Abstract
PURPOSE
Recent trials have shown potential benefit of extended adjuvant endocrine therapy and relatively high risk of recurrence (RoR) after 5 years in hormone receptor-positive (HR+) human epidermal growth factor receptor 2–negative (HER2−) breast cancer. Although risk of late relapse in HR+ HER2− breast cancer is fairly well defined, the risk in HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab-based chemotherapy remains largely unknown.
METHODS
We included 3,177 patients with HER2+ breast cancer treated with adjuvant chemotherapy alone or with trastuzumab from the North Central Cancer Treatment Group N9831 (ClinicalTrials.gov identifier: NCT00005970) and National Surgical Adjuvant Breast and Bowel Project B-31 (ClinicalTrials.gov identifier: NCT00004067) trials.
RESULTS
Overall, HR+ breast cancer was significantly associated with improved recurrence-free survival (RFS) during the first 5 years (hazard ratio, 0.65; 95% CI, 0.56 to 0.77; P < .001). Among patients treated with trastuzumab, cumulative hazard for RFS was lower in patients with HR+ HER2+ breast cancer during the first 5 years (10.96% v 17.48%; hazard ratio, 0.60; 95% CI, 0.45 to 0.79; P < .001). However, there was no significant difference in RFS based on HR status during years 5 to 10 (hazard ratio, 1.32; 95% CI, 0.93 to 1.88; P = .12). A comparable degree of trastuzumab benefit was observed in HR+ and HR− breast cancers ( P for interaction = .87). Furthermore, we observed low RoR in years 5 to 10 among patients with HR+ HER2+ breast cancer: 3.23% in patients without lymph node involvement (N0) and 6.39% in patients with involvement of one to three lymph nodes (N1).
CONCLUSION
The benefit of adjuvant trastuzumab persists for a long time. A distinct pattern of recurrence was observed between HR+ and HR− HER2+ disease but with similar degree of benefit from adjuvant trastuzumab. RoR in years 5 to 10 in HR+ HER2+ breast cancer is low, particularly in patients with N0 or N1 disease.
INTRODUCTION
Several studies have demonstrated a difference in the pattern of disease recurrence between patients with hormone receptor (HR)–positive (HR+) and HR-negative (HR−) breast cancer, and it is generally recognized that patients with HR+ breast cancer continue to be at risk for recurrence many years after the initial diagnosis.1,2 In HR+ HER2− breast cancer, multiple studies have shown relatively high risk of late relapse, with more than 50% of recurrences occurring after 5 years.3,4 In contrast, patients with HR− breast cancer have higher risk of recurrence (RoR) in the first few years, but RoR considerably declines after 5 years.5 To date, most published data are from studies that focused on patients with HR+ human epidermal growth factor receptor 2 (HER2)–negative (HER2−) breast cancer. The pattern of relapse in HR+ versus HR− among HER2-positive (HER2+) breast cancer and the incidence of late relapse among patients with HR+ HER2+ breast cancer are largely unknown.
With the advent of anti-HER2 therapies, the outcome of patients with HER2+ breast cancer has improved in the past several years. Unlike HR+ HER2− breast cancer, the risk of late relapses in patients with HR+ HER2+ disease remains unknown. Currently, there are limited data available regarding the risk of late recurrence in patients with HER+ breast cancer treated with adjuvant trastuzumab-based chemotherapy. We aimed to determine the pattern of recurrence in HR+ versus HR− in patients with HER2+ breast cancer and the risk of late relapse in patients with HR+ HER2+ breast cancer treated with adjuvant trastuzumab-based chemotherapy in the North Central Cancer Treatment Group (NCCTG) and the National Surgical Adjuvant Breast and Bowel Project (NSABP, now NRG Oncology) B-31, trials. NCCTG is now a part of the Alliance for Clinical Trials in Oncology.
