Miller-Payne Grading Research Articles

The effect of neoadjuvant chemotherapy on pathological response and the hormone receptor profile in locally advanced breast carcinomas

Background: The impact of neoadjuvant chemotherapy (NACT) on tumour biomarkers and the histopathological response to treatment in breast cancer specimens remains controversial. Chemotherapy and hormonal therapy decisions for breast cancer management are influenced by the expression of tumour biomarkers: estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2). On the other hand, pathological response is an indicator of chemotherapy effectiveness. The study of the effect of NACT in breast cancer is an important issue.Objectives: To assess the changes to biological markers ER, PR, and HER2, and the pathological response in locally advanced breast cancer patients after neoadjuvant chemotherapy.Methods: 100 patients with locally advanced breast cancer were assessed with core needle biopsy for biological markers (ER, PR, HER2) and pathological grading. Subsequently they were treated with six cycles of taxane based NACT followed by surgical resection. Biological markers and the pathological response (assessed by the Miller Payne grading system) were re-evaluated to assess changes.Results: The patient mean age was 45.62 ± 7.12 years. Most patients (56%) were postmenopausal. Clinical disease stage ranged between any T N2, T3 N1-2, T4 N0-2. Post NACT, pathological complete response rate was 14%, ER positivity decreased from 80 (80%) to 78 (78%) (p = 0.67). PR positive dropped from 66 to 62% (p = 0.002), and HER2 receptor positivity was increased from 22% to 28% (p-value 0.000).Conclusion: It was observed that biological markers (ER, PR, HER2) and the histopathological response of breast cancer may change after NACT. This change may affect treatment decisions.

Biomarker Alteration to Neoadjuvant Chemotherapy Predict Pathological Response and Prognosis in Breast Cancer Patients

Background: The values of biomarkers expression might be changed following neoadjuvant chemotherapy (NACT), but little is known about the change range and its relationship to prognosis. This study aimed to investigate the potential changes of biomarkers expression before and after neoadjuvant chemotherapy, then predicting the pathological response and prognosis to NACT. Methods: A total of 119 patients who were initially diagnosed of breast cancer and underwent neoadjuvant chemotherapy were included in the study. Miller-Payne grading system was used to evaluate the pathologic response after neoadjuvant chemotherapy. Survival curves were estimated using the Kaplan-Meier method, and the log-rank test was used to test for differences between groups. Results: The high expression of ER, PR and Ki67 pre-NACT, the biomarkers expression post-NACT is also high (All P  values <0.05). We found that the change of biomarkers expression before and after chemotherapy were all considered as medium changes (range between 10 to 30), while only PR expression change after NACT were associated with distant disease-free survival ( P <0.001) and overall survival ( P =0.031,6). PR expression also related to pathologic response ( P =0.028) but not ER, HER2 and Ki-67. Furthermore, a total of 67 down regulated of Ki67 expression compared with 37 up regulated expression, the results showed that decreasing expression of Ki67 had fewer local recurrence compared with Ki67 increasing expression after NACT. Conclusions: Our research have provided the prognostic value of biomarkers expression change following the neoadjuvant chemotherapy. These findings might help optimize the choice of targeted therapy and improve the predictive effect to patient survival.

Intravoxel incoherent motion diffusion-weighted MRI for predicting response to neoadjuvant chemotherapy in breast cancer

PurposeTo determine the diagnostic performance of intravoxel incoherent motion (IVIM) diffusion-weighted (DW) magnetic resonance imaging (MRI) parameters in predicting response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and methodsForty-six patients with stage II or III breast cancer underwent MRI including DW imaging with 10 b values before and after 2cycles of NAC. Apparent diffusion coefficient (ADC) and IVIM parameters (D, D*, and f) were obtained using histogram analysis derived from whole-tumor volumes. After surgery, imaging parameters were compared with histopathologic responses using the Miller-Payne grading system. ResultsBefore NAC, Dmean, D50, and D75 were higher in good responders than in minor responders (P≤0.043). After NAC, ADCmean, ADC50, ADC75, Dmean, D25, D50, and D75 were higher in good responders (P≤0.037). Skewness of ADC and D were lower in good responders after NAC (P≤0.005). Most histogram metrics of posttreatment ADC and D had similar AUC values with reasonable accuracy for prediction of good response (AUC≥0.7, P<0.05). ConclusionD and ADC are useful for the prediction of response to NAC in breast cancer patients. Additional information is obtained by application of the IVIM model in DW imaging analysis and histogram analysis using whole-tumor volume data.

