Miller-Payne Grading System Research Articles

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast.

Breast cancer ranks as one of the most prevalent malignant tumors among women, significantly endangering their health and lives. While radical surgery has been a pivotal method for halting disease progression, it alone is insufficient for enhancing the quality of life for patients. To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy (NAC). Employing a case-control study design, this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022. According to the Miller-Payne grading system, the pathological response, i.e. efficacy, of the NAC in the initial breast lesion after NAC was evaluated. Of these, 59 patients achieved a pathological complete response (PCR), while 119 did not (non-PCR group). Ultrasound characteristics prior to NAC were compared between these groups, and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches. In the PCR group, the incidence of posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II were significantly lower compared to the non-PCR group (P < 0.05). The area under the curve values for predicting NAC efficacy using posterior echo attenuation, lesion diameter, and Alder grade were 0.604, 0.603, and 0.583, respectively. Also, rates of pathological stage II, lymph node metastasis, vascular invasion, and positive Ki-67 expression were significantly lower in the PCR group (P < 0.05). Logistic regression analysis identified posterior echo attenuation, lesion diameter ≥ 2.0 cm, Alder blood flow grade ≥ II, pathological stage III, vascular invasion, and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients (P < 0.05). While ultrasound characteristics such as posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II exhibit limited predictive value for NAC efficacy, they are significantly associated with poor response to NAC in breast cancer patients.

Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer Predicted by CD4+, CD8+, and FOXP3+ Tumor-Infiltrating Lymphocytes.

Response to neoadjuvant chemotherapy (NC) in individuals with invasive breast cancer (IBC) must be monitored, and biomarkers are needed. NC can activate an anti-tumour immune response in its microenvironment, known as Tumor-infiltrating Lymphocytes (TIL). TIL components believed to have great potential as predictors are CD4+, CD8+, and FOXP3+ TIL. This study aims to explore TIL components that can potentially be predictive biomarkers of NC pathological responses. A sample size of 40 were analyzed based on the relationship between CD4+, CD8+, and FOXP3+ TIL expression with the Miller-Payne (MP) grading system. Age, tumour grade, PR, ER, Ki-67, and HER2 were also evaluated. CD4+, CD8+, and FOXP3+ TIL expressions were analayzed by IHC staining, while other data were collected from archives. Data was analyzed using univariate and multivariate analysis. Univariate analysis showed a significant relationship between CD4+ TIL and MP (p<0.001), CD8+ and MP (p=0.004), and FOXP3 with MP (p<0.001). The simultaneous integration of the three biomarkers in one model was not good enough to be a predictive model. Therefore, an exploratory analysis was conducted by testing several alternative models that combined two of the three existing biomarkers. It turned out that CD4+ TIL in model 2 (CD4+CD8+) and FOXP3+ TIL in model 4 (CD8+FOXP3+) showed significant coefficient values. Moreover, all of the threshold coefficients in model 4 are significant. This study shows that CD4+, CD8+, and FOXP3+ TIL have promising potential as predictive biomarkers. In particular, FOXP3+ is dominant in predictive models of pathological response in patients with IBC.

Early prediction of pathological response to neoadjuvant chemotherapy of breast tumors: a comparative study using amide proton transfer-weighted, diffusion weighted and dynamic contrast enhanced MRI.

To examine amide proton transfer-weighted (APTw) combined with diffusion weighed (DWI) and dynamic contrast enhanced (DCE) MRI for early prediction of pathological response to neoadjuvant chemotherapy in invasive breast cancer. In this prospective study, 50 female breast cancer patients (49.58 ± 10.62 years old) administered neoadjuvant chemotherapy (NAC) were enrolled with MRI carried out both before NAC (T0) and at the end of the second cycle of NAC (T1). The patients were divided into 2 groups based on tumor response according to the Miller-Payne Grading (MPG) system. Group 1 included patients with a greater degree of decrease in major histologic responder (MHR, Miller-Payne G4-5), while group 2 included non-MHR cases (Miller-Payne G1-3). Traditional imaging protocols (T1 weighted, T2 weighted, diffusion weighted, and DCE-MRI) and APTw imaging were scanned for each subject before and after treatment. APTw value (APTw0 and APTw1), Dmax (maximum diameter, Dmax0 and Dmax1), V (3D tumor volume, V0 and V1), and ADC (apparent diffusion coefficient, ADC0 and ADC1) before and after treatment, as well as changes between the two times points (ΔAPT, ΔDmax, ΔV, ΔADC) for breast tumors were compared between the two groups. APT0 and APT1 values significantly differed between the two groups (p = 0.034 and 0.01). ΔAPTw values were significantly lower in non-MHR tumors compared with MHR tumors (p = 0.015). ΔDmax values were significantly higher in MHR tumors compared with non-MHR tumors (p = 0.005). ADC0 and ADC1 values were significantly higher in MHR tumors than in non-MHR tumors (p = 0.038 and 0.035). AUC (Dmax+DWI + APTw) = AUC (Dmax+APTw) > AUC (APTw) > AUC (Dmax+DWI) > AUC (Dmax). APTw imaging along with change of tumor size showed a significant potential in early prediction of MHR for NAC treatment in breast cancer, which might allow timely regimen refinement before definitive surgical treatment.

