key: cord-0919663-gswnknyr
authors: Bargon, Claudia A; Batenburg, Marilot C T; van Stam, Lilianne E; van der Molen, Dieuwke R Mink; van Dam, Iris E; van der Leij, Femke; Baas, Inge O; Ernst, Miranda F; Maarse, Wiesje; Vermulst, Nieke; Schoenmaeckers, Ernst J P; van Dalen, Thijs; Bijlsma, Rhodé M; Young-Afat, Danny A; Doeksen, Annemiek; Verkooijen, Helena M
title: Impact of the COVID-19 pandemic on patient-reported outcomes of breast cancer patients and survivors
date: 2020-11-05
journal: JNCI Cancer Spectr
DOI: 10.1093/jncics/pkaa104
sha: 17274d16f5d6e9fbbefb5ed24454f739a89a31fa
doc_id: 919663
cord_uid: gswnknyr

BACKGROUND: The COVID-19 pandemic (officially declared on the 11(th) of March, 2020), and the resulting measures, are impacting daily life and medical management of breast cancer patients and survivors. We evaluated to what extent these changes have affected quality of life, physical and psychosocial wellbeing of patients (being) treated for breast cancer. METHODS: This study was conducted within a prospective, multicentre cohort of breast cancer patients and survivors (UMBRELLA). Shortly after the implementation of COVID-19 measures, an extra survey was sent to 1,595 participants, including validated EORTC QLQ-C30/BR23 and HADS questionnaires. Patient-reported outcomes (PROs) were compared to the most recent PROs collected within UMBRELLA pre-COVID-19. The impact of COVID-19 on PROs was assessed using mixed model analysis, adjusting for potential confounders. RESULTS: 1,051 patients and survivors (65.9%) completed the survey; 31.1% (n = 327) reported a higher threshold to contact their general practitioner amid the COVID-19 pandemic. A statistically significant deterioration in emotional functioning was observed (82.6 [SD = 18.7] to 77.9 [SD = 17.3], p < .001), and 505 (48.0%, 95%CI = 45.0 to 51.1%) reported moderate to severe loneliness. Small improvements were observed in QoL, physical-, social- and role functioning. In the subgroup of 51 patients under active treatment, social functioning strongly deteriorated (77.3 [95%CI = 69.4 to 85.2] to 61.3 [95%CI = 52.6 to 70.1], p = .002). CONCLUSION: During the COVID-19 pandemic, breast cancer patients and survivors were less likely to contact physicians and experienced a deterioration in their emotional functioning. Patients undergoing active treatment reported a substantial drop in social functioning. One in two reported loneliness that was moderate or severe. Online interventions supporting mental health and social interaction are needed during times of social distancing and lockdowns.

Standard deviation National restrictions varied from total lockdown to targeted quarantine and social distancing. [4] [5] [6] In the Netherlands, specific governmental measures included stay-at-home orders when experiencing mild symptoms, social distancing (1.5 metre), closure of schools and public places and cancelling all public events. Despite drastic efforts, the World Health Organization (WHO) officially declared the COVID-19 outbreak a pandemic on March 11, 2020. 7 As the COVID-19 pandemic has put health care systems under unprecedented stress, urgent re-arrangements of non-COVID-19 related health care has been of vital importance. 6, [8] [9] [10] [11] To prioritize hospital capacity for critically ill COVID-19 patients, elective care was suspended as much as possible, while only emergency care and semi-urgent oncological procedures were continued. 6, [12] [13] [14] For breast cancer, surgical procedures were postponed when possible, various types of treatment (chemo-and radiotherapy) were adapted, and follow-up appointments cancelled, postponed or transformed into (video)calls. 9, 15 Also, paramedical (after)care such as medical rehabilitation and psychological support was scaled down to a minimum, and national breast cancer screening programmes were temporarily halted. 12, 16 Delays and changes in breast cancer diagnosis, treatment and follow-up protocols due to COVID-19 may potentially induce concerns about recurrence or survival. 16 This, in combination with concerns about the new viral threat in general, could impair patients' and survivors' mental and emotional wellbeing. Previous literature showed that, in general, woman with a history of breast cancer have an increased risk of anxiety and depression, and that social support is crucial for supporting quality of life and mental health in patients (being) treated for breast cancer. [17] [18] [19] Measures of social distancing or lockdown may interfere with networks of support, and have a negative impact on mental health and emotional functioning. However, to date, no previous studies have used patient-reported outcome scores (PROs) of breast cancer patients and survivors in the context of COVID-19.

