Chemotherapy For Invasive Breast Cancer Research Articles

Effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for invasive breast cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the Use of G-CSF 2022.

Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy. A systematic literature review was conducted according to the "Minds Handbook for Clinical Practice Guideline Development" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data. Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01-0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported. Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.

Abstract PO5-16-09: Associations of age, body mass index, diabetes and hypertension with relative dose intensity among women receiving anthracycline- and/or taxane-based chemotherapy for invasive breast cancer

Abstract Research suggests that medical comorbidity is associated with reduced relative dose intensity (RDI) in patients receiving chemotherapy for treatment of breast cancer. We aimed to determine factors associated with RDI of specific chemotherapy drugs in anthracycline- and/or taxane-based regimens. Women with a diagnosis of lymph node positive, invasive breast cancer who received neoadjuvant or adjuvant chemotherapy with either doxorubicin (DOX) + paclitaxel (PAC) or docetaxel (DOCE)-containing regimens at a single centerfrom2012 to2019 were included in this retrospective study. Age, race, comorbidities, height, weight, and chemotherapy regimen and dose were abstracted from the electronic health record. BMI was calculated using height and weight measured in clinic at the time initial chemotherapy orders were written and categorized according to US national guidelines (18.5 to < 25, 25 to < 30, and >30kg/m2). Presence of diabetes (DM) and hypertension (HTN) at time of diagnosis were determined by chart review. The oncologists’ initial chemotherapy orders (dose and duration) were used as the basis for RDI calculations. Cumulative actual dose received and duration of treatment were compared to planned dose and duration for individual chemotherapy drug and by regimen (DOX+PAC vs. DOCE). Associations between patient characteristics and RDI were evaluated in bivariate and multivariable analyses. A total of 230 women met the inclusion criteria, with 125 receiving a DOX+PAC regimen and 105 receiving a DOCE-based regimen. A higher percentage of women on DOX+PAC received >85% RDI compared to women receiving DOCE (80.8% vs 67.6%). Women aged 65+ years had lower median RDI [IQR] for DOCE than younger women (0.83 [0.67 - 0.98] vs 0.94 [0.84 - 1.00], p = 0.04), and a lower percentage in the older group received >85% RDI (35.3% vs 73.9%, p< 0.01). Median RDIs of PAC and DOX+PAC were lower for Black women than for White and Asian women (PAC: 0.91 [0.75 - 1.00] vs 1.00 [0.89 - 1.00], p = 0.02, DOX+PAC: 0.92[0.87-0.99] vs. 0.97 [0.91-1.00], p = 0.03), and the percent of Black women receiving >85% RDI of PAC was also lower (55.3% vs 77.6%, p = 0.01). BMI category was associated with median RDI for PAC (p= 0.03) and DOX+PAC (p = 0.01), with women in the >30kg/m2 category having the lowest median RDIs and PAC RDI >85% (p < 0.01). Median RDI of DOX+PAC was lower for women with DM (0.89 [0.84-0.92] vs. 0.96 [0.88-1:00], p = 0.03), and a lower percentage of women with DM received DOX RDI >85% compared to women without DM (66.7% vs 91.6%, p < 0.01). Median RDI was lower among women with HTN compared to women without for PAC (0.85 [0.73 - 1.00] vs 0.98 [0.83 - 1.00], p = 0.01) and DOX+PAC (0.91 [0.84 - 0.97] vs 0.97 [0.90 - 1.00], p = 0.01), and a lower percentage of women with HTN received >85% RDI for PAC (50.0% vs 73.3%, p = 0.01). Multiple logistic regression models adjusted for age (continuous), race, BMI (continuous), DM, and HTN had modestly improved predictive value compared to null models (McFadden’s R2 = 0.10 to 0.19); each year of increased age was associated with lower odds of RDI > 85% for DOX (OR [95% confidence interval] 0.91 [0.84-0.97], p = < 0.01), DOX+PAC (0.95 [0.90-0.99], p = 0.02), and DOCE (0.93 [0.88-0.97], p < 0.01), and DM with lower odds for DOX (0.26 [0.07-0.95], p = 0.04). Our findings of associations between increasing age, Black race, BMI, DM, and HTN and reduced RDI are consistent with prior research and present new data regarding associations between medical comorbidities and individual components of chemotherapy regimens. Citation Format: Heather Wopat, Annette Aldous, Adam Ciarleglio, Kendall Anderson, Kim Robien. Associations of age, body mass index, diabetes and hypertension with relative dose intensity among women receiving anthracycline- and/or taxane-based chemotherapy for invasive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-16-09.

Response to Neoadjuvant Chemotherapy in Invasive Breast Cancer Predicted by CD4+, CD8+, and FOXP3+ Tumor-Infiltrating Lymphocytes.

