Abstract
PURPOSE:
Aromatase inhibitor (AI) associated symptoms are large contributors to early discontinuation. Though guidelines exist for management of these symptoms, little is known about the degree to which physicians address symptoms and adhere to the guidelines for treatment.
PATIENTS:
In this retrospective chart review, 179 women with hormone receptor positive breast cancer who were prescribed an AI between October 15, 2012 and September 14, 2017 were randomly selected from the institution’s National Association of Central Cancer Registry.
METHODS:
Patient medical records were reviewed to identify the prevalence of symptom documentation and management. Documented symptoms were categorized into musculoskeletal, vasomotor, and urogenital. Symptom treatment guidelines were compiled from the National Comprehensive Cancer Network (NCCN) and the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO). Treatments were categorized as either guideline or non-guideline. Among patients with symptoms recorded, Chi square tests and time-to-event models were used to examine 1) factors associated with treatment and 2) factors associated with guideline-based treatment.
RESULTS:
Among 179 women prescribed an AI, 82% had at least one symptom and 46% had multiple symptoms. Of the 147 women with any documented symptom, 97 (66%) received some form of symptom-palliating treatment. Seventy-seven patients (52%) received guideline-based treatments or guideline-based treatments in combination with non-guideline based treatments. There were no differences in receipt of treatment overall (i.e. guideline or non-guideline-based for either vasomotor musculoskeletal by age, race, or stage.
CONCLUSIONS:
Although 82% of patients had symptoms documented in their medical records, just over half of those patients received guideline-based treatment.
MICRO-ABSTRACT
Aromatase inhibitor (AI) associated symptom management is a poorly studied contributor to early AI discontinuation. This retrospective chart review included 179 randomly selected women prescribed an AI. Eighty-two percent of patients had at least one symptom and 52% of those patients were treated based on guidelines. AI-associated symptoms were documented well, but not treated to the same extent.
INTRODUCTION
Breast cancer is currently the most diagnosed cancer in the United States (U.S), with 268,600 new cases diagnosed last year and 3.8 million women living with a history of breast cancer in U.S. 1 Despite efficacious screening and treatments, breast cancer is the second leading cause of mortality from malignancy in the U.S.2 One likely contributor to these suboptimal outcomes is medication nonadherence, described by the World Health Organization as a leading cause of preventable death.3,4 Aromatase inhibitors (AIs) are now prescribed for over 80% of postmenopausal women with estrogen receptor positive breast cancer. AIs block the enzyme aromatase, inhibiting the peripheral conversion of androgens to estrogens to diminish tumor growth in estrogen or progesterone receptor (hormone receptor) positive breast tumors.5 AIs are recommended for use as adjuvant therapy for 5 to 10 years following initial breast cancer treatment.6 However, AI adherence has been shown to be poor in a series of studies, and there are currently few interventions that have been proven to substantially improve adherence rates.7,8
Symptoms associated with AIs are well described in trials and include musculoskeletal pain, genitourinary symptoms (e.g. vaginal dryness, dyspareunia), and vasomotor symptoms (e.g., hot flashes, night sweats).9,10 Current literature suggests that up to 90% of patients taking AIs will experience at least one symptom, with the majority reporting musculoskeletal complaints.9–12 The National Comprehensive Cancer Network (NCCN) and the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) have each published summaries for AI-associated symptom palliation using both pharmacologic and nonpharmacological interventions.
