Association of residual ductal carcinoma in situ with breast cancer treatment outcomes after neoadjuvant chemotherapy according to hormone receptor status.

PURPOSE: This research aimed to clarify the impact of residual ductal carcinoma in situ(DCIS) in surgical specimens obtained after neoadjuvant chemotherapy(NAC) for breast cancer on the associated prognosis outcomes. METHODS: This retrospective study was performed on a cohort of 1,009 patients who achieved pCR following NAC for breast cancer and underwent subsequent breast surgery at a single institution between January 2008 and December 2019. Overall survival, local recurrence-free survival, distant metastasis-free survival, and disease-free survival of the residual and non-residual DCIS groups were the outcomes compared, with further subgroup analysis performed according to hormone receptor status. RESULTS: 260 individuals (25.8%) presented with residual DCIS. Based on a median follow-up of 54.0 months, no significant differences in outcomes were observed between the two groups. Patients with residual DCIS and hormone receptor-negative (HR-) breast cancer demonstrated a significant decrease in distant metastasis-free survival (p = 0.030) compared to those without residual DCIS. In the HR + cohort, no significant difference was observed between the two groups. Multivariate analysis of the HR- cohort demonstrated a significant association between residual DCIS and an elevated risk for distant recurrence (hazard ratio = 2.3, 95% confidence interval = 1.01-5.20, p = 0.047). CONCLUSIONS: Residual DCIS following NAC may impact breast cancer outcomes, particularly with respect to the occurrence of distant metastasis in HR- patients. Therefore, clinicians must vigilantly monitor patients with residual DCIS after NAC, and further research is needed to expand our understanding of the clinical implications of residual DCIS.

Impact of Angiotensin Converting Enzyme Inhibitors on Pathologic Complete Response With Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer.

INTRODUCTION: The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. We examined the association of RAS inhibitors (RASi)-namely angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB)-with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) preceding radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively investigated concurrent RASi use with NAC prior to RC in 302 patients with MIBC from 3 academic institutions. Outcomes included pathologic complete response (pCR) and overall survival (OS). Pathologic features, performance status (PS), clinical stage, type/number of cycles of NAC, and toxicities were collected. RESULTS: Overall pCR rate was 26.2% and 5-year OS was 62%. Concurrent ACEi intake with NAC approached significance for association with pCR (odds ratio [OR] = 1.71; 95% CI, 0.94-3.11; P = .077). Patients with cT3/4N0-N1 disease receiving ACEi had higher pCR rates (30.8% vs. 17.7%, P = .056) than those not on ACEi. Female sex had a statistically significant favorable interaction for pCR with ACEi intake (P = .044). ACEi intake was not associated with OS, while pCR, PS and lower clinical stage were significantly associated with improved OS. CONCLUSION: ACEi intake is potentially associated with increased pCR in patients with MIBC receiving NAC prior to RC, and this association is more pronounced in patients with higher clinical stage of disease at the initiation of therapy and female sex. Our data suggest the potential relevance of the RAS as a therapeutic target in aggressive MIBC.

Initial MRI findings predictive of a pathological complete response to neoadjuvant treatments in HER2-positive breast cancers.

PURPOSE: This study aimed to determine if initial MRI findings could predict a pathological complete response (pCR) following neoadjuvant systemic therapy (NST) in HER2-positive breast cancers. METHODS: The study retrospectively included 111 patients (Center 1, training set) and 71 patients (Center 2, validation set) with HER2-positive cancer who underwent NST. Initial clinicopathological data and MRI findings were recorded. Continuous variables were analyzed using the Mann-Whitney and Student's t-tests, while categorical variables were analyzed using the χ2 or Fisher's exact test. Univariate analysis was conducted to determine the associations between these variables and pathological complete response (pCR), defined as the absence of invasive malignant cells in the breast and lymph nodes. Interobserver reproducibility was assessed for associated non-mass enhancement (NME) parameter by analyzing 50 MR studies (intraclass correlation coefficient). RESULTS: pCR was achieved in 67 patients, 51 (46 %) from Center 1 and 16 (23%) from Center 2 (p = 0.003), with significant differences between Centers 1 and 2 in tumor-infiltrating lymphocyte levels and lymphovascular invasion (p < 0.001). The initial presence of suspicious associated NME was the only significant parameter predictive of pCR (p < 0.001 for Center 1 and 0.04 for Center 2). The inter-observer reproducibility for this MRI feature was good, with an intraclass correlation coefficient of 0.872 (95 % CI: 0.73-1.00). CONCLUSION: The presence of suspicious associated NME in HER2-positive cancers on the initial MRI study was predictive of achieving pCR after NST. This significant preliminary finding warrants confirmation through prospective multicenter studies.

