Markers Associated With Tumor Recurrence in Patients With Breast Cancer Achieving a Pathologic Complete Response After Neoadjuvant Chemotherapy

Xie, Liyun; Wang, Kun; Chen, Hai-Lu; Shi, Yanxia; Zhang, Yuanqi; Lin, Hui‐Yi; Liang, Yuan-Ke; Xiao, Ying-Sheng; Wu, Zhi‐Yong; Yuan, Zhongyu; Qiu, Siqi

doi:10.3389/fonc.2022.860475

Cited by 9 publications

(10 citation statements)

References 39 publications

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“…This ranking indicates that the HER2-negative population, which includes the triple-negative patients, is mostly associated with increased risk for five-year recurrence. It also shows that patients with HER2-positive expression before neoadjuvant therapy have a better prognosis, which is consistent with findings in prior publications [ 44 , 45 ]. One possible explanation for this is the anti-HER2 targeted therapy that became part of the standard of care in recent years [ 46 ].…”

Section: Discussionsupporting

confidence: 92%

Multimodal Prediction of Five-Year Breast Cancer Recurrence in Women Who Receive Neoadjuvant Chemotherapy

Rabinovici-Cohen

Rejo

Hexter

et al. 2022

Cancers

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In current clinical practice, it is difficult to predict whether a patient receiving neoadjuvant chemotherapy (NAC) for breast cancer is likely to encounter recurrence after treatment and have the cancer recur locally in the breast or in other areas of the body. We explore the use of clinical history, immunohistochemical markers, and multiparametric magnetic resonance imaging (DCE, ADC, Dixon) to predict the risk of post-treatment recurrence within five years. We performed a retrospective study on a cohort of 1738 patients from Institut Curie and analyzed the data using classical machine learning, image processing, and deep learning. Our results demonstrate the ability to predict recurrence prior to NAC treatment initiation using each modality alone, and the possible improvement achieved by combining the modalities. When evaluated on holdout data, the multimodal model achieved an AUC of 0.75 (CI: 0.70, 0.80) and 0.57 specificity at 0.90 sensitivity. We then stratified the data based on known prognostic biomarkers. We found that our models can provide accurate recurrence predictions (AUC > 0.89) for specific groups of women under 50 years old with poor prognoses. A version of our method won second place at the BMMR2 Challenge, with a very small margin from being first, and was a standout from the other challenge entries.

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Section: Discussionsupporting

confidence: 92%

Multimodal Prediction of Five-Year Breast Cancer Recurrence in Women Who Receive Neoadjuvant Chemotherapy

Rabinovici-Cohen

Rejo

Hexter

et al. 2022

Cancers

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“…Secondly, our study stopped at the primary outcome of complete pathological response due to limited data. As for the prognostic outcome, Asaoka 61 and Xie 62 reached a consensus that cN(+) was found to be the most significant predictor of cancer recurrence in patients with acquired breast pCR. Besides, cN(+) and HER2-positive subtype were 2 clinicopathological prognostic factors that were significantly associated with unfavorable outcomes in terms of DFS.…”

Section: Discussionmentioning

confidence: 99%

Axillary Downstaging and the Impact of Clinical Axillary Status on Efficacy of Neoadjuvant Therapy for HER2-Positive Breast Cancer: A Network Meta-Analysis

Luo

Jiang

Liu

et al. 2023

Technol Cancer Res Treat

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Background: Lymph node downstaging and the achievement of total-pCR (ypT0/is ypN0) after neoadjuvant therapy are of great importance in HER-2 positive breast cancer. We aim to provide an overall review of neoadjuvant regimens for lymph node downstaging and to indirectly compare the total-pCR by various neoadjuvant regimens with network meta-analysis in HER2-positive patients according to their clinical lymph node status. Methods: Five English databases were searched comprehensively and systematically for relevant RCTs and case-control studies. The data extracted from the included studies were analyzed with the use of Review Manager 5.3 or STATA 15.0 software. Results: A total of 1508 published manuscripts were identified, and 17 studies including 4747 patients were finally included in our analysis. The network meta-analysis of total-pCR showed that dual-target therapy is significantly better than single-target therapy in clinically node-positive patients, and carboplatin performed significantly better than anthracycline in single-target condition. Lapatinib performed poorly in clinically node-positive patients. However, lapatinib in combination with trastuzumab was ranked at the top in the clinically node-negative group, and pertuzumab showed dissatisfied performance in contrast to the primacy of pertuzumab in clinically node-positive groups. Conclusion: In summary, different lymph node statuses led to the diverse first choice of neoadjuvant regimen. We highly recommended TCbHP as the first choice for the neoadjuvant treatment in clinically node-positive HER-2 positive breast cancer. Since lapatinib with trastuzumab ranked top in the clinically node-negative group, we looked forward to discovering the potential value of TKI in clinically node-negative patients, which needs further analysis in the future.

