Oncotype DX Breast Recurrence Score Research Articles

Discordance in Oncotype DX Breast Recurrence Score® Results for Bilateral Breast Cancer.

The Oncotype DX Breast Recurrence Score® assay is a clinically useful tool to determine the benefit of chemotherapy in the treatment of early-stage, hormone-receptor-positive breast cancer. Bilateral breast cancer (BBC) is found in ~ 5% of patients with breast cancer, and data regarding discordance of Oncotype DX results between BBC defined by current TAILORx subgroups are limited. Our goals are to study the rate of Oncotype DX discordance between BBC and investigate whether such differences can affect chemotherapy treatment discussions. Patients with BBC were identified in US samples submitted to Genomic Health for 21-gene testing between January 2019 and July 2020. The risk categories were defined as 0-25 and 26-100 as well as 0-17, 18-30, and 31-100 for all patients. Subgroup analysis was also performed for node-negative women age ≤ 50 years with Recurrence Score results of 0-15, 16-20, 21-25, and 26-100. 944 BBC patients with known nodal status (702 node negative, 242 node positive) were identified and included. Among node-negative patients aged > 50 years, the rate of discordance in Recurrence Score by group (0-25 and 26-100) was 4.2% (n = 598). For node-negative patients aged ≤ 50 years, the risk group was discordant in < 3% when considering the risk grouping of 0-25 and 26-100. However, upon subgroup analysis based on TAILORx analysis, the rate of discordance was 48.1% in these younger patients (n = 104). This study shows that a clinically relevant rate of discordance in Oncotype DX results in patients with BBC may impact medical decision-making regarding chemotherapy.

ASO Visual Abstract: Discordance in Oncotype DX Breast Recurrence Score® Results for Bilateral Breast Cancer

ASO Visual Abstract: Discordance in Oncotype DX Breast Recurrence Score® Results for Bilateral Breast Cancer

Association between estrogen receptor status and Oncotype Dx breast recurrence score.

e12519 Background: The 21 gene assay Oncotype Dx Breast Recurrence Score (RS) is currently the standard of care to determine if adjuvant chemotherapy is needed in early stage node negative, hormone receptor positive, HER-2 negative breast cancer. In current American society of clinical oncology (ASCO) guidelines there is little or no benefit of adjuvant chemotherapy in patients older than 50 years whose tumors have Oncotype DX RS &lt;26, and for patients 50 years or less whose tumors have Oncotype DX RS &lt;16. We sought to evaluate the percentage of estrogen receptor (ER) expression as a surrogate measure of determining adjuvant chemotherapy by examining the relationship between ER expression and RS. Methods: We identified 301 patients from years 2015 to 2019 from our cancer registry with early stage hormone receptor positive breast cancer and had oncotype DX testing performed. We divided patients into three groups: Group 1 (ERG1) with ER &lt;10%; Group 2 (ERG2) with ER 10-49%; and Group 3 (ERG3) with ER equal or &gt;50%. We also collected information on tumor size (cm), tumor grade, Nottingham score, and ki-67 percentage. A sub-group analysis was performed for patients &lt; 50 years age (n=30). We compared all continuous variables across ER groups using the Kruskal-Wallis rank test and individual between group comparisons using the Wilcoxon rank sum test. All statistical tests performed utilized a two-tailed p value of &lt;0.05 with the Bonferroni correction for multiple comparisons. Results: Among 301 patients with early stage hormone receptor positive breast cancer, 89.1% were ductal, 7.9% lobular, and 2.9% mixed histology. Median age was 68, 58 and 66 for ERG1, ERG2, and ERG3, respectively (p = 0.41). Median RS was 36 (ERG1), 23 (ERG2), and 16 (ERG3) (p = 0.78 for ERG1 vs. ERG2; p = 0.01 for ERG1 vs. ERG3). As expected, tumor grade, tumor size, and Nottingham score decreased significantly from ERG1 to ERG3. For patients &lt;50 years, median age was 44, 46 and 45 for ERG1, ERG2, and ERG3, respectively (p = 0.75). Median RS was 10 (ERG1), 24 (ERG2) and 18 (ERG3) (p = 0.04 for ERG1 vs. ERG2; p = 0.17 for ERG1 vs. ERG3). Conclusions: We found a significant association between estrogen receptor levels and Oncotype Dx recurrence score (RS) in patients with early stage hormone receptor positive breast cancer patients. Further studies are needed to determine the predictive ability of hormone receptor levels on the outcomes of patients treated for early stage hormone receptor positive breast cancer.

