A machine learning-based algorithm to eliminate breast and axillary surgery in patients with breast cancer and pathological complete response after neoadjuvant chemotherapy.
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ABSTRACT:
SUBMITTER: de Nonneville A
PROVIDER: S-EPMC10632564 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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A machine learning-based algorithm to eliminate breast and axillary surgery in patients with breast cancer and pathological complete response after neoadjuvant chemotherapy.
de Nonneville Alexandre A Boudin Laurys L Houvenaeghel Gilles G Gonçalves Anthony A Bertucci François F
Annals of translational medicine 20230306 11
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Project description:BackgroundAxillary node status is used in clinical practice to guide the selection of axillary surgery in breast cancer patients. However, to date, the optimal axillary management following neoadjuvant therapy (NAT) for breast cancer remains controversial. Our study aimed to investigate the association of molecular subtype, clinical stage, and ypN status after NAT in breast cancer patients, especially those achieving breast pathological complete remission (pCR).Patients and methodsPatients receiving ⩾4 cycles of NAT were retrospectively included between January 2009 and January 2020. ypN status was compared among patients with different breast pCR statuses, clinical stages, and molecular subtypes in univariate and multivariate analyses.ResultsA total of 1999 patients were included: 457 (22.86%), 884 (44.22%), and 658 (32.92%) patients with cT1-2N0, cT1-2N1, and locally advanced breast cancer (LABC), respectively. Altogether, 435 (21.8%) patients achieved breast pCR: 331 with ypN- and 104 with ypN+ status. Patients achieving breast pCR had a significantly lower ypN+ rate than those without pCR [23.9% versus 62.5%, odds ratio (OR) = 0.14, 95% confidence interval (CI) = 0.09-0.21]. For patients with breast pCR, the ypN+ rate was 6.4%, 25.7%, and 33.9% in cT1-2N0, cT1-2N1, and LABC patients, respectively (p < 0.001). Furthermore, the ypN+ rate was 30.8%, 16.8%, 17.5%, 29.6%, and 27.6% in breast pCR patients with the Luminal A, Luminal B (HER2+), HER2-amplified, Luminal B (HER2-), and triple-negative subtype, respectively. Luminal B (HER2+) (OR = 0.20, 95% CI = 0.05-0.82) and HER2-amplified (OR = 0.19, 95% CI = 0.05-0.83) tumors were associated with lower ypN+ rates. Moreover, 100% of breast pCR patients with cT1-2N0 and HER2-positive disease achieved pathological pN0.ConclusionIn breast pCR patients after NAT, clinical stage and molecular subtype were significantly associated with ypN status. Patients with cT1-2N0 and HER2-positive disease who achieved breast pCR had a very low ypN+ rate, possibly indicating the possibility for de-escalation of axillary surgery in this patient subgroup.
| S-EPMC7934036 | biostudies-literature
Project description: Not available
| S-EPMC11480878 | biostudies-literature
Project description: Not available
| S-EPMC7051245 | biostudies-literature
Project description:BackgroundThe diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful.Patients and methodsProspective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers.ResultsA total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000.ConclusionThe pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.
| S-EPMC10078899 | biostudies-literature
Project description:PurposeSentinel lymph node biopsy (SLNB) alone following neoadjuvant chemotherapy (NAC) remains controversial in patients with breast cancer who are initially lymph node-positive. The present study aimed to evaluate the impact of SLNB and axillary lymph node dissection (ALND) on breast cancer recurrence and survival in patients who converted from lymph node-positive to pathological node-negative (ypN0) after NAC.MethodsThis single-center retrospective study included 223 patients who converted to axillary lymph node-negative status after NAC and underwent breast and axillary surgery between January 2006 and December 2015. This study compared the overall survival (OS), disease-free survival (DFS), ipsilateral axillary lymph node recurrence rates and incidence of postoperative complications, especially, arm lymphedema and shoulder stiffness between SLNB and ALND.ResultsThis study included 223 patients with axillary pathological complete response (pCR) after NAC and surgery. The SLNB and ALND groups included 94 and 129 patients, respectively. The median follow-up time was 57 (range, 6-155) in the SLNB group and 99 (range 2-159) months in the ALND group. The corresponding 5-year OS and DFS rates were 96.3% and 94.2% (p = 0.392), and 89.2% and 86.4% (p = 0.671), respectively. Four patients (4.3%) in the SLNB group and nine (7.0%) in the ALND group developed locoregional recurrences. Ipsilateral axillary lymph node recurrence and distant metastasis were observed in one (1.1%) and three (2.3%) patients, and in 10 (10.6%) and 11 (8.5%) patients, respectively. Patients in the ALND group were more likely than their SLNB counterparts to experience complications, such as shoulder stiffness (9 [7.0%] vs. 4 [4.3%] patients, p = 0.57). The rate of lymphedema in the ALND group was three times that in the SLNB group (35 [27.1%] vs. 8 [8.5%] patients, p < 0.001).ConclusionAs an alternative to ALND, SLNB has oncological safety in patients with axillary pathological complete response after NAC.
