Human pathology · 2026
Clinicopathologic and histologic determinants of the oncotype DX recurrence score in ER+/HER2- breast cancer: AJCC stage-matched comparisons and predictors of a very low recurrence score.
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Sadeghian Zohre, Rhode Sara, Sultan Hadi, Abdo Theresa, Alhalabi Ahmad, Goez-Gutierrez Elvia, Nahleh Zeina, Yoon Esther
Аннотация
CONTEXT: The Oncotype DX Recurrence Score (RS) is used to guide adjuvant chemotherapy decisions in estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. Although RS is widely used in routine practice, the extent to which score distributions differ by histologic types-specifically invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC)- within the same pathologic anatomic AJCC stages is not well studied.
DESIGN: We performed a retrospective study of ER+/HER2-invasive breast carcinomas with available RS results from 2020 to 2024 (n = 322, including IDC [n = 254] and ILC [n = 68]). RS distributions were evaluated by clinicopathologic features and histologic type. IDC and ILC were compared within pathologic anatomic AJCC stage and progesterone receptor (PR)-stratified subgroups. Moreover, two histologic types were compared for eligibility for the prespecified very-low RS endpoint (stage IA, node-negative tumors, RS < 11). Multivariable logistic regression was used to identify independent predictors of RS < 11.
RESULTS: Mean RS was similar in IDC and ILC (17.2 vs 17.1), although the score range was broader in IDC (0-83) than in ILC (5-37). Overall, PR- tumors showed significantly higher RS than PR + tumors in both stage IA and stage IIA disease (both p = 0.001). In subgroup analyses, IDC demonstrated a higher RS than ILC in the PR + stage IIB subgroup only (p = 0.03). More IDC cases met the criteria for very-low RS endpoint relevant to AJCC prognostic-stage assignment (stage IA, node-negative tumors with RS < 11), which was statistically significant (28.9% of IDC versus 8.9% of ILC; p = 0.006). On multivariable analysis, ILC remained independently associated with lower odds of RS < 11 compared with IDC (adjusted OR, 0.25; 95% CI, 0.08-0.75; p = 0.013), and PR negativity was also independently associated with lower odds of RS < 11 (adjusted OR 0.12, 95% CI 0.02-0.94, p = 0.043).
CONCLUSIONS: IDC and ILC showed similar mean RS values, but IDC had a wide range of score distribution. In-depth analysis also uncovered the subtle impact of histologic type at different pathologic anatomic AJCC stages. In particular, ILC was less likely than IDC to demonstrate a very-low RS (<11) in stage IA, node-negative ER+/HER2-disease. These findings suggest that histologic subtype may provide useful context for interpretation of RS, especially in pretest counseling regarding the likelihood of very-low genomic risk.
DESIGN: We performed a retrospective study of ER+/HER2-invasive breast carcinomas with available RS results from 2020 to 2024 (n = 322, including IDC [n = 254] and ILC [n = 68]). RS distributions were evaluated by clinicopathologic features and histologic type. IDC and ILC were compared within pathologic anatomic AJCC stage and progesterone receptor (PR)-stratified subgroups. Moreover, two histologic types were compared for eligibility for the prespecified very-low RS endpoint (stage IA, node-negative tumors, RS < 11). Multivariable logistic regression was used to identify independent predictors of RS < 11.
RESULTS: Mean RS was similar in IDC and ILC (17.2 vs 17.1), although the score range was broader in IDC (0-83) than in ILC (5-37). Overall, PR- tumors showed significantly higher RS than PR + tumors in both stage IA and stage IIA disease (both p = 0.001). In subgroup analyses, IDC demonstrated a higher RS than ILC in the PR + stage IIB subgroup only (p = 0.03). More IDC cases met the criteria for very-low RS endpoint relevant to AJCC prognostic-stage assignment (stage IA, node-negative tumors with RS < 11), which was statistically significant (28.9% of IDC versus 8.9% of ILC; p = 0.006). On multivariable analysis, ILC remained independently associated with lower odds of RS < 11 compared with IDC (adjusted OR, 0.25; 95% CI, 0.08-0.75; p = 0.013), and PR negativity was also independently associated with lower odds of RS < 11 (adjusted OR 0.12, 95% CI 0.02-0.94, p = 0.043).
CONCLUSIONS: IDC and ILC showed similar mean RS values, but IDC had a wide range of score distribution. In-depth analysis also uncovered the subtle impact of histologic type at different pathologic anatomic AJCC stages. In particular, ILC was less likely than IDC to demonstrate a very-low RS (<11) in stage IA, node-negative ER+/HER2-disease. These findings suggest that histologic subtype may provide useful context for interpretation of RS, especially in pretest counseling regarding the likelihood of very-low genomic risk.