1 (86.9%) and 8 patients were Stage 2 (13.1%) following surgery. Patients with high histologic grade (HG), or with Ki-67>=25% were significantly more likely to have intermediate/high RS based on RS >11 and >18 (Table 1). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed local recurrences (4.9%) treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n=42), the clinicopathological characteristics including age < 40, age < 50, high histologic or nuclear grade, high Ki67-scores (>=20%, >=25%, >=30%), presence of lymphovascular invasion, luminal-A type tumor, multifocality, lymph node positivity, tumor size more than 2 cm, RS>=18 or RS>11 were not significantly found to be associated with 10-year locoregional recurrence free survival (LRRFS). However, patients with a RS >=16 have significantly shown a poorer 10-year LRRFS cpmpared to those with RS < 16 (RS < 16; 100% vs RS>=16; 75%, p=0.039, Table 2). Conclusions: These results suggest that Oncotype DX assay may be of little value in patients with high histologic grade or high Ki67 scores (>= 25%) as treatment decision criteria to determine any benefit from chemotherapy. Furthermore, patients with a RS >=16 are more likely to benefit from adjuvant chemotherapies, whereas those with a RS < 16 have an excellent outcome and local control on long term follow-up with endocrine treatment alone. Further prospective studies should be performed to validate these findings in future. Table 1. Correlation of 21-gene Recurrence Score (RS) including different cut-off values with Ki-67 scores and histopathological factors Table 2. Clinicopathologic factors and 21-gene Recurrence Score (=RS) associated with disease free survival (DFS) and locoregional recurrence free survival free survival (=LRRFS). (DFS is equal to LRRFS since none of the patients developed distant metastases) Citation Format: Cihan Uras, Neslihan Cabıoğlu, Fatma Tokat, Halil Kara, Ozlem ER, Taner Korkmaz, Nuran Bese, Umit Ince. FAVORABLE LOCOREGIONAL CONTROL IN CLINICALLY NODE-NEGATIVE HORMONE-RECEPTOR POSITIVE BREAST CANCER WITH LOW 21-GENE RECURRENCE SCORES: A SINGLE INSTITUTIONAL STUDY WITH 10-YEAR FOLLOW-UP [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 P2-11-31.

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 > 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< 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< 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 >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 P3-05-27: The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence

Abstract Background: Invasive early breast cancer (IBC) often presents with a co-existing ductal carcinoma in situ (DCIS) component, while about 5% of the cases present with an extensive (>25%) intraductal component (EIC). The presence of a DCIS component was previously shown to be associated with favorable clinico-pathological characteristics and survival outcomes. However, the association between co-existing DCIS and genomic risk of recurrence is unclear. Methods: Patients with early hormone receptor positive (HR+) HER2neu-negative (HER2-) breast cancer and known OncotypeDX breast recurrence score (RS), who underwent breast surgery in our institute, were included. A natural language processing (NLP) algorithm was used to identify co-existence of extensive DCIS (DCIS-H) and non-extensive DCIS (DCIS-L) in surgical pathological reports. Genomic risk was determined using OncotypeDX RS, while clinical risk was calculated according to the MINDACT criteria, based on tumor size and grade. The genomic and clinical risks of DCIS-H, DCIS-L and pure IBC (No-DCIS) were compared. Results: A total of 45 (5%) DCIS-H cases, 468 (56%) DCIS-L cases and 328 (39%) No-DCIS cases were identified. DCIS-H cases presented with less aggressive clinico-pathological characteristics, such as lower proportions of histologic grade III (10% vs 26% vs 21%) and lower proportions of node-positive disease (13% vs 18% vs 21%), compared to DCIS-L and No-DCIS cases, respectively. The distribution of OncotypeDX RS significantly varied between the groups. DCIS-H tumors were less likely to have a high RS and more likely to have a low or intermediate RS compared to DCIS-L and No-DCIS tumors (High RS: 4% vs 20% vs 20%, Low + intermediate RS: 96% vs 80% vs 80%, respectively; p=0.04). Additionally, the proportions of high clinical risk cases were lower in the DCIS-H group compared to the DCIS-L and No-DCIS groups (42% vs 53% vs 50%, respectively; p=0.002). Based on genomic and clinical risk and current guidelines, we found that women presented with an extensive DCIS component (DCIS-H) had a lower probability of receiving an adjuvant chemotherapy recommendation compared to women presented with a non-extensive DCIS component (DCIS-L) or pure IBC (No-DCIS) (11% vs 29% vs 25%, respectively; p=.035). No differences in disease recurrence were detected between the groups. Conclusions: Co-existing extensive DCIS in invasive early HR+Her2- breast cancer is significantly correlated with lower genomic and clinical risk of recurrence and a smaller chance for chemotherapy recommendation. The rarity of this condition (5% of cases) limited our ability to detect differences in outcomes. These findings warrant future studies of the underlying genomic landscape of co-existing extensive DCIS. Citation Format: Yael Bar, Kfir Bar, Judith Ben- Dror, Didi Feldman, Meishar Shahoha, Ahuva Weiss-Meilik, Nachum Dershowitz, Wolf Ido, Amir Sonnenblick. The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence [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 P3-05-27.

