Psychosocial Wellbeing among Patients with Breast Cancer during COVID-19

The impact of coronavirus disease 2019 (COVID-19) on the wellbeing of breast cancer (BC) patients is not well understood. This study described psychosocial problems among these patients in the United States (US) during the COVID-19 pandemic. Data were collected from BC patients via an online self-report survey between 30 March–6 July 2021 to assess the prevalence of COVID-19 diagnosis history and potential depression, health-related quality of life, COVID-related stress, and financial toxicity. Patients with early-stage (eBC) and metastatic (mBC) disease were compared. Of 669 patients included in the analysis, the prevalence of COVID-19 diagnosis history (10.9% versus 7.7%) and potential depression (33.7% versus 28.3%) were higher in mBC than eBC patients. Patients with eBC (versus mBC) had higher scores on nearly all Functional Assessment of Cancer Therapy-Breast scales (all, p < 0.001). For the Psychological Impact of Cancer subscales measuring negative coping strategies, the emotional distress score was the highest (9.1 ± 1.8) in the overall sample. Comprehensive Score for Financial Toxicity scores were higher in eBC than in mBC patients (24.2 ± 11.3 vs. 21.3 ± 10.2, p < 0.001). Overall, the COVID-19-related stress score was highest for danger/contamination fears (8.2 ± 5.6). In conclusion, impairments to psychosocial wellbeing among patients during the pandemic were observed, particularly financial toxicity and poor mental health and emotional functioning, with greater problems among mBC patients.


Introduction
As of October 2022, over 624 million individuals have been diagnosed with coronavirus disease 2019 (COVID-19) globally, with over 6.5 million deaths [1]. There is a high risk of COVID-19 infection in cancer patients and cancer survivors owing to their immunosuppressive state compared to individuals without cancer, including increased vulnerability towards severe symptoms, poorer outcomes, and mortality [2][3][4][5].
COVID-19 has triggered dramatic disruptions or delays to services and care largely due to unprecedented strain on health systems and increased susceptibility to the physical and psychological effects of social isolation and economic upheaval [6,7]. Among those with cancer, there are serious concerns regarding infection risk, changes in treatment and downstream effects on cancer outcomes, and social determinants of health, which are more pronounced among patients with advanced cancer [6,7]. Furthermore, recent realworld data demonstrated an increase in cancer-related deaths due to the pandemic's effect on health systems [8]. A recent study reported that, compared with pre-pandemic data, mortality associated with breast, colorectal, lung, and esophageal cancer is projected to increase by 7.9-9.6%, 15.3-16.6%, 4.8-5.3%, and 5.8-6.0%, respectively, in the next five years due to the postponement of cancer diagnosis [9]. TOUCH, The Breasties, SurvivingBreastCancer.org, and the Metaplastic Breast Cancer Global Alliance), with approximately 39% recruited from the Breastcancer.org patient community. A subset of survey participants was enrolled in Ciitizen (now part of Invitae Corporation, San Francisco, CA, USA). Ciitizen leverages the Health Insurance Portability and Accountability Act (HIPAA) right of access on patients' behalf to collect and store their medical records and turns medical record documents into structured, longitudinal data that can be shared with whomever the patients want, for their own clinical treatment or for observational research and clinical trials. Key clinical and treatment data are extracted from the medical records to provide the patient with a visual summary of their treatment journey that can be used for second opinions or other personal care coordination needs. The extracted data are used for research purposes for patients who have consented to share their data for research use. In addition to receiving their own medical records, survey participants who enrolled in Ciitizen consented to share their de-identified data for the study. The current article focuses on the self-report survey results of participating patients with BC.

Study Sample
Eligible patients were aged ≥18 years, self-reported currently having a diagnosis of Stage 1, 2, or 3 or Stage 4 BC (eBC or mBC, respectively), and provided informed consent. Those who self-reported currently having Stage 0 BC or ductal carcinoma in situ (DCIS) were ineligible.

