Neoadjuvant Chemotherapy For Invasive Breast Cancer Research Articles

The role of shear wave elastography in early prediction of response to neaodjuvant chemotherapy in cases of breast cancer

BackgroundBreast cancer is the most common malignant tumor and the commonest cause of death in female between 35 and 55 years of age. Neoadjuvant chemotherapy (NACT) is used in large scale nowadays in management of breast cancer. Recent studies propose that shear wave elastography (SWE) can early predict tumor therapy response during NACT for invasive breast cancer.Aim of workTo study the ability of SWE to predict pathological complete response (pCR) during NACT as early as first cycle.Subjects and methodsThe study analyzed data of 48 patients breast cancer who were scheduled for receiving NACT before surgery. During treatment, SWE examination was done at first four cycles.ResultsForty-eight breast cancer cases were included in the study with one hundred and ninety two examinations done. The cutoff point of stiffness ratio percent change post-first cycle in differentiating pCR and npCR groups was − 20% (AUC 0.755, sensitivity 81.8%, specificity 61.5%). The cutoff point of stiffness ratio percent change post-second cycle in differentiating pCR and npCR groups was − 49% (AUC 0.741, sensitivity 72.7%, specificity 76.9%). The stiffness ratio could predict pCR in early cycles of NACT.ConclusionsUS using shear wave elastography is an available, cheap, non-contrast, non-ionizing radiation method that predicts pCR in cases of breast cancer at neoadjuvant setting as early as first cycle.

Early prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer MRI images using combined Pre-trained convolutional neural network and machine learning

ObjectiveTimely diagnosis of breast cancer can ameliorate the treatment plan, thus reducing the mortality rate. We propose a model integrating pre-trained Convolutional neural network (CNN) with machine learning for prognosticating pathologic complete response(PCR) using breast cancer dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) prior to commencement of neoadjuvant chemotherapy(NACT).For predicting pathologic complete response (PCR) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for breast cancer prior to the start of neoadjuvant chemotherapy, we present a hybrid model integrating a pre-trained Convolutional neural network (CNN) with machine learning (NACT). Material & MethodsIn this retrospective study, 64 patients receiving NACT for invasive breast cancer are examined. Deep learning-based pre-trained CNN models ResNet-50 and ResNet-18 were used to extract features from patient visit 1 MRI images (before the initiation of NACT). Mann-Whitney U tests is used to assess features and their relevance (significance level p less than 0.05 and confidence interval is 95 %). Furthermore, features extracted and features selected were independently given as an input to different machine learning classifiers for the prediction of response of NACT. Classification performance was assessed under different data division protocols using accuracy, specificity, sensitivity, and area under the receiver operating characteristic curve (AUROC). ResultThe hybrid combination using ResNet-18 as feature extractor, fine K-nearest neighbor(KNN) as classifier and feature selected using Mann-Whitney U test outperformed the result. Accuracy of 99.8% and AUROC of 1 is obtained under hold-out validation protocol while accuracy of 99.3%, and AUROC of 0.99 is obtained under 10-fold cross-validation. ConclusionThe proposed model employing DCE-MRI images acquired before starting chemotherapy has considerable accuracy in classifying PCR and non-PCR patients. The efficacy of the prediction model can improve considerably on the back of a larger dataset.

Initial Results of 68Ga-FAPI-46 PET/MRI to Assess Response to Neoadjuvant Chemotherapy in Breast Cancer.

