Follow-up Of Breast Cancer Patients Research Articles

CtDNA monitoring for breast cancer at high risk of recurrence: Interim analysis of JCOG1204A1.

518 Background: Monitoring ctDNA after definitive surgery has emerged as an accurate predictor of breast cancer (BC) recurrence. However, further data is needed to determine the proportion and dynamics of ctDNA positivity in different BC subtypes. Here we present ctDNA status and dynamics in patients from an ancillary study (A1) of the prospective randomized phase III JCOG1204 trial (UMIN000012429; Registration: November 2013 - January 2020, N = 1034) in which intensive post-operative follow-up is compared to standard follow-up in BC patients at high risk of recurrence. Methods: Eligible patients enrolled in JCOG1204 were required to have either (1) ≥4 lymph node metastases for estrogen receptor (ER)+ BC without neoadjuvant therapy, (2) ≥1 lymph node metastases for ER- without neoadjuvant therapy, or (3) ≥1 lymph node metastases after neoadjuvant therapy. Additional inclusion criteria for ancillary study JCOG1204A1 include no more than 4 years after surgery and relapse-free at the enrollment. A personalized, tumor-informed assay (Signatera, Natera Inc.) was used for ctDNA surveillance every 3 - 6 months for 2 years for ER- or 5 years for ER+ BC. ctDNA status, time of ctDNA detection and association with subtype were examined. The JCOG DSMC approved the publication of this interim analysis. Results: A total of 248 patients were enrolled (July 2020-October 2023) in JCOG1204A1. Personalized assays were successfully designed for 88% patients, the main reason for failure was insufficient tissue (83%; 25/30). A total of 1440 plasma ctDNA samples were collected from 211 patients. The median age at the time of surgery was 50 years. The most prevalent subtype was ER+ HER2- (Luminal; n = 130), followed by ER- HER2- (TN; n = 38), ER- HER2+ (HER2; n = 24), and ER+ HER2+ (Luminal-HER2; n = 18). 25 patients (11.8%) had at least one positive ctDNA result, with overall sample-level positivity proportion of 4.5% (65 / 1440); 76% (19/25) became detectable with longitudinal testing. Surveillance in TN [the first time point median 31.5 months (12.6-55.8) from surgery] did not result in ctDNA detection. Of the 130 patients with Luminal subtype [the first time point median 36.6 months (12-57) from surgery], 21 (16.2%) had ctDNA first detected at a median 43.5 months (18-72). Additionally, 5 patients (2.4%) had ctDNA detection for the first time after 5 years of surgery. The proportion of ctDNA positivity increased by ~2% annually in Luminal subtype; varied rates of ctDNA level increase have been observed. Conclusions: Monitoring ctDNA in high-risk BC reveals a detection proportion of 11.8% at the patient level (TNBC: 0%; Luminal: 16.2%) Longitudinal testing revealed ctDNA detection in patients with luminal subtype beyond 5 years from surgery, suggesting a correlation with late recurrence. Subsequent reports will focus on investigating the association of ctDNA status with relapse and overall survival.

Abstract PO3-06-02: Ten years axillary recurrence and survival after omission of axillary lymph node dissection in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node: A Danish national register study

