Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases.

BACKGROUND: Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups. METHODS: We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44. RESULTS: Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy-only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy-only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin. CONCLUSIONS: The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).

Completion axillary lymph node dissection for the identification of pN2-3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial.

BACKGROUND: In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1-2, grade 1-2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2-3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial. METHODS: In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1-T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1-2, histological grade 1-2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing. FINDINGS: Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52-71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6-59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery. INTERPRETATION: As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. FUNDING: Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.

International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations.

Novel systemic therapies for breast cancer are being rapidly implemented into clinical practice. These drugs often have different mechanisms of action and side-effect profiles compared with traditional chemotherapy. Underpinning practice-changing clinical trials focused on the systemic therapies under investigation, thus there are sparse data available on radiotherapy. Integration of these new systemic therapies with radiotherapy is therefore challenging. Given this rapid, transformative change in breast cancer multimodal management, the multidisciplinary community must unite to ensure optimal, safe, and equitable treatment for all patients. The aim of this collaborative group of radiation, clinical, and medical oncologists, basic and translational scientists, and patient advocates was to: scope, synthesise, and summarise the literature on integrating novel drugs with radiotherapy for breast cancer; produce consensus statements on drug-radiotherapy integration, where specific evidence is lacking; and make best-practice recommendations for recording of radiotherapy data and quality assurance for subsequent studies testing novel drugs.

A BRILLIANT-BRCA study: residual breast tissue after mastectomy and reconstruction.

INTRODUCTION: Different types of mastectomies leave different amounts of residual breast tissue. The significance of the residual breast volume (RBV) is not clear. Therefore, we developed an MRI tool that allows to easily assess the RBV. In this study we evaluated factors associated with RBV after skin or nipple sparing mastectomy (SSM/NSM) in breast cancer BRCA pathogenic variant (PV) carriers who underwent both therapeutic and risk reducing SSM/NSM and its relation to breast cancer outcomes using an innovative MRI-based tool. METHODS: Data of breast cancer BRCA PV who were treated between 2006 and 2020 were retrieved from of the oncogenetics unit databases. Only patients who underwent SSM/NSM and had a postoperative breast MRI available for analysis were included. Data collected included demographics, clinicopathological features, and outcomes. The MRI tool was developed by a breast cancer imaging laboratory. A logistic regression test and 95% confidence interval (CI) were used to assess the associated risk of increased RBV. A forward stepwise linear regression was used to correlate tumour-patient specific factors and RBV, and a Kaplan-Meier curve to show the probability of locoregional relapse. RESULTS: A total of 84 patients undergoing 89 mastectomies were included. At a median follow-up of 98 months, 5 local, 2 regional, and 4 distant recurrences were observed. RBV was not significantly related with breast cancer outcomes (p value = NS). A higher body mass index (BMI) was associated with a higher RBV (p < 0.0001). A larger number of involved axillary nodes was associated with a smaller RBV (p = 0.025). The RBV on the risk-reducing mastectomy side was significantly higher compared to the breast cancer side (p value = 0.007). Local recurrences occurred in the vicinity of the primary tumour.

Spot-scanning proton therapy for early breast cancer in free breathing versus deep inspiration breath-hold.

BACKGROUND AND PURPOSE: Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH. MATERIAL AND METHODS: Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2-3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time. RESULTS: All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality. INTERPRETATION: The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.

Prognosis of breast cancer patients with brain metastasis treated with radiotherapy.

