Predicting Treatment Response of Breast Cancer to Neoadjuvant Chemotherapy Using Ultrasound-Guided Diffuse Optical Tomography

PURPOSE: To prospectively investigate ultrasound-guided diffuse optical tomography (US-guided DOT) in predicting breast cancer response to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Eighty-eight breast cancer patients, with a total of 93 lesions, were included in our study. Pre– and post–last chemotherapy, size and total hemoglobin concentration (THC) of each lesion were measured by conventional US and US-guided DOT 1 day before biopsy (time point t0, THC THC0, SIZE S0) and 1 to 2 days before surgery (time point tL, THCL, SL). The relative changes in THC and SIZE of lesions after the first and last NAC cycles were considered as the variables ΔTHC and ΔSIZE. Receiver operating characteristic curve was performed to calculate ΔTHC and ΔSIZE cutoff values to evaluate pathologic response of 93 breast cancers to NAC, which were then prospectively used to predicate response of 61 breast cancers to NAC. RESULTS: The cutoff values of ΔTHC and ΔSIZE for evaluation of breast cancers NAC treatment response were 23.9% and 42.6%. At ΔTHC 23.9%, the predicted treatment response in 61 breast lesions for the time points t1 to t3 was calculated by area under the curve (AUC), which were AUC₁ 0.534 (P = .6668), AUC₂ 0.604 (P = .1893), and AUC₃ 0.674(P =. 0.027), respectively; for ΔSIZE 42.6%, at time points t1 to t3, AUC₁ 0.505 (P = .9121), AUC₂ 0.645 (P = .0115), and AUC₃ 0.719 (P = .0018). CONCLUSION: US-guided DOT ΔTHC 23.9% and US ΔSIZE 42.6% can be used for the response evaluation and earlier prediction of the pathological response after three rounds of chemotherapy.     

Analyzing Spatial Heterogeneity in DCE- and DW-MRI Parametric Maps to Optimize Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer

The purpose of this study is to investigate the ability of multivariate analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted MRI (DW-MRI) parametric maps, obtained early in the course of therapy, to predict which patients will achieve pathologic complete response (pCR) at the time of surgery. Thirty-three patients underwent DCE-MRI (to estimate K^trans, v_e, k_ep, and v_p) and DW-MRI [to estimate the apparent diffusion coefficient (ADC)] at baseline (t₁) and after the first cycle of neoadjuvant chemotherapy (t₂). Four analyses were performed and evaluated using receiver-operating characteristic (ROC) analysis to test their ability to predict pCR. First, a region of interest (ROI) level analysis input the mean K^trans, v_e, k_ep, v_p, and ADC into the logistic model. Second, a voxel-based analysis was performed in which a longitudinal registration algorithm aligned serial parameters to a common space for each patient. The voxels with an increase in k_ep, K^trans, and v_p or a decrease in ADC or v_e were then detected and input into the regression model. In the third analysis, both the ROI and voxel level data were included in the regression model. In the fourth analysis, the ROI and voxel level data were combined with selected clinical data in the regression model. The overfitting-corrected area under the ROC curve (AUC) with 95% confidence intervals (CIs) was then calculated to evaluate the performance of the four analyses. The combination of k_ep, ADC ROI, and voxel level data achieved the best AUC (95% CI) of 0.87 (0.77–0.98).     

