Chemotherapy For Primary Breast Cancer Research Articles

De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study.

Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline. In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed. 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group. In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline. Dutch Cancer Society. For the Dutch translation of the abstract see Supplementary Materials section.

1552O Chemotherapy-induced peripheral neuropathy (CIPN) prevention trial evaluating the efficacy of hand-cooling and compression in patients undergoing taxan-based (neo-)adjuvant chemotherapy for primary breast cancer: First results of the prospective, randomized POLAR trial

CIPN is a common, dose-limiting side effect of taxane-based chemotherapy. Currently there is no established strategy for prevention or treatment. Smaller studies suggest that cooling or compression could have a preventive effect. In this randomized trial we investigated the effectiveness of one-sided hand-cooling or compression for the prevention of CIPN. 122 breast cancer patients who received weekly (nab-)paclitaxel-based (neo-)adjuvant chemotherapy were 1:1 randomized to either cooling or compression of the dominant hand. No intervention was performed on the other hand. Cooling was performed with a frozen glove (Elasto-Gel; 84400APT Cedex, Akromed), compression was applied by two surgical gloves (one size smaller than tight-fitting size) 30 minutes before, during and 30 minutes after taxane therapy. The primary endpoint was efficacy to prevent grade ≥2 sensory polyneuropathy evaluated by Common Terminology Criteria for Adverse Events v4.0 (CTCAE). In a second hierarchical test, CIPN rates between both intervention groups were compared. CIPN was further assessed by the Total Neuropathy Score (TNSc), patient self-report questionnaires (EORTC-QLQ-CIPN20), MR-neurography (n=21) and nerve conduction studies. Additionally, we evaluated onycholysis, skin toxicity, quality of life, CIPN-associated dose-reductions, treatment discontinuations and potential risk factors. Cooling and compression were highly effective in preventing grade ≥2 CIPN (cooling: 25 vs. 46%; p-value=0.0008; compression: 23 vs. 39%; p-value=0.0016) with similar efficacy (no significant difference was found: p-value=0.7303). MR-neurography was highly sensitive for detecting CIPN showing increased T2 nerve-to-muscle signal ratio indicating edematous nerve changes. Updated results will be presented. POLAR is the first trial to compare cooling and compression for preventing CIPN. Both interventions were highly effective and almost halved the risk of grade ≥2 CIPN. These findings could play an important role beyond gynecological oncology.

Radiation therapy on the axilla after neoadjuvant chemotherapy.

The introduction of primary systemic therapy has established a new treatment paradigm for breast cancer patients. However, recommendations for regional node irradiation after neoadjuvant chemotherapy are not supported by level I evidence, yet. In addition to strategies optimising systemic treatments and surgery, current discussions focus on tailoring radiation therapy for breast cancer. Especially in view of the increasingly pivotal role of neoadjuvant chemotherapy, gauging the extent of radiation therapy in the breast and nodal volumes. The current review focuses on recent evidence regarding radiation therapy of the breast and axilla in patients receiving neoadjuvant chemotherapy for primary breast cancer based on a PubMed and EMBASE literature search for publication years 2020-2022.

Abstract P4-06-06: Role of lymphatic SEC62 expression in prediction of treatment response in patients undergoing neoadjuvant chemotherapy for primary breast cancer