Role of postmastectomy radiation therapy in breast cancer patients with different pathological responses to neoadjuvant chemotherapy

AbstractObjectiveThe purpose of the present study was to investigate the role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy in breast cancer patients of clinical stage II–III with different pathological responses to neoadjuvant chemotherapy.MethodsWe retrospectively analyzed 79 clinical stage II–III breast cancer patients who underwent mastectomy after neoadjuvant chemotherapy between 2008 and 2013. According to the Miller–Payne grading system, we defined grades 1–2 as the poor response group, and grades 3–5 as the good response group. The 5‐year curves for locoregional recurrence free survival (LRRFS), distant disease‐free survival, and overall survival were constructed using the Kaplan–Meier method, and compared using the log–rank test.ResultsFor all patients, the median age was 48 years (range 29–68 years). At a median follow up of 56 months, the 5‐year LRRFS was 97.8% and 81.8% (P = 0.01), the 5‐year distant disease‐free survival was 73.9% and 75.8% (P = 0.14), and the 5‐year overall survival for both was 84.8% (P = 0.96). In the subgroup analysis, the LRRFS, distant disease‐free survival, and overall survival of the subgroup with a good response did not benefit from PMRT. However, the LRRFS of the poor response subgroup can significantly benefit from PMRT (P = 0.04).ConclusionsPMRT was effective in reducing the local‐regional recurrence rate for patients with a Miller–Payne grade 1–2; therefore, we suggest that PMRT should be considered for these patients.

Evaluation of the Tumor Response After Neoadjuvant Chemotherapy in Breast Cancer Patients: Correlation Between Dynamic Contrast-enhanced Magnetic Resonance Imaging and Pathologic Tumor Cellularity

BackgroundWe evaluated the tumor response after neoadjuvant chemotherapy (NAC) in breast cancer patients using dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging parameters assessed using a commercially available computer-aided system. We also analyzed their correlation with pathologic tumor cellularity. Materials and MethodsWe retrospectively reviewed the data from 130 patients with breast cancer who had undergone NAC followed by surgery from January to October 2013. Maximum diameter, volume, peak enhancement, and persistent, plateau, and washout-enhancing components were measured using a computer-aided system on DCE MR images and correlated with the Miller-Payne grading system. Patients with a Miller-Payne grade of 5 were classified into the pathologic complete response (pCR) group. Patients with grades 1, 2, 3, and 4 were included in the non-pCR group. Diagnostic performance was evaluated using receiver operating characteristic curve analysis. ResultsTwenty patients were included in the pCR group and 110 patients in the non-pCR group. Of the 6 parameters, the rate of tumor volume reduction (r = 0.729, P < .001) showed the strongest correlation with the Miller-Payne grading system, followed by the maximum diameter (r = 0.706, P < .001) and washout component (r = 0.606, P < .001). The area under the receiver operating characteristic curve (Az value) was the largest for the rate of volume reduction (Az = 0.895), followed by the maximum diameter (Az = 0.891). ConclusionThe tumor volume changes in breast cancers before and after NAC, measured automatically using a commercially available computer-aided system and a clinical DCE MR imaging protocol might be the most accurate tool for evaluation of the pathologic response after NAC.

Abstract P5-16-13: Predictive and prognostic value of Ki-67 expression in triple-negative breast cancer before and after neoadjuvant chemotherapy with weekly paclitaxel plus carboplatin