Parameterizing the Logistic Model of Tumor Growth by DW-MRI and DCE-MRI Data to Predict Treatment Response and Changes in Breast Cancer Cellularity during Neoadjuvant Chemotherapy

Diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging (MRI) data of 28 patients were obtained pretreatment, after one cycle, and after completion of all cycles of neoadjuvant chemotherapy (NAC). For each patient at each time point, the tumor cell number was estimated using the apparent diffusion coefficient and the extravascular extracellular (v_e) and plasma volume (v_p) fractions. The proliferation/death rate was obtained using the number of tumor cells from the first two time points in conjunction with the logistic model of tumor growth, which was then used to predict tumor cellularity at the conclusion of NAC. The Pearson correlation coefficient between the predicted and the experimental number of tumor cells measured at the end of NAC was 0.81 (P = .0043). The proliferation rate estimated after the first cycle of therapy was able to separate patients who went on to achieve pathologic complete response from those who did not (P = .021) with a sensitivity and specificity of 82.4% and 72.7%, respectively. These data provide preliminary results indicating that incorporating readily available quantitative MRI data into a simple model of tumor growth can lead to potentially clinically relevant information for predicting an individual patient's response to NAC.     

Evaluation of Neoadjuvant Chemotherapy Response in Women with Locally Advanced Breast Cancer Using Ultrasound Elastography

PURPOSE: Ultrasound elastography is a new imaging technique that can be used to assess tissue stiffness. The aim of this study was to investigate the potential of ultrasound elastography for monitoring treatment response of locally advanced breast cancer patients undergoing neoadjuvant therapy. METHODS: Fifteen women receiving neoadjuvant chemotherapy had the affected breast scanned before, 1, 4, and 8 weeks following therapy initiation, and then before surgery. Changes in elastographic parameters related to tissue biomechanical properties were then determined and compared to clinical and pathologic tumor response after mastectomy. RESULTS: Patients who responded to therapy demonstrated a significant decrease (P < .05) in strain ratios and strain differences 4 weeks after treatment initiation compared to non-responding patients. Mean strain ratio and mean strain difference for responders was 81 ± 3% and 1 ± 17% for static regions of interest (ROIs) and 81 ± 3% and 6 ± 18% for dynamic ROIs, respectively. In contrast, these parameters were 102±2%, 110±17%, 101±4%, and 109±30% for non-responding patients, respectively. Strain ratio using static ROIs was found to be the best predictor of treatment response, with 100% sensitivity and 100% specificity obtained 4 weeks after starting treatment. CONCLUSIONS: These results suggest that ultrasound elastography can be potentially used as an early predictor of tumor therapy response in breast cancer patients.     

Exploratory Cost-Effectiveness Analysis of Response-Guided Neoadjuvant Chemotherapy for Hormone Positive Breast Cancer Patients

PurposeGuiding response to neoadjuvant chemotherapy (guided-NACT) allows for an adaptative treatment approach likely to improve breast cancer survival. In this study, our primary aim is to explore the expected cost-effectiveness of guided-NACT using as a case study the first randomized controlled trial that demonstrated effectiveness (GeparTrio trial).ResultsOur exploratory CEA predicted that guided-NACT as proposed by the GeparTrio, costs additional €110, but results in 0.014 QALYs gained per patient. This scenario of guided-NACT was considered cost-effective at any willingness to pay per additional QALY. At the prevailing Dutch willingness to pay threshold (€80.000/QALY) cost-effectiveness was expected with 78% certainty.ConclusionThis exploratory CEA indicated that guided-NACT (as proposed by the GeparTrio trial) is likely cost-effective in treating HR+ EBC women. While prospective validation of the GeparTrio findings is advisable from a clinical perspective, early CEAs can be used to prioritize further research from a broader health economic perspective, by identifying which parameters contribute most to current decision uncertainty. Furthermore, their use can be extended to explore the expected cost-effectiveness of alternative guided-NACT scenarios that combine the use of promising imaging techniques together with personalized treatments.     

