Key Points
Question
What is the clinical impact of the Breast Cancer Index (BCI) on physicians’ decisions and confidence in extending endocrine therapy and on patients’ preference and comfort with the decision?
Findings
In this cohort study of 2900 women, completed physician and patient questionnaires from the BCI Registry were analyzed. After BCI testing, 41.7% of physicians changed their extended endocrine therapy (EET) recommendation, with a 43.8% increase in their confidence, and 51.0% of patients changed their preference for EET.
Meaning
These findings demonstrate that BCI provides clinical utility in guiding EET.
This cohort study evaluates how use of the Breast Cancer Index (BCI) is associated with physicians’ decisions regarding extended endocrine therapy, as well as patient preference and comfort with these decisions.
Abstract
Importance
The Breast Cancer Index (BCI) is an established genomic assay that provides individualized risks of overall and late distant recurrence and predicts the likelihood of extended endocrine therapy (EET) benefit in patients with early-stage, hormone receptor–positive (HR+) breast cancer. Previous findings from the first 1000 patients in the prospective BCI Registry showed that physicians changed their EET recommendation in more than 40% of patients.
Objective
To investigate the use of the BCI in the full registry cohort and how physicians integrate prognostic and predictive results in real care settings.
Design, Setting, and Participants
The BCI Registry study is a US multicenter evaluation of long-term clinical outcome, decision impact, and medication adherence among patients enrolled from April 2021 to January 2024. Participants included women diagnosed with early-stage, HR+ breast cancer. Physician and patient questionnaires about recommendations or preferences for EET and confidence or comfort with these decisions were collected. For this cohort study, data were analyzed from January 2025 to March 2026.
Exposure
Patients received BCI testing and endocrine therapy. The BCI prognostic model calculated a risk score to classify patients as having low or high risk of late distant recurrence, while the BCI predictive component used the BCI HOXB13/IL17BR (H/I) ratio to classify patients as having low or high likelihood of EET benefit.
Main Outcomes and Measures
Change in physicians’ and patients’ recommendations or preferences for EET, and their confidence or comfort with these decisions. Pre-BCI and post-BCI results were analyzed using the McNemar test. Fisher exact test was used to determine the association between BCI categories and clinical variables.
Results
The final analysis included 2900 women with completed physician and patient questionnaires (mean [SD] age, 65.2 [10.3] years). Among these patients, 2570 (88.6%) were postmenopausal, 2245 (77.4%) were N0, and 2501 (86.2%) were HER2-negative. After BCI testing, 1209 physicians (41.7%) changed their EET recommendation (P < .001), and 1479 patients (51.0%) changed their preference for EET (P < .001). Among 1100 patients classified as BCI (H/I)–High, EET recommendations increased from 671 pre-BCI (61.0%) to 1014 post-BCI (92.2%). Among 1800 patients classified as BCI (H/I)–Low, the number of physicians not recommending EET increased from 856 (47.6%) to 1576 (87.6%). Physician confidence in their recommendation increased for 1269 patients (43.8%; P < .001), and 1260 patients (43.4%) were more comfortable with the EET decision (P < .001).
Conclusions and Relevance
This cohort study of patients from the BCI Registry highlights the important treatment guidance provided by the BCI to reduce EET undertreatment or overtreatment and further substantiates its clinical utility to individualize patient care.