Comparative study of pathological response evaluation systems after neoadjuvant chemotherapy for breast cancer: developing predictive models of multimodal ultrasound features including shear wave elastography combined with puncture pathology.

This study created a predictive preoperative nomogram dependent on multimodal ultrasound characteristics and primary lesion biopsy results for various pathologic response assessment systems following neoadjuvant chemotherapy (NAC). This retrospective study included 145 breast cancer patients treated at Gansu Cancer Hospital between January 2021 and June 2022 who underwent shear wave elastography (SWE) prior to completing NAC. Intra- and peritumoral SWE features, including maximum (Emax), mean (Emean), minimum (Emin), and standard deviation (Esd) elasticity, were measured individually and linked with the Miller-Payne grading system and residual cancer burden (RCB) class. Univariate analysis was used for conventional ultrasound and puncture pathology. Binary logistic regression analysis was used to screen for independent risk factors and to develop a prediction model. Intratumor Emean and peritumoral Esd differed significantly from the Miller-Payne grade [intratumor Emean: r=0.129, 95% confidence interval (CI): -0.002 to 0.260; P=0.042; peritumoral Esd: r=0.126, 95% CI: -0.010 to 0.254; P=0.047], RCB class (intratumor Emean: r=-0.184, 95% CI: -0.318 to -0.047; P=0.004; peritumoral Esd: r=-0.139, 95% CI: -0.265 to 0.000; P=0.029) and RCB score components (r=-0.277 to -0.139; P=0.001-0.041). Two prediction model nomograms-pathologic complete response (pCR)/non-pCR and good responder/nonresponder-for the RCB class were developed using binary logistic regression analysis for all significant variables in SWE, conventional ultrasound, and puncture results. The area under the receiver operating characteristic curve for the pCR/non-pCR and good responder/nonresponder models was 0.855 (95% CI: 0.787-0.922) and 0.845 (95% CI: 0.780-0.910), respectively. According to the calibration curve, the nomogram had excellent internal consistency between estimated and actual values. The preoperative nomogram can effectively guide clinicians to predict pathological response of breast cancer after NAC and has the potential to guide individualized treatment.

Computed Tomography-Based Radiomics Analysis for Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

Previous studies have pointed out that magnetic resonance- and fluorodeoxyglucose positron emission tomography-based radiomics had a high predictive value for the response of the neoadjuvant chemotherapy (NAC) in breast cancer by respectively characterizing tumor heterogeneity of the relaxation time and the glucose metabolism. However, it is unclear whether computed tomography (CT)-based radiomics based on density heterogeneity can predict the response of NAC. This study aimed to develop and validate a CT-based radiomics nomogram to predict the response of NAC in breast cancer. A total of 162 breast cancer patients (110 in the training cohort and 52 in the validation cohort) who underwent CT scans before receiving NAC and had pathological response results were retrospectively enrolled. Grades 4 to 5 cases were classified as response to NAC. According to the Miller-Payne grading system, grades 1 to 3 cases were classified as nonresponse to NAC. Radiomics features were extracted, and the optimal radiomics features were obtained to construct a radiomics signature. Multivariate logistic regression was used to develop the clinical prediction model and the radiomics nomogram that incorporated clinical characteristics and radiomics score. We assessed the performance of different models, including calibration and clinical usefulness. Eight optimal radiomics features were obtained. Human epidermal growth factor receptor 2 status and molecular subtype showed statistical differences between the response group and the nonresponse group. The radiomics nomogram had more favorable predictive efficacy than the clinical prediction model (areas under the curve, 0.82 vs 0.70 in the training cohort; 0.79 vs 0.71 in the validation cohort). The Delong test showed that there are statistical differences between the clinical prediction model and the radiomics nomogram ( z = 2.811, P = 0.005 in the training cohort). The decision curve analysis showed that the radiomics nomogram had higher overall net benefit than the clinical prediction model. The radiomics nomogram based on CT radiomics signature and clinical characteristics has favorable predictive efficacy for the response of NAC in breast cancer.