Improving imaging-based response after neoadjuvant chemotherapy (NAC) in breast cancer assessment could obviate histologic confirmation of pathologic complete response (pCR) and facilitate deescalation of chemotherapy or surgery. Fibroblast activation protein inhibitor (FAPI) PET/MRI is a promising novel molecular imaging agent for the tumor microenvironment with intense uptake in breast cancer. We assessed the diagnostic performance of follow-up breast 68Ga-FAPI-46 (68Ga-FAPI) PET/MRI in classifying the response status of local breast cancer and lymph node metastases after completion of NAC and validated this approach immunohistochemically. Methods: In women who completed NAC for invasive breast cancer, follow-up 68Ga-FAPI PET/MRI and corresponding fibroblast activation protein (FAP) immunostainings were retrospectively analyzed. Metrics of 68Ga-FAPI uptake and FAP immunoreactivity in women with or without pCR were compared using the Mann-Whitney U test. Diagnostic performance to detect remnant invasive cancer was calculated for tracer uptake metrics using receiver-operating-characteristic curves and for masked readers' visual assessment categories of PET/MRI and MRI alone. Results: Thirteen women (mean age ± SD, 47 ± 9 y) were evaluated. Seven of the 13 achieved pCR in the breast and 6 in the axilla. FAP immunoreactivity was significantly associated with response status. The 68Ga-FAPI PET/MRI mean breast tumor-to-background ratio was 0.9 (range, 0.6-1.2) for pCR and 2.1 (range, 1.4-3.1) for no pCR (P = 0.001). Integrated PET/MRI could classify breast response correctly in all 13 women based on readers' visual assessment or tumor-to-background ratio. Evaluation of MRI alone resulted in at least 2 false-positives. For lymph nodes, PET/MRI readers had at least 2 false-negative classifications, whereas MRI alone resulted in 2 false-negatives and 1 false-positive. Conclusion: To our knowledge, this was the first analysis of 68Ga-FAPI PET/MRI for response assessment after NAC for breast cancer. The diagnostic performance of PET/MRI in a small study sample trended toward a gain over MRI alone, clearly supporting future prospective studies.

Factors Associated With Surgical Modality Following Neoadjuvant Chemotherapy in Patients with Breast Cancer

BackgroundThe breast-conserving surgery (BCS) rate for patients with breast cancer in China is much lower than that in Europe and the United States. This study aimed to identify factors affecting the choice of surgical modality following neoadjuvant chemotherapy (NAC) in patients with breast cancer in northwest China. Patients and MethodsPatients who underwent mastectomy or BCS after NAC for invasive breast cancer from January 2013 to December 2017 were enrolled in the study. Single-factor and multivariate logistic regression analyses were applied to identify the association between the type of surgery and demographic characteristics or clinical pathological factors of patients. ResultsThis study enrolled 916 patients. Among them, 191 patients (20.9%) and 725 patients (79.1%) underwent BCS and mastectomy, respectively. Patients with high education were less likely to undergo mastectomy compared with patients with less education (P < .001; odds ratio [OR] = 0.50; 95% confidence interval [CI], 0.35-0.71). Patients with cT3 tumors were nearly six times more likely to undergo mastectomy compared with patients with cT1 tumors (P = .003; OR = 5.74; 95% CI, 2.07-15.97). Moreover, patients older than 50 years of age (P < .001; OR = 2.84; 95% CI, = 1.93-4.16) were more likely to be offered mastectomy. No association between the type of surgery and pathological complete response (P = .351) was observed. ConclusionPretreatment clinical disease size remains a strong predictor of surgical management, whereas response to NAC appeared to play no role in the surgical decision, suggesting that the potential surgical benefits of NAC may be still under-recogonized in northwest China.

Abstract PS7-77: Pathological response after neoadjuvant chemotherapy and long-term outcomes among very young women with HER2 negative breast cancer