Racial disparity in OncotypeDX score in early stage, hormone receptor positive, HER-2 negative, node negative breast cancers: A systemic review and meta-analysis.

e12555 Background: Oncotype DX Breast Recurrence Score (RS) is the currently used risk-assessment tool for early-stage, hormone receptor-positive, HER-2 negative, node-negative breast cancer in the US. Studies showed inconsistency in RS distribution and treatment among races. Causes may include variations in somatic mutations like Ki-67, which have been reported to express higher in African American (AA) and Asian populations than in Non-Hispanic White (NHW) population, germline mutations in BRCA and TP53, that are not in the RS algorithm, and financial burden of the testing. We analyzed data from different countries to investigate racial disparity in RS. Methods: We searched Medline, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, indexed from January 2010 to January 2021. More than 85% of studies were conducted in the pre-TAILORx study phase. To include data that are available and better represent different races, we included studies that used the previous cutoff value, low-risk ( &lt; 18), intermediate-risk (18-30), high-risk ( &gt; 30). Retrospective studies using Surveillance, Epidemiology, and End Results or National Cancer Database were excluded to avoid overlap data. A total of 17 studies, 9789 patients from seven countries (US, Japan, China, Taiwan, Kuwait, UAE, Israel) were pooled. The Odds Ratio (OR) was extracted with a 95% confidence interval (CI) for RS distribution and post-RS treatment. Both fixed-effect and random-effect meta-analysis were performed. Results: Among AA and NHW, AA were 1.7 times more likely to have high recurrence score (OR = 1.75; 95% CI = 1.46 - 2.10; P &lt; 0.0001), with no heterogeneity among studies (I2 = 0%, heterogeneity P = 0.59). Asian were 1.59 more likely than NHW to be high-risk using a random effects model (OR = 1.59; 95% CI = 1.06 - 2.40; P = 0.0259). High-risk Asian were two times more likely to receive adjuvant chemotherapy post-RS comparing to NHW (OR: 2.31, CI: 1.07 - 4.98, fixed effect model; OR: 2.85, CI: 0.48, 17.05, random effects model), while high-risk AA were less likely to receive chemotherapy comparing to NHW (OR: 0.74, CI: 0.54-1.01, fixed effect model; OR: 0.73, CI: 0.54-0.99, random effects model). Intermediate-risk Asian and AA were more likely to receive chemotherapy compared to NHW (Asian to NHW; OR: 1.68, CI: 1.16-2.43, with fixed effect model, OR: 1.68, CI: 0.94-3.02, with random effects model; AA to NHW; OR: 1.16, CI: 0.93-1.46 with fixed effect model; OR: 1.06, CI: 0.62-1.79 with random effect model). Conclusions: We identified racial disparity in RS and post-RS treatment. Future research is required to elucidate the causes for AA and Asian receiving higher recurrence scores, a need for tailoring RS cutoffs for different races, and the utilization in adequate post-RS treatment.

Cost-effectiveness of the Oncotype DX Breast Recurrence Score test in postmenopausal women with node-positive early breast cancer based on the RxPONDER trial.

534 Background: The Oncotype DX test is a predictive and prognostic multigene assay used to guide adjuvant chemotherapy in HR+/HER2- early breast cancer. The ability of the Oncotype DX test to predict the benefit of chemotherapy in node-positive early breast cancer was demonstrated in SWOG-8814. This evidence, in combination with findings from a bespoke analysis of the TransATAC study, informed an economic evaluation of the Oncotype DX test by the National Institute for Health and Care Excellence in the UK. This study examined the impact of new evidence from the RxPONDER trial on the cost-effectiveness of the Oncotype DX test in postmenopausal women with node-positive early breast cancer. Methods: The cost-effectiveness of the Oncotype DX test compared to clinical risk tools only in postmenopausal HR+/HER2- early breast cancer was estimated using a model in Microsoft Excel. The pre-RxPONDER analysis using the old cut points (RS 0-17, RS 18-30, RS 31-100) was informed by TransATAC and SWOG-8814. The model was updated with 5-year probability of distant recurrence as first site estimates based on new RS cut points (RS 0-25, RS 26-100) from RxPONDER. The impact on incremental lifetime costs and quality-adjusted life-years (QALYs) gained was examined based on the list price for the Oncotype DX test in the UK. Results: The impact of adding data from RxPONDER into the cost-effectiveness analysis is summarized in the table below. Conclusions: The RxPONDER trial demonstrated that the addition of chemotherapy to endocrine therapy had no benefit for distant recurrence in postmenopausal women with RS 0-25, regardless of clinical features, which suggests that most patients with 1-3 positive nodes can be safely spared adjuvant chemotherapy. In the model this was reflected in reduced cost of chemotherapy and higher QALYs from avoiding short and long-term adverse effects of chemotherapy. Targeted chemotherapy of a minority (17%) of patients with RS 26-100 reduced the cost of distant recurrence and improved survival based on the model results. RxPONDER provides direct evidence to inform the probability of distant recurrence with endocrine and chemo-endocrine therapy, whilst previous models have had to synthesize multiple sources of DRFI and chemotherapy treatment effect. Future studies should examine the impact of the RxPONDER findings on chemotherapy treatment decision-making in routine clinical practice.[Table: see text]

PONDx: real-life utilization and decision impact of the 21-gene assay on clinical practice in Italy

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS® results in Italy and its impact on treatment decisions. Physicians’ treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2− early BC population studied (N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.