Abstract Background: Neoadjuvant chemotherapy (NCT) is one of the main treatment strategies for patients with locally advanced breast cancer. This study was designed to demonstrate the utility of a platinum-containing treatment regimen in the neoadjuvant setting and to identify the predictive or prognostic value of Ki-67 among patients with triple-negative breast cancer (TNBC) Methods: Data from 280 patients with stage II–III TNBC were collected. All patients underwent four cycles of NCT with paclitaxel (80 mg/m2) and carboplatin (AUC 2 mg*min/ml) on days 1, 8, and 15 of a 28-day cycle. Ki-67 values were evaluated in both biopsy and excision specimens. The clinical responses to NCT were evaluated based on MRI and ultrasound examinations in accordance with the response evaluation criteria in solid tumors (RECIST) version 1.1. The pathological evaluation of surgical specimens was conducted at by the Miller-Payne (MP) grading system. Logistic regression analysis was performed to identify independent predictors of pathological complete response (pCR). Survival analysis was performed to evaluate the prognostic value of various clinical and pathological variables. Results: The overall pCR rate was 33.9%. Both the categorical and linear Ki-67 were independently correlated with pCR (P&amp;lt;0.001). There were also statistically significant differences among Ki-67 categories with respect to clinical response (P&amp;lt;0.001), Miller-Payne (MP) grades (P&amp;lt;0.001), and node status (P&amp;lt;0.001). A significant reduction of Ki-67 after NCT was most likely observed in patients with a relatively better response. Among 185 patients with a residual tumor after NCT, the tumor cell proliferation significantly decreased from a median Ki-67 value of 20.0% before chemotherapy to 15% after chemotherapy. The mean absolute reductions in Ki-67 were 29.4%, 8.5%, and -10.2% in patients with an ideal response (MP 5/4), a partial response (MP 3) and a poor response (MP2/1), respectively. In the multivariate model for non-pCR patients, Ki-67 reduction presented an independent prognostic value for relapse of disease (HR=0.986, 95% CI: 0.978-0.994; P=0.001). Residual node involvement was also an independent predictor of patient outcome (HR=0.895, 95% CI: 0.355-2.259 for 1-3 nodes and HR=2.424, 95% CI: 1.048-5.608 for more than 4 nodes, using 0 nodes as a reference; P=0.002). Better survival was more frequently observed in patients with a greater reduction in the Ki-67 value and fewer involved nodes. Conclusions: The primary Ki-67 might help in further classifying TNBCs into subtypes with different responses to chemotherapy. The significant reduction of Ki-67 after treatment could indicate a favorable prognosis in non-pCR patients. Citation Format: Wang R-X, Chen S, Jin X, Shao Z-M. Predictive and prognostic value of Ki-67 expression in triple-negative breast cancer before and after neoadjuvant chemotherapy with weekly paclitaxel plus carboplatin [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-13.

Abstract P5-16-08: Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy

Abstract Purpose: We seek to investigate the prognostic factors that could possibly affect the local-regional recurrence (LRR) of breast cancer patients who do not achieve pathological complete response (pCR) after neoadjuvant chemotherapy (NCT), and to build a prognostic nomogram to predict patients' outcome. Methods: The retrospective analysis included 510 patients who had received NCT followed by surgery and radiotherapy. The NCT regimens included anthracycline-containing, vinorelbinecontaining, and taxane-containing regimens for a median of 3 cycles. The clinical responses to neoadjuvant chemotherapy were evaluated based on MRI and ultrasound examinations and in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Miller-Payne (MP) grading system was employed to evaluate the decrease in cancer cellularity. Multivariate analyses were used to identify independent predictors of LRR. Results: The median follow-up for the entire study population was 61 months (range 5-128 months). There were 40 isolated local recurrences, 17 regional-only recurrences and 5 patients with local and regional recurrences. Sixteen patients (25.8%) occurred synchronously with distant metastasis, and no LRR was detected after distant failure. Fifteen patients had recurrences in the supraclavicular field. The 5-year cumulative LRR-free survival rate was 88.0% (95% CI: 85.2%-90.1%). The 5-year overall survival and disease-free survival rates were 79.0% (75.5%-82.6%) and 63.1% (58.9%-67.3%), respectively. Multivariate analysis revealed that positivity for ≥ 4 lymph nodes and Ki-67 index ≥ 14% were independent factors for LRR-free recurrence. The prognostic model was established based on the sum of both independent prognostic factors, with positivity for ≥ 4 lymph nodes and Ki-67 index ≥ 14% individually contributing 1 point to the risk score. The patients in the validation set were assigned to a low-risk group (0 point), median-risk group (1 point) and high-risk group (2 points). The 5-year LRR-free survival rates in the low, intermediate, and high-risk groups were 95.5%, 89.1%, and 67.1%, respectively (p &amp;lt; 0.001). We also show the annual LRR rate among these 3 groups using our single-institution data, as well as to review relevant literature-based data to compare with our observations. Four publications that reported ARR (annual recurrence rate) after surgery for primary breast cancer were identified as eligible. In the relevant literature, the annual risk of local-regional recurrence peaked between two and three years after the initial diagnosis. In contrast, the ARR curve of the high risk subgroup for neoadjuvant patients exhibited one peak near 1 year (17% per annum). The median and low-risk subgroups did not have an obvious recurrence peak. Conclusion: This prognostic model has considerable clinical value in predicting local-regional recurrence, which could help clinicians to design appropriate local-regional treatment specifically and to perform surveillance individually. Citation Format: Chen S, Huang L, Shao Z-M. Risk factors of locoregional relapse in locally advanced breast cancer treated with neoadjuvant chemotherapy following mastectomy and radiotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-08.