BACKGROUND: Life expectancy for patients diagnosed with metastatic breast cancer (BC) has improved in recent years, especially due to better systemic treatment. This has led to an increased incidence of brain metastases (BM), and BC is now the leading cause of BM in women. Treatment of BM primarily consists of surgery and/or radiotherapy. We aimed to investigate survival time and prognostic factors for BC patients treated with radiotherapy for BM. MATERIAL & METHODS: During the period 1st of January 2015 to 1st of June 2020, 144 consecutive BC patients treated for BM from one centre were retrospectively analyzed. The patients were either diagnosed with BM as the first metastatic lesion, or developed BM during palliative therapy for distant non-brain metastasis. The study was approved by the Central Denmark Region. RESULTS: Median age at BM diagnosis was 66 years, and 90% of the patients already had extracranial metastatic disease at BM diagnosis. Median overall survival after diagnosis of BM was 6.1 months. Short survival was observed for patients with poor performance status, leptomeningeal metastasis or more than three solid BM. Several of these factors were overrepresented in patients with estrogen receptor-positive (ER+) tumours who had poorer survival than patients with different receptor status. CONCLUSION: The number of metastatic BC patients developing BM is high, and survival following local treatment remains poor. Several prognostic factors appear to influence survival after radiotherapy. Treatment of BC patients with BM should be individualized according to performance status, leptomeningeal disease, number of BM, and receptor status of the disease.

Diagnosis and treatment of breast cancer in Denmark during the COVID-19 pandemic: a nationwide population-based study.

BACKGROUND: The COVID-19 pandemic was a global health crisis with population-wide behavioural restrictions imposed worldwide to reduce transmission of infection and to limit the potential burden on the healthcare systems. We examined whether there was any change in the diagnosis or treatment of breast cancer during the pandemic as compared to previous years. MATERIAL AND METHODS: The study population comprised all women aged ≥18 years diagnosed with breast cancer in 2015-2021 with data obtained from the clinical quality registry of the Danish Breast Cancer Cooperative Group (DBCG). Data on socioeconomic factors were retrieved from Statistics Denmark. Prevalence ratios (PR) with 95% confidence intervals (CI) were estimated from a generalised linear model (GLM) with a log link for the Poisson family with robust standard errors (SE) of each outcome, using the COVID-19 pandemic period in Denmark as the exposure of interest. RESULTS: In total, 30,598 breast cancers were diagnosed during the study period. There was a small decrease (4.5%) in the total number of breast cancer cases in 2020 compared with previous years. During the pandemic, a lower proportion of the patients diagnosed with breast cancer had a short educational level (28.5 vs. 26.9%; PR = 0.91; 95% CI: 0.88-0.95), a low income (20.5 vs. 19.0%; PR = 0.90; 0.85-0.95) and fewer than expected in the age group 60-69 years (27.8 vs. 25.3; PR = 0.90; 0.86-0.94) were diagnosed, as compared with the pre-pandemic period. No difference in type of surgery or tumour size was observed. A higher proportion of patients received neo-adjuvant chemotherapy (49.0 vs 55.0%; PR = 1.15; 1.06-1.24), whereas a lower proportion received adjuvant chemotherapy (93.5 vs 85.6%; PR = 0.92; 0.90-0.93) during the pandemic, compared with the pre-pandemic period. CONCLUSIONS: During the pandemic, a small decrease in the number of breast cancer diagnoses was observed particularly among socially disadvantaged groups. Overall, the quality of breast cancer treatment was maintained.

Development of a national deep learning-based auto-segmentation model for the heart on clinical delineations from the DBCG RT nation cohort.

BACKGROUND: This study aimed at investigating the feasibility of developing a deep learning-based auto-segmentation model for the heart trained on clinical delineations. MATERIAL AND METHODS: This study included two different datasets. The first dataset contained clinical heart delineations from the DBCG RT Nation study (1,561 patients). The second dataset was smaller (114 patients), but with corrected heart delineations. Before training the model on the clinical delineations an outlier-detection was performed, to remove cases with gross deviations from the delineation guideline. No outlier detection was performed for the dataset with corrected heart delineations. Both models were trained with a 3D full resolution nnUNet. The models were evaluated with the dice similarity coefficient (DSC), 95% Hausdorff distance (HD95) and Mean Surface Distance (MSD). The difference between the models were tested with the Mann-Whitney U-test. The balance of dataset quantity versus quality was investigated, by stepwise reducing the cohort size for the model trained on clinical delineations. RESULTS: During the outlier-detection 137 patients were excluded from the clinical cohort due to non-compliance with delineation guidelines. The model trained on the curated clinical cohort performed with a median DSC of 0.96 (IQR 0.94-0.96), median HD95 of 4.00 mm (IQR 3.00 mm-6.00 mm) and a median MSD of 1.49 mm (IQR 1.12 mm-2.02 mm). The model trained on the dedicated and corrected cohort performed with a median DSC of 0.95 (IQR 0.93-0.96), median HD95 of 5.65 mm (IQR 3.37 mm-8.62 mm) and median MSD of 1.63 mm (IQR 1.35 mm-2.11 mm). The difference between the two models were found non-significant for all metrics (p > 0.05). Reduction of cohort size showed no significant difference for all metrics (p > 0.05). However, with the smallest cohort size, a few outlier structures were found. CONCLUSIONS: This study demonstrated a deep learning-based auto-segmentation model trained on curated clinical delineations which performs on par with a model trained on dedicated delineations, making it easier to develop multi-institutional auto-segmentation models.