Meme kanserinde neoadjuvan kemoterapi yanıtlarını öngörmede belirleyici olarak açlık kan şekeri ve vücut kitle indeksi

Aim: Obesity is a well-known modifiable risk factor for breast cancer. Impaired fasting glucose is a component of metabolic syndrome and a significant risk for diabetes. We aimed to research the effect of these two major components of metabolic syndrome on neoadjuvant chemotherapy (NAC) response in breast cancer.Methods: We conducted 161 patients who had received NAC from January 2016 to January 2022. Fasting plasma glucose levels were measured at least two times and BMI was recorded before starting NAC. Impaired fasting glucose is defined as plasma glucose levels of 100 to 125 mg per dL. Analyses were compared into two groups according to FPG levels below or above 100 mg/dl and according to BMI obese (BMI30≥ kg/m2), or non-obese (BMI &amp;lt;30 kg/m2). The pathologic response was evaluated, and patients were divided into five groups according to the Miller-Payne grading system classified from grade V to I, complete pathologic response, loss of more than 90% of tumor cells, reduced 30% and 90% of tumor cells, lost less than 30% of tumor cells, and had no reduction in cellularity and no change malignant cells respectivelyResults: In the pathologic responses, 70.8% of patients with impaired fasting glucose levels were grade 1 non-reduction with NAC. Disease free-survival was shorter in the group that had impaired fasting glucose than in the group that had normal fasting plasma glucose (FPG) (p=0.031). In univariate analysis clinical stage 3 (p &amp;lt;0.001), postmenopausal status (p=0.037), human epidermal growth factor receptor 2 (HER-2) negativity (p&amp;lt;0.001), estrogen receptor (ER) positivity (p &amp;lt;0.001), progesterone receptor (PR) positivity (p &amp;lt;0.001) rate were higher in grade 1 unresponsive patients compared to patients with pathological response grade 2, grade 3 and grade 4. In multivariate analysis showed that fasting plasma glucose, clinical stage, HER-2 status, and ER status were independent predictor factors for pathological complete response (pCR). BMI had no impact on pCR. Our trial showed that the ratio of pCR in patients with impaired fasting glucose was 2.5 times lower than that in patients who had normal FPG levels [HR: 2.5, 95%CI 1.08–5.92, p = 0.03].Conclusion: Fasting plasma glucose significantly impacted both pCR and recurrence.

Contrast-enhanced ultrasonography for early prediction of response of neoadjuvant chemotherapy in breast cancer.

Neoadjuvant chemotherapy (NAC) is widely accepted as a primary treatment for inoperable or locally advanced breast cancer before definitive surgery. However, not all advanced breast cancers are sensitive to NAC. Contrast-enhanced ultrasonography (CEUS) has been considered to assess tumor response to NAC as it can effectively reflect the condition of blood perfusion and lesion size. Therefore, this study aimed to evaluate the diagnostic performance of CEUS to predict early response in different regions of interest in breast tumors under NAC treatment. This prospective study included 82 patients with advanced breast cancer. Parameters of TIC (time-intensive curve) between baseline and after the first cycle of NAC were calculated for the rate of relative change (Δ), including Δpeak, ΔTTP (time to peak), ΔRBV (regional blood volume), ΔRBF (regional blood flow) and ΔMTT (mean transit time). The responders and non-responders were distinguished by the Miller-Payne Grading (MPG) system and parameters from different regions of tumors were compared in these two groups. For ROI 1(the greatest enhancement area in the central region of the tumor), there were significant differences in Δpeak1, ΔRBV1 and ΔRBF1 between responders and non-responders. For ROI 2 (the greatest enhancement area on edge of the tumor), there were significant differences in Δpeak2 and ΔRBF2 between the groups. The Δpeak1 and ΔRBF2 showed good prediction (AUC 0.798-0.820, p ≤ 0.02) after the first cycle of NAC. When the cut-off value was 0.115, the ΔRBF2 had the highest diagnostic accuracy and the maximum NPV. Quantitative TIC parameters could be effectively used to evaluate early response to NAC in advanced breast cancer.

