Chemotherapy In Breast Cancer Patients Research Articles

Cardiac Energetics Before, During, and After Anthracycline-Based Chemotherapy in Breast Cancer Patients Using 31P Magnetic Resonance Spectroscopy: A Pilot Study.

Purpose: To explore the utility of phosphorus magnetic resonance spectroscopy (31P MRS) in identifying anthracycline-induced cardiac toxicity in patients with breast cancer.Methods: Twenty patients with newly diagnosed breast cancer receiving anthracycline-based chemotherapy had cardiac magnetic resonance assessment of left ventricular ejection fraction (LVEF) and 31P MRS to determine myocardial Phosphocreatine/Adenosine Triphosphate Ratio (PCr/ATP) at three time points: pre-, mid-, and end-chemotherapy. Plasma high sensitivity cardiac troponin-I (cTn-I) tests and electrocardiograms were also performed at these same time points.Results: Phosphocreatine/Adenosine Triphosphate did not change significantly between pre- and mid-chemo (2.16 ± 0.46 vs. 2.00 ± 0.56, p = 0.80) and pre- and end-chemo (2.16 ± 0.46 vs. 2.17 ± 0.86, p = 0.99). Mean LVEF reduced significantly by 5.1% between pre- and end-chemo (61.4 ± 4.4 vs. 56.3 ± 8.1 %, p = 0.02). Change in PCr/ATP ratios from pre- to end-chemo correlated inversely with changes in LVEF over the same period (r = −0.65, p = 0.006). Plasma cTn-I increased progressively during chemotherapy from pre- to mid-chemo (1.35 ± 0.81 to 4.40 ± 2.64 ng/L; p = 0.01) and from mid- to end-chemo (4.40 ± 2.64 to 18.33 ± 13.23 ng/L; p = 0.001).Conclusions: In this small cohort pilot study, we did not observe a clear change in mean PCr/ATP values during chemotherapy despite evidence of increased plasma cardiac biomarkers and reduced LVEF. Future similar studies should be adequately powered to take account of patient drop-out and variable changes in PCr/ATP and could include T1 and T2 mapping.

Mutant Allele Frequency-Based Intra-Tumoral Genetic Heterogeneity Related to the Tumor Shrinkage Mode After Neoadjuvant Chemotherapy in Breast Cancer Patients.

The shrinkage mode of tumor extent after neoadjuvant chemotherapy (NAC) is an important index to evaluate the odds of breast-conserving surgery. However, there is no sufficient measurement to predict the shrinkage mode after NAC. In this study, we analyzed 24 patients' formalin-fixed, paraffin-embedded samples before and after treatment and analyzed 456 cancer-related genes panel by using target next-generation sequencing. Meanwhile, the pathological shrinkage mode was reconstructed in three dimensions after surgery, and the genetic heterogeneity level was estimated by mutant-allele tumor heterogeneity (MATH). We measured the genetic intra-tumor heterogeneity and explored its correlation with the shrinkage mode after NAC. A total of 17 matched pair samples of primary tumor tissue and residual tumor tissue were successfully accessed. It was found that the most common mutated genes were TP53 and PIK3CA in both samples before and after NAC, and no recurrent mutations were significantly associated with the shrinkage mode. Besides, the MATH value of formalin-fixed, paraffin-embedded samples before and after NAC was analyzed by the area under the curve of the receiver operating characteristic, and it is feasible to classify patients into concentric shrinkage mode and non-concentric shrinkage mode in NAC based on the MATH threshold of 58. Our findings indicate that the MATH value was associated with the shrinkage mode of breast cancer in a non-linear model. Patients with the MATH value below the threshold of 58 before and after NAC displayed a concentric shrinkage mode. The area under the curve was 0.89, with a sensitivity of 0.69 and specificity of 1. Our study might provide a promising application of intra-tumor heterogeneity that is measured by MATH to make a choice of surgery.

Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

Gene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.

Association between the genetic polymorphisms of the pharmacokinetics of anthracycline drug and myelosuppression in a patient with breast cancer with anthracycline-based chemotherapy