A national repository of complete radiotherapy plans: design, Results, and experiences.

BACKGROUND: Previously, many radiotherapy (RT) trials were based on a few selected dose measures. Many research questions, however, rely on access to the complete dose information. To support such access, a national RT plan database was created. The system focuses on data security, ease of use, and re-use of data. This article reports on the development and structure, and the functionality and experience of this national database. METHODS AND MATERIALS: A system based on the DICOM-RT standard, DcmCollab, was implemented with direct connections to all Danish RT centres. Data is segregated into any number of collaboration projects. User access to the system is provided through a web interface. The database has a finely defined access permission model to support legal requirements. RESULTS: Currently, data for more than 14,000 patients have been submitted to the system, and more than 50 research projects are registered. The system is used for data collection, trial quality assurance, and audit data set generation.Users reported that the process of submitting data, waiting for it to be processed, and then manually attaching it to a project was resource intensive. This was accommodated with the introduction of triggering features, eliminating much of the need for users to manage data manually. Many other features, including structure name mapping, RT plan viewer, and the Audit Tool were developed based on user input. CONCLUSION: The DcmCollab system has provided an efficient means to collect and access complete datasets for multi-centre RT research. This stands in contrast with previous methods of collecting RT data in multi-centre settings, where only singular data points were manually reported. To accommodate the evolving legal environment, DcmCollab has been defined as a 'data processor', meaning that it is a tool for other research projects to use rather than a research project in and of itself.

European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer.

High-quality randomised clinical trials testing moderately fractionated breast radiotherapy have clearly shown that local control and survival is at least as effective as with 2 Gy daily fractions with similar or reduced normal tissue toxicity. Fewer treatment visits are welcomed by patients and their families, and reduced fractions produce substantial savings for health-care systems. Implementation of hypofractionation, however, has moved at a slow pace. The oncology community have now reached an inflection point created by new evidence from the FAST-Forward five-fraction randomised trial and catalysed by the need for the global radiation oncology community to unite during the COVID-19 pandemic and rapidly rethink hypofractionation implementation. The aim of this paper is to support equity of access for all patients to receive evidence-based breast external beam radiotherapy and to facilitate the translation of new evidence into routine daily practice. The results from this European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus state that moderately hypofractionated radiotherapy can be offered to any patient for whole breast, chest wall (with or without reconstruction), and nodal volumes. Ultrafractionation (five fractions) can also be offered for non-nodal breast or chest wall (without reconstruction) radiotherapy either as standard of care or within a randomised trial or prospective cohort. The consensus is timely; not only is it a pragmatic framework for radiation oncologists, but it provides a measured proposal for the path forward to influence policy makers and empower patients to ensure equity of access to evidence-based radiotherapy.

Atlas-based auto-segmentation for delineating the heart and cardiac substructures in breast cancer radiation therapy.

