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1.

Purpose

Breast cancer (BC) patients who achieve a favorable residual cancer burden (RCB) after neoadjuvant chemotherapy (NACT) have an improved recurrence-free survival. Those who have an unfavorable RCB will have gone through months of ineffective chemotherapy. No ideal method exists to predict a favorable RCB early during NACT. Diffuse optical tomography (DOT) is a novel imaging modality that uses near-infrared light to assess hemoglobin concentrations within breast tumors. We hypothesized that the 2-week percent change in DOT-measured hemoglobin concentrations would associate with RCB.

Methods

We conducted an observational study of 40 women with stage II–IIIC BC who received standard NACT. DOT imaging was performed at baseline and 2 weeks after treatment initiation. We evaluated the associations between the RCB index (continuous measure), class (categorical 0, I, II, III), and response (RCB class 0/I = favorable, RCB class II/III = unfavorable) with changes in DOT-measured hemoglobin concentrations.

Results

The RCB index correlated significantly with the 2-week percent change in oxyhemoglobin [HbO2] (r = 0.5, p = 0.003), deoxyhemoglobin [Hb] (r = 0.37, p = 0.03), and total hemoglobin concentrations [HbT] (r = 0.5, p = 0.003). The RCB class and response significantly associated with the 2-week percent change in [HbO2] (p ≤ 0.01) and [HbT] (p ≤ 0.02). [HbT] 2-week percent change had sensitivity, specificity, positive, and negative predictive values for a favorable RCB response of 86.7, 68.4, 68.4, and 86.7%, respectively.

Conclusion

The 2-week percent change in DOT-measured hemoglobin concentrations was associated with the RCB index, class, and response. DOT may help guide NACT for women with BC.
  相似文献   

2.
Patients who have no residual invasive cancer following neoadjuvant chemotherapy for breast carcinoma have a better overall survival than those with residual disease. Many classification systems assessing pathological response to neoadjuvant chemotherapy include residual ductal carcinoma in situ (DCIS) only in the definition of pathological complete response. The purpose of this study was to investigate whether patients with residual DCIS only have the same prognosis as those with no residual invasive or in situ disease. A retrospective analysis of a prospectively maintained database identified 435 patients, who received neoadjuvant chemotherapy for operable breast cancer between February 1985 and February 2003. Of these, 30 (7%; 95% CI 5-9%) had no residual invasive disease or DCIS and 20 (5%; CI 3-7%) had residual DCIS only. With a median follow-up of 61 months, there was no statistical difference in disease-free survival, 80% (95% CI 60-90%) in those with no residual invasive or in situ disease and 61% (95% CI 35-80%) in those with DCIS only (P=0.4). No significant difference in 5-year overall survival was observed, 93% (95% CI 75-98%) in those with no residual invasive or in situ disease and 82% (95% CI 52-94%) in those with DCIS only (P=0.3). Due to the small number of patients and limited number of events in each group, it is not possible to draw definitive conclusions from this study. Further analyses of other databases are required to confirm our finding of no difference in disease-free and overall survival between patients with residual DCIS and those with no invasive or in situ disease following neoadjuvant chemotherapy for breast cancer.  相似文献   

3.

Introduction

Neoadjuvant chemotherapy has become the standard of care for the diverse population of women diagnosed with locally advanced breast cancer. Serum biomarker levels are increasingly being investigated for their ability to predict therapy response and aid in the development of individualized treatment regimens. Multianalyte profiles may offer greater predictive power for neoadjuvant treatment response than the individual biomarkers currently in use.

Methods

Serum samples were collected from 44 patients enrolled in a phase I–II, open-label study of liposomal doxorubicin and paclitaxel in combination with whole breast hyperthermia for the neoadjuvant treatment of locally advanced breast cancer (stage IIB or stage III). Samples were collected prior to each of four rounds of treatment and prior to definitive surgery. Samples were assayed by Luminex assay for 55 serum biomarkers, including cancer antigens, growth/angiogenic factors, apoptosis-related molecules, metastasis-related molecules, adhesion molecules, adipokines, cytokines, chemokines, hormones, and other proteins.