AimsExploring the genetic polymorphisms involved in the metabolism of anthracyclines can explain the causes of individual differences in myelosuppression during anthracycline-based chemotherapy. Main methodsBy PCR and Sanger sequencing, SNP of candidate genes participating into the pharmacokinetics of anthracycline, including chemotherapeutic drug intake (SLC22A16 rs6907567), metabolism (AKR1A1 rs2088102, CBR1 rs20572) and transfer (ABCG2 rs2231142) are detected in 194 breast cancer patients undergoing anthracycline-based postoperative adjuvant chemotherapy. Key findingsThe CBR1 rs20572 (C>T) polymorphic allele, the ABCG2 rs2231142 (G>T) polymorphic allele, or the two polymorphic allele in combination significantly reduced the risk of leukopenia (OR 0.412, 95% CI 0.187–0.905, p = 0.025) and neutropenia (OR 0.354, 95% CI 0.148–0.846, p = 0.018). Either polymorphic allele T of CBR1 rs20572, or polymorphic allele C of AKR1A1 rs2088102 combined with the presence of both ABCG2 rs2231142(G>T) and SLC22A16 rs6907567(A>G) mutations were at extremely low risk of severe anemia of grades 3 and 4 (OR 0.058, 95% CI 0.006–0.554, p = 0.008, OR 0.065, 95% CI 0.006–0.689, p = 0.022, OR 0.037, 95% CI 0.004–0.36, p = 0.015, respectively). SignificanceThese results suggested CBR1 rs20572, ABCG2 rs2231142, SLC22A16 rs6907567 and AKR1A1 rs2088102 might be potential protective factors for the reduction of hematologic toxicity incidence during anthracycline-based chemotherapy in breast cancer patients.

Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases.

The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed. We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases. The median follow-up was 7.2years, with a confidence interval (CI) of 7.1-7.3years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80-2.85, p = 0.208) for OS and 1.12 (95% CI 0.63-1.97, p = 0.705) for RFS. Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.

P078 - Application of conventional ultrasonography combined with contrast-enhanced ultrasonography in the lymph nodes and evaluation of the efficacy of neoadjuvant chemotherapy in breast cancer patients

P078 - Application of conventional ultrasonography combined with contrast-enhanced ultrasonography in the lymph nodes and evaluation of the efficacy of neoadjuvant chemotherapy in breast cancer patients

Influences on pathologic complete response in breast cancer patients after neoadjuvant chemotherapy

PurposePathologic complete response is associated with longer disease-free survival and better overall survival after neoadjuvant chemotherapy in breast cancer patients. We, therefore, evaluated factors influencing pathologic complete response.MethodsPatients receiving neoadjuvant chemotherapy from 2015 to 2018 at the Saarland University Hospital were included. Patients’ age, tumor stage, tumor biology, genetic mutation, recurrent cancer, discontinuation of chemotherapy, and participation in clinical trials were extracted from electronic medical records. Binary logistic regression was performed to evaluate the influence of these factors on pathologic complete response.ResultsData of 183 patients were included. The median patient’s age was 54 years (22–78). The median interval between diagnosis and onset of chemotherapy was 28 days (14–91); between end of chemotherapy and surgery 28 days (9–57). Sixty-two patients (34%) participated in clinical trials for chemotherapy. A total of 86 patients (47%) achieved pathologic complete response. Patient’s age, genetic mutation, recurrent cancers, or discontinuation of chemotherapy (due to side effects) and time intervals (between diagnosis and onset of chemotherapy, as well as between end of chemotherapy and surgery) did not influence pathologic complete response. Patients with high Ki67, high grading, Her2 positive tumors, as well as patients participating in clinical trials for chemotherapy had a higher chance of having pathologic complete response. Patients with Luminal B tumors had a lower chance for pathologic complete response.ConclusionParticularly patients with high risk cancer and patients, participating in clinical trials benefit most from chemotherapy. Therefore, breast cancer patients can be encouraged to participate in clinical trials for chemotherapy.

The Role of Chemotherapy in Patients With HER2-Negative Isolated Locoregional Recurrence of Breast Cancer: A Multicenter Retrospective Cohort Study.

Background: The role of chemotherapy for isolated locoregional recurrence (iLRR) of breast cancer has not been firmly established after local therapies.Methods: We performed a multicenter, retrospective analysis to evaluate the clinical implications of chemotherapy in breast cancer patients with HER2-negative iLRR.Results: Of a total of 277 patients, 146 (52.7%) received chemotherapy for iLRR. Median follow-up duration was 56.1 months. Eighty-six (31.0%) patients had luminal B-like and 100 (36.1%) had TNBC iLRR. There was a trend of longer disease free survival (DFS) in the chemotherapy group (4-year DFS: 70.4 vs. 59.5%, HR = 0.68, 95% CI 0.45–1.02, log-rank p = 0.059). When adjusted with clinically relevant factors, DFS was significantly prolonged with chemotherapy (adjusted HR = 0.61, 95% CI 0.40–0.94, p = 0.023). Subgroup analyses for DFS showed patients with disease free interval (DFI) <5 years or prior chemotherapy had a benefit from chemotherapy (adjusted HR = 0.57, p = 0.018; adjusted HR = 0.51, p = 0.005, respectively). Regarding the molecular subtypes, a longer DFS with chemotherapy was observed both in luminal B-like (4-year DFS: 77.8 vs. 55.0%, HR = 0.51, 95% CI 0.27–0.99, log-rank p = 0.048) and in TNBC patients (4-year DFS: 61.9 vs. 42.8%, HR = 0.49, 95% CI 0.24–1.02, log-rank p = 0.056), but not in luminal A-like.Conclusions: The chemotherapy for iLRR of breast cancer should be individualized for each patient, considering DFI, prior chemotherapy, and molecular subtypes.