METHODS
Patient Population
NCCTG N9831 (ClinicalTrials.gov identifier: NCT00005970), a randomized, multicenter, phase III trial, enrolled women with primary, operable node-positive or high-risk node-negative HER2+ breast cancer. Patients were randomly assigned to one of three arms: Arm A received only standard adjuvant chemotherapy with doxorubicin and cyclophosphamide, followed by weekly paclitaxel (AC-T); arm B received AC-T followed by trastuzumab after completion of chemotherapy; and arm C received AC-T concurrently with trastuzumab. NSABP B-31 (ClinicalTrials.gov identifier: NCT00004067), a two-arm, randomized, phase III trial, enrolled patients with operable, node-positive HER2+ breast cancer. Eligible patients were randomly assigned to AC-T, with paclitaxel either every 3 weeks or weekly, or to AC-T concurrently with trastuzumab. To match the trastuzumab-treated arm in the NSABP B-31 trial, only patients in arm C of the NCCTG N9831 trial were included in this analysis.
Analysis was performed according to T and N stage,6 with T1 referring to a tumor 2 cm or smaller; T2, a tumor between 2 cm and 5 cm; N0, no node involvement; N1, involvement of one to three nodes; N2, involvement of four to nine nodes; and N3, involvement of 10 or more nodes. Each participant signed an institutional review board–approved, protocol-specific informed consent document in accordance with federal and institutional guidelines. The primary results of these two trials were published in 2005,7 2011,8,9 and 2014.10
Intrinsic Subtype Classification
Using NanoString platform (NanoString Technologies, Seattle, WA), the mRNA abundance was measured to evaluate PAM50 subtype signature in the NCCTG N9831 and NSABP B-31 trials. Gene expression data for the NSABP B-31 trial was acquired from the database of Genotypes and Phenotypes (https://www.ncbi.nlm.nih.gov/gap/); one of the PAM50 genes, CCNE1, was not included in the data set, but this exclusion of this gene had little impact on subtype assignment.11 NanoString data for PAM50 genes plus housekeeping genes were analyzed using the Prosigna algorithm (NanoString Technologies) to defined intrinsic subtype, as previously described.12
Statistical Analysis
For outcome analysis, recurrence-free survival (RFS) was defined as the time from randomization to breast cancer recurrence, which included local, regional, or distant recurrence of breast cancer or breast cancer–related death. Patients without disease recurrence at the time of last follow-up or death were censored at the date of last follow-up or death. Observed follow-up time was calculated as years between randomization and recurrence or death, or the last contact, if no event occurred. Continuous variables were compared between the two studies, using Wilcoxon rank-sum test; categorical variables were compared using the χ2 test. Log-rank P values were used to assess RFS differences among groups. The Kaplan-Meier method was used to estimate RFS rates, and Cox proportional hazard models were used to generate point estimates of hazard ratios and corresponding 95% CIs.
Cox proportional hazards regression models were used to identify univariable and multivariable predictors for relapse between years 0 to 5 and years 5 to 10. When analyzing relapse between 5 to 10 years, only patients without relapse or death at 5 years were included, so the calculation of cumulative hazard started at year 5 and patients who had survived without relapse at 10 years were censored at 10 years. Annual hazard of recurrence was defined as the fraction of patients whose disease recurred during a 1-year interval. Hazard rates in time periods were calculated using the maximum likelihood estimates from a piece-wise exponential Cox regression model, and comparisons between subgroups within time intervals were made using log-rank tests restricted just to follow-up contributions from the specified time interval.13 All tests were two-sided, with α level set at 0.05 for statistical significance. All analyses were based on the study database frozen on January 8, 2018, for NCCTG N9831 and December 21, 2017, for NSABP B-31.
RESULTS
Patient Characteristics
A total of 3,177 patients were included in this combined analysis—1,762 patients from the NCCTG N9831 trial and 1,415 patients from the NSABP B-31 trial (Appendix Fig A1, online only). The baseline characteristics of patients in each trial are listed in Table 1. The mean age (± standard deviation) of patients was similar in both trials (49.4 ± 10.3 years in NCCTG N9831 and 49.6 ± 9.9 years in NSABP B-31), with a mean of 49.5 ± 10.2 years in the combined cohort. The median time to recurrence or death was 2.5 (range, 0.0 to 13.8) years in all patients; median follow-up time for patients without an event was 8.0 (0.0 to 15.3) years in the combined cohort (10.4 years in NCCTG N9831 and 7.0 years in NSABP B-31). In both trials, 54.5% of patients had HR+ disease (57.0% in NCCTG N9831 and 51.4% in NSABP B-31), and 48.0% (50% in NSABP B-31 and 46% in NCCTG N9831) of patients in the overall population were treated with adjuvant trastuzumab-based chemotherapy.
