Abstract
Background
Patients with newly diagnosed breast cancer and high levels of anxiety often pursue more aggressive surgical interventions. The neoadjuvant treatment (NAT) setting could provide a window of opportunity to address patients’ anxiety. However, the impact of anxiety on surgical decisions in the setting of NAT for breast cancer has not been previously studied.
Materials and Methods
A prospective database of patients with breast cancer treated with NAT at BC Cancer was used to identify patients treated with NAT and subsequent surgical resection. Patients with bilateral breast cancer or BRCA mutations or those referred to the hereditary cancer program were excluded. An anxiety score of 0–3 was assigned based on responses to the Edmonton Symptom Assessment System and Psychosocial Screen for Cancer. Clinicopathological information and treatment data were retrieved and cross‐referenced between the low‐anxiety (scores 0–1) and high‐anxiety (scores 2–3) cohorts.
Results
From 2012 to 2016, 203 patients met eligibility criteria. Of these, 93 patients (45.8%) had low anxiety and 110 patients (54.2%) had high anxiety. Overall, 161 patients (79.3%) had locally advanced cancers; no differences in stage, grade, or biomarkers were found between the low‐ and high‐anxiety cohorts. Patients with high self‐reported anxiety at initial consultation were younger (mean 56 years vs. 60 years; p = .011) and more likely to undergo mastectomy for breast‐conserving surgery–eligible disease and bilateral mastectomy for unilateral disease compared with those with low anxiety (37.3% vs. 18.3%; likelihood ratio 9.15; p = .002). No significant differences in treatment timelines were identified between the two cohorts.
Conclusion
Patients with high anxiety at initial consultation were nine times more likely to undergo aggressive surgery compared with patients with low anxiety. These findings underscore the need for early identification of patients who may benefit from tailored supportive and educational services to address sources of anxiety and knowledge gaps.
Implications for Practice
The prevalence of anxiety among women with newly diagnosed breast cancer is being increasingly acknowledged. However, health care providers have not fully appreciated the impact of anxiety on the surgical management of patients with early‐stage breast cancer. This study highlights the importance of self‐reported anxiety on surgical management. The preoperative period provides a unique window of opportunity to address sources of anxiety and provide targeted educational materials over a period of 4–6 months, which may ultimately lead to less aggressive surgery when it is not needed.
Keywords: Anxiety, Preoperative treatment, Psychooncology, Early‐stage breast cancer, Surgical treatment
Short abstract
This article reviews the effect of patient anxiety on decisions related to surgical treatment of early stage breast cancer and the use of self‐reported anxiety as a clinical tool to tailor educational and supportive resources.
Introduction
At the time of diagnosis of breast cancer, patients receive a large amount of information in a relatively short period of time 1. Decisions regarding surgical management are often made quickly when the sequence of events begins with surgery and rarely allow for concomitant prophylactic contralateral mastectomy (PCM). However, patients treated neoadjuvantly benefit from a longer period to reach a decision and consider a wider breadth of options. The impact of high anxiety on surgical decision‐making has been demonstrated in various cancer settings 1, 2, 3, 4, 5, 6. For women with breast cancer, a desire to reduce the risk of contralateral breast cancer and improve survival is most often identified as a driving factor in their decision to have a PCM 7, 8. However, knowledge gaps exist 3, 9, and patients are increasingly vulnerable to misinformation given widely available non–peer‐reviewed online content and social media. Indeed, many women report that their choices for locoregional management of breast cancer are reflective of their desire to reduce the risk of systemic recurrence and breast cancer mortality 9.
The additional value of using standardized tools to assess reported physical, psychological, and emotional symptoms in patients with cancer has become increasingly important to guide initiatives to improve patient experience 10, 11, 12. One of the most commonly used tools, the Edmonton Symptom Assessment Scale (ESAS), addresses nine common symptoms experienced by patients with cancer, including depression, anxiety, and wellbeing 13, 14. The severity of each symptom is rated on a numeric scale from 0 to 10, indicating that the symptom is either absent or, to the other extreme, the worst possible severity (supplemental online Appendix 1). Additional cancer‐specific tools have been developed to screen for emotional distress in patients with cancer 15, including the Psychosocial Screen for Cancer (PSSCAN‐R). This tool consists of a 21‐item questionnaire that has been favored because of its brevity, breadth, and inclusion of both positive and negative aspects of patients’ quality of life, namely, the level of distress and social support 16. Subsequent validation results and normative data suggest an optimal cutoff score of 11 to achieve the highest sensitivity and specificity 17. Finally, the Canadian Problem Checklist (CPC) is an additional tool exploring patients’ self‐reported needs across six psychosocial domains, which has been used to identify at‐risk patients who may benefit from psychological support most urgently 18.