The purpose of this study was to measure the impact of the COVID-19 pandemic on patientreported quality of life, physical and psychosocial functioning in a prospective cohort of patients (being) treated for breast cancer.

The present study was conducted within the ongoing prospective multicentre Utrecht cohort for

Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA). 20 The Hospital Anxiety and Depression Scale (HADS) was used to assess symptoms of anxiety and depression. 24 Patients and survivors with scores above seven are at risk of having anxiety or depressive disorders. 25 Overall, emotional, and social loneliness was assessed using the 6-item De Jong-Gierveld Loneliness Scale. 26 Scores between two and four represent moderate loneliness, a score above four represents severe loneliness. 27 Scores above two on each of the 3-item subscales for emotional and social loneliness indicate emotional/social loneliness. 27 Additional questions were developed to assess presence of (symptoms resembling) COVID- 

Between October 2013 and April 2020, 3,239 patients (being) treated for breast cancer were enrolled in UMBRELLA (Fig. 1 ). Of all UMBRELLA-participants, 1,595 met the inclusion criteria for the present study and were sent the extra COVID-19 survey, of whom 1,051 patients and survivors (65.9%) responded. Mean age was 56 years (SD=9.8) and median time since diagnosis was 24 months (IQR=6-42, Table 1 ). Most patients and survivors (55.7%) were treated for a stage 1 tumour and received breast conserving surgery (77.4%). Fifty-one patients (4.9%) were receiving active treatment (chemo-and/or radiotherapy) for breast cancer ( Table 2) . Median time between completion of the most recent pre-COVID-19 questionnaire and the COVID-19 survey was 4 months (IQR=3-6).

In total, one (0.1%) had confirmed COVID-19 infection and 100 (9.5%) indicated to have been possibly 

For 1,022 patients and survivors (97.2%) pre-and during COVID-19 EORTC scores (Fig. 2) , and for 942 (89.6%) pre-and during COVID-19 HADS scores could be compared. Overall, mean scores for the EORTC subdomains QoL, physical, and role functioning statistically significantly improved during COVID-19 (Table 4 ). Mean scores for the EORTC subdomain emotional functioning worsened statistically significantly from 82.6 (SD=18.7) to 77.9 (SD=17.3, p<0.001). Also, median HADS total score and depression score deteriorated statistically significantly during COVID-19 (Table 3 ).

In the subgroup of actively treated patients, there was a strong and statistically significant drop in social functioning of 16 Table 5 ).

Among the non-actively treated patients and survivors, age-adjusted analyses showed that emotional functioning worsened statistically significantly in all groups, whereas physical functioning improved statistically significantly in all groups (Table 5) . QoL, role, and social functioning improved statistically significantly in non-actively treated patients and survivors who were enrolled in UMBRELLA <24 months (Table 5) . HADS depression score increased from 2 (IQR=1-5) to 4 (IQR=2-7, p<0.001).

The COVID-19 pandemic has a substantial impact on patients (being) treated for breast cancer. One in three reported to be less likely to contact their general practitioner, and 15.4% indicated to be less likely to contact their breast cancer physician due to barriers induced by COVID-19 restrictions. In patients actively receiving treatment, social functioning decreased substantially, and in patients and survivors who were no longer receiving active treatment, deterioration of emotional functioning was observed. Loneliness was reported by almost half of all patients and survivors.

The high proportion indicating to experience a higher barrier to contact their general practitioner (31.1%) is in line with the upsetting findings of the Dutch cancer registry (NKR), who reported a nationwide decrease up to 40% in cancer diagnoses during COVID-19. 16 Jones and colleagues 28 (United Kingdom) also expressed their concerns about patients potentially feeling higher barriers to consult a general practitioner for non-specific symptoms. Patients might experience (moral)

dilemmas, including concerns about wasting the physicians' time, insufficient capacity or exposure to the virus in a healthcare institution. 15 Moreover, an average referral drop of 37% to all medical specialties was observed in the Netherlands during the outbreak. 29 Fortunately, most patients and survivors (84.6%) did not report a higher barrier to reach out to their breast cancer physician. Thus, although the threshold to contact a general physician was higher in a concerning proportion of patients and survivors, the pandemic seemed to have minimal impact on interaction with the breast cancer team once diagnosed. This does highlight the importance of creating public awareness about the risk potential delays in seeking medical help could cause, aiming to lower barriers for patients and survivors to contact their general practitioner when experiencing non-breast cancer related symptoms. 16 In addition to the decrease in cancer diagnoses during the pandemic, a decrease in mental health also raises concerns about future disease outcomes. Previous studies showed that lower levels of anxiety and depression, as well as social support, seem to positively affect treatment adherence. 30, 31 Among patients who were receiving active breast cancer treatment during the COVID-19