Introduction
Extended endocrine therapy (EET) has been shown to reduce the risk of late distant recurrence of early-stage, hormone receptor–positive (HR+) breast cancer by 1% to 5% but is associated with adverse effects, including bone and cardiovascular toxic effects, uterine cancer, and tolerability issues that lead to treatment discontinuation or nonadherence.1,2,3,4 Clinically validated biomarkers can provide personalized information to guide treatment decision-making for EET. The Breast Cancer Index (BCI) is recognized in the National Comprehensive Cancer Network and American Society of Clinical Oncology clinical practice guidelines for use in clinical decision-making regarding EET.5,6
The BCI gene expression assay includes 2 components: the Molecular Grade Index (MGI) assesses tumor proliferation, while the HOXB13/IL17BR (H/I) ratio is an endocrine response biomarker. The BCI test report provides both a prognostic and predictive result. The BCI prognostic score uses an algorithmic combination of MGI and H/I ratio to assess risk of overall (0-10 years) and late (5-10 years) distant recurrence. An adjusted BCI model was shown to stratify premenopausal and postmenopausal patients at minimal risk of distant recurrence over 10 years.7,8,9 The predictive component is the BCI (H/I) ratio, which predicts the likelihood of EET benefit across various adjuvant endocrine treatment backgrounds.10,11,12,13,14,15
The BCI Registry is a prospective, large-scale, multicenter study investigating the long-term clinical outcomes of patients with early-stage HR+ breast cancer, the impact of BCI results on treatment decision-making, and patient medication adherence to EET regimens.16 An early analysis based on the first 1000 patients enrolled in the registry showed that after BCI testing, physicians changed EET recommendations in 40% of cases, and 45% of patients changed their preference for EET.16 Patients also reported reduced concern about EET cost, safety, and benefit after receiving BCI results. Here, we report updated findings from the BCI Registry study based on the full cohort.
Methods
Patients and Study Design
The study design, patient population, and methods of the BCI Registry study were previously published.16 In brief, the registry recruited approximately 3000 women with a diagnosis of stage I to III HR+ breast cancer who remained recurrence free after 4 to 7 years of primary adjuvant endocrine therapy from April 2021 to January 2024 at 112 clinics across the US. All participants provided written informed consent before enrollment and collection of tumor samples. The study was reviewed and approved by the US Oncology Institutional Review Board. This report closely follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for cohort studies.
Physicians and patients completed the pre-BCI test questionnaires at the time of enrollment (day 0). Post-BCI test questionnaires were subsequently completed after BCI test reporting and within 6 months from enrollment per protocol. The physician questionnaire assessed physicians’ recommendations for EET and confidence level with their recommendation. The patient questionnaire assessed endocrine therapy history and adherence; expectations about risk of recurrence; preference about continuing endocrine therapy beyond 5 years; concerns around cost, adverse effects, drug safety, and benefit; and their comfort with the treatment decision. The physician and patient discussed BCI test results before completion of the post-BCI questionnaire. Clinical information and questionnaire responses were recorded in an electronic data capture system. Patient follow-up remains ongoing, with study completion anticipated in 2028.
BCI Testing
BCI assay methods have been previously published.15,17,18 In brief, formalin-fixed, paraffin-embedded tumor specimens were analyzed by Biotheranostics in a Clinical Laboratory Improvement Amendments–certified, College of American Pathologists–accredited laboratory. Formalin-fixed, paraffin-embedded tumor sections were macrodissected to enrich tumor content before RNA extraction. Total RNA was reverse transcribed, and the resulting cDNA was preamplified by polymerase chain reaction (PCR) using the PreAmp Master Mix Kit (Thermo Fisher Scientific), and TaqMan PCR analysis was performed. BCI, BCIN+, and BCI (H/I) were calculated as previously described.15,18
The BCI prognostic model calculates a risk score that stratifies patients as having low or high risk for late (5-10 years) distant recurrence using a prespecified cut point, while the BCI predictive component categorizes patients as having low or high likelihood of benefit from EET based on BCI (H/I) ratio and a prespecified cut point.
Statistical Analysis
Data were analyzed from January 2025 to March 2026. Primary analyses included a comparison of each questionnaire item before and after BCI testing. Changes in physician treatment recommendations were analyzed using the McNemar test. Physician confidence and patient preference, perceptions, and comfort levels regarding treatment recommendations before and after BCI testing were analyzed using the Wilcoxon signed rank test. Fisher exact test evaluated the relationship between BCI categories and clinical parameters. Descriptive statistics were used to summarize and display the distribution of pre-BCI and post-BCI responses. Differences in mean BCI prognostic risk scores between patients whose physicians recommended EET vs those whose physicians recommended against EET after results from the BCI predictive analysis were assessed using analysis of variance. Factors associated with discordant EET decision-making were evaluated separately in the BCI (H/I)–High and BCI (H/I)–Low subgroups using multivariable logistic regression with stepwise variable selection based on Akaike Information Criterion. Adjusted odds ratios (AORs) comparing patients whose physicians recommended EET vs those whose physicians did not recommend EET, 95% CIs, and likelihood ratio test P values were reported for variables retained in the final models. Statistical significance was defined as a 2-tailed P < .05. Statistical analyses were performed using R, version 4.2.1 (R Foundation for Statistical Computing).