The Predictive Importance of Body Mass Index on Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer

Purpose: The aim of the study was to investigate the effects of body mass index (BMI) on the response to neoadjuvant chemotherapy (NACT) in Turkish patients with local and locally advanced breast cancer. Methods: The pathological responses for the breast and axilla were assessed according to the Miller-Payne grading (MPG) system. Tumors were grouped into molecular phenotypes and classified as response rates according to the MPG system after the completion of NACT. A 90% or greater reduction in tumor cellularity was considered a good response to treatment. Additionally, patients were grouped according to BMI into <25 (group A) and ≥25 (group B). Results: In total, 647 Turkish women with breast cancer were included in the study. In the univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and BMI were assessed to determine which of these factors were associated with a ≥90% response rate. Stage, HER2 positivity, triple-negative breast cancer (TNBC; ER-negative, PR-negative, and HER2-negative breast cancer), grade, Ki-67 levels, and BMI were found to be the statistically significant factors for a ≥90% response rate. In the multivariate analysis, grade III disease, HER2 positivity, and TNBC were found to be the factors associated with a high pathological response. Meanwhile, hormone receptor (HR) positivity and a higher BMI were associated with a decreased pathological response in patients receiving NACT for breast cancer. Conclusion: Our results show that a high BMI and HR positivity are associated with a poor response to NACT in Turkish patients with breast cancer. The findings presented in this study may guide novel studies to examine the NACT response in obese patients with and without insulin resistance.

Dynamic changes in intrinsic subtype, immunity status, and risk score before and after neoadjuvant chemo- and HER2-targeted therapy without pCR in HER2-positive breast cancers: A cross-sectional analysis.

Very few studies have been done in HER2 positive patients without complete pathological response (pCR) after combined neoadjuvant chemo- and HER2-target therapy to investigate changes in intrinsic subtype, risk of recurrence (ROR) score, and immunity status before and after treatment.Patients with nonmetastatic HER2-positive breast cancer failed to achieve pCR after neoadjuvant chemotherapy plus trastuzumab were included in current study. We examined the distribution of PAM50 subtypes, ROR score and immunity score in 25 paired baseline and surgical samples. The Miller–Payne grading system was used to evaluate the efficacy of the neoadjuvant therapy. It was observed that the distribution of intrinsic subtype, ROR category and immunity subgroup varied according to hormone receptor (HR) status. HER2-enriched and basal-like subtypes, median-high ROR categories and immunity-weak subgroup were dominant in baseline tumors. Compared to baseline samples, conversion of intrinsic subtype, ROR categories and immunity subgroups were found in 15 (60.0%), 13(52.0%), and 11(44.0%) surgical samples, respectively. The PAM50 subtype, ROR category, and immunity subgroup were concordant between baseline and surgical samples where nonluminal subtypes, median-high ROR categories and i-weak subgroup were still common.In conclusion, the HER2-positive breast cancer is highly heterogeneous with a distribution of 72-gene expression varying according to HR co-expression. The dynamics of the 72-gene expression pre- and posttreatment may become novel biomarker for guiding adjuvant therapy and hence warrant further investigation.

Identifying Circulating Tumor DNA Mutations Associated with Neoadjuvant Chemotherapy Efficacy in Local Advanced Breast Cancer.

Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer. Neoadjuvant chemotherapy (NACT) has become standard therapy for local advanced breast cancer (LABC). The aim of our study was to investigate plasma ctDNA as a prognostic marker for outcome in patients with LABC treated with NACT. A total of 56 patients with LABC were involved in this study. ctDNA mutations were investigated by using a 100 gene panel-target capture next-generation sequencing. The patients then received standard NACT therapy: adriamycin and cyclophosphamide and paclitaxel (AC-T) or AC-TH (AC-T+ Trastuzumab) regimen. The efficacy of NACT was evaluated by Miller-Payne grading system. A predictive and weight model was used to screen ctDNA point mutation biomarkers for NACT. The ctDNA mutational profile of LABC patients was identified. For nonsynonymous mutations, the top 5 mutated genes were MTHFR (51/56, 91.1%), XPC (50/56, 89.3%), ABCB1 (48/51, 94.1%), BRCA2 (38/56, 67.9%), and XRCC1 (38/56, 67.9%). In addition, the mutation frequencies of PIK3CA and TP53 were 32.1% (18/56) and 26.8% (15/56), respectively. The predictive model indicated that XRCC1 44055726 (TG>-) mutation (25/56, 44.6%) was significantly associated with Miller-Payne 4-5 and Miller-Payne 3-5 responses. While mTOR 11249132(G>C) mutation (23/56, 41.1%) was associated with Miller-Payne 1-4 or Miller-Payne 1-3 responses. Furthermore, XRCC1 44055726 (TG>-) accompanied by mTOR wild type predicted a good NACT efficacy in all response classification systems. The ROC curves to discriminate good neoadjuvant chemotherapy efficiency (Miller-Payne 4-5) and poor efficiency (Miller-Payne 1-3) were created, and AUC value was 0.77. Our results suggested that ctDNA mutation of XRCC1 44055726 (TG>-) might be a positive biomarker for NACT therapy in LABC, while mTOR 11249132(G>C) mutation was potentially associated with NACT resistance.

Using the apparent diffusion coefficient histogram analysis to predict response to neoadjuvant chemotherapy in patients with breast cancer: comparison among three region of interest selection methods.

BackgroundThe apparent diffusion coefficient (ADC) value using histogram analysis is helpful to predict responses to neoadjuvant chemotherapy (NAC) in breast cancer. However, the measurement method has not reached a consensus. This study was to assess the diagnostic performance of the ADC histogram analysis at predicting patient response prior to NAC in breast cancer patients using different region of interest (ROI) selection methods.MethodsA total of 75 patients who underwent diffusion weighted imaging (DWI) prior to NAC were retrospectively enrolled from February 2017 to December 2019. Images were measured using small 2-dimensional (2D) ROI, large 2D ROI, and volume ROI methods. The measurement time and ROI size were recorded. Histopathologic responses were acquired using the Miller-Payne grading system after surgery. The inter- and intra-observer repeatability was analyzed and the ADC histogram values from the three ROI methods were compared. The efficacy of each method at predicting patient response prior to NAC was assessed using the area under the receiver operating characteristic curve (AUC) for the whole study population and subgroups according to molecular subtype.ResultsAmong the 75 enrolled patients, 26 (34.67%) were responsive to NAC therapy. The ADC histogram values were significantly different among the three ROI methods (P≤0.038). Inter- and intra-observer repeatability of the large 2D ROI method and the volume ROI method was generally greater than that observed with the 2D ROI method. The 10% ADC value of the large 2D ROI method showed the greatest AUC (0.701) in the whole study population and in the luminal subgroup (AUC 0.804). The volume ROI method required significantly more time than the other two ROI methods (P<0.001).ConclusionsThe small 2D ROI method is not appropriate for predicting response prior to NAC in breast cancer patients due to the poor repeatability. When choosing the ROI method and the histogram parameters for predicting response prior to NAC in breast cancer patients using ADC-derived histogram analysis, 10% of the large 2D ROI method is recommended, especially in luminal A subtype patients.

Diagnostic performance of breast imaging with ultrasonography, magnetic resonance and mammography in the assessment of residual tumor after neoadjuvant chemotherapy in breast cancer patients