For patients undergoing neoadjuvant therapy (NAT) for breast cancer, a longer period of discussion ensues regarding the relative risks and merits of breast‐conserving surgery (BCS), unilateral mastectomy, and bilateral mastectomy. However, the effect of anxiety at initial diagnosis and the impact of psychological support on surgical decisions is unknown in the setting of preoperative systemic treatment.
Materials and Methods
This was a cohort study of patients with breast cancer undergoing NAT in which anxiety scores were compared with the type of surgery received. The BC Cancer NAT prospective institutional database was used to identify patients with breast cancer treated with NAT. The database, established in 2012, includes details of demographics, pathology, treatment, and outcomes for all patients with breast cancer offered NAT for breast cancer at the BC Cancer, Vancouver Center, in Canada. The purpose of this database is to inform quality assurance and quality improvement initiatives, and it includes demographic information as well as treatment information and outcomes. Database accuracy was routinely ensured by ongoing quarterly quality assessment, in which 10–20 charts were randomly selected for in‐depth audit, and percent agreement among data managers was reported quarterly. This database is maintained on an encrypted server, only accessible to the database managers. Data used for research purposes are then deidentified prior to analyses. This project was conducted in accordance and approval with the University of British Columbia BCCA Research Ethics Board.
Patients with histologically proven clinical stage I–III breast cancer who completed NAT from 2012 to 2017 and went on to have surgical resection were included. Patients with previous breast cancer or synchronous contralateral breast cancers, those with BRCA1 or 2 mutations, those awaiting referral to the hereditary cancer program, and those who had other potential indications for bilateral mastectomy were excluded. Patients with incomplete records were also excluded.
Anxiety Score Calculation
Charts were audited for the PSSCAN‐R, ESAS, and CPC forms completed at initial consultation. A scoring system was created to incorporate all available information pertaining to anxiety at initial medical oncology consultation (Fig. 1). Patients were assigned a score of 0 if they scored <11 on the PSSCAN‐R anxiety questions, scored <3 on the ESAS anxiety scale, and did not have any of the specified fields filled out on the CPC. Patients were assigned a score of 1 if they scored both <11 on the PSSCAN‐R anxiety questions and < 3 on the ESAS anxiety scale but filled out at least one of the prespecified fields on the CPC. Patients were assigned a score of 2 if they scored either ≥11 on the PSSCAN‐R anxiety questions or ≥3 on the ESAS anxiety scale, regardless of fields filled out on the CPC. A score of 2 was also assigned if the patient scored both ≥11 on the PSSCAN‐R anxiety questions and ≥3 on the ESAS anxiety scale but did not have any of the specified fields filled out on the CPC. Patients were assigned a score of 3 if they scored ≥11 on the PSSCAN‐R anxiety questions, scored ≥3 on the ESAS anxiety scale, and filled out at least one of the specified fields on the CPC. Patients were then divided into low‐ and high‐anxiety cohorts, defined as low anxiety for patients with a score of 0 or 1 and high anxiety for patients with a score of 2 or 3.
Figure 1.
Anxiety score calculation using PSSCAN‐R, ESAS, and CPC. Abbreviations: CPC, Canadian Problem Checklist; ESAS, Edmonton Symptom Assessment Scale; PSSCAN‐R, Psychosocial Screen for Cancer, Revised.
Outcome Assessment
Information on age, clinical stage, grade, receptor status, initial surgical plan, and final surgery performed was extracted from the database. The final surgery performed was recorded as bilateral mastectomy, unilateral mastectomy for BCS‐eligible patients, unilateral mastectomy for BCS‐ineligible patients, or BCS. Patient eligibility for BCS was determined from surgical consultation reports. The rates of conservative surgery (BCS for eligible patients or mastectomy for BCS‐ineligible patients) and aggressive surgery (bilateral mastectomy for patients without bilateral disease or mastectomy for BCS‐eligible patients) were compared across the low‐anxiety and high‐anxiety cohorts. The association of anxiety to treatment timelines was also assessed. Achievement of target treatment timelines for medical oncology consultation to chemotherapy initiation (≤14 days), chemotherapy completion to surgery (≤30 days), and surgery to radiation therapy initiation (≤30 days) was compared between the low‐ and high‐anxiety cohorts. Use of counseling services was also compared relative to conservative or aggressive surgery between anxiety cohorts.