Abstract Background: Until 2012, breast cancer patients with micrometastases (pN1mi) or isolated tumor cells (pN0(i)) in the sentinel node (SN) received axillary lymph node dissection (ALND). ALND is associated with lymphedema, paresthesia, functional impairment, and pain. In 2012, national Danish guidelines for patients with pN1mi and pN0(i) were changed reflecting several randomized clinical trials showing non-inferior prognosis when ALND was omitted. Since 2012, appr. 450 Danish breast cancer patients have been spared ALND each year. Development of axillary recurrence(AR) from minimal metastatic disease left in the axilla may take longer than experienced after macrometastatic disease. Hence, long-term follow-up is needed to evaluate the safety of omitting ALND for patients with pN1mi and pN0(i). Therefore, we aimed to investigate these outcomes with 10 years of follow-up. Methods: In this national register-based study, we included all women with primary breast cancer surgery between 01.01.2008 and 31.12.2021, who had pN1mi and pN0(i) in the SN. Women treated between 01.01.2008-31.12.2011 had received ALND, while in women treated between 01.01.2012 and 31.12.202,1 ALND was omitted. The two groups were compared with SN-negative patients (pN0) without ALND. The primary outcome was AR, and the secondary outcome was overall survival (OS). Information on surgery, nodal status, and recurrence were retrieved from the national Danish breast cancer group (DBCG) database. The definitions of pN1mi, pN0(i) and pN0 were according to AJCC, 8TH edition. We analyzed patient- and tumor characteristics with descriptive statistics, χ2 and Fisher exact test. The cumulative incidence of AR was calculated. OS was estimated using the Kaplan-Meier method and compared with a log-rank test. The effect of ALND was estimated with a Cox proportional hazards model, adjusting for age at operation, histology, malignancy grade, hormone receptor, HER2 status, and whether they received adjuvant systemic treatment or radiation therapy. With all statistical analysis, a two-tailed α-level of 0.05 was used. Results: 22,790 patients were included in the study. Overall,14.3% had pN1mi, 8.6% had pN0(i) and 77.1% had pN0. Of pN1mi or pN0(i) patients, 1490 had an ALND; 1227 patients with pN1mi and 263 patients with pN0(i). In 3737 patients ALND was omitted: 2036 with pN1mi and 1701 with pN0(i). Regarding the primary outcome, 1.1% of patients with pN1mi or pN0(i) had an AR, while 0.5% of the pN0 patients had AR. Analyzing patients with pN1mi or pN0(i) with or without ALND, 0.2% and 1.5%, respectively, had an AR. In subanalysis of patients with pN1mi with or without ALND, 0.2% and 1.8%, respectively, had an AR. In a subanalysis of patients with pN0(i), no patients with pN0(i) and ALND had an AR, while 1.1% of patients with pN0(i) had an AR when ALND was omitted. OS after 10 years of follow-up for the group of patients with pN1mi or pN0(i) was 81.5%; 83.7% for patients with and 79.12% for patients without ALND. For pN0 patients without ALND OS was 82%. This difference between the three groups was statistically significant(p< 0,01). However, when adjusting for risk factors, there was no statistically significant difference in OS between the patients with pN1mi or pN0(i) with and without ALND (p=0.6). Likewise, no statistically significant difference was found in OS, when looking at the subgroups of pN1mi with or without ALND (p=0.5) and pN0(i) with and without ALND(p=0.41). Conclusion: In this large register-based nationwide study we found a slightly higher rate of AR after 10 years of follow-up in breast cancer patients with micrometastases or isolated tumor cells in the SN if ALND was omitted. However, the axillary recurrence rate was low (< 2%), and after adjusting for other risk factors the increased recurrence rate did not affect OS. These results confirm the safety of omitting ALND in these patients. Citation Format: Riazan Hawaz-ali, Frederikke Munck, Tove Tvedskov, Niels Kroman. Ten years axillary recurrence and survival after omission of axillary lymph node dissection in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node: A Danish national register study [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 PO3-06-02.

A novel approach for segmentation and quantitative analysis of breast calcification in mammograms.

Breast cancer is a major threat to women's health globally. Early detection of breast cancer is crucial for saving lives. One important early sign is the appearance of breast calcification in mammograms. Accurate segmentation and analysis of calcification can improve diagnosis and prognosis. However, small size and diffuse distribution make calcification prone to oversight. This study aims to develop an efficient approach for segmenting and quantitatively analyzing breast calcification from mammograms. The goal is to assist radiologists in discerning benign versus malignant lesions to guide patient management. This study develops a framework for breast calcification segmentation and analysis using mammograms. A Pro_UNeXt algorithm is proposed to accurately segment calcification lesions by enhancing the UNeXt architecture with a microcalcification detection block, fused-MBConv modules, multiple-loss-function training, and data augmentation. Quantitative features are then extracted from the segmented calcification, including morphology, size, density, and spatial distribution. These features are used to train machine learning classifiers to categorize lesions as malignant or benign. The proposed Pro_UNeXt algorithm achieved superior segmentation performance versus UNet and UNeXt models on both public and private mammogram datasets. It attained a Dice score of 0.823 for microcalcification detection on the public dataset, demonstrating its accuracy for small lesions. For quantitative analysis, the extracted calcification features enabled high malignant/benign classification, with AdaBoost reaching an AUC of 0.97 on the private dataset. The consistent results across datasets validate the representative and discerning capabilities of the proposed features. This study develops an efficient framework integrating customized segmentation and quantitative analysis of breast calcification. Pro_UNeXt offers precise localization of calcification lesions. Subsequent feature quantification and machine learning classification provide comprehensive malignant/benign assessment. This end-to-end solution can assist clinicians in early diagnosis, treatment planning, and follow-up for breast cancer patients.

MR-contrast enhanced mammography (CEM) for follow-up of breast cancer patients: a "pros and cons" debate.