Understanding current practice patterns regarding AI-associated symptoms is an important step toward improving AI adherence. However, real-world evidence for the extent of symptom recognition and guideline-based palliation by physicians remains largely unknown. Symptom documentation is necessary for patient-centered, team-based cancer care.13–16 Two single-center studies from the Netherlands and from Illinois examined arthralgias only, reporting that 48% and 74% of patients, respectively, had these symptoms recorded in the chart.11,17 Even less is known about adherence to guidelines for AI-related symptom palliation. Only the single Illinois study investigated AI guideline adherence, reporting that 41% of patients with arthralgias had no treatment documented.11
We hypothesized that documentation of AI-associated musculoskeletal symptoms occurs substantially less frequently than the actual prevalence of AI-associated symptoms.11,12,18 Based on the Illinois study as well as literature showing slow diffusion of guidelines across many areas of medicine,19–21 we further hypothesized that 50% or fewer patients would receive AI-related symptom palliation, and many of these treatments would not be non-guideline based. We examined these hypotheses in a randomly selected recent cohort of patients receiving adjuvant AIs at a large academic center.
MATERIALS AND METHODS
Study population.
This was a retrospective study of 179 women with breast cancer who received aromatase inhibitor (AI) therapy at a large multidisciplinary academic healthcare system in Wisconsin. Patients who had received a prescription for AI therapy from one of the institution’s medical oncology providers between October 15th, 2012 and September 14th, 2017 were randomly selected from the institution’s North American Association of Central Cancer Registries (NAACCR). Additional eligibility criteria included female sex, age ≥18 years, and first occurrence of stage I-III hormone receptor positive breast cancer.
Symptom documentation.
Major symptom categories were compiled from guidelines published by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO).6,22,23 Collected symptoms included musculoskeletal (myalgias, arthralgias), vasomotor (night sweats, hot flashes, flushing), and genitourinary (vaginal dryness, dyspareunia, incontinence). Symptoms were recorded in the collection database if documented in the electronic medical record (EMR).
Guideline-based treatments for aromatase inhibitor-associated symptoms.
Guideline-based palliative treatments for each major symptom category were compiled from the National Comprehensive Cancer Network (NCCN) and the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) breast cancer recommendations and included both pharmacologic and nonpharmacologic options.6,22,23 Switching to another aromatase inhibitor or to an alternate anti-endocrine therapy (tamoxifen) was also included based on guideline recommendations. Pharmacists (EW), scientists with expertise in patient symptom reports in women’s health (KF), and clinicians (JN, EW, SK) reviewed the final list of recommendations shown in Table 1. Among the non-guideline-based treatments were medication holds, opioids, and non-steroidal anti-inflammatory drugs (NSAIDs).
Table 1.
Guideline-based symptom-palliating treatments by symptom category.
| Guideline based treatments recommended by the National Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO) | ||
|---|---|---|
| Musculoskeletal | Vasomotor | Genitourinary |
| Acupuncture Physical therapy Physical activity Switch Aromatase Inhibitor |
SSRI (paroxetine, escitalopram, citalopram, fluoxetine, sertraline) SNRI (venlafaxine, desvenlafaxine) Anticonvulsant (gabapentin, pregabalin) Alpha agonist (clonidine) Acupuncture Exercise/weight loss Lifestyle changes Cognitive behavioral therapy Switch Aromatase Inhibitor |
Vaginal lubricant Vaginal moisturizer Counseling Referral Switch Aromatase Inhibitor |
Data collection.
Data was collected through review of patient demographic fields and oncology office visits in the EMR by a trained team member. Records between the date of first AI prescription and either July 1, 2018 or five years after the AI start date were reviewed. Each of the following descriptors were recorded if documented within the EMR: date of birth, race, ethnicity, specific AI initially prescribed with date, tumor stage, HER2 status, surgery and date, chemotherapy and date of initiation, radiation and date of initiation. Each record of symptoms within an oncology encounter note was then recorded. Recorded symptoms were collected from free text and structured fields.
Treatments addressing AI-associated symptoms were also recorded with dates for each documentation in the EMR. (Table 1). A single treatment could be listed for multiple symptom categories if there was documented intent to treat multiple symptoms. Full medication lists were also electronically examined between first AI prescription and either July 1, 2018 or five years after the AI start date.
Statistical analysis.