Study Measures
Demographics included age, race, US region, community type, household size, education, employment status, marital status, and income. Clinical/health characteristics included COVID-19 diagnosis history (ever diagnosed versus [vs.] not ever diagnosed), body mass index (BMI), BC type (eBC vs. mBC), BC stage at initial diagnosis, disease duration, diagnosed comorbidities, and current BC treatments; for the Charlson Comorbidity Index (CCI), weights are assigned to 11 health conditions and then summed; higher scores indicate greater comorbidity burden [31].

Statistical Analyses
Analyses were performed using IBM SPSS ® version 28.0. Descriptive statistics were reported for demographics, clinical/health characteristics, and psychosocial wellbeing. This analysis included means and standard deviations (SDs) for continuous variables, with frequencies and percentages reported for categorical variables.
Comparisons by BC type and COVID-19 diagnosis history on FACT-B, PIC, COST, and CSS scores were performed using independent samples t-tests. Prevalence of COVID-19 diagnosis history and potential depression were reported as percentages with 95% confidence intervals (CIs). Spearman correlations (ρ) were conducted to examine the relationship between psychosocial wellbeing measures. Generalized linear models (GLMs), specifying negative binomial distribution and log link function, were used to examine the association between BC type and CSS subscales, adjusting for potential confounders. Based on a backward stepwise elimination procedure, GLM for CSS danger controlled for community type, potential depression, number of adults in the household, and income. GLM for CSS socioeconomic consequences controlled for education, current treatment with hormone therapy, community type, race, potential depression, current treatment with chemotherapy, and income. GLM for CSS traumatic stress controlled for potential depression, current treatment with targeted therapy, and income. Additionally, GLMs for all CSS scales controlled for age, BMI, CCI score, and COVID-19 diagnosis history due to conceptual relevance (i.e., COVID-19 risk factors). For correlations, t-tests, and GLMs, p-values < 0.05, 2-tailed, were considered statistically significant.

Patient Characteristics
Overall, 669 patients with BC (aged 28-82 years) were included in the analyses. The number of patients who participated in the study by US state is depicted in Figure 1, with demographic and clinical/health characteristics of the study sample reported in Table 1.
Comparisons by BC type and COVID-19 diagnosis history on FACT-B, PIC, COST, and CSS scores were performed using independent samples t-tests. Prevalence of COVID-19 diagnosis history and potential depression were reported as percentages with 95% confidence intervals (CIs). Spearman correlations (ρ) were conducted to examine the relationship between psychosocial wellbeing measures. Generalized linear models (GLMs), specifying negative binomial distribution and log link function, were used to examine the association between BC type and CSS subscales, adjusting for potential confounders. Based on a backward stepwise elimination procedure, GLM for CSS danger controlled for community type, potential depression, number of adults in the household, and income. GLM for CSS socioeconomic consequences controlled for education, current treatment with hormone therapy, community type, race, potential depression, current treatment with chemotherapy, and income. GLM for CSS traumatic stress controlled for potential depression, current treatment with targeted therapy, and income. Additionally, GLMs for all CSS scales controlled for age, BMI, CCI score, and COVID-19 diagnosis history due to conceptual relevance (i.e., COVID-19 risk factors). For correlations, t-tests, and GLMs, p-values < 0.05, 2-tailed, were considered statistically significant.

Patient Characteristics
Overall, 669 patients with BC (aged 28-82 years) were included in the analyses. The number of patients who participated in the study by US state is depicted in Figure 1, with demographic and clinical/health characteristics of the study sample reported in Table 1.    SD, standard deviation. * N = 11 patients were not included in the BMI calculation as some patients (n = 7) selected "prefer not to answer" on weight, and the remaining n = 4 had a BMI value that was an extreme outlier (defined as value ≥3 SDs above or below the mean for the overall patient sample). † Patients could select >1 response option.

Correlations between Psychosocial Wellbeing Measures
Most psychosocial wellbeing measures demonstrated adequate reliability, with Cronbach's alpha values either approaching or exceeding 0.80 with the current sample. For PHQ-8 and COST, these values were 0.85 and 0.90, respectively, and on all three CSS subscales, Cronbach's alpha was 0.92. These values were 0.74 and 0.75 for PIC cognitive distress and cognitive avoidance subscales, respectively. However, PIC emotional distress (0.68) and fighting spirit (0.46) subscales evidenced less internal consistency, possibly due, at least in part, to the small number of items in these subscales. As FACT-BC subscale scores are calculated slightly differently for males and females, we computed separate reliability estimates for this subscale and found values of 0.80 and 0.72 for males and females, respectively. For all other FACT-B metrics, Cronbach's alpha values ranged from 0.77 (FACT-General) to 0.88 (FACT-Physical Wellbeing).

