Approximately 5% of new cancer diagnoses in the United States occur in adolescents and young adults (AYA) who are between 15 and 39 years old (SEER, 2022) at the time of diagnosis. Breast cancer accounts for up to 30% of cancer diagnoses among young women (Miller et al., 2020; Scott et al., 2020; Cathcart-Rake et al., 2021) and often presents aggressively with a higher frequency of adverse histopathological characteristics, worse prognosis, and higher risk of recurrence (Gewefel and Salhia, 2014; Johnson et al., 2018). In 2020, the 5-year relative survival rate for young women breast cancer was estimated to be 86% (Miller et al., 2020), making survivorship an important consideration. Research in AYA cancer survivorship has intensified recently (Smith et al., 2013; Nichols et al., 2021), although a considerable amount of what is published about AYA cancer survivorship has been extrapolated from childhood cancer survivor cohorts (Prasad et al., 2015; Jacola et al., 2016; Miller et al., 2020). As a result, survivorship research specific to young women with breast cancer is lagging.

Health-related quality of life (HRQOL), a broad concept encompassing the perceived physical and mental health of individuals (CDC, 2021), is an important endpoint in clinical trials (Haslam et al., 2020). Women with breast cancer reported the highest prevalence of unmet needs in survivorship (Miroševič et al., 2019), underscoring the urgency of continued research on HRQOL in this population. Younger age at breast cancer diagnosis has been identified as a risk factor for reduced HRQOL in breast cancer survivors (Ganz et al., 2003). For instance, Champion et al. (2014) showed that women diagnosed prior to the age of 45 years were more likely to report depressive symptoms, fatigue, and more attention problems than women diagnosed after age 45. Another study reported that female breast cancer survivors who were diagnosed between 35 and 50 years old had a steeper decline in HRQOL in the first 3 years after treatment and recovered more slowly compared with survivors who were diagnosed at an older age (Roine et al., 2021). Notably, while younger age at diagnosis has been established as a risk factor for reduced HRQOL in breast cancer survivors, HRQOL in young adult breast cancer was not specifically addressed. Patients with breast cancer who are in their 20 and 30 s may experience different social and physical challenges than older patients (Quinn et al., 2015), highlighting the importance of studying HRQOL in young women with breast cancer.

A variety of factors besides younger age have been implicated in poor long-term HRQOL in breast cancer survivors. These factors range from somatic predictors (e.g., fatigue, upper extremity lymphedema, obesity, and menopausal symptoms such as hot flashes and sleep disturbances) (Rossi and Pagani, 2017; Saha et al., 2017; Schmidt et al., 2019; Dominici et al., 2021; Jørgensen et al., 2021; Lei et al., 2021; Park et al., 2021) to social factors (e.g., lower socioeconomic status, lack of private insurance, and race/ethnicity) (Ashing-Giwa and Lim, 2009; Derouen et al., 2013; Samuel et al., 2016; Claridy et al., 2018; Dominici et al., 2021) and mental health concerns (Van Esch et al., 2012; Schoormans et al., 2015; Carreira et al., 2018). While HRQOL in breast cancer survivors of all ages may be impacted by these factors, some predictors are more pertinent to younger survivors. For instance, concerns about premature menopause and infertility are more common among survivors diagnosed prior to age 51 and adversely affect HRQOL (Howard-Anderson et al., 2012). Relatedly, young patients with breast cancer typically require intensive therapy due to aggressive tumors that are often diagnosed at a later, more advanced stage (Murphy et al., 2019; Cathcart-Rake et al., 2021). The associated side effects of intense treatment regimens pose a greater risk of poor physical and emotional well-being (Samuel et al., 2016). Dominici et al. (2021) showed that long-term HRQOL was dependent on local therapy strategy in breast cancer survivors who were diagnosed prior to age 40. Young women who underwent more extensive surgeries (e.g., unilateral/bilateral mastectomies) reported lower HRQOL than peers who received breast-conserving therapy.