60P Real-life use of Oncotype DX Breast Recurrence Score® test for the management of patients with node-negative and node-positive breast cancer in the autonomous community of Galicia (Spain)

Oncotype DX® is a 21-gene assay to guide adjuvant treatment decisions in HR+, HER2- early stage breast cancer. The aim of the study was to evaluate the impact of Recurrence Score® (RS) on decision-making (% change in treatment recommendation), to assess real-life utilization of Oncotype DX test in node-negative, micrometastases, and 1-3 positive lymph nodes patients.

56P The impact of tumour detection method on genomic and clinical risk and chemotherapy recommendation in early hormone receptor positive breast cancer

Symptomatic breast cancers share aggressive clinico-pathological characteristics compared to screen-detected breast cancers. The decision to administer adjuvant chemotherapy for early hormone receptor positive (HR+) HER-2 negative (HER2-) breast cancer patients, is guided by both the genomic and the clinical risk of disease recurrence. We assessed the association between the method of cancer detection and genomic and clinical risk, and its effect on adjuvant chemotherapy recommendation. Patients with early HR+ HER2- breast cancer, and known OncotypeDX Breast Recurrence Score (RS) test were included. A natural language processing (NLP) algorithm was used to identify the method of cancer detection. The clinical and genomic risks of symptomatic and screen-detected tumors were compared. The NLP algorithm identified the method of detection of 401 patients, with 216 (54%) diagnosed by routine screening, and the remainder secondary to symptoms. The distribution of OncotypeDX RS varied between the groups. In the symptomatic group there were lower proportions of low RS (13 vs 23%) and higher proportions of high RS (24 vs. 13%) compared to the screen-detected group (p=.03). Symptomatic tumors were significantly more likely to have a high clinical risk (59 vs 40%; p<.0001). Based on genomic and clinical risk and current guidelines, we found that women aged 50 and under, with symptomatic cancer, had an increased probability of receiving adjuvant chemotherapy recommendation compared to women with screen-detected cancers (57 vs. 35%; p=.03). We demonstrated an association between the method of cancer detection and both genomic and clinical risk. Symptomatic breast cancer, especially in young women, remains a poor prognostic factor that should be taken into account when evaluating patient prognosis and determining adjuvant treatment plans.

Multigene tests for breast cancer: the physician's perspective.

Breast cancer is the most common tumour in women and the first cause of death for cancer in the female population. Preserving the quality of life has therefore become an important objective in the management of the disease. The benefits of adjuvant chemotherapy in patients with HR+ HER2- early breast cancer should always be balanced against its potential short and long-term adverse effects, and identifying the appropriate patients for whom chemotherapy can offer the highest clinical benefit is critical. Besides clinical and pathological factors, today four multigene tests able to guide the choice of the adjuvant therapy early breast cancer are available in Italy: Oncotype DX®, EndoPredict®, MammaPrint® e Prosigna®. This review evaluates the main characteristics of these diagnostic tests, the studies on clinical utility, their economic impact and their inclusion in international and national guidelines. The Oncotype DX Breast Recurrence Score® test is the only multigene test validated, with level IA evidence, to guide the adjuvant therapy decisions: hormone therapy alone for most patients with RS results 0–25, and chemotherapy for patients with RS results 26–100. Clinical data demonstrate that the Oncotype DX test is able to significantly impact therapeutic decisions, reducing chemotherapy use up to 49% and supporting the use of chemotherapy (up to 12%) in potentially under-treated patients. Based on the level of clinical evidence and established clinical utility, several multigene tests have been included in the main international guidelines, with recommendations ranging from “strong” to “moderate”.

Abstract PS5-37: The feasibility of obtaining oncotype DX breast recurrence score® results from metastatic sites of patients with hormone receptor positive metastatic breast cancer