Background Parenchymal Enhancement of the Contralateral Normal Breast: Association with Tumor Response in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

PURPOSE: This study investigated the association between background parenchymal enhancement (BPE) and pathologic response to neoadjuvant chemotherapy (NAC). METHODS: A total of 46 patients diagnosed with invasive breast cancer were analyzed. Each patient had three magnetic resonance imaging (MRI) studies, one pre-treatment and two follow-up (F/U) MRI studies. BPE was measured as the averaged enhancement of the whole fibroglandular tissues. The pre-treatment BPE and the changes in the F/U MRI were compared between patients achieving pathologic complete response (pCR) versus those not. Subgroup analyses based on age, estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) status of their cancers were also performed. RESULTS: The pre-treatment BPE was higher in the pCR group than that in the non-pCR group. Compared to baseline, BPE at F/U-1 was significantly decreased in the pCR group but not in the non-pCR group. In subgroup analysis based on age, these results were seen only in the younger group (< 55 years old), not in the older group (≥ 55 years old). Older patients had a significantly lower pre-treatment BPE than younger patients. In analysis based on molecular biomarkers, a significantly decreased BPE at F/U-1 was only found in the ER-negative pCR group but not in the non-pCR, nor in the ER-positive groups. CONCLUSIONS: A higher pre-treatment BPE showing a significant decrease early after starting NAC was related to pCR in pre/peri-menopausal patients.     

A Systematic Evaluation of Multi-Gene Predictors for the Pathological Response of Breast Cancer Patients to Chemotherapy

Previous studies have reported conflicting assessments of the ability of cell line-derived multi-gene predictors (MGPs) to forecast patient clinical outcomes in cancer patients, thereby warranting an investigation into their suitability for this task. Here, 42 breast cancer cell lines were evaluated by chemoresponse tests after treatment with either TFAC or FEC, two widely used standard combination chemotherapies for breast cancer. We used two different training cell line sets and two independent prediction methods, superPC and COXEN, to develop cell line-based MGPs, which were then validated in five patient cohorts treated with these chemotherapies. This evaluation yielded high prediction performances by these MGPs, regardless of the training set, chemotherapy, or prediction method. The MGPs were also able to predict patient clinical outcomes for the subgroup of estrogen receptor (ER)-negative patients, which has proven difficult in the past. These results demonstrated a potential of using an in vitro-based chemoresponse data as a model system in creating MGPs for stratifying patients’ therapeutic responses. Clinical utility and applications of these MGPs will need to be carefully examined with relevant clinical outcome measurements and constraints in practical use.     

Effect of Imaging Parameter Thresholds on MRI Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes

The purpose of this study is to evaluate the predictive performance of magnetic resonance imaging (MRI) markers in breast cancer patients by subtype. Sixty-four patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy were enrolled in this study. Each patient received a dynamic contrast-enhanced (DCE-MRI) at baseline, after 1 cycle of chemotherapy and before surgery. Functional tumor volume (FTV), the imaging marker measured by DCE-MRI, was computed at various thresholds of percent enhancement (PE_t) and signal-enhancement ratio (SER_t). Final FTV before surgery and percent changes of FTVs at the early and final treatment time points were used to predict patients’ recurrence-free survival. The full cohort and each subtype defined by the status of hormone receptor and human epidermal growth factor receptor 2 (HR+/HER2-, HER2+, triple negative) were analyzed. Predictions were evaluated using the Cox proportional hazard model when PE_t changed from 30% to 200% in steps of 10% and SER_t changed from 0 to 2 in steps of 0.2. Predictions with high hazard ratios and low p-values were considered as strong. Different profiles of FTV as predictors for recurrence-free survival were observed in each breast cancer subtype and strong associations with survival were observed at different PE_t/SER_t combinations that resulted in different FTVs. Findings from this retrospective study suggest that the predictive performance of imaging markers based on FTV may be improved with enhancement thresholds being optimized separately for clinically-relevant subtypes defined by HR and HER2 receptor expression.     

Association of Pretreatment Anemia with Pathological Response and Survival of Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Population-Based Study

Background

Anemia related to adjuvant chemotherapy might predict compromised survival in patients with breast cancer. The present population-based study was to investigate the correlation of pretreatment anemia with pathological response and long-term prognosis of breast cancer patients receiving neoadjuvant chemotherapy (NCT).