Finally, most research efforts to date have focused on long-term outcomes (Champion et al., 2014; Cohee et al., 2017; Dominici et al., 2021; Roine et al., 2021). As a result, little is known about HRQOL in the early stages of survivorship. Research conducted in the first year of treatment across a variety of cancers in AYAs identified an unmet need for mental health or fertility counseling services (Quinn et al., 2015), disruptions in work (Schmidt et al., 2019), educational pursuits (Parsons et al., 2012), and parenting (Bailey et al., 2010). The needs of patients and survivors change as they adjust to their cancer diagnosis and survivorship (Costanzo et al., 2007; Husson et al., 2017). Characterizing patterns of HRQOL and factors associated with reduced HRQOL in AYA breast cancer could improve preventative care and patient empowerment (Howard-Anderson et al., 2012; Gewefel and Salhia, 2014).

In summary, there is a knowledge gap regarding early changes in HRQOL in young women with breast cancer, limiting effective surveillance of HRQOL in this population. To address this gap, we aimed to characterize HRQOL in the first year following diagnosis in women with breast cancer who were diagnosed between 18 and 39 years old. We also sought to explore the impact of patient- and treatment-related factors on modulating HRQOL. Given findings of poor HRQOL in long-term breast cancer survivors (Champion et al., 2014; Roine et al., 2021), we hypothesized that HRQOL would decline during the first year of treatment.

Young women who were diagnosed with breast cancer in young adulthood report excellent HRQOL at diagnosis and even exhibit some improvement over a 12-month period. Our results suggest deficits in HRQOL may not emerge until later in survivorship. There is strong evidence for impaired long-term HRQOL in breast cancer survivors, particularly those who were diagnosed at a younger age (Kroenke et al., 2004; Howard-Anderson et al., 2012; Champion et al., 2014; Carreira et al., 2018; Maurer et al., 2021; Park et al., 2021). The results from the present study are in line with recent work in early breast cancer (Criscitiello et al., 2021), although others have reported declines in HRQOL during treatment in general cohorts of patients with breast cancer (Schoormans et al., 2015; Maurer et al., 2021). Improvements in HRQOL during treatment have also been reported in pediatric cancer populations who undergo intense treatment regimens (Mitchell et al., 2016; Garas et al., 2019). As with long-term breast cancer survivors, pediatric cancer survivors also exhibit poor HRQOL later in survivorship (Kunin-Batson et al., 2014; van der Plas et al., 2020). It seems reasonable to expect that initial improvements in HRQOL are attributable to a sense of relief that the cancer is being treated (Garas et al., 2019), which, in the short run, may outweigh the negative late effects of treatment (Criscitiello et al., 2021). Our results suggest that young adult breast cancer survivors may share this relief to some extent during the first year of treatment and survivorship. However, it is possible that HRQOL diminishes further into survivorship due, in part, to changes in perceived support and increased cumulative burden of treatment-related late effects.

Perceived support from family, friends, and healthcare professionals is an important factor in HRQOL in cancer patients (Usta, 2012; Hurtado-de-Mendoza et al., 2021) and appears to modulate the perceived severity of chemotherapy-related symptoms (Oh et al., 2020). There is evidence to suggest that perceived social support may diminish the further patients that are from diagnosis. A study by Arora et al. (2007) showed that patients with breast cancer reported high levels of emotional support from family and friends at diagnosis; however, emotional support had significantly declined at follow-up. It is possible that diminishing support contributes to decreased HRQOL further in survivorship of breast cancer survivors. Moreover, young breast cancer survivors (diagnosed < 50 years) with a small social network appear to be particularly vulnerable to low HRQOL in comparison with older survivors (Bloom et al., 2012).

Treatment for breast cancer has been associated with long-term neurocognitive difficulties that are often referred to as “chemo-brain” (Janelsins et al., 2017; Ketterl et al., 2019; Eide and Feng, 2020; Schroyen et al., 2021). Neurocognitive difficulties may encompass memory loss, difficulty concentrating, and other relatively subtle changes that can have a detrimental impact on daily functioning (Chan et al., 2016; Sousa et al., 2020) and are negatively associated with HRQOL (Kunin-Batson et al., 2014; Eide and Feng, 2020; van der Plas et al., 2020; Wagner et al., 2020). AYA cancer survivors across various types of cancers have identified neurocognitive deficits as a key issue (Jim et al., 2018). It is possible that functional difficulties of cancer treatment do not manifest until later in survivorship, even though physiological brain changes are already afoot. In their systematic review, Sousa et al. (2020) reported that there was no evidence for functional change acutely after chemotherapy for breast cancer, even though brain changes were already noted. Others showed that alterations in blood markers of inflammation and neuronal integrity increased the patients with longer breast cancer that are from diagnosis (Schroyen et al., 2021). The notion of “allostatic load” may explain the lag between physiological changes and functional deficits. Allostatic load conveys the cumulative impact of physiological “wear and tear” on the brain and body that eventually results in deterioration in physical and mental health (Suvarna et al., 2020; Schroyen et al., 2021). Thus, a longitudinal assessment of a wide variety of markers indicative of physiological “wear and tear” (e.g., quantitative neuroimaging, blood markers of brain injury, and subtle cognitive decline) is a promising tool to help preserve HRQOL in young breast cancer survivors.