Results

Biomarker levels were compared retrospectively with clinical and pathologic treatment responses. Univariate analysis of the data identified several groups of biomarkers that differed significantly among treatment outcome groups early in the course of neoadjuvant chemotherapy. Multivariate statistical analysis revealed multibiomarker panels that could differentiate between treatment response groups with high sensitivity and specificity.

Conclusion

We demonstrate here that serum biomarker profiles may offer predictive power concerning treatment response and outcome in the neoadjuvant setting. The continued development of these findings will be of considerable clinical utility in the design of treatment regimens for individual breast cancer patients.

Trial registration

#NCT00346229.  相似文献   

4.
杨云  黄元夕 《现代肿瘤医学》2020,(20):3546-3549
目的:探讨乳腺癌新辅助化疗疗效及其与生物标志物检测水平变化的相关性。方法:通过对乳腺癌新辅助化疗患者疗效的评估以及空心针穿刺标本和手术标本的免疫组织化学染色比较,分析新辅助化疗疗效与生物标志物改变情况,以及二者的关系、影响因素。结果:在76例新辅助化疗的患者中,达到病理完全缓解(pCR)的患者有14例(18.4%),临床有效率达75.00%。对新辅助化疗疗效的相关因素分析,发现雌激素受体(ER)、孕激素受体(PR)状态与疗效相关(P均<0.05)。进一步对14例达到pCR患者的生物标志物进行分析,ER阴性的患者有10例(71.4%)、PR阴性的患者有9例(64.3%)。对比生物标志物,发现新辅助化疗患者Ki-67改变差异有统计学意义(P<0.05),而ER、PR、p53改变情况差异无统计学意义(P均>0.05)。结论:新辅助化疗具有较高的临床缓解率,新辅助化疗疗效与ER、PR状态有关,ER、PR表达较弱者相对较容易达到pCR,并且新辅助化疗后患者生物标志物只有Ki-67改变。  相似文献   

5.
6.
7.

BACKGROUND:

With advances in oncologic treatment, cosmesis after mastectomy has assumed a pivotal role in patient and provider decision making. Multiple studies have confirmed the safety of both chemotherapy before breast surgery and immediate reconstruction. Little has been written about the effect of neoadjuvant chemotherapy on decisions about reconstruction.

METHODS:

The authors identified 665 patients with stage I through III breast cancer who received chemotherapy and underwent mastectomy at Dana‐Farber/Brigham & Women's Cancer Center from 1997 to 2007. By using multivariate logistic regression, reconstruction rates were compared between patients who received neoadjuvant chemotherapy (n = 180) and patients who underwent mastectomy before chemotherapy (n = 485). The rate of postoperative complications after mastectomy was determined for patients who received neoadjuvant chemotherapy compared with those who did not.

RESULTS:

Reconstruction was performed immediately in 44% of patients who did not receive neoadjuvant chemotherapy but in only 23% of those who did. Twenty‐one percent of neoadjuvant chemotherapy recipients and 14% of adjuvant‐only chemotherapy recipients underwent delayed reconstruction. After controlling for age, receipt of radiotherapy, and disease stage, neoadjuvant recipients were less likely to undergo immediate reconstruction (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.37, 0.87) but were no more likely to undergo delayed reconstruction (OR, 1.29; 95% CI, 0.75, 2.20). Surgical complications occurred in 30% of neoadjuvant chemotherapy recipients and in 31% of adjuvant chemotherapy recipients.

CONCLUSIONS:

The current results suggest that patients who receive neoadjuvant chemotherapy are less likely to undergo immediate reconstruction and are no more likely to undergo delayed reconstruction than patients who undergo surgery before they receive chemotherapy. Cancer 2011. © 2011 American Cancer Society.  相似文献   