Comparison of radiomics-based machine-learning classifiers for the pretreatment prediction of pathologic complete response to neoadjuvant therapy in breast cancer.

Background: Machine learning classifiers are increasingly used to create predictive models for pathological complete response (pCR) in breast cancer after neoadjuvant therapy (NAT). Few studies have compared the effectiveness of different ML classifiers. This study evaluated radiomics models based on pre- and post-contrast first-phase T1 weighted images (T1WI) in predicting breast cancer pCR after NAT and compared the performance of ML classifiers. Methods: This retrospective study enrolled 281 patients undergoing NAT from the Duke-Breast-Cancer-MRI dataset. Radiomic features were extracted from pre- and post-contrast first-phase T1WI images. The Synthetic Minority Oversampling Technique (SMOTE) was applied, then the dataset was randomly divided into training and validation groups (7:3). The radiomics model was built using selected optimal features. Support vector machine (SVM), random forest (RF), decision tree (DT), k-nearest neighbor (KNN), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM) were classifiers. Receiver operating characteristic curves were used to assess predictive performance. Results: LightGBM performed best in predicting pCR [area under the curve (AUC): 0.823, 95% confidence interval (CI) [0.743-0.902], accuracy 74.0%, sensitivity 85.0%, specificity 67.2%]. During subgroup analysis, RF was most effective in pCR prediction in luminal breast cancers (AUC: 0.914, 95% CI [0.847-0.981], accuracy 87.0%, sensitivity 85.2%, specificity 88.1%). In triple-negative breast cancers, LightGBM performed best (AUC: 0.836, 95% CI [0.708-0.965], accuracy 78.6%, sensitivity 68.2%, specificity 90.0%). Conclusion: The LightGBM-based radiomics model performed best in predicting pCR in patients with breast cancer. RF and LightGBM showed promising results for luminal and triple-negative breast cancers, respectively.

Efficacy and prognosis of HER2-Low and HER2-Zero in triple-negative breast cancer after neoadjuvant chemotherapy.

Mounting evidence showed that HER2-Low breast cancer patients could benefit from the novel anti-HER2 antibody-drug conjugates (ADCs) treatment, which pointed the way towards better therapy for HER2-Low patients. The purpose of this study was to describe the clinicopathological features, along with chemotherapeutic effects and survival outcomes of HER2-Low and HER2-Zero in TNBC who received neoadjuvant chemotherapy (NACT). We retrospectively evaluated 638 triple-negative breast cancer patients who were treated with neoadjuvant chemotherapy between August 2014 and August 2022. Pathologic complete response (pCR) and survival outcomes were analyzed in HER2-Low cohort, HER2-Zero cohort and the overall patients, respectively. In the entire cohort, 342 (53.6%) patients were HER2-Low and 296 (46.4%) patients were HER2-Zero. No significant difference was found between HER2-Low and HER2-Zero patients based on all the clinical-pathological characteristics. 143 cases (22.4%) achieved pCR after NACT in the overall TNBC patients. The pCR rate of the HER2-Low patients and the HER2-Zero patients was 21.3% and 23.6%, respectively, exhibiting no statistical difference (p = 0.487). The survival of pCR group after NACT significantly improved compared to non-pCR group either in HER2-Low patients or in HER2-Zero patients. Although we found that patients with HER2-Low had longer DFS than patients with HER2-Zero, there was no considerable difference (p = 0.068). However, HER2-Low patients had a dramatically longer OS than HER2-Zero patients (p = 0.012). The data from present study confirmed the clinical importance of HER2-Low expression in TNBC. Further effort is needed to determine whether HER2-Low could be a more favorable prognostic marker for individual treatment.

Utility of Axillary Staging in Older Patients with HER2-Positive Breast Cancer.