Response to neoadjuvant chemotherapy (NC) in individuals with invasive breast cancer (IBC) must be monitored, and biomarkers are needed. NC can activate an anti-tumour immune response in its microenvironment, known as Tumor-infiltrating Lymphocytes (TIL). TIL components believed to have great potential as predictors are CD4+, CD8+, and FOXP3+ TIL. This study aims to explore TIL components that can potentially be predictive biomarkers of NC pathological responses. A sample size of 40 were analyzed based on the relationship between CD4+, CD8+, and FOXP3+ TIL expression with the Miller-Payne (MP) grading system. Age, tumour grade, PR, ER, Ki-67, and HER2 were also evaluated. CD4+, CD8+, and FOXP3+ TIL expressions were analayzed by IHC staining, while other data were collected from archives. Data was analyzed using univariate and multivariate analysis. Univariate analysis showed a significant relationship between CD4+ TIL and MP (p<0.001), CD8+ and MP (p=0.004), and FOXP3 with MP (p<0.001). The simultaneous integration of the three biomarkers in one model was not good enough to be a predictive model. Therefore, an exploratory analysis was conducted by testing several alternative models that combined two of the three existing biomarkers. It turned out that CD4+ TIL in model 2 (CD4+CD8+) and FOXP3+ TIL in model 4 (CD8+FOXP3+) showed significant coefficient values. Moreover, all of the threshold coefficients in model 4 are significant. This study shows that CD4+, CD8+, and FOXP3+ TIL have promising potential as predictive biomarkers. In particular, FOXP3+ is dominant in predictive models of pathological response in patients with IBC.

Value of radiomics based on CE-MRI for predicting the efficacy of neoadjuvant chemotherapy in invasive breast cancer

To establish and validate a radiomics nomogram based on contrast-enhanced (CE)-MRI for predicting the efficacy of neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer with non-mass enhancement (NME). A cohort comprising 117 HER2-positive breast cancer patients showing NME on CE-MRI between January 2012 and December 2019 were retrospectively analysed in our study. Patients were classified as pathological complete respone (pCR) according to surgical specimens and axillary lymph nodes without invasive tumour cells. Clinicopathological data were recorded, and images were assessed by two radiologists. A total of 1130 radiomics features were extracted from the primary tumour and six radiomics features were selected by the maximal relevance and minimal redundancy and least absolute shrinkage and selection operator algorithms. Univariate logistic regression was used to screen meaningful clinical and imaging features. The rad-score and independent risk factors were incorporated to build a nomogram model. Calibration and receiver operator characteristic curves were used to confirm the performance of the nomogram in the training and testing cohorts. The clinical usefulness of the nomogram was evaluated by decision curve analysis. The difference in the rad-score between the pCR and non-pCR groups was significant in the training and testing cohorts (p < 0.01). The nomogram model showed good calibration and discrimination, with AUCs of 0.900 and 0.810 in the training and testing cohorts. Decision curve analysis indicated that the radiomics-based model was superior in terms of patient clinical benefit. The MRI-based radiomics nomogram model could be used to pre-operatively predict the efficacy of NAC in HER2-positive breast cancer patients showing NME. HER2-positive breast cancer showing segmental enhancement on CE-MRI was more likely to achieve pCR after NAC than regional enhancement and diffuse enhancement.The MRI-based radiomics nomogram model could be used to pre-operatively predict the efficacy of NAC in HER2-positive breast cancer that showed NME.

Are baseline mammographic and ultrasound features associated with metastasis free survival in women receiving neoadjuvant chemotherapy for invasive breast cancer?

ObjectivesTo identify associations between baseline ultrasound (US) and mammographic features and metastasis free survival (MFS) in women receiving neo-adjuvant chemotherapy (NACT) for breast cancer. MethodsThe data were collected as part of an ethically approved prospective study. Women with invasive breast cancer receiving NACT who were metastasis free at diagnosis were included. Baseline US and mammography were performed. Imaging was assessed by an experienced breast radiologist who was blinded to outcomes. US imaging features documented included posterior effect, skin thickening, size and stiffness using shear wave elastography (SWE). The mammographic features documented were spiculation and microcalcification. The development of metastatic disease was ascertained from computer records. Statistical analysis was performed using Kaplan Meier survival curves and Receiver Operator Characteristic (ROC) analysis. Results171 women with 172 cancers were included in the study and 55 developed metastatic disease. Mean follow-up was 6.0 years. Women with mammographic calcification had significantly poorer metastasis free survival (MFS) compared to women without calcification (p = 0.043, 6 yr MFS 50 % vs 69 %). Women bearing cancer with distal shadowing had poorer MFS than women without shadowing (p = 0.025, 6 yr MFS 47 % vs. 73 %). Women with US skin thickening had poorer MFS compared to women without skin thickening (p = 0.032, 6 yr MFS 52 % vs. 68 %). Mammographic spiculation, US size and stiffness at SWE had no significant association with MFS. ConclusionWe have identified mammographic and US features associated with MFS in women receiving NACT. Such information may be useful when counselling patients about the benefits and risks of NACT.