8.
《Annals of oncology》2012,23(12):3051-3057
BackgroundThe aim of this study was to investigate the clinicopathological characteristics of GATA binding protein 3 (GATA3)-positive breast cancers as well as the association of GATA3 expression with response to chemotherapy.Patients and methodsTumor specimens obtained before neoadjuvant chemotherapy [paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide)] from breast cancer patients (n = 130) were subjected to immunohistochemical and mutational analysis of GATA3 and DNA microarray gene expression analysis for intrinsic subtyping.ResultsSeventy-four tumors (57%) were immunohistochemically positive for GATA3. GATA3-positive tumors were significantly more likely to be lobular cancer, estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, Ki67-negative, and luminal A tumors. Somatic mutations were found in only three tumors. Pathological complete response (pCR) was observed in 8 (11%) GATA3-positive tumors and in 22 (39%) GATA3-negative tumors. Multivariate analysis showed that tumor size, human epidermal growth factor receptor 2 (HER2), and GATA3 were independent predictors of pCR.ConclusionsGATA3-positive breast cancers showed luminal differentiation characterized by high ER expression and were mostly classified as luminal-type tumors following intrinsic subtyping. Interestingly, GATA3 was an independent predictor of response to chemotherapy, suggesting that GATA3 might be clinically useful as a predictor of a poor response to chemotherapy.  相似文献   

9.
 目的 探讨三阴性乳腺癌(TNBC)的临床病理特点及远期生存率。并分析其新辅助化疗的疗效与生存率的相关性。方法 研究对象为535例乳腺癌患者,其中TNBC患者75例,非TNBC患者460例,对其临床和病理资料以及 5年的无病生存(DFS)率及总生存(OS)率进行回顾性分析,并与同期的非TNBC患者进行对比。535例中88例患者接受术前新辅助化疗,TNBC患者26例,非TNBC患者62例,分析其化疗疗效与远期生存的相关性。结果 TNBC患者与非TNBC患者相比,中位年龄轻(35岁比44岁),绝经前患者居多(88.0 % 比67.2 %,P=0.009);浸润性导管癌多见(92. 0 % 比80.4 %,P=0.020),组织学分级Ⅱ级者居多(56.0 %比17.2 %,P=0.000);淋巴结转移阳性者较少(33.3 %比53.9 %,P=0.001);TNBC组5年DFS(66.67 %)、OS(80.0 %)明显低于非TNBC组(74.78 %、90.0 %)。接受新辅助化疗的TNBC患者与非TNBC患者相比,化疗的总有效(OR)率(88.46 %比82.26 %)、临床完全缓解(cCR)率(65.38 %比37.10 %)、部分缓解(PR)率(23.08 %比45.16 %)差异均有统计学意义(P<0.05)。新辅助化疗的TNBC患者与非TNBC患者相比,5年的OS率(73.08 %比80.65 %)差异具有统计学意义(P=0.049);5年的DFS率(65.38 %比72.58 %)差异具有统计学意义(P=0.253)。分层分析发现:获得cCR的TNBC与非TNBC患者的5年DFS及OS差异无统计学意义(P>0.05)。未获得cCR TNBC患者的5年DFS及OS均显著低于非TNBC患者(P<0.05),临床OR对两组的5年DFS及OS无影响(P>0.05)。结论 TNBC多见于年轻的绝经前妇女,主要病理类型为浸润性导管癌,核分级高,淋巴结转移少见,但相对非TNBC患者有较低的DFS率和OS率,TNBC患者对新辅助化疗更敏感,更易获得cCR,获得cCR的TNBC患者预后好,未获得cCR的TNBC患者远期生存率明显低于非TNBC患者  相似文献   

