Socioeconomic Disparities in Breast Cancer Survival: Examining Potential Mediator Role of Oncotype DX(ODX) Test and Stage at Diagnosis Among HR+/HER2- Breast Cancer Women
Simple Summary
Abstract
1. Introduction
1.1. Background
1.2. Importance of the Study
1.3. SES, Genomic Testing, and Stage
1.4. Research Aims
2. Methods and Material
2.1. Data Source and Study Design
2.2. Outcome
2.3. Exposure
2.4. Mediator
2.5. Covariates/Confounders
2.6. Statistical Analysis
3. Results
3.1. Factors Associated with OS and BCSS for Women with Stage I-II Breast Cancer
3.2. Mediation Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
List of Abbreviations
References
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Variable | Total | Low SES | High SES | p-Value |
---|---|---|---|---|
(N = 8931) | (n = 4663, 52.21%) | (n = 4268, 47.79%) | ||
n (%) | n (%) | n (%) | ||
Race/Ethnicity | ||||
White | 6679 (74.78) | 2934 (43.93) | 3745 (56.07) | <0.0001 |
Black | 2145 (24.02) | 1685 (78.55) | 460 (21.45) | |
Others | 107 (1.20) | 44 (41.12) | 63 (58.88) | |
Age at diagnosis (year) | ||||
20–49 | 1328 (14.87) | 697 (52.48) | 631 (47.52) | 0.9255 |
50–59 | 2002 (22.42) | 1032 (51.55) | 970 (48.45) | |
60–69 | 2886 (32.31) | 1502 (52.04) | 1384 (47.96) | |
70–79 | 1956 (21.90) | 1027 (52.51) | 929 (47.49) | |
80 and over | 759 (8.50) | 405 (53.36) | 354 (46.64) | |
Insurance | ||||
No insurance | 198 (2.22) | 138 (69.70) | 60 (30.30) | <0.0001 |
Medicaid | 974 (10.91) | 723 (74.23) | 251 (25.77) | |
Private | 4760 (53.30) | 2214 (46.51) | 2546 (53.49) | |
Medicare | 2769 (31.00) | 1468 (53.02) | 1301 (46.98) | |
Other public health insurance b | 121 (1.35) | 62 (51.24) | 59 (48.76) | |
Unknown | 109 (1.22) | 58 (53.21) | 51 (46.79) | |
Urban–rural residence | ||||
Urban (100% urban) | 4148 (46.44) | 1951 (47.03) | 2197 (52.97) | <0.0001 |
Mostly urban (50–100%) | 2690 (30.12) | 1331 (49.48) | 1359 (50.52) | |
Mostly rural (0–50%) | 1263 (14.14) | 713 (56.45) | 550 (43.55) | |
Rural (100% rural) | 830 (9.29) | 668 (80.48) | 162 (19.52) | |
Body mass index in kg/m2 | ||||
Underweight (<18.5) | 249 (2.79) | 134 (53.82) | 115 (46.18) | <0.0001 |
Normal weight (18.5–<25) | 1821 (20.39) | 775 (42.56) | 1046 (57.44) | |
Overweight (25–<30) | 2351 (26.32) | 1215 (51.68) | 1136 (48.32) | |
Obesity (≥30) | 4510 (50.50) | 2539 (56.30) | 1971 (43.70) | |
Charlson comorbidity scores | ||||
0 | 7110 (79.61) | 3569 (50.20) | 3537 (49.80) | <0.0001 |
1 | 1372 (15.36) | 800 (58.42) | 570 (41.58) | |
2+ | 458 (5.13) | 294 (64.63) | 161 (35.37) | |
AJCC stage | ||||
I | 6186 (69.26) | 3125 (50.52) | 3061 (49.48) | <0.0001 |
II | 2633 (29.48) | 1471 (55.87) | 1162 (44.13) | |
III | 112 (1.25) | 67 (59.82) | 45 (40.18) | |
Tumor grade | ||||
Grade I | 2807 (31.43) | 1399 (49.84) | 1408 (50.16) | <0.0001 |