Abstract Background: Identifying when to start CDK4/6 inhibitors or use chemotherapy in hormone receptor positive (HR+) metastatic breast cancer (MBC) remains challenging. The 21-gene Oncotype DX Breast Recurrence Score® test is validated to predict chemotherapy benefit in early stage HR+ breast cancer but has not been studied for use in the MBC setting.Objective: To assess the feasibility of obtaining Recurrence Scores from metastatic sites after standard of care biopsy in HR+, HER2 negative patients and correlate Recurrence Score results from matched primary breast cancer when available. Methods: A total of 48 metastatic biopsies were retrieved retrospectively from the residual tissue of patients with primary HR+, HER2 negative breast cancer. This included 36 from bone and 12 from other sites [liver (7), lung (1), rectum (1), brain (1), skin (2)]. Slides were sent to Genomic Health Inc. for RNA isolation and Recurrence Score result determination using standardized protocols. Recurrence Score results were available for 18 matched primary and metastatic biopsy samples. The percent success rate for Recurrence Score result was determined for the various metastatic sites and results compared between matched primary and metastatic site. Results: Recurrence Score results were obtained in 48% of metastatic biopsies (23 of 48 samples) including bone (17), liver (4), lung (1), and skin (1). Reasons for Recurrence Score failure included insufficient RNA (17), poor quality RNA (1), failed QC (4), and other (3). The mean Recurrence Score from the 23 metastatic sites was 35 (range: 1–66). Notably, 70% (16/23) of successful metastatic biopsies yielded Recurrence Scores in the high-risk range (&amp;gt;25). None of the 23 metastatic biopsies gained HER2 by RT-PCR. Among the 18 paired samples, higher recurrence score results were observed in all but three of the metastatic biopsy samples with mean Recurrence Score results of 20 (range 7 to 41) for the primary and 35 (range 1-66) for the metastatic site. For paired samples, 72% of metastatic biopsies yielded Recurrence Scores &amp;gt;25 compared to 17% of primary sample. Primary Recurrence Scores were not predictive of metastatic scores (r2=0.052). Estrogen receptor (ER) expression status was conserved in 87% whereas progesterone receptor (PR) was lost in 69% of the metastatic lesion. Among the pairs, 5 had de novo metastatic disease. In these, the Recurrence Score was higher in the metastatic biopsy in each case compared to the matched primary (mean 36 versus 23, respectively). Among de novo cases, there was 100% concordance in ER positive and HER2 negative expression and only 60% concordance in PR expression between primary and metastatic sites. Conclusion: Using standard of care metastatic biopsy samples, a Recurrence Score result was successfully generated in 48% of samples including bone. This small series demonstrates wide variability in Recurrence Score results in metastatic disease with overall higher scores, common loss of PR, and minimal correlation to matched primary disease. Further examination of the potential significance of the Recurrence Score for treatment decisions in the metastatic setting requires additional tissue sampling during biopsy as insufficient RNA was the primary reason for failure. Citation Format: Julie Anne L Gemmill, Patricia Thompson, Rebecca Batiste, Caterina Vacchi-Suzzi, Christina Preece, Jules Cohen, Lea Baer, Carolyn Mies, Michelle Turner, Christy A Russell, Alison Stopeck. The feasibility of obtaining oncotype DX breast recurrence score® results from metastatic sites of patients with hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-37.

Abstract PD4-03: Can genomic profiling eliminate the need for SLNB in ER positive, T1-2 breast cancer?

Abstract Background: As tumor biology has taken precedence over anatomic staging, NCCN guidelines now allow for genomic profiling to make adjuvant treatment recommendations for Nmi-N1 breast cancer (BC). This makes nodal status, determined by sentinel lymph node biopsy (SLNB), less influential. Although generally safe, SLNB adds an incision, operative time, monetary costs, and carries risks of chronic paresthesia (9%) or lymphedema (2-6%). We hypothesized that, if ultrasound (US) excludes occult nodal metastasis and genomic profiling is used in making chemotherapy recommendations for N0-N1 disease, SLNB will be the sole indicator of a need for chemotherapy in &amp;lt;5% of patients. Methods: This was a retrospective data and tissue analysis of patients treated at our breast center (11/2011 – 12/2015). Postmenopausal women with ER positive, HER2 negative, pT1-2 BC with non-suspicious axillary US who underwent SLNB without preoperative chemotherapy were included. For each patient, we compared recommended adjuvant therapy (per NCCN guidelines) based on SLNB results, versus the recommendation had SLNB been negative. For N0-N1 cases, we used Oncotype DX Breast Recurrence Score® test to determine chemotherapy. For Nmi-N1 cases, chemotherapy was considered for Recurrence Score® (RS) 18-25 and recommended for RS &amp;gt; 25. When not in the electronic medical record (EMR), RS result was obtained from stored specimens, with patient consent. Patients without a RS result were excluded from the chemotherapy outcomes analysis. Results: Of 217 included patients, nodal status was as follows: N0, n=184 (85%); Nmi-N1, n=29 (13%); N2-3, n=4 (2%). Therefore, in 85% of patients SLNB did not influence any adjuvant treatment recommendation. In 4.1% of patients, SLNB resulted in a recommendation for axillary lymph node dissection (Table). In 15.2% of patients (n=33), SLNB resulted in a consideration (13.4%) or recommendation for (1.8%) nodal irradiation. RS result was available in 147 patients (68% of cohort). However, only 8 of those with unknown RS result (4% of cohort) were node-positive; for node-negative patients, RS would not affect any study outcome (change in treatment based on SLNB). Among patients with RS result, based on actual SLNB result, chemotherapy was recommended or considered in 30 patients. In 23 of these, chemotherapy would have been recommended regardless of SLNB result based on RS &amp;gt; 25. Therefore, SLNB made a difference in whether to recommend or consider chemotherapy in 4.7% of patients (7/147). Conclusions: SLNB changed the recommendation whether to receive chemotherapy (no to yes, or no to consider) in only 4.7% of patients. More often, SLNB influenced the chemotherapy regimen recommended (2nd vs. 3rd generation), or local therapy recommendations. With increasing role for genomic profiling, the role of SLNB in determining adjuvant therapy is diminishing. When chemotherapy would not be considered, omission of SLNB may be considered in postmenopausal patients with ER positive, T1-2 BC and negative axillary US. If genomic profiling were performed prior to surgery, the results could change surgical management. In women with RS 0-11, SLNB is highly unlikely to alter the recommendation against chemotherapy. In women with RS &amp;gt; 25, chemotherapy is recommended regardless of SLN status, but a positive SLN would affect the regimen recommended. SLNB is most influential in patients with RS 18-25. Use of genomic profiling preoperatively to tailor whether SLNB is performed should be prospectively validated. Table. Comparison of adjuvant treatment recommendations based on SLNB result vs. presumed negative SLNBBased on presumed negative SLNBBased on actual SLNB result% for whom SLNB would change treatment recommendation8Axillary lymph node dissection recommended1094.1% (9/217)Nodal irradiation recommended2041.8% (4/217)Nodal irradiation considered302913.4% (29/217)Chemotherapy recommended423240.6% (1/147)Chemotherapy considered5064.1% (6/147)Third-generation chemotherapy recommended6064.1% (6/147)Third-generation chemotherapy considered7064.1% (6/147)1)For &amp;gt;2 positive SLN, or gross extranodal extension (ENE). Since surgeon determination of gross ENE was not consistently available, &amp;gt; 2 mm of ENE on pathology was used to defined “gross” extension. 2)For N2-3 disease 3)For Nmi-N1 disease 4)For RS &amp;gt; 25, or N2-3 5)For Nmi-N1 disease, with RS 18-25 6)For Nmi-N1 disease with RS &amp;gt; 25; or N2-3; this group is a subset of those for whom chemotherapy would be recommended 7)For Nmi-N1 disease with RS 18-25; this group is a subset of those for whom chemotherapy would be recommended 8)Patients without Recurrence Score result were excluded from analysis of chemotherapy outcomes; fractions are included to show the denominator used for each calculation. Citation Format: Rubie Sue Jackson, Elaine Lee, Carol Tweed, Charles Mylander, Laura Martino, Martin Rosman, Kip Waite, Nicholas Huerta, Lorraine Tafra. Can genomic profiling eliminate the need for SLNB in ER positive, T1-2 breast cancer? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-03.