BACKGROUND: This study aimed to develop and validate an automatic multi-atlas segmentation method for delineating the heart and substructures in breast cancer radiation therapy (RT). MATERIAL AND METHODS: The atlas database consisted of non-contrast-enhanced planning CT scans from 42 breast cancer patients, each with one manual delineation of the heart and 22 cardiac substructures. Half of the patients were scanned during free-breathing, the rest were scanned during a deep inspiration breath-hold. The auto-segmentation was developed in the MIM software system and validated geometrically and dosimetrically in two steps: The first validation in a small dataset to ensure consistency of the atlas. This was succeeded by a final test where multiple manual delineations in CT scans of 12 breast cancer patients were compared to the auto-segmentation. For geometric evaluation, the dice similarity coefficient (DSC) and the mean surface distance (MSD) were used. For dosimetric evaluation, the RT doses to each substructure in the manual and the automatic delineations were compared. RESULTS: In the first validation, a high geometric and dosimetric performance between the automatic and manual delineations was observed for all substructures. The final test confirmed a high agreement between the automatic and manual delineations for the heart (DSC = 0.94) and the cardiac chambers (DSC: 0.75-0.86). The difference in MSD between the automatic and manual delineations was low (<4 mm) in all structures. Finally, a high correlation between mean RT doses for the automatic and the manual delineations was observed for the heart and substructures. CONCLUSIONS: An automatic segmentation tool for delineation of the heart and substructures in breast cancer RT was developed and validated with a high correlation between the automatic and manual delineations. The atlas is pivotal for large-scale evaluations of radiation-associated heart disease.

Proton therapy for early breast cancer patients in the DBCG proton trial: planning, adaptation, and clinical experience from the first 43 patients.

BACKGROUND: The Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark. MATERIAL AND METHODS: Forty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes. RESULTS: The nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5-3.4 Gy, 50 Gy) and 1.1 Gy (0.0-1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3-5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five. CONCLUSION: This proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD.

Symptom trajectories in breast cancer survivors: growth mixture analysis of patient-reported pain, fatigue, insomnia, breast and arm symptoms.

BACKGROUND: Variations in symptom development among breast cancer (BC) survivors are understudied. We examined: (Q1) Symptom trajectories of pain, fatigue, insomnia, breast, and arm symptoms in BC survivors, (Q2) possible patterns or cluster-like associations between trajectory classification of different symptoms, and (Q3) characteristics of survivors assigned to high-burden symptom trajectories. MATERIAL AND METHODS: Participants were 968 women (mean age = 59.6 years) treated for early-stage BC and followed across a three-year postoperative period. As part of routine follow-up procedures, patients reported symptom burden and functioning levels at each hospital visit using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the BC-specific module (QLQ-BR-23). Growth mixture modeling (GMM) analysis was used to differentiate potential subgroups of individuals with similar longitudinal symptom patterns, i.e., symptom trajectories (Q1). With this approach, groups experiencing persistent, highly distressing cancer- and treatment-related late effects (LEs) may be identified. Latent class analysis (LCA) was used for Q2 and logistic regression analysis for Q3. RESULTS: GMM identified two relatively parallel trajectories across the tested symptoms: The majority of the sample exhibited a low-burden symptom trajectory (74.4-89.2%) and a minority by a high-burden symptom trajectory (10.8-25.6%). LCA revealed that approximately one in five women (18.8%) were likely to be members of the high-burden symptom trajectory across all tested symptoms. In addition to a high probability of being burdened over time across multiple symptoms, these women were also characterized by poorer self-reported physical and social functioning. CONCLUSION: A substantial minority followed a high-burden symptom trajectory for several years following BC treatment. Associations were found in trajectory classification across symptoms, indicating that cancer-related LEs appear in clusters of multiple concurrent symptoms.

Patient-reported outcomes in postmenopausal breast cancer survivors - comparisons with normative data.