Methods

From 1999 to 2011, a total of 655 patients with operable or locally advanced breast cancer who underwent NCT before definitive surgery were reviewed. The patients were subdivided into anemic (baseline hemoglobin (Hb)<12.0g/dL) and non-anemic (Hb≥12.0g/dL) groups. Comparison was made between anemic and non-anemic groups concerning the rate of pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS). Logistic and Cox regression models were utilized to determine the predictive value of pretreatment anemia in outcomes of patients undergoing NCT.

Results

166 women (25.3%) were anemic before treatment. Patients in the anemic group were less likely to achieve pCR in NCT than their non-anemic counterparts (odds ratio (OR) 0.428, 95% confidence interval (CI) 0.198–0.927, p = 0.031). Patients with baseline anemia displayed inferior 10-year RFS (59.1% vs 66.0%, p = 0.022 by log-rank), OS (75.3% vs 90.9%, p<0.001) and CSS (82.4% vs 94.4%, p<0.001) compared with those without. After adjustment for confounders, pretreatment anemia was demonstrated to correlate with elevated risk of relapse (hazard ratio (HR) 1.453, 95% CI 1.077–1.962, p = 0.015), cancer-specific mortality (HR 2.961, 95% CI 1.679–5.222, p<0.001) and all-cause mortality (HR 2.873, 95% CI 1.757–4.699, p<0.001).

Conclusions

Pretreatment anemia was associated with worse pathological response to NCT as well as survival status in breast cancer. Further studies are warranted to identify optimal interventions and improve the prognosis of this subgroup.     

香菇多糖联合TA方案化疗治疗晚期乳腺癌的临床观察

目的:观察香菇多糖联合TA方案(紫杉醇、阿霉素)治疗晚期乳腺癌患者的近期疗效及毒副反应。方法:将确诊为Ⅳ期的52例乳腺癌患者随机分为对照组及治疗组,两组均采用TA方案化疗,治疗组加用香菇多糖,观察两组近期疗效及毒副反应,计算和比较两组治疗前后的CD4+/CD8+值。结果:治疗组及对照组的治疗总有效率分别为67.86%、62.50%,其差异无统计学意义(P>0.05);两组的生活质量(Karnofsky评分)改善率分别为71.43%和41.67%,治疗组显著高于对照组,差异有统计学意义(P<0.05)。两组治疗后CD4+及CD8+细胞绝对计数均较治疗前下降,差异有统计学意义(P<0.05)。治疗组CD4+/CD8+值上升,但与治疗前比较差异无统计学意义(P>0.05),对照组CD4+/CD8+值较治疗前下降,差异无统计学意义(P>0.05);两组治疗后CD4+/CD8+值差异有统计学意义(P<0.05)。治疗组毒副反应较对照组明显减轻(P<0.05)。结论:香菇多糖联合TA化疗方案能有效改善晚期乳腺癌患者的生存质量、调节免疫力并减轻毒副反应。     

Magnetic Resonance Metabolic Profiling of Breast Cancer Tissue Obtained with Core Needle Biopsy for Predicting Pathologic Response to Neoadjuvant Chemotherapy

The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB) samples using high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.     

CD133 Is a Useful Surrogate Marker for Predicting Chemosensitivity to Neoadjuvant Chemotherapy in Breast Cancer

Background

Neoadjuvant chemotherapy (NAC) is a standard care regimen for patients with breast cancer. However, the pathologic complete response (pCR) rate remains at 30%. We hypothesized that a cancer stem cell marker may identify NAC-resistant patients, and evaluated CD133 and ALDH1 as a potential surrogate marker for breast cancer. The aim of this study was to find a surrogate maker to predict chemosensitivity of NAC for breast cancer.