Abstract PS1-14: Impact of axillary dissection and patterns of care in patients with ypN1 triple negative breast cancer receiving regional nodal irradiation

Abstract Background: The benefit of axillary lymph node dissection (ALND) in patients with pN1 disease on sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy for invasive breast cancer in patients receiving regional nodal irradiation (RNI) is unclear, even in patients with high risk histologic features such as triple negative disease. We sought to determine any association of ALND with improved survival, as well as patterns of care in this cohort using the National Cancer Database (NCDB). Methods: The NCDB was queried for women ages 18-75 with cT1-3N1 and ypT0-T3N1M0 breast cancer that underwent definitive surgical resection with axillary staging followed by adjuvant regional nodal irradiation, with triple negative receptor status. Only patients who were treated from 2012 - 2015 were included for appropriate coding of the extent of axillary surgery. Overall survival was estimated using the Kaplan-Meier method and Cox proportional hazards models. An analysis of the number of lymph nodes removed, rate of RNI utilization, and rate of ALND was performed using the Wilcoxon rank-sum test, proportions of RNI utilization compared using the Chi-squared test, and correlation of these to year of diagnosis was evaluated with the Pearson correlation coefficient. Results: A total of 572 women were identified that met inclusion criteria. The median age was 53 (range 24-75) years. 67 (11.7%) of women had SLNB alone and 505 (88.3%) had ALND with or without SLNB. Four year OS was 66.7% in patients undergoing ALND compared to 70.6% in those that had SLNB alone (p = 0.47). Charlson-Deyo comorbidity index (CDCC) (p = 0.01) and clinical T3 stage (p = 0.03) were significantly associated with survival. After adjusting for age, histology, clinical and pathologic T-stage, and CDCC, there was no significant relationship between receipt of ALND and overall survival (OS), however CDCC (p = 0.01) and cT3 or pT3 (p = 0.02 and p =0.01) remained significantly associated with OS. The mean number of lymph nodes sampled from 2012 to 2015 increased from 11.68 to 13.46 (p = 0.07). The rate of RNI increased from 55.6% in 2012 of patients to 58.4% in 2015 (p = 0.6). The rate of ALND increased from 83.9% in 2012 to 90.8% in 2015 (p = 0.2). Pearson correlation coefficients between mean number of lymph nodes sampled, rate of RNI, and rate of ALND were 0.83. 0.13, and 0.95 respectively. Conclusions: There was no difference in overall survival between patients with cT1-3N1M0 and ypT0-3N1M0 triple negative breast cancer receiving SLNB compared to ALND with adjuvant RNI, even when adjusting for tumor size and comorbidities, which remained significant risk factors. There was a trend towards an increase in the mean number of lymph nodes sampled and increased utilization of ALND, though these failed to reach statistical significance. We await the results of the Alliance 011202 randomized trial to provide prospective guidance of the utility of ALND in this high risk subgroup. Table 1. Baseline Characteristics For Triple-Negative PatientsSLNB (n=67)ALND (n=505)Median Age (Years)5353Histology (n, %)Ductal61 (91%)452 (90%)Lobular2 (3%)15 (3%)Other4 (6%)38 (7%)T-Stage (n,%)cT111 (16%)73 (15%)cT234 (51%)290 (57%)cT322 (33%)142 (28%)CDCC (n,%)054 (81%)441 (87%)19 (13%)51 (10%)24 (6%)8 (2%)30 (0%)5 (1%)Mean CDCC0.250.16Facility Type (n,%)Community5 (7%)36 (7%)Comprehensive Community27 (40%)171 (34%)Academic/Research13 (19%)160 (32%)Integrated Network13 (19%)72 (14%)Other/Unknown9 (14%)66 (13%)Lymphovascular Invasion (%)32.84%32.48%Median Tumor Size (cm)3.63.3Median Nodes Examined412Median Nodes Positive12 Citation Format: Michael Kharouta, Nicholas Damico, Megan Miller, Eleanor Harris, Janice Lyons. Impact of axillary dissection and patterns of care in patients with ypN1 triple negative breast cancer receiving regional nodal irradiation [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 PS1-14.

Tumor Sphericity Predicts Response in Neoadjuvant Chemotherapy for Invasive Breast Cancer.

This retrospective study examined magnetic resonance imaging (MRI)–derived tumor sphericity (SPH) as a quantitative measure of breast tumor morphology, and investigated the association between SPH and reader-assessed morphological pattern (MP). In addition, association of SPH with pathologic complete response was evaluated in patients enrolled in an adaptively randomized clinical trial designed to rapidly identify new agents for breast cancer. All patients underwent MRI examinations at multiple time points during the treatment. SPH values from pretreatment (T0) and early-treatment (T1) were investigated in this study. MP on T0 dynamic contrast-enhanced MRI was ranked from 1 to 5 in 220 patients. Mean SPH values decreased with the increased order of MP. SPH was higher in patients with pathologic complete response than in patients without (difference at T0: 0.04, 95% confidence interval [CI]: 0.02–0.05, P < .001; difference at T1: 0.03, 95% CI: 0.02–0.04, P < .001). The area under the receiver operating characteristic curve was estimated as 0.61 (95% CI, 0.57–0.65) at T0 and 0.58 (95% CI, 0.55–0.62) at T1. When the analysis was performed by cancer subtype defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, highest area under the receiver operating characteristic curve were observed in HR−/HER2+: 0.67 (95% CI, 0.54–0.80) at T0, and 0.63 (95% CI, 0.51–0.76) at T1. Tumor SPH showed promise to quantify MRI MPs and as a biomarker for predicting treatment outcome at pre- or early-treatment time points.