Association of Race/Ethnicity and the 21-Gene Recurrence Score With Breast Cancer–Specific Mortality Among US Women

Given the widespread use of the 21-gene recurrence score for identifying candidates for adjuvant chemotherapy, it is important to examine the performance of the Oncotype DX Breast Recurrence Score test in diverse patient populations to validate this approach for tailoring treatment in women in racial/ethnic minority groups. To examine whether breast cancer-specific mortality for women with hormone-dependent breast cancer differs by race/ethnicity across risk categories defined by the Oncotype DX Breast Recurrence Score test and whether the prognostic accuracy of the 21-gene recurrence score differs by race/ethnicity. This retrospective, population-based cohort study used the Surveillance, Epidemiology, and End Results Oncotype DX 2004-2015 database to obtain breast cancer-specific survival data on US women 18 years and older who were diagnosed with first primary stage I to III, estrogen receptor-positive breast cancer between January 1, 2004, and December 31, 2015, and had tumor testing through the Genomic Health Clinical Laboratory. Data were analyzed from April 20 to September 27, 2020. The primary outcome was breast cancer-specific mortality among women from different racial/ethnic groups stratified by the 21-gene recurrence score risk categories. Secondary analyses compared the prognostic accuracy of the recurrence score among the different racial/ethnic groups. A total of 86 033 patients with breast cancer (mean [SD] age, 57.6 [10.6] years) with Oncotype DX Breast Recurrence Score test information were available for the analysis, including 64 069 non-Hispanic White women (74.4%), 6719 non-Hispanic Black women (7.8%), 7944 Hispanic women (9.2%), 6950 Asian/Pacific Islander women (8.0%), and 351 American Indian/Alaska Native women (0.4%). Black women were significantly more likely than non-Hispanic White women to have a recurrence score greater than 25 (17.7% vs 13.7%; P < .001). Among women with axillary node-negative tumors, competing risk models adjusted for age, tumor characteristics, and treatment found higher breast cancer-specific mortality for Black compared with non-Hispanic White women within each recurrence score risk stratum, with subdistribution hazard ratios of 2.54 (95% CI, 1.44-4.50) for Black women with recurrence scores of 0 to 10, 1.64 (95% CI, 1.23-2.18) for Black women with recurrence scores of 11 to 25, and 1.48 (95% CI, 1.10-1.98) for Black women with scores greater than 25. The prognostic accuracy of the recurrence score was significantly lower for Black women, with a C index of 0.656 (95% CI, 0.592-0.720) compared with 0.700 (95% CI, 0.677-0.722) (P = .002) for non-Hispanic Whites. In this cohort study, Black women in the US were more likely to have a high-risk recurrence score and to die of axillary node-negative breast cancer compared with non-Hispanic White women with comparable recurrence scores. The Oncotype DX Breast Recurrence Score test has lower prognostic accuracy in Black women, suggesting that genomic assays used to identify candidates for adjuvant chemotherapy may require model calibration in populations with greater racial/ethnic diversity.