Methodology/Findings

A total of 102 patients with breast cancer were treated with NAC consisting of epirubicin followed by paclitaxel. Core needle biopsy (CNB) specimens and resected tumors were obtained from all patients before and after NAC, respectively. Chemosensitivity and prognostic potential of CD133 or ALDH1 expression was evaluated by immunohistochemistry. Clinical CR (cCR) and pCR rates were 18% (18/102) and 29% (30/102), respectively. Forty-seven (46%) patients had CD133-positive tumors before NAC, and CD133 expression was significantly associated with a low pCR rate (p = 0.035) and clinical non-responders. Multivariate analysis revealed that CD133 expression was significantly (p = 0.03) related to pCR. Recurrence was more frequent in patients with CD133-positive tumors (21/47, 45%) than that in patients with CD133-negative tumors (7/55, 13%). The number of patients with CD133-positive tumors (62%) after NAC was higher than that (46%) before NAC. Furthermore, most patients with CD133-positive tumors before NAC maintained the same status after NAC.

Conclusion/Significance

CD133 before NAC might be a useful marker for predicting the effectiveness of NAC and recurrence of breast cancer after NAC.     

Association Between Background Parenchymal Enhancement and Pathologic Complete Remission Throughout the Neoadjuvant Chemotherapy in Breast Cancer Patients

PURPOSE: To retrospectively investigate the quantitative background parenchymal enhancement (BPE) of the contralateral normal breast in patients with unilateral invasive breast cancer throughout multiple monitoring points of neoadjuvant chemotherapy (NAC) and to further determine whether BPE is associated with tumor response, especially at the early stage of NAC. MATERIALS AND METHODS: A total of 90 patients with unilateral breast cancer who then received six or eight cycles of NAC before surgery were analyzed retrospectively. BPE was measured in dynamic contrast-enhanced MRI at baseline and after 2nd, 4th, and 6th NAC, respectively. Correlation between BPE and tumor size was analyzed, and the association between pathologic complete remission (pCR) and BPE was also analyzed. RESULTS: The BPE of contralateral normal breast showed a constant reduction throughout NAC therapy regardless of the menopausal status (P < .001 in all). Both the BPEs and the changes of BPE in each of the three monitoring points were significantly correlated with those in tumor size (P < .05 in all), and the reduction of BPE after 2nd NAC had the largest diagnostic value for pCR (AUC = 0.726, P < .001), particularly in hormonal receptor (HR)-negative patients (OR = 0.243, 95%CI = 0.083 to 0.706, P = .009). CONCLUSION: The BPE of contralateral normal breast had a constant decreased tendency similar to the change of tumor size in NAC. Reduction of BPE at the early stage of NAC was positively associated with pCR, especially in HR-negative status.     

Obesity or Overweight Is Associated with Worse Pathological Response to Neoadjuvant Chemotherapy among Chinese Women with Breast Cancer

Background

To evaluate the relationship between body mass index (BMI) and response to neoadjuvant chemotherapy (NCT) for breast cancer among Chinese women.

Patients and Methods

A total of 307 eligible patients were assigned to receive four cycles of paclitaxel and carboplatin before standard surgery for breast cancer from 2007 to 2011 at Shanghai Cancer Hospital. The patients were categorized as obese, overweight, normal weight, or underweight based on BMI according to World Health Organization (WHO) criteria. Pathological complete response (pCR) was defined as no invasive cancer in the breast or axillary tissue. A logistic regression and the Chi-squared test were used for detecting the predictors of pCR and determining the relationship between BMI category and pCR rate in the subgroup analysis with respect to other variables.

Results

Categorical BMI, estrogen receptor (ER), and progesterone receptor (PR) status were independent predictors of pCR according to the multivariate analysis. Patients with BMI≥25 were less likely to achieve a pCR to NCT compared with patients with BMI<25 (Odds ratio: 0.454, p = 0.033, multivariate analysis). In the subgroup analysis, the predictive value of BMI for pCR to NCT was significantly shown in post-menopausal patients (p = 0.004) and hormonal receptor status-negative patients (p = 0.038). The incidence of treatment-induced toxicity was similar among the different BMI categories.