Abstract Background Chromosome 3q26 amplifications have been shown to represent a frequent alteration in various cancer entities including breast cancer. SEC62 - a 3q26 encoded gene - was identified as a potential onco- and tumor-driver gene for the pathogenesis of breast cancer. Sec62 seems to induce an increased stress tolerance, enhanced cell migration and proliferation in SEC62 overexpressing cells. Patients with SEC62 overexpressing breast cancer have been shown to have a higher rate of lymph node metastasis and poorer overall prognosis. Hence, we aspired to further evaluate the function of lymphatic SEC62 expression and its predictive role on the response to neoadjuvant chemotherapy. Objectives We aimed to assess the role of lymph node SEC62 expression as a predictive biomarker for response to neoadjuvant chemotherapy, besides we sought to evaluate potential differences in SEC62 expression levels in metastatic lymph node core biopsies and final pathology specimen according to breast cancer subtype. Material & Methods All nodal positive patients treated for primary breast cancer with neoadjuvant chemotherapy at the Department of Gynaecology and Obstetricts, Saarland University Hospital, Homburg, Germany between 01/2009 and 12/2019 were enrolled in this retrospective study. We analyzed SEC62 expression in tissue samples by immunohistochemistry (IHC). Sec62 immunoreactivity was evaluated using the immunoreactive score (IRS) according to Remmele and Stegner (0-12). For the assessment of the Sec62 protein content of the tumor cells, we rated Sec62 “low” for a score of 0-8, and “high” for 9-12 as described in previous publications. IHC was performed on initial lymph node core biopsy (CB) tissue (pre-treatment) or sentinel node biopsy specimen and on definite pathology specimen (PS) obtained during axillary dissection after completion of neoadjuvant chemotherapy.SEC62 expressions in both samples were compared and correlated with response to neoadjuvant chemotherapy, evaluated pathologically using the semi-quantitative response to neoadjuvant chemotherapy scoring system by Sinn et al. ranging from 0 (no effect) to 4 (no tumor detectable). Results 103 patients were assessed for eligibility. 15 cases were excluded, due to incomplete clinical information or insufficient slide quality, leaving 88 patients for final analysis. Median patient age was 55 (32-78) years and median response to neoadjuvant chemotherapy score of 2 (0-4). 11 (12.5%) patients had luminal A, 31 (35.2%) luminal B, 21 (23.9%) Her2/neu positive and 25 (28.4%) triple negative breast cancer. Median SEC62 expression in lymph node core biopsies was significantly higher compared to expression in final specimen (p<0.01). While no differences in basic expression of SEC62 in CB and the response to neoadjuvant chemotherapy were detected, patients with an IRS score ≤ 8 in PS and patients with a difference of IRS score ≥6 between CB and PS showed a significantly higher median response to neoadjuvant chemotherapy score compared to other patients (p< 0.01). Analyzing median Sec62 IHC expression in final pathology specimen, we observed significantly lower Sec62 scores for Her2/neu positive and triple negative patients compared to other subtypes (p<0.01). Median SEC62 expression showed the highest decrease between CB and PS in Her2/neu positive and triple negative patients. Regarding response to neoadjuvant chemotherapy, the effects described above could be observed in all breast cancer subtypes, but were strongest in triple negative patients. Conclusion We identified lymph node SEC62 expression as a promising biomarker for prediction of response to neoadjuvant chemotherapy in breast cancer patients. This effect seems to be strongest in patients with triple negative breast cancer. Citation Format: Julia Zimmermann, Anna Jung, Merle Doerk, Mariz Kasoha, Barbara Linxweiler, Maximilian Linxweiler, Mathias Wagner, Rainer Bohle, Marc Radosa, Erich Solomayer, Julia C Radosa. Role of lymphatic SEC62 expression in prediction of treatment response in patients undergoing neoadjuvant chemotherapy for primary breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-06-06.

286 Poster - PIK3CA mutations and predicting the therapeutic effects of neoadjuvant chemotherapy in primary breast cancer

Background: PIK3CA mutations are known to be associated with a reduced pathological complete response (pCR) rate in HER2+ breast cancer, but the relationship between PIK3CA mutations and the therapeutic effects of neoadjuvant chemotherapy in hormone receptor (HR) -positive or HR −/HER2− breast cancer is not clear. We herein analyzed PIK3CA mutations in primary breast cancers of patients who had undergone neoadjuvant chemotherapy. We also investigated the associations of these mutations with the therapeutic effects of neoadjuvant chemotherapy.