TABLE 1.
Patient Characteristics in the NCCTG N9831 and NSABP B-31 Trials
Baseline Characteristics in HR+ and HR− HER2+ Breast Cancer
Comparing baseline characteristics between HR+ and HR− HER2+ breast cancer (Table 2), there was no difference in age (P = .5254) and nodal status (P = .4309). HR− HER2+ breast tumors are more likely to be categorized as HER2-enriched, on the basis of the Prosigna algorithm: 88.4% compared with 67.9% in HR+ HER2+ breast cancer. As might be expected, HR+ HER2+ breast cancers are more likely to be classified as luminal subtypes: 12.4% of HR+ were classified as luminal A compared with 2.2% in HR− HER2+ tumors. A similar trend was observed in the luminal B subtype, with 18.4% in HR+ versus 0.6% in HR− HER2+ tumors.
TABLE 2.
Patient Characteristics by Hormone Receptor Status in the NCCTG N9831 and NSABP B-31 Trials
Outcome of HR+ Versus HR− HER2+ Breast Cancer
Overall, patients with HR+ breast cancer had significantly better RFS at 10 years (73.84%; 95% CI, 71.51% to 76.25%) compared with the HR− group (69.22%; 95% CI, 66.59% to 71.96%; P < .001). Patients with HR− HER2+ breast cancer had a significantly shorter median time to relapse or death (1.9 years) compared with patients with HR+ HER2+ breast cancer (2.9 years; P < .001). However, a similar benefit of adjuvant trastuzumab was observed in both HR+ (hazard ratio, 0.46; 95% CI, 0.37 to 0.57; P < .001) and HR− (hazard ratio, 0.47; 95% CI, 0.38 to 0.58; P < .001) HER2+ breast cancer (Fig 1). For HR+ HER2+ breast cancer, 10-year RFS was 81.39% (95% CI, 78.54% to 84.34%) in patients who were treated with adjuvant trastuzumab-based chemotherapy, compared with 65.17% (95% CI, 61.52% to 69.03%) in patients who received chemotherapy alone (hazard ratio, 0.46; 95% CI, 0.37 to 0.57; P < .001). Comparable benefit was observed in HR− HER2+ breast cancer, with 10-year RFS of 77.78% (95% CI, 74.46% to 81.25%) in patients who received adjuvant trastuzumab-based chemotherapy, compared with 59.27% (95% CI, 55.27% to 63.56%) in patients who received chemotherapy alone (hazard ratio, 0.47; 95% CI, 0.38 to 0.58; P < .001). Furthermore, the benefit of adjuvant trastuzumab-based chemotherapy was seen in both trials in years 0 to 5 (hazard ratio, 0.42; 95% CI, 0.35 to 0.49; P < .001) and years 5 to 10 (hazard ratio, 0.69; 95% CI, 0.49 to 97; P = .03).
FIG 1.
Kaplan-Meier curves of relapse-free survival by hormone receptor (HR) status and treatment arm in the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 trials.
Similar to what has been previously reported in HR+ HER2− breast cancer,13 RoR was higher in patients with HR− HER2+ breast cancer during the first 5 years (Fig 2A; Appendix Table A1 (online only). In the multivariable analysis of both treatment groups, HR+ was significantly associated with improved RFS during the first 5 years (hazard ratio, 0.65; 95% CI, 0.56 to 0.77; P < .001). However, there was no significant difference during years 5 to 10 (hazard ratio, 1.32; 95% CI, 0.93 to 1.88; P = .12). Similar findings were also observed with the mixed-effects Cox model analysis (Appendix Table A2 (online only). The peak of recurrence for HR− HER2+ disease was at the 2-year time point, with an annualized hazard rate of recurrence of 10.42% (95% CI, 8.70% to 12.38%). In contrast, the peak of recurrence in HR+ HER2+ disease occurred at the 3-year time point, with an annualized hazard rate of recurrence of 6.62% (95% CI, 5.36% to 8.09%). Similar trends were observed in patients who were treated with chemotherapy alone (Fig 2B; Appendix Table A3 (online only) and those treated with adjuvant trastuzumab-based chemotherapy (Fig 2C; Appendix Table A4 (online only).