| S-EPMC8724374 | biostudies-literature
Project description:Importance:A pathologic complete response (pCR; no invasive or in situ cancer) occurs in 40% to 50% of patients with HER2-positive (HER2+) and triple-negative (TN) breast cancer. The need for surgery if percutaneous biopsy of the breast after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter referred to as breast pCR) has been questioned, and appropriate management of the axilla in such patients is unknown. Objective:To identify patients among exceptional responders to NCT with a low risk for axillary metastases when breast pCR is documented who may be eligible for an omission of surgery clinical trial design. Design, Setting, and Participants:This prospective cohort study at a single-institution academic national comprehensive cancer center included 527 consecutive patients with HER2+/TN (T1/T2 and N0/N1) cancer treated with NCT followed by standard breast and nodal surgery from January 1, 2010, through December 31, 2014. Main Outcomes and Measures:Patients who achieved a breast pCR were compared with patients who did not based on subtype, initial ultrasonographic findings, and documented pathologic nodal status. Incidence of positive findings for nodal disease on final pathologic review was calculated for patients with and without pCR and compared using relative risk ratios with 95% CIs. Results:The analysis included 527 patients (median age, 51 [range, 23-84] years). Among 290 patients with initial nodal ultrasonography showing N0 disease, 116 (40.4%) had a breast pCR and 100% had no evidence of axillary lymph node metastases after NCT. Among 237 patients with initial biopsy-proved N1 disease, 69 of 77 (89.6%) with and 68 of 160 (42.5%) without a breast pCR had no evidence of residual nodal disease (P?<?.01). Patients without a breast pCR had a relative risk for positive nodal metastases of 7.4 (95% CI, 3.7-14.8; P?<?.001) compared with those with a breast pCR. Conclusions and Relevance:Breast pCR is highly correlated with nodal status after NCT, and the risk for missing nodal metastases without axillary surgery in this cohort is extremely low. These data provide the fundamental basis and rationale for management of the axilla in clinical trials of omission of cancer surgery when image-guided biopsy indicates a breast pCR.
| S-EPMC5547923 | biostudies-other
Project description:BackgroundTo investigate the association of axillary pathologic complete response (pCR) rate among breast cancer patients with pCR after neoadjuvant chemotherapy (NCT).MethodsThe retrospective clinical data of 1,903 patients who were treated with NCT between March, 2010 and December, 2018, were collected from one Chinese database and analyzed. The correlations between clinicopathological characteristics and breast pCR with axillary pCR were calculated by χ2 test. Binary logistic regression analysis was used for multivariate analysis. The relative risk of positive axillary nodes after NCT in patients with and without breast pCR was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by initial N stage and tumor subtype.ResultsThe rate of axillary pCR was increased in the cases with initial cN0, Ki67 high expression, HR+HER2+/HR-HER2+/TN subtypes, and breast pCR. After NCT, the relative risk of nodal disease burden was 4.81 in patients without breast pCR compared with patients with breast pCR. The relative risk of positive nodal status in patients with cN0, cN1, cN2, and cN3 disease without vs. with breast pCR was 6.45, 4.88, 5.69 and 6.24, respectively. The relative risk of positive nodal status in patients with HR+HER2-, HR+HER2+, HR-HER2+, and TN disease was 4.02, 4.50, 3.82 and 4.18, respectively. Of cN0 patients with breast pCR, only 4 out of 44 (9%) with HER2-positive disease had 1 or 2 axillary lymph node metastases at final surgical pathology compared to 30 out of 98 (31%) of those without breast pCR. There was no evidence of positive nodal residue among all 21 patients (100%) with TN disease compared to 65% (36 of 55) of patients without breast pCR.ConclusionsNodal status is strongly correlated with breast pCR after NCT. Patients with initial cN0/1 TN/HER2 positive disease who achieve breast pCR at surgery have a low risk of nodal metastasis. These results suggest that the failure rate of missing positive lymph nodes among those patients was very low and that it is safe for such patients to undergo sentinel lymph node biopsy (SLNB) after NCT. This study also provides a theoretical basis for clinical trials focused on the avoidance of axillary surgery in selected patients.