Background/Aim: Following the administration of neoadjuvant chemotherapy (NAC), a complete pathological response (pCR) is seen at rates of up to 50-70% in breast cancer patients, especially in triple-negative (TNBC) and HER-2 enriched subgroups and related to increased pCR rates, studies to predict the pathological response with preoperative evaluation are ongoing. The aim of this study was to investigate the correlation of preoperative imaging in breast cancer patients receiving NAC with the pathological response. Methods: The study, organized as a retrospective cohort study, included 129 breast patients who underwent surgery after NAC between April 2014 and February 2020. The demographic data of the patients, the clinical and radiological findings before and after NAC, operation findings, and the histopathological evaluation results were collected retrospectively from the patient files. The radiological images of the patients were examined by separating into groups of patients with ultrasonography (US), magnetic resonance imaging (MRI), US+MRI, and mammography (MG)+US. The NAC response on preoperative breast US and MG was evaluated according to the RECIST-1.1 system, and the NAC response on MRI with the Goorts et al grading system. In the histopathological examination of operation material, the Miller Payne grading system for breast tissue was used in the determination of NAC response. Results: The mean age of the patients in the study was 49.17 (11.00) years. The vast majority of the patients (87.6%) were diagnosed with invasive ductal cancer, with 27.13% in luminal A, 35.65% in luminal B, 31.0% in HER-2 enriched, and 6.2% in TNBC subgroups. A statistically significant correlation was determined between the pathological response and the US+MRI, MRI, and US+MG groups, with agreement at a moderate level (Kappa: 0.653, P<0.001; Kappa:0.443, P<0.001; Kappa:0.481, P=0.005, respectively). Within all the groups, the group with the highest sensitivity and accuracy were seen to be the patients evaluated with US+MRI (66.67%, 90.91%, respectively). Conclusion: The results of this study demonstrated that there is a correlation between the pathological response and US+MRI, MRI, and US+MG evaluation after NAC. The US+MRI group was found to have the highest sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. When possible, the use of these two imaging methods together in the preoperative evaluation of patients is a successful method in the prediction of pathological response.

Prediction of treatment responses to neoadjuvant chemotherapy in breast cancer using contrast-enhanced ultrasound.

Elucidation the efficacy of neoadjuvant chemotherapy (NAC) in breast cancer is important for informing therapeutic decisions. This study aimed at evaluating the potential value of contrast-enhanced ultrasound (CEUS) parameters in predicting breast cancer responses to NAC. We performed CEUS examinations before and after two cycles of NAC. Quantitative CEUS parameters [maximum intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (mTT)], tumor diameter, and their changes were measured and compared to histopathological responses, according to the Miller-Payne Grading (MPG) system (score 1, 2, or 3: minor response; score 4 or 5: good response). Prediction models for good response were developed by multiple logistic regression analysis and internally validated through bootstrap analysis. The receiver operating characteristic (ROC) curve was used to evaluate the performance of prediction models. A total of 143 patients were enrolled in this study among whom 98 (68.5%) achieved a good response and while 45 (31.5%) exhibited a minor response. Several imaging variables including diameter, IMAX, changes in diameter (Δdiameter), IMAX (ΔIMAX) and TTP (ΔTTP) were found to be significantly associated with good therapeutic responses (P<0.05). The areas under the curve (AUC) increased from 0.748 to 0.841 in the multivariate model that combined CEUS parameters and molecular subtypes with a sensitivity and specificity of 0.786, 0.745, respectively. Tumor molecular subtype was the primary predictor of primary endpoint. CEUS is a potential tool for predicting responses to NAC in locally advanced breast cancer patients. Compared to the other molecular subtypes, triple negative and HER2+/ER- subtypes are more likely to exhibit a good response to NAC.

Tumour-stroma ratio is associated with Miller-Payne grading system and pathological response to neoadjuvant chemotherapy in HER2-negative breast cancer

Background: In breast cancer, the tumour-stroma ratio (TSR) has shown to be a strong prognosticator, portraying that patients with stroma-low tumours have better survival outcomes than patients with stroma-high tumours. However, the precise role of the TSR as a predictive marker for neoadjuvant chemotherapy outcome is yet unknown. Therefore, we evaluated this association for HER2-negative breast cancer in the prospective, randomized, multicenter DIRECT and NEOZOTAC trials.

Higher efficacy and reduced adverse reactions in neoadjuvant chemotherapy for breast cancer by using pegylated liposomal doxorubicin compared with pirarubicin

