Pathological Response Of Breast Cancer Research Articles

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

Abstract P2-02-08: MRI in predicting pathological response of breast cancer after neoadjuvant chemotherapy: Correlation with tumor size and morphology changes

Abstract PURPOSE Contrast enhanced MR imaging is widely used to monitor the response of neoadjuvant chemotherapy (NAC) in breast cancer patients. The objectives of the study are 1) to assess the response of neoadjuvant chemotherapy (NAC) according to molecular biomarker status using MRI, 2) to evaluation of changes in morphological variation, and 3) to compare MR imaging-pathological size discrepancy depending on molecular biomarker status. MATERIALS AND METHODS Between May 2007 and March 2012, a total of 47 patients (age range, 34-65 years; mean age, 48 years) underwent NAC prior to surgery. Among them, 34 patients who performed MRI before and after NAC were enrolled. The extent of the lesion is measured by longest diameter. The response to NAC was calculated as reduction rate between pre NAC MRI and post NAC MRI. Histological grading system - Miller and Payne grade - was also recorded. Patients were divided into subgroups based on human epidermal growth factor receptor 2 (HER2), hormone receptors (HRs), and the proliferation marker Ki-67 status. The morphologic changes were classified into 1) concentric reduction, 2) fragmentation, 3) non-mass like, and 4) architectural distortion. RESULTS Total of 34 lesions from 34 patients were included. Among them, 12 lesions (35.3%) were pathologically proven to have no residual tumor (Miller and Payne grade 5). The mean MR reduction rate tended to be higher in HER2-positive (62.7%) and triple negative subgroups (61.9%) than HR-positive subgroup (47.7%). The mean MR imaging-pathologic size discrepancy tended to be smaller in triple negative subgroup (0.5cm) than HER2-positive (1.2cm) and HR-positive subgroups (1.4cm). All results showed no statistical significance (P>0.05). Ki-67 expression showed no significant correlations in tumor response (r = 0.17, P = 0.4) and MR imaging-pathologic size discrepancy (r = 0.1, P = 0.6). The majority of morphologic change is concentric reduction (57.6%). MRI is tended to overestimate residual size of the lesion (62.5%) CONCLUSION HER2-positive and triple negative subgroups showed relatively better response. Tumors were most likely to response in the manner of concentric reduction. The mean MR imaging-pathologic size discrepancy tended to be smaller in triple negative subgroup. MRI is reliable method in predicting histopathological response to NAC, but is more likely to overestimate the residual size of the lesion. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-02-08.

Can a pre-operative MRI predict the pathologic response of breast cancer to neo-adjuvant chemotherapy?

Background: Neo-adjuvant chemotherapy is being increasingly used for breast cancer. MRI is used for assessing tumour response. Literature on correlation of pathologic response and MRI response is scanty.

Prediction of response of breast cancer to neoadjuvant chemotherapy by MR diffusion-weighted imaging:a study of correlation between apparent diffusion coefficient value and pathologic response

Objective To characterize the value of ADC and their changes (⊿ADC%) before and during the neoadjuvant chemotherapy,and their value in predicting the pathologic response of breast cancer to neoadjuvant chemotherapy. Methods Diffusion weighted imaging and dynamic contrast enhanced magnetic resonance examinations were performed in 35 women with breast cancer before treatment and after the second and the forth cycle of neoadjuvant chemotherapy.All patients were divided into MHR (major histological response) group and NMHR (non-major histological response) group according to the final pathologic response.One-way ANOVA and t test were used to compare the differences of cancer tissue and normal tissue.Rank sum test was used to compare the difference of ADC and ⊿ADC% between two groups.ROC analysis of ADC values and ⊿ADC% were used to identify which parameter could be used to predict the pathologic response to neoadjuvant chemotherapy.Results After the forth cycle,the ADC value and ⊿ADC% in MHR group [1.54×10~(-3) mm~2/s (1.01-1.88)×10~(-3) mm~2/s and 42.70% (6.31%-67.86%)]were significant higher than those in NMHR group [1.22×10~(-3) mm~2/s (0.83-1.83)×10~(-3) mm~2/s,14.88%(-28.87%-39.69%,P<0.05)].However,the ADC value and ⊿ADC% in the two groups were not different before treatment and after second cycle treatment:1.15×10~(-3) mm~2/s(0.85-1.62)×10~(-3) mm~2/s and 12.00%(-12.96%-30.65%)in MHR;1.15×10~(-3) mm~2/s(0.94-1.60)×10~(-3) mm~2/s and 10.74%(-20.80%-41.81%,P<0.05)in NMHR.Only the ⊿ADC_3% showed high efficacy in predicting the pathologic response(area under ROC curve was 0.88).Conclusion The rate of ADC change in late cycle could be used to predict the pathologic reaponse of breast cancer to neoadjuvant chemotherapy. Key words: Breast neoplasms; Drug therapy; combination; Diffusion magnetic resonance imaging