Women with a personal history of breast cancer (PHBC) are at an increased risk of either a local recurrence or a new primary breast cancer. Thus, surveillance is essential for the detection of recurrent disease at the earliest possible stage, allowing for prompt treatment, and potentially improving overall survival. Nowadays, mammography follow-up is the only surveillance imaging technique recommended by international guidelines. Nevertheless, sensitivity of mammography is lower after breast cancer treatment, particularly during the first 5 years, due to increased density or post-treatment changes. Contrast-enhanced breast imaging techniques, such as MRI or contrast-enhanced mammography (CEM), are very sensitive to detect malignant enhancement, especially in dense breasts. This Special Report will provide arguments in favor of and against breast cancer follow-up with MRI or CEM, in a debate style between experts in Breast Imaging. Finally, the scientific points of pros and cons arguments will be summarized to help objectively decide the best follow-up strategy for women with a personal history of breast cancer. CLINICAL RELEVANCE STATEMENT: A personalized approach to follow-up imaging after conservative breast cancer treatment could optimize patient outcomes, using mammography as a baseline for most patients, and MRI or CEM selectively in patients with higher risks for a recurrence. KEY POINTS: • Women with a personal history of breast cancer are at an increased risk of either a local recurrence or a new primary breast cancer. • Breast cancer survivors may benefit from additional imaging with MRI/CEM, in case of increased risk of a second breast cancer, with dense breasts or a cancer diagnosis before age 50 years. • As survival after local recurrence seems to depend on the initial stage at diagnosis, imaging should be more focused on detecting tumors in the earliest stages.

Deciphering the Functional Status of Breast Cancers through the Analysis of Their Extracellular Vesicles.

Breast cancer (BC) accounts for the highest incidence of tumor-related mortality among women worldwide, justifying the growing search for molecular tools for the early diagnosis and follow-up of BC patients under treatment. Circulating extracellular vesicles (EVs) are membranous nanocompartments produced by all human cells, including tumor cells. Since minimally invasive methods collect EVs, which represent reservoirs of signals for cell communication, these particles have attracted the interest of many researchers aiming to improve BC screening and treatment. Here, we analyzed the cargoes of BC-derived EVs, both proteins and nucleic acids, which yielded a comprehensive list of potential markers divided into four distinct categories, namely, (i) modulation of aggressiveness and growth; (ii) preparation of the pre-metastatic niche; (iii) epithelial-to-mesenchymal transition; and (iv) drug resistance phenotype, further classified according to their specificity and sensitivity as vesicular BC biomarkers. We discuss the therapeutic potential of and barriers to the clinical implementation of EV-based tests, including the heterogeneity of EVs and the available technologies for analyzing their content, to present a consistent, reproducible, and affordable set of markers for further evaluation.

Circulating Tumor Cells in Breast Cancer: A Step Toward Precision Medicine for Real-Time Monitoring of Metastasis

Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive score based on degradation of glycosaminoglycans in the extracellular matrix for assessment of metastasis in patients with breast cancer. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of Metastases in patients with breast cancer. Cytokeratin 18 (CK18), Cytokeratin 19 (CK19) and CA15.3 were assayed in metastatic breast cancer patients (88), non-metastatic breast cancer patients (129) and healthy control (32). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CTC-MBS = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1. CTC-MBS score produces AUC of 1 for differentiate patients with metastatic breast cancer from those with non-metastatic breast cancer with sensitivity and specificity of a cut-off 0 (i.e., less than 0 the case is considered metastatic, whereas above 0 it is considered non-metastatic. CTC-MBS score is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer and could replace CA15.3 during screening and follow-up of breast cancer patients.

Echocardiographic Study of Left Ventricular Pressure-Strain Loop in Evaluating Changes in Left Ventricular Myocardial Work in Breast Cancer Patients After Chemotherapy.

This study aimed to evaluate the changes in the left ventricular (LV) myocardial work (MW) in breast cancer patients following chemotherapy by left ventricular pressure-strain loop (LVPSL).A total of 50 patients with newly breast cancer undergoing postoperative adjuvant chemotherapy containing anthracycline were selected. Echocardiography was performed before the treatment (T0), the second (T2) and fourth (T4) cycles of chemotherapy, and 3 (P3 m) and 6 (P6 m) months after the end of chemotherapy. The standard dynamic images of the required sections were collected. After off-line analysis, the routine, global myocardial strain, and global MW parameters were obtained, and the average regional MW index (RMWI) and regional MW efficiency (RMWE) at three levels of LV were calculated.Compared with those at T0 and T2, the global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and global longitudinal strain (GLS) gradually decreased and global wasted work (GWW) gradually increased at T4, P0, and P6 m. The mean RMWI and RMWE of the three levels of LV exhibited a gradually decreasing trend at T4, P0, and P6 m compared with those at T0 and T2. The GWI, GCW, GWE, mean RMWI, and RMWE (basal, medial, and apical) were negatively correlated with the GLS (r = -0.76, -0.66, -0.67, -0.76, -0.77, -0.66, -0.67, -0.59, and -0.61, respectively), whereas the GWW was positively correlated with the GLS (r = 0.55).The mean RMWI and RMWE are effective parameters to reflect the cardiotoxicity of LV, and LVPSL has certain value in the evaluation of the left ventricular myocardial work (LVMW) during anthracycline treatment and follow-up in breast cancer patients.