Association between gastrin-releasing peptide receptor expression as assessed with [68Ga]Ga-RM2 PET/CT and histopathological tumor regression after neoadjuvant chemotherapy in primary breast cancer

IntroductionThe gastrin-releasing peptide receptor is overexpressed in breast cancer (BC) tissue and can be visualized by positron emission tomography (PET) using the GRPR antagonist [68Ga]Ga-RM2. This study assessed tumor binding of RM2 before and after neoadjuvant chemotherapy (NAC) in primary BC with reference to residual tumor size in the resected specimen. Materials and methodsIn this retrospective study, five female patients with biopsy-confirmed estrogen receptor (ER)-positive primary BC (one with bilateral tumors) underwent [68Ga]Ga-RM2 PET/CT before and after NAC. PET/CT was acquired 1 h after injection of 143–224 MBq [68Ga]Ga-RM2. Time from pre-NAC PET to beginning of NAC was 23 ± 4.9 days, from end of NAC to post-NAC PET 18.7 ± 6.3 days, and from post-NAC PET to surgery 9.5 ± 10.8 days. In vivo tumor uptake of [68Ga]Ga-RM2 was assessed before and after NAC and correlated with histopathological response. ResultsAll tumors (6/6) showed strongly increased [68Ga]Ga-RM2 uptake compared to normal breast tissue on pre-NAC PET (mean SUVmax 13.2 ± 7.3; mean SUVpeak 9.4 ± 4.4). [68Ga]Ga-RM2 uptake was significantly reduced on post-NAC PET in all primary tumors (mean SUVmax 2.3 ± 0.8, −79 ± 11%; p = 0.0125; mean SUVpeak 1.6 ± 0.4, −79 ± 10%; p = 0.0096). Residual tumor size in resected specimens correlated well with SUVmax (r = 0.91, p = 0.0057) and SUVpeak (r = 0.88, p = 0.0196) on [68Ga]Ga-RM2 PET/CT after NAC. Conclusion and implications for patient careIn this pilot study, residual uptake of [68Ga]Ga-RM2 in ER-positive primary BC correlated well with residual vital tumor size after NAC. This suggests that [68Ga]Ga-RM2 PET/CT merits further investigation for response assessment to NAC in patients with ER-positive BC.

Abstract P3-11-22: Efficacy of two kinds of granulocyte colony-stimulating factors to support neoadjuvant dose-dense chemotherapy in primary breast cancer