Histogram analysis of apparent diffusion coefficients after neoadjuvant chemotherapy in breast cancer.

To evaluate the changes in the apparent diffusion coefficient (ADC) histogram during neoadjuvant chemotherapy (NAC) for breast cancer, and to compare the observed changes in pathologically verified responders and non-responders. Sixty-two patients received NAC followed by surgery. Responders were defined by a tumor cell reduction of at least 30% using the Miller-Payne grading system. All the patients underwent 3T magnetic resonance with diffusion-weighted imaging (b values of 0 and 750s/mm2) before the NAC and after the completion of two cycles of NAC. Mean, minimum, 10th, 25th, 50th, and 75th percentile of ADCs significantly increased after NAC and maximum ADC significantly decreased. Skewness became less positive and kurtosis decreased. A tendential, although not statistically significant, higher increase in mean, minimum, 10th, 25th, 50th, 75th, and 90th percentiles of ADCs was observed in responders in comparison with non-responders. ADC histogram analysis quantitatively demonstrates the alterations during the treatment course.

Value of Ki-67 expression in triple-negative breast cancer before and after neoadjuvant chemotherapy with weekly paclitaxel plus carboplatin.

Neoadjuvant chemotherapy (NCT) is one of the main treatment strategies for patients with locally advanced breast cancer. In this study, we focused on the predictive and prognostic value of Ki-67 in triple-negative breast cancer (TNBC) patients who received NCT. Data from 280 patients with stage II–III TNBC were collected. All patients were treated according to the same protocol with weekly paclitaxel and carboplatin. The overall pCR rate was 33.9%. Both the categorical and linear Ki-67 were independently correlated with pCR (P < 0.001). There were also statistically significant differences among Ki-67 categories with respect to clinical response (P < 0.001), Miller-Payne (MP) grades (P < 0.001), and node status (P < 0.001). A significant reduction of Ki-67 after NCT was most likely observed in patients with a relatively better response. In the multivariate model for non-pCR patients, Ki-67 reduction presented an independent prognostic value for relapse of disease (HR = 0.986, 95% CI: 0.978–0.994; P = 0.001). This study had indicated that the primary Ki-67 might help in further classifying TNBCs into subtypes with different responses to chemotherapy and a significant reduction of Ki-67 after treatment could indicate a favorable prognosis in non-pCR patients.

The Value of 18F-FDG PET/CT Imaging Combined With Pretherapeutic Ki67 for Early Prediction of Pathologic Response After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

To evaluate the value of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) and pretherapeutic Ki67 in predicting pathologic response in locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC).As a training set, total 301 LABC patients treated with NAC were retrospectively analyzed to evaluate the potential predictive value of pretherapeutic Ki67 for pathologic complete response (pCR) after NAC. Another 60 LABC patients were prospectively included as a validation set to evaluate the value of Ki67 combined PET/CT as pCR predictors. Ki67 was assessed in pretherapy core needle biopsy specimens and PET/CT scans were performed at baseline (before initiating NAC), after the 2nd, and 4th cycle of NAC. Maximum standardized uptake value (SUVmax) and its changes relative to baseline (ΔSUVmax%) were used as parameters of PEC/CT.In the training set, Ki67 was a predictor of pCR to NAC, with area under the curve (AUC) of 0.624 (P = 0.003) in receiver-operating characteristic (ROC) analysis. In the validation set, Ki67 alone did not show significant value in predicting pCR in the validation set. ΔSUVmax% after then 2nd or 4th course are predictors of pCR to NAC with the AUC of 0.774 (P = 0.002) and 0.791 (P = 0.002), respectively. When combined with ΔSUVmax% after the 2nd and 4th course NAC, Ki67 increased the value of ΔSUVmax% in predicting pCR with the AUC of 0.824 (P = 0.001). Baseline SUVmax and after 2nd, 4th course NAC had no predictive value for pCR, but SUVmax after the 2nd and 4th course showed remarkable predictive value for nonpathologic response (Grade 1 in Miller-Payne Grading System) with the AUC of 0.898 (P = 0.0001) and 0.801 (P = 0.003).Both PET/CT and Ki67 can predict pCR to NAC in LABC patients in the early phases of treatment. PET/CT combined Ki67 is a better pCR predictor for response to NAC. This helps the physician to predict the probability of pCR, and facilitates the optimization of individual treatment plan in case of ineffective and/or excessive chemotherapy.