Selection of neoadjuvant treatment based on the 21-GENE test results in luminal breast cancer

Neoadjuvant chemotherapy (NAC) is an optimal option in early breast cancer, but in ER-positive/HER2-negative (luminal) is still controversial, although a survival benefit has recently been observed when a histological response by Symmans’ method type 0 or I is achieved. The 21-gene Oncotype DX Breast Recurrence Score® assay (Oncotype DX®) is a validated test to assess the survival benefit of adjuvant chemotherapy in these patients but its role in the neoadjuvant setting is less established. We analyzed the results of the Oncotype DX® test in a cohort of 122 consecutive patients selected to receive NAC based on classical clinicopathological parameters and the correlation between the Oncotype DX® results and the pathological response assessed by Symmans’ method. Median age was 56.5 (range 31–84) years. Initial tumor size was T1 (<20 mm) in 46 patients (37.7%), 57 (46.7%) had a T2 tumor (20–50 mm), and 19 (15.6%) had a tumor size more than 50 mm. 59 (48.4%) had axillary node involvement. The median expression estrogen and progesteron receptors by immunohistochemistry was 280 and 120 respectively and median Ki67 index was 28%. The Recurrence Score (RS) results were <11 in 21 patients (17.2%) patients, RS 11 to 25 in 58 (47.5%), and RS > 25 in 43 (35.2%). Considering the Oncotype DX test results, neoadjuvant chemotherapy was administered to 60 patients (49%), 11 (9%) received adjuvant chemotherapy and 51 (42%) no chemotherapy. Testing with the assay has therefore led to 42% fewer chemotherapy treatments. Among 60 patients receiving NAC, pathologic response was achieved for 5 patients (8.3%) with RCB-0 and 15 RCB-1 (25%). We did not find any pathological response RCB-0 and RCB-I in the 20 patients who received NAC and had a Recurrence Score result <21 for the premenopausal group, or a RS result <25 for the postmenopausal group. For patients with highest Recurrence Score results (RS > 21 or 25 according to menopausal status) it was 12% (5/40) RCB-0 and 40% (16/40) RCB-I. ConclusionsThe Oncotype DX test could be a useful tool to select patients candidates for neoadjuvant chemotherapy in luminal breast cancer. Neoadjuvant chemotherapy could be avoided in 42% of patients. We found a correlation between Recurrence Score results and pathological response with 14% of RCB-0 and a total of 47% of significant pathological response type RCB-0 and RCB-I in patients with highest Recurrence Score results. Interestingly, patients with a Recurrence Score result inferior to 32 did not get any histological response type 0 and only 5% RCB-I.

Oncotype DX Breast Recurrence Score Distribution and Chemotherapy Benefit Among Women of Different Age Groups With HR-Positive, HER2-Negative, Node-Negative Breast Cancer in the SEER Database.

Objective: To explore the distribution of Oncotype DX Breast Recurrence Score (RS), the proportion of receiving chemotherapy, and the relationship between RS and chemotherapy benefit according to detailed age groups in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-negative (HR+/HER2−/N0) breast cancer.Methods: This was an extensive, comprehensive, population-based retrospective study. Data on individuals with breast cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program. The cohort was divided into five groups by age (≤ 35, 36–50, 51–65, 66–80, >80 years). RS distribution and chemotherapy proportion among different age groups were analyzed, and the overall survivals between patients receiving chemotherapy and those not/unknown were compared in each age group.Results: The study cohort comprised 49,539 patients and the largest age group was 51–65 years. The percentage of patients with low-risk RS (0–10) increased with age, whereas those with intermediate-risk RS (11–25) decreased with age (except for the group of 36–50 years, which had the highest rate of intermediate-risk RS). The age group ≤35 years has the greatest rate of high-risk RS (26–100). The proportion of receiving chemotherapy decreased with age in all RS risk categories. Overall survival was benefited by chemotherapy only in the age group of 66–80 years with intermediate- and high-risk RS, and chemotherapy seemed to do more harm than good for patients older than 80 years.Conclusions: In the present study, we identified the distribution of RS, the proportion of receiving chemotherapy, and the relationship between RS and chemotherapy benefit according to a detailed age grouping for women with HR+/HER2−/N0 breast cancer, which may help in making individualized clinical decisions.

Oncotype DX Breast Recurrence Score®: A Review of its Use in Early-Stage Breast Cancer.

Oncotype DX Breast Recurrence Score® is a 21-gene prognostic and predictive assay indicated for use in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node (LN)-negative or up to three LN-positive, early-stage breast cancer. The assay is used worldwide and is conducted at a CLIA-certified central laboratory in the USA. The 21-gene assay generates a Recurrence Score for each tumour sample, based on expression levels of 16 breast cancer-related genes, normalized to five reference genes. The Recurrence Score is a continuous variable that provides an individualized estimate of 9-year distant recurrence risk and the likelihood of adjuvant chemotherapy benefit. The 21-gene Recurrence Score assay is extensively validated in clinical studies, which are well supported by real-world registry studies. The assay informs treatment decisions and reduces adjuvant chemotherapy use in routine clinical practices, and is estimated to be cost-effective. The 21-gene Recurrence Score assay is included in all major international treatment guidelines. Currently, it is the only multigene assay validated for prediction of chemotherapy benefit, as well as for prognosis.