Results
Patient Characteristics
Among 3023 patients with early-stage, HR+ breast cancer enrolled in the BCI Registry study, 2977 patients had verified clinical data and BCI testing results. The final analyzable cohort included 2900 patients for whom both physician and patient questionnaires were completed both before and after BCI testing (eFigure 1 in Supplement 1).
Clinicopathologic characteristics of the study cohort are summarized in Table 1. The mean (SD) age at enrollment was 65.2 (10.3) years (range, 31-93 years). Overall, 2570 patients (88.6%) were postmenopausal, 2245 (77.4%) had N0 disease, 2501 (86.2%) had HER2-negative (HER2−) disease, 2129 (73.4%) had T1 tumors, and 1565 (54.0%) had grade 2 tumors. Most patients (1870 [64.5%]) did not receive any chemotherapy. Adjuvant endocrine therapy consisted of tamoxifen for 409 patients (14.1%), an aromatase inhibitor (AI) for 2108 (72.7%), and sequential tamoxifen–AI therapy for 373 (12.9%). Additional clinicopathological characteristics of the cohort can be found in eTable 1 in Supplement 1.
Table 1. Clinicopathologic Characteristics of the Breast Cancer Index (BCI) Registry Cohort.
| Characteristic | Patients, No (%) (N = 2900) |
|---|---|
| Age at registry enrollment, y | |
| <40 | 23 (0.8) |
| 40-49 | 200 (6.9) |
| 50-59 | 634 (21.9) |
| 60-74 | 1488 (51.3) |
| ≥75 | 555 (19.1) |
| Menopausal status at registry enrollment | |
| Premenopausal | 281 (9.7) |
| Perimenopausal | 49 (1.7) |
| Postmenopausal | 2570 (88.6) |
| T stage | |
| T1 | 2129 (73.4) |
| T2 | 708 (24.4) |
| T3 | 63 (2.2) |
| Tumor grade | |
| 1 | 818 (28.2) |
| 2 | 1565 (54.0) |
| 3 | 517 (17.8) |
| Nodal status | |
| N0 | 2245 (77.4) |
| N1 (1-3) | 655 (22.6) |
| HER2 status | |
| HER2– | 2501 (86.2) |
| HER2+ | 376 (13.0) |
| Uncertain | 23 (0.8) |
| Ki-67 proliferation index | |
| <20 | 1172 (40.4) |
| ≥20 | 955 (32.9) |
| Unknown | 773 (26.7) |
| Prior chemotherapy | |
| Adjuvant | 748 (25.8) |
| Neoadjuvant | 246 (8.5) |
| Both | 36 (1.2) |
| None | 1870 (64.5) |
| Prior adjuvant endocrine therapy | |
| Tamoxifen | 409 (14.1) |
| Aromatase inhibitor | 2108 (72.7) |
| Sequential | 373 (12.9) |
| Unknown | 10 (0.3) |
| BCI predictive | |
| BCI (H/I)–High | 1100 (37.9) |
| BCI (H/I)–Low | 1800 (62.1) |
| BCI prognostic | |
| BCI low-risk | 1348 (46.5) |
| BCI high-risk | 1552 (53.5) |
Abbreviation: H/I, HOXB13/IL17BR ratio.
At baseline, 2399 patients (82.7%) reported adverse effects from endocrine therapy, including 1783 (61.5%) with muscle and joint complaints, 1735 (59.9%) with hot flashes, 1174 (40.4%) with vaginal complaints, 1123 (38.7%) with psychological complaints, and 1040 (35.9%) with sexual complaints (eTable 2 in Supplement 1). Most adverse effects were reported as mild or moderate, but 717 patients (24.7%) reported at least 1 severe adverse effect. Of all reported adverse effects, muscle and joint complaints (1012 [34.9%]) and hot flashes (946 [32.7%]) were most commonly reported as moderate or severe.