The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: a case control study

BackgroundPreoperative chemotherapy (PCT) has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR) of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment.Methods118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide), VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide) and EFC (epirubicin+5-fluorouracil+cyclophosphamide) were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR.ResultsThere was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p < 0.05). HER2 expression is significantly associated with increased PR in DEC regimen (p < 0.05), but not predictive for PR in EFC and VFC groups. No significant correlation was found between biomarkers PgR, Topo-II, P-gp, MRP or GST-pi and PR to any tested PCT regimen. After adjusted by a stratification variable of ER or HER2, DEC regimen was more effective in inducing PR in comparison with VFC and EFC regimens.ConclusionER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR, Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens investigated. Results obtained in this clinical study may be helpful for the selection of appropriate treatments for breast cancer patients.

Evaluation of response to neoadjuvant chemotherapy in primary breast cancer using PET.

Abstract Abstract #4019 Purpose&amp;#x2028; To estimate the usefulness of PET scan to assess the response of neoadjuvant chemotherapy, PET scan results were compared with conventional imaging modalities(US and MRI).&amp;#x2028; Patients and Methods&amp;#x2028; Fourty-one patients undergoing neoadjuvant chemotherapy between December 2004 and March 2008 were included. PET scan was performed before and after chemotherapy. Pathologic results were classified into two groups; pathological complete response(pCR) and non-pCR. Clinical responses were assessed with the results of imaging modalities such as post-chemotherapy size or pSUV(postTx), size difference between treatment(delta) and reduction rate(RR) of size or pSUV, and they are compared with postoperative pathologic results.&amp;#x2028; Results&amp;#x2028; 7 out of 41 patients (17.1%) had pCR. The results of US shows that postTx size (1.7±1.5cm) of pCR was not dfferent from those of non-pCR (3.6±3.0cm), and the delta (3.1±1.9cm) and RR (67.7±29.1%) of pCR were higher than those of non-pCR (1.3±1.3cm, 31.0±25.4%), respectively. As a result of MRI, postTx size, delta, RR of pCR was differ from those of non-pCR (1.0±1.7cm vs 2.8±1.7cm p&amp;lt;0.05; 4.5±1.0cm vs 2.3±1.8cm, p&amp;lt;0.05; 88.0±20.8% vs 44.6±24.7%, p&amp;lt;0.01). In PET scan, only postTx pSUV of pCR was differ from that of non-pCR (1.4±1.3 vs 5.3±8.3cm, p&amp;lt;0.05). As a result of receiver operating characteristic curve analyses for the prediction of pathological response of breast cancer, area under curve values (95% confidence interval) of US, MRI, PET for delta were 0.83(0.69∼0.98), 0.91(0.80∼1.01), 0.62(0.38∼0.86), and those of RR were 0.80(0.60∼0.99), 0.90(0.77∼1.02), 0.72(0.47∼0.96), respectively&amp;#x2028; Conclusions&amp;#x2028; We suggest that MRI is useful method to evaluate the response of neoadjuvant chemotherapy. Although PET scan shows less effective for evaluating the response of chemotherapy than MRI, PET scan with the ability to detect the distant metastatic lesions may be helpful to decide the proper management plans for advanced breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4019.