Abstract P5-08-04: Mammo-50: Mammographic surveillance in early breast cancer patients aged over 50 years – patient reported outcomes 3 years post diagnosis

Abstract Introduction: There is a lack of evidence or consensus on the optimum frequency and duration of mammographic surveillance and follow-up for breast cancer patients aged 50 years and older at diagnosis. Mammo-50 will provide clinicians with valuable, risk-adjusted information to guide their future practice and is due to report December 2023. Quality of life (QoL) was assessed in a sub-study of the main trial. Methods: A multi-centre, randomised controlled, phase III trial of annual mammography versus 2-yearly for conservation surgery and 3-yearly for mastectomy patients with an observational cohort to explore reasons for non-participation. The trial randomised 5235 women between April 2014 and September 2018 and a further 915 registered in the cohort; 90% of women agreed to participate in the QoL sub-study. QoL questionnaires were completed at trial entry (3 years post-surgery) and then annually for up to 10 years. The distress thermometer was used as a patient reported measure of distress and concerns throughout the trial. The trial team contacted the patient’s clinical care team informing them of the reasons causing patients’ high levels of distress. Results: A total of 4521 (74%) women completed the distress thermometer at baseline. Of these, 289 (6.4%) reported high levels of distress (score 8-10), 825 (18.2%) medium levels of distress (score 5-7), 2033 (45.0%) low levels of distress (1-4) and 1374 (30.4%) reported no distress. Levels of distress were similar across clinical characteristics including surgery type, disease type and ER status, but differed for hormone therapy use (p=0.004). Women who had stopped hormone therapy tended to have higher levels of distress than those who had never had hormone therapy or for whom hormone therapy was ongoing. The most common reasons for causing high levels of distress (score, 8-10) in the 289 patients were sleep problems and/or nightmares (135 (47%)), fatigue, exhaustion or extreme tiredness (132 (46%)), worry, fear or anxiety (111 (38%)), hot flushes (94 (33%)), pain (89 (31%)), memory or concentration (84 (29%)) and sadness or depression (84 (29%)) of patients. Conclusions: Within the Mammo-50 trial, 6.4% of women reported high levels of distress upon trial entry. A quarter of women reported high/medium levels of distress with sleep, fatigue, worry, hot flushes, memory and sadness/depression being the main concerns. Levels of distress were highest in those women who had stopped hormone therapy. These results have been fed back to the UK NCRI breast cancer symptom management group whose remit it is to identify and provide guidelines for supporting women with unmet needs. Acknowledgement and disclaimer: This study is funded by the NIHR HTA programme (project ref. 11/25/03). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Citation Format: Amy F. Campbell, Andrea Marshall, Janet A. Dunn, Peter K. Donnelly, Andy J. Evans, Nada I. Elbeltagi, David A. Cameron, Riccardo A. Audisio, Lesley Turner, Eila Watson, Sophie J. Gasson, Annie M. Young, Alastair M. Thompson, Mammo-50 Trial Management Group. Mammo-50: Mammographic surveillance in early breast cancer patients aged over 50 years – patient reported outcomes 3 years post diagnosis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-04.

Prognostic value of alkaline phosphatase and bone-specific alkaline phosphatase in breast cancer: A systematic review and meta-analysis.

