Health-related quality of life (QoL) is a multi-dimensional concept divided into four domains, namely, physical, psychological, social, and spiritual (1, 2). Physical well-being captures physical functional ability, physical symptoms (e.g., pain, nausea), fertility, strength, and sleep. Psychological well-being includes symptoms of anxiety and depression, fear of recurrence, cognition, distress, enjoyment of life, and overall QoL perception. Social well-being reflects family distress, roles, and relationships, appearance, employment, isolation, and finances. Spiritual well-being captures the meaning of illness, religiosity, transcendence, hope, uncertainty, and positive changes. These domains are interrelated with each influencing the other while being affected by health conditions such as cancer and its treatment (3–5).

Breast cancer was the second leading cause of death among women in the United States until 2020 (6) and is expected to surpass heart disease in the next decade (7). A breast abnormality such as a lump begins a cycle of concern around biopsy and its results (8) even if the results indicate no malignancy (9). If malignancy is found, conventional medical care begins with surgery; however, some women may first undergo a course of chemotherapy to shrink the tumor before surgery (neoadjuvant therapy). For early-stage breast cancer, the most common surgery is the breast-conserving lumpectomy with sentinel node mapping. Following surgery, additional symptoms and concerns may include altered body image, pain, decreased arm range of motion, scars, brachial plexopathy, as well as, the knowledge of more advanced cancer with positive nodes. If adjuvant chemotherapy or targeted therapy is indicated, it is administered after surgery, may last for 6–12 months, and cause multiple symptoms, such as fatigue, nausea, and symptoms related to chemotherapy-induced menopause. Radiation therapy is administered after surgery either before or most often after adjuvant chemotherapy. If chemotherapy is not indicated, then 6 week radiation therapy follows surgery. Finally, hormonal therapy or trastuzumab is given for receptor-positive breast cancer for years after chemotherapy and/or radiation is complete (10–12).

For women with breast cancer, the evidence suggests that physical QoL is most affected by chemotherapy as opposed to other treatments (13, 14). More than 60% of women with breast cancer had clinically significant problems with fatigue and sleep (15). The poly-symptom experience of people with solid tumor cancers has been well-documented in the literature (16–19). Among people who have just finished chemotherapy, the median severity of pain and fatigue was 6 on a 0–10 scale (20), and sustained levels of post-treatment pain and fatigue, and peripheral neuropathy have been reported for people who have finished treatment for breast or other solid tumor cancers (21, 22).

Social support is of paramount importance during cancer treatment because it has been shown to reduce the risk of psychological distress and accompanying emotional support has been associated with better social and emotional well-being (23–29). The benefits of social and emotional support for the QoL of a cancer survivor are at least partly related to the reduction in negative appraisal and stressful response to illness (30–35). The spiritual domain of QoL has also been found to be positively related to psychological well-being and negatively related to symptom distress among breast cancer survivors (36, 37).

Psychological distress (depression and anxiety) is highly prevalent in breast cancer survivors and has negative consequences for multiple QoL domains (38–40). Depression occurs in up to 60% of cancer survivors across cancer sites and treatments (41). Between 35 and 65% report anxiety during treatment (42) and 45% experience both depression and anxiety (43, 44). Major depression occurs in approximately 16% of survivors, with subthreshold depressive disorders appearing in almost 22% during treatment (15). These prevalence rates are about 3 times higher than in the general population (45, 46). Psychological distress can interfere with cognitive functioning (e.g., memory, attention, and decision making) (47, 48) and motivation to enact self-management behaviors related to chronic diseases and their treatment (49–51).