Abstract Purpose: To describe the pathological response rates (according to the MD Anderson RCB score) achieved by patients with 35 years old or younger, with HER2 negative breast cancer, who received neoadjuvant chemotherapy (NAC) and long term outcomes according to the response. Methods: A retrospective review of 526 medical records of women aged less than or equal to 35 years at diagnosis between 2009 and 2014 at INEN in Lima-Peru, who received NAC for invasive breast cancer, was performed. HER2 positive patients were excluded because of a lack of access to neoadjuvant anti-HER2 therapy during this period in our hospital. Descriptive statistics were used to describe baseline characteristics. OS was calculated from the date of diagnosis to death or last follow-up and presented as Kaplan-Meier curves. The comparison among patients who achieved pCR (RCB-0) and those with residual disease, was based on a log-rank test. Results: Seventy women (One with synchronous bilateral disease) were selected according to selection criteria, median age: 31.7 years old (IQR: 30.0-33.2). Hormone receptor-positive: 38 (53.5%). Clinical stage: IIA: 13(18.3%), IIB: 8(11.3%), IIIA: 25(35.2%), IIIB: 21 (29.6%) and IIIC: 4 (5.6%). Type of NAC: Anthracyclines 6 (8.6%), Anthracyclines and taxanes 55 (78.6%), Platin 5 (7.1%), Taxanes 4 (5.7%). Type of surgery: Conservative 16 (22.5%), radical 50 (70.4%), toilet 5 (7.0%). Type of pathological response RCB-0: 9(12.7%), RCB-I: 2(2.8%), RCB-II:29(40.8%), RCB-III: 24(33.8%), non-pCR: 7(9.9%). With a median follow-up of 46.5m, 5y OS: 100/100/79.3/45.8% according to RCB-0/I/II/III respectively (p=0.004). Conclusions: "Very young" women reach fewer pCR rates than reported for "young" and older women. Even so, RCB-0 can be considered as a biomarker of excellent prognosis and could be used as a surrogate biomarker to evaluate the efficacy of neoadjuvant therapy even in very young women who receive NAC. Citation Format: Fernando Valencia, Jorge Laboriano, Luis A. Chirinos, Henry L. Gomez. Pathological response after neoadjuvant chemotherapy and long-term outcomes among very young women with HER2 negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-77.

A Novel Marker, Based on Ultrasound Tomography, for Monitoring Early Response to Neoadjuvant Chemotherapy.

To evaluate the combination of tumor volume and sound speed as a potential imaging marker for assessing neoadjuvant chemotherapy (NAC) response. This study was carried out under an IRB-approved protocol (written consent required). Fourteen patients undergoing NAC for invasive breast cancer were examined with ultrasound tomography (UST) throughout their treatment. The volume (V) and the volume-averaged sound speed (VASS) of the tumors and their changes were measured for each patient. Time-dependent response curves of V and VASS were constructed individually for each patient and then as averages for the complete versus partial response groups in order to characterize differences between the two groups. Differences in group means were assessed for statistical significance using t-tests. Differences in shapes of group curves were evaluated with Kolmogorov-Smirnoff tests. On average, tumor volume and sound speed in the partial response group showed a gradual decline in the first 60 days of treatment, while the complete response group showed a much steeper decline (P < 0.05). The shapes of the response curves of the two groups, corresponding to the entire treatment period, were also found to be significantly different (P < 0.05). Furthermore, large simultaneous drops in volume and sound speed in the first 3 weeks of treatment were characteristic only of the complete responders (P < 0.05). This study demonstrates the feasibility of using UST to monitor NAC response, warranting future studies to better define the potential of UST for noninvasive, rapid identification of partial versus complete responders in women undergoing NAC.

Can Shear Wave Elastography Variables Predict the Pathological Response to Neoadjuvant Chemotherapy in Patients with Invasive Breast Cancer?

This study was designed to evaluate the performance of shear wave elastography (SWE) parameters inin predicting the pathological response of invasive breast cancer to neoadjuvant chemotherapy (NAC). The prospective study recruited 25 eligible patients from August 2016 to August 2017. SWE was performed 1 d before biopsy (time point t0, elasticity E0), after the first and second, fourth cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. Tumour stiffness was assessed by quantitative SWE velocity. SWE parameters measured included changes in bidimensional tumour size on SWE time, quantitative SWE velocity, the relative changes in them after the first and second, fourth NAC cycles were considered as the variables [Δt1, Δt2, Δt4]. The pathological response was classified according to the residual cancer burden (RCB) protocol, RCB-0 (pCR,0); RCB-I (minimal residual disease, 0-1.36); RCB-II(moderate residual disease, 1.36-3.28); and RCB-III(extensive residual disease, >3.28). The responsive group include RCB 0 and RCB-I, the unresponsive group included RCB II and RCBIII. Correlations between SWE variables and RCB scores were evaluated. The predictive diagnostic performances of SWE parameters, and the predictive RCB (predRCB) score determined by a linear regression model were compared. SWE variables were significantly different among the RCB 0/I and RCBII/III groups. The SWE variables of Δt2had significantly better diagnostic performance than other variables regarding predicting the pathological. Our results suggest that SWE can be potentially used as an early predictor of tumor therapy response during NAC for invasive breast cancer.

