Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor-Positive Breast Cancer
ABSTRACT The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known.
The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS.
A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit.
The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.
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ABSTRACT: Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26–3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26–2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age <50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies. Electronic supplementary material The online version of this article (doi:10.1186/2193-1801-3-727) contains supplementary material, which is available to authorized users.SpringerPlus 12/2014; 3(1):727. DOI:10.1186/2193-1801-3-727
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ABSTRACT: Abstract Introduction The use of chemotherapy in node-negative, (O)Estrogen Receptor (ER)-positive breast cancer has changed significantly since the introduction of Oncotype DX to determine systemic recurrence risk based on tumour genomic signature. Aims This study aims to: 1.Document longitudinal changes in chemotherapy use, 2.Assess the impact of new evidence on local protocol. Methods A cohort study was undertaken, including consecutive patients with early node-negative, ER-positive breast cancer diagnosed between 2006 and May 2013, including a period of prospective clinical trial (Trial Assigning Individualised Options for Treatment (TAILORx)) recruitment. Data were collected regarding patient demographics, tumour clinico-pathological features, Oncotype DX use and recurrence score and chemotherapy use. All therapeutic decisions were made following multidisciplinary discussion, with adherence to guidelines and consideration of trial protocol and Oncotype DX recurrence scores. Results 479 consecutive patients were included in the study, of whom 241 (50%) underwent Oncotype DX testing, 97 as part of the TAILORx clinical trial. Oncotype DX testing began on a trial basis in 2007 and until October 2011, only patients enrolled on TAILORx availed of genomic profiling. From October 2011, Oncotype DX was used in all eligible patients as per National Cancer Control Programme (NCCP) guidelines. A total of 216 (45%) patients received chemotherapy. The use of chemotherapy changed in inverse proportion to the availability of the genomic assay. Of those patients in whom Oncotype DX was utilised, 138 (57%) were spared chemotherapy. Conclusion This study validates the use of molecular testing in the rationalisation of systemic therapy.European Journal of Cancer 09/2014; 50(16). DOI:10.1016/j.ejca.2014.08.002 · 4.82 Impact Factor
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ABSTRACT: This retrospective study evaluated the impact of intermediate Recurrence Score(®) results on adjuvant treatment decisions in estrogen receptor-positive (ER+) early invasive breast cancer, comparing treatment recommendations pre-testing with actual treatments received post-testing. Of the 111 patients included in the analysis, 78 (70.3%) had hormonal therapy (HT) and 33 (29.7%) had chemohormonal therapy (CHT) recommendations pre-testing. The Recurrence Score was significantly higher in those with a pre-testing CHT recommendation compared with those with a pre-testing HT recommendation (median of 24 vs. 22; P = 0.047; Mann-Whitney-Wilcoxon [MWW] test). Post-testing, treatment of 24 patients (21.6%) was different from their pre-testing recommendation. The difference between CHT recommendation rate pre-testing and the rate of CHT received post-testing was nonsignificant for the entire cohort and for patients' subgroups (by age, tumor size, and grade) (P >0.17; McNemar's test). Following classification of the cohort into two Recurrence Score subcategories (low-intermediate, [18-25]; high-intermediate, [26-30]), changes in treatment decisions (pre-testing recommendations vs. actual treatments received post testing) were reported for 16.5% of low-intermediate and 34.4% of high-intermediate patients. Post-testing, the rate of CHT decreased (by 58%) in the low-intermediate subcategory and increased (by 64%) in the high-intermediate subcategory (P <0.01, both subcategories). In logistic regression analyses, the Recurrence Score subcategory was the only significant predictor of changes in treatment decisions (pre-testing recommendations vs. actual treatments received post testing; P <0.01). The only significant difference between the two subsets of patients with such a change (HT to CHT, 11 patients; CHT to HT, 13 patients) was the Recurrence Score (median of 28 vs. 20, respectively; P = 0.0014; MWW test). These findings demonstrate that intermediate Recurrence Score results provide clinically relevant information and impact treatment decisions in ER + early breast cancer.SpringerPlus 02/2014; 3:71. DOI:10.1186/2193-1801-3-71