The literature on cancer- and treatment-related changes in neurocognitive outcomes has mixed findings. Several studies, meta-analyses, and systematic reviews indicate small to moderate effect sizes for diminished cognitive functioning due to adjuvant chemotherapy (52–54). Another meta-analysis found consistent differences with normative scores only for visual memory, and small effect sizes in comparison to normative scores for executive function, information processing speed, and verbal memory (55). The most recent systematic review and meta-analysis supported elevated risk of neurocognitive dysfunction among women with breast cancer compared with controls, and women treated with chemotherapy compared with other modalities, although, strong statistical evidence was found in only three of 24 studies included in the meta-analysis (56). Mechanisms theorized to underpin cognitive changes have been proposed and included links between cytokines and epigenetic reprogramming (57), particularly with chemotherapy (58, 59). Boivin et al. (60) proposed that immunologic marker CD8+ was sensitive to a broad range of poorer QoL and neurocognitive functioning outcomes, especially in women undergoing chemotherapy (60). Finally, studies of neurocognitive functioning included various measures, from objective performance-based measures to self-report, which are often only weakly correlated and reflect potentially different constructs of cognitive ability (objective tests) vs. the functional effect of cognitive ability in everyday life (self-report) (61).

Understanding which QoL domains affected the most and when, beginning with time from cancer diagnosis and extending past the end of cancer treatment would inform supportive care interventions. This study was a case/control prospective observational cohort comparison (patients with breast cancer biopsy vs. matched control women with a benign biopsy diagnosis). As such, the present study aimed to compare the QoL outcomes in physical, psychological, social, and spiritual domains immediately after biopsy results and 4 and 12 months later among three groups of women with (a) benign biopsy results, (b) malignant tumors not treated with chemotherapy, and (c) malignant tumors treated with chemotherapy. We hypothesized that immediately after biopsy results, the groups with malignancy would have worse psychological QoL, including depression, anxiety, and cognition but better spiritual well-being; at 4 and 12 months, women with malignancy treated with chemotherapy will have worse physical, social, and psychological QoL compared with the other two groups.

This research is based on longitudinal data on the QoL for a cohort of women recruited at the time of biopsy for a breast abnormality and followed for 1 year. The study was approved by the Institutional Review Board of Michigan State University and the affiliated oncology settings.

The entire sample of 159 women included 87 women with histologically proven breast cancer defined as ductal carcinoma in situ or invasive ductal or invasive lobular carcinoma and 72 women with a non-proliferative epithelial cell breast biopsy performed within the previous 4 months. The demographic characteristics of the study sample and descriptive statistics of the outcomes at baseline for the entire sample and three groups of interest are summarized in Table 1. A total of five women (three in benign group, one in chemotherapy, and one in no chemotherapy group) dropped out between intake at 4 months, and an additional two women in the benign group were lost to follow-up between 4 and 12 months. Women with malignant biopsy results not treated with chemotherapy were older, whereas those treated with chemotherapy had worse psychological and social QoL at baseline, and worse scores on depression at baseline. The benign group had the lowest spirituality scores at baseline. Among CogState scores, only monitoring accuracy was worse in the group that later received chemotherapy (Table 1).

The comparison of groups with benign vs. malignant findings adds to the existing literature on the effects of breast cancer diagnosis and chemotherapy treatment on physical, psychological, social, and spiritual QoL. When comparing the benign biopsy (no breast cancer) group, no chemotherapy breast cancer, and chemotherapy breast cancer treatment groups, differences at the time of diagnosis were found on psychological, social, and spiritual QoL, favoring the benign group except for spirituality. Controlling for the QoL measures at the time of diagnosis and age, education, income, and chemotherapy group had more depressive symptoms than the no chemotherapy breast cancer and the control groups. We observed higher (better) QoL scores for the benign biopsy than the breast cancer groups on psychological, social, and physical QoL domains, respectively; and the chemotherapy treatment group had the worse scores for all these domains. However, the breast cancer groups were higher on spiritual QoL (more affirmation of positive spirituality items) than the benign (no breast cancer) group, even though, they were comparable at diagnosis. The fact that spiritual QoL can be higher for the participants with breast cancer during treatment while psychological and social QoL can be worse (compared with the benign biopsy group) is important to note. This is because this finding suggests that spirituality is not necessarily dependent on emotional well-being during treatment for a life-threatening disease for women diagnosed with breast cancer. Higher spirituality may buffer psychological distress resulting from cancer diagnosis (70).