Statistical Analysis
Descriptive statistics were used to summarize patient demographics, tumor characteristics, treatment details, and anxiety scores. Anxiety scores calculated from the PSSCAN‐R, ESAS, and CPC were correlated with surgical data from the BC Cancer NAT database. Chi‐square tests and likelihood ratios (LRs) were used to compare the rates of conservative surgery (BCS for eligible patients or mastectomy for BCS‐ineligible patients) and aggressive surgery (bilateral mastectomy for patients without bilateral disease or mastectomy for patients eligible for BCS) in patients with low anxiety and high anxiety. Independent‐samples t tests were used to assess for statistical significance for all continuous variables whereas chi‐square tests were used for other categorical variables. All statistical analyses were performed with the Statistical Package for Social Sciences (SPSS for Windows, version 24.0; SPSS Inc., Chicago, IL).
Results
Cohort Characteristics
From 2012 to 2017, a total of 361 patients treated with NAT and surgical resection included in the BC Cancer NAT database were identified, and 203 patients met eligibility criteria. Overall, 55 patients had missing or incomplete data, and 103 patients had bilateral disease, had a BRCA1 or 2 mutation, and/or had been referred for hereditary counseling (Fig. 2). The mean age of patients was 58 years, range of 36–92 years (Table 1). A total of 161 patients (79.3%) had locally advanced breast cancer (defined as stage IIb or greater disease), 2 patients (1.0%) had stage I disease, and 40 patients (19.7%) had stage IIa disease. With regard to grade, 15 patients (7.4%) had grade 1 tumors, 113 patients (55.7%) had grade 2 tumors, and 71 patients (35.0%) had grade 3 tumors. An additional 4 cases (2.0%) had missing information on tumor grade. Histological biomarker status was triple negative for 13 patients (6.4%), human epidermal growth receptor 2 (HER2) positive for 91 patients (44.8%), and estrogen receptor (ER) positive, HER2 negative for 99 patients (48.8%). Among the whole study population, 161 patients (79.3%) received neoadjuvant chemotherapy and 42 patients (20.7%) received neoadjuvant endocrine therapy.
Figure 2.
Consort diagram of patient population.
Table 1.
Patient characteristics
| Variable | Anxiety level | p value | ||
|---|---|---|---|---|
| Low anxiety (n = 93) | High anxiety (n = 110) | Total (n = 203) | ||
| Age at consultation, years | .011 | |||
| Median | 60 years | 56 years | 58 years | |
| Clinical stage, n (%) | .698 | |||
| Ia | 0 (0) | 2 (1.8) | 2 (1.0) | |
| IIa | 19 (20.4) | 21 (19.1) | 40 (19.7) | |
| IIb | 43 (46.2) | 42 (38.2) | 85 (41.9) | |
| III | 21 (33.3) | 28 (40.9) | 49 (37.4) | |
| Grade, n (%) | .263 | |||
| 1 | 8 (8.6) | 7 (6.4) | 15 (7.4) | |
| 2 | 56 (60.2) | 57 (51.8) | 113 (55.7) | |
| 3 | 27 (29.0) | 44 (40.0) | 71 (35.0) | |
| N/A | 2 (2.2) | 2 (1.8) | 4 (1.9) | |
| Receptor status, n (%) | .228 | |||
| Triple negative | 7 (7.5) | 5 (4.5) | 12 (5.9) | |
| HER2+ | 36 (38.7) | 55 (50.0) | 91 (44.8) | |
| ER+/HER2− | 50 (53.8) | 50 (45.5) | 100 (49.3) | |
| Treatment, n (%) | .056 | |||
| Chemotherapy | 68 (73.1) | 93 (84.5) | 161 (79.3) | |
| Endocrine therapy | 25 (26.9) | 17 (15.5) | 42 (20.7) | |
Abbreviations: ER, estrogen receptor; HER2, human epidermal growth receptor 2; N/A, not available.