13. ASSESSING THE ONCOTYPE DX BREAST RECURRENCE SCORE ASSAY ON CORE BIOPSY TO PREDICT RESPONSE TO NEOADJUVANT TREATMENT IN PATIENTS WITH BREAST CANCER - A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: The Oncotype DX breast recurrence score (RS) has been validated to predict the benefits of adjuvant chemotherapy in patients with oestrogen receptor (ER)-positive, HER2-negative breast cancer. The use of Oncotype DX for predicting chemosensitivity in the neoadjuvant setting is not well established. This systematic review aimed to determine if RS performed on core needle biopsy at diagnosis predicted complete pathological response (PCR) to neoadjuvant chemotherapy (NACT) in patients with invasive breast cancer.

Statistical machine learning model to predict Oncotype DX risk category in women over age 50.

524 Background: The 21-gene Oncotype DX Breast Recurrence Score multigene assay (RS) identifies women with ER positive, HER negative, axillary node-negative breast cancer (BC) for whom chemotherapy provides no invasive disease-free survival benefit compared to endocrine therapy alone. International adoption of RS testing is limited by cost and resource availability. We created a supervised statistical machine learning model using standard clinicopathologic data to predict RS risk category in women &gt; 50 years old. Methods: From 2012 to 2018, women with ER positive, HER2 negative, pathologically node-negative BC of all ages were retrospectively identified from a prospective institutional database. Standard clinicopathologic data and RS were collected. Per institutional protocol, RS are ordered for all early-stage, ER positive tumors &gt; 5 mm. Data were randomly split into training (n=3755) and validation sets (n=1609). A random forest model with 500 trees was developed on the training set, then evaluated on the validation set. Model predictors included age, tumor size, histologic subtype, hormone receptor status, lymphovascular invasion, and overall grade. The model was used to predict RS category (low risk: RS ≤ 25, high risk: RS &gt; 25) in women &gt; 50 years old. Results: 5364 unique tumors in 5189 women were identified. 3731 (70%) of tumors were identified in women &gt; 50 years; median age was 63 years (IQR 57-69). In women &gt; 50, median tumor size was 12 mm (IQR 9-17). Most tumors were invasive ductal (79%), low or intermediate grade (79%), and LVI was absent in 82% of tumors. Median ER staining by IHC was 95%; 28% of tumors had negative or weakly positive PR staining (1-20%). The model correctly classified 96.8% of patients as low risk (95% CI: 95.7-97.7). Negative predictive value for identifying low risk category was also high (92.3%, 90.7-93.6). Sensitivity for identifying high-risk women was 44.7% (37.4-52.1) and positive predictive value was 67.2% (58.2-75.3). A classification table on the validation set includes tumors with complete data available, including predictors and RS. Conclusions: Our model was highly specific (96.8%) for identifying women &gt; 50 with RS ≤ 25 who do not benefit from adjuvant chemotherapy. This model may be utilized in lieu of RS testing if cost and availability are prohibitive. True RS &gt; 25 was not as well predicted. The model will be refined following pathologic review of discordant cases to reduce false negatives. [Table: see text]

Practice-changing use of the 21-gene oncotype DX breast recurrence score test in Latin American hospitals.

e12539 Background: The 21-gene test is clinically validated to predict chemotherapy (CT) benefit in node-negative (N0) and node-positive (up to 3 axillary nodes, N+) HR+, HER2− early-stage breast cancer (ESBC). TAILORx showed no CT benefit overall in N0 patients with RS 0-25, but younger patients with RS 16-25 might have some. Clinical guidelines worldwide incorporate the 21-gene test; still, the impact of the test on treatment decisions is unclear in Latin America, where patients often present younger and with more advanced disease. We present a physician survey of the impact of Recurrence Score results on treatment decisions in clinical practice in Latin America. Methods: This multicenter, non-therapeutic, prospective survey enrolled consecutive patients who had 21-gene testing during routine care at 14 community and academic sites in Argentina, Colombia, Mexico, and Peru. Tests were paid for by patients. The physician survey captured patient and tumor characteristics and treatment decisions by physicians pre- and post-assay result. The survey included patients treated before and after TAILORx results reported in 6/2018. Overall net percent change in CT recommendation and 95% Clopper Pearson confidence intervals (CI) were estimated. The proportion with a change between pre-assay treatment recommendation and actual treatment received was calculated overall and by Recurrence Score groups per TAILORx. Results: Between 3/2015 and 12/2019, the survey was completed for 647 patients. 20% had N+ ESBC. Mean patient age was 54 y (24-85 y); 55% were postmenopausal. 17%/63%/20% had grade 1/2/3 tumors; 70%/30% had tumors ≤2/ &gt; 2 cm in size. Recurrence Score results were: 20% RS 0-10, 56% RS 11-25, and 24% RS 26-100. Overall, CT recommendations fell from 325 patients pre-assay to 199 patients post-assay, a 39% decrease (95% CI 33.4 to 44.3) (36% decrease in N0; 46% decrease in N+). The direction of change was consistent with Recurrence Score results. Among N0 patients, the decrease in CT recommendations was 28% (95% CI 18.9 to 39.5) before TAILORx reported and 36% (95% CI 28.4 to 43.7) after. Conclusions: This large survey of 21-gene test practice patterns was the first conducted in Latin America and showed the relevance of 21-gene testing in low- and medium-resource countries to minimize CT over- and underuse in ESBC. Our results showed substantial reductions in CT use overall. After TAILORx, CT use was further reduced, indicating the practice-changing potential of that study.