Factors Affecting Sleep Quality of Breast Cancer Patients with Chemotherapy

BACKGROUND: Poor sleep quality becomes the effect of chemotherapy in breast cancer patients. AIM: This study aimed to examine the factors that influence breast cancer patients’ sleep quality undergoing chemotherapy. METHODS: This research used an observational method with cross-sectional design. There were 26 breast cancer patients undergoing chemotherapy at Djojonegoro Regional Hospital in Temanggung, Central Java. The characteristics of the respondent are recorded, including the demographic characteristics, respondents’ sleep quality, and the physiological status data of the respondent. The researchers use the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality. Data were analyzed using Kendall’s Tau and Spearman’s rank correlation test and the Pearson Product-Moment Correlation test. RESULTS: The result showed that breast cancer patients’ sleep quality is classified as poor with PSQI score of 10.96 ± 3.13. The average age of the respondent was 50.08 ± 7.31 years. The major characteristic of the respondent were 80.77% had married, 42.30% had elementary education, 61.54% did not work, and 61.54% had Rp 0, - income. Based on breast cancer patients undergoing chemotherapy, the respondents lived in rice field environment (42.30%), diagnosed with breast cancer &lt;1 year (69.23%), had &lt;1 year chemotherapy (96.15%), had under mastectomy on the left breast (80.76%), and underwent chemotherapy as much as 7.23 ± 4.80 times. Based on sleep quality, the respondents lived with nuclear family (61.54%), had no comorbidities (76.92%), did not consume other drugs (100%), did not consume sleeping pills (80.76%), and used lights during sleep (65.38%). There is a correlation between sleep quality and age and with whom the respondent lives in the same house. CONCLUSION: It was concluded that breast cancer patients undergoing chemotherapy had poor sleep quality, and the factors related to sleep quality were age and with whom the respondent lived in the same house.

Accuracy and Reproducibility of Contrast-Enhanced Mammography in the Assessment of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients with Calcifications in the Tumor Bed.

This study aimed to evaluate contrast-enhanced mammography (CEM) accuracy and reproducibility in the detection and measurement of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with calcifications, using surgical specimen pathology as the reference. Pre- and post-NAC CEM images of 36 consecutive BC patients receiving NAC in 2012–2020, with calcifications in the tumor bed at diagnosis, were retrospectively reviewed by two radiologists; described were absence/presence and size of residual disease based on contrast enhancement (CE) only and CE plus calcifications. Twenty-eight patients (77.8%) had invasive and 5 (13.9%) in situ-only residual disease at surgical specimen pathology. Considering CE plus calcifications instead of CE only, CEM sensitivity for invasive residual tumor increased from 85.7% (95% CI = 67.3–96%) to 96.4% (95% CI = 81.7–99.9%) and specificity decreased from 5/8 (62.5%; 95% CI = 24.5–91.5%) to 1/8 (14.3%; 95% CI = 0.4–57.9%). For in situ-only residual disease, false negatives decreased from 3 to 0 and false positives increased from 1 to 2. CEM pathology concordance in residual disease measurement increased (R squared from 0.38 to 0.45); inter-reader concordance decreased (R squared from 0.79 to 0.66). Considering CE plus calcifications to evaluate NAC response in BC patients increases sensitivity in detection and accuracy in measurement of residual disease but increases false positives.