pandemic, a major clinically and statistically significant decrease in social functioning was observed (Table 5) . 32 The mean score approached the threshold score for clinical importance of 58. 33 here; lower tolerance of uncertainty is related to higher appraisal of a health threat and higher levels emotion-focused coping strategies. 39 A previous study showed that, during the 2009 H1N1 viral outbreak, emotion-focused coping was related with increased levels of depression. 39 Interestingly, despite the deterioration in emotional functioning in all non-actively treated patients and survivors, there was a statistically significant increase in global QoL, role functioning, social functioning, and physical functioning. For QoL, physical and social functioning these increases did not reach the minimal clinically important difference (MCID) scores (10, 7 and 7, respectively). 32 Although cautiousness is therefore advised when interpreting these results, they do emphasize that, regardless the COVID-19 pandemic, PROs did not deteriorate in these domains. This may partly be explained by the fact that these PROs generally tend to increase over time since diagnosis. 38 In our study, however, median time between pre-and during COVID-19 PROs was only 4 months.

Furthermore, the shared crisis may put patients' and survivors' perceived QoL in relation to their disease in a different perspective, and may even accelerate reconceptualization of their QoL. 40 The observed increase in social and role functioning suggests that patients and survivors reported an increased ability to fulfil responsibilities associated with occupational, and/or family roles.

Governmental measures encouraging work from home and prohibiting social events (i.e., less social obligations) in times of social distancing or lockdown may also play a role.

The impact of the COVID-19 pandemic seemed worse among patients and survivors with suspected COVID-19 infection. The largest effect was seen in a substantial drop in QoL and an 14 increase in symptoms of dyspnoea and depression. This is in line with the findings of our Italian colleagues 41 , who reported worsening of QoL in 44.1% of patients 60 days after the onset of the first COVID-19 symptoms (n=143). This may partly be explained by the fact that this subgroup will have likely experienced a more profound period of self-or imposed-isolation.

In general, experiencing health problems can induce loneliness and vice versa. 42 Especially in times when face-to-face contact is not an option, and when the global need for psychological and/or peer support is rising due to the viral threat, efforts are needed to rapidly implement e-mental health (screening) programmes and digital psychological interventions. Only by adapting to the new circumstances will we be able to treat both ongoing and emerging mental health care conditions due to COVID-19, and prevent long-term problems. 11, 46 Considering that a second wave of COVID-19 or another future outbreak with similar impact is probable, 15, 47 In conclusion, COVID-19 is having a substantial impact on breast cancer patients and survivors. Emotional functioning deteriorated in non-actively treated patients and survivors following the COVID-19 pandemic, one in two patients and survivors reported loneliness that was moderate or severe, and one in three reported to be less likely to contact their health care providers. In actively treated patients, social functioning decreased substantially.

The authors received no financial support for the research (including study design; data collection, analysis, interpretation of data; and writing of the report), authorship, and/ or (the decision to submit the article for) publication.

Role of the funder: Not applicable.

The authors have no conflicts of interest to disclose.

We would like to thank Janet van Dasselaar for her support with the clinical data management, and Rosalie van den Boogaard for support with IRB approval. We are greatly indebted to the Medical Ethics Committee of the UMC Utrecht for expedited ethical review of the protocol.

The corresponding author (HM Verkooijen) confirms that she had full access to all the data in the study and had final responsibility for the decision to submit for publication. Each author has contributed significantly to, and is willing to take public responsibility for, the following 

The data underlying this article will be shared on reasonable request to the corresponding author. b Last valid score measured within the last two years before the start of the COVID-19 pandemic.

c Crude median HADS scores were compared with a two-sided Wilcoxon signed rank test. d A HADS total score > 7 indicates a possible anxiety disorder or depression and a score > 11 indicates a probable depression or anxiety disorder. e A scores between 2 and 4 represent moderate loneliness, a score > 4 represents severe loneliness. b Last valid score measured within the last two years before the start of the COVID-19 pandemic.

c Crude mean EORTC scores were compared with a two-sided paired samples t-test. d MD differs from difference mean scores due to rounding. 