Prevalence of COVID-19 and Potential Depression
The overall prevalence of COVID-19 diagnosis history was 9.4% (95% CI: 7.4-11.8%) Patients with mBC (vs. eBC) had a higher prevalence of COVID-19 diagnosis history, alt hough this difference was not statistically significant (10.9% vs. 7.7%, p = 0.157; Figure 2A) Prevalence of (A) COVID-19 diagnosis history by BC type, (B) potential depression by BC type, and (C) potential depression by COVID-19 diagnosis history. COVID-19, coronavirus diseas 2019; eBC: early-stage breast cancer; mBC: metastatic breast cancer. Note: Error bars show 95% con fidence intervals. A total of 8 patients were excluded from estimates of COVID-19 diagnosis histor prevalence for BC type subgroups and from estimates of potential depression for COVID-19 diag nosis history subgroups (n = 7 responded "not sure" and n = 1 responded "prefer not to answer" o survey item about COVID-19 diagnosis history).

Psychosocial Wellbeing
The psychosocial wellbeing measures assessed in this study are presented in Table 2  The overall prevalence of potential depression was 31.1% (95% CI: 27.7-34.7%). The prevalence of potential depression was higher among patients with mBC (vs. eBC: 33.7% vs. 28.3%, p = 0.131; Figure 2B), but this difference did not reach statistical significance. Similar rates of potential depression were observed by COVID-19 diagnosis history (ever diagnosed: 30.6% vs. not ever diagnosed: 31.1%, p = 0.947; Figure 2C).
The mean COST score for the overall sample was 22.7 ± 10.8. The mean COST score was higher for patients with eBC (vs. mBC; 24.2 ± 11.3 vs. 21.3 ± 10.2, p < 0.001). COST scores did not differ by COVID-19 diagnosis history.

COVID-19-Related Stress and Associated Factors
The highest CSS scores were observed for the danger (8.2 ± 5.6) subscale, followed by scores on socioeconomic consequences (3.7 ± 4.8) and traumatic stress (3.0 ± 4.2). CSS scores did not differ by BC type or COVID-19 diagnosis history (Table 2).
Parameter estimates from multivariable models are shown in Table 3. Multivariable analysis showed no significant association between BC type and CSS danger (B = −0.04,  Adjusted means by BC type and for those variables that demonstrated a statistically significant association with each CSS subscale are shown in Figure 3. For CSS danger subscale scores, differences between depression (potential depression [adjusted mean]: 9.87 vs. no potential depression: 7.60) and income (<$75,000: 9.81 vs. ≥$75,000: 7.65) groups were of similar magnitude. The largest mean differences in CSS socioeconomic subscale scores were observed among depression (potential depression: 4

Summary and Contributions
This study described psychosocial problems, including potential depression, COVID-19-related stress, psychological coping with cancer, HRQoL, and economic burden, in US patients with BC during the COVID-19 pandemic. Patients reported impairments to psychosocial wellbeing, specifically high rates of potential depression, poor HRQoL, emotional distress, and financial toxicity. Higher prevalence of COVID-19 diagnosis history and potential depression, lower HRQoL, and greater financial toxicity were found in patients with mBC than eBC.
Current treatment use in this study was generally comparable to a cross-sectional study assessing the psychosocial impact of BC during COVID-19, in which 74% received hormone or chemotherapy treatment prior to surgery [28]. However, only 11% of patients in our study had had surgery in the past 3 months. This could be attributed to disruptions in non-COVID-related health services during the pandemic [28]. Depression and anxiety are common psychiatric conditions among patients with BC [38,39], and they were likewise the most frequently reported comorbidities in this study.
The prevalence of COVID-19 diagnosis history was approximately 5.5 times higher than the self-reported positive test rate in the US general adult population [40]. However, data were collected for that study earlier in the pandemic than the current study (April-May 2020 vs. March-July 2021); thus, the prevalence differential may be smaller if considering equivalent time periods. The slightly higher prevalence of COVID-19 diagnosis history observed in mBC than eBC is similar to a prospective registry study that assessed the characteristics and outcomes of BC patients diagnosed with COVID-19, in which twothirds of those with COVID-19 were treated for mBC, suggesting that COVID-19 was more prevalent in patients with mBC [41].
Patients with BC often suffer from chronic psychological stress caused by diagnosis or treatment-induced physical functioning changes, side effects, or impaired social