Abstract Background and objective: Adjuvant chemotherapy is a critical part of systematic treatment of primary breast cancer. Chemotherapy induced neutropenia (CIN) is a common adverse event during adjuvant chemotherapy as well as a major factor limiting the implementation of the planned schedule of chemotherapy, causing the delay and drug reduction. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) effectively stimulates the proliferation of neutrophil progenitors, promotes differentiation of these cells into mature neutrophils, and promote the release of neutrophils from the marrow, thus reducing the probability of CIN and related complications. Dose-Dense (DD) chemotherapy has become a commonly recommended regimen for primary breast cancer because of improvement of disease-free survival (DFS) and Overall Survival (OS). rhG-CSF should be administered prophylactically due to the high incidence of marrow suppression during dose-dense regimen. Little high-level clinical evidence to determine a unified rhG-CSF regimen. Single injection of long-acting pegfilgrastim and continuous multiple usage of short-acting filgrastim are two major ways to support dose-dense adjuvant chemotherapy. Based on a single database, we retrospectively assessed the efficacy and safety of two different rhG-CSF in supporting the dose-dense adjuvant chemotherapy (ddEC) in primary breast cancer, aiming to test the effectiveness of two different rhG-CSF as well as comparison of the advantages and disadvantages of the two methods. Methods: Data of patients who received dose-dense neoadjuvant chemotherapy with support of rhG-CSF at Peking University Cancer Hospital Breast Cancer Prevention and Treatment Center from Jul, 2015 to Jun, 2018 were retrospectively collected. All of these patients were planned to receive four cycles of ddEC (Epirubicin 100mg/m2 and cyclophosphamide 600 mg/m2) with using one of the following rhG-CSF schedules in parallel: 1) filgrastim 200-300μg/d on day 4, 6, 8, 10; 2) pegfilgrastim 6mg on day 2. The relative dose intensity (RDI) was calculated. Results: A total of 555 patients were enrolled and 2,176 cycles were completed in this study, 254 were treated with pegfilgrastim and 301 were treated with short-term filgrastim. 536 patients (96.6%, 95%CI: 95.1%-98.1%) completed all four cycles of treatment. Chemotherapy delay occurred in 42 patients (7.6%, 95%CI: 5.4%-9.8%) for 47 cycles (2.2%, 95%CI:11.6%-2.8%). 18 patients (3.2%, 95%CI:1.7% - 4.7%) had CIN-related chemotherapy delay. 532 patients achieved RDI≥85% (99.4%, 95%CI:98.7%-100%). FN occurred in 25 patients (4.5%, 95%CI:2.8% - 6.2%). In the subgroup of using pegfilgrastim, Chemotherapy delay occurred in 10 patients (3.9%, 95%CI:1.5%-6.3%), 243 patients achieved RDI≥85% (99.4%, 95%CI: 98.7%-100%), and FN occurred in 11 patients (4.3%, 95%CI: 1.8%-6.8%). In the subgroup of using short-term filgrastim, chemotherapy delay occurred in 15 patients (5.0%, 95%CI: 2.5%-7.5%), 289 patients achieved RDI≥85% (96%, 95CI: 93.8%-98.2%), and FN occurred in 14 patients (4.7%, 95%CI: 2.3%-7.1%). FN is more likely in patients using short-term filgrastim (6.3%vs2.8%, p=0.048), causing more chemotherapy delay (10.8%vs4.1%, p=0.003). Age, tumor size, status of axillary lymph nodes, pathological type and baseline of ANC were not correlated with non-febrile neutropenia in patients using short-term filgrastim. Conclusion: Two schedules of rhG-CSF are effective and safe in supporting four cycles of neoadjuvant ddEC. The effects of these two methods were similar in the completion rate of chemotherapy(RDI≥85%) and safety(incidence of FN). Citation Format: Jingyi Zhao, Yingjian He, Zhaoqing Fan, Jinfeng Li, Xinguang Wang, Yang Yang, Xue Chen, Tao Ouyang. Efficacy of two kinds of granulocyte colony-stimulating factors to support neoadjuvant dose-dense chemotherapy in primary breast cancer [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 P3-11-22.

Abstract P4-02-10: Generation of nomograms to predict non-sentinel node metastasis and poorer patient response to neoadjuvant chemotherapy in primary breast cancer: A 10-year study

