Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy.
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ABSTRACT:
SUBMITTER: Stemmer SM
PROVIDER: S-EPMC6841708 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy.
Stemmer Salomon M SM Steiner Mariana M Rizel Shulamith S Ben-Baruch Noa N Uziely Beatrice B Jakubowski Debbie M DM Baron Julie J Shak Steven S Soussan-Gutman Lior L Bareket-Samish Avital A Fried Georgeta G Rosengarten Ora O Itay Amit A Nisenbaum Bella B Katz Daniela D Leviov Michelle M Tokar Margarita M Liebermann Nicky N Geffen David B DB
NPJ breast cancer 20191108
The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10 ...[more]
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Project description:The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28. B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor-positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided. There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02). RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of appropriate candidates for comprehensive radiotherapy.
| S-EPMC5721938 | biostudies-literature
Project description:IntroductionBreast cancer in young women (<50 years) has been associated with an increased risk of recurrence and decreased survival compared with patients older than 50. The objective of this analysis was to determine, from a large database of patients with early-stage breast cancer, if the Recurrence Score(®) result (Oncotype DX(®), Genomic Health, Inc, Redwood City, CA, USA) provided clinically meaningful differences in predicted risk of recurrence in younger-compared with older-patients.MethodsTumor samples from patients with estrogen receptor (ER)-positive breast cancers that were successfully processed in the Genomic Health central lab between June 2004 and December 2013 for Recurrence Score and quantitative gene expression of ER, progesterone receptor (PR), and Her/2neu, were included. Descriptive statistics were used to describe the distribution of scores by age group: <40, 40-49, 50-59, 60-69, and ≥70 years, nodal status, and histologic subtype.ResultsSpecimens from 394,031 patients [3.3% (n = 13,029) aged <40 years; 15.6% (n = 61,643) aged ≥70 years] were included; 81.6% of patients had invasive ductal carcinoma. Nodal status was specified for 362,001 patients (87.0% negative). Median Recurrence Score results were similar across risk groups. Low (<18)- and high (≥31)- risk Recurrence Score results were seen in 58.5% and 8.5% of patients, respectively. A greater proportion of patients aged <40 (14.1%) than ≥70 (8.8%) years had a high-risk score. ER expression increased as a function of age and PR single-gene and invasion gene group expression were similar across age groups.ConclusionThese data indicate that in patients with ER-positive breast cancer, age alone does not reflect the underlying individual tumor biology, suggesting that the Recurrence Score result may add potentially useful information for personalized treatment decisions.FundingGenomic Health, Inc.
| S-EPMC4679789 | biostudies-literature
Project description:Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER)-positive breast cancers resistant to the antiestrogen, tamoxifen. In this study, biomarkers co-ordinately up-regulated by NFKB and AP-1 with prognositic significance are identified in a largely TAM-treated set of ER+ node negative breast cancers. The prognostic value with respect to age is also investigated. Keywords: biomarker identification
2007-04-02 | GSE7378 | GEO
Project description:PurposeOncotype DX, a gene expression assay widely employed to aid decision making on adjuvant chemotherapy use in patients with primary oestrogen receptor-positive (ER+) breast cancer, produces a recurrence score (RS) related to distant disease recurrence (DR) risk (RS%). In node-negative patients, RS can be integrated with clinicopathological parameters to derive RS-pathology-clinical (RSPC) that improves prognostic accuracy.MethodsData were collected on patients having clinically indicated tests with an intermediate clinical risk of distant recurrence, and for whom the decision to prescribe chemotherapy remained unclear. Correlation between RS% and RSPC scores was examined. An agreement table was constructed using risk-categorised data. Association between RS%-derived categorical risk assignments and treatment recommendation was evaluated.ResultsData on 171 tests (168 patients) were available. Median DR risk by RS% was 11% (range 3-34%), by RSPC it was 15% (range 4-63%). Correlation between RS% and RSPC was 0.702 (p < 0.001). RS% classified 57.3% of cases as low-, 32.2% intermediate- and 10.5% high-risk for DR; by RSPC proportions were 33.9, 35.7, and 30.4%, respectively. The number of patients receiving chemotherapy recommendations was: 14/87 (16.1%) categorised as low-risk by RS%, 27/49 (55.1%) as intermediate-risk and 12/13 (92.3%) as high-risk. Of 149 patients recommended for endocrine treatment alone, 28 (18.8%) were categorised by RS% as low-risk but by RSPC as intermediate- or high-risk.ConclusionsIn this group of patients, RSPC assessed fewer patients as low-risk and more as high-risk than did RS%. The discordances between the scores indicate that RSPC estimates of risk should be considered when selecting patients for endocrine therapy alone.