Patients were categorized by whether they had any symptoms recorded by the medical oncology team. Using guideline categories, all treatments were designated as guideline-based or non-guideline-based treatment. Among patients with symptoms recorded, Chi square tests and time-to-event models were used to examine 1) factors associated with treatment and 2) factors associated with guideline-based treatment.
Two sensitivity analyses were conducted with alternative definitions of treatment. First, medication “holds,” which were not considered guideline-based in the primary analysis, were categorized as “guideline-based” treatments if the hold was immediately followed by a medication switch. Second, in the case of vasomotor symptoms, where prescription medications are recommended by guidelines (palliative treatments for vasomotor and genitourinary symptoms are behavioral and over-the-counter), we considered whether some patients were prescribed medications without chart documentation. Since many guideline-based prescription medications for vasomotor symptoms can also be used for other indications (e.g. gabapentin and SNRIs are also-recommended for chemotherapy-associated neuropathy), we could not be certain that EMR prescriptions for medications present without other indications were AI-targeted.24 We therefore did not include these prescriptions as evidence of treatment in our primary analysis. However, in a sensitivity analysis of treatment of vasomotor symptoms, we included as treatments any guideline-based medication prescriptions present in the EMR within one year of first symptom documentation.
RESULTS
Of the 179 patients studied, 162 (90.5%) were non-Hispanic white. Thirty percent of women were younger than 60, 38% between 60 and 69, and 32% older than 69. The majority of patients had stage I cancer (59%). Thirty-five percent of patients received chemotherapy prior to initiation of their AI.
Eighty-three percent of women had at least one symptom documented in the EMR. Forty-six percent had more than one symptom documented. Musculoskeletal symptoms were documented most frequently; 73 percent of patients had musculoskeletal symptoms documented in the EMR. Fifty percent of patients had vasomotor, and 9 percent had genitourinary symptoms documented (Table 2). There were no differences in unadjusted analyses of symptom documentation by age, race, stage, first AI prescribed, receipt of chemotherapy, or symptom type, using a p value of 0.05. Only patients who received radiation were more likely to have symptoms documented in the EMR (p=0.048).
Table 2.
Baseline Demographics and Cohort Characteristics
| Characteristics | All Patients in Study Group n = 179 | Patients without Documented Symptoms n = 32 | Patients with Documented Symptoms n = 147 |
|---|---|---|---|
| Race/Ethnicity, n (%) | |||
| Non-Hispanic White | 162 (90.5) | 30 (93.8) | 132 (89.8) |
| Non-Hispanic Black | 11 (6.15) | 2 (6.25) | 9 (6.12) |
| Hispanic | 3 (1.68) | 0 (0.00) | 3 (2.04) |
| Other | 3 (1.68) | 0 (0.00) | 3 (2.04) |
| Age, n (%) | |||
| <60 | 54 (30.2) | 6 (18.8) | 48 (32.7) |
| 60–69 | 68 (38.0) | 12 (37.5) | 56 (38.1) |
| >69 | 57 (31.8) | 14 (43.8) | 43 (29.3) |
| Stage | |||
| I | 106 (59.2) | 15 (46.9) | 91 (61.9) |
| II | 56 (31.3) | 15 (46.9) | 41 (27.9) |
| III | 17 (9.50) | 2 (6.25) | 15 (10.2) |
| First Aromatase Inhibitor Prescribed | |||
| Anastrozole | 153 (85.5) | 28 (87.5) | 125 (85.0) |
| Exemestane | 8 (4.47) | 1 (3.12) | 7 (4.76) |
| Letrozole | 18 (10.1) | 3 (9.38) | 15 (10.2) |
| Prior Chemotherapy | |||
| Not Received | 116 (64.8) | 21 (65.6) | 95 (64.6) |
| Received | 63 (35.2) | 11 (34.4) | 52 (35.4) |
| Radiation | |||
| Received Radiation * | 114 (63.7) | 15 (46.9) | 99 (67.3) |
| Category of Symptom Documented | |||
| Musculoskeletal Only | 50 (27.9) | - | 50 (34.0) |
| Vasomotor Only | 13 (7.26) | - | 13 (8.84) |
| Genitourinary Only | 2 (1.12) | - | 2 (1.36) |
| Multiple | 82 (45.8) | - | 82 (55.8) |
| None | 32 (17.9) | 32 (100) | - |
Difference in symptom documentation by radiation status p=.048.