Pegylated liposomal doxorubicin as neoadjuvant therapy for stage II–III locally advanced breast cancer

Conventional anthracyclines represent a cornerstone drug in the treatment of breast cancer. Pegylated liposomal doxorubicin (PLD) has similar efficacy to anthracyclines with reduced toxicity. This study was to compare the efficacy and safety of PLD-based neoadjuvant chemotherapy (NAC) with epirubicin-based treatment for breast cancer. 81 breast cancer patients were enrolled in this retrospective study. The objective response rate (ORR) in the PLD group was 74.1%, the 3-year disease-free survival(DFS) and overall survival(OS) were 81.5% and 88.9%. The PLD group achieved similar efficacy to the EPI group. The PLD group showed a low rate of neutropenia , nausea and vomiting, but a higher rate of mucositis and hand-foot syndrome. In neoadjuvant chemotherapy for invasive breast cancer, PLD provides comparable efficacy to epirubicin with a safe cardiac toxicity profile and manageable adverse effects.

Abstract P3-08-16: The impact of residual ductal carcinoma in situ on breast cancer recurrence in the neoadjuvant I-SPY2 TRIAL

Abstract Background: Patients who achieve a pathological complete response (pCR- defined as no invasive cancer) after neoadjuvant chemotherapy (NAC) for breast cancer (BC) have improved outcomes, but there is still controversy about the significance of residual ductal carcinoma in situ (DCIS) on local recurrence rate (LRR). The I-SPY 2 TRIAL is an adaptive neoadjuvant platform trial evaluating novel experimental regimens in comparison to standard chemotherapy in women with high-risk breast cancer. The purpose of this study is to determine if residual DCIS after NAC in early BC affects LRR in patients with or without residual invasive disease in the I-SPY 2 TRIAL. Methods: 933 I-SPY 2 patients with residual cancer burden (RCB) and follow-up data were included in this analysis. Residual DCIS was defined as any carcinoma in situ &amp;gt; 0% on RCB evaluation. Local recurrence was defined as recurrence in breast, chest wall or locoregional nodes and/or skin and subcutaneous tissue. We stratified our cohort into four groups: those without residual invasive disease (defined as RCB0) ± residual DCIS, and those with residual invasive disease (RCB&amp;gt;0) ± residual DCIS. We estimated LRR within each group using the Kaplan Meier method; and used Cox proportional hazards models to assess LRR differences between groups, with: patients with no residual disease (invasive or in situ) as reference group. Results: Among 933 patients assessed, median follow up time was 3.9 years. RCB 0 status was achieved in 337 patients (36%). Of these, 267 (29%) had no residual DCIS, which represents our reference group, and 70 (7%) had residual DCIS. Among 596 (64%) patients who had RCB&amp;gt;0, 296 (32%) had residual DCIS. For patients with RCB0 without DCIS and RCB0 with DCIS, the LRR at 3 years were similar: 2% vs 3% respectively (Hazard ratio: 1.29 [0.26-6.39]). Results were also similar in the RCB&amp;gt;0 group, with a LRR of 10% at 3 years in those without residual DCIS, and 11% in those with residual DCIS. Both RCB&amp;gt;0 groups had significantly higher LRR when compared to the patients with RCB0 without DCIS (Hazard ratio: 5.25 [2.20-12.5]) and HR 5.85 [2.47-13.9] respectively). Conclusion: There was no association between residual DCIS and LRR after neoadjuvant chemotherapy, regardless of resolution of invasive disease. Further work is needed to determine whether residual DCIS should drive locoregional therapy decisions after neoadjuvant chemotherapy for invasive breast cancer. Citation Format: Marie Osdoit, Christina Yau, W. Fraser Symmans, Judy C. Boughey, Smita M. Asare, Ron Balassanian, Jodi M. Carter, Yunn-Yi Chen, Kimberly Cole, Laila Khazai, Molly Klein, Dina Kokh, Gregor Krings, Sunati Sahoo, Gretchen Ahrendt, Akiko Chiba, Cheryl Ewing, Constantine Godellas, Nora Jaskowiak, Brigid Killelea, Helen Krontiras, Rachael Lancaster, Julie Lang, M. Catherine Lee, Arpana Naik, Roshni Rao, Julia Tchou, Shannon Tierney, Eleni Tousimis, Tod Tuttle, Anne Wallace, I-SPY 2 TRIAL Consortium, Bev Parker, Laura J. Esserman, Rita A. Mukhtar. The impact of residual ductal carcinoma in situ on breast cancer recurrence in the neoadjuvant I-SPY2 TRIAL [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-16.