BACKGROUND: The utility of sentinel lymph node biopsy (SLNB) in older patients remains controversial. Advancements in human epidermal growth factor receptor 2 (HER2)-directed therapy have revolutionized disease response rates and prognosis, supporting efforts to re-evaluate the utility of SLNB. We aimed to assess the differences in treatment and overall survival (OS) in older patients with HER2-positive breast cancer based on SLNB. METHODS: Using the National Cancer Database (2010-2020), patients ≥ 70 years of age diagnosed with cT1-2/cN0/M0, HER2-positive breast cancer were identified. Logistic regression assessed associations with SLNB, systemic therapy, and radiation. Cox proportional hazard models were used to identify factors associated with OS. Analyses were stratified by treatment sequence, i.e. upfront surgery or neoadjuvant therapy (NAT) followed by surgery. RESULTS: Of the 17,609 patients included, 94% underwent upfront surgery (n = 16,492) and the remaining underwent NAT (n = 1117). Those who underwent SLNB were more likely to receive adjuvant therapy, irrespective of nodal status {upfront surgery/systemic therapy (odds ratio [OR] 2.82, 95% confidence interval [CI] 2.17-3.67); upfront surgery/radiation (OR 3.97, 95% CI 3.03-5.21); NAT/radiation (OR 5.69, 95% CI 1.83-17.69)}. The breast pathologic complete response (pCR) rate was highest among the hormone receptor (HR)-negative/HER2-positive subtype (50.0%), of which none were found to be ypN+. Comorbidity burden was associated with significantly lower rates of adjuvant systemic therapy and worse OS. CONCLUSIONS: Patients who underwent SLNB, regardless of pN status, were more likely to receive adjuvant therapy. Nodal positivity is exceedingly rare for patients with a breast pCR following NAT, especially among the HR-negative/HER2-positive subtype. It is reasonable to consider omission of SLNB in select subgroups of older patients with HER2-positive breast cancer.

Pre-operative MRI in evaluating pathologic complete response to neoadjuvant chemotherapy in patients with breast cancer: a study focused on influencing factors of baseline clinical-pathological and imaging features.

Purpose: To investigate what pre-treatment clinical-pathological features and MRI characteristics influence the performance of breast MRI in assessing the pathologic complete response (pCR) of breast cancer patients to Neoadjuvant Chemotherapy (NAC). Methods: A total of 225 patients with pathologically-confirmed breast cancer who underwent pre- and post-NAC breast MRI between January 2020 and April 2023 were retrospectively analyzed. All patients were categorized into radiologic complete response (rCR) and non-rCR groups based on pre-operative MRI. Univariable and multivariable logistic regression were used to identify independent clinicopathological and imaging features associated with imaging-pathological discordance. The performance of pre-operative MRI for predicting pCR to NAC was assessed according to the baseline characteristics of the clinicopathological data and pre-NAC MRI. In addition, the discrepancy between the pre-operative MRI and post-operative pathological findings was further analyzed by a case-control approach. Results: Among 225 patients, 99 (44.0%) achieved pCR after NAC. MRI showed the overall sensitivity of 97.6%, specificity of 58.6%, accuracy of 80.4%, a positive predictive value (PPV) of 75.0%, and a negative predictive value (NPV) of 95.1% in identifying pCR. Of baseline features, presence of ductal carcinoma in situ (DCIS) (OR, 3.975 [95% CI: 1.448-10.908], p = 0.007), luminal B (OR, 5.076 [95% CI: 1.401-18.391], p = 0.013), HER2-enriched subtype (OR, 10.949 [95% CI: 3.262-36.747], p < 0.001), multifocal or multicentric lesions (OR, 2.467 [95% CI: 1.067-5.706], p = 0.035), segmental or regional distribution of NME (OR, 8.514 [95% CI: 1.049-69.098], p = 0.045) and rim enhancement of mass (OR, 4.261 [95% CI: 1.347-13.477], p = 0.014) were significantly associated with the discrepancy between MRI and pathology. Conclusion: Presence of DCIS, luminal B or HER2-enriched subtype, multicentric or multifocal lesions, segmental or regional distribution of NME and rim enhancement of mass may lead to a decrease in diagnostic accuracy of MRI in patients of breast cancer treated with NAC.

Ten-Year Follow-Up After Chemotherapy and Conversion Surgery for Human Epidermal Growth Factor Receptor 2-Positive Stage IV Esophagogastric Junction Cancer With a Pathological Complete Response: A Case Report.