10.
BACKGROUND: This study investigated the role of magnetic resonance imaging (MRI) in evaluation of pathologically complete response and residual tumors in patients who were receiving neoadjuvant chemotherapy (NAC) for both positive and negative HER-2 breast cancer. METHODS: Fifty-one individuals, comprised of 25 HER-2 positive and 26 HER-2 negative patients, were included in the study. Serial MRI studies were acquired before, during, and after NAC. On the basis of the final MRI, response was determined to be a clinically complete response ([CCR], no enhancement), probable CCR (residual enhancement equal to or less than that of glandular tissue), or residual tumor. All patients received surgery. Pathological outcomes were categorized as 1) no residual cancer, 2) no residual invasive cancer but ductal carcinoma in situ (DCIS) present, or 3) residual invasive cancer. The pathologically complete response (pCR) was defined as no invasive cancer. RESULTS: Complete clinical response as seen through MRI, including CCR and probable CCR, was identified in 35 (35 of 51, 69%) patients. MRI correctly diagnosed pCR in 26 (26 of 35, 74%) patients, including 18 of 19 (95%) patients in the HER-2 positive group and 8 of 16 (50%) patients in the HER-2 negative group (P < .005). The accuracy of MRI in identifying pCR varied according to the chemotherapy agent that was administered. MRI was more accurate in identifying pCR in patients who were receiving trastuzumab and less accurate in patients receiving bevacizumab. The high false-negative rate found in HER-2 negative patients was associated with residual disease that presented as scattered cells or small foci. In cases with residual bulk tumor, the lesion size, determined by MRI, correlated highly with that found in histopathological measurements (r = 0.93). CONCLUSIONS: MRI may predict pCR with high accuracy in HER-2 positive patients, but it has a high false-negative rate in HER-2 negative patients, particularly in patients who are receiving antiangiogenic agents. Results indicate that the chemotherapy agent should be taken into consideration when using MRI to interpret therapeutic outcomes. More studies are needed to establish the role of MRI in managing, especially surgical planning, patients who are receiving NAC.  相似文献   

11.
Neoadjuvant chemotherapy (also known as preoperative or primary chemotherapy) is the treatment of choice for patients with locally advanced breast cancer. One of the main advantages of neoadjuvant chemotherapy is that it allows for assessment of pathologic response to treatment. Clinical and radiologic evaluations of response to neoadjuvant chemotherapy are based on change in tumor size, and the correlation with pathologic response is often inaccurate. Pathologic evaluation of tumor size remains the gold standard for evaluation of residual tumor after chemotherapy. Chemotherapy-induced histomorphologic change is commonly observed in posttreatment resection specimens and can contribute to the less-than-perfect correlation between the clinical assessment of tumor size and the pathologic measurement. Therefore, accurate histologic mapping to the macroscopic and radiologic appearance of the tumor bed is necessary. Cytopathologic changes are also common in residual cancer cells after neoadjuvant chemotherapy and have uncertain clinical relevance. There is a role for the development of new histologic approaches to augment the pathologic and clinical assessment and provide information on the differential response, particularly for tumors in which less than pathologic complete response is achieved.  相似文献   

12.
Patients with large or nonoperable breast cancers often receive neoadjuvant chemotherapy to facilitate full resection of the tumor and enable conservation of the breast. However, currently available methods for evaluation of response during therapy are limited and the actual effect of the treatment is only recognized at surgery upon completion of chemotherapy. Timely assessment of response could allow individual tailoring of the treatment and save noneffective drugs and unnecessary toxicity. Here, we suggest that tumor derived DNA methylation in the serum may reflect changes in tumor burden and allow early recognition of responders versus nonresponders. In this pilot study, we collected 7 consecutive serum samples from 52 patients with locally advanced breast cancer during neoadjuvant chemotherapy. We selected RASSF1, which was methylated in more than 80% of the tumors, for serum analysis. Using the "methylation sensitive PCR and high resolution melting," we detected RASSF1 methylation in the serum of 21 patients prior to therapy. In four patients who achieved complete pathological response, RASSF1 methylation in the serum became undetectable early during therapy. In contrast, in 17 patients that had partial or minimal pathological response, serum RASSF1 methylation persisted longer or throughout the treatment (complete versus partial response p = 0.02). These findings support further development of this assay for monitoring response during neoadjuvant therapy.  相似文献   