| S-EPMC7475504 | biostudies-literature
Project description:The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II-III) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2-enriched tumors showed a higher GSTP1 MI than basal-like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P-FEC in ER-negative tumors but not in ER-positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2-enriched tumors than basal-like tumors. Fresh frozen tumor samples obtained by vacuum-assisted core biopsy from one hundred and fifteen patients were subjected to RNA extraction and hybridization on Affymetrix microarrays.
2012-03-20 | E-GEOD-32646 | biostudies-arrayexpress
Project description:Increasing use of neoadjuvant therapy in large tumors or node positive disease in breast cancer patients or hormone negative and HER 2 overexpressing cancers often gives rise to complete clinical response, with resolution of disease in the breast and axilla. These results have raised important questions to deescalate loco-regional surgical treatment options with minimum recurrence risk and treatment related morbidity. Although there is excellent prognosis following clinical response, the primary goal of surgery still remains to confirm complete pathological response in the biopsied node that was previously positive and now clinically/radiologically negative (ycN0). Biopsied lymph nodes are often marked with a clip to allow future identification at the time of definitive surgery. The goal of lymph node surgery in oncology is that it should be accurate, hence the significance of localizing the biopsied node. This article aims to review the different options to localize the deemed positive node at the time of definitive surgery, in order to help determine pathological response after neoadjuvant therapy.
| S-EPMC8394061 | biostudies-literature
Project description:BackgroundPathological complete response (pCR) of axillary lymph nodes (ALNs) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC), and ALN status is an important prognostic factor for breast cancer patients. This study aims to develop a new predictive clinical model to assess the ALN pCR rate after NAC.MethodsThis was a retrospective series of 467 patients who had biopsy-proven positive ALNs at diagnosis and underwent ALN dissection from 2007 to 2014 at the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences. We analyzed the clinicopathologic features of the patients and developed a nomogram to predict the probability of ALN pCR. A multivariable logistic regression stepwise model was used to construct a nomogram to predict ALN pCR in node-positive patients. The adjusted area under the receiver operating characteristic curve (AUC) was calculated to quantify the ability to rank patients by risk. Internal validation was performed using the 50/50 hold-out validation method. The nomogram was externally validated with prospective cohorts of 167 patients from 2016 to 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences and 114 patients from 2018 to 2020 at Beijing Tiantan Hospital.ResultsIn this retrospective study, 115 (24.6%) patients achieved ALN pCR after NAC. Multivariate analysis showed that clinical tumor stage (Odds ratio [OR]: 0.321, 95% confidence interval [CI]: 0.121-0.856; P = 0.023); primary tumor response (OR: 0.189; 95% CI: 0.123-0.292; P < 0.001), and estrogen receptor status (OR: 0.530, 95% CI: 0.304-0.925; P = 0.025) were independent predictors of ALN pCR. The nomogram was constructed based on the result of multivariate analysis. In the internal validation of performance of nomogram, the AUCs for the training and test sets were 0.719 and 0.753, respectively. The nomogram was validated in external cohorts with AUCs of 0.720, which demonstrated good discriminatory power in these data sets.ConclusionWe developed a nomogram to predict the likelihood of axillary pCR in node-positive breast cancer patients after NAC. The predictive model performed well in multicenter prospective external validation. This practical tool could provide information to surgeons regarding whether to perform additional ALN dissection after NAC.Trial registrationChiCTR.org.cn, ChiCTR1800014968.
| S-EPMC8812621 | biostudies-literature