Abstract P5-21-06: Clinical outcomes according to pathological complete response (pCR) and proliferation index of residual tumor (RT) after neoadjuvant chemotherapy (NC) in invasive breast cancer (IBC)

Abstract BACKGROUND: IBC is a heterogeneous disease with several subtypes molecularly identified by gene expression profile. Since subtypes defined by immuhistochemistry (IHC) panel are similar although not identical to molecular subtypes, IHC may represent an easier alternative to identify them. PURPUSE: To assess the clinical outcomes of pts who received NC for IBC and the differences by IHC-related subtypes. METHODS: We retrospectively reviewed the clinical records of the pts treated with NC for stage II-III IBC from 2000 to 2013. For each pt we recorded baseline tumor size, type of NC [which consisted of anthracyclines (A) + taxanes (T) in HER2- and T + trastuzumab (H) ± A in HER2+ pts), type of surgery, pathological response (pCR defined as the absence of invasive cells in the breast and the lymph nodes regardless of DCIS). IHC subtypes were defined according to ER and PgR expression, Ki-67 level, and HER2 status: Luminal A (LA): ER and PR+, neg HER2 and Ki67&amp;lt; 14% (= 3%) Luminal B (LB): ER and/or PR+, neg HER2 and Ki67≥14% (=30%) Luminal HER2 (LHER2): ER and/or PR+, positive HER2 and any Ki67 (=27%) HER2 positive (HER2+): neg ER and PR, positive HER2 and any Ki67 (=12%) Triple negative (TN): neg ER and PR, neg HER2 and any Ki67 (13%) Unknown subtype in 33 cases (15%) The loco-regional and distant RFS and OS were evaluated according to pCR. pCR and survival outcomes were also assessed on the basis of both pre- and post- NC Ki67 levels. RESULTS: In the consecutive series of 213 pts who received NC median age was 50 yrs (r. 25-75). The NC consisted of an A+T based regimen in HER2 negative (145 pts) and of a T+ H with A (31 pts) or without A (34 pts) in HER2+ disease. Only 14 did not receive surgery: 10 for distant metastases development and 4 because still on NC. Quadrantectomy was performed in 120 pts (60%). Among all pts, pCR was achieved in 44 pts(22%) with further 4 pts showing a RT ≤1 mm. Relationship between pCR and subtypes, ki67 and recurrence rate LA (%)LB (%)LHER2 (%)HER2+TN (%)Median Ki67 (%)Recurrence Rate (%)pCR012.542.527.517.5484.5No pCR10042.329.28.814.63731.5p Value &amp;lt;0.001 =0.001 All but 19 HER2+ pts (84) received H obtaining pCR in 38% of cases regardless chemotherapy type (A-based 35% vs Not A- 38%) The median follow-up was 45 months (range 1-166 ms). The 4y-RFS and OS were better in which achieved pCR than those did no (RFS 92 vs to 74%; p=0.0014 and OS 95 vs 78%; p=0.0074). Median Ki67 in pretreated core biopsy was 40 compared to 27% in post-NC RT. Patients with high (&amp;gt;30%) post-NC Ki67 levels showed significantly higher risk for disease relapse (4 y-RFS 60%; p=0.0019) and death (4y OS 71%; p=0.018) compared with patients with &amp;lt;15% (4y-RFS 93 and OS 88%) or &amp;gt;15-30 Ki67 levels (4y-RFS 83 and OS 82%). CONCLUSIONS: According to literature data, pts achieving pCR after NC showed better RFS and OS compared to no pCR pts. The pCR rate was significantly higher in aggressive subtypes (HER2 and TN). In HER2 disease, pCR was achieved by using chemo + H, irrespective of A-addition. Interestingly high pre-NC KI67 levels seem to predict the possibility obtaing pCR, while post-NC Ki67 levels seem to be of prognostic value in pts who do not receive pCR. Citation Format: Antonella Ferro, Alessia Caldara, Mariachiara Dipasquale, Chiara Trentin, Renza Triolo, Mattia Barbareschi, Daniela Bernardi, Marco Pellegrini, Daniela Cazzolli, Gabriella Berlanda, Fabio Gasperetti, Francesca Maines, Paolina Tuttobene, Orazio Caffo, Enzo Galligioni. Clinical outcomes according to pathological complete response (pCR) and proliferation index of residual tumor (RT) after neoadjuvant chemotherapy (NC) in invasive breast cancer (IBC) [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 P5-21-06.