Abstract INTRODUCTION: The ability to predict non-sentinel node (non-SLN) metastasis in breast cancer patients has been an area of intense research for the past decade. This study aimed to identify predictors of non-SLN metastasis and level 3 node involvement. Further objectives included identifying factors which predicted poorer patient response to neoadjuvant chemotherapy (NAC). The final objective was to create mathematical models to predict non-SLN metastasis and level 3 disease. METHODS: Electronic patient records of 1088 patients who underwent ANC between 2007-2016 at the Royal Hallamshire Hospital, Sheffield, UK were reviewed. Clinicopathological characteristics were used to identify factors predicting lymph node metastasis. Significant predictors of axillary disease were incorporated into a nomogram using the first 75% of the cohort. Internal validation of the nomogram was performed using the remaining 25% of the study population. Four nomograms were created to predict non-SLN metastasis and level 3 disease in those who were had not received chemotherapy and those who underwent NAC. RESULTS: Larger tumour size (OR=1.025; CI=1.016-1.034; p<0.001), grade 3 (OR=3.706; CI=2.102-6.534) and grade 2 tumours (OR=2.174; CI=1.245-3.795) compared to grade 1 tumours (p<0.001), presence of lymphovascular invasion (LVI) (OR=2.832; CI=2.064-3.885; p<0.001), ER-negative tumours (OR=2.339; CI=1.472-3.717; p<0.001), and number of positive SLNs (OR=1.756; CI=1.333-2.313; p<0.001) were all significantly associated with non-SLN metastasis. In addition to these characteristics, lobular carcinomas (OR=1.832; CI=1.157-2.899; p=0.034) and multifocal tumours (OR=1.717; CI=1.108-2.662; p=0.016) were also significantly associated with level 3 disease. In patients who underwent NAC, larger tumour size (OR=1.040; CI=1.025-1.056; p<0.001), presence of LVI (OR=3.030; CI=1.673-5.488; p=0.001), and HER2-negative tumours (OR=1.983; CI=1.177-3.343; p=0.01) significantly predicted non-SLN metastasis, despite treatment. These same variables significantly predicted level 3 metastasis. In patients who did not receive NAC, the nomogram to predict non-SLN metastasis produced an AUC of 0.721 (CI=0.674-0.768). Internal validation produced an AUC of 0.781 (CI=0.708-0.854). A nomogram was produced to predict level 3 disease in non-NAC patients (AUC=0.771, CI=0.716-0.826). Validation provided accurate results (AUC=0.726, CI=0.625-0.826). A nomogram to predict non-SLN metastasis in NAC patients produced an AUC of 0.767 (CI=0.669-0.864). Validation produced an AUC of 0.838 (CI=0.666-1.000). An AUC of 0.806 (CI=0.0.711-0.901) was derived from the nomogram predicting level 3 disease in NAC patients. Validation produced an AUC of 0.879 (CI=0.742-1.000). CONCLUSION: Generation of a nomogram accurately predicted non-SLN metastasis and level 3 disease in those who did not receive NAC and those who underwent previous NAC. Incorporation of these mathematical models into the management of those with axillary disease will allow patients to make a more informed decision, whether they wish to proceed with full ANC, participate in a clinical trial, or choose to have their axilla re-staged following neoadjuvant chemotherapy. Citation Format: Sam Jenkins. Generation of nomograms to predict non-sentinel node metastasis and poorer patient response to neoadjuvant chemotherapy in primary breast cancer: A 10-year study [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 P4-02-10.

Overuse of Neo-adjuvant Chemotherapy for Primary Breast Cancer.

In recent years, there has been a wider use of chemotherapy in the pre-operative setting for breast cancer (i.e., as neo-adjuvant chemotherapy). Most clinicians would agree that neo-adjuvant chemotherapy is justified for patients with inflammatory breast cancer, locally advanced breast cancer, or patients with large tumors and small breasts who are keen to undergo breast-conserving surgery. However, in the USA and many other western countries, neo-adjuvant chemotherapy is now used for greater numbers of breast cancer patients who do not fall within these categories. Yet, randomized trials have consistently shown that there are no differences in overall survival (OS) between breast cancer patients treated with neo-adjuvant chemotherapy versus adjuvant chemotherapy. However, neo-adjuvant chemotherapy may increase the risk of loco-regional recurrence after breast-conserving surgery, perhaps because of an increased risk of leaving behind residual tumor foci. Moreover, the effects of neo-adjuvant chemotherapy on the primary tumor does not appear to be a suitable way for assessing the potential overall benefits of systemic therapy regimens on distant micrometastases and risk of death. Yet, based on the results of the KATHERINE and CREATE-X trials, one might argue that neo-adjuvant chemotherapy should be recommended for patients with HER-2-positive and triple-negative tumors to identify the subsets of patients who do not achieve pathologic complete response (PCR). Patients with HER-2-positive tumors who do not achieve PCR may benefit from additional treatment with T-DM1, and those with triple-negative tumors who do not achieve PCR may benefit from additional treatment with capecitabine.

Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial

BackgroundHow the immune microenvironment changes during neoadjuvant chemotherapy of primary breast cancer is not well understood.MethodsWe analyzed pre- and post-treatment samples from 60 patients using the NanoString PanCancer IO360™ assay to measure the expression of 750 immune-related genes corresponding to 14 immune cell types and various immune functions, and assessed TIL counts and PD-L1 protein expression by immunohistochemistry. Treatment associated changes in gene expression levels were compared using t-test with Bonferroni correction. TIL count, PD-L1 protein and immune metagenes were compared using Wilcoxon test. Baseline immune markers were correlated with pathologic complete response (pCR) using estrogen receptor and treatment arm adjusted logistic regression.ResultsAt baseline, high TIL counts and high expression of chemoattractant cytokines (CCL21, CCL19) and cytotoxic T cell markers were associated with higher pCR rate. High expression of stromal genes (VEGFB, TGFB3, PDGFB, FGFR1, IGFR1), mast and myeloid inflammatory cell metagenes, stem cell related genes (CD90, WNT11, CTNNB1) and CX3CR1, and IL11RA were associated with residual disease (RD). After treatment, in cases with pCR, TIL counts and most immune genes decreased significantly. Among RD cases, TIL counts and PD-L1 expression did not change but cellular stress and hypoxia associated genes (DUSP1, EGR1), and IL6, CD36, CXCL2, CD69 and the IL8/VEGF metagene increased.ConclusionsActivated T cells in the tumor microenvironment are associated with pCR whereas stromal functions are associated with residual disease. Most immune functions decrease during neoadjuvant chemotherapy but several immunotherapy targets (PD-L1, IL6, IL8) remain expressed in RD suggesting potential therapeutic strategies.

Dissimilar patterns of tumor-infiltrating immune cells at the invasive tumor front and tumor center are associated with response to neoadjuvant chemotherapy in primary breast cancer

BackgroundTumor-infiltrating lymphocytes (TILs) are described as an important immune modulator in the tumor microenvironment and are associated with breast cancer (BC) outcome. The spatial analysis of TILs and TIL subtype distribution at the invasive tumor front (ITF) and the tumor center (TC) might provide further insights into tumor progression.MethodsWe analyzed core biopsies from 87 pre-therapeutic BC patients for total TILs and the following subtypes: CD3+, CD4+, CD8+, CD20+ and CD68+ cells in correlation to clinicopathological parameters and disseminated tumor cells (DTCs) in the bone marrow.ResultsTILs and TIL subtypes showed significantly different spatial distribution among both tumor areas. TILs, especially CD3+ T cells were associated with the tumor status and tumor grading. BC patients responding to neoadjuvant chemotherapy had significantly more TILs and CD3+ T cells at the TC. The presence of DTCs after NACT was related to CD4+ infiltration at the TC.ConclusionThe dissimilar spatial association of TILs and TIL subtypes with clinicopathological parameters, NACT response and minimal residual disease underlines the necessity of detailed TIL analysis for a better understanding of immune modulatory processes.

Prediction of local recurrence risk after neoadjuvant chemotherapy in patients with primary breast cancer: Clinical utility of the MD Anderson Prognostic Index.

BackgroundLocoregional recurrence after neoadjuvant chemotherapy for primary breast cancer is associated with poor prognosis. It is essential to identify patients at high risk of locoregional recurrence who may benefit from extended local therapy. Here, we examined the prediction accuracy and clinical applicability of the MD Anderson Prognostic Index (MDAPI).MethodsProspective clinical data from 456 patients treated between 2003 and 2011 was analyzed. The Kaplan-Meier method was used to examine the probabilities of locoregional recurrence, local recurrence and distant metastases according to individual prognosis score, stratified by type of surgery (breast conserving therapy or mastectomy). The possible confounding of the relationship between recurrence risk and MDAPI by established risk factors was accounted for in multiple survival regression models. To define the clinical utility of the MDAPI we analyzed its performance to predict locoregional recurrence censoring patients with prior or simultaneous distant metastases.ResultsMastectomized patients (42% of the patients) presented with more advanced tumor stage, lower tumor grade, hormone-receptor positive disease and consequently lower pathological complete response rates. Only a few patients presented with high-risk scores (2,7% MDAPI≥3). All patients with high-risk MDAPI score (MDAPI ≥3) who developed locoregional recurrence were simultaneously affected by distant metastases.ConclusionOur data do not support a clinical utility of the MDAPI to guide local therapy.