Recent reports have focused on the usefulness of conversion surgery, in which chemotherapy is given to patients with unresectable advanced gastric cancer (GC), and radical surgery is subsequently performed if resection becomes possible; however, no consensus has been reached regarding the usefulness of this strategy. We report on a 74-year-old man who was diagnosed with esophagogastric junction cancer (T3N3M1 (LYM): stage IV). Chemotherapy was chosen and seven courses of S1 + cisplatin (SP) + trastuzumab (HCN) and two courses of S1 + HCN were administered. Approximately 10 months after the start of chemotherapy, the tumor had almost disappeared and we therefore decided to perform conversion surgery. Pathologic examination of the specimen and dissected lymph nodes showed no cancer. Postoperatively, the patient underwent chemotherapy until the second postoperative year, and no metastasis or recurrence was observed for nine years after surgery. Conversion surgery after chemotherapy resulted in recurrence-free survival in this case; however, further studies are needed to elucidate the effect of surgery after chemotherapy for patients with stage IV GC, as chemotherapy continues to evolve.

Impact of Presenting Stage on Overall Survival in Patients Treated with Neoadjuvant Chemotherapy for Triple Negative Breast Cancer.

PURPOSE: For operable triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), clinical prognostication and postoperative decision-making relies exclusively on whether a pathologic complete response (pCR) is achieved or not. We evaluated whether extent of disease at presentation further influenced overall survival (OS) among patients with pCR or with residual disease (RD) following NAC. METHODS: Patients with stage I-III TNBC who underwent NAC were identified from the National Cancer Database from 2010 to 2019. Overall survival was assessed by disease extent using the Kaplan-Meier method and Cox proportional hazards regression for univariate and multivariable analysis. RESULTS: A total of 35,598 patients met inclusion criteria, and 11,967 achieved pCR. Ten-year OS was 88.5% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (90.9%) and was worst in those with cT3-4, cN2-3 disease (72.0%). A total of 23,631 patients had RD. Ten-year OS was 60.1% and varied by cT and cN category at presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (73.0%) and was worst in those with cT3-4, cN2-3 disease (36.3%). Notably, OS was significantly poorer for patients with cT3-4, cN2-3 disease at diagnosis and pCR versus those with cT1-2 cN0 and RD (aHR 1.30, 95% confidence interval 1.03-1.63, p = 0.03). CONCLUSIONS: Among patients with TNBC, extent of disease at presentation was prognostic for OS independently of response to NAC. Patients with advanced stage at presentation had poorer OS even in the context of pCR. Further investigation is needed to evaluate whether additional adjuvant therapy strategies should be considered for these patients.

Breast Cancer: Multi-b-Value Diffusion Weighted Habitat Imaging in Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy.

RATIONALE AND OBJECTIVES: The aim of this study was to ascertain whether the utilization of multiple b-value diffusion-weighted habitat imaging, a technique that depicts tumor heterogeneity, could aid in identifying breast cancer patients who would derive substantial benefit from neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: This prospective study enrolled 143 women (II-III breast cancer), who underwent multi-b-value diffusion-weighted imaging (DWI) in 3-T magnetic resonance (MR) before NAC. The patient cohort was partitioned into a training set (consisting of 100 patients, of which 36 demonstrated a pathologic complete response [pCR]) and a test set (featuring 43 patients, 16 of whom exhibited pCR). Utilizing the training set, predictive models for pCR, were constructed using different parameters: whole-tumor radiomics (ModelWH), diffusion-weighted habitat-imaging (ModelHabitats), conventional MRI features (ModelCF), along with combined models ModelHabitats+CF. The performance of these models was assessed based on the area under the receiver operating characteristic curve (AUC) and calibration slope. RESULTS: In the prediction of pCR, ModelWH, ModelHabitats, ModelCF, and ModelHabitats+CF achieved AUCs of 0.733, 0.722, 0.705, and 0.756 respectively, within the training set. These scores corresponded to AUCs of 0.625, 0.801, 0.700, and 0.824 respectively in the test set. The DeLong test revealed no significant difference between ModelWH and ModelHabitats (P = 0.182), between ModelHabitats and ModelHabitats+CF (P = 0.113). CONCLUSION: The habitat model we developed, incorporating first-order features along with conventional MRI features, has demonstrated accurate predication of pCR prior to NAC. This model holds the potential to augment decision-making processes in personalized treatment strategies for breast cancer.

Contrast-enhanced pelvic magnetic resonance imaging (MRI) for the prediction of treatment response in mucinous rectal cancer.