Numerous studies have reported the clinical value of alkaline phosphatase (ALP) and its bone-specific isoforms (bone-specific alkaline phosphatase (BAP)) in breast cancer. The purpose of this meta-analysis was to summarize the prognostic value of serum ALP and BAP in breast cancer, especially focused on bone metastasis and survival. PRISMA guidelines were followed to conduct this review. Observational studies were searched in PubMed, Cochcrane Library and EMBASE to January 1, 2022. Data were extracted to explore the prognostic value of ALP and BAP. The quality of the included studies was assessed and the outcome effects were evaluated. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. Publication bias was assessed. There was a total of 53 studies with 22,436 patients included. For the primary outcome of survival, high levels of both ALP and BAP were associated with short survival time. The hazard ratio of high ALP level on overall survival was 1.72 (95% CI 1.37, 2.16, P < 0.001). For the secondary outcomes, a high ALP level (not BAP) was detected in breast cancer compared with healthy controls, and high levels of both ALP and BAP were risk factors for bone metastasis, while ALP (not BAP) was a risk factor for non-bone metastasis. This study showed that high levels of both serum ALP and BAP were associated with metastasis (BAP was associated with bone metastasis) and survival in breast cancer. The biomarkers could provide useful information for the early diagnostic assessment and monitoring in the follow-up of breast cancer patients.

Applying competing risks analysis to recurrences of primary breast cancer.

in time-to-event analysis, competing risks are observed when a subject is at risk of multiple types of events. A competing risk is an event that prevents the event of interest from happening or modifies its chance to occur. the purposes of this article are to provide an overview of competing risks analysis and to illustrate its application to the follow-up of breast cancer patients in order to estimate the risk of disease recurrence. cohort study. population-based random sample of patients with stage I-III primary female breast cancer diagnosed in 2000-2013, aged 15 years or older, resident in the Forlì health care district (northern Italy), treated surgically and with available information regarding disease laterality. subhazard ratio, hazard ratio and cumulative incidence function for loco-regional recurrences and distant metastasis during 10 years of follow-up. breast cancer recurrences were evaluated taking into account death from any cause and occurrence of a second primary breast cancer as competing risks. Recent developments in competing risks methodology were used. The results obtained were compared with those from the Cox regression model, in which the competing risks were not accounted for. estimating the risk of recurrence without accounting for the competing risks resulted in a divergence of the hazard/subhazard functions. Competing risks analysis is preferable when the statistical assumption of independence of end-points may be violated.

Analysis of the complications of endocrine therapy with tamoxifen in breast cancer: clinical and pharmacogenetic aspects. Prospective pharmacogenetic cohort study

Background. Tamoxifen is the drug of choice in ER-positive breast cancer (BC) therapy for perimenopausal women and one of the endocrine therapy options for menopausal patients. The pharmacological effect of tamoxifen can be influenced by the activity of cytochrome P450 (CYP) enzymes and P-glycoprotein transporters (Pg), and the genes encoding them have broad polymorphism, affecting serum concentrations of active metabolites. This article presents the overall results of a prospective population-based study of the clinical significance of genetic polymorphism of tamoxifen metabolic enzymes and transporters in breast cancer patients after radical treatment receiving adjuvant endocrine therapy with tamoxifen in outpatient settings during 2018-2019. The study was approved by the Research Ethics Committee of the Russian Medical Academy of Continuing Professional Education.&#x0D; Aim. To analyze the clinical presentation of endocrine therapy with tamoxifen in the adjuvant regimen and to assess the association of polymorphisms of genes encoding cytochrome P450 enzymes and drug transporter proteins with adverse events in BC patients.&#x0D; Materials and methods. One hundred and four women with stage I-III luminal breast cancer receiving adjuvant tamoxifen were examined for the presence of CYP2D6, CYP2C, and the following CYP3A gene polymorphisms: CYP2D6*4, CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, as well as the ABCB1 gene polymorphic marker (C3435T) encoding the P-glycoprotein. The allelic variants were identified using the real-time polymerase chain reaction; the test was performed in the Research Center of the Russian Medical Academy of Continuing Professional Education. The study material was buccal epithelium (double sampling) taken after informed consent signing.&#x0D; Results. Association analysis showed the association of different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9, and ABCB1 with tamoxifen adverse drug reactions, indicating the clinical significance of these polymorphisms.&#x0D; Conclusion. With the implementation of genetic testing of the studied polymorphisms into the routine clinical practice of oncologists prescribing tamoxifen and gynecologists involved in the follow-up of breast cancer patients receiving endocrine therapy in the adjuvant mode, there will be an opportunity for more effective and safer pharmacotherapy.