FIG 2.
Annualized hazard rates for relapse or death by hormone receptor (HR) status. (A) Rates in the North Central Cancer Treatment Group (NCCTG) N9831 and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trials. (B) Rates in the NCCTG N9831 and NSABP B-31 trials in patients treated with chemotherapy alone. (C) Rates in the NCCTG N9831 and NSABP B-31 trials in patients treated with trastuzumab-based chemotherapy.
Outcome of HR+ HER2+ Breast Cancer Treated With Adjuvant Trastuzumab-Based Chemotherapy Between Years 0 to 5 and 5 to 10
Among 2,048 patients who survived 5 years without recurrence, more than 90% of patients survived without additional recurrence, regardless of their HR status or treatment arm. In the combined analysis in patients with lymph node involvement treated with adjuvant trastuzumab-based chemotherapy, patients with HR+ HER2+ disease had significantly lower RoR during the first 0 to 5 years (hazard ratio, 0.60; 95% CI, 0.45 to 79; P < .001; Table 3). The cumulative hazard for relapse in HR+ HER2+ disease was 10.96% (95% CI, 8.78% to 13.08%) compared with 17.48% (95% CI, 14.59% to 20.27%) in HR− HER2+ disease in the first 5 years. For years 5 to 10, the cumulative hazard of relapse or death in HR+ HER2+ patients treated with adjuvant trastuzumab-based chemotherapy was 8.6% (95% CI, 6.16% to 10.97%), which was slightly higher than in patients with HR− HER2+ disease (5.75%).
TABLE 3.
Cumulative Hazard and Hazard Ratio with Univariate Cox Regression Analysis of Relapse or Death Among Patients With Lymph Node Involvement Who Received Adjuvant Trastuzumab-Based Chemotherapy in the NCCTG N9831 and NSABP B-31 Trials, by Hormone Receptor Status
Using the univariate Cox regression analysis, there appeared to be no significant difference in the outcome between HR+ HER2+ and HR− HER2+ subgroups between years 5 to 10 (hazard ratio, 1.62; 95% CI, 0.97 to 2.71; P = .065). However, when adjusted for lymph node status, age, and trial using multivariate Cox regression analysis, the adjusted hazard ratio was 1.7 (95% CI, 1.01 to 2.85; P < .05). During years 5 to 10, patients with HR+ HER2+ breast cancer with N3 disease appeared to have higher RoR compared with patients with HR− HER2+ breast cancer (adjusted hazard ratio, 4.39; 95% CI, 0.94 to 20.50; P = .06). However, the adjusted hazard ratio of patients with N1 and N2 disease was 1.42 (95% CI, 0.81 to 2.48; P = .221).
Given that NCCTG N9831 was the only trial in this analysis to include patients with no lymph node involvement, we additionally analyzed the RoR among those patients alone (Table 4). Only 3.23% (95% CI, 0% to 9.25%) of patients with HR+ HER2+ disease with N0 disease and 6.39% (95% CI, 3.09% to 9.59%) with N1 disease developed recurrence in years 5 to 10, compared with the recently reported 11% and 19% RoR after 5 years in HR+ HER2− disease with N0 and N1 disease, respectively.4
TABLE 4.
Cumulative Hazard and Hazard Ratio with Univariate Cox Regression Analysis of Relapse or Death Among Patients With or Without Lymph Node Involvement Who Received Adjuvant Trastuzumab-Based Chemotherapy in the NCCTG N9831 Trial, by Hormone Receptor Status
Intrinsic Subtypes and Outcome
In the NCCTG N9831 trial, intrinsic subtype classification information is only available for 982 patients (55.7%). As we described previously,12 there was no statistically significant difference between the cohort with intrinsic subtype classification and overall cohort. Using the Prosigna algorithm to determine the intrinsic subtype, 77.4% of patients had HER2-enriched subtype, 10.1% had luminal B subtype, 7.7% had luminal A subtype, and 4.8% had basal-like subtype. Regardless of the treatment patients received, those with luminal A subtype had the best outcome, with 10-year RFS of 77.32% (95% CI, 70.45% to 84.87%), followed by the luminal B subtype (73.17%; 95% CI, 66.36% to 80.68%), HER2-enriched subtype (68.67%; 95% CI, 66.12% to 71.32%), and basal-like subtype (64.0%; 95% CI, 54.59% to 75.04%; P < .001; Appendix Table A5 (online only).