The ongoing evaluation and evolution of breast cancer surgical care.

Surgery has always been the backbone of breast cancer management. Throughout the past century, there have been great advances in chemotherapy regimens, especially in the neo-adjuvant setting. As a result of this progress, a patient's disease can be potentially down-staged and thus surgical intervention can therefore be de-escalated for the breast as well as the axilla. Current clinical trials are evaluating the role of imaging and core needle biopsy as predictive tools for the efficacy of neo-adjuvant chemotherapy. Results from these trials may help to clarify how the intricate relationship among imaging, pathology, radiotherapy, and surgery will affect the future management of patients undergoing neo-adjuvant chemotherapy for invasive breast cancer.

Re-Excision Rates in Breast-Conserving Surgery for Invasive Breast Cancer after Neoadjuvant Chemotherapy with and without the Use of a Radiopaque Tissue Transfer and X-ray System

Background: Significant re-excision rates in breast-conserving surgery (BCS) after neoadjuvant systemic chemotherapy may result from difficulties in defining the surgical target particularly in cases with excellent treatment response. Devices allowing an exact topographic localisation of the lesion in the resected tissue could reduce re-excision rates by optimising the intraoperative detection of involved margins. Methods: 80 patients with invasive breast cancer receiving BCS after neoadjuvant chemotherapy were included in this non-randomized case-control study. 40 patients with specimen radiography performed in a standard approach (control group) were compared to 40 patients with use of a radiopaque tissue transfer system (study group). Results: 19/80 (23.75%) patients required re-excision because of involved margins; among those, 14/40 (35%) were in the control group and 5/40 (12.5%) in the study group. The association between the use of the radiopaque tissue transfer system and the lower re-excision rate was statistically significant (p = 0.023). Conclusion: Our analysis provides a rationale for the routine use of a radiopaque tissue transfer system for specimen radiography in BCS after neoadjuvant chemotherapy for invasive breast cancer in order to reduce re-excision rates.

Comparable efficacy and less toxicity of pegylated liposomal doxorubicin versus epirubicin for neoadjuvant chemotherapy of breast cancer: a case-control study.

BackgroundPegylated liposomal doxorubicin (PLD) and epirubicin are both superior variants of doxorubicin and are commonly applied as basic chemotherapeutics in breast cancer. However, the direct comparison of their efficacy and side effects has not been adequately reported. This study aimed to compare the efficacy and toxicity of PLD and epirubicin as neoadjuvant chemotherapy for invasive breast cancer.Patients and methodsWomen (n = 43) with invasive breast cancer who received neoadjuvant chemotherapy with the regimens containing PLD (PLD group) were analyzed and 1:2 matched with those (n = 86) who received regimens containing epirubicin (epirubicin group) according to clinical TNM staging and taxane combination.ResultsThe PLD group achieved similar clinical response rate in neoadjuvant chemotherapy compared to the epirubicin group (76.7% vs 75.6%). The PLD group had a lower rate of grade 3 & 4 neutropenia (30.2% vs 60.5%), vomiting (7.0% vs 28.0%), and grade 3 & 4 alopecia (9.3% vs 43.0%), yet a higher rate of mouth ulceration (46.5% vs 11.7%). For the cardiac toxicity, the PLD group had a significantly lower rate of ventricular premature beat compared with the epirubicin group (7.0% vs 20.9%, p = 0.043), and cardiac ultrasonography monitoring showed non-significantly less PLD group patients’ left ventricular ejection fraction decline more than 10% compared with the epirubicin group (4.7% vs 8.1%, p = 0.463).ConclusionIn neoadjuvant chemotherapy for invasive breast cancer, PLD provides potentially similar efficacy and relatively less toxicity compared to epirubicin.

Abstract P5-08-02: Identify key regulators to modulate chemo-sensitivity of triple negative breast cancer by integrative analysis