Background: In mucinous rectal cancer, it can be difficult to differentiate between cellular and acellular mucin. The purpose of this study was to evaluate, in patients with mucinous rectal cancer, the value of static enhancement (enh) and pharmacokinetic parameters of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting pathologic complete response. Methods: This retrospective cross-sectional study performed at Memorial Sloan Kettering Cancer Center included 43 patients (24 males and 19 females; mean age, 57 years) with mucinous rectal cancer who underwent MRI at baseline as well as after neoadjuvant chemoradiotherapy but before surgical resection between 2008 and 2019. Two radiologists independently segmented tumors on contrast-enhanced axial 3D T1-weighted images and sagittal DCE magnetic resonance images. On contrast-enhanced axial T1-weighted images, the static parameters enh and relative enhancement (renh) were estimated. On DCE images, the pharmacokinetic parameters Ktrans, kep, relative Ktrans (rKtrans), and relative kep (rkep) were estimated. Associations between all parameters with pathologic complete response were tested using Wilcoxon signed-rank tests. Receiver operating characteristic (ROC) analysis was performed to assess the area under the curve (AUC) for each parameter. Results: Of the 43 patients who were included in the study, 42/43 (98%) had evaluable contrast-enhanced axial T1-weighted images and 35/43 (81%) had evaluable DCE images. Of the patients with evaluable contrast-enhanced axial T1-weighted images, 9/42 (21%) had pathologic complete response and 33/42 (79%) did not have pathologic complete response. For reader 1, enh(pre-neoadjuvant chemotherapy), enh(post-neoadjuvant chemotherapy), and renh were significant predictors of pathologic complete response [P=0.045 (AUC =0.73), 0.039 (AUC =0.74), and 0.0042, respectively]. For reader 2, enh(pre-neoadjuvant chemotherapy) and renh were significant predictors [P=0.021 (AUC =0.77) and 0.002, respectively]. For renh, the AUC was 0.83 for reader 1, and 0.82 for reader 2. Meanwhile, of those patients with evaluable DCE images, 9/35 (26%) had pathologic complete response and 26/35 (74%) did not have pathologic complete response. Ktrans(pre-neoadjuvant chemotherapy), kep(pre-neoadjuvant chemotherapy), and rkep were significant predictors [P=0.016 (AUC =0.73), 0.00057 (AUC =0.81), and 0.0096 (AUC =0.74), respectively]. Conclusions: Static and pharmacokinetic parameters of contrast-enhanced MRI show promise to predict neoadjuvant treatment response. Static enh parameters, which are simpler to assess, showed the strongest prediction.

Association between pathologic complete response and biochemical indicators after neoadjuvant therapy for HER2-positive breast cancer.

PURPOSE: This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR). METHODS: Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR. RESULTS: In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR. CONCLUSIONS: Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.

Pathologic Complete Response, Total Neoadjuvant Therapy and the Survival Paradox in Locally Advanced Rectal Cancer.

BACKGROUND: Pathologic complete response (pCR) after preoperative chemoradiation (nCRT) correlates with improved overall survival for patients with locally advanced rectal cancers (LARCs). Escalation protocols including total neoadjuvant therapy (TNT), which delivers multi-agent chemotherapy and chemoradiation before surgery, are associated with increased complete response rates. However, TNT is not associated with improved overall survival. The authors hypothesized that the route to pCR may be an important predictor of oncologic outcome. METHODS: Adults with LARC between 2006 and 2017 were identified in the National Cancer Database. The cohort was limited to those who received neoadjuvant radiation (45-70 Gy) and underwent proctectomy. RESULTS: Of 25,880 patients, 16 % received TNT and 84 % had nCRT followed by either multi-agent (27 %), single-agent (14 %), or no adjuvant chemotherapy (44 %). Overall, 18 % achieved pCR, with higher rates in the TNT cohort than in the nCRT (18 %) or multi-agent (14 %) chemotherapy cohorts. With control for covariates, the OS in the pCR cohort was similar for the patients that received single-agent therapy and those that received multi-agent adjuvant therapy, and superior to the TNT and no adjuvant therapy cohorts. Conversely, among the patients who did not achieve pCR, those who received single-agent chemotherapy had OS comparable with those who had multi-agent adjuvant therapy and TNT, which was better than no adjuvant therapy. CONCLUSION: Patients achieving pCR after TNT had worse OS than those who had CRT alone, suggesting that the neoadjuvant route by which pCR is achieved is prognostically relevant. Therefore, in the era of neoadjuvant therapy escalation, pCR does not necessarily portend a uniformly favorable prognosis.