Among patients who received adjuvant trastuzumab-based chemotherapy, patients with luminal A subtype also had the best outcome, with 10-year RFS of 89.84% (95% CI, 82.31% to 98.05%), followed by luminal B subtype (82.27%; 95% CI, 74.57% to 90.77%), HER2-enriched subtype (76.78%; 95% CI, 73.48% to 80.22%), and basal-like subtype (74.19.0%; 95% CI, 62.12% to 88.59%; P = 0.014; Appendix Table A6 (online only). Of note, patients without lymph node involvement who had HER2-enriched subtype also had an excellent 10-year RFS of 89.01% (95% CI, 80.32% to 98.64%). The cumulative hazard and hazard ratio of relapse or death according to intrinsic subtypes and hormone receptor status are also reported in Appendix Table A7 (online only).
DISCUSSION
With the advent of anti-HER2 therapy, the outcome of patients with HER2+ breast cancer has dramatically improved. Although the outcome of patients with HER2+ breast cancer is generally perceived as favorable with the use of adjuvant trastuzumab-based chemotherapy, little is known about the effects of anti-HER2 therapies on the patterns of late relapses in this group of patients. To our knowledge, this analysis is the first to address the risk of late relapses in subsets of patients with HER2+ breast cancer who were treated with adjuvant trastuzumab.
Overall, our analysis demonstrated persistent benefit of adjuvant trastuzumab in the long term. Furthermore, similar degree of benefit from adjuvant trastuzumab was observed among patients with HR+ and HR− HER2+ breast cancer. In HR+ HER2− breast cancer, several studies have demonstrated substantial risk of late relapse beyond 5 years after the initial diagnosis. Saphner et al13 demonstrated that although patients with HR− HER2− disease had higher initial RoR, their annual hazard rate of relapse declined over time. In contrast, patients with HR+ HER2− breast cancer had relatively constant RoR over time that surpassed that of patients with HR− HER2− breast cancer after 5 years.13 This observation was confirmed in several subsequent studies.1,2,14 Similar to this observation, our analysis also demonstrated a distinct pattern of recurrence in patients with HER2+ breast cancer in the first 5 years among HR+ and HR− HER2+ disease. Patients with HR− HER2+ breast cancer had a significantly higher annualized hazard rate of relapse in the first 5 years compared with patients with HR+ HER2+ disease. However, after 5 years, patients with HR+ HER2+ breast cancer who received adjuvant trastuzumab-based chemotherapy had no significant difference in the annualized hazard rate of relapse compared with patients with HR− HER+ breast cancer, particularly in patients with N0, N1, and N2 disease. Nevertheless, there appeared to be a higher RoR between years 5 to 10 in patients with HR+ HER2+ breast cancer with more lymph node involvement, particularly those with N3 disease.
A recent meta-analysis of 62,923 women with HR+ breast cancer by the Oxford Overview demonstrated that despite 5 years of adjuvant endocrine therapy, patients still had substantial risk of distant recurrence.4 By 10 years, patients without lymph node involvement had an 11% risk of distant recurrence and risk of distant recurrence was projected to increase to as high as 22% by year 20. In patients with N1 and N2 disease, the risk of distant recurrence was projected to be 31% and 52% by year 20, respectively. However, only 2% of the patients in that analysis had HER2+ breast cancer, and trastuzumab was not administered in any of the included trials.4 In the Oxford analysis,4 5% of patients with HR+ breast cancer without lymph node involvement had disease recurrence between years 5 to 10, compared with 3.23% in our combined analysis, and 9% compared with 6.39% in patients with N1 disease, respectively. A more pronounced difference was observed in patients with N2 HR+ HER2−, with 14% RoR in the Oxford analysis,4 compared with 5.1% in our combined analysis.