913 Patient Satisfaction with Personalised Stratified Follow-Up After Treatment for Breast Cancer at West Middlesex University Hospital

Abstract Aim Personalised stratified follow up (PSFU) is a programme that ensures safe follow-up of breast cancer patients following treatment completion, avoids un-necessary appointments, whilst offering rapid access to clinicians when required. A protocol for PSFU was designed and the programme introduced to West Middlesex University Hospital in 2019. We aim to assess patient satisfaction with nurse-led end of treatment consultations. Method 200 Patients were enrolled from January 2019 to September 2021.The study was registered with the Clinical Governance department. All patients were initially contacted by telephone and later questionnaires were sent out either by post or using Google Docs via text messaging. Data was collected both from questionnaires and Somerset cancer registry platform and analysed using Microsoft Excel. Results Out of 200 patients, 150 were successfully contacted by telephone and sent questionnaires, with 68% response rate. This was largely electronic. 48% had video or phone consultations, with the rest attending in person. 90% thought they had sufficient time for discussion, with 82% feeling well informed regarding their management at the end of the consultation. 86% were satisfied or very satisfied with the consultation. 35% had their consultation within 3 months of completing treatment and 29% within 6 months. Conclusion Patients were largely satisfied with their end of treatment consultations. This was in spite of delays caused by the COVID-19 pandemic. Longer term follow up is required to determine satisfaction with the PSFU programme as a whole, and its efficiency.

Changes of Tumor Markers in Patients with Breast Cancer during Postoperative Adjuvant Chemotherapy.

Objective Serum tumor marker (STM) elevation can detect metastasis earlier than imaging diagnosis and, although not recommended by guidelines, is still widely used in clinical practice for postoperative follow-up of breast cancer patients. The purpose of this study was to investigate the change rules of CEA and CA153 in patients with HER2-negative breast cancer during postoperative adjuvant chemotherapy and their influencing factors. Materials and Methods The medical records of patients with HER2-negative early breast cancer who visited Xuanwu Hospital from September 2018 to June 2021 were retrospectively analyzed. Demographic characteristics and baseline data of CEA and CA153 at initial diagnosis were collected. Data of CEA, CA153, biochemistry (including ALT, AST, rGT, triglycerides, cholesterol, and blood glucose) and blood routine (including white blood cells, neutrophils, monocytes, lymphocytes, and platelets) were also collected before chemotherapy, at the end of chemotherapy and more than 3 months after the end of chemotherapy. LY/MONO, NEUT/LY, PLT/LY, and systemic immune inflammation index (SII) were calculated and statistically analyzed using SPSSAU software. Results A total of 90 patients were enrolled, all of whom were female, with a mean age of 55.11 ± 10.60 y. The value of CEA at initial diagnosis was 2.10 ± 1.11 ng/mL, and high expression was mostly correlated with past history of chronic diseases and tumor lymph node metastasis; the value of CA153 was 11.80 ± 6.60 U/mL, and high expression was correlated with high SII at initial diagnosis. Surgery did not affect the values of serum CEA and CA153. At the end of chemotherapy, CEA and CA153 were 2.68 ± 1.34 ng/mL and 18.51 ± 8.50 U/mL, respectively, which were significantly increased compared with those before chemotherapy, and were linearly correlated with the values before chemotherapy. They decreased (CEA 2.45 ± 1.19 ng/mL, CA153 10.87 ± 5.96 U/mL) again three months after the end of chemotherapy, manifested as “spiking” phenomenon, which was associated with lymph node metastasis at diagnosis, body metabolic disorders, and chronic inflammatory status. Conclusion CEA and CA153 were increased presenting as “spiking” phenomena in patients with early HER2-negative breast cancer during postoperative adjuvant chemotherapy, and the peak of increase was linearly correlated with the indicators before chemotherapy. Clinical attention should be paid to this change to avoid excessive diagnosis and treatment leading to medical resource consumption.

Taste alterations during neo/adjuvant chemotherapy and subsequent follow-up in breast cancer patients: a prospective single-center clinical study.

Dysgeusia and taste alterations (TAs) are side effects of cytotoxic chemotherapy and affect patients' quality of life; however, the prevalence, types, and duration of TAs and their potential relationship with other clinical disturbances are not well-described. Our primary aim was to prospectively evaluate the characteristics of TAs in early breast cancer (EBC) patients during (neo)adjuvant chemotherapy and up to 1year after its completion. From April 2014 to June 2018, 182 EBC patients entered the study and received (neo)adjuvant chemotherapy, mostly with taxane and anthracycline-containing regimens (65% of cases). A dietitian performed TAs assessment through the Common Terminology Criteria for Adverse Event v4.0 (CTCAE) and the Chemotherapy-induced Taste Alteration Scale (CiTAS) questionnaire during chemotherapy and follow-up according to defined time points: at baseline (T0, before starting chemotherapy); at the first follow-up visit, (T1, 2months after starting chemotherapy); at the final follow-up visit (T2, 1week after completing chemotherapy); after that, every 3months up to 12months. Dysgeusia was reported by 69.8% of patients at T1 and declined subsequently; salty flavor distortion was the most frequently reported TA (51.6% of cases). CiTAS was significantly different between T0 and T2 (p < 0.001). Dysgeusia occurred more frequently in patients reporting nausea, mucositis, diarrhea, and appetite modification. TAs are common but transient during chemotherapy and occurred frequently with other distressing gastrointestinal side effects. The assessment of these side effects is crucial in managing EBC patients during (neo)adjuvant chemotherapy.