Abstract P2-03-07: Prediction of the pathological response to neoadjuvant chemotherapy in patients with breast cancer using sonazoid-enhanced ultrasonography

Abstract Background: Altered blood flow in malignant tumors is evidenced by contrast-enhanced ultrasonography (CEUS) because of its image perfusion capabilities. This study aimed to investigate the value of CEUS in the evaluation of the response of breast cancer lesions to neoadjuvant chemotherapy (NAC). We evaluated whether the prediction of a pathological complete response (pCR) using CEUS was more precise than that using other standard evaluation methods such as magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). Methods: Ten patients (mean age, 50.2 years) who underwent NAC for invasive breast cancer between September 2012 and April 2013 were eligible for this cohort study. Clinical tumor response was evaluated using contrast-enhanced MRI, PET/CT, and CEUS following NAC. A pCR was defined as the absence of invasive cancer in the breast and lymph nodes according to the Japanese Breast Cancer Society criteria. A clinically complete response (cCR) was defined as the absence of residual disease on MRI and PET/CT. The HI VISION ASCENDUS (Hitachi Aloka Medical Corp.) was used for ultrasonography. Tumors were observed 50 s after Sonazoid injection at a dose of 0.01 ml/kg. A time-intensity curve of tumor signal intensity was drawn. The brightness of the tumor was digitized and the curve was created on the basis of brightness changes over time. The intensity of brightness of the breast cancer lesions was calculated as the increased rate of brightness (IRB) using the following formula: maximal intensity/intensity before contrast. Results: Four (40%) of the 10 patients were diagnosed with pCR by NAC. Among 4 (40%) patients diagnosed with cCR by MRI, 1 (25%) achieved pCR. All patients were diagnosed with pCR by PET/CT. The IRB values of the 10 patients who received CEUS before surgery were 1.0, 1.1, 1.2, 1.2, 1.3, 1.6, 1.8, 1.9, 2.5, and 4.2. The IRB values of the 4 patients diagnosed with pCR were 1.0, 1.1, 1.2, and 1.2. IRB values were significantly lower in patients who achieved pCR than in those who did not (pCR vs. no pCR, 1.1 ± 0.9 vs. 2.2 ± 1.0, P &amp;lt; 0.05). Furthermore, among the patients who achieved pCR, the IRB values of 2 patients with no residual ductal carcinoma in situ (DCIS) were 1.0 and 1.1, whereas those of 2 patients with residual DCIS were both 1.2. In the 4 patients who achieved cCR as diagnosed by MRI and PET/CT, 3 with pathological residual disease had detectable IRB by CEUS. table 1caseageStageSub typeMRIPET-CTpathological responseIncrease rate of brightness (IRB)167T2N1 IIBLuminal HER2PRCRCR1237T2N0 IIAHER2 positivePRCRCR1.1346T3N1 IIIAHER2 positiveCRCRCR1.2446T2N3c IIICLuminal HER2PRCRCR1.2564T2N0 IIAHER-2 positiveCRCRPR1.3658T2N1 IIBLuminal BCRCRPR1.6738T2N0 IIALuminal BPRCRPR1.8857T1cN0 ILuminal HER-2PRCRPR1.9939T2N1 IIBLuminalBSDCRSD2.51050T2N1 IIBTriple negativePRCRSD4.2 Conclusions: The prediction of pCR after NAC in patients with breast cancer is more precise with Sonazoid-enhanced ultrasonography than with standard methods such as MRI and PET/CT. Furthermore, CEUS may be useful for predicting residual DCIS on the basis of brightness intensity. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-03-07.