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“…Thirdly, despite the favorable prognostic effect of invasive disease eradication, a few of patients with pCR eventually relapse ( 9 , 10 ). Tumor recurrences are in the range of 10-15% at 5 years from surgery, as reported in the large pooled analysis of German Breast Group neoadjuvant studies on 2188 patients ( 41 ), and from a recent meta-analysis on 5748 patients ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

“…The efficacy of additional treatments in HER2-positive breast cancer patients not achieving a pCR after neoadjuvant therapy is being investigated in several studies ( 6 ), and has been reported as beneficial by the KATHERINE trial ( 7 ). Noteworthy, not all patients with an incomplete tumor response to neoadjuvant therapy relapse - two third of them are indeed disease-free at five years from surgery ( 8 ) - while up to 20% of patients who achieve a pCR eventually recur ( 9 ). This creates uncertainty, and calls into question the prognostic relevance of pCR.…”

Section: Introductionmentioning

confidence: 99%

End-of-neoadjuvant treatment circulating microRNAs and HER2-positive breast cancer patient prognosis: An exploratory analysis from NeoALTTO

Cosimo

Ciniselli²,

Pizzamiglio³

et al. 2023

Front. Oncol.

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BackgroundThe absence of breast cancer cells in surgical specimens, i.e., pathological complete response (pCR), is widely recognized as a favorable prognostic factor after neoadjuvant therapy. In contrast, the presence of disease at surgery characterizes a prognostically heterogeneous group of patients. Here, we challenged circulating microRNAs (miRNAs) at the end of neoadjuvant therapy as potential prognostic biomarkers in the NeoALTTO study.MethodsPatients treated within the trastuzumab arm (i.e., pre-operative weekly trastuzumab for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks; post-operative FEC for 3 cycles followed by trastuzumab up to complete 1 year of treatment) were randomized into a training (n= 54) and testing (n= 72) set. RT-PCR-based high-throughput miRNA profile was performed on plasma samples collected at the end of neoadjuvant treatment of both sets. After normalization, circulating miRNAs associated with event free survival (EFS) were identified by univariate and multivariate Cox regression model.ResultsStarting from 23 circulating miRNAs associated with EFS in the training set, we generated a 3-circulating miRNA prognostic signature consisting of miR-185-5p, miR-146a-5p, miR-22-3p, which was confirmed in the testing set. The 3-circulating miRNA signature showed a C-statistic of 0.62 (95% confidence interval [95%CI] 0.53-0.71) in the entire study cohort. By resorting to a multivariate Cox regression model we found a statistical significant interaction between the expression values of miR-194-5p and pCR status (p.interaction =0.005) with an estimate Hazard Ratio (HR) of 1.83 (95%CI 1.14- 2.95) in patients with pCR, and 0.87 (95%CI 0.69-1.10) in those without pCR. Notably, the model including this interaction along with the abovementioned 3-circulating miRNA signature provided the highest discriminatory capability with a C-statistic of 0.67 (95%CI 0.58-0.76).ConclusionsCirculating miRNAs are informative to identify patients with different prognosis among those with heterogeneous response after trastuzumab-based neoadjuvant treatment, and may be an exploitable tool to select candidates for salvage adjuvant therapy.

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Markers Associated With Tumor Recurrence in Patients With Breast Cancer Achieving a Pathologic Complete Response After Neoadjuvant Chemotherapy

Cited by 9 publications

References 39 publications

Multimodal Prediction of Five-Year Breast Cancer Recurrence in Women Who Receive Neoadjuvant Chemotherapy

Multimodal Prediction of Five-Year Breast Cancer Recurrence in Women Who Receive Neoadjuvant Chemotherapy

Axillary Downstaging and the Impact of Clinical Axillary Status on Efficacy of Neoadjuvant Therapy for HER2-Positive Breast Cancer: A Network Meta-Analysis

End-of-neoadjuvant treatment circulating microRNAs and HER2-positive breast cancer patient prognosis: An exploratory analysis from NeoALTTO

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