P0191 Histogram analysis of apparent diffusion coefficients after neoadjuvant chemotherapy in breast cancer

Background The purpose of our study was to evaluate change of the apparent diffusion coefficient (ADC) histogram during the neoadjuvant chemotherapy (NAC) in breast cancer, and to compare changes between pathologically verified responders and non-responders. Methods 62 patients received NAC followed by surgery. We defined responders and non-responders based on 30% reduction in tumour cells using the Miller-Payne Grading System. All patients underwent 3T magnetic resonance (MR) with diffusion-weighted imaging (DWI) before the NAC and after the completion of two cycles of NAC. ADC histogram analysis encompassing the entire tumour was performed and various ADC parameters (mean, minimum, 10th, 25th, 50th, 75th, 90th percentile, maximum ADCs, skewness, and kurtosis) were obtained. Findings Mean, minimum, 10th, 25th, 50th, and 75th percentile ADCs significantly increased after NAC ( p =0.0129, p =0.0004, p =0.0047, p =0.0002, p =0.0006, p =0.0030) and maximum ADC significantly decreased (p=0.0003). Skewness changed into less positive ( p p =0.0168) after NAC. Although there was no statistical significance, mean, minimum, 10th, 25th, 50th, 75th, and 90th percentile ADCs tended to decrease more in responders compared with non-responders. Interpretation There is significant change in distribution of ADC after NAC. ADC histogram analysis quantitatively demonstrates the alterations more precisely during the treatment course.

Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer.

BackgroundThe pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.MethodsA consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG) and Residual Disease in Breast and Nodes (RDBN).ResultsTen patients (11.4%) achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03). MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.ConclusionMPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease-free survival, and RDBN was more suitable for evaluation of local recurrence-free survival. Survival following neoadjuvant chemotherapy correlated with the pathological reaction rather than the molecular subtype of breast cancer. The molecular subtype of breast cancer was not correlated with pathological response in patients who did not achieve a pathological complete response.

Prognostic and predictive value of NanoString-based immune-related gene signatures in a neoadjuvant setting of triple-negative breast cancer: relationship to tumor-infiltrating lymphocytes.

The prognostic significance of tumor-infiltrating lymphocytes and immune signals has been described previously in triple-negative breast cancer (TNBC). Furthermore, recent studies have shown that immunologic parameters are relevant for the response to neoadjuvant chemotherapy (NAC) in breast cancer as well as for outcomes after adjuvant chemotherapy. However, immune signals are variable, and which signals are important is largely unknown. We, therefore, evaluated the expression of immune-related genes in TNBC treated with NAC. We retrospectively evaluated biopsy tissue from 55 patients with primary TNBC treated with NAC (anthracycline, cyclophosphamide, and docetaxel) against the NanoString nCounter GX Human Immunology Panel (579 immune-related genes). Higher expression of cytotoxic molecules, T cell receptor signaling pathway components, cytokines related to T helper cell type 1 (Th1), and B cell markers was associated with a pathologic complete response (pCR). Higher expression of NFKB1, MAPK1, TRAF1, CXCL13, GZMK, and IL7R was significantly associated with pCR, higher Miller-Payne grade, and lower residual cancer burden class. Expression of NFKB1, TRAF1, and CXCL13genes, in particular, was significantly correlated with a longer disease-free survival rate. Conversely, patients those who failed to achieve a pCR showed increased expression of genes related to neutrophils. Higher expression of cytotoxic molecules, T cell receptor signaling pathway components, Th1-related cytokines, and B cell markers is correlated with pCR and survival in TNBC patients treated with NAC. Our results suggest that the activation status of neutrophils may provide additional predictive information for TNBC patients treated with NAC.

Progesterone receptor loss identifies luminal-type local advanced breast cancer with poor survival in patients who fail to achieve a pathological complete response to neoadjuvant chemotherapy.