Prognostic and Predictive Classification by BCI
The BCI prognostic model stratified 1348 patients (46.5%) as having low risk of late distant recurrence and 1552 (53.5%) as having high risk of late distant recurrence. Among 2245 patients with N0 disease, 1209 (53.9%) were classified as having low risk and 1036 (46.1%) as having high risk. Among 655 patients with N1 disease, 139 (21.2%) were classified as having low risk and 516 (78.8%) as having high risk. The BCI predictive component classified 1800 tumors (62.1%) as BCI (H/I)–Low (low likelihood to benefit), and 1100 (37.9%) were classified as BCI (H/I)–High (high likelihood to benefit) (Table 2).
Table 2. Physician Treatment Recommendations Pre–Breast Cancer Index (BCI) and Post-BCI Testing for Extended Endocrine Therapy (EET)a.
| Risk category/ likelihood to benefit | Physician treatment recommendations for EET, No. (%) | |||||||
|---|---|---|---|---|---|---|---|---|
| Total patients (N = 2900) | Pre-BCI recommendation | Post-BCI recommendation | ||||||
| No EET (n = 1281) | Yes EET (n = 1606) | Not Answered (n = 13) | No EET (n = 1655) | Yes EET (n = 1234) | Not Answered (n = 11) | |||
| Low risk/low likelihood to benefit | 1119 (38.6) | 610 (54.5) | 501 (44.8) | 8 (0.7) | 1043 (93.2) | 73 (6.5) | 3 (0.3) | |
| Low risk/high likelihood to benefit | 229 (7.9) | 111 (48.5) | 118 (51.5) | 0 | 54 (23.6) | 175 (76.4) | 0 | |
| High risk/low likelihood to benefit | 681 (23.5) | 246 (36.1) | 434 (63.7) | 1 (0.2) | 533 (78.3) | 147 (21.6) | 1 (0.1) | |
| High risk/high likelihood to benefit | 871 (30.0) | 314 (36.1) | 553 (63.5) | 4 (0.4) | 25 (2.9) | 839 (96.3) | 7 (0.8) | |
The percentages within pre-BCI vs post-BCI recommendations were calculated per BCI prognostic and predictive categories.
When both prognostic and predictive results were combined, 1119 patients (38.6%) were classified as low risk/low likelihood to benefit, 229 (7.9%) as low risk/high likelihood to benefit, 681 (23.5%) as high risk/low likelihood to benefit, and 871 (30.0%) as high risk/high likelihood to benefit (Table 2).
Physician Treatment Recommendations for EET
Among 2900 patients, the number of physicians who recommended EET decreased from 1606 (55.4%) before BCI testing to 1234 (42.6%) after BCI testing, while the number of patients not recommended for EET increased from 1281 (44.2%) to 1655 (57.0%) (P < .001) (Figure 1 and Table 2).
Figure 1. Sankey Diagram Showing Physician Pre–Breast Cancer Index (BCI) and Post-BCI Testing Recommendations for Extended Endocrine Therapy (EET).
Among the 1100 patients classified as BCI (H/I)–High, the number recommended for EET increased from 671 (61.0%) before BCI testing to 1014 (92.2%) after BCI testing, while the number of patients not recommended for EET decreased from 425 (38.6%) to 79 (7.2%) (eFigure 2 in Supplement 1). Among the 1800 classified as BCI (H/I)–Low, an increased number of physicians recommended against EET from 856 (47.6%) before BCI testing to 1576 (87.6%) after BCI testing, while the number recommended for EET decreased from 935 (51.9%) to 220 (12.2%).
Among the 1552 patients classified as BCI high risk, EET recommendations remained unchanged, shifting from 987 patients (63.6%) recommended EET before BCI testing to 986 (63.5%) after BCI testing, while nonrecommendation rates remained stable (560 [36.1%] vs 558 [36.0%]). Conversely, among 1348 patients at low risk of distant recurrence, physicians who did not recommend EET increased from 721 (53.5%) before BCI testing to 1097 (81.4%) after BCI testing, while the proportion recommending EET decreased from 619 (45.9%) to 248 (18.4%) (eFigure 2 in Supplement 1).