These findings regarding depressive symptoms (part of psychological QoL) align with the literature indicating that breast cancer survivors have greater mental health problems than cancer-free controls (56, 71–73). The previous qualitative analysis revealed that all women in this sample reported a difficult time pre-diagnosis (74). Because enrollment into the present study happened at the time of biopsy for a breast abnormality, we were able to discern the effect of the diagnosis vs. subsequent treatment. Greater depressive symptoms in the cancer groups were found at the time of diagnosis, but not 4 months and 1 year later when controlling for depression at the time of diagnosis. This finding is consistent with the literature on high (50%) prevalence of depressive symptoms shortly after cancer diagnosis and diminishing over the next year, while remaining higher than in the general population even years after cancer treatment completion (75–77). Even though, for most people with cancer depressive symptoms are not sufficiently severe to warrant a full clinical diagnosis of depression (78–81), but depressive symptomatology needs attention, as it has been suggested to be a predictor of better survival and reduced morbidity in several cancer populations (82).

Further, cancer treatment gives rise to multiple physical and emotional symptoms (19). The biological changes due to chemotherapy or other treatments and the resulting inflammatory processes may be responsible for the impairments in physical QoL (17, 83, 84), and these findings regarding physical QoL agree with the literature and contribute to the evidence that even a year after the cancer diagnosis, physical QoL remains worse for women with cancer compared to controls.

On the other hand, for some of the problems such as memory and concentration, chemotherapy may not be the cause, but rather, the stress of the diagnosis may be a significant contributor to early concerns expressed by women with cancer. The objective computer-based measures of cognition and attention showed no differences over time (85). It is possible that if patients report perceived problems with cognition (sometimes referred to as “chemo brain”), a broad evaluation may be needed to identify contributing issues related to all domains of QoL. The findings of this research are consistent with those obtained by Darby (86) in a study of 60 women (30 on chemotherapy and 30 controls), who found some problems in attention and learning prior to the start of chemotherapy, with only minor changes during and after the chemotherapy period (86). Neither cognitive test scores nor self-report of their cognitive performance of the women differed over the course of treatment or by the group; though initially, at the time of diagnosis before the initiation of treatment, the chemotherapy group demonstrated lower monitoring accuracy compared with the other two groups.

The effects of breast cancer disease and treatment, especially chemotherapy, on neuropsychological functioning have been examined in studies with patients with breast cancer over decades (87–89). The cognitive fatigue from the psychosocial stress associated with breast cancer disease and treatment may be largely responsible for diminished neuropsychological performance in people on active treatment (90) and years after finishing treatment (91). Finally, the use of immunological biomarkers during differing types of breast cancer treatment may help disentangle the effects of the disease itself and its treatment from the psychosocial stress, causing cognitive fatigue and diminished capacity (92, 93).

The limitations of the present study include relatively small sample size and unequal group sizes resulting from biopsy results and planned treatment. Women in the sample were also well-educated and the results may not generalize to those with lower education levels. Because the women in the sample were not randomly assigned to groups receiving and not receiving chemotherapy, any differences found between these groups in the outcome variables must be interpreted cautiously. Further, multiple clinical factors and preferences of women played a role in treatment decisions after a malignant biopsy result. We did not disentangle these factors because data on preferences of the women and medical record data were not uniformly available. Even if clinical data were available, extraneous confounding variables cannot be ruled due to the observational nature of this study.

These findings and those of others suggest that interventions to improve the emotional and cognitive components of QoL may be especially important at the time of cancer diagnosis. A threatening illness, such as breast cancer, can be conceptualized as a traumatic event in the life of a woman and her significant others. While the benign group experienced relief after diagnosis, the emotional problems intensified among those diagnosed with cancer. The cancer diagnosis experience evokes emotions and memories; and often these are negative, causing distress, which may affect multiple other QoL components. Supportive care interventions initiated at the time of diagnosis may be particularly impactful for psychological QoL, including depression and cognition.

The raw data supporting the conclusions of this article will be made available by the authors upon request, without undue reservation.

The studies involving human participants were reviewed and approved by Michigan State University's Biomedical & Health Institutional Review Board (BIRB) application #05-1031S Breast Cancer SEQL (Spirituality, Emotional Well-being and Quality of Life) Project (IRRC#6059M) (PI: Michael J. Boivin). The patients/participants provided their written informed consent to participate in this study.

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

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.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.