The aim of this study was to investigate the potential of progesterone receptor (PgR) as a biomarker for differentiating estrogen receptor (ER)-positive patients who fail to achieve a pathological complete response to neoadjuvant chemotherapy (NCT) with different prognoses. A total of 327 consecutive, locally advanced breast cancer patients with ER-positive disease were included in this study. According to their HER-2 and Ki-67 status, the patients were classified into the Luminal-A or Luminal-B subtype. We evaluated the clinical and pathological response to NCT and relapse or death occurring during follow-up according to PgR status in the different luminal subtypes. In the Luminal-B subtype, patients with PgR- tumors had a relatively higher pathological complete response (pCR) rate (29.5% vs. 4.7% pCR, P < 0.001) and Miller-Payne grades (45.5% vs. 23.5% of grade 4-5, P = 0033) compared to PgR+ tumors. In Luminal-B patients with residual tumor after NCT, PgR loss was also independently correlated with poor relapse-free survival (P = 0.017; HR = 0.430; PgR- as a reference) and overall survival (P = 0.013; HR = 0.355; PgR- as a reference). However, in the Luminal-A subtype, there were no statistically significant differences between PgR+ and PgR- disease in response to NCT or survival. Our findings have demonstrated the prognostic value of PgR loss in the neoadjuvant setting, indicating that ER+/PgR- Luminal-B tumors warrant further attention due to their high risk of relapse after primary treatment.

Abstract P3-06-33: Comparison of pathologic response evaluation systems after neoadjuvant chemotherapy among different molecular subtypes of breast cancers

Abstract Background: Several ways to assess pathologic response of breast cancer after neoadjuvant chemotherapy (NAC) are currently available. However, clinical usefulness of assessment systems in each molecular subtype of breast cancer is unclear. Therefore, we compared four pathologic response assessment systems predicting patients’ clinical outcome in specific subtypes of breast cancer. Methods: In total, 598 tumors from 590 female breast cancer patients who received anthracycline and taxane-based NAC and subsequent surgery from 2010 to 2012 were analyzed. Molecular subtypes were defined by immunohistochemistry (HER2 and hormone receptor (HR): estrogen receptor and progesterone receptor). Miller-Payne grading, Residual Cancer Burden, Residual Disease in Breast and Nodes and ypTNM stage were evaluated. Results of each assessment system were analyzed for survival with Kaplan-Meier and Cox hazard model. Median follow-up period was 35.2 months (range 21.1-54.4 months). Results: Pathologic complete response was achieved in 4.4% (12/275) of HR+/HER2-, 10.7% (8/75) of HR+/HER2+, 17.8% (16/90) of HR-/HER2+, and 29.7% (47/158) of triple negative (TN) tumors. Results of all four examined assessment systems were significantly correlated with disease-free and overall survival in all tumors. In HR+/HER2- and TN tumors, all systems were associated with disease-free and overall survival. Comparison of pathologic response assessment systems after neoadjuvant chemotherapy for disease-free and overall survivalDisease-free survivalHR+/HER2-HR+/HER2+HR-/HER2+TNMiller Payne gradeHR (95% CI)0.629 (0.429-0.925)0.310 (0.159-0.607)0.647 (0.428-0.977)0.451 (0.343-0.593)P value.018&amp;lt;0.001.039&amp;lt;0.001RCB classHR (95% CI)2.621 (1.398-4.914)2.454 (0.917-6.564)1.696 (0.929-3.094)2.966 (1.982-4.441)P value.003.074.085&amp;lt;0.001RDBN levelHR (95% CI)2.892 (1.642-5.093)2.587 (1.015-6.595)2.189 (1.118-4.286)3.065 (2.108-4.456)P value&amp;lt;0.001.047.022&amp;lt;0.001ypTNM StageHR (95% CI)2.975 (1.606-5.512)2.062 (0.918-4.632)2.004 (1.121-3.582)2.950 (2.152-4.044)P value.001.080.019&amp;lt;0.001Overall survivalMiller Payne gradeHR (95% CI)0.416 (0.222-0.778)0.399 (0.177-0.896)0.633 (0.357-1.124)0.397 (0.294-0.537)P value.006.026.119&amp;lt;0.001RCB classHR (95% CI)8.611 (1.924-38.531)2.971 (0.733-12.032)1.900 (0.771-4.680)2.976 (1.927-4.594)P value.005.127.163&amp;lt;0.001RDBN levelHR (95% CI)11.369 (2.618-49.375)3.042 (0.801-11.550)1.970 (0.805-4.821)3.262 (2.145-4.961)P value.001.102.138&amp;lt;0.001ypTNM StageHR (95% CI)5.812 (1.666-20.270)2.623 (0.851-8.080)1.619 (0.739-3.546)3.040 (2.150-4.300)P value.006.093.228&amp;lt;0.001RCB, residual cancer burden; RDBN; residual disease breast and nodes. Especially in TN, Kaplan-Meier survival curves for disease-free survival were clearly separated by all assessment methods. However, in HR+/HER2+ and HR-/HER2+ tumors, the association of patients’ survival with response assessment results was variable according to the examined systems. Conclusion: By the available pathologic assessment systems after neoadjuvant chemotherapy, HR+/HER2- and TN breast cancers could be effectively classified into groups showing different prognosis. However, for the evaluation of pathologic response of HR+/HER2+ and HR-/HER2+ tumors, the development of effective assessment methods is warranted. Citation Format: In Ah Park, Hee Jin Lee, In Hye Song, Gyungyub Gong. Comparison of pathologic response evaluation systems after neoadjuvant chemotherapy among different molecular subtypes of breast cancers [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-33.