Use of Routine Health Datasets to Assess the Appropriateness of Diagnostic Tests in the Follow-Up of Breast Cancer Patients: A Population-Based Study on 3930 Patients.

PurposeClinical practice guidelines (CPGs) recommend against intensive follow-up in asymptomatic women with breast cancer (BC). The present study assessed the adherence to CPGs of diagnostic tests ordering during BC follow-up by exploring routinely collected health data through an algorithm developed to distinguish patients according to their status at follow-up.Patients and MethodsA retrospective population-based cohort study was performed monitoring the diagnostic tests ordered during 5 years of follow-up in all BC cases incident in 2013 in the Veneto Region, Italy. Data were extracted from the Veneto Tumour Registry, the Hospital Discharge Records and the Outpatients’ Records of Diagnostic and Therapeutic Procedures. The algorithm was developed using information on infusion of anticancer agents, imaging exams ordered, and death.ResultsThe algorithm classified patients by status at follow-up in four groups: (i) probably no-evidence-of-disease (NED), (ii) suspicious signs of relapse not confirmed, (iii) increased risk of relapse and (iv) advanced disease at presentation or progressive disease. A total of 3930 consecutive incident cases were followed-up for 5 years, corresponding to 17,184 person-years, 15,345 of which pertaining to NED cases. In NED cases, 32,900 tumour markers and 15,858 imaging exams were ordered. Liver ultrasonography and chest radiography were most frequently ordered.ConclusionIn contrast with recommendations of CPGs, a substantial overordering of tumour markers and imaging exams occurred in NED BC patients. The developed algorithm can be repeatedly applied to routine health datasets for regular monitoring of the adherence to CPGs and of the impact of interventions to improve appropriateness.

Comprehensive management guideline for breast cancer follow-up and healthcare (2022 edition)

In recent years, with the emphasis on breast cancer screening and the improvement of standardized diagnosis and treatment, cure rate and survival time of breast cancer patients have been significantly improved in China. Accompanied by prolonged follow-up period, patients are facing increasing cancer and other related health issues, which calls for a more accurate and long-term follow-up plan and focus on broader health risks. Health issues on cardiovascular system, bone density, blood lipid and psychology caused by anti-cancer treatment, senescence or changes in hormone levels have become new challenges in the management of patients with breast cancer, not only affecting the life quality, but also impacting disease recurrence and death. Therefore, in addition to standardized treatment, scientific and standardized follow-up, comprehensive management of patients' concomitant diseases, interdisciplinary cooperation and holistic rehabilitation are also vital links to treatment. This could improve the therapeutic efficacy of anti-cancer treatment and the quality of life of patients. Based on the current landscape of treatment and follow-up of breast cancer patients in China, the experts committee updated the "Comprehensive Management Guideline for Breast Cancer Follow-up and Concomitant Diseases (2019 edition)" and revised it as "Guidelines for breast cancer follow-up and health management in China (2022 edition)" according to the latest literature and guidelines and medical advice from interdisciplinary experts. This new guideline is composed of four parts: path diagram, follow-up management, comprehensive healthcare management, and patient reported outcome. It aims to standardize the long-term follow-up of breast cancer patients, guide clinicians to actively provide comprehensive interdisciplinary healthcare management, and further improve the prognosis and life quality of breast cancer patients in China.

Risk factors associated with loss to follow-up of breast cancer patients: A retrospective analysis