Abstract Triple negative breast cancer (TNBC), which is characterized by lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2), is frequently associated with aggressive behavior and adverse patient outcomes and comprises a heterogeneous subgroup of tumors of diverse genomic features. Currently, TNBC patients are managed with only a few approved therapies and treatment strategies, including taxane-anthracycline chemotherapy. However, there is a subgroup of women with TNBC whose tumors are extremely sensitive to chemotherapy, but there are many women for whom chemotherapy is of uncertain benefit (1). To identify candidate therapeutic treatments for chemo-resistant patients of TNBC, we combined TNBC causal network modeling and chemo-response associated genes. We detected the differentially expressed genes according to chemo-responses by investigating expression profiles of TNBC samples with annotated information about responses to neoadjuvant chemotherapy(2), and constructed TNBC causal molecular network modeling by integrating epigenetic data with genetic, genomic, and transcriptomic data available for the Cancer Genome Atlas (TCGA) data(3). We leveraged the global causal network with genes associated with chemo-responses and detected highly connected chemo-sensitive subnetwork, which are enriched for Extracellular Matrix related pathways. The chemo-sensitive subnetwork was used to identify potential treatments to enhance chemosensitivity in two ways: 1) to identify key drivers that perturb genes within subnetwork based on number of directed connections, and 2) to identify repurposed therapeutics by comparing our chemo-sensitive subnetwork to the transcriptomic response to drug treatment(4). We identified the activity of microRNA let-7g was the most upstream key regulator that perturbs several collagen genes, suggesting the potential mechanism of chemosensitivity involved the extracellular matrix pathway. Additionally, we predicted candidate drugs including Genistein to modulate chemo-sensitivity, which was experimentally validated in TNBC cell lines. Taken together, the results demonstrated that our novel integrative approach of multi-omics data is useful to identify potential therapeutic targets to treat chemo-resistant TNBC patients by modulating chemo-sensitivity. 1. Bianchini, G., Balko, J.M., Mayer, I.A., Sanders, M.E. and Gianni, L. (2016) Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nature reviews. Clinical oncology. 2. Hatzis, C., Pusztai, L., Valero, V., Booser, D.J., Esserman, L., Lluch, A., Vidaurre, T., Holmes, F., Souchon, E., Wang, H. et al. (2011) A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. Jama, 305, 1873-1881. 3. Cancer Genome Atlas, N. (2012) Comprehensive molecular portraits of human breast tumours. Nature, 490, 61-70. 4. Lamb, J., Crawford, E.D., Peck, D., Modell, J.W., Blat, I.C., Wrobel, M.J., Lerner, J., Brunet, J.P., Subramanian, A., Ross, K.N. et al. (2006) The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science, 313, 1929-1935. Citation Format: Lee E, Ito K, Irie HY, Zhu J. Identify key regulators to modulate chemo-sensitivity of triple negative breast cancer by integrative analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-08-02.

Abstract P2-12-06: Re-excision rates in breast conserving surgery for invasive breast cancer after neoadjuvant chemotherapy with and without the use of a radiopaque tissue transfer and X-ray system

Abstract Background: Published re-excision rates after breast conserving surgery for invasive breast cancer vary between 20 and 50%. In patients after neoadjuvant chemotherapy even higher re-excision rates may result from difficulties in defining the surgical target particularly in cases with excellent treatment response. Specimen radiography is reducing re-excision rates, however, defining involved margins is often difficult using standard approaches. Devices allowing horizontal and vertical examination and an exact topographic localization of the lesion in the resected tissue could reduce re-excision rates by an intraoperative detection of involved margins. Methods: 80 patients with invasive breast cancer receiving breast conserving surgery after neoadjuvant chemotherapy and an indication for wire marking by mammography were included in this analysis. All tumors were marked with titanium clips prior to chemotherapy. In 40 patients specimen radiography was performed in a standard approach (control group), in 40 patients a tissue transfer and X-ray system based on a non-radiopaque board with radiopaque topographic markers and a stand for cranio-caudal X-rays was used (study group). A univariate analysis was carried out to evaluate the association between the use of the radiopaque tissue transfer system and the re-excision rate using a logistic regression model. Calculations were performed using the XLSTAT Biomed Software (Version 19.03, Addinsoft, NY, USA.). Results: 19/80 patients (23.75%) required re-excision because of involved margins; among those patients, 14/40 (35%) were in the control group and 5/40 (12.5%) in the study group. The association between the use of the radiopaque tissue transfer system and the lower re-excision rate was statistically significant (p=0.023). Conclusion: Our analysis provides a rationale for the use of a radiopaque tissue transfer system for specimen radiography in breast conserving surgery after neoadjuvant chemotherapy for invasive breast cancer in order to reduce re-excision rates. Based on these results we are planning a study including also patients receiving primary surgery. Citation Format: Kolberg H-C, Akpolat-Basci L, Stephanou M, Wetzig S, Cubuk Y, Gerharz J, Liedtke C. Re-excision rates in breast conserving surgery for invasive breast cancer after neoadjuvant chemotherapy with and without the use of a radiopaque tissue transfer and X-ray system [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-06.

Prognostic Value of Tumor-Infiltrating Lymphocyte Density Assessed Using a Standardized Method Based on Molecular Subtypes and Adjuvant Chemotherapy in Invasive Breast Cancer.

This study investigated the prognostic value of tumor-infiltrating lymphocyte (TIL) density as determined by molecular subtype and receipt of adjuvant chemotherapy in invasive breast cancer (IBC). Stromal TIL densities were evaluated in 1489 IBC samples using recommendations proposed by the International TILs Working Group. Cases were allocated to high- and low-TIL density groups using a cutoff of 10%. Of the 1489 IBC patients, 427 (28.7%) were assigned to the high-TIL group and 1062 (71.3%) to the low-TIL group. High TIL density was found to be significantly associated with large tumor size (p=0.001), high histologic grade (p<0.001), and high Ki-67 labeling index (p<0.001). Triple-negative and human epidermal growth factor receptor 2 (HER2)-positive subtypes had significantly higher TIL densities than luminal A or B (HER2-negative) subtypes (p<0.001). High TIL density was significantly associated with prolonged disease-free survival (DFS) by univariate (p<0.001) and multivariate (p<0.001) analyses. In the low-TIL-density group, the patients who did not receive adjuvant chemotherapy showed better DFS (p<0.001), but no such survival difference was observed in the high-TIL group (p=0.222). For the patients who received adjuvant anthracycline, high-TIL density was found to be an independent prognostic factor of favorable DFS in the luminal B (HER2-negative; p=0.003), HER2-positive (p=0.019), and triple-negative (p=0.017) subtypes. Measurements of TIL density in routine clinical practice could give useful prognostic information for the triple-negative, HER2-positive, and luminal B (HER2-negative) IBC subtypes, especially for patients administered adjuvant anthracycline.