The present study aimed to investigate the efficacy and toxicity of pegylated liposomal doxorubicin (PLD) in preoperative neoadjuvant chemotherapy for patients with breast cancer by comparing with conventional anthracycline. This study is a non-randomized controlled trial. Prospective analysis was conducted after matching as required. A total of 146 patients with confirmed diagnosis of breast cancer by histopathological examinations were enrolled into the observation group and control group in 1:1 ratio. Each of the cases in the observation group was required to correspond to another in the control group according to the requirements including age, molecular subtype, axillary node status, and regimen of the preoperative neoadjuvant chemotherapy. The chemotherapy was based on regimens consisting of anthracyclines, paclitaxel or docetaxel, and/or platinum. PLD was used at least twice in the observation group, with traditional anthracycline as a contrast in the control group. Clinical responses as well as cardiac side effects and other adverse reactions were evaluated by clinical and imaging examinations such as electrocardiogram (ECG) and color Doppler ultrasound during the chemotherapy. Pathologic examinations were performed following the surgeries after preoperative neoadjuvant chemotherapy. All the patients in both groups completed the preoperative neoadjuvant chemotherapy according to their original regimens. The postoperative pathological evaluation revealed a higher pathologic complete response (PCR) rate and significantly more patients of grade V of the Miller-Payne grading system in the observation group as compared to the control group (p = 0.047). In addition, the observation group recorded an evidently lower occurrence of the adverse cardiac events (p = 0.014), ECG changes (p = 0.048), and the relatively severe adverse reactions such as myelosuppression. Compared with conventional anthracycline drugs, PLD has a better pathologic response and safety performance, as well as a similar clinical effectiveness in preoperative neoadjuvant chemotherapy for breast cancer.

A Decision-Making Supporting Prediction Method for Breast Cancer Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) may increase the resection rate of breast cancer and shows promising effects on patient prognosis. It has become a necessary treatment choice and is widely used in the clinical setting. Benefitting from the clinical information obtained during NAC treatment, computational methods can improve decision-making by evaluating and predicting treatment responses using a multidisciplinary approach, as there are no uniformly accepted protocols for all institutions for adopting different treatment regiments. In this study, 166 Chinese breast cancer cases were collected from patients who received NAC treatment at the First Bethune Hospital of Jilin University. The Miller–Payne grading system was used to evaluate the treatment response. Four machine learning multiple classifiers were constructed to predict the treatment response against the 26 features extracted from the patients’ clinical data, including Random Forest (RF) model, Convolution Neural Network (CNN) model, Support Vector Machine (SVM) model, and Logistic Regression (LR) model, where the RF model achieved the best performance using our data. To allow a more general application, the models were reconstructed using only six selected features, and the RF model achieved the highest performance with 54.26% accuracy. This work can efficiently guide optimal treatment planning for breast cancer patients.

Radiomic signatures derived from multiparametric MRI for the pretreatment prediction of response to neoadjuvant chemotherapy in breast cancer.

To investigate the ability of radiomic signatures based on MRI to evaluate the response and efficiency of neoadjuvant chemotherapy (NAC) for treating breast cancers. 152 patients were included in this study at our institution between March 2017 and September 2019. All patients with breast cancer underwent a preoperative breast MRI and the Miller-Payne grading system was applied to evaluate response to NAC. Quantitative parameters were compared between patients with sensitive and insensitive responses to NAC and between those with pathological complete responses (pCR) and non-pCR. Four radiomic signatures were built based on T2W imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging and their combination, and radiomics scores (Rad-score) were calculated. The combination of the clinical factors and Rad-scores created a nomogram model. Multivariate logistic regression was performed to assess the association between MRI features and independent clinical risk factors. 20 features and 18 features were selected to build the radiomic signature for evaluating sensitivity and the possibility of pCR, respectively. The combined radiomic signature and nomogram model showed a similar discrimination in the training (AUC 0.91, 0.92, 95% confidence interval [CI], 0.85-0.96, 0.86-0.98) and validation (AUC 0.93, 0.91, 95% CI, 0.86-1.00, 0.82-1.00) sets. The clinical factor model exhibited reduced performance (AUC 0.74, 0.64, 95% CI, 0.64-0.84, 0.46-0.82) in terms of NAC sensitivity and pCR. The combined radiomic signature and nomogram model exhibited potential predictive power for predicting effective NAC treatment which can aid in the prognosis and guidance of treatment regimens. Identifying a means of assessing the efficacy of NAC before surgery can guide follow-up treatment and avoid chemotherapy-induced toxicity.

The Clinical Importance of Androgen Receptor Status in Response to Neoadjuvant Chemotherapy in Turkish Patients with Local and Locally Advanced Breast Cancer

Purpose: To investigate whether androgen receptor (AR) status affects neoadjuvant chemotherapy (NACT) in stage II and III Turkish breast cancer patients. Methods: The histological response for breast and axilla was assessed according to the Miller-Payne grading system. In light microscopy, nuclear staining in tumor cells was evaluated, and nuclear staining above 1% was accepted as positive for AR expression. The patients were divided into 3 groups according to the intensity of AR staining: low, moderate, and high. Results: In total, 71 women with breast cancer were included in the study. In univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER-2) status were tested to determine which of these factors were associated with >90% responsiveness. AR negativity was found to be the only statistically significant factor. In multivariate analysis, AR positivity at each intensity was found to be the single important factor affecting decreasing pathologic response in patients receiving NACT for breast cancer. Conclusion: Our results show that AR positivity is associated with poor response to NACT in Turkish breast cancer patients and that AR positivity is independent of stage, hormone receptor status, HER-2 status, and disease stage.