Among 1119 patients classified as low risk/low likelihood to benefit (Table 2), the number of physicians who did not recommend EET increased from 610 (54.5% before to 1043 (93.2%) after BCI testing. In contrast, among 229 patients classified as low risk/high likelihood to benefit, EET recommendations increased from 118 (51.5%) before to 175 (76.4%) after BCI testing. Similarly, among 681 patients with high risk/low likelihood to benefit, recommendations against EET increased from 246 (36.1%) before to 533 (78.3%) after BCI testing. Conversely, among 871 patients classified as high risk/high likelihood to benefit, EET recommendations increased from 553 (63.5%) before BCI testing to 839 (96.3%) after BCI testing.
Overall, 1209 physicians (41.7%) changed their EET recommendation (P < .001) (Figure 1). Among 791 patients with a recommendation change from “Yes EET” to “No EET,” 780 (98.6%) were classified as low risk and/or low likelihood to benefit from EET, including 453 (57.3%) with both low risk and low likelihood to benefit (eTable 3 in Supplement 1). Among 418 patients with a recommendation change from “No EET” to “Yes EET,” 394 (94.3%) were classified as high risk and/or high likelihood to benefit from EET, including 296 (70.8%) with both high risk and high likelihood to benefit (eTable 3 in Supplement 1).
For the 1281 patients not recommended for EET before BCI testing, 603 physicians (47.1%) cited low risk of recurrence, 221 (17.3%) cited risk of osteoporosis, 110 (8.6%) cited adverse effects, and 264 (20.6%) cited multiple reasons (eTable 4 in Supplement 1). Regardless of the specific reason, BCI classified approximately one-half of the patients as high risk and/or high likelihood to benefit from EET.
The number of physicians with high confidence in their treatment recommendation (confident or strongly confident) increased from 1860 (64.1%) before BCI testing to 2571 (88.7%) after testing (Figure 2A). In particular, BCI testing led to a 21.6 percentage-point increase (n = 626) in the proportion of physicians who felt strongly confident in their EET recommendation. Conversely, the number of physicians with low confidence levels (not at all confident, not confident, or ambivalent) decreased from 948 (32.6%) before testing to 314 (10.9%) after testing (Figure 2A). Overall, 1269 physicians (43.8%) felt more confident in their treatment recommendation after BCI testing (P < .001) (Figure 2B).
Figure 2. Bar Graphs Showing Confidence and Comfort Levels in Pre–Breast Cancer Index (BCI) and Post-BCI Decisions for Extended Endocrine Therapy (EET).
A and B, physician confidence in treatment recommendations. C and D, patient comfort regarding EET pre-BCI and post-BCI testing. The bar graphs (panels A and C) illustrate the reported confidence and comfort levels; the waterfall plots (panels B and D) illustrate changes in confidence and comfort levels among physicians and patients.
Clinical and Genomic Correlates of EET Recommendations Not Concordant With BCI Predictive Results
Patients classified as BCI (H/I)–High who were not recommended for EET after BCI testing (n = 79) had more favorable clinicopathologic features compared with those for whom EET was recommended (n = 1014), including a higher proportion of T1 tumors (67 [84.8%] vs 692 [68.2%]; P = .006), more G1 tumors (35 [44.3%] vs 147 [14.5%]; P < .001), a higher percentage of HER2− (73 [92.4%] vs 772 [76.1%]; P = .003), lower Ki-67 expression (<20%: 48 [60.7%] vs 296 [29.2%]; P < .001) and less use of adjuvant chemotherapy (17 [21.5] vs 348 [34.3%,]; P < .001) (eTable 5 in Supplement 1). Importantly, their mean (SD) BCI prognostic risk was significantly lower compared with those for whom EET was recommended (4.34% [2.90%] vs 9.37% [4.58%]; P < .001). Multivariable analysis with variable selection identified T stage, nodal status, Ki-67 proliferation index, and BCI prognostic risk categories as the variables retained in the final model. However, only T stage, Ki-67, and BCI prognostic risk categories were independently associated with discordant EET decision-making among patients classified as BCI (H/I)–High (eTable 6 in Supplement 1).