13.
14.
乳腺癌新辅助化疗疗效评价方法的比较   总被引:1,自引:0,他引:1  
目的 比较查体、超声和钼靶在乳腺癌新辅助化疗(NAC)疗效评价中的差异.方法 通过查体、超声和钼靶分别测量、记录141例NAC患者肿瘤状况,分析治疗前后原发灶、淋巴结的变化.结果 全组中晚期患者居多,Ⅰ期仅占8.5%.化疗前查体的乳腺肿块较超声检查明显偏大(P<0.01).评价疗效时,原发灶查体误判完全缓解(CR)率高达46.8%(22/47),而超声误判残留率为84.0%(21/25).43例行钼靶检查患者中,有23例(53.5%)患者困难以测量肿块大小而无法评价疗效;5例有钙化的患者,虽化疗后肿块缩小,但钙化范围无变化.在治疗中,25例有效患者行原发灶空芯针穿刺,在9例穿刺病理阴性者中,仅有3例达pCR;16例穿刺阳性者均未达pCR.超声检查怀疑腋窝淋巴结转移的患者,通过空芯针穿刺的病理阳性率为88.3%(53/60),超声检查不怀疑者仍有20.0%(1/5)为阳性.24例超声未探及腋窝肿大淋巴结患者中,有9例(37.5%)前哨淋巴结活检阳性.化疗前淋巴结病理阳性患者64例,化疗后转阴36例(56.3%).全组原发灶及淋巴结均达病理完全缓解(pCR)者21例,占14.9%(21/141).结论 乳腺癌患者化疗前对腋窝淋巴结进行空芯针穿刺或前哨淋巴结活检明确病理状态非常重要,查体、超声及铜靶检查对原发灶肿瘤大小的判断都有相当的误差,可采用病灶穿刺来评价NAC的疗效,但对结果 的判断还需综合分析.  相似文献   

15.
Objective:The aim of this study was to study changes of HER-2 expression after neoadjuvant chemotherapy in the breast cancer cases.Methods:One hundred and thirty-seven female patients with primary breast cancers,who received neoadjuvant chemotherapy,underwent core needle puncture and Mammotome biopsy before chemotherapy,and the biopsy results were used as the basis of histological diagnosis,fluorescence in situ hybridization (FISH) was performed to test HER2 status of tumor tissues before and after chemothe...  相似文献   

16.
局部进展期乳腺癌经过新辅助化疗可以提高切除率和增加保乳机会,对于可手术乳腺癌患者行新辅助化疗和术后辅助化疗的生存期相似,而新辅助化疗达到病理完全缓解(pCR)患者的生存期则明显提高.但新辅助化疗还存在众多的分歧和争议,主要是完全缓解率低、无确切的术前疗效评价方法 、缺少一种疗效、生存预测和监测手段、不能个体化选择新辅助化疗等.因此,当前乳腺癌新辅助化疗临床研究关注的焦点是利用现有的临床、病理和分子指标个体化预测新辅助化疗pCR率或生存时间,一般认为pCR的提高通常与下列因素有关,如年龄轻、肿瘤直径小或分期早、肿瘤分级高、ER/PR阴性、HER-2阳性、增殖分子标志高表达、MCM、Ki-67表达以及浸润性导管癌(而非浸润性小叶癌)等,这些肿瘤分子特征和病理类型可能帮助预测新辅助化疗效果,可能是新辅助化疗个体化应用研究的方向.  相似文献   

17.
《Annals of oncology》2011,22(8):1748-1754
BackgroundTumour expression of cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), erythroblastic leukaemia viral oncogene homologue-2 (ErbB2), Ki-67 and p53 in breast cancer are associated with poorer outcomes. We investigated in vivo changes of these proteins with neoadjuvant chemotherapy.Patients and methodsFour core biopsies were taken from 100 breast cancer patients at baseline, during and upon completion of neoadjuvant chemotherapy. Immunohistochemical expression of these proteins were evaluated and correlated with clinicopathological features, clinical response and progression-free survival (PFS).ResultsThere was a statistically significant change from positivity to negativity in COX-2 expression with chemotherapy (P = 0.002), predominantly in clinical responders (P = 0.002). COX-2-positive tumours that remained positive had shorter PFS than those that turned negative. Estrogen receptor (ER)+ and COX-2+ tumours at baseline that remained COX-2+ fared worse than those that became COX-2 negative (PFS 27 versus 52 months, P = 0.002). No significant changes in IHC expression were observed for ER, progesterone receptor, ErbB2, EGFR, p53 or Ki67.ConclusionsChemotherapy induced change in COX-2 expression from positivity to negativity predominantly among clinical responders and is associated with longer PFS. Interaction between COX-2 and ER was observed, suggesting that some hormone receptor-positive patients may benefit from combining COX-2 inhibition with hormonal therapy.  相似文献   