A Single Centre Experience with Phenotype Dependent Perioperative Chemotherapy for Primary Breast Cancer

Background: Standard adjuvant or neo-adjuvant chemotherapy of primary breast cancers consists of docetaxel and the combination of anthracyclin-cyclophosphamide in two steps. According to international literature, the neo-adjuvant treatment of triple negative tumours by the combination of docetaxel-carboplatin allows a high rate of pathological complete remission and the adjuvant treatment of small, node negative HER2+ tumours by the combination of paclitaxel-trastuzumab allows a negligible recurrence rate together with a very good tolerance. Methods: Our aim was the retrospective analysis of the alternative chemotherapy regimens in our patient population. Results: The neo-adjuvant docetaxel-carboplatin allowed a 55% pathological complete remission rate among 20 patients. With the adjuvant paclitaxel-trastuzumab, we did not notice any recurrence among 5 patients at a median follow-up of 18 months. Conclusion: Our results correspond to the literature data. The spread of the protocols in the clinical practice is proposed.

Prediction of pathological complete response to neoadjuvant chemotherapy for primary breast cancer comparing interim ultrasound, Shear Wave elastography and MRI

Abstract Background Prediction of pathological complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NACT) may influence planned surgical approaches in the breast and axilla. The aim of this project is to assess the value of interim shear wave elastography (SWE), ultrasound (US) and magnetic resonance imaging (MRI) after 3 cycles in predicting pCR. Methods 64 patients receiving NACT had baseline and interim US, SWE and MRI examinations. The mean lesion stiffness at SWE, US and MRI diameter was measured at both time points. We compared four parameters with pCR status: a) Interim mean stiffness ≤ or > 50 kPat; b) Percentage stiffness reduction; c) Percentage US diameter reduction and d) Interim MRI response using RECIST criteria. The Chi square test was used to assess significance. Results Interim stiffness of ≤ or > 50 kPat gave the best prediction of pCR with pCR seen in 10 of 14 (71 %) cancers with an interim stiffness of ≤ 50 kPat, compared to 7 of 50 (14 %) of cancers with an interim stiffness of > 50 kPat, (p < 0.0001) (sensitivity 59 %, specificity 91 %, PPV 71 %, NPV 86 % and diagnostic accuracy 83 %). Percentage reduction in stiffness was the next best parameter (sensitivity 59 %, specificity 85 %, p < 0.0004) followed by reduction in MRI diameter of > 30 % (sensitivity 50 % and specificity 79 %, p = 0.03) and % reduction in US diameter (sensitivity 47 %, specificity 81 %, p = 0.03). Similar results were obtained from ROC analysis. Conclusion SWE stiffness of breast cancers after 3 cycles of NACT and changes in stiffness from baseline are strongly associated with pCR after 6 cycles.

O2-8-5 - Prognostic value of subtype changes after neoadjuvant chemotherapy in primary breast cancer

O2-8-5 - Prognostic value of subtype changes after neoadjuvant chemotherapy in primary breast cancer

Assessing residual cancer cells using MRI and US after preoperative chemotherapy in primary breast cancer to omit surgery.