Risk of COVID-19 for patients with cancer

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Conducting Clinical Research During the COVID-19

Pandemic: Protecting Scientific Integrity

Thinking Globally, Acting Locally -The U.S. Response to Covid-19

Disease Control, Civil Liberties, and Mass Testing -Calibrating Restrictions during the Covid-19 Pandemic

Early look at the future of healthcare during the COVID-19 pandemic

WHO Director-General's opening remarks at the media briefing on COVID-19 -11

Fair Allocation of Scarce Medical Resources in the Time of Covid-19

COVID-19 Emergency and the Need to Speed Up the Adoption of Electronic Patient-Reported Outcomes in Cancer Clinical Practice

Ensuring and Sustaining a Pandemic Workforce

Telehealth in Oncology During the COVID-19 Outbreak: Bringing the House Call Back Virtually

COVID-19: global consequences for oncology

Surgery in a Time of Uncertainty: A Need for Universal Respiratory Precautions in the Operating Room

COVID-19 and the Financial Health of US Hospitals

Safeguarding cancer care in a post-COVID-19 world

Fewer cancer diagnoses during the COVID-19 epidemic in the Netherlands

Assessment of quality of life in women five years after breast cancer surgery, members of Breast Cancer Self-Help Groups -nonrandomized, cross-sectional study

A prospective and population-based inquiry on the use and acceptability of peer support for women newly diagnosed with breast cancer. Support Care Cancer

Associations Between Breast Cancer Survivorship and Adverse Mental Health Outcomes: A Systematic Review

The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA): objectives, design, and baseline results

The Trials within Cohorts design faced methodological advantages and disadvantages in the exercise oncology setting

The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology

Brussels: European Organisation for Research and Treatment of Cancer

Van Hemert AM. A validation study of the Hospital Anxiety and Depression Scale (HADS) in different groups of Dutch subjects

The hospital anxiety and depression scale

Manual of the loneliness scale

Impact of the COVID-19 pandemic on the symptomatic diagnosis of cancer: the view from primary care

ZorgDomein heeft actuele cijfers over zorgbehandelingen die zich opstapelen door corona crisis

A literature review to investigate the link between psychosocial characteristics and treatment adherence in cancer patients

Minimally Important Differences for Interpreting EORTC QLQ-C30 Scores in Patients With Advanced Breast Cancer. JNCI Cancer Spectr

Thresholds for Clinical Importance Were Established to Improve Interpretation of the EORTC QLQ-C30 in Clinical Practice and Research

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Managing COVID-19 in Patients With Cancer: A Double Blow for Oncologists

Outcome of Oncology Patients Infected With Coronavirus

The EORTC emotional functioning computerized adaptive test: phases I-III of a cross-cultural item bank development

Severe depression more common in patients with ductal carcinoma in situ than early-stage invasive breast cancer patients

Intolerance of uncertainty, appraisals, coping, and anxiety: the case of the 2009 H1N1 pandemic

Integrating response shift into health-related quality of life research: a theoretical model

Gemelli Against COVID-19 Post-Acute Care Study Group

Persistent Symptoms in Patients After Acute COVID-19

Risk factors for loneliness in patients with cancer: a systematic literature review and meta-analysis

Nearly 1 in 10 Dutch people frequently lonely in 2019

The COVID-19 pandemic: The 'black swan' for mental health care and a turning point for e-health

The outbreak of COVID-19 coronavirus and its impact on global mental health

First-wave COVID-19 transmissibility and severity in China outside Hubei after control measures, and second-wave scenario planning: a modelling impact assessment

Implications for Telehealth in a Postpandemic Future: Regulatory and Privacy Issues

Still a Cancer Patient"-Associations of Cancer Identity With Patient-Reported Outcomes and Health Care Use Among Cancer Survivors

Nationaal Borstkankeroverleg Nederland (NABON)

Abbreviations: IQR; Interquartile Range, n; number, SD

For quality of life, and functioning scales a higher score indicates a better outcome. For insomnia a lower score indicates a better outcome. Abbreviations: CI, Confidence Interval

Mean Difference (difference in mean scores between pre-COVID-19 and during COVID-19)

reference group

In addition, active treatment scores were adjusted for type of radiotherapy and type of surgery