Abstract PS9-61: Incidence of intravenous (IV) hydration post anthracycline-cyclophosphamide (AC) chemotherapy in breast cancer patients

Abstract Background: Managing delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy (HEC) is an unmet need. AC-based HEC is often administered to breast cancer patients. The National Comprehensive Cancer Network and American Society of Clinical Oncology antiemetic guidelines recommend that if breakthrough CINV occurs, treatment should include an antiemetic agent from a different class not used in prophylaxis, as well as intravenous hydration and/or dexamethasone. The primary objective of this study is to retrospectively determine the incidence of IV hydration in post AC chemotherapy in breast cancer patients. Methods: The charts of 270 breast cancer patients receiving AC chemotherapy at University of Alabama at Birmingham (UAB) and on initial 3-drug prophylactic antiemetic regimens were retrospectively reviewed to determine the frequency, incidence, and timing of IV hydration. The hydration incidence was determined for 4 consecutive cycles of AC chemotherapy. The need for hydration was recorded post chemotherapy (e.g., nausea, vomiting, anorexia, loss of appetite, decreased oral intake). Physician and nurse chart notes were reviewed, including documented hydration visits post AC chemotherapy to outpatient infusion areas, local hospital emergency departments, or local hospital inpatient admissions. This report focuses on the patients who were on a guideline-recommended 3-drug regimen (palonosetron [Palo] + Neurokinin-1 [NK1] + dexamethasone [Dex], or ondansetron [Ond] + NK1 + Dex). These patients were followed and monitored for 4 consecutive cycles of AC chemotherapy, and the incidence of hydrations in different cycles was evaluated. Results: 270 patients were included in this analysis; 179 patients received Palo + NK1 + Dex (Group 1) and 91 patients received Ond + NK1 + Dex (Group 2) antiemetic regimens. Of the 179 patients in Group 1, 28 (16%) received hydration post chemotherapy, and 20 (22%) of the 91 patients in Group 2 received hydration (P=0.198, Chi-square test). Demographics and clinical characteristics of the 48 patients receiving hydration are presented in the Table. 28 patients in Group 1 had a total of 36 hydrations, the majority (20 [56%]) of which were in Cycle 1. 26/28 patients received rescue antiemetic treatment at the time of hydration, and 11 had a change in their prophylactic antiemetic regimen after hydration in subsequent chemotherapy cycles. Similarly, in Group 2, 20 patients had a total of 25 hydrations, with the majority (13 [52%]) in Cycle 1. 19 patients received rescue antiemetic treatment at the time of hydration, and 10 had a change in their prophylactic antiemetic regimen in subsequent chemotherapy cycles. Conclusions: The incidence of IV hydration post chemotherapy in breast cancer patients following AC-based HEC regimens occurred predominantly in the first cycle. Unscheduled hydrations, which occur when patients require evaluation in the clinic, and/or emergency department, may be complementary events for breakthrough measurement in CINV and could serve as a surrogate of associated healthcare utilization costs. Further clinical trials may consider evaluating unscheduled hydrations rates as part of a composite complete response endpoint (no breakthrough, no rescue medication, no unscheduled hydration). Table: Demographic and Antiemetic Regimens for Patients Requiring Post-chemo HydrationGroup 1Group 2Palo + NK1 + DexOnd + NK1 + Dex(n=179)(n=91)Post-chemo hydration, n (%)28 (16)20 (22)Demographics and Clinical Characteristics of Patients with Post-chemo Hydration (n=48)Median age, years (range)s56 (35-73)58 (33-70)Sex, n (%)Female27 (96)20 (100)Male1 (4)0ECOG Performance Status, n (%)015 (53)12 (60)112 (43)7 (35)201 (5)Unknown1 (4)0IV access, n (%)Central26 (93)20 (100)Peripheral2 (7)0Antiemetic Regimens Prior to Chemotherapy and Hydration RequirementsTotal number of patients requiring hydration, n (%)28 (16)20 (22)Total number of hydrations, n3625Number of hydrations in Cycle 1, n (%)20 (56)13 (52)Visits, n (%)Office16 (57)12 (60)Emergency department12 (43)8 (40)Rescue antiemetic(s) at time of hydration, n (%)26 (93)19 (95)Prophylactic antiemetic regimen switched, n (%)11 (39)10 (50)Dex = dexamethasone; ECOG = Eastern Cooperative Oncology Group; IV = intravenous;NK1 = Neurokinin-1; Ond = ondansetron; Palo = palonosetron. Citation Format: Rudolph M. Navari, Michael C. Mosier. Incidence of intravenous (IV) hydration post anthracycline-cyclophosphamide (AC) chemotherapy in breast cancer patients [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 PS9-61.