BackgroundLoss to follow-up (LTFU) during post-operative surveillance of breast cancer patients is detrimental. The pattern of LTFU and its risk factors in Chinese breast cancer patients remains unknown. MethodEligible non-metastatic breast cancer patients who underwent surgery at our institution between 2009 and 2012 were included. The clinicopathological features, as well as the LTFU status, were retrieved from the REDCap database. LTFU was defined as the absence of patients for at least 12 months since her last contact. 5-year LTFU was defined as the LTFU status of each patients at 5 years after surgery. The incidence and potential risk factors of LTFU were analyzed. A LTFU-risk score was developed to quantify the risk of LTFU. ResultsA total of 1536 patients with breast cancer were included, and 411(26.8%) patients were 5-year LTFU. 198 patients were LTFU in the first year. Univariate and multivariate analysis revealed that age (younger and older), a lack of medical insurance, longer distance from residence to the hospital, pathology (DCIS/Paget’s/Phyllodes), lymph node metastasis, the absence of endocrine therapy and fewer than five contact numbers were significantly and independently associated with the risk of LTFU. A LTFU-risk score was developed and was predictive of LTFU. ConclusionsA series of risk factors were significantly associated with post-operative LTFU of breast cancer patients. Patients with different risks of LTFU could possibly be identified, and surveillance plans could be individualized for different patients, so as to effectively reduce the overall LTFU rate, and optimize the allocation of medical resources.

Prognostic value of circulating Bcl-2 and anti-p53 antibodies in patients with breast cancer: A long term follow-up (17.5 years).

Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis. This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.5-year follow-up of breast cancer patients. We also analyzed the correlations of Bcl-2 and p53Abs with various clinicopathological parameters in order to assess their impact on tumor aggressiveness. Serum Bcl-2 and p53Abs levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) in 82 patients with invasive breast cancer and twenty individuals without malignancy. Serum Bcl-2 and p53Abs levels in breast cancer patients were significantly higher than those in controls. Patients with high levels of Bcl-2 (cut-off 200 U/ml) had a poorer prognosis (17.5-year survival) than those with lower Bcl-2 values. In combined analysis the subgroup of patients with elevated p53Abs (cut-off 15 U/ml) and elevated Bcl-2 (cut-offs 124 U/ml and 200U/ml) had the worse prognosis in 17.5-year survival. In correlation analysis p53Abs and Bcl-2 were associated with unfavorable clinicopathological parameters. Our results suggest that breast cancer patients with high serum levels of p53Abs and Bcl-2 present an especially unfavorable group in a long follow-up.

The use of telemedicine to maintain breast cancer follow‐up and surveillance during the COVID‐19 pandemic

As a result from restricted economic activities and social distancing due to the coronavirus disease-2019 (COVID-19) pandemic, we observed a 49.4% decrease in outpatient appointments at our Institution. to minimize this impact on screening and oncological follow-up of breast cancer patients, telemedicine appointments were established. The authors demonstrate how a cancer center in the largest city in Brazil has managed outpatient appointments during the COVID-19 pandemic. This is a retrospective study of patients who had their appointments through telemedicine at the AC Camargo Cancer Center between June 2020 and October 2020, during the COVID-19 pandemic. Of the 77 patients who had telemedicine appointments, 36 (46.8%) accounted for breast cancer follow-up, 20 (26%) for breast cancer screening, 10 (13%) for benign breast disease evaluation, 7 (9%) for a second opinion, and 4 (5.2%) for general orientations. Routine surveillance/follow-up exams were requested for 45 (58.4%) patients and breast image exams and a request to return for a personal appointment for 30 (39%) patients. Two (2.6%) patients were requested to schedule a personal appointment immediately for a physical exam. In conclusion, telemedicine may be a feasible alternative to reduce personal outpatient appointments for cancer follow-up and breast cancer screening during the COVID-19 pandemic.

Diagnostic accuracy of non-contrast abdominopelvic computed tomography scans in follow-up of breast cancer patients.

To evaluate the effectiveness of follow-up with non-enhanced CT (NECT) in patients with breast cancer. The present retrospective study included 1396 patients with breast cancer. Group A included patients with no metastasis to evaluate the diagnostic performance of NECT in detecting newly developed metastasis. Group B included patients with known hepatic metastasis to evaluate the accuracy of NECT for the assessment of hepatic metastasis. Group A included 895 patients (mean age 52.8 years). Among them, 145 patients had 160 metastases. The per-patient sensitivities for diagnosing newly developed metastasis were 68.3 and 53.8% according to the two reviewers, while the per-lesion sensitivities were 89.4 and 85.0%. Sensitivities for bone metastasis were 98.9 and 95.9%, while sensitivities for hepatic metastasis were 73.7 and 68.4%. In group B, the accuracy of hepatic metastasis response evaluation according to the RECIST criteria was 70.8% for reviewer 1 and 63.8% for reviewer 2. NECT showed inadequate diagnostic performance in detecting newly developed metastasis and in evaluating the response of hepatic metastasis. However, NECT can be utilized as a follow-up modality in patients with decreased renal function or hypersensitivity to iodinated contrast media. The risk of side effects of contrast media should be considered as important when NECT can be utilized as a follow-up modality in decreased renal function patients.