Correlation between HER2 amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2 positive breast cancer.

e12641 Background: HER2 targeted therapy in combination with chemotherapy have changed the aggressive natural history of HER2-positive tumors. To select patients to be treated with this type of agents, determination of HER2 status is usually carried out by immunohistochemistry, followed by in situ hybridization in equivocal cases (2+). There are contradictory data in literature regarding correlation between level of HER2 amplification determined by FISH and early and long-term treatment benefits. Objectives: The aim of this study was to correlate quantitative results of FISH (ratio HER2/CEN17 and number of HER2 signals/nucleus) with the grade of response to neoadjuvant treatment with trastuzumab and chemotherapy. Methods: We analyzed 100 consecutive cases of stage I-III breast carcinomas treated with trastuzumab and chemotherapy in the neoadjuvant setting at A Coruña University Hospital between 2005 and 2016. At Santiago University Hospital, 4 tissue microarrays were prepared and the IQFISH (Dako-Agilent) technique was performed using pretreatment biopsies. Results: HER2 amplification was found in 92 of 100 cases studied. Pathological Complete Response (pCR) (Miller-Payne grading system) was obtained in 58% of the patients whose tumors showed amplification. No pCR was obtained in the 8 patients whose tumors were negative by FISH (not amplified). Analysis of the quantitative results demonstrated a statistical significant direct correlation between pCR and both HER2/CEN17 ratios and HER2 gene copies/nucleus (p = 0.002 and p= 0.004, respectively). We also demonstrated an association between the HER2 amplification level (both ratios and numbers of HER2 signals) and a trend toward improved disease free survival (DFS) (p = 0.451 and p= 0.619, respectively). Conclusions: HER2 amplification level determined by FISH it is a good and available predictive factor of response and must be included in pathologic reports because it can provide valuable information to oncologists on the possibilities of achieving pCR after neoadjuvant treatment in HER2-positive breast cancer. Key words: Breast cancer, FISH, HER2 amplification, trastuzumab, neoadjuvant therapy, pathological complete response.

Tumour-infiltrating lymphocytes and response to neoadjuvant letrozole in patients with early oestrogen receptor-positive breast cancer: analysis from a nationwide phase II DBCG trial

BackgroundThe presence of tumour-infiltrating lymphocytes (TILs) is associated with response to neoadjuvant chemotherapy among patients with triple-negative and HER2-positive breast cancer. However, the significance of TILs is less clear in luminal breast cancer. Here, we in postmenopausal patients with primary oestrogen receptor-positive (ER+), HER2 normal, operable breast cancer assessed the importance of inducing TILs during 4 months of letrozole on response in a neoadjuvant phase II study.MethodsParticipants were postmenopausal women with ER+, HER2 normal operable breast cancer assigned to 4 months of neoadjuvant letrozole. Pretreatment core biopsies and surgical specimens were assessed centrally for the percentage of TILs on haematoxylin and eosin-stained slides according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines. Pathological response was assessed by the Residual Cancer Burden (RCB) index and a modified Miller-Payne grading system and was analysed according to change in TILs.ResultsTumour specimens were available from 106 of the 112 patients treated per protocol. TIL concentration increased with mean 6.8 percentage point (p < 0.0001) during treatment (range − 39 to 60). An increase in TILs was significantly associated with pathological response with OR = 0.71 (95% CI 0.53–0.96; p = 0.02) per 10% absolute increase for pathological response and correspondingly OR = 0.56 (95% CI 0.40–0.78; p = 0.0007) for lower RCB index per 10% increase.ConclusionIncreasing TILs during letrozole was significantly associated with a poor treatment response. An increase in TILs during endocrine therapy might imply immunogenicity, and these patients could be targetable by immunotherapy.Trial registrationClinicalTrials.govNCT00908531, registered 27 May 2009.