Abstract PS1-44: Impact of a standardized protocol for management of axilla after neoadjuvant chemotherapy in breast cancer patients at a cancer center

Abstract Background: Axillary lymph node status is one of the most important prognostic factors in breast cancer (BC). Neoadjuvant Chemotherapy (NACT) has been indicated for locally advanced tumors, and for HER2-positive and triple negative tumors larger than 2.0 and 1.0 cm, respectively, regardless of axillary status. This approach allows to assess biological response of the tumor, predicting prognosis and may permit more conservative surgeries in breast and axilla. However, there is no consensus about the best approach on management of axilla after NACT. Objective: To evaluate the rate of axillary downstaging after NACT in BC patients using a standardized protocol with a clip marker placement on positive lymph nodes prior to chemotherapy at a Cancer Center. Methods: This single-center, Institutional Review Board (IRB)-approved, retrospective study evaluated 471 BC patients who underwent NACT from January/2014 to December/2018. All included patients were evaluated for histological type, clinical T and N stages before NACT, modality of breast surgery (mastectomy vs. lumpectomy), type of axillary dissection (Axillary Lymph Node Dissection [ALND], sentinel lymph node biopsy [SLNB], or SLNB followed by ALND), placement or not of a clip marker in axillary lymph nodes before NACT, reason for the ALND and the pathological response by residual cancer burden (RCB) criteria. Patients were divided in two groups, before and after institution of a standardized protocol for axillary management after NACT in January/2017, which consists of: (1) biopsy of clinically suspect axillary lymph nodes before NACT, and placement of a clip marker in one positive lymph node in patients with 1-2 suspected lymph nodes (N1); (2) SLNB after NACT using blue dye and radioactive isotope injection; (3A) in the presence of clip marker in an axillary lymph node, confirmation of its extraction is performed through radiography of the surgical specimen and, (3B) in the absence of clip markers on axillary lymph nodes, removal of at least 03 sentinel lymph nodes should be performed; (4) no further axillary dissection is performed if all SLN are negative on frozen section analysis; any residual lymph node disease and/or absence of previously placed clip marker on SLNB specimen indicate ALND.Results: Patients’ mean age was 47 years (range 24-87 years), 67.2% (n=316) were cT2-T3, 83.5% (n=393) cN+ (N1 and N2), 62.6% (n = 295) had mastectomy. ALND was performed in 64.7% (n=303) patients, SLNB in 33.3% (n=156) and SLNB followed by ALND in 1.9% (n=9). In the subgroup of N+ patients (n=385), it was possible to perform SNB in 25.6% (n=98). 165 of 471 patients (35%) were included in standardized protocol for axillary management; the rate of SLNB in N+ patients was statistically higher in this group when compared to patients treated before the implementation of the protocol (34.4% vs. 22.8%; p=0.025).Conclusion: The results of the present study demonstrate a significant increase in sparing ALND after the implementation of a standardized protocol for management of axilla after NACT. However, further multi-institutional studies are still needed to support its widely adoption, as well as clinical trials to assess overall and disease-free survival in those patients who had omitted ALND after NACT. Citation Format: Marina de Paula Canal, Caroline Rocha, Marina Sonagli, Almir Bitencourt, Solange Sanches, Monique Tavares, Cynthia Osório, Fabiana Baroni Makdissi. Impact of a standardized protocol for management of axilla after neoadjuvant chemotherapy in breast cancer patients at a cancer center [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 PS1-44.

Abstract SS1-06: Racial disparities in pathological complete response among breast cancer patients receiving neoadjuvant chemotherapy