Treatment of symptoms.
Of the 147 women with any documented symptom, 97 (66%) received some form of symptom-palliating treatment. Seventy-seven patients (52%) received either guideline-based treatments or guideline-based treatments in combination with non-guideline-based treatments. Twenty-eight patients (19%) received only guideline-based treatments. Twenty patients (14%) received only non-guideline-based treatments.
Of the 130 women who had musculoskeletal symptoms, 80 (62%) received some form of symptom-palliating treatment. Fifty-nine (74%) of those treated received at least one guideline-based treatment, while the rest received only non-guideline-based treatment. Thirty (34%) of the 89 patients with vasomotor symptoms received some form of palliating treatment. Twenty-nine (97%) of those treated received at least one guideline-based treatment. Seven (44%) of the 16 patients with genitourinary symptoms received some form of symptom-palliating treatment. Five (71%) of those patients received at least one guideline-based treatment (Figure 1).
Figure 1.
Treatment Among Symptomatic Patients and Distribution of Guideline-Based Treatments
Because of the relatively low number of patients, analyses of factors associated with receipt of treatment were limited to patients with musculoskeletal and vasomotor symptoms, and analyses of factors associated with receipt of guideline-based treatment were limited to patients with musculoskeletal symptoms. There were no differences in receipt of treatment overall for either musculoskeletal or vasomotor symptoms (i.e. guideline or non-guideline-based by age, race, or stage (Tables 3a and 3b). There were also no differences in receipt of guideline-based treatment by age, race, or stage in patients with musculoskeletal symptoms.
Table 3a.
Factors Associated with Symptom Palliation among Patients with Documented Musculoskeletal Symptoms
| Any Treatment Received n=80 (%) | No Treatment Received n=49 (%) | Adjusted Hazard Ratio | 95% Confidence Interval | |
|---|---|---|---|---|
| Age | ||||
| <60 | 28 (35.0) | 17 (34.7) | - | - |
| 60–69 | 35 (43.75) | 17 (34.7) | 1.18 | 0.70 – 1.99 |
| >69 | 17 (21.25) | 15 (30.6) | 0.81 | 0.44 – 1.49 |
| Race/Ethnicity | ||||
| Non-Hispanic White | 73 (91.25) | 45 (91.8) | 0.91 | 0.41 – 2.03 |
| Other | 7 (8.75) | 4 (8.2) | - | - |
| Stage | ||||
| I | 48 (60.00) | 28 (57.1) | - | - |
| II | 23 (28.75) | 16 (32.7) | 0.85 | 0.51 – 1.41 |
| III | 9 (11.25) | 5 (10.2) | 0.97 | 0.46 – 2.02 |
Table 3b.