Practice-changing use of 21-gene oncotype DX breast recurrence score assay in a public hospital in Brazil: Results of 155 cases.

e12518 Background: The 21-gene assay estimates risk of recurrence expressed as a Recurrence Score result between 0 and 100. The assay is clinically validated to predict chemotherapy (CT) benefit in node-negative (N0) and node-positive (up to three axillary nodes, N1) hormone receptor-positive (HR+) early-stage breast cancer (ESBC). The TAILORx study, which randomized 6711 women with N0 ESBC and Recurrence Score result 11-25 to hormonal therapy (HT) ± CT, demonstrated that patients older than 50 years derived no benefit from CT+HT, although younger patients with Recurrence Score result 16-25 may derive some benefit. The 21-gene assay has been incorporated in practice guidelines worldwide, based on evidence of clinical utility in N0 and N1 ESBC. We evaluated the impact of the 21-gene test on treatment decisions for patients with N0 and N1 ESBC at Sistema Único de Saúde in Brazil. Methods: Eligible patients were post-surgery with T1/T2 tumors, had HR+, HER2−, N0 or N1 ESBC, and were candidates for adjuvant systemic therapy. Treatment recommendations, CT+HT or HT alone, were captured before and after 21-gene test results. All patients were seen at Pérola Byington Hospital, a public hospital in São Paulo, Brazil. TAILORx results were used to guide decisions for or against CT for each patient. Results: From 08/2018 to 04/2019, 155 women were enrolled. Patient mean age was 57.6 years (29-78), 116 (75%) were postmenopausal, and 53 (34%) had N1 breast cancer. Based on clinical data alone, 151 patients had pre-assay recommendations of CT. Post-assay, 106 of 151 patients (70%) had changes in CT recommendation: 104 (69%) initially recommended CT received HT alone, and 2 (1%) initially recommended HT alone received CT+HT (Table). Using the modified Adjuvant!Online criteria for clinical risk classification, 109 of 155 patients (70%) had high risk, 48 (44%) of whom received CT. Of 46 patients with low clinical risk, 10 (22%) received CT. CT use trended with histologic grade: 11% with grade 1, 69% with grade 2, and 61% with grade 3. Most of our patients had tumor bigger than 2 cm (61%) with 8% bigger than 4 cm. Conclusions: The change in clinical practice at this public hospital was greater than expected: 69% of initial treatment recommendations were changed with the Recurrence Score result to omit CT. Clinicopathologic criteria did not correlate well with Recurrence Score results and did not identify those most likely to benefit from CT. A cost-effectiveness study is underway at our institution. [Table: see text]

The impact of Oncotype DX breast cancer assay results on clinical practice: a UK experience

BackgroundGenomic tests are increasingly being used by clinicians when considering adjuvant chemotherapy for patients with oestrogen receptor-positive (ER+), human epidermal growth factor 2-negative (HER2−) breast cancer. The Oncotype DX breast recurrence score assay was the first test available in the UK National Health Service. This study looked at how UK clinicians were interpreting Recurrence Scores (RS) in everyday practice.MethodsRS, patient and tumour characteristics and adjuvant therapy details were retrospectively collected for 713 patients from 14 UK cancer centres. Risk by RS-pathology-clinical (RSPC) was calculated and compared to the low/intermediate/risk categories, both as originally defined (RS < 18, 18–30 and > 30) and also using redefined boundaries (RS < 11, 11–25 and > 25).Results49.8%, 36.2% and 14% of patients were at low (RS < 18), intermediate (RS 18–30) and high (RS > 30) risk of recurrence, respectively. Overall 26.7% received adjuvant chemotherapy. 49.2% of those were RS > 30; 93.3% of patients were RS > 25. Concordance between RS and RSPC improved when intermediate risk was defined as RS 11–25.ConclusionsThis real-world data demonstrate the value of genomic tests in reducing the use of adjuvant chemotherapy in breast cancer. Incorporating clinical characteristics or RSPC scores gives additional prognostic information which may also aid clinicians’ decision making.