Evaluation oncotype DX® 21-gene recurrence score andclinicopathological parameters: a single institutional experience.

Oncotype DX recurrence score (RS) is a clinically validated assay, which predicts the likelihood of disease recurrence in oestrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer (BC). In this study we aimed to compare the performance of Oncotype DX against the conventional clinicopathological parameters using a large BC cohort diagnosed in a single institution. A cohort (n= 430) of ER+/HER2- BC patients who were diagnosed at the Nottingham University Hospitals NHS Trust and had Oncotype DX testing was included. Correlation with the clinicopathological and other biomarkers, including the proliferation index, was analysed. The median Oncotype DX RS was 17.5 (range=0-69). There was a significant association between high RS and grade 3 tumours. No grade 1BC or grade 2 tumours with mitosis score 1 showed high RS. Low RS was significantly associated with special tumour types where none of the patients with classical lobular or tubular carcinomas had a high RS. There was an inverse association between RS and levels of ER and progesterone receptor (PR) expression and a positive linear correlation with Ki67 labelling index. Notably, six patients who developed recurrence had an intermediate RS; however, four of these six cases (67%) were identified as high-risk disease when the conventional clinical and molecular parameters were considered. Oncotype DX RS is correlated strongly with the conventional clinicopathological parameters in BC. Some tumour features such as tumour grade, type, PR status and Ki67 index can be used as surrogate markers in certain scenarios.

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.

Multiparametric MR Imaging Radiomics Signatures for Assessing the Recurrence Risk of ER+/HER2- Breast Cancer Quantified With 21-Gene Recurrence Score.

While the Oncotype DX 21-gene recurrence score (RS) has been recommended for guiding ER+/HER2- breast cancer treatment decisions, it is limited by cost and availability. To develop a multiparametric MRI-based radiomics model for assessing ER+/HER2- breast cancer patients' 21-gene RS. Retrospective. A total of 151 patients with pathologically confirmed ER+/HER2- breast cancers, who underwent preoperative breast MR examinations and 21-gene expression assays, divided into training (n=106) and validation (n=45) cohorts. T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhancement (DCE) sequence at 1.5T or 3T. A total of 1046 radiomics features were extracted from each MRI sequence with a manual lesion segmentation method. After feature dimension reduction by the recursive feature elimination method and dataset balance by the synthetic minority oversampling technique, linear support vector machine classifier models were built to distinguish high RS (RS ≥ 26) from low RS (RS < 26) from T2WI, DWI apparent diffusion coefficient (ADC) maps, DCE and their combination (multiparametric). A model based on clinical characteristics and a fusion model combining clinical characteristics and multiparametric MRI were also built. Receiver operating characteristic (ROC) curve analysis and De Long's test with Bonferroni correction were used. A P value <0.01 was considered statistically significant. The area under the ROC curve (AUC) value of multiparametric radiomics model was 0.92, significantly higher than DCE (0.83), T2WI (0.78), and ADC (0.77) models in the training cohort. The radiomics model also achieved good performance in the validation cohort (AUC=0.77). The fusion model had significantly higher performance than the clinical model in both the training (AUC=0.92 and 0.64, respectively) and validation cohorts (AUC=0.78 and 0.62, respectively). The proposed multiparametric MRI-based radiomics models may have potential to help distinguish ER+/HER2- breast cancer patients' recurrence risk. 3. Stage 2.

Favorable locoregional control in clinically node-negative hormone-receptor positive breast cancer with low 21-gene recurrence scores: a single-institution study with 10-year follow-up

BackgroundRecent studies have shown a lower likelihood of locoregional recurrences in patients with a low 21-gene recurrence score (RS). In this single-institution study, we investigated whether there are any associations between different cutoff values of 21-gene RS, histopathological factors, and outcome in patients with long-term follow-up.MethodsThe study included 61 patients who had early-stage (I-II) clinically node-negative hormone receptor-positive and HER2-negative breast cancer and were tested with the 21-gene RS assay between February 2010 and February 2013. Demographic, clinicopathological, treatment, and outcome characteristics were analyzed.ResultsThe median age was 48 years (range, 29–72 years). Patients with high histologic grade (HG), Ki-67 ≥ 25%, or Ki-67 ≥ 30% were more likely to have intermediate/high RS (≥ 18). Based on the 21-gene RS assay, only 19 patients (31%) received adjuvant chemotherapy. At a median follow-up of 112 months, 3 patients developed locoregional recurrences (4.9%), which were treated with endocrine therapy alone. Among patients treated with endocrine treatment alone (n = 42), the following clinicopathological characteristics were not found to be significantly associated with 10-year locoregional recurrence free survival (LRRFS): age < 40 years, age < 50 years, high histological or nuclear grade, high Ki-67-scores (≥ 15%, ≥ 20%, ≥ 25%, ≥ 30%), presence of lymphovascular invasion, luminal-A type, multifocality, lymph node positivity, tumor size more than 2 cm, RS ≥ 18, and RS > 11. However, patients with RS ≥ 16 had significantly poorer 10-year LRRFS compared to those with RS < 16 (75% vs. 100%, respectively; p = 0.039).ConclusionsThe results suggest that patients with clinically node-negative disease and RS ≥ 16 are more likely to benefit from adjuvant chemotherapies. However, those with RS < 16 have an excellent outcome and local control in long-term follow-up with endocrine treatment alone.