Abstract P1-01-04: Evaluation of tumor response after neoadjuvant chemotherapy in breast cancer patients: Correlation between dynamic contrast-enhanced MRI and pathologic tumor cellularity

Abstract Purpose: The objective of the study was to analyze whether the measurement of changes of the tumor on magnetic resonance imaging (MRI), could be applied to predict pathologic response after neoadjuvant chemotherapy. Methods: Between January 2013 and October 2013, 155 patients (age range, 31-74 years; mean age, 47.6 years) with pathologically proven breast cancer who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. Pre-and post-treatment measurements and changes in tumor size and dynamic curve pattern of MRI were analyzed. Histological regression was scored on the residual overall tumor cellularity based on Miller-Payne grading system. Results: The change of maximal diameter (ρ = 0.681, p &amp;lt; 0.001), angio-volume of tumor (ρ = 0.683, p &amp;lt; 0.001) and washout ratio of dynamic curve (ρ = 0.607, p &amp;lt; 0.001) measured on MRI showed strong correlation with histological regression. Among them, the correlation factor was highest in the change of angio-volume. The change of plateau ratio of dynamic curve showed moderate correlation (ρ = 0.574, p &amp;lt; 0.001) with histological regression. However, the change of persistent ratio of dynamic curve showed weak correlation (ρ = 0.206, p = 0.011). Conclusions: The change of maximal diameter, angio-volume of tumor and washout ratio of dynamic curve measured on MRI showed strong correlation with residual cellularity in lesions after neoadjuvant chemotherapy and could be applied to predict pathologic response. Citation Format: Hak Hee Kim, Won Kyung Kim, Joo Hee Cha, Hee Jung Shin, Eun Young Chae, Woo Jung Choi. Evaluation of tumor response after neoadjuvant chemotherapy in breast cancer patients: Correlation between dynamic contrast-enhanced MRI and pathologic tumor cellularity [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-01-04.

Abstract 1880: Pathologic response pattern of breast cancer after neoadjuvant chemotherapy: its correlation with molecular subtypes

Abstract Background: Several ways to assess pathologic response of breast cancer after neoadjuvant chemotherapy (NAC) are currently used, including Miller-Payne system and residual cancer burden. However, the relationship between pathologic response pattern and molecular subtype of breast cancer is unclear. Methods: We investigated the pathologic response pattern of breast cancer after NAC in each molecular subtype. Female breast cancer patients who received NAC and subsequent breast operation were retrospectively analyzed. The NAC regimen used for breast cancer was primarily anthracycline and taxane-based, depending on the axillary lymph node involvement. We evaluated the molecular subtypes by immunohistochemistry, pretreatment tumor sizes by MRI, absolute invasive tumor cellularities in pretreatment biopsy and operation specimens, pathologic complete response (pCR) rates, posttreatment pathologic tumor sizes, overall residual tumor cellularities, and grades for Miller-Payne system. Results: A total of 119 patients (age: 45.2 ± 9.5 yr) were enrolled. Sixty-six cases were hormone receptor positive (ER or PR positive), 18 cases were HER2 positive (ER and PR negative), and 35 cases were triple negative. There were no significant differences in pretreatment tumor size by MRI and absolute cellularity in biopsy between three groups. After NAC, hormone receptor positive tumors showed the lowest pCR rate (18.2 %) while triple negative tumors showed the highest pCR rate (45.7 %, p=0.013). In patients with residual carcinoma, hormone receptor positive tumors showed the largest ypT size (p=0.016), the least reduction of tumor size (p=0.001), and the least absolute invasive tumor cellularity (p=0.006). Overall residual tumor cellularity and Miller-Payne grade were not significantly different between three groups (p=0.4 and p=0.703, respectively). Conclusion: These results suggest that each molecular subtype of breast cancer shows characteristic pathologic response patterns following NAC. Citation Format: In-Hye Song, Hee Jin Lee, Gyungyub Gong. Pathologic response pattern of breast cancer after neoadjuvant chemotherapy: its correlation with molecular subtypes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1880. doi:10.1158/1538-7445.AM2014-1880