| S-EPMC5847032 | biostudies-literature
Project description:PurposePrognostic value of Oncotype DX Breast Recurrence Score (RS) in male patients with breast cancer is understudied. We evaluated associations of RS with overall mortality in male patients with breast cancer and compared it with female counterparts.Experimental designWith a cohort of 848 male and 110,898 female patients with breast cancer identified from the National Cancer Database (2010-2014), we estimated HRs and 95% confidence intervals (CI) for overall mortality associated with RS using Cox regression models. RS was evaluated continuously, as well as by categorization following respective traditional (?17, 18-30, and ?31) and TAILORx (?10, 11-25, and ?26) cutoffs.ResultsRS was positively associated with mortality in male patients (HR = 1.13; 95% CI, 1.02-1.26 per unit RS increment) up to RS > 21, after which the risk plateaued. Among female patients, mortality began to increase with RS only when RS > 23 (HR = 1.02; 95% CI, 1.01-1.02 per unit of RS increment). The intermediate- (HR = 5.37; 95% CI, 1.79-16.11) and high-risk diseases (HR = 4.28; 95% CI, 1.22-14.97) defined by TAILORx, but not traditional cutoffs established for female patients, were associated with elevated mortality risk in men even after adjustment for demographic, clinical characteristics, and treatments, except chemotherapy.ConclusionsRS is associated with mortality in male patients with breast cancer at a much lower threshold than that for female patients. Studies are needed to establish specific guidelines for RS thresholds for male patients with breast cancer.
| S-EPMC7380510 | biostudies-literature
Project description:The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N?=?709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors???2?cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score?<?18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score???31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score?<?18, 18-30, and???31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score?<?18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score?<?18, recurrence rate was 7.7% in chemotherapy-treated (n?=?27) and 2.9% in chemotherapy-untreated patients (n?=?352); P?=?0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients (n?=?102) was significantly lower than in untreated patients (n?=?156) (1.0% vs. 9.7% P?=?0.019); in Recurrence Score???25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n?=?89) and 4.4% in chemotherapy-untreated patients (n?=?488); P?=?0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1-3 positive nodes and Recurrence Score?<?18.
| S-EPMC5591314 | biostudies-literature
Project description:PURPOSE:For patients with medial compartment arthritis who have failed non-operative treatment, either a total knee arthroplasty (TKA) or a unicompartmental knee arthroplasty (UKA) can be undertaken. This analysis considers how the choice between UKA and TKA affects long-term patient-reported outcome measures (PROMs). METHODS:The Knee Arthroplasty Trial (KAT) and a cohort of patients who received a minimally invasive UKA provided data. Propensity score matching was used to identify comparable patients. Oxford Knee Score (OKS), its pain and function components, and the EuroQol 5 Domain (EQ-5D) index, estimated on the basis of OKS responses, were then compared over 10 years following surgery. Mixed-effects regressions for repeated measures were used to estimate the effect of patient characteristics and type of surgery on PROMs. RESULTS:Five-hundred and ninety UKAs were matched to the same number of TKAs. Receiving UKA rather than TKA was found to be associated with better scores for OKS, including both its pain and function components, and EQ-5D, with the differences expected to grow over time. UKA was also associated with an increased likelihood of patients achieving a successful outcome, with an increased chance of attaining minimally clinically important improvements in both OKS and EQ-5D, and an 'excellent' OKS. In addition, for both procedures, patients aged between 60 and 70 and better pre-operative scores were associated with better post-operative outcomes. CONCLUSION:Minimally invasive UKAs performed on patients with the appropriate indications led to better patient-reported pain and function scores than TKAs performed on comparable patients. UKA can lead to better long-term quality of life than TKA and this should be considered alongside risk of revision when choosing between the procedures. LEVEL OF EVIDENCE:II.
| S-EPMC5907625 | biostudies-literature
Project description:BACKGROUND:The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. METHODS:In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan-Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients' outcomes during the period from 5 to 20 years. RESULTS:Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1-3), and 34% with four to nine nodes involved (T1N4-9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1-3, and 41% with T2N4-9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. CONCLUSIONS:After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.).
| S-EPMC5734609 | biostudies-literature
Project description:Although the 21-gene recurrence score (RS) assay has been validated to assess the risk of distant recurrence in hormone receptor-positive breast cancer patients, the relationship between RS and the risk of locoregional recurrence (LRR) remains unclear. The purpose of this study was to determine if RS is associated with LRR in breast cancer patients and whether this relationship varies based on the type of local treatment [mastectomy or breast-conserving therapy (BCT)].163 consecutive estrogen receptor-positive breast cancer patients at our institution had an RS generated from the primary breast tumor between August 2006 and October 2009. Patients were treated with lumpectomy and radiation (BCT) (n = 110) or mastectomy alone (n = 53). Patients were stratified using a pre-determined RS of 25 and then grouped according to local therapy type.Median follow-up was 68.2 months. Patients who developed an LRR had stage I or IIA disease, >2 mm surgical margins, and received chemotherapy as directed by RS. While an RS > 25 did not predict for a higher rate of LRR, an RS > 24 was associated with LRR in our subjects. Among mastectomy patients, the 5-year LRR rate was 27.3 % in patients with an RS > 24 versus 10.7 % (p = 0.04) in those whose RS was ? 24. RS was not associated with LRR in patients who received BCT.Breast cancer patients treated with mastectomy for tumors that have an RS > 24 are at high risk of LRR and may benefit from post-mastectomy radiation.
| S-EPMC4869872 | biostudies-literature
Project description:Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART) in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004-2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1) mortality, 2) virologic failure, and 3) mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127) of participants died, 6% (n = 31) were lost-to-follow-up and 23% (107/472) experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10-year ART outcomes. A low level of formal education does not appear to be a barrier to successful long-term ART.
| S-EPMC5731768 | biostudies-literature