Conversely, patients classified as BCI (H/I)–Low who were recommended for EET after BCI testing (n = 220) were significantly younger than those not recommended EET (n = 1576) (<50 years: 37 [16.8%] vs 110 [7.0%]; P < .001), had more T2/T3 tumors (93 [42.3%] vs 342 [21.7%]; P < .001), had more G2/G3 tumors (174 [79.1%] vs 991 [62.9%]; P < .001), had more N1 disease (102 [46.4%] vs 268 [17.0%]; P < .001), and were more likely to have received adjuvant chemotherapy (79 [35.9%] vs 300 [19.0%]; P < .001) (eTable 5 in Supplement 1). Consistent with these clinicopathologic features, their mean (SD) BCI prognostic risk was significantly higher compared with patients classified as BCI (H/I)–Low who were not recommended EET (8.24% [4.73%] vs 4.82% [3.39%]; P < .001).
After multivariable analysis and variable selection, age, menopausal status, T stage, nodal status, prior chemotherapy, and BCI prognostic risk categories were retained in the final multivariable model. Only age, T stage, nodal status, and BCI prognostic risk categories were independently associated with discordant EET decision-making among patients classified as BCI (H/I)–Low (eTable 7 in Supplement 1).
Patient Perceptions About EET and Cancer Recurrence
Overall, the number of patients who indicated a slight or strong preference for EET decreased from 2199 (75.8%) before BCI testing to 1555 (53.6%) after BCI testing (Table 3). Among patients classified as low risk/low likelihood to benefit (n = 1119), the number recommended to receive EET decreased from 833 (74.5%) before BCI testing to 309 (27.7%) after BCI testing. Conversely, among patients classified as low risk/high likelihood to benefit (n = 229), the proportion remained relatively unchanged, from 180 (78.6%) before to 174 (76.0%) after BCI testing. Among patients classified as high risk/low likelihood to benefit (n = 681), the number decreased from 505 (74.1%) before BCI testing to 299 (43.9%) after BCI testing. In contrast, among patients classified as high risk/high likelihood to benefit (n = 871), the proportion increased from 681 (78.2%) before to 773 (88.7% after BCI testing.
Table 3. Pre–Breast Cancer Index (BCI) and Post-BCI Patient Preference for Extended Endocrine Therapy (EET) After 5 Yearsa.
| Risk category/ likelihood to benefit | Total patients (N = 2900) | Patient preference for EET, No. (%) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Pre-BCI | Post-BCI | ||||||||
| Do not want to continue (n = 691) | Slightly in favor (n = 1271) | Strongly prefer (n = 928) | Not answered (n = 10) | Do not want to continue (n = 1307) | Slightly in favor (n = 722) | Strongly prefer (n = 833) | Not answered (n = 38) | ||
| Low risk/low likelihood to benefit | 1119 (38.6) | 282 (25.2) | 501 (44.8) | 332 (29.7) | 4 (0.3) | 788 (70.4) | 211 (18.9) | 98 (8.8) | 22 (1.9) |
| Low risk/high likelihood to benefit | 229 (7.9) | 48 (21.0) | 120 (52.4) | 60 (26.2) | 1 (0.4) | 52 (22.7) | 81 (35.4) | 93 (40.6) | 3 (1.3) |
| High risk/low likelihood to benefit | 681 (23.5) | 174 (25.6) | 276 (40.5) | 229 (33.6) | 2 (0.3) | 374 (54.9) | 177(26.0) | 122 (17.9) | 8 (1.2) |
| High risk/high likelihood to benefit | 871 (30.0) | 187 (21.5) | 374 (43.0) | 307 (35.2) | 3 (0.3) | 93 (10.7) | 253 (29.0) | 520 (59.7) | 5 (0.6) |
The percentages within pre-BCI vs post-BCI recommendations were calculated per BCI prognostic and predictive categories.
More than one half of all patients (1479 [51.0%]) changed their preference for EET after BCI testing (eTable 8 in Supplement 1). Of these, 987 patients (66.7%) indicated a decreased preference for EET and 492 (33.3%) indicated an increased preference for EET. The changes in patient preferences for EET were associated with BCI test results: 881 patients (89.3%) with a decreased preference for EET were BCI (H/I)–Low (P < .001), and 387 patients (78.7%) with an increased preference for EET were BCI (H/I)–High (P < .001).