Abstract Background: With the increasing use of neoadjuvant chemotherapy in breast cancer patients, it is important to better understand how host factors interact with tumor characteristics to determine response to neoadjuvant chemotherapy. Pathological complete response (pCR) is a strong surrogate for long term survival in certain subtypes of breast cancer. Racial disparities in breast cancer survival have been well documented, but few studies have been conducted to examine the extent of racial disparities in pCR after neoadjuvant chemotherapy. Method: We established a cohort of patients with breast cancer treated at an academic medical center in the ethnically diverse City of Chicago — the Chicago Multiethnic Epidemiologic Breast Cancer cohort (ChiMEC). Among patients who received neoadjuvant chemotherapy, we examined whether racial disparity existed in the rate of pCR, defined as ypT0/isypN0. Multivariable logistic regression models were used to estimate the odds ratios (ORs) of black relative to white patients, adjusting for clinical tumor stage and molecular subtype. We also explored whether there were racial difference in treatment characteristics, including days from diagnosis to the first neoadjuvant chemotherapy and dosage of 7 most commonly used drugs (Carboplatin, Cyclophosphamide, Docetaxel, Doxorubicin, Paclitaxel, Trastuzumab and Pertuzumab) using Wilcoxon rank-sum tests. Results: The study consisted of 595 stage I-III breast cancer patients who received neoadjuvant chemotherapy (51% Whites and 40% Blacks). Among them, 32.5% of the White patients achieved pCR while only 23.9% of the Black patients achieved pCR (Table). After adjusting for tumor subtype and clinical stage, Black patients still had a significantly lower odds of achieving pCR compared to Whites (OR=0.67, 95% CI: 0.44-1.00). The racial difference in pCR rates existed in all four molecular subtypes, though most pronounced in the HR-/HER2+ subgroup (OR=0.35, 95% CI: 0.13-0.97). Further adjusting for time from diagnosis to first chemotherapy reduced the racial difference (OR=0.76, 95% CI: 0.50-1.15), suggesting that some of this racial disparity could be explained by delay in treatment initiation. This hypothesis is also supported by the observation that the largest racial difference in treatment initiation was in the HR-/HER2+ subgroup, with White patients taking an average of 30.9 days to get their first chemotherapy after diagnosis while Black patients taking an average of 45.4 days (P = 0.019). In addition, the study found that Black patients received significantly less cycles of Cyclophosphamide and Doxorubicin (i.e., the AC regimen) than White patients (P = 0.024). Conclusion: Our study showed that Black patients had a lower pCR rate after neoadjuvant chemotherapy, and this racial disparity was largest among HR-/HER2+ patients. Although delayed initiation of treatment may partially contribute to this racial disparity, treatment differences in this single institution study are relatively small so most of racial disparity in response to neoadjuvant therapy could be due to biological difference beyond subtypes. Host and tumor characteristic that modulate response to therapy in diverse populations deserve further exploration to optimize design of innovative clinical trials and reduce disparities in clinical outcomes. Racial disparity in pCR stratified by subtype and adjusted for tumor and treatment characteristicspCR rateOdds Ratio (95% CI)Adjusted Odds Ratio (95% CI)*Adjusted Odds Ratio (95% CI)+WhiteBlackBlack vs. WhiteBlack vs. WhiteBlack vs. WhiteOverall32.5%23.9%0.66 (0.45-0.96)0.67 (0.44-1.00)0.76 (0.50-1.15)SubtypeHR+/HER2-17.5%12.3%0.66 (0.27-1.63)0.69 (0.28-1.72)0.74 (0.30-1.85)HR+/HER2+28.6%22.9%0.74 (0.31-1.77)0.77 (0.32-1.86)0.86 (0.35-2.09)HR-/HER2+70.0%43.3%0.33 (0.12-0.88)0.35 (0.13-0.97)0.44 (0.16-1.23)TNBC35.4%26.3%0.65 (0.35-1.21)0.78 (0.42-1.47)0.88 (0.47-1.68)* adjusted for subtype, clinical T stage and clinical N stage+ adjusted for subtype, clinical T stage, clinical N stage and days from diagnosis to first chemotherapy Citation Format: Fangyuan Zhao, Meghan Steiner, Abiola Ibraheem, Gini Fleming, Nora Jaskowiak, Rita Nanda, Olufunmilayo I. Olopade, Dezheng Huo. Racial disparities in pathological complete response among breast cancer patients receiving neoadjuvant chemotherapy [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 SS1-06.

Abstract PD9-06: Peripheral blood gene signatures predict response to neoadjuvant chemotherapy in breast cancer patients

Abstract Purpose: Neoadjuvant chemotherapy (NAC), the standard of care for a subset of breast cancer patients, is known to have immunologic effects. With emerging data showing improved response rates with anti-PD-1/PD-L1 immunotherapy in combination with chemotherapy, the effects of NAC on systemic and local anti-tumor immunity require further study. Biomarkers of anti-tumor immunity are needed to identify which patients are most likely to respond to immunotherapy. Our previous work has shown that changes in the peripheral blood can be observed over the course of NAC for breast cancer. Peripheral blood biomarkers are attractive because of the relative ease of sampling compared to site of disease. Residual cancer burden (RCB) is a useful surrogate marker of long-term prognosis, as patients who experience a pathologic complete response (pCR) have better outcomes than those with residual disease (RD). Methods: We previously identified an 8 gene signature of cytotoxicity, derived from single cell RNA sequencing of PD-1Hi CD8+ T cells, which are enriched for tumor-reactive T cells. Using a custom NanoString panel, we tested expression of this gene signature in whole blood collected prior to definitive surgery in 88 breast cancer patients (TNBC, n=21; HER2+, n=17; ER+, n= 54; PR+, n=53) across two cohorts (VUMC, n=58; DFCI, n=30), 64 of whom had received NAC (pCR, n=11; RD, n=53). We further investigated peripheral blood gene expression using RNA sequencing (n=58; 34 post-NAC, 24 untreated). Results: In two cohorts of breast cancer patients, expression of the 8 gene signature (FGFBP2 + GNLY + GZMB + GZMH + NKG7 + LAG3 + PDCD1 - HLA-G) was highest in patients with RD who experienced a recurrence within three years compared to those with pCR (p&amp;lt;0.01) or those with the highest RCB (RCB III) compared to those with RCB 0/I/II who did not have a recurrence with three years (p&amp;lt;0.05). RNA sequencing showed higher expression of interferon alpha, interferon gamma, and complement gene sets in patients experiencing a pCR compared to those with RD by gene set enrichment analysis (FDR-corrected q-values &amp;lt; 0.05). Conclusions: Expression of immune-related genes in the peripheral blood may predict response to NAC in breast cancer patients and be a useful biomarker for those who would benefit from additional therapies. These results will be further tested in a large cohort of longitudinal samples from breast cancer patients receiving NAC alone or in combination with pembrolizumab from the I-SPY-2 trial, to determine whether peripheral blood gene signatures can predict response to immunotherapy in breast cancer. Citation Format: Margaret L Axelrod, Paula I Gonzalez-Ericsson, Xiaopeng Sun, Riley E Bergman, Joshua Donaldson, Sara M Tolaney, Ian E Krop, Ana C Garrido-Castro, Melinda E. Sanders, Ingrid A Mayer, Justin M Balko. Peripheral blood gene signatures predict response to neoadjuvant chemotherapy in breast cancer patients [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 PD9-06.