Grade II | 4390 (49.15) | 2262 (51.53) | 2128 (48.47) | |
Grade III/IV | 1488 (16.66) | 866 (58.20) | 622 (41.80) | |
Grade unknown, NR | 246 (2.75) | 136 (55.28) | 110 (44.72) | |
Surgery and reported radiation | ||||
Lumpectomy plus radiation | 4457 (49.90) | 2198 (49.32) | 2259 (50.68) | <0.0001 |
Mastectomy plus radiation | 566 (6.34) | 303 (53.53) | 263 (46.47) | |
Lumpectomy with no/unknown radiation | 738 (8.26) | 421 (57.05) | 317 (42.95) | |
Mastectomy with no/unknown radiation | 3170 (35.49) | 1741 (54.92) | 1429 (45.08) | |
Oncotype DX test | ||||
Yes | 3970 (44.45%) | 1974 (49.72) | 1996 (50.28) | <0.0001 |
No | 4961 (55.55%) | 2689 (54.20) | 2272 (45.80) | |
Chemotherapy received | ||||
Yes | 2140 (23.96) | 1184 (55.33) | 956 (44.67) | 0.0042 |
No | 6586 (73.74) | 3373 (51.21) | 3213 (48.79) | |
Unknown | 205 (2.30) | 106 (51.71) | 99 (48.29) | |
Hormone therapy received | ||||
Yes | 6729 (75.34) | 3418 (50.80) | 3311 (49.20) | <0.0001 |
No | 1677 (18.78) | 959 (57.19) | 718 (42.81) | |
Unknown | 525 (5.88) | 286 (54.48) | 239 (45.52) | |
Cause of death | ||||
Patients alive at last contact | 7771 (87.01) | 3958 (50.93) | 3813 (49.07) | <0.0001 |
BC deaths | 207 (2.32) | 133 (64.25) | 74 (35.75) | |
Other cause deaths | 953 (10.67) | 572 (60.02) | 381 (39.98) |
Variable | ODX Receipt | ODX Not Receipt | p-Value |
---|---|---|---|
(n = 3970, 44.45%) | (n = 4961, 55.55%) | ||
n (%) | n (%) | ||
Socio-economic Status (SES) | |||
Group 1 (Low SES) | 1974 (42.33) | 2689 (57.67) | <0.0001 |
Group 2 (High SES) | 1996 (46.77) | 2272 (53.23) | |
Race/Ethnicity | |||
White | 3055 (45.74) | 3624 (54.26) | <0.0001 |
Black | 861 (40.14) | 1284 (59.86) | |
Others | 54 (50.47) | 53 (49.53) | |
Age at diagnosis (year) | |||
20–49 | 659 (49.62) | 669 (50.38) | <0.0001 |
50–59 | 1072 (53.52) | 930 (46.45) | |
60–69 | 1463 (50.69) | 1423 (49.31) | |
70–79 | 684 (34.97) | 1272 (65.03) | |
80 and over | 92 (12.12) | 667 (87.88) | |
Insurance | |||
No insurance | 82 (41.41) | 116 (58.59) | <0.0001 |
Medicaid | 389 (39.94) | 585 (60.06) | |
Private | 2368 (49.75) | 2392 (50.25) | |
Medicare | 1024 (40.00) | 1745 (63.00) | |
Other public health insurance b | 68 (56.20) | 53 (43.80) | |
Unknown | 39 (35.78) | 70 (64.22) | |
Urban–rural residence | |||
Urban (100% urban) | 1814 (43.73) | 2334 (56.27) | 0.1635 |
Mostly urban (50–100%) | 1211 (45.02) | 1479 (54.98) | |
Mostly rural (0–50%) | 591 (46.79) | 672 (53.21) | |
Rural (100% rural) | 354 (42.65) | 476 (57.35) | |
Body mass index (BMI) in kg/m2 | |||
Underweight (<18.5) | 113 (45.38) | 136 (54.62) | 0.9873 |
Normal weight (18.5–<25) | 813 (44.66) | 1008 (55.35) | |
Overweight (25–<30) | 1043 (44.36) | 1308 (55.64) | |
Obesity (≥30) | 2001 (44.37) | 2509 (55.63) | |