The number of patients reporting a high comfort level (comfortable or strongly comfortable) about the EET decision increased from 2078 (71.6%) before testing to 2493 (86.0%) after testing (Figure 2C). In particular, BCI testing was associated with a 23.3 percentage-point increase (675 of 2900) in the proportion of patients who reported feeling strongly comfortable with the EET decision. Conversely, the number of patients reporting low comfort level (not at all comfortable, not comfortable, or ambivalent) about the EET decision decreased from 802 (27.6%) before testing to 386 (13.3%) after testing. A total of 1260 patients (43.4%) felt more comfortable with their EET decision after BCI testing (P < .001) (Figure 2D).
Among 1348 patients classified as BCI low-risk, the number of those reporting no fear about their cancer returning increased from 479 (35.5%) before BCI testing to 640 (47.5%) after BCI testing, while those who feared their cancer might return (somewhat likely or very likely) decreased from 865 (64.1%) to 704 (52.2%) (eFigure 3A in Supplement 1). However, among BCI high-risk patients (n = 1552), there was no significant change with respect to their fear of cancer returning.
After BCI testing, significantly more patients reported less concern about EET costs (692 [23.9%] vs 402 [13.9%]), drug safety (756 [26.1%] vs 574 [19.8%]) and EET benefit (902 [31.1%] vs 665 [22.9%]) (P < .001 for all) (eFigure 3B in Supplement 1). There was no significant difference between the number of patients who reported less concern vs those who reported more concern about EET adverse effects (780 [26.9%] vs 717 [24.7%]; P = .35).
Discussion
This final decision-impact analysis of the prospective BCI Registry cohort study provides further evidence of the important treatment guidance and clinical utility of BCI in informing decisions regarding EET. The data show that BCI influenced both physicians’ treatment recommendations and patients’ preferences, enabling more personalized and informed care.
In this full cohort, 41.7% of physicians changed their treatment recommendation for EET after receiving BCI results, and 43.8% reported increased confidence in their recommendation. Notably, EET treatment recommendations were the lowest among patients for whom the BCI indicated a low risk of recurrence and a low likelihood of EET benefit, potentially sparing patients from overtreatment and its associated adverse effects. Conversely, BCI testing was associated with the highest rate of recommendations for EET among patients with high risk and high likelihood of benefit profiles, thereby identifying patients most likely to derive clinically meaningful benefit from extended endocrine therapy.
The analysis of the 4 BCI result categories demonstrated that the BCI predictive result was the main criterion that physicians used for decision-making regarding EET recommendation, while the BCI prognostic score was additionally associated with treatment decision (eFigure 2 in Supplement 1). After BCI testing, EET recommendations increased from 61.0% to 92.2% among patients classified as BCI (H/I)-High and decreased from 51.9% to 12.2% among those classified as BCI (H/I)-Low. However, EET recommendations remained unchanged among patients with high risk based on BCI prognostic scores; nearly two-thirds of patients (63.6% vs 63.5%) recommended EET both before and after BCI testing. In contrast, EET recommendation decreased from 45.9% to 18.4% among patients with low risk. These data highlight the major impact of BCI (H/I) as a predictive biomarker, while the BCI prognostic model may further guide EET decision-making.
A novel and informative result from the current study was the analysis of clinical and genomic correlates for EET recommendations that were discordant with BCI predictive results. Multivariable logistic regression demonstrated that both clinicopathological factors and BCI prognostic results influenced discordant treatment decisions. For patients classified as BCI (H/I)–High, whereas T stage, Ki-67, and BCI prognostic risk categories were independently associated with EET recommendation, BCI prognostic score was most strongly associated with not recommending EET, with odds approximately 8 times higher among patients with low risk vs high risk. Conversely, among patients classified as BCI (H/I)–Low, nodal status and BCI prognostic risk categories were the most significant predictors of EET recommendation. The odds of making a discordant EET recommendation (ie, recommending EET) were approximately 2 times higher among patients classified as BCI high-risk than those classified as BCI low-risk. These data demonstrate that when physicians make EET recommendations discordant with BCI predictive results, BCI prognostic results had a notable influence on these decisions.
Patient-reported outcomes were also positively affected by BCI results. Approximately 43% of patients reported feeling more comfortable with their EET decision after BCI testing. In addition, receiving BCI test results was associated with reduced patient concerns about EET cost, drug safety, and treatment benefit, while concerns about adverse effects remained largely unchanged. A BCI low-risk result was associated with a decrease in the fear of cancer recurrence.
