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Biomarker Dynamics and Long-Term Treatment Outcomes in Breast Cancer Patients with Residual Cancer Burden after Neoadjuvant Therapy.

ABSTRACT: A residual cancer burden after neoadjuvant therapy (NAT) for breast cancer (BC) is associated with worse treatment outcomes compared to patients who achieved pathologic complete remission. This single-institutional retrospective study of 767 consecutive patients, including 468 patients with assessable residual cancer burden (aRCB) after NAT, with a median follow-up of 36 months, evaluated the biomarkers assessed before NAT from a biopsy and after NAT from a surgical specimen, their dynamics, and effect on long-term outcomes in specific breast cancer subtypes. The leading focus was on proliferation index Ki-67, which was significantly altered by NAT in all BC subtypes (p < 0.001 for HER2 positive and luminal A/B HER2 negative and p = 0.001 for TNBC). Multivariable analysis showed pre-NAT and post-NAT Ki-67 as independent predictors of survival outcomes for luminal A/B HER2 negative subtype. For TNBC, post-NAT Ki-67 was significant alone, and, for HER2 positive, the only borderline association of pre-NAT Ki-67 was observed in relation to the overall survival. Steroid and HER2 receptors were re-assessed just in a portion of the patients with aRCB. The concordance of both assessments was 92.9% for ER status, 80.1% for PR, and 92.2% for HER2. In conclusion, these real-world data of a consecutive cohort confirmed the importance of biomarkers assessment in patients with aRCB, and the need to consider specific BC subtypes when interpreting their influence on prognosis.

SUBMITTER: Holanek M

PROVIDER: S-EPMC9318288 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The residual cancer burden index was developed as a method to quantify residual disease ranging from pathological complete response to extensive residual disease. The aim of this study was to evaluate the inter-Pathologist reproducibility in the residual cancer burden index score and category, and in their long-term prognostic utility. Pathology slides and pathology reports of 100 cases from patients treated in a randomized neoadjuvant trial were reviewed independently by five pathologists. The size of tumor bed, average percent overall tumor cellularity, average percent of the in situ cancer within the tumor bed, size of largest axillary metastasis, and number of involved nodes were assessed separately by each pathologist and residual cancer burden categories were assigned to each case following calculation of the numerical residual cancer burden index score. Inter-Pathologist agreement in the assessment of the continuous residual cancer burden score and its components and agreement in the residual cancer burden category assignments were analyzed. The overall concordance correlation coefficient for the agreement in residual cancer burden score among pathologists was 0.931 (95% confidence interval (CI) 0.908-0.949). Overall accuracy of the residual cancer burden score determination was 0.989. The kappa coefficient for overall agreement in the residual cancer burden category assignments was 0.583 (95% CI 0.539-0.626). The metastatic component of the residual cancer burden index showed stronger concordance between pathologists (overall concordance correlation coefficient=0.980; 95% CI 0.954-0.992), than the primary component (overall concordance correlation coefficient=0.795; 95% CI 0.716-0.853). At a median follow-up of 12 years residual cancer burden determined by each of the pathologists had the same prognostic accuracy for distant recurrence-free and survival (overall concordance correlation coefficient=0.995; 95% CI 0.989-0.998). Residual cancer burden assessment is highly reproducible, with reproducible long-term prognostic significance.

Project description:BACKGROUND:The integration of residual cancer burden (RCB) and post-treatment Ki67 as residual proliferative cancer burden (RPCB) has been proposed as a stronger predictor of long-term outcome in unselected patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT), as compared with RCB. However, no specific analysis in hormone-receptor-positive (HR+) human epidermal growth receptor 2-negative (HER2-) BC is available so far. MATERIALS AND METHODS:A cohort of 130 patients with HR+/HER2- BC who underwent NACT between 2000 and 2014 was included. Archival surgical specimens were evaluated for RCB. RPCB was calculated by combining RCB and Ki67 as previously described. Patients were categorized in four RCB and RPCB categories (pathological complete response and tertiles). Disease-free survival (DFS) and overall survival (OS) estimates were determined by Kaplan-Meier analysis and compared using the log-rank test. Overall change of ?2 and c-indexes were used to compare the performance of the prognostic models. RESULTS:RPCB was calculated for 85 patients. After a median follow up of 8.5?years, RCB was associated with OS (p = .048) but not with DFS (p = .152); RPCB was instead significantly associated with both DFS and OS (p = .034 and p < .001, respectively). In terms of OS, RPCB provided a significant amount of prognostic information beyond RCB (??2 5.73, p < .001). In addition, c-index for OS prediction was significantly higher for RPCB as compared with RCB (0.79 vs. 0.61, p = .03). CONCLUSION:This is the first study evaluating RPCB in patients with HR+/HER2- BC treated with NACT. In this independent cohort, RPCB was a strong predictor of DFS and OS. The better performance of RPCB versus RCB was in part due to the ability of RPCB to discriminate a subgroup of patients with a particularly worse prognosis after NACT, who may be candidates for clinical trials evaluating novel adjuvant strategies. IMPLICATIONS FOR PRACTICE:The present work validated residual proliferative cancer burden (RPCB) as a strong predictor of long-term outcome in patients with hormone receptor-positive human epidermal growth receptor 2-negative (HR+/HER2-) breast cancer (BC) treated with neoadjuvant chemotherapy. In addition, results from the present study suggest RPCB as a promising tool to identify patients with HR+/HER2- BC who might potentially benefit from the inclusion in clinical trials evaluating novel or escalated postneoadjuvant treatment strategies because it allowed to discriminate a subgroup of patients with particularly poor prognosis despite having received subsequent endocrine therapy in the adjuvant setting.

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Biomarker Dynamics and Long-Term Treatment Outcomes in Breast Cancer Patients with Residual Cancer Burden after Neoadjuvant Therapy.

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