Electromechanical changes of the myocardium after anthracycline chemotherapy

Abstract Funding Acknowledgements Type of funding sources: None. Background and objectives The most common side effects of chemotherapeutics in breast cancer is on the cardiovascular system. Global longitudinal strain (GLS) is the only parameter recommended for follow-up in current guidelines with limited evidence. Other strain imaging parameters and electrical changes after chemotherapy is not well studied. It is not known whether electrical or mechanical changes occur initially. The aim of this study is to evaluate repolarization parameters on ECG and mechanical changes together after chemotherapy in breast cancer patients. Subjects and method Consecutive patients who received chemotherapy due to breast cancer were included. Strain echocardiography and ECGs were performed pre-treatment (T0) and 3rd month after chemotherapy (T2). Additionally, just in three hours of first dose of chemotherapy (T1) another ECG was performed. QT and QT correction for heart rate (QTc), QT dispersion (QT disp) and QTc dispersion (QTc disp), T wave peak to end time (Tpe) and Tpe corrected for QT-QTc measurements were performed (figüre 1 and 2). GLS, longitudinal strain for myocardial layers, circumferential strain (CS), radial strain (RS) and torsion measurements were performed. All mechanical and electrical parameters from different time intervals were compared. Results Thirty-five consecutive patients (35 females, mean age 48.9 ± 11.8 years) who received chemotherapy (mean doxorubicin cumulative dose 415 ± 32 mg/m2) due to breast cancer were included. There was no significant change in mean GLS values before and after treatment (T0 -%18.8 ± 6.82, T1 18.6 ± 3.5 p = 0,863 respectively). However, there was a significant decrease in CS, RS and torsion (T0 -%17,2 ± 3,5, T1-%13 ± 2,84 p &amp;lt;0,001, T0 %45,1 ± 8,3, T1 %35,6 ±10 p &amp;lt;0,001 and T0 %12,1 ± 3.5, T1 %7.7 ± 2.1 p &amp;lt;0,001, respectively). QT, QTc, QTc disp and Tpe, Tpe/QTc parameters were prolonged just after chemotherapy and were still prolonged 3 months after ((QTc: T1 440.01 ± 27.63, T2 468.00 ± 38.98, T3 467.86 ± 35.09), (QTc disp T1 55.48 ± 20.22, T2 78.59 ± 16.15, T3 66.16 ± 14.62), (Tpe (QTc) T1 104 ± 18.52, T2 148.62 ± 19.16, T3 139.77 ± 21.63), (Tpe/QTc T1 0.213 ± 0.05, T2 0.281 ± 0.08, T3 0.258 ± 0.06). Conclusion Electrical and mechanical functions of the heart could be impaired together acutely even three months after doxorubicin chemotherapy. Cardio toxicity should be evaluated in terms of both electrically and mechanically. Abstract Figure. ECG repolarization parameters

Toxicity Effects of Anthracycline-Converted Herceptin and Azo-Functionalized Fe₃O₄ Nanoparticles on the Heart of Patients with Breast Cancer Based on Echocardiography.