Transcriptomic recurrence score improves recurrence prediction for surgically treated patients with intermediate-risk clear cell kidney cancer.

Risk stratification of kidney cancer patients after nephrectomy may tailor surveillance intensity and selection for adjuvant therapy. Transcriptomic approaches are effective in predicting recurrence, but whether they add value to clinicopathologic models remains unclear. Data from patients with clear cell renal cell carcinoma (ccRCC) was downloaded from The Cancer Genome Atlas. Clinicopathologic variables were used to calculate SSIGN (stage, size, grade, and necrosis) scores. The 16 gene recurrence score (RS) signature was generated using RNA-seq data. Transcriptomic risk groups were calculated using the original thresholds. SSIGN groups were divided into low, intermediate, and high risk. Disease-free status was the primary endpoint assessed. SSIGN and RS were calculated for 428 patients with non-metastatic ccRCC. SSIGN low-, intermediate-, and high-risk groups demonstrated 2.7%, 15.2%, and 27.5%, 3-year recurrence risk, respectively. On multivariable analysis, the RS was associated with disease-free status (sub-distribution hazard ratio (sHR) 1.43 per 25 RS [95% CI (1.00-1.43)], p= 0.05). By risk groups, RS further risk stratified the SSIGN intermediate-risk group (sHR 2.22 [95% CI 1.10-4.50], p= 0.03). SSIGN intermediate-risk patients with low and high RS had a 3-year recurrence rate of 8.0% and 25.2%, respectively. Within this risk group, the area under the curve (AUC) at 3 years was 0.69 for SSIGN, 0.74 for RS, and 0.78 for their combination. Transcriptomic recurrence scores improve risk prediction even when controlling for clinicopathologic factors. Utility may be best suited for intermediate-risk patients who have heterogeneous outcomes and further refinement for clinical utility is warranted.

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.

21 Gene Recurrence Score to Select for Patients with T3N0 ER+HER2- Breast Cancer Likely to Benefit with Postmastectomy Radiation

<h3>Purpose/Objective(s)</h3> Postmastectomy radiation therapy (PMRT) is an option for patients with breast cancer who have T3N0 disease treated with mastectomy. Whether there is a benefit to PMRT in this subgroup of patients is a matter of debate. The 21 gene recurrence score (RS) can be used to select for patients likely to benefit from chemotherapy. Whether the use of the RS to select for patients likely to benefit from PMRT is currently not known. The purpose of the present study is to determine if the RS can select for patients with T3N0 ER+HER2- breast cancer likely to benefit from PMRT. The hypothesis is that patients with a low RS may not benefit from PMRT. <h3>Materials/Methods</h3> This study was conducted using patients from the National Cancer Data Base (NCDB). Patients included in this study were women diagnosed with ER+HER2- breast cancer with pT3N0 disease who were treated with mastectomy. The use of neoadjuvant chemotherapy was not allowed. Overall survival was compared between all patients using the Kaplan- Meier analysis and after stratifying patients by RS. Multivariable logistic regression ascertained factors associated with PMRT use. Cox proportional hazards modeling determined variables associated with OS. <h3>Results</h3> A total of 1,807 patients met the selection criteria, of whom 1,031 (57.1%) received PMRT, and 763 (42.2%) did not receive PMRT. Among all patients, use of PMRT was associated with improved OS (5-year OS 93.9% vs 89.5%, p=0.0079). After stratifying patients by RS, no OS difference was observed with the use of PMRT amongst patients with a low RS (5-year OS 95.0% vs 92.2%, p = 0.0941), whereas amongst patients with an intermediate/ high RS, improvement with the use of PMRT was observed (5-year OS 93.4% vs 88.5%, p = 0.0375). Factors predictive of PMRT use include use of chemotherapy and receipt of treatment at a nonacademic facility. On multivariate analysis, factors predictive of worse OS include increasing age, Charlson Deyo Comorbidity score ≥ 2, and omission of PMRT. <h3>Conclusion</h3> PMRT may have limited benefit in patients with ER+HER2- T3N0 breast cancer with a low RS. However, PMRT was associated with an OS benefit in these patients who had a high RS. Further research is required to confirm these findings and to determine the ability of the RS to select for patients most likely to benefit from PMRT.