The present study also explored factors that may modulate HRQOL in young women with breast cancer, including sociodemographic factors, genetic susceptibility, hormone receptor status, comorbidities, and treatment-related factors. Anxiety/depression was significantly associated with a change in overall HRQOL and functional well-being. Critically, our target population intersects at two demographics that report an elevated risk of anxiety and depression in cancer survivorship: young age and female sex (Yi and Syrjala, 2017). Approximately 28% of patients had anxiety/depression at diagnosis, which could conceivably have contributed to lower emotional well-being at baseline in this sample (Figure 2D). Somewhat surprisingly, patients with anxiety/depression reported overall improvement in HRQOL relative to patients who did not have anxiety/depression at baseline. Young women with anxiety/depression reported lower emotional well-being at baseline and essentially caught up with the non-anxious/non-depressed group 1 year later. One potential explanation is patients with anxiety/depression may have difficulty with emotion regulation in stressful situations (Jazaieri et al., 2015), resulting in greater mood fluctuations than in non-anxious/non-depressed patients. Furthermore, it is possible that the observed improvements in anxiety/depression are related to factors that were not assessed here, such as physical exercise (Patsou et al., 2018). As described above, these improvements may be temporary. Van Esch et al. (2012) reported that anxiety symptoms at breast cancer diagnosis significantly predicted HRQOL 2 years after surgery. Another study showed that the negative impact of depression on HRQOL in breast cancer survivors increased with increased time from diagnosis (Schoormans et al., 2015). Continued surveillance is essential to ensure that these potentially vulnerable, young breast cancer survivors receive the appropriate care (Stafford et al., 2015; Carreira et al., 2018).

Other factors that modulated change in aspects of HRQOL included a family history of cancer, clinical staging at diagnosis, reconstruction, and marital status. Although significant associations were identified, none of these factors appeared to have a clinically meaningful impact on HRQOL during the first year of treatment. For instance, individuals with a family history of cancer reported an average increase of less than four points in emotional well-being. Trends were similar for the other factors that modulated change in HRQOL: Social well-being scores of young women with stage II–III cancer declined with less than two points from baseline to 12 months post-diagnosis, while that of the 0–I group increased one point. Notably, in their research on sociodemographic factors related to HRQOL in breast cancer survivors, Patsou et al. (2018) reported that marital status was not associated with depression/anxiety in survivors age 50 and younger; however, marital status did have a negative impact on depressive symptoms in older breast cancer survivors. These results highlight the possibility that the impact of potential risk factors varies based on age at diagnosis. Collectively, our findings suggest that patient and demographic factors have a minimal impact on changes in HRQOL early in the course of treatment and survivorship in young women with breast cancer.

Health-related quality of life for AYA breast cancer survivors aligns with population norms and remains mostly stable during the first year of treatment. Patient- and treatment-related factors had a limited impact on change in HRQOL during the first year of treatment. While some significant associations were demonstrated (e.g., greater improvement in HRQOL among anxious/depressed patients relative to non-anxious/depressed patients), the clinical significance of these changes remains to be determined. Given that breast cancer at a young age has been clearly associated with poor long-term HRQOL, further study on this population is required to ensure adequate HRQOL is maintained in the long term.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

Written, informed consent was obtained from participants before enrollment in the BMER study. Directly identifiable information was removed from the data. This project was approved by the Institutional Review Board for Human Subjects Research at the University of Iowa (ID 202106560).

EP, HA, and SP contributed to the conceptualization, design, and methodology of the study. EP, HA, MC, and SM contributed to the investigation. BL and SM were performed statistical analysis. BL and EP visualized the data. HA and EP wrote the initial draft of the manuscript. SP and EP contributed to funding acquisition. All authors had full access to the data in the study, take responsibility for the integrity of the data and accuracy of the data analysis, revised, read, and approved the submitted version of the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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