Charlson score | |||
0 | 3259 (45.87) | 3847 (54.13) | <0.0001 |
1 | 553 (40.38) | 817 (59.62) | |
2+ | 158 (34.72) | 297 (65.28) | |
AJCC stage | |||
I | 2871 (46.41) | 3315 (53.59) | <0.0001 |
II | 1088 (41.32) | 1545 (58.68) | |
III | 11 (9.82) | 101 (90.18) | |
Tumor grade | |||
Grade I, Well-differentiated | 1190 (42.39) | 1617 (57.61) | <0.0001 |
Grade II, Moderate to Moderately well-differentiated | 2073 (47.22) | 2317 (52.78) | |
Grade III/IV, Poorly differentiated/undifferentiated, anaplastic | 624 (41.94) | 864 (58.06) | |
Grade unknown, NR | 83 (33.74) | 163 (66.26) | |
Surgery | |||
Lumpectomy plus radiation | 2194 (49.23) | 2263 (50.77) | <0.0001 |
Mastectomy plus radiation | 149 (26.33) | 417 (73.67) | |
Lumpectomy with no/unknown radiation | 251 (34.01) | 487 (65.99) | |
Mastectomy with no/unknown radiation | 1376 (43.41) | 1794 (56.59) | |
Hormone therapy received | |||
Yes | 3189 (47.39) | 3540 (52.61) | <0.0001 |
No | 576 (34.35) | 1101 (65.65) | |
Unknown | 205 (39.05) | 320 (60.95) |
Variable | Overall Survival (OS) | |||
---|---|---|---|---|
Crude Model c | Adjusted Model | |||
HR | 95% CI | HR | 95% CI | |
Socio-economic Status (SES) | ||||
Group 1 (Low SES) | 1.45 | 1.29–1.63 | 1.16 | 1.02–1.32 |
Group 2 (High SES) | 1 | 1 | ||
Race/Ethnicity | ||||
White | 1 | 1 | ||
Black | 1.19 | 1.05–1.35 | 0.99 | 0.86–1.14 |
Others | 0.47 | 0.21–1.05 | 0.53 | 0.24–1.18 |
Age at diagnosis (year) | ||||
20–50 years | 1 | 1 | ||
50–60 years | 1.48 | 1.09–2.02 | 1.72 | 1.26–2.36 |
60–70 years | 2.4 | 1.81–3.18 | 2.82 | 2.11–3.78 |
70–80 years | 4.88 | 3.70–6.43 | 4.71 | 3.48–6.37 |
80–90 years | 10.85 | 8.19–14.38 | 8.63 | 6.29–11.84 |
Insurance | ||||
No insurance | 1.33 | 0.86–2.06 | 1.5 | 0.96–2.33 |
Medicaid | 2.23 | 1.87–2.66 | 1.53 | 1.27–1.84 |
Private | 1 | 1 | ||
Medicare | 2.42 | 2.13–2.75 | 1.19 | 1.03–1.37 |
Other public health insurance b | 1.12 | 0.63–1.98 | 0.9 | 0.51–1.61 |
Unknown | 1.26 | 0.67–2.37 | 1.02 | 0.54–1.92 |
Urban–rural residence | ||||
Urban (100% urban) | 1 | 1 | ||
Mostly urban (50–100%) | 1.06 | 0.93–1.21 | 1.21 | 1.05–1.39 |
Mostly rural (0–50%) | 1.08 | 0.91–1.29 | 1.2 | 1.00–1.44 |
Rural (100% rural) | 1.22 | 1.00–1.48 | 1.11 | 0.90–1.36 |
Body mass index (BMI) in kg/m2 | ||||
Underweight (<18.5) | 1.41 | 1.04–1.92 | 1.5 | 1.10–2.04 |
Normal weight (18.5–<25) | 1 | 1 | ||
Overweight (25–<30) | 0.8 | 0.67–0.95 | 0.72 | 0.60–0.85 |
Obesity (≥30) | 0.94 | 0.81–1.08 | 0.84 | 0.72–0.97 |
Charlson score | ||||
0 | 1 | 1 | ||
1 | 1.85 | 1.61- 2.13 | 1.49 | 1.29–1.72 |
2+ | 4.02 | 3.37–4.80 | 2.99 | 2.49–3.59 |
AJCC stage | ||||
I | 1 | 1 | ||
II | 1.69 | 1.50–1.90 | 1.6 | 1.40–1.82 |
III | 3.88 | 2.66–5.68 | 2.58 | 1.72–3.87 |
Tumor grade | ||||
Grade I, Well-differentiated | 1 | 1 | ||