Enhanced magnetic resonance imaging (MRI) and ultrasonography (US) are used to assess residual lesions after preoperative chemotherapy before surgery. However, residual lesion assessments based on preoperative imaging often differ from postoperative pathologic diagnoses. We retrospectively reviewed the accuracy of preoperative residual lesion assessments, including ductal carcinoma in situ (DCIS) cases to find criteria for cases in which surgery can be omitted. We reviewed 201 patients who received preoperative chemotherapy and surgery in our hospital from January 2013 to November 2016. Presurgical evaluations regarding the possible existence of residual lesions, and clinical Complete Response (cCR) or non-cCR, were compared with postoperative pathological diagnoses. Of the 201 patients, 52 were diagnosed with cCR, and 39 with pathological complete response (pCR). Predictions for residual lesions were 86.4% sensitive, 76.9% specific, and 84.6% accurate. When patients were divided into 4 groups by estrogen receptor (ER) and HER2 status, sensitivity in each group was ER+/HER2-: 91.4%; ER-/HER2-: 94.1%; ER+/HER2+: 78.6%; and ER-/HER2+: 78.5%. Of the 22 patients preoperatively assessed with cCR, but diagnosed with non-pCR, the median invasive residual tumor size was 2mm (range 0-46mm); 5 patients (22.7%) had only DCIS. Predicting residual lesions after preoperative chemotherapy by using MRI and US is a reasonable strategy. However, current methods are inadequate for identifying patients who can omit surgery; therefore, a new strategy for detecting small tumors in these patients is needed.

1605P - Safety and effectiveness of sensor-controlled scalp cooling in women receiving chemotherapy for primary breast cancer

1605P - Safety and effectiveness of sensor-controlled scalp cooling in women receiving chemotherapy for primary breast cancer

Long non-coding RNA CRALA is associated with poor response to chemotherapy in primary breast cancer.

BackgroundBreast cancer is the most commonly diagnosed cancer in women, and has become the second leading cause of cancer death among women worldwide. Chemoresistance has become an important problem in breast cancer clinics. The identification of new mechanisms affecting chemosensitivity is of great clinical value for the treatment of breast cancer.MethodsThe expression levels of chemoresistance‐associated long non‐coding RNA (CRALA), a newly discovered long non‐coding RNA, were measured by quantitative real time‐PCR in 79 pre‐treatment biopsied primary breast cancer samples. Small interfering RNAs were used to knockdown CRALA expression. The effect of CRALA on chemosensitivity was evaluated using cell growth assay.ResultsNon‐responding tumors (poor response to chemotherapy, 32 samples) had fourfold higher CRALA expression than responding tumors (good response to chemotherapy, 47 samples). CRALA is upregulated in chemoresistant breast cancer cell lines compared to their parental lines. Silencing of CRALA in chemoresistant breast cancer cells resensitizes the cells to chemotherapy in vitro. Furthermore, univariate and multivariate analysis showed that higher CRALA expression was significantly associated with poor prognosis in 144 breast cancer patients.ConclusionThe study findings indicate that CRALA expression may be an important biomarker for predicting the clinical response to chemotherapy and prognosis in breast cancer patients. It is possible to target CRALA to reverse chemoresistance in breast cancer patients.

Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0\xa0T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer

ObjectivesTo investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer.MethodsThis was a retrospective study of 88 consenting women (age: 30–79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2–3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated.ResultsMean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%.ConclusionsLesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy.Key Points• Texture analysis provides a means of measuring lesion heterogeneity on MRI images.• Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response.• Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes.• Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

Korean red ginseng extract enhances paclitaxel distribution to mammary tumors and its oral bioavailability by P-glycoprotein inhibition

1. Drug efflux by P-glycoprotein (P-gp) is a common resistance mechanism of breast cancer cells to paclitaxel, the primary chemotherapy in breast cancer. As a means of overcoming the drug resistance-mediated failure of paclitaxel chemotherapy, the potential of Korean red ginseng extract (KRG) as an adjuvant chemotherapy has been reported only in in vitro. Therefore, we assessed whether KRG alters P-gp mediated paclitaxel efflux, and therefore paclitaxel efficacy in in vitro and vivo models.2. KRG inhibited P-gp protein expression and transcellular efflux of paclitaxel in MDCK-mdr1 cells, but KRG was not a substrate of P-gp ATPase. In female rats with mammary tumor, the combination of paclitaxel with KRG showed the greater reduction of tumor volumes, lower P-gp protein expression and higher paclitaxel distribution in tumors, and greater oral bioavailability of paclitaxel than paclitaxel alone.3. From these results, KRG increased systemic circulation of oral paclitaxel and its distribution to tumors via P-gp inhibition in rats and under the current study conditions.