Conclusion

Higher BMI was associated with worse pCR to NCT. Further approaches to investigating the mechanism of this influence of BMI on treatment response and a more appropriate schedule for calculating NCT dose for high-BMI-patients should be considered.     

新辅助化疗在局部晚期宫颈癌治疗中的疗效观察

目的：探讨新辅助化疗联合手术治疗较传统手术治疗Ib2、IIa2局部晚期宫颈癌的临床疗效。方法：选取2008年6月～2011年12月在黑龙江省哈尔滨医科大学附属第三医院初治宫颈癌患者120例,临床分期为Ib2期、IIa2期,术前均经病理证实为宫颈鳞癌,将其分为两组：研究组（新辅助化疗联合手术治疗组）;对照组（单纯手术治疗组）。研究组给予1～2个疗程的新辅助化疗后评估其化疗疗效,有效者化疗结束后行广泛性子宫切除＋盆腔淋巴结清扫术;对照组直接行手术治疗。结果：新辅助化疗能够使肿瘤体积较化疗前缩小或消失,临床有效率高达81.43%,从而降低了宫颈癌的临床分期,提高手术的切除率,扩大手术适应征,降低术后病理高危因素,同时手术治疗能保留卵巢功能,提高年轻宫颈癌患者生活质量。结论：术前新辅助化疗可以提高手术治疗局部晚期宫颈癌的临床疗效。     

A Pilot Study of Diffusion-Weighted MRI in Patients Undergoing Neoadjuvant Chemoradiation for Pancreatic Cancer

PURPOSE: In the current study we examined the ability of diffusion MRI (dMRI) to predict pathologic response in pancreatic cancer patients receiving neoadjuvant chemoradiation. METHODS: We performed a prospective pilot study of dMRI in patients with resectable pancreatic cancer. Patients underwent dMRI prior to neoadjuvant chemoradiation. Surgical specimens were graded according to the percent tumor cell destruction. Apparent diffusion coefficient (ADC) maps were used to generate whole-tumor derived ADC histogram distributions and mean ADC values. The primary objective of the study was to correlate ADC parameters with pathologic and CT response. RESULTS: Ten of the 12 patients enrolled on the study completed chemoradiation and had surgery. Three were found to be unresectable at the time of surgery and no specimen was obtained. Out of the 7 patients who underwent pancreaticoduodenectomy, 3 had a grade III histopathologic response (> 90% tumor cell destruction), 2 had a grade IIB response (51% to 90% tumor cell destruction), 1 had a grade IIA response (11% to 50% tumor cell destruction), and 1 had a grade I response (> 90% viable tumor). Median survival for patients with a grade III response, grade I-II response, and unresectable disease were 25.6, 18.7, and 6.1 months, respectively. There was a significant correlation between pre-treatment mean tumor ADC values and the amount of tumor cell destruction after chemoradiation with a Pearson correlation coefficient of 0.94 (P = .001). Mean pre-treatment ADC was 161 × 10^− 5 mm²/s (n = 3) in responding patients (> 90% tumor cell destruction) compared to 125 × 10^− 5 mm²/s (n = 4) in non-responding patients (> 10% viable tumor). CT imaging showed no significant change in tumor size in responders or non-responders. CONCLUSIONS: dMRI may be useful to predict response to chemoradiation in pancreatic cancer. In our study, tumors with a low ADC mean value at baseline responded poorly to standard chemoradiation and would be candidates for intensified therapy.     

Clinical Efficacy of Including Capecitabine in Neoadjuvant Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Capecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients.

Methods

The electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1.

Results

Five studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87–1.40, p = 0.43), pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83–1.18, p = 0.90), overall response rate (ORR; RR = 1.00, 95% CI 0.94–1.07, p = 0.93), or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93–1.04, p = 0.49).

Conclusions

Neoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.