18.
《Annals of oncology》2019,30(6):927-933
BackgroundHER2-positive (+) breast cancers, defined by HER2 overexpression and/or amplification, are often addicted to HER2 to maintain their malignant phenotype. Yet, some HER2+ tumors do not benefit from anti-HER2 therapy. We hypothesize that HER2 amplification levels and PI3K pathway activation are key determinants of response to HER2-targeted treatments without chemotherapy.Patients and methodsBaseline HER2+ tumors from patients treated with neoadjuvant lapatinib plus trastuzumab [with endocrine therapy for estrogen receptor (ER)+ tumors] in TBCRC006 (NCT00548184) were evaluated in a central laboratory for HER2 amplification by fluorescence in situ hybridization (FISH) (n = 56). HER2 copy number (CN) and FISH ratios, and PI3K pathway status, defined by PIK3CA mutations or PTEN levels by immunohistochemistry were available for 41 tumors. Results were correlated with pathologic complete response (pCR; no residual invasive tumor in breast).ResultsThirteen of the 56 patients (23%) achieved pCR. None of the 11 patients with HER2 ratio <4 and/or CN <10 achieved pCR, whereas 13/45 patients (29%) with HER2 ratio ≥4 and/or CN ≥10 attained pCR (P = 0.0513). Of the 18 patients with tumors expressing high PTEN or wild-type (WT) PIK3CA (intact PI3K pathway), 7 (39%) achieved pCR, compared with 1/23 (4%) with PI3K pathway alterations (P = 0.0133). Seven of the 16 patients (44%) with HER2 ratio ≥4 and intact PI3K pathway achieved pCR, whereas only 1/25 (4%) patients not meeting these criteria achieved pCR (P = 0.0031).ConclusionsOur findings suggest that there is a clinical subtype in breast cancer with high HER2 amplification and intact PI3K pathway that is especially sensitive to HER2-targeted therapies without chemotherapy. A combination of HER2 FISH ratio and PI3K pathway status warrants validation to identify patients who may be treated with HER2-targeted therapy without chemotherapy.  相似文献   

19.
Objective: The aim of this study was to evaluate the impact of different molecular subtypes defined by immunohistochemistry (IHC) staining on the response rate for patients with locally advanced breast cancer received neoadjuvant chemotherapy. Methods: One hundred and seven breast cancer patients admitted from 2007 to 2011 who received 4 cycles of docetaxel/epirubicin-combined (TE) neoadjuvant chemotherapy were retrospectively reviewed, the patients were classified into 4 subtypes: luminal A, luminal B, HER-2 and triple negative breast cancer (TNBC) according to different combination patterns of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor-2 (HER-2) expression defined by IHC method. The correlation between response rate and the molecular subtypes were analyzed. Results: The pathological complete response (PCR), clinical complete response (CCR), clinical partial response (CPR), and clinical stable disease (CSD) rate of whole group was 15.89% (17/107), 22.43% (24/107), 63.55% (68/107), 14.02% (15/107), respectively, and the overall response rate (ORR) was 85.98% (92/107). The PCR rate and ORR of luminal A, luminal B, HER-2 and TNBC subtypes was 4.76% and 73.81%; 16.67% and 83.33%;17.65% and 100.00%; 30.00% and 96.67%, respectively. The PCR and ORR rate of HER-2/TNBC subtypes was higher than that of luminal A/B subtypes (P = 0.019, P = 0.002, respectively). Conclusion: Different molecular subtypes display different response rate for patients with locally advanced breast cancer received neoadjuvant TE chemotherapy, HER-2/TNBC subtypes have a higher PCR and ORR rate than that of luminal A/B subtypes.  相似文献   

20.
新辅助化疗除了可以缩小乳腺肿瘤病灶,进而减少外科手术切除范围外,部分患者还可通过新辅助化疗达到原发灶和腋窝淋巴结转移病灶的pCR。对于这部分降期和pCR的乳腺癌患者,经过新辅助化疗后,如何更加合理的选择外科手术方式是临床医师常常面对的难题。因此,笔者回顾性分析新辅助化疗相应的临床研究,就新辅助化疗对乳腺癌患者手术方式的影响进行综述。  相似文献   

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