Summary and Contributions
This study described psychosocial problems, including potential depression, COVID-19related stress, psychological coping with cancer, HRQoL, and economic burden, in US patients with BC during the COVID-19 pandemic. Patients reported impairments to psychosocial wellbeing, specifically high rates of potential depression, poor HRQoL, emotional distress, and financial toxicity. Higher prevalence of COVID-19 diagnosis history and potential depression, lower HRQoL, and greater financial toxicity were found in patients with mBC than eBC.
Current treatment use in this study was generally comparable to a cross-sectional study assessing the psychosocial impact of BC during COVID-19, in which 74% received hormone or chemotherapy treatment prior to surgery [28]. However, only 11% of patients in our study had had surgery in the past 3 months. This could be attributed to disruptions in non-COVID-related health services during the pandemic [28]. Depression and anxiety are common psychiatric conditions among patients with BC [38,39], and they were likewise the most frequently reported comorbidities in this study.
The prevalence of COVID-19 diagnosis history was approximately 5.5 times higher than the self-reported positive test rate in the US general adult population [40]. However, data were collected for that study earlier in the pandemic than the current study (April-May 2020 vs. March-July 2021); thus, the prevalence differential may be smaller if considering equivalent time periods. The slightly higher prevalence of COVID-19 diagnosis history observed in mBC than eBC is similar to a prospective registry study that assessed the characteristics and outcomes of BC patients diagnosed with COVID-19, in which two-thirds of those with COVID-19 were treated for mBC, suggesting that COVID-19 was more prevalent in patients with mBC [41].
Patients with BC often suffer from chronic psychological stress caused by diagnosis or treatment-induced physical functioning changes, side effects, or impaired social functioning and HRQoL [16]. Furthermore, patients with BC are at increased risk of developing mental health conditions during the pandemic due to restrictions on daily life [20]. Our study findings support this proposition, as the prevalence of potential depression was higher in this study (31.1%), relative to a multinational systematic review and meta-analysis conducted pre-pandemic that reported a pooled prevalence of potential depression of 24.6% and 24.1% in the Americas region and high sociodemographic index countries, respectively [42]. Additionally, in the current study, the prevalence of potential depression among patients with BC was 4 times higher than the US general adult population [43]. The prevalence of potential depression was higher in mBC than eBC patients, consistent with prior research findings [38].
The scores on all FACT-B metrics in the present study were low, indicating poor HRQoL. Among all the FACT-B metrics assessed, scores on emotional and functional wellbeing were the lowest, suggesting the greatest HRQoL impairment in those domains. A survey of patients with eBC in seven countries, including the US, conducted just prior to the pandemic reported mean FACT-B and FACT-General total scores of 99.0 and 72.5, respectively, which was slightly higher than the FACT-B (94.3) and FACT-General (71.4) scores of patients with eBC in the current study [44]. Further, patients with mBC (vs. eBC) had lower scores on nearly all FACT-B metrics, suggesting worse HRQoL among those with mBC, which is consistent with another study that revealed lower HRQoL for mBC in each FACT-B domain [45].
Of the PIC subscales, scores were observed to be highest on emotional distress, indicating this was the most commonly employed negative strategy for coping with cancer. Furthermore, patients with mBC (vs. eBC) had higher PIC scores on cognitive distress and cognitive avoidance subscales. Our findings are similar to a previous cross-sectional study conducted during the pandemic, wherein patients with BC experienced more severe physical conditions, further worsening emotional distress and cognitive impairment from disruptions in medical services [20].
Additionally, economic concerns may further negatively impact psychosocial wellbeing, given financial challenges were widespread during the COVID-19 pandemic [46]. Our results echoed previous findings in which a majority of patients with cancer experienced financial toxicity [37], with the current study showing this impact being more pronounced among those with mBC. However, the low COVID-related stress observed in this study was similar to a recent study that demonstrated low CSS scores on danger, socioeconomic consequences, and traumatic stress subscales [19].
Patients with and without a COVID-19 diagnosis history were similar on all psychosocial wellbeing measures. This may be because we assessed COVID-19 diagnosis history, and diagnosis may not have been recent, whereas the longest recall period for psychosocial wellbeing measures was the previous 2 weeks. Additionally, it is possible that some patients tested positive for COVID-19 but were asymptomatic or had mild symptoms, thereby experiencing little impact on psychosocial wellbeing. Finally, COVID-19 diagnosis may not necessarily be the driver of poor psychosocial wellbeing; rather, it may be that general pressures of the pandemic, such as daily activity restrictions, healthcare disruptions, and social isolation, may lead to decrements in psychosocial wellbeing.
Overall, this study provides unique insights into the psychosocial problems experienced by US patients with BC during the COVID-19 pandemic and underscores the considerable unmet needs in this patient population. The collective findings suggest that BC imposes substantial psychosocial problems, particularly among those with mBC, with negative impacts observed across multiple domains. Our study results highlight the necessity for interventions that comprehensively enhance patient wellbeing and can help clinicians and public health policymakers identify specific areas in which patients may require further support.