Factors Associated with Symptom Palliation among Patients with Documented Vasomotor Symptoms
| Any Treatment Received n=30 (%) | No Treatment Received n=58 (%) | Adjusted Hazard Ratio | 95% Confidence Interval | |
|---|---|---|---|---|
| Age | ||||
| <60 | 12 (40.0) | 19 (32.76) | - | - |
| 60–69 | 12 (40.0) | 20 (34.48) | 1.19 | 0.53 – 2.71 |
| >69 | 6 (20.0) | 19 (32.76) | 0.74 | 0.27 – 2.03 |
| Race/Ethnicity | ||||
| Non-Hispanic White | 26 (86.7) | 50 (86.2) | 1.06 | 0.34 – 3.34 |
| Other | 4 (13.3) | 8 (13.8) | - | - |
| Stage | ||||
| I | 16 (53.3) | 38 (65.5) | - | - |
| II | 9 (30.0) | 17 (29.3) | 1.22 | 0.51 – 2.91 |
| III | 5 (16.7) | 3 (5.2) | 2.19 | 0.78 – 6.16 |
In sensitivity analyses, we found that all patients who had a medication temporarily held also had other guideline-based treatments prescribed afterward (i.e. were included in “both” in the Figure). Since these holds occurred prior to other treatments, there were differences in the hazard ratios in the sensitivity analysis of factors associated with guideline-based musculoskeletal symptoms, but these were small (Appendix Table 1). When guideline-based treatment prescriptions that were not noted in chart notes were included in the definition of treatments for vasomotor symptoms, the number of patients who had treatment increased from 34% to 50% (44 of 88). Model results were very similar, except using this definition of symptom treatment, there was an association of higher stage with increased treatments (Appendix Table 2)
DISCUSSION
Eighty-three percent of breast cancer patients taking AIs in an academic medical oncology practice had AI-related symptoms documented in at least one of the three major categories attributed to the medications (musculoskeletal, vasomotor, and genitourinary). The majority of patients with musculoskeletal symptoms had EMR-documented treatment, but the majority of patients with vasomotor and genitourinary symptoms had no treatment documented. A substantial number of patients with symptoms in all categories received non-guideline-based treatments.
The rate of AI-related symptom documentation observed in our cohort was somewhat higher than we hypothesized from prior literature. In a study of patients with several cancer types at one Canadian center, for example, less than half of patients with severe shortness of breath had this symptom documented in chart notes.25 In a multisite study in advanced breast cancer, less than half of patients with each of twelve symptoms had the symptom documented in their chart.26 We cannot directly assess reasons for the higher rates of documentation in our study, but it is possible that this reflects stronger recognition by clinicians of the high prevalence of AI- related symptoms. These symptoms have been reported in multiple publications,9–12 so awareness may be particularly high. It is also notable, however, that the patients in our study were receiving adjuvant treatment, and were generally no longer receiving any other oncologic treatments, allowing clinicians to focus on toleration of a single medication in a patient who had no evidence of disease. Future research should examine how symptom type, treatment type, and perhaps treatment phase affect physician recognition of and documentation of symptoms.
Although clinicians recognized and documented many AI-related symptoms in our cohort, palliative treatments were documented less frequently. The only alternative treatment for these patients available per the guidelines besides AIs is tamoxifen. Unfortunately, tamoxifen can cause similar side effects, so attention to patients’ toleration of these medications is essential. Both observational studies and trials suggest that many patients’ symptoms from these medications can be improved or palliated.27–29 In our study, it is possible that some patients had no documentation of palliative treatments because these treatments were never offered. Alternatively, it is possible that treatments for symptoms were offered, but patients declined them. Guidelines strongly recommend that symptom recognition be followed by discussion of treatment options.6,22–24 Much of cancer care is provided in teams,30 and therefore documentation of any individual provider’s discussions with patients is essential to improve patient-centeredness, quality, and efficiency. To our knowledge, there are only two other studies that assessed clinician management of AI-associated symptoms. Those studies focused only on musculoskeletal symptoms, and the use of guideline-adherent palliative treatments for AI-associated musculoskeletal symptoms in our population (62%) was consistent with their findings.11 There have not been prior publications that examined palliative treatment rates for vasomotor or genitourinary symptoms, and thus our study adds this to the literature. Future research is needed to confirm our findings, identify barriers to use of current palliative treatments, and understand how best to counsel patients about the treatment options.
Although the prevalence of musculoskeletal symptoms (73%) in our population was high, non-guideline palliative treatments were especially common. Almost one-half of patients with musculoskeletal symptoms were prescribed a non-guideline-based treatment. This could be partially attributable to the frequent recommendation of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of arthralgias. We postulate that compared to possibly lesser-known and more expensive guideline-based therapies such as yoga or acupuncture, NSAIDs are better-known treatments that are perceived as low-cost and low-risk, though not guideline-based. Acupuncture is not covered by most insurance, so patients must pay out of pocket. Patient socioeconomic status was not collected, but could be a contributor to the type of treatments prescribed. Overall, our findings suggest that that improvements in guideline adherence have the potential to improve care for a large number of patients but may need to include financial supports to reach some patients.
Nearly three-quarters of patients who received guideline-based symptom palliation switched AIs as one or more of their interventions to palliate symptoms of the initial AI. In trials where patients switched from one AI to another due to symptoms, 39–72% of women were able to tolerate the second AI, reducing discontinuation.31,32 In addition to the efficacy of switching, it does not require patients to commit to lifestyle modifications or take additional medications. As such, it may be the most easily accepted option for patients. Additionally, medication switching may require less patient counseling from the prescribing provider because the patient is not starting a new class of treatment.
Prior studies suggest that over half of women with breast cancer have sexual concerns,33 such as vaginal dryness and dyspareunia, or want to discuss sexual concerns with a health care provider.34 One study reported that over 90% of AET users had sexual problems broadly,35 while another reported 56% had vaginal dryness specifically.36 In our study, only 9% of EMRs included documentation of genitourinary symptoms, suggesting that they are less likely to be recorded in the chart. Our study cannot determine whether this was because of lack of discussion or lack of documentation of a discussion, but we suspect it is the latter, as barriers to communication about sexual problems in oncology care have been documented in multiple studies.37 Our chart review was limited to oncology encounters, and it is possible that these symptoms may be addressed in other departments such as gynecology or internal medicine. However, a recent national study suggests widespread unmet needs regarding communication about sexual problems that are not limited to oncology and are greater among women.38
Limitations of this study include the single site and the retrospective, observational nature of its design. As noted above, symptom identification and prescribed treatments were only recorded in our data collection system if documented by the clinician in the patient chart, which may have led to underestimates in symptom and treatment prevalence. Patient surveys or automated electronic measurement of symptoms may better capture the true prevalence of symptoms. As discussed above, survey or audiotape studies might better capture the degree of symptom discussion, and nonprescription treatment recommendations.
In summary, the majority of patients prescribed aromatase inhibitors had symptoms documented in the EMR, consistent with both a high symptom burden and high recognition of this symptom burden, at least for musculoskeletal and vasomotor symptoms. Genitourinary symptom documentation appeared to be substantially lower. Many patients in all three symptom categories were prescribed guideline-approved palliative treatments, but a substantial number either were not treated or received only nonguideline-based treatments. Future studies should identify barriers to documentation of genitourinary symptoms, and treatments for all three symptom categories, with a goal of developing and testing interventions to help clinicians overcome those barriers.
Table 4.
Factors Associated with Guideline-Based Symptom Palliation among Patients Who Received Treatment for Musculoskeletal Symptoms
| Guideline-Based Treatment Received n=59 (%) | Only Non-Guideline Treatment Received n=21 (%) | Adjusted Hazard Ratio | 95% Confidence Interval | |
|---|---|---|---|---|
| Age | ||||
| <60 | 22 (37.3) | 6 (28.57) | - | - |
| 60–69 | 24 (40.7) | 11 (52.38) | 0.73 | 0.44 – 1.43 |
| >69 | 13 (22.0) | 4 (19.05) | 0.90 | 0.48 – 1.90 |
| Race/Ethnicity | ||||
| Non-Hispanic White | 54 (91.5) | 19 (90.5) | 0.86 | 0.39 – 2.47 |
| Other | 5 (8.5) | 2 (9.5) | - | - |
| Stage | ||||
| I | 34 (57.6) | 14 (66.7) | - | - |
| II | 18 (30.5) | 5 (23.8) | 1.25 | 0.70 – 2.23 |
| III | 7 (11.9) | 2 (9.5) | 0.88 | 0.40 – 2.08 |
CLINICAL PRACTICE POINTS.