Clinical and Pathological Response to Neoadjuvant Chemotherapy Based on Primary Tumor Reduction is Correlated to Survival in Hormone Receptor-Positive but not Hormone Receptor-Negative Locally Advanced Breast Cancer

This study was designed to examine the relationship between different methodologies for response evaluation and long-term survival estimation in patients underwent neoadjuvant chemotherapy (NCT) for breast cancer. We retrospectively analyzed 569 patients who were diagnosed with LABC and received NCT followed by breast and axilla surgery. The RECIST 1.1 criteria and Miller-Payne (MP) grading scale were used to evaluate patient responses to NCT. Univariate and multivariate survival analyses were performed to investigate the correlation between treatment response and long-term patient survival. Clinical response (RFS [P<0.001]; OS [P=0.003]), pathological response evaluated by pCR (RFS [P<0.001]; OS [P<0.001]), and MP grade (RFS [P<0.001]; OS [P<0.001]) were significant predictors of risks of relapse and survival. However, in hormone receptor-positive (ER and/or PR+) subtypes, the clinical response (P=0.004 for Luminal-A and P=0.038 for Luminal-B) and MP grade (P=0.002 for Luminal-A and P<0.001 for Luminal-B) significantly predicted RFS independently according to multivariate Cox regression model. MP grade (P=0.015 for Luminal-A and P=0.009 for Luminal-B) also was an independent predictor of patients' OS. However, these two methods failed to predict patient survival in hormone receptor-negative (ER and PR-) subtypes. Our findings indicate that the value of response evaluation methods varies for different breast cancer subtypes. Conceiving of further prospective approaches for new individualized response-evaluation models are needed in the neoadjuvant setting.

Utility of MRI and PET/CT after neoadjuvant chemotherapy in breast cancer patients: correlation with pathological response grading system based on tumor cellularity

MRI and PET/CT are useful for assessing breast cancer patients after neoadjuvant chemotherapy (NAC). To investigate the utility of MRI and PET/CT in the prediction of pathologic response to neoadjuvant chemotherapy using Miller-Payne grading system in patients with breast cancer. From January 2008 to December 2010, 59 consecutive patients with pathologically proven breast cancer, who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. The maximal diameter decrease rate and volume reduction rate by three-dimensional (3D) MRI and standardized uptake value (SUV) reduction rate by PET/CT were calculated and correlated with the Miller-Payne grading system using the Spearman rank correlation test. Patients with Miller-Payne grades 1 or 2 were classified into the non-responder group and patients with grades 3, 4, and 5 were in the responder group. To differentiate between responders and non-responders, receiver-operating characteristic (ROC) analysis was performed. The volume reduction rate was 64.87 ± 46.95, diameter decrease rate was 48.09 ± 35.02, and SUV decrease rate was 62.10 ± 32.17. Among three parameters, the volume reduction rate was most correlated with histopathologic grades of regression (ρ = 0.755, P < .0001) followed by diameter decrease rate (ρ = 0.660, P < 0.0001), and SUV decrease rate of primary breast mass (ρ = 0.561, P = 0.0002). The area under the ROC curve (Az) value was largest in the volume reduction rate (Az = 0.9), followed by SUV decrease rate (Az = 0.875), and diameter decrease rate (Az = 0.849). The best cut-offs for differentiating responders from non-responders in the ROC curve analysis were a 50% decrease in diameter, 68.9% decrease in volume, and 60.1% decrease in SUV after NAC. Volumetric measurement using 3D MRI combined with conventional diameter measurement may be more accurate to evaluate pathologic response after NAC.

A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer

Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m2 daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller–Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer.