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Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.

ABSTRACT: BACKGROUND:Biomarkers to improve the risk-benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinically valuable. We compared the prognostic ability of the breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an immunohistochemical prognostic model (IHC4) for both early and late recurrence in patients with oestrogen-receptor-positive, node-negative (N0) disease who took part in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial. METHODS:In this prospective comparison study, we obtained archival tumour blocks from the TransATAC tissue bank from all postmenopausal patients with oestrogen-receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4 values had already been derived. We did BCI analysis in matched samples with sufficient residual RNA using two BCI models-cubic (BCI-C) and linear (BCI-L)-using previously validated cutoffs. We assessed prognostic ability of BCI for distant recurrence over 10 years (the primary endpoint) and compared it with that of the 21-gene recurrence score and IHC4. We also tested the ability of the assays to predict early (0-5 years) and late (5-10 years) distant recurrence. To assess the ability of the biomarkers to predict recurrence beyond standard clinicopathological variables, we calculated the change in the likelihood-ratio ?(2) (LR-??(2)) from Cox proportional hazards models. FINDINGS:Suitable tissue was available from 665 patients with oestrogen-receptor-positive, N0 breast cancer for BCI analysis. The primary analysis showed significant differences in risk of distant recurrence over 10 years in the categorical BCI-C risk groups (p<0·0001) with 6·8% (95% CI 4·4-10·0) of patients in the low-risk group, 17·3% (12·0-24·7) in the intermediate group, and 22·2% (15·3-31·5) in the high-risk group having distant recurrence. The secondary analysis showed that BCI-L was a much stronger predictor for overall (0-10 year) distant recurrence compared with BCI-C (interquartile HR 2·30 [95% CI 1·62-3·27]; LR-??(2)=22·69; p<0·0001). When compared with BCI-L, the 21-gene recurrence score was less predictive (HR 1·48 [95% CI 1·22-1·78]; LR-??(2)=13·68; p=0·0002) and IHC4 was similar (HR 1·69 [95% CI 1·51-2·56]; LR-??(2)=22·83; p<0·0001). All further analyses were done with the BCI-L model. In a multivariable analysis, all assays had significant prognostic ability for early distant recurrence (BCI-L HR 2·77 [95% CI 1·63-4·70], LR-??(2)=15·42, p<0·0001; 21-gene recurrence score HR 1·80 [1·42-2·29], LR-??(2)=18·48, p<0·0001; IHC4 HR 2·90 [2·01-4·18], LR-??(2)=29·14, p<0·0001); however, only BCI-L was significant for late distant recurrence (BCI-L HR 1·95 [95% CI 1·22-3·14], LR-??(2)=7·97, p=0·0048; 21-gene recurrence score HR 1·13 [0·82-1·56], LR-??(2)=0·48, p=0·47; IHC4 HR 1·30 [0·88-1·94], LR-??(2)=1·59, p=0·20). INTERPRETATION:BCI-L was the only significant prognostic test for risk of both early and late distant recurrence and identified two risk populations for each timeframe. It could help to identify patients at high risk for late distant recurrence who might benefit from extended endocrine or other therapy. FUNDING:Avon Foundation, National Institutes of Health, Breast Cancer Foundation, US Department of Defense Breast Cancer Research Program, Susan G Komen for the Cure, Breakthrough Breast Cancer through the Mary-Jean Mitchell Green Foundation, AstraZeneca, Cancer Research UK, and the National Institute for Health Research Biomedical Research Centre at the Royal Marsden (London, UK).

SUBMITTER: Sgroi DC

PROVIDER: S-EPMC3918681 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.

Sgroi Dennis C DC Sestak Ivana I Cuzick Jack J Zhang Yi Y Schnabel Catherine A CA Schroeder Brock B Erlander Mark G MG Dunbier Anita A Sidhu Kally K Lopez-Knowles Elena E Goss Paul E PE Dowsett Mitch M

The Lancet. Oncology 20130912 11

<h4>Background</h4>Biomarkers to improve the risk-benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinically valuable. We compared the prognostic ability of the breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an immunohistochemical prognostic model (IHC4) for both early and late recurrence in patients with oestrogen-receptor-positive, node-negative (N0) disease who took part in the ...[more]