Anxiety Scores
Questionnaire completion rate was 78.7% for all eligible patients. Of the 203 patients with evaluable responses, 93 patients (45.8%) had low anxiety scores and 110 patients (54.2%) had high anxiety scores at initial medical oncology consultation (Table 1). Patients in the high‐anxiety cohort were younger compared with those in the low‐anxiety cohort (mean age 56 years and 60 years, respectively; p = .011). Stage, grade, and biomarkers were similar between groups. Locally advanced breast cancer was present in 74 patients (79.6%) with low anxiety and 87 patients (79.1%) with high anxiety (p = .93). Grade 3 tumors were present in 44 patients (40.0%) and 27 patients (29.0%) with low and high anxiety, respectively (p = .104). Biomarker status in the low‐ and high‐anxiety patients was not significantly different (p = .37). Triple‐negative biomarkers were present in 7.5% and 4.5% of the low‐ and high‐anxiety patient cohorts, respectively. HER2‐positive biomarkers were present in 38.7% of the patients with low anxiety and 50.0% of the patients with high anxiety. Finally, ER‐positive/HER2‐negative biomarkers were present in 53.8% and 45.5% of the low‐ and high‐anxiety patient cohorts. Those with high anxiety were more likely to receive chemotherapy compared with patients with low anxiety (84.5% and 72.0%, respectively; LR 4.72; p = .030).
Anxiety and Surgical Decision‐Making
Patients with high self‐reported anxiety at initial consultation were more likely to undergo mastectomy for BCS‐eligible disease or bilateral mastectomy for unilateral disease compared with those with low self‐reported anxiety at initial consultation (37.3% vs. 18.3%; LR 9.15; p = .002; Fig. 3). Of the 110 patients with high anxiety, 46 patients (42%) used counseling services before surgery. No significant differences in surgical decision‐making were observed in the 46 patients with high anxiety who had counseling compared with the 64 patients with high anxiety who did not have counseling (32.6% vs. 40.6%; p = .39).
Figure 3.
Rates of surgery in patients with high and low anxiety.
Anxiety and Treatment Timelines
After excluding patients who received endocrine therapy, had missing timeline data, or received radiation before surgery, 144 patients remained for analysis of target treatment timeline achievement. No significant differences in achievement of target treatment timelines were identified when comparing the low‐ and high‐anxiety cohorts for time from medical oncology consultation to chemotherapy initiation (target within 14 days; 68.4% and 71.3%, respectively; p = .71), time of chemotherapy completion to surgery (target within 30 days; 36.8% and 27.6%, respectively; p = .24), or time of surgery to radiation initiation (target within 30 days; 1.8% and 3.4%, respectively; p = .55).
Discussion
This study reveals that patients with high anxiety were nine times more likely to undergo aggressive surgery and four times more likely to receive chemotherapy compared with patients with low anxiety, despite having similar clinical stage, grade, and biomarkers at the time of consultation. Additionally, counseling resources were underused by patients, although no direct correlation between the use of services and anxiety level was observed. However, it should be noted that overall numbers were small. The findings of this study further validate the significant impact of anxiety on surgical decision‐making in the cancer setting. Although more aggressive surgery has been related to higher anxiety levels in the setting of breast cancer 2, 3, 4, this study suggests a much greater impact than what was previously understood. In fact, several prior studies assessing the rate of contralateral prophylactic mastectomy in patients with breast cancer focused largely on patient education, reporting patients’ perception of higher rates of secondary malignancies and a poor understanding of the factors associated with a higher risk of death but also a false perception that more aggressive locoregional treatment could reduce the risk of breast cancer events, particularly distant recurrences 9. In this study, we report here that despite similar education provided to both those with high anxiety scores and those with low anxiety scores at initial consultation, those in the higher‐anxiety group had a nine times higher chance of undergoing more aggressive surgery than medically necessary. Patient anxiety on understanding and perception of risk is complex, and these findings underscore the reason why patient education alone may not have an impact on these outcomes.
The study findings highlight the fact that self‐reported anxiety levels can inform and assist physicians in identifying patients who are more likely to undergo more aggressive surgery than medically necessary. Although using a single scale to stratify patients may be practical, this novel approach to quantifying anxiety was preferred in order to capture emotional distress, quality of life, social support, and other important psychosocial needs, beyond the physical symptoms associated with cancer. In turn, these patients may benefit from tailored counseling and support services, and indeed the opportunity to identify and link patients with these resources seems opportune in the neoadjuvant setting. The neoadjuvant setting may also be conducive to additional opportunities for communication to discuss surgical management options with patients, including the respective risks and merits as their response to treatment is assessed. In fact, recent trials have suggested a benefit from subsequent adjuvant treatment for patients with residual disease following NAT 19, 20, which will undoubtedly lead to higher rates of NAT. Consequently, avoiding unnecessary aggressive surgery with a potential for higher complications is critical as it may ultimately delay or interfere with the delivery of additional systemic therapy with a proven survival advantage. The NAT timeline could therefore allow for ongoing discussions and multidisciplinary collaboration to address patients’ anxiety and to bridge the knowledge gaps through the development of targeted educational materials and support services.
Among the limitations of this study, it should be noted that the source of data was a prospective institutional database, which poses some selection bias for patients offered neoadjuvant treatment as opposed to adjuvant treatment. Additionally, the triple‐negative breast cancer (TNBC) population is slightly underrepresented in this study, as patients below the age of 60 with a TNBC are referred for hereditary cancer testing and thus were excluded from this analysis. Nonetheless, the majority of patients included in this study were defined as locally advanced, which is representative of patients included in NAT trials. The high‐anxiety cohort was also younger, which could have skewed the results in favor of more aggressive surgical management, although the patients’ eligibility for BCS was abstracted directly from surgical consultation notes, irrespective of age. It should also be noted that rates of reconstructive surgery were not incorporated in this model, although both patients with low anxiety and those with high anxiety would have been offered an equal opportunity and access to reconstruction. Furthermore, it remains unclear if the association between low and high anxiety levels is consistent across various time points during NAT, as the outcomes for this study were assessed at a single time point prior to receiving systemic treatment. Perhaps a change in anxiety levels over time could have an impact on final surgical management, although this remains speculative. Additionally, it is also unclear if the introduction of additional opportunities for tailored education, counseling, and support services can alter the decision to pursue aggressive surgical interventions.
This study identifies opportunities for future work in the area of patient anxiety at initial consultation and impact on disease management and outcomes. It also raises the question of whether assessment of anxiety at multiple time points can further our understanding of the effect of anxiety on patients’ treatment decisions, although it is unclear if the evolution of self‐reported levels of anxiety would alter rates of aggressive surgery. Although there have been recent studies looking at the role of prehabilitation, very little attention has been drawn to addressing the psychosocial and emotional needs of patients undergoing NAT. To this effect, a collaborative effort across Canada is underway to develop such an intervention. A greater understanding of patient needs would also be a valuable topic of future research to further understand the most beneficial educational and supportive strategies. Finally, future collaborations with patient and family counseling services may further our understanding of potential barriers, such as the lack of educational materials, resource availability, or perceived stigma of anxiety and mental health issues that may be associated with the underuse of existing supportive services.
Conclusion
Patients with high anxiety were more likely to undergo mastectomy for BCS‐eligible disease or bilateral mastectomy for unilateral disease compared with patients with low anxiety. Patients with high anxiety who used supportive services had similar rates of aggressive surgery compared with patients with high anxiety who did not use supportive services, although this may be reflective of the lack of tailored support services for this patient population. As the uptake of NAT increases, it will become increasingly important to avoid unnecessary aggressive surgeries that may interfere with subsequent adjuvant treatment. This study emphasizes the importance of facilitating patient–physician communication and patient‐centered care by providing feedback to the oncology team regarding patients’ level of anxiety and should be the topic of future research.
Author Contributions
Conception/design: Nathalie LeVasseur, Huaqi Li, Winson Cheung, Elaine Mckevitt, Rebecca Warburton, Christine Simmons
Provision of study material or patients: Nathalie LeVasseur, Huaqi Li, Stephen Chia, Christine Simmons
Collection and/or assembly of data: Huaqi Li, Kaylie‐Anne Willemsma, Adam Deruchie Tan
Data analysis and interpretation: Nathalie LeVasseur, Stephen Chia, Christine Simmons
Manuscript writing: Nathalie LeVasseur, Christine Simmons
Final approval of manuscript: Nathalie LeVasseur, Huaqi Li, Winson Cheung, Paula Myers, Elaine Mckevitt, Rebecca Warburton, Kaylie‐Anne Willemsma, Adam Deruchie Tan, Stephen Chia, Christine Simmons
Disclosures
Nathalie LeVasseur: Abbvie (RF), Pfizer, TerSera (SAB); Winson Cheung: Pfizer, Celgene (RF); Stephen Chia: Novartis, Pfizer, Roche, Eli Lilly and Company (C/A); Christine Simmons: Novartis, Pfizer, Roche, Eli Lilly and Company (C/A). The other authors indicated no financial relationships.
(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board
Acknowledgments
We thank the Breast Cancer Outcomes Unit for data management support. This project was conducted in accordance and approval with the University of British Columbia BC Cancer Research Ethics Board and with the 1964 Helsinki declaration and its later amendments. This study was supported by the operating funds of the Breast Cancer Outcomes Unit.
Disclosures of potential conflicts of interest may be found at the end of this article.
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