Limitations and Strengths
This study's results should be interpreted in light of relevant limitations. First, healthier patients and those interested in research may have been more likely to choose to participate in the study. Second, although our sample was distributed across all US regions, the first wave of the pandemic differentially impacted communities regarding the degree of restrictions imposed on healthcare and daily activities. Accordingly, patients living in communities with greater (vs. fewer) restrictions may have experienced larger decrements in psychosocial wellbeing. Third, self-reported health and clinical data are not independently verified and may potentially be subject to recall bias. Furthermore, given the study data are cross-sectional, causality cannot be inferred.
The inclusion of a broad array of validated psychosocial wellbeing measures, both general and BC-specific, is a notable strength of the current study. Consequently, the results are able to provide a more comprehensive assessment of the psychosocial problems experienced by patients with BC during the COVID-19 pandemic. Additionally, the large, geographically diverse sample is likewise an important strength of this study, which can enhance the external validity of the findings.

Future Work
Further research is warranted to ascertain whether temporal fluctuations in psychosocial wellbeing during the COVID-19 pandemic have occurred among patients with BC, as well as to examine longitudinal trends by US region. Moreover, given few patients with BC had a history of COVID-19 diagnosis, a future study will need to include a larger sample of these individuals to determine whether COVID-19 diagnosis has an incremental negative impact on psychosocial wellbeing above that which can be attributed to BC, as well as to gauge the magnitude of incremental impact. Similarly, it may also be fruitful to assess the extent to which COVID-19 severity and the presence of long-term sequelae following recovery from COVID-19 infection influence psychosocial wellbeing among patients with BC. An important next step for future research will be to evaluate the impact of psychosocial problems on key clinical outcomes, such as disease progression, survival, and response to treatment, and economic outcomes, including healthcare resource utilization, work productivity loss, and costs (direct and indirect), within the context of the COVID-19 pandemic. Such data may be vital for informing healthcare policymakers' decisions regarding resource allocation and patient support in the event of future public health emergencies.

Conclusions
The current study provides important insights into psychosocial problems associated with BC during the COVID-19 pandemic in the US. COVID-19 diagnosis history was prevalent among patients with BC. Results also suggest impairments to psychosocial wellbeing regarding financial toxicity and poor mental health and emotional functioning, with greater psychosocial problems observed for those with mBC than eBC. Ultimately, these findings underscore the unique vulnerability, burden, and unmet needs among patients with BC, especially those with mBC, during the COVID-19 pandemic.  Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.

Data Availability Statement:
The study dataset is not publicly available due to the data collection only being granted exemption determination from an IRB for this specific protocol. The data presented in this study are available upon reasonable request from the corresponding author.