Current literature suggests that up to 90% of patients taking AIs will experience at least one symptom, with the majority reporting musculoskeletal complaints. Treatments that alleviate those symptoms have been shown to be effective in randomized trials. However, real-world data regarding for the extent of symptom recognition and guideline-based palliation by physicians remains largely unknown. In this study, we found that eighty-three percent of breast cancer patients taking AIs in an academic medical oncology practice had AI-related symptoms documented in at least one of the three major categories attributed to the medications (musculoskeletal, vasomotor, and genitourinary). The majority of patients with musculoskeletal symptoms had EMR-documented treatment, but the majority of patients with vasomotor and genitourinary symptoms had no treatment documented. A substantial number of patients with symptoms in all categories received non-guideline-based treatments. These findings could help lead to development of interventions to reduce barriers to use of guideline-based care.
ACKNOWLEDGEMENTS
Research reported in this publication was supported in part by the National Institute on Aging of the National Institutes of Health under Award Number T35AG029793. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
APPENDICES
Appendix Table 1.
Factors Associated with Guideline-Based Symptom Palliation among Patients Who Received Treatment for Musculoskeletal Symptoms when Treatment “Holds” were considered to be Guideline-Based Care
| Guideline-Based Treatment Received n=59 (%) | Only Non-Guideline Treatment Received n=21 (%) | Adjusted Hazard Ratio | 95% Confidence Interval | |
|---|---|---|---|---|
| Age | ||||
| <60 | 22 (37.3) | 6 (28.57) | - | - |
| 60–69 | 24 (40.7) | 11 (52.38) | 0.73 | 0.44 – 1.43 |
| >69 | 13 (22.0) | 4 (19.05) | 0.90 | 0.48 – 1.90 |
| Race/Ethnicity | ||||
| Non-Hispanic White | 54 (91.5) | 19 (90.5) | 0.86 | 0.39 – 2.47 |
| Other | 5 (8.5) | 2 (9.5) | - | - |
| Stage | ||||
| I | 34 (57.6) | 14 (66.7) | - | - |
| II | 18 (30.5) | 5 (23.8) | 1.25 | 0.70 – 2.23 |
| III | 7 (11.9) | 2 (9.5) | 0.88 | 0.40 – 2.08 |
Appendix Table 2.
Factors Associated with Symptom Palliation of Vasomotor Symptoms Including Both Documented Treatments and Prescriptions without Documentation.
| Hazard Ratio | 95% Confidence Interval | |
|---|---|---|
| Age | ||
| 60–69 | 0.92 | 0.45 – 1.81 |
| >70 | 0.80 | 0.37 – 1.73 |
| Race/Ethnicity | ||
| White | 1.32 | 0.49 – 3.54 |
| Stage | ||
| II | 1.28 | 0.63 – 2.56 |
| III | 2.75 | 1.16 – 6.50 |
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
REFERENCES
- 1.American Cancer Society. Breast Cancer Facts & Figures 2019–2020. Atlanta: American Cancer Society, Inc. 2019 [Google Scholar]
- 2.U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on November 2018 submission data (1999–2016): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. June 2019; www.cdc.gov/cancer/dataviz. [Google Scholar]
- 3.World Health Organization. Adherence to long-term therapies: evidence for action. 2003; http://www.who.int/chp/knowledge/publications/adherence_report/en/. Accessed June 5, 2018.