Grade II, Moderate to Moderately well-differentiated | 1.14 | 0.99–1.32 | 1.17 | 1.01–1.35 |
Grade III/IV, Poorly differentiated/undifferentiated, anaplastic | 1.74 | 1.48–2.05 | 1.98 | 1.65–2.36 |
Grade unknown, NR | 1.64 | 1.20–2.22 | 1.43 | 1.05–1.96 |
Surgery | ||||
Lumpectomy plus radiation | 0.57 | 0.50–0.65 | 0.79 | 0.69–0.90 |
Mastectomy plus radiation | 1.12 | 0.90–1.40 | 1.15 | 0.91–1.46 |
Lumpectomy with no/unknown radiation | 1.54 | 1.28–1.84 | 1.3 | 1.08–1.56 |
Mastectomy with no/unknown radiation | 1 | 1 | ||
Oncotype DX test | ||||
Yes | 1 | 1 | ||
No | 2.65 | 2.32–3.03 | 1.67 | 1.45–1.93 |
Chemotherapy received | ||||
Yes | 1 | 1 | ||
No | 1.22 | 1.06–1.41 | 1.12 | 0.94–1.33 |
Unknown | 0.96 | 0.62–1.48 | 0.84 | 0.53–1.33 |
Hormone therapy received | ||||
Yes | 1 | 1 | ||
No | 1.69 | 1.48–1.93 | 1.28 | 1.12–1.47 |
Unknown | 1.38 | 1.09–1.76 | 1.18 | 0.92–1.53 |
Variable | Breast Cancer—Specific Survival (BCSS) | |||
---|---|---|---|---|
Crude Model c | Adjusted Model | |||
HR | 95% CI | HR | 95% CI | |
Socio-economic Status (SES) | ||||
Group 1 (Low SES) | 1.68 | 1.26–2.23 | 1.37 | 1.01–1.87 |
Group 2 (High SES) | 1 | 1 | ||
Race/Ethnicity | ||||
White | 1 | 1 | ||
Black | 1.33 | 0.99–1.80 | 0.99 | 0.71–1.39 |
Others | 0.9 | 0.22–3.64 | 0.76 | 0.19–3.12 |
Age at diagnosis (year) | ||||
20–50 years | 1 | 1 | ||
50–60 years | 0.89 | 0.54–1.48 | 1.37 | 0.82–2.30 |
60–70 years | 1.07 | 0.68–1.70 | 2.03 | 1.24–3.33 |
70–80 years | 1.66 | 1.05–2.63 | 3.41 | 2.00–5.84 |
80–90 years | 2.33 | 1.37–3.96 | 4.99 | 2.64–9.45 |
Insurance | ||||
No insurance | 2.36 | 1.14–4.86 | 2.03 | 0.97–4.26 |
Medicaid | 1.87 | 1.25–2.81 | 1.44 | 0.94–2.19 |
Private | 1 | 1 | ||
Medicare | 1.59 | 1.17–2.16 | 1.2 | 0.85–1.71 |
Other public health insurance b | 1.3 | 0.41–4.11 | 1.02 | 0.32–3.27 |
Unknown | 0.57 | 0.08–4.10 | 0.71 | 0.10–5.17 |
Urban–rural residence | ||||
Urban (100% urban) | 1 | 1 | ||
Mostly urban (50–100%) | 1.22 | 0.88–1.69 | 1.23 | 0.89–1.71 |
Mostly rural (0–50%) | 1.37 | 0.92–2.04 | 1.39 | 0.92–2.09 |
Rural (100% rural) | 1.44 | 0.92–2.27 | 1.17 | 0.72–1.88 |
Body mass index (BMI) in kg/m2 | ||||
Underweight (<18.5) | 1.47 | 0.72–3.00 | 1.51 | 0.73–3.11 |
Normal weight (18.5–<25) | 1 | 1 | ||
Overweight (25–<30) | 0.81 | 0.54–1.22 | 0.69 | 0.46–1.05 |
Obesity (≥30) | 0.93 | 0.66–1.32 | 0.77 | 0.54–1.11 |
Charlson score | ||||
0 | 1 | 1 | ||
1 | 1.24 | 0.87–1.78 | 1.04 | 0.72–1.50 |
2+ | 1.65 | 0.94–2.90 | 1.43 | 0.80–2.56 |
AJCC stage | ||||
I | 1 | 1 | ||
II | 3.8 | 2.86–5.04 | 2.35 | 1.72–3.21 |
III | 10.18 | 5.09–20.36 | 3.78 | 1.78–8.02 |
Tumor grade | ||||
Grade I, Well-differentiated | 1 | 1 | ||
Grade II, Moderate to Moderately well-differentiated | 2.6 | 1.63–4.15 | 2.19 | 1.37–3.51 |
Grade III/IV, Poorly differentiated/undifferentiated, anaplastic | 7.87 | 4.93–12.55 | 5.17 | 3.15–8.49 |