BACKGROUND: Survival rates for breast cancer (BC) are increasing, leading to growing interest in treatment-related late-effects. The aim of the present study was to explore late effects using Patient-Reported Outcome Measures in postmenopausal BC survivors in standard follow-up care. The results were compared to age- and gender-matched data from the general Danish population. MATERIAL AND METHODS: Postmenopausal BC survivors in routine follow-up care between April 2016 and February 2018 at the Department of Oncology, Aarhus University Hospital, Denmark were asked to complete the EORTC QLQ-C30 and BR23 questionnaires together with three items on neuropathy, myalgia, and arthralgia from the PRO-CTCAE. Patients were at different time intervals from primary treatment, enabling a cross-sectional study of reported late effects at different time points after primary treatment. The time intervals used in the analysis were year ≤1, 1-2, 2-3, 3-4, 4-5 and 5+. The QLQ-C30 results were compared with reference data from the general Danish female population. Between-group differences are presented as effect sizes (ESs) (Cohen's d). RESULTS: A total of 1089 BC survivors participated. Compared with the reference group, BC survivors reported better global health status 2-3 and 4-5 years after surgery (d = 0.26) and physical functioning 2-3 years after (0.21). Poorer outcomes in BC survivors compared with the reference group were found for cognitive functioning (0-4 and 5+ years), fatigue (0-2 years), insomnia (1-3 years), emotional functioning (3-4 years), and social functioning (≤1 year after surgery) with ESs ranging from 0.20 to 0.41. For the remaining outcomes, no ESs exceeded 0.20. CONCLUSION: Only small to medium ESs were found for better global health and physical functioning and poorer outcomes for cognitive functioning, fatigue, insomnia, emotional functioning, and social functioning in postmenopausal BC survivors, who otherwise reported similar overall health-related quality of life compared with the general Danish female population.

Patterns in detection of recurrence among patients treated for breast cancer.

PURPOSE: The Danish follow-up program for breast cancer (BC) patients has recently been changed. Today most patients are offered open access to an outpatient clinic, whereas the scheduled visits are phased out. This strategy has been studied in regards to psychological and health-related quality of life outcomes, but not in regards to detection of recurrence and survival. The aim of this study was to quantify the recurrences detected at scheduled outpatient visits in Denmark before the implementation of revised follow-up guidelines. METHODS: We conducted a cross-sectional study among 310 patients with recurrent BC. Information was retrieved on tumor characteristics, type of visit when recurrence was detected, recurrence localization, symptoms reported, and duration of symptoms from the Danish Breast Cancer Group database and medical records. RESULTS: The recurrences were locoregional (26%), locoregional and distant (15%), or distant (59%). Among patients still in outpatient follow-up (n = 199), recurrence was detected at a patient-requested extra outpatient visit (15%), by the general practitioner or other specialist (47%), at a scheduled outpatient visit (21%), or on a scheduled mammogram (11%). Among patients with recurrences detected at scheduled outpatient visits, the majority (88%) reported symptoms related to the recurrence. Most frequent symptoms were pain (37%), dyspnoea (15%), and fatigue (12%). CONCLUSIONS: One-fifth of BC recurrences among patients attending outpatient follow-up were detected at scheduled outpatient visits. Very few of these were asymptomatic. Whether there will be a delay in detection of the symptomatic recurrences when the number of visits is reduced is unknown.

Spatial location of local recurrences after mastectomy: a systematic review.

PURPOSE: We performed a systematic review to document the spatial location of local recurrences (LR) after mastectomy. METHODS: A PubMed search was conducted in August 2019 for the following terms: breast [Title/Abstract] AND cancer [Title/Abstract] AND recurrence [Title/Abstract] AND mastectomy [Title/Abstract]. The search was filtered for English language. Exclusion criteria included studies that did not specify the LR location or studies reporting LR associated with inflammatory breast cancer, or other breast cancers such as phyllodes tumours, lymphoma or associated with sarcoma/angiosarcoma. RESULTS: A total of 3922 titles were identified, of which 21 publications were eligible for inclusion in the final analysis. A total of 6901 mastectomy patients were included (range 25-1694). The mean LR proportion was 3.5%. Among the total of 351 LR lesions, 81.8% were in the subcutaneous tissue and the skin, while 16% were pectoral muscle recurrences. CONCLUSION: Local recurrences are mostly located within the subcutaneous tissue and the skin, assumed to result from unrecognized/subclinical tumour foci left behind after mastectomy, surgical implantation of tumour cells in the wound/scar and/or tumour emboli within the subcutaneous lymphatics. Pectoral muscle recurrences are less frequent and may be attributed to residual disease along the posterior surgical margin and/or lymphatic involvement.