PMID: 24035531

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Project description:Purpose: Hormone receptor (HR)-positive breast cancer patients with tumor size ?1.0 cm and negative node have favorable outcomes. The 21-gene Recurrence Score (RS) could predict response to chemotherapy for HR+ breast cancer, but its role in T1bN0 disease is challenging. Methods: T1bN0 breast cancer patients diagnosed between January 2014 and June 2019 with RS results were included and categorized as Low- (RS < 18), Intermediate- (RS 18-30), or High-risk (RS > 30) groups. Univariate and multivariate analysis were used to assess factors associated with RS distribution and chemotherapy recommendation. Chemotherapy decisions change and patient adherence after 21-gene RS testing were also evaluated. Results: Among 237 patients with T1bN0 tumors, proportions of Low-, Intermediate-, and High-risk RS were 19.8, 63.3, and 16.9%, respectively. Multivariate analysis found that ER expression (P = 0.011), PR expression (P < 0.001), and Ki-67 index (P = 0.001) were independently associated with RS distribution. Adjuvant chemotherapy was recommended for 31.6% of patients, which was more frequently given to patients with higher tumor grade [Odds ratio (OR) = 2.99 for grade II, OR = 59.19 for grade III, P = 0.006], lymph vascular invasion (OR = 8.22, P = 0.032), Luminal-B subtype (OR = 5.68, P < 0.001), and Intermediate-to High-risk RS (OR = 10.01 for Intermediate-risk, OR = 192.42 for High-risk, P < 0.001). Chemotherapy decision change was found in 18.6% of patients, mainly in those with Intermediate- to High-risk RS tumor with the majority from no-chemotherapy to chemotherapy. The treatment compliance rate after the 21-gene RS testing with MDT was 95.4%. Conclusion: RS category was related to ER, PR, and Ki-67 expression, which was recognized as an independent factor of chemotherapy recommendation in T1bN0 breast cancer. The 21-gene RS testing would lead to a chemotherapy decision change rate of 18.6% as well as a high treatment adherence, which can be applied in T1bN0 patients.

Project description:BackgroundEndocrine therapy is administered to hormone-positive breast cancer patients to prevent distant metastasis. It is important to evaluate the risk of recurrence and to determine which patients are viable candidates for such treatment because hormone therapy has side effects that can include postmenopausal symptoms. The Clinical Treatment Score post-five years (CTS5), a simple tool for identifying candidates for endocrine therapy, was recently introduced; however, CTS5 only has been applied in validation studies with postmenopausal women. We aimed to validate CTS5 among premenopausal breast cancer patients.MethodsWe identified patients treated between 1994 and 2014 at Samsung Medical Center in Seoul, Korea, and followed their treatment outcomes for more than 60 months after surgery using clinicopathologic parameters. According to menopausal status, we divided the study population into two groups: pre- and postmenopausal women. After calculating CTS5 values based on some parameters, we stratified the rate of late distant recurrence (DR) and analyzed the correlation between CTS5 value and late DR by risk.ResultsAmong 16,904 patients treated surgically for breast cancer, 2,605 with hormone receptor-positive breast cancer who received endocrine therapy were included. Of these, 1,749 (67.14%) patients were premenopausal women, and the median age was 44.00 years. When categorizing study participants according to CTS5-related risk for late DR, 86.79% were categorized as low risk, 5.95% were categorized as intermediate risk, and 7.26% were categorized as high risk. The annual rate of DR was 1.41% for those in the present study and was similar between pre- and postmenopausal participants (1.40 vs. 1.42). Distant metastasis-free survival was not different between the two groups (hazard ratio: 0.817, 95% confidence interval [CI]: 0.547-1.221). The area under the receiver operating characteristic curve at 10 years for premenopausal and postmenopausal patients was 61.75 (95% CI: 52.97-70.53) and 72.71 (95% CIs: 63.30-82.12), respectively.ConclusionsAlthough CTS5 was able to predict late DR, it should be applied with caution in premenopausal women. A CTS5 calculator for premenopausal women might be needed to not underestimate the risk of recurrence in Korea.

Project description:ImportanceThe 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain.ObjectiveTo examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone.Design, setting, and participantsThis cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019.Main outcomes and measuresThe LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models.ResultsThe final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P = .02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P = .03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P = .04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P = .051).Conclusions and relevanceThis study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making.

Dataset Information

Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.

Publications

Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.

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