Beyond standard HR and HER2 status, there are several multigene tests currently used in clinic to assess individual RoR and benefit of adjuvant chemotherapy. In patients with HR+ HER2− breast cancer, Prosigna PAM50 RoR, the Breast Cancer Index (Biotheranostics, San Diego, CA), and EndoPredict (Myriad Genetic Laboratories, Salt Lake City, UT) have prognostic value in predicting the risk of late relapse beyond 5 years after the initial diagnosis.13 The PAM50 RoR score is based on the 50-gene panel developed to identify intrinsic subtypes of breast cancer. However, ROR score also integrates information on tumor size. In previous studies in the translational arm of the Anastrozole or Tamoxifen Alone or Combined trial16 and Austrian Breast and Colorectal Cancer Study Group 8 trial,17 ROR score added significant prognostic information on risk of late relapse beyond conventional clinical pathologic parameters. Interestingly, similar to previous reports in HR+ HER2− breast cancer, our study demonstrated the prognostic value of Prosigna PAM50 intrinsic subtype in predicting risk for late relapse in patients with HR+ HER2+ breast cancer. Albeit rare, patients with luminal A tumors had excellent long-term outcome, with 89.8% RFS at 10 years compared with luminal B (82.3%), HER2-enriched (76.8%), and basal-like (74.19%) subtypes.
Our study has several limitations, the first being the lack of longer follow-up. The Oxford Overview4 provided up to 20 years of follow-up data, whereas we had only up to 10 years of follow-up data. Furthermore, our combined analysis had a smaller sample size. After separating patients with HR+ HER2+ breast cancer treated with trastuzumab according to lymph node involvement, there were only 43, 278, 125, and 69 patients with N0, N1, N2, and N3 disease, respectively. Therefore, the results of this study should be viewed with caution. Moreover, because of potential multiple comparisons, the Bonferroni correction method may be applied. To avoid overinterpretation, each P value need to be less than .025 to consider statistically significant. Late relapse among patients with HR+ HER2+ breast cancer who received adjuvant trastuzumab can be better assessed in a meta-analysis of additional adjuvant trastuzumab trials. In addition, it is unclear whether the risk of late relapse in patients with HR+ HER2+ breast cancer will be even lower with the use of additional anti-HER2 therapies such as pertuzumab, neratinib, and ado-trastuzumab emtansine.
Currently, there is no prospective, randomized, controlled clinical trial specifically addressing the benefit of extended adjuvant endocrine therapy in HER2+ patients. Nevertheless, because patients who were treated with adjuvant trastuzumab and completed 5 years of adjuvant endocrine therapy without recurrence had low RoR, particularly patients with N0 and N1 disease, it is unclear whether the benefit of extended adjuvant endocrine therapy will outweigh the risks and adverse effects associated with these extended therapies. For extended adjuvant endocrine therapy with tamoxifen, the absolute benefit of tamoxifen in reducing RoR was reported to be 2.8% to 4%, with the relative reduction of approximately 15%, in both ATLAS and aTTom trials.18-20 However, this benefit may be offset by increased risks of endometrial cancer (range, 1.6% to 3.1%) and thromboembolism with relative risk of 1.87 for pulmonary embolism.18 The benefit of 10 years versus 5 years of adjuvant aromatase inhibitor remains controversial. Recent trials demonstrated the benefit of extended adjuvant aromatase inhibitors appeared to be limited to reducing the risk of second breast cancer, but there was none or only a small benefit for distant metastasis.21-25
In summary, we demonstrated in this study persistent long-term benefit of adjuvant trastuzumab in patients with HER2+ breast cancer. Similar degree of benefit from adjuvant trastuzumab was observed in both HR+ and HR− disease. Given concerning adverse effects and potentially less benefit of extended adjuvant endocrine therapy, particularly in patients with N0 or N1 disease, our findings highlight the need to develop better risk-prediction models and biomarkers to identify which patients have sufficient risk for late relapse to warrant the use of extended endocrine therapy in HER2+ breast cancer.
APPENDIX
FIG A1.
CONSORT diagram of the North Central Cancer Treatment Group (NCCTG N9831) and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trials.
TABLE A1.
Annualized Hazard Rate of Relapse or Death by Hormone Receptor Status in the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 Trials
TABLE A2.
The Mixed-Effects Cox Model Analysis of Relapse or Death Among Patients in the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 Trials
TABLE A3.
Annualized Hazard Rate of Relapse or Death, by Hormone Receptor Status, in Patients Treated with Chemotherapy Alone in North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 Trials
TABLE A4.