Residual Glandular Breast Tissue After Mastectomy: A Systematic Review.

BACKGROUND: The goal of mastectomy is remove all of the glandular breast tissue (BGT) without compromising skin flaps viability. The purpose of this systematic review was to localize and/or estimate the amount of residual BGT (rBGT) after mastectomy and to identify factors that could be related to rBGT and/or residual disease. METHODS: We conducted a PubMed search. The report was subdivided according to the method used to evaluate the presence of rBGT. A total of 16 publications were included in our final report. Two main methods for identifying rBGT included imaging (i.e., MRI scan) and histological evaluation at the time of mastectomy. RESULTS: The rate of rBGT was reported in up to 100% of the patients and was found to be associated mainly with the type of surgical resection, indication, and surgeon's expertise. Residual breast tissue can be found in all areas of the remaining chest wall, mostly in the skin-flaps, and more frequently underneath the nipple-areola complex.

Prevention, Detection, and Management of Heart Failure in Patients Treated for Breast Cancer.

PURPOSE OF REVIEW: Long-term survival has increased significantly in breast cancer patients, and cardiovascular side effects are surpassing cancer-related mortality. We summarize risk factors, prevention strategies, detection, and management of cardiotoxicity, with focus on left ventricular dysfunction and heart failure, during breast cancer treatment. RECENT FINDINGS: Baseline treatment of cardiovascular risk factors is recommended. Anthracycline and trastuzumab treatment constitute a substantial risk of developing cardiotoxicity. There is growing evidence that this can be treated with beta blockers and angiotensin antagonists. Early detection of cardiotoxicity with cardiac imaging and circulating cardiovascular biomarkers is currently evaluated in clinical trials. Chest wall irradiation accelerates atherosclerotic processes and induces fibrosis. Immune checkpoint inhibitors require consideration for surveillance due to a small risk of severe myocarditis. Cyclin-dependent kinases4/6 inhibitors, cyclophosphamide, taxanes, tyrosine kinase inhibitors, and endocrine therapy have a lower-risk profile for cardiotoxicity. Preventive and management strategies to counteract cancer treatment-related left ventricular dysfunction or heart failure in breast cancer patients should include a comprehensive cardiovascular risk assessment and individual clinical evaluation. This should include both patient and treatment-related factors. Further clinical trials especially on early detection, cardioprevention, and management are urgently needed.

Adjuvant radiotherapy does not affect hemostasis.

Cancer is associated with increased risk of venous thromboembolic disease. Venous thromboembolic disease accounts for a substantial addition to morbidity and mortality rates in cancer patients and is the second leading cause of death in cancer patients, exceeded only by the underlying cancer. Only few previous studies have investigated the influence of radiotherapy on hemostasis and whether radiotherapy in itself causes an increased risk of venous thromboembolic disease. The aim was to investigate if adjuvant radiotherapy affects hemostasis after surgery and chemotherapy in patients with breast cancer. Radiotherapy consisted of either 40 Gy/15 fractions or 50 Gy/25 fractions. Blood samples were obtained from 39 consecutive women before and immediately after the first, the intermediate, and the final radiation fraction. Platelet function was measured using impedance aggregometry, and thrombin generation was determined in platelet-poor plasma using calibrated automated thrombogram. Furthermore, P-selectin, international normalized ratio, fibrinogen, activated partial thromboplastin time, coagulation factor VIII, von Willebrand factor, C-reactive protein (CRP), and soluble thrombomodulin were measured before and after radiation treatment. Platelet aggregation was within reference interval before initiation of radiotherapy, and remained unaffected during the radiation course. Neither serum P-selectin, thrombin generation, fibrinogen, coagulation factor VIII, von Willebrand factor, CRP nor thrombomodulin were substantially influenced by radiation treatment. The present study showed that radiotherapy did not affect hemostasis, neither by a single radiation dose nor during the radiation course, in early breast cancer patients receiving adjuvant radiotherapy.