Predictive value of [18F]FDG PET for pathological response of breast cancer to neo-adjuvant chemotherapy

The aim of this prospective study was to evaluate the predictive value of [18F]fluorodeoxyglucose positron emission tomography (FDG PET) for the pathological response of breast cancer after completion of neo-adjuvant chemotherapy. Fifty patients with newly diagnosed, non-inflammatory, large or locally advanced breast cancer undergoing neo-adjuvant chemotherapy were eligible for this study. Clinical assessment was accomplished by comparing initial tumor size with preoperative tumor size. Pathological responses were classified into three groups: pathological non-response (pNR), pathological partial response (pPR) and pathological complete response (pCR). To determine the effect of reduction rate (RR) of peak standardized uptake values for tumor responses, logistic regression analyses were performed. To identify an optimal threshold value of RR for the prediction of pathological response, receiver operating characteristic analysis was performed. Eight per cent (four of 50) of the patients had pCR and 46% had pPR. Ten per cent of patients had clinical CR and 52% had clinical PR. In clinical response, the RRs (+/- SD) of CR (-83.4 +/- 12), PR (-81.8 +/- 22.7) and NR (-79.7 +/- 31.9) showed no statistical differences (P > 0.05). However, for pathological responses, the RR of CR (-96.5 +/- 3.4) had a lower value than those of PR (-87.9 +/- 15.1) and NR (-56.2 +/- 29.6) (P = 0.0006; CR versus PR, P < 0.05; CR versus NR, P < 0.05; PR versus NR, P < 0.01). When -88% of RR was used as threshold value for differentiation between pCR and pPR, the area under the curve (AUC) was 0.788 [standard error (SE) 0.106; 95% confidence interval (CI) 0.589-0.920]. The sensitivity and specificity were 100% and 56.5%, respectively. When -79% of RR was used as threshold value for differentiation between pathological responders and non-responders, the AUC was 0.838 (SE 0.059; 95% CI 0.707-0.927). The sensitivity and specificity were 85.2% and 82.6%, respectively. Despite some limitations, this study suggests a possible predictive value of FDG PET for the assessment of the pathological response of primary breast cancer after neo-adjuvant chemotherapy. However, these findings deserve further investigation on a larger number of patients, and more frequent and earlier PET scans in each patient need to be performed to allow a better validation of the differentiation between the responder and non-responder groups.

Glutathion s transferase π indicates chemotherapy resistance in breast cancer

Background Breast cancer is the most common malignant disease of women. Pathologic response of breast cancer to chemotherapy has a great prognostic importance. Glutathion S Transferases (GSTs) might detoxify chemotherapeutic drugs within the cancer cells, thus contributing to chemotherapy resistance. The pi isoenzyme of GSTs seems to be of great relevance. Thus, we hypothesized that GSTpi expression in cancer biopsy can be a prognostic indicator for resistance to chemotherapy. To test this hypothesis, we evaluated before and after chemotherapy, tumor size, apoptosis of tumor cells with TUNEL assay, and proliferation of tumor cells by determining PCNA expression in biopsy samples, or in the surgically removed tumor tissue of GSTpi (−), and GSTpi (+) cases. Materials and methods GSTpi immunoreactivity was determined in 42 female patients with breast cancer. Patients were divided into two groups according to the expression of GSTpi in the pre-treatment biopsy specimen: (+) ( n = 22) and ( n = 20) samples were analyzed. Surgery was performed 2 weeks after a single intravenous injection of the chemotherapeutic drugs [5-fluorouracil, adriamycin, mitomycin (FAM protocol)]. Results Pre-chemotherapy values of tumor size, apoptosis, or proliferation did not differ between GSTpi (−) and (+) samples. Chemotherapy significantly inhibited tumor growth, and cell proliferation, and induced apoptosis in GSTpi (−) cases. However, these effects were significantly reduced in GSTpi (+) patients. Conclusion These results suggest, that the presence of GSTpi in breast cancer tissue is a bad prognostic indicator, and these tumors are largely resistant to chemotherapy. Thus, GSTpi might be important in inactivating one or more of the chemotherapeutic agents used in this treatment.

Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy.

To determine whether [(18)F]-fluorodeoxy-D-glucose ([(18)F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [(18)F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P =.037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P =.013), complete macroscopic (P =.003), or complete microscopic (P =.001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P =.076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P =.037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P =.038; K, P =.012). [(18)F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.