Ki-67 expression and its effect on response to neo-adjuvant chemotherapy in invasive breast cancer

Objective: To investigate the response to neoadjuvant chemotherapy (NAC) among different molecular subtypes of breast cancers using molecular classification with Ki-67 (ER+ PR+ HER2+ Ki-67) or without Ki-67 (ER+ PR+ HER2). Methods: One hundred and twenty-seven cases of invasive breast cancer confirmed by core needle biopsy before NAC were collected from January 2007 to December 2009 and diagnosed at West China Hospital, Sichuan University. The cases were classified into different molecular subtypes using molecular classifications with or without Ki-67. Their clinical and pathological response to NAC was evaluated and compared. Results: The different subtypes using both molecular classifications showed significant difference in clinical response(with Ki-67: χ(2)=22.40, P<0.01; without Ki-67: χ(2)=9.202, P=0.027)but not pathological(P>0.05) response to NAC. By multivariate analysis, Ki-67 was predictive for a clinical complete response (P=0.041) and clinical overall response (P<0.01); also Ki-67 was the only clinicopathological factor predictive of pathological response(P=0.041). Conclusion: The molecular classification with Ki-67 is better to predict breast cancers responsiveness to NAC than the molecular classification without Ki-67.

Abstract P3-17-09: Resolution of DCIS in patients with early breast cancer receiving primary chemotherapy for invasive breast cancer

Abstract Background Ductal Carcinoma in Situ (DCIS) plays a pivotal role in surgical planning for patients who are to undertake primary chemotherapy. As DCIS is not thought to be responsive to chemotherapy, many women with large primaries or extensive DCIS on initial diagnosis will be planned for and undergo mastectomy. To investigate the role of chemotherapy in invasive breast cancer with concomitant ductal carcinoma in situ (DCIS), we examined patients who had primary systemic therapy for a primary invasive cancer with either radiologically or histologically proven DCIS to see if there were patients in whom there was no evidence of DCIS at resection. Methods This was a retrospective single centre study. Examining the records of all patients who had received primary chemotherapy between January 2010 and October 2014. Patients were identified through the Guy's breast cancer database and chemotherapy prescribing system. To fully assess the DCIS status, all patients were cross-referenced with the electronic notes on our electronic noting system (MOSAIQ), radiology on Patient Archiving and Communication System (PACS) and histology on our Electronic Patient Record (EPR). Results 1526 patients were identified, of whom 156 underwent primary chemotherapy. Of these, 46 patients had a pre-chemotherapy biopsy confirming DCIS, of whom 30 also had radiological evidence of DCIS. A further 26 had micro-calcification on their initial imaging which was presumed to be DCIS. Twelve of the 46 patients with biopsy proven DCIS at presentation did not have DCIS at resection. Of these 9 had a mastectomy, with 5 achieving a pathological complete response (pCR), of whom 4 had a complete radiological response (rCR). Of the 26 who had micro-calcification pre-chemotherapy, 15 did not have DCIS in the resection specimen. Of these, 10 had a mastectomy, with 6 having a pCR of whom 3 also had rCR. Conclusion This retrospective study suggests that chemotherapy can influence DCIS, with 12 biopsy proven having a pCR post treatment. This may indicate that some patients may be spared mastectomy. Although there were patients with radiological evidence of DCIS, without a confirmatory biopsy we cannot be sure that these were malignant. This highlights the need to ensure that all suspicious areas distant from the primary tumour should be biopsied before treatment. In conclusion, for patients who have an excellent clinical and radiological response, even in the presence of DCIS at presentation, more intensive evaluation is indicated if conservative surgery is a possibility. Citation Format: Chowdhury MHR, Thillai K, Lucey A, Michalarea V, Mera A, Karapanagiotou E, Sandri I, Mansi J. Resolution of DCIS in patients with early breast cancer receiving primary chemotherapy for invasive breast cancer [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 P3-17-09.

Use and Patterns of Supportive Care Among Patients Receiving Myelosuppressive Chemotherapy for Breast Cancer, Colorectal Cancer, Lung Cancer, or Non-Hodgkin's Lymphoma in US Clinical Practice

Background: Supportive care with colony-stimulating factors (CSFs) and antimicrobials (AMBs) is recommended for many patients receiving myelosuppressive chemotherapy for solid tumors or non-Hodgkin's lymphoma (NHL). However, evidence on the use and patterns of pharmacotherapy given to prevent, control, or relieve complications and side effects (such as febrile neutropenia [FN]), and to improve patient comfort and quality of life, among this patient population in US clinical practice is limited.Methods: A retrospective cohort design and data from four US health systems-Geisinger Health System, Henry Ford Health System, Kaiser Permanente Northwest, and Reliant Medical Group-spanning 2009-2013 were employed. The study population comprised all patients who received myelosuppressive chemotherapy for invasive breast cancer, invasive colorectal cancer, invasive lung cancer, or NHL. Data were collected via a standardized case report form (CRF) using electronic medical records systems, administrative data warehouses, medical charts, and cancer registries, and included patient demographics and clinical profile, cancer, treatment, and outcomes. For each subject, the first qualifying chemotherapy course, and each cycle and each FN episode within the course, was identified. Supportive care included prophylactic use of CSF agents (i.e., filgrastim, tbo-filgrastim, pegfilgrastim, and sargramostim) and AMBs (including antibiotics, antifungals, and antivirals), and were characterized on a cycle-specific basis in terms of agent received, dose, route of administration, timing, and duration of administration, as appropriate. Analyses described herein were descriptive in nature, and were based on an interim dataset.Results: The study population included a total of 527 patients who received myelosuppressive chemotherapy for breast cancer (n=281), colorectal cancer (n=95), lung cancer (n=95), or NHL (n=56) (Table). Among all subjects, mean (SD) age was 60 (13) years (40% aged ≥65 years), 17% had cardiovascular disease, 16% had lung disease, and 11% had diabetes; 33% of all patients had metastatic disease (7% of these patients had metastasis to bone), and 36% had previously received myelosuppressive therapy. Forty-two percent of all patients received CSF prophylaxis in cycle 1, and 55% received CSF prophylaxis in ≥1 cycles during their course; the mean number of CSF prophylaxis cycles, among those receiving these agents, was 3.9 (mean number of cycles in total, 7.1). Most patients received prophylaxis with pegfilgrastim (66%), and the remainder with filgrastim (34%). AMB prophylaxis was administered to 5% of patients in cycle 1 and 10% of patients at any time during their course. FN incidence proportion during the chemotherapy course was 14.2%, and was highest in cycle 1 (6.6%).Conclusion: In this retrospective evaluation of patients receiving myelosuppressive chemotherapy for breast cancer, colorectal cancer, lung cancer, or NHL, less than one-half of all patients (on average) received supportive care with CSF or AMB prophylaxis beginning in cycle 1 and few additional patients received CSF/AMB prophylaxis in subsequent cycles. FN was not uncommon, especially in the first cycle. Careful consideration should be given to identifying patients within this population who are at elevated risk of FN to ensure appropriate use of supportive care. [Display omitted] DisclosuresWeycker:Amgen, Inc.: Research Funding. Silvia:Amgen, Inc.: Research Funding. Richert-Boe:Amgen, Inc.: Research Funding. Bensink:Amgen, Inc.: Employment, Equity Ownership. Brady:Amgen, Inc.: Research Funding. Lamerato:Amgen, Inc.: Research Funding. Lipkovich:Amgen, Inc.: Research Funding. Siddiqui:Amgen, Inc.: Research Funding. Chandler:Amgen, Inc.: Employment, Equity Ownership.

Pathologic Complete Response Rates after Neoadjuvant Chemotherapy for Invasive Breast Cancer Vary by Facility Type and Volume at Commission on Cancer Accredited Centers

Pathologic Complete Response Rates after Neoadjuvant Chemotherapy for Invasive Breast Cancer Vary by Facility Type and Volume at Commission on Cancer Accredited Centers

Contrast-enhanced ultrasound (CEUS) in assessing early response among patients with invasive breast cancer undergoing neoadjuvant chemotherapy.

Background One of the big challenges in onco-radiology is to find a reliable imaging method that may predict early response during the first cycles of any neoadjuvant chemotherapy. Purpose To evaluate the use of real-time harmonic contrast-enhanced ultrasound (CEUS) in predicting early response in breast cancer tumors under neoadjuvant chemotherapy (NAC) treatment. Material and Methods Nineteen consecutive patients with invasive breast cancer were evaluated with a bolus dose of 2.4 mL contrast agent using CEUS, before and after two cycles of epirubicin and docetaxel. The lognormal function was used for quantitative analysis of kinetic data to evaluate early response. Results There was statistically significant difference in time-to-peak ( tp) between responders and non-responders (two sample t-test, P = 0.027) where tp was significantly longer at the week 5 than at the baseline scan among responders when compared to non-responders. Conclusion In-flow of intravascular contrast agent in tumors is significantly slower in responders at real-time harmonic CEUS, and might be effectively used for the evaluation of early response to chemotherapy in invasive breast cancer. However, further investigations in a larger and more heterogeneous population should be performed to corroborate the reliability of the method.