In a prior analysis of the BCI Registry, conducted after 1000 patients were enrolled, physicians changed their EET recommendation for 40% of cases and reported increased confidence in the recommendation in 39% of cases after BCI testing.16 After BCI testing, 41% of patients reported higher comfort levels with the EET decision, and 21% to 29% reported lower levels of concern around EET cost, safety, and benefit. Two other prospective decision-impact studies in patients with stage I to III ER+ breast cancer have been completed for the BCI.19,20 Prior study results are consistent with this analysis of the BCI Registry study, further substantiating the significant impact of BCI on EET decision-making.
Limitations
This study has some limitations. With more than 3000 patients enrolled, the BCI Registry is the largest study to date to evaluate the effects of BCI on the decisions and perceptions around EET for both physicians and patients. Some bias might exist because of the self-reported, subjective nature of some questionnaire items and variability in timing. Bias is inherent to subjective items such as confidence, comfort, or concern, and stated preferences may not reflect actual behavior. Some selection bias may result from physicians’ familiarity and comfort with genomic testing; therefore, changes in treatment recommendations may be lower for physicians skeptical of genomic testing. Even so, consistency of the results between the current findings and the previous BCI Registry analysis of 1000 patients,16 and consistency with prior studies,19,20 further support the reliability of the current results.
Conclusions
This cohort study of patients from the BCI Registry confirms the clinical utility of BCI to support EET decision-making for both physicians and patients. BCI results led to significant changes in physicians’ treatment recommendations and patients’ preferences for EET, increased physician confidence, improved patient satisfaction regarding the treatment decision, and reduced patient concerns about the cost, drug safety, and benefit of EET.
eTable 1. Additional Clinicopathological Characteristics
eTable 2. Patient Responses at Baseline regarding Side Effects of Endocrine Therapy
eTable 3. Changes in Physician Recommendations for EET Following BCI Testing
eTable 4. Physician’s Reasons for Not Recommending EET Before BCI Testing
eTable 5. Clinicopathologic Characteristics of Post-BCI Physician Treatment Recommendations for EET Stratified by BCI Predictive Categories
eTable 6. Multivariable Logistic Regression Analysis of Factors Associated With Discordant Post-BCI Physician EET Recommendations for Patients Stratified as BCI (H/I)-High
eTable 7. Multivariable Logistic Regression Analysis of Factors Associated With Discordant Post-BCI Physician EET Recommendations for Patients Stratified as BCI (H/I)-Low
eTable 8. Changes in Patient Preference for Continuing EET After BCI Testing
eFigure 1. BCI Registry Case Flow
eFigure 2. Pre-BCI Vs Post-BCI Physician Treatment Recommendations for EET
eFigure 3. Pre-BCI and Post- BCI Patient (A) Thoughts About Their Cancer Returning, (B) Changes In Concerns About EET
Data Sharing Statement
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eTable 1. Additional Clinicopathological Characteristics
eTable 2. Patient Responses at Baseline regarding Side Effects of Endocrine Therapy
eTable 3. Changes in Physician Recommendations for EET Following BCI Testing
eTable 4. Physician’s Reasons for Not Recommending EET Before BCI Testing
eTable 5. Clinicopathologic Characteristics of Post-BCI Physician Treatment Recommendations for EET Stratified by BCI Predictive Categories
eTable 6. Multivariable Logistic Regression Analysis of Factors Associated With Discordant Post-BCI Physician EET Recommendations for Patients Stratified as BCI (H/I)-High
eTable 7. Multivariable Logistic Regression Analysis of Factors Associated With Discordant Post-BCI Physician EET Recommendations for Patients Stratified as BCI (H/I)-Low
eTable 8. Changes in Patient Preference for Continuing EET After BCI Testing
eFigure 1. BCI Registry Case Flow
eFigure 2. Pre-BCI Vs Post-BCI Physician Treatment Recommendations for EET
eFigure 3. Pre-BCI and Post- BCI Patient (A) Thoughts About Their Cancer Returning, (B) Changes In Concerns About EET
Data Sharing Statement