The multifunctional nano-carrier system can simultaneously achieve multiple functions such as diagnostic imaging, targeted delivery of anti-tumor drugs, and combined therapy. Application potential Fe₃O₄ magnetic nanoparticles have the characteristics of low toxicity, superparamagnetism and good photothermal properties. Therefore, a multifunctional magnetic nanocarrier with both magnetic targeting and photothermal properties can be prepared by surface modification of Fe₃O₄ o DOX is an anti-tumor drug widely used in clinical treatment, and its severe toxic and side effects greatly limit its application. In this paper, a temperature-sensitive magnetic nanocarrier was first constructed and proved to have good superparamagnetism, photothermal properties, and biocom-patibility Then, Fe₃O₄-Azo-DOX drug-loaded nanoparticles were constructed by covalently bonding DOX. The prepared Fe₃O₄-Azo-DOX nanoparticles have high stability, sensitive photothermal response and low toxicity. Finally, Fe₃O₄-Azo-DOX was applied to the study of combined photother-motherapy and chemotherapy in vitro and in vivo. Based on Fe₃O₄ nanoparticles, a temperature-sensitive Fe₃O₄-Azo nanocarrier was constructed and its related properties were characterized. Furthermore, anthracycline nanodrugs were used in chemotherapy of breast cancer patients, and their effects were analyzed according to echocardiography parameter change. The results show that Fe₃O₄-Azo nanoparticles have a good photothermal heating effect. MCF-7 breast cancer cells were selected as a model to investigate the cytotoxicity of Fe₃O₄-Azo. The results proved that they have excellent biocompatibility and can be used as drug carriers. A Fe₃O₄-Azo nanocarrier was used to load DOX to construct a NIR-responsive nano-drug delivery system. By studying the NIR controlled release of Fe₃O₄-Azo-DOX under different pH conditions, it can be seen that it has NIR-responsive release function and the best release effect at pH 5.7. It was found that LVEF, LVFS, and E/A were significantly lower after chemotherapy than before (P < 0.05), which had a certain clinical value in cardiotoxicity The in vitro antitumor effect of Fe₃O₄-Azo-DOX was studied, and the results showed that the combined effect of photothermal-chemotherapy was significantly better than the photothermal treatment based on Fe₃O₄-Azo carrier alone and the chemotherapy based on free DOX alone.

Retrospective audit on time to surgery delays after completion of neoadjuvant chemotherapy in breast cancer patients.

Background: The ideal time period to surgery (TTS) after completion of neoadjuvant chemotherapy (NAC) with no compromise on survival outcomes is a debatable topic. The ideal interval from published literature is as low as 21 days, 40 days and up to 8 weeks. Medway Multidisciplinary team (MDT) accepted 28 days as reasonable time interval to recover from chemotherapy side effects. This retrospective clinical audit is a review of all cases of neoadjuvant chemotherapy looking at the conformity to the set audit standards.

Association between clinicopathological features of breast cancer with adipocytokine levels and oxidative stress markers before and after chemotherapy.

Adipocytokines and markers of oxidative stress have been shown to exhibit potential for detection of advanced stage, HER2/neu status and lymph node metastases in patients with breast cancer, as well as in determining the efficiency of anti-cancer treatments. In the present study, blood concentrations of apelin (APLN), retinol-binding protein 4 (RBP4), 8-hydroxydeoxyguanosine (8-oxo-dG) and total antioxidant capacity (TAC) in women with breast cancer with different clinicopathological features were measured prior to and following adjuvant chemotherapy. The study included 60 women with breast cancer stratified according to tumor grade and size, HER-2/neu expression, and lymph node and hormone receptor status. Blood samples were taken before and after two cycles of adjuvant chemotherapy. None of the clinicopathological features were associated with the baseline concentrations of RBP4, 8-oxo-dG or TAC. An increased baseline concentration of APLN was observed in HER-2/neu positive patients. Moreover, through multivariate logistical regression analysis, APLN was shown to be independently associated with a positive HER/neu status. Chemotherapy treatment did not affect the levels of RBP4 or APLN, or TAC values when assessing all the patients, and when assessing the stratified groups of patients. Only 8-oxo-dG was found to be significantly decreased following drug administration (P=0.0009). This preliminary study demonstrated that APLN is a significant and independent predictor of HER-2/neu positive breast cancer. A significant reduction in 8-oxo-dG levels following chemotherapy may indicate its potential clinical utility in monitoring the effects of chemotherapy in breast cancer patients.

Prospective Registry Trial Assessing the Use of Magnetic Seeds to Locate Clipped Nodes After Neoadjuvant Chemotherapy for Breast Cancer Patients.

Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds.

Working During Chemotherapy for Breast Cancer Patients

Working During Chemotherapy for Breast Cancer Patients