Grade unknown, NR | 3.41 | 1.46–7.98 | 2.5 | 1.06–5.90 |
Surgery | ||||
Lumpectomy plus radiation | 0.69 | 0.51–0.94 | 0.95 | 0.69–1.31 |
Mastectomy plus radiation | 2.32 | 1.52–3.53 | 1.41 | 0.90–2.21 |
Lumpectomy with no/unknown radiation | 1.26 | 0.77–2.06 | 1.48 | 0.89–2.45 |
Mastectomy with no/unknown radiation | 1 | 1 | ||
Oncotype DX test | ||||
Yes | 1 | 1 | ||
No | 2.02 | 1.50–2.72 | 1.29 | 0.94–1.77 |
Chemotherapy received | ||||
Yes | 1 | 1 | ||
No | 0.34 | 0.26–0.44 | 0.51 | 0.36–0.73 |
Unknown | 0 | - | 0 | - |
Hormone therapy received | ||||
Yes | 1 | 1 | ||
No | 1.11 | 0.78–1.57 | 0.97 | 0.68–1.40 |
Unknown | 1.02 | 0.55–1.88 | 0.91 | 0.49–1.70 |
Mediator | Indirect Effect (95% CI) | Relative Effect (95% CI) |
---|---|---|
Overall survival (OS) | ||
Stage | 0.030 (0.011, 0.049) | 11.20 (5.50, 21.40) |
Oncotype DX | 0.024 (0.006, 0.043) | 9.00 (4.30, 19.30) |
Socioeconomic status (Direct effect) | 0.216 (0.091, 0.342) | 79.80 (61.80, 88.50) |
Total effect | 0.270 (0.144, 0.446) | |
Breast cancer-specific survival (BCSS) | ||
Stage | 0.058 (0.034, 0.091) | 13.30 (6.50, 45.20) |
Oncotype DX | 0.019 (0.004, 0.038) | 4.40 (0.90, 15.90) |
Socioeconomic status (Direct effect) | 0.352 (0.049, 0.671) | 81.50 (41.00, 91.20) |
Total effect | 0.432 (0.130, 0.755) |
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Shrestha, P.; Yu, Q.; Peters, E.S.; Trapido, E.; Hsieh, M.-C.; Ferguson, T.; Chu, Q.D.; Wu, X.-C. Socioeconomic Disparities in Breast Cancer Survival: Examining Potential Mediator Role of Oncotype DX(ODX) Test and Stage at Diagnosis Among HR+/HER2- Breast Cancer Women. Cancers 2025, 17, 1802. https://doi.org/10.3390/cancers17111802
Shrestha P, Yu Q, Peters ES, Trapido E, Hsieh M-C, Ferguson T, Chu QD, Wu X-C. Socioeconomic Disparities in Breast Cancer Survival: Examining Potential Mediator Role of Oncotype DX(ODX) Test and Stage at Diagnosis Among HR+/HER2- Breast Cancer Women. Cancers. 2025; 17(11):1802. https://doi.org/10.3390/cancers17111802
Chicago/Turabian StyleShrestha, Pratibha, Qingzhao Yu, Edward S. Peters, Edward Trapido, Mei-Chin Hsieh, Tekeda Ferguson, Quyen D. Chu, and Xiao-Cheng Wu. 2025. "Socioeconomic Disparities in Breast Cancer Survival: Examining Potential Mediator Role of Oncotype DX(ODX) Test and Stage at Diagnosis Among HR+/HER2- Breast Cancer Women" Cancers 17, no. 11: 1802. https://doi.org/10.3390/cancers17111802
APA StyleShrestha, P., Yu, Q., Peters, E. S., Trapido, E., Hsieh, M.-C., Ferguson, T., Chu, Q. D., & Wu, X.-C. (2025). Socioeconomic Disparities in Breast Cancer Survival: Examining Potential Mediator Role of Oncotype DX(ODX) Test and Stage at Diagnosis Among HR+/HER2- Breast Cancer Women. Cancers, 17(11), 1802. https://doi.org/10.3390/cancers17111802