The role of laboratory indices on treatment response and survival in breast cancer receiving neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NACT) is the standard treatment for locally advanced, high-risk breast cancer. Pathological complete response (pCR) improves survival. Peripheral blood-derived indices reflecting systemic inflammation and nutritional status have long been used as predictive and prognostic markers in solid malignancies. This retrospective study investigates whether eight commonly used indices in patients receiving NACT affect pCR and survival. This study includes 624 locally advanced breast cancer patients who received NACT. The biomarker indices were calculated from peripheral blood samples taken two weeks before starting chemotherapy. The indices' optimal cut-off values were determined using ROC Curve analysis. During a median follow-up period of 42 months, recurrence was detected in 146 patients, and 75 patients died. pCR was observed in 166 patients (26.6%). In univariate analysis, NLR, PLR, SII, PNI, HALP, and HRR were statistically significantly associated (p = 0.00; p = 0.03; p = 0.03; p = 0.02; p = 0.00; p = 0.02 respectively), but in multivariate analysis, only NLR was significantly predictive for pCR(p = 0.04). In multivariate analysis, the HGB/RDW score significantly predicted DFS(p = 0.04). The PNI score was identified as a marker predicting survival for both OS and PFS (p = 0.01, p = 0.01, respectively). In conclusion, peripheral blood-derived indices have prognostic and predictive values on pCR and survival. However, further studies are needed to validate our findings.

A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

Purpose: This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram. Methods: The CSBrS-012 study (2010-2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally. Results: In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively. Conclusion: We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

Immune cell patterns before and after neoadjuvant immune checkpoint blockade combined with chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. PATIENTS AND METHODS: A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. RESULTS: In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. CONCLUSIONS: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

Prognostic Importance of Axillary Lymph Node Response to Neoadjuvant Systemic Therapy on Axillary Surgery in Breast Cancer-A Single Center Experience.

Neoadjuvant systemic treatment (NST) is the standard treatment for HER2+, triple-negative (TN), and highly proliferative luminal HER2- early breast cancer. Pathologic complete response (pCR) after NST is associated with improved outcomes. We evaluated the predictive factors for axillary-pCR (AXpCR) and its impact on the extent of axillary node surgery. This retrospective study included 92 patients (median age of 50.4 years) with an initially node-positive disease. Patients were treated with molecular subtype-specific NST (4.3% were luminal A-like, 28.3% luminal HER2-, 26.1% luminal HER2+, 18.5% HER2+ non-luminal, and 22.8% TN). Axillary-, breast- and total-pCR were achieved in 52.2%, 48.9%, and 38% of patients, respectively. In a binary logistic regression model for the whole population, the only independent factor significantly associated with AXpCR was breast-pCR (OR 7.4; 95% CI 2.6-20.9; p < 0.001). In patients who achieved breast-pCR, aggressive subtypes (HER2+ and TN; OR 11.24) and clinical tumor stage (OR 0.10) had a significant impact on achieving AXpCR. Axillary lymph node dissection was avoided in 53.3% of patients. In conclusion, in node-positive patients with HER2+ and TN subtypes, who achieved breast-pCR after NST, de-escalation of axillary surgery could be considered in most cases.

Neoadjuvant Chemotherapy in Patients with HER2-Negative Breast Cancer: A Report from Clinical Breast Cancer Registry of Iran.

BACKGROUND: Neoadjuvant chemotherapy (NCT) has become an increasingly popular approach in management of breast cancer (BC). This study was conducted to evaluate the pathologic response and 36-month recurrence and survival rates of patients with human epidermal growth factor receptor 2 (HER2)-negative BC treated with different NCT regimens. METHODS: A total of 163 female patients with HER2-negative BC who received NCT during 2017-2020 were identified from the Clinical Breast Cancer Registry of Iran and entered the study. The prescribed NCT regimens included 4 cycles of doxorubicin plus cyclophosphamide, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of paclitaxel, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of docetaxel or 6 cycles of doxorubicin plus cyclophosphamide plus docetaxel (TAC). RESULTS: Thirty-two patients (19.6%) experienced pathologic complete response (pCR). TAC regimen, triple negative-BC and ki67>10% were significantly associated with increased pCR. The recurrence, overall survival (OS) and disease-free survival (DFS) rate at 36 months for all patients were 16.6%, 84.7% and 79.8%, respectively. Type of neoadjuvant regimen as well as age, hormone receptor status, Ki67, grade, clinical stage, type of surgery and pathologic response to chemotherapy did not significantly influence the survival and recurrence; however, TAC results in improved recurrence, OS and DFS rates. CONCLUSION: This study provides further evidence that NCT is a viable treatment option for patients with HER2-negative BC. The TAC regimen resulted in a significantly higher pCR rate compared to other regimens, but did not result in a significant improvement in recurrence, OS and DFS and rates.