Annualized Hazard Rate of Relapse or Death by hormone receptor status in patients who were treated with adjuvant trastuzumab-based chemotherapy in the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 Trials
TABLE A5.
Kaplan-Meier Estimates of RFS Rate Based on Demographic and Treatment Groups in the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 Trials
TABLE A6.
Kaplan-Meier Estimates of RFS Rate Based on Demographic and Treatment Groups of Patients Treated with Trastuzumab-Based Adjuvant Chemotherapy in the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 Trials
TABLE A7.
Cumulative Hazard and Hazard Ratio with Univariate Cox Regression Analysis of Relapse or Death Among Patients With Lymph Node Involvement Who Received Adjuvant Trastuzumab-Based Chemotherapy in the North Central Cancer Treatment Group N9831 and National Surgical Adjuvant Breast and Bowel Project B-31 Trials, by HR Status and Intrinsic Subtypes
Footnotes
Presented at the San Antonio Breast Cancer Symposium Meeting 2018, December 4-8, 2018, San Antonio, TX.
Supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA18082 (to the Alliance for Clinical Trials in Oncology), U24CA196171, U10CA180868, UG1CA189867, U10CA180822, and U24CA196067; Genentech; and in part by funds to E.A.T. from the Breast Cancer Research Foundation (Grant No. BCRF-17-161), Bankhead-Coley Research Program (Grant No. 6BC05), and the DONNA Foundation.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Pennsylvania Department of Health specifically disclaims responsibility for any analysis, interpretations, or conclusions.
Clinical Trial Information: NCT00005970 (NCCTG N9831) and NCT00004067 (NSABP B-31)
AUTHOR CONTRIBUTIONS
Conception and design: Saranya Chumsri, Soonmyung Paik, Edith A. Perez, E. Aubrey Thompson
Financial support: E. Aubrey Thompson
Provision of study material or patients: Zhuo Li, Katherine L. Pogue-Geile, Soonmyung Paik, Edith A. Perez, E. Aubrey Thompson
Collection and assembly of data: Saranya Chumsri, Nan Song, Katherine Pogue-Geile, Patrick G. Gavin, Soonmyung Paik, Edith A. Perez, E. Aubrey Thompson
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Incidence of Late Relapses in Patients With HER2-Positive Breast Cancer Receiving Adjuvant Trastuzumab: Combined Analysis of NCCTG N9831 (Alliance) and NRG Oncology/NSABP B-31
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Saranya Chumsri
Consulting or Advisory Role: Syndax, Puma Biotechnology, Novartis, Eisai, Immunomedics
Research Funding: Merck, Array BioPharma
Daniel J. Serie
Employment: InterVenn Biosciences
Stock and Other Ownership Interests: InterVenn Biosciences
Afshin Mashadi-Hossein
Employment: NanoString Technologies, Celgene Corporation
Stock and Other Ownership Interests: NanoString Technologies, Celgene Corporation
Gerardo Colon-Otero
Research Funding: Novartis (Inst)
Nan Song
Patents, Royalties, Other Intellectual Property: Patent Application Serial No. 14/738,757 entitled “Methods of Subtyping CRC and their Association with Treatment of Colon Cancer Patients with Oxaliplatin,” published on December 24, 2015.
Katherine L. Pogue-Geile
Research Funding: National Surgical Adjuvant Breast and Bowel Project (Inst)
Patents, Royalties, Other Intellectual Property: US Patent Application Serial No. 14/738,757, entitled “Methods of Subtyping CRC and their Association with Treatment of Colon Cancer Patients with Oxaliplatin,” published on December 24, 2015.
Soonmyung Paik
Stock and Other Ownership Interests: ImmunOncia Therapeutics
Consulting or Advisory Role: Medpacto
Alvaro Moreno-Aspitia
Stock and Other Ownership Interests: Merrimack
Patents, Royalties, Other Intellectual Property: Royalties from the development of a xenograft model. Royalties were assigned to go to my institution, not to me.
Edith A. Perez
Employment: Genentech
Stock and Other Ownership Interests: Roche
Consulting or Advisory Role: Seattle Genetics, Puma, Daiichi Sankyo
No other potential conflicts of interest were reported.
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