- 4.Hershman DL, Shao T, Kushi LH, et al. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126(2):529–537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Avvaru SP, Noolvi MN, Aminbhav TM, Chkraborty S, Dash A, Shukla SS. Aromatase Inhibitors Evolution as Potential Class of Drugs in the Treatment of Postmenopausal Breast Cancer Women. Mini Reviews in Medicinal Chemistry. 2018;18(7):609–621. [DOI] [PubMed] [Google Scholar]
- 6.Gradishar WJ, Anderson BO, Balassanian R, al. E. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer Version 3, . 2017. [Google Scholar]
- 7.Partridge AH, LaFountain A, Mayer E, Taylor BS, Winer E, Asnis-Alibozek A. Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer. J Clin Oncol. 2008;26(4):556–562. [DOI] [PubMed] [Google Scholar]
- 8.Hershman DL, Kushi LH, Shao T, et al. Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol. 2010;28(27):4120–4128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high- risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014;383(9922):1041–1048. [DOI] [PubMed] [Google Scholar]
- 10.Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women. New Eng J Med. 2011;364(25):2381–2391. [DOI] [PubMed] [Google Scholar]
- 11.Menas P, Merkel D, Hui W, Lawton J, Harper A, Carro G. Incidence and management of arthralgias in breast cancer patients treated with aromatase inhibitors in an outpatient oncology clinic. J Oncol Pharm Pract. 2012;18(4):387–393. [DOI] [PubMed] [Google Scholar]
- 12.Oberguggenberger A, Hubalek M, Sztankay M, et al. Is the toxicity of adjuvant aromatase inhibitor therapy underestimated? Complementary information from patient-reported outcomes (PROs). Breast Cancer Res Treat. 2011;128(2):553–561. [DOI] [PubMed] [Google Scholar]
- 13.Baker A. Crossing the Quality Chasm: A New Health System for the 21st Century. BMJ 2001;323(7322):1192. [PubMed] [Google Scholar]
- 14.Why The Nation Needs A Policy Push On Patient-Centered Health Care. Health Affairs. 2010;29(8):1489–1495. [DOI] [PubMed] [Google Scholar]
- 15.Barry CA, Bradley CP, Britten N, Stevenson FA, Barber N. Patients’ unvoiced agendas in general practice consultations: qualitative study. BMJ. 2000;320(7244):1246–1250. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.What Is Patient-Centered Care? Catalyst Carryover. 2017;3(1). [Google Scholar]
- 17.Boonstra A, van Zadelhoff J, Timmer-Bonte A, Ottevanger PB, Beurskens CH, van Laarhoven HW. Arthralgia during aromatase inhibitor treatment in early breast cancer patients: prevalence, impact, and recognition by healthcare providers. Cancer Nurs. 2013;36(1):52–59. [DOI] [PubMed] [Google Scholar]
- 18.Beckwee D, Leysen L, Meuwis K, Adriaenssens N. Prevalence of aromatase inhibitor- induced arthralgia in breast cancer: a systematic review and meta-analysis. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2017;25(5):1673–1686. [DOI] [PubMed] [Google Scholar]
- 19.Denis JL, Hebert Y, Langley A, Lozeau D, Trottier LH. Explaining diffusion patterns for complex health care innovations. Health care management review. 2002;27(3):60–73. [DOI] [PubMed] [Google Scholar]
- 20.Carpenter WR, Reeder-Hayes K, Bainbridge J, et al. The role of organizational affiliations and research networks in the diffusion of breast cancer treatment innovation. Med Care. 2011;49(2):172–179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Rogers E. Diffusion of Innovations. 4th ed. New York: Simon & Schuster; 1995. [Google Scholar]
- 22.Denlinger CS, Sanft T, Baker KS, et al. Survivorship, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(9):1140–1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Hollowell K, Olmsted CL, Richardson AS, et al. American Society of Clinical Oncology- recommended surveillance and physician specialty among long-term breast cancer survivors. Cancer. 2010;116(9):2090–2098. [DOI] [PubMed] [Google Scholar]
- 24.Sanft T, Denlinger CS, Armenian S, et al. NCCN Guidelines Insights: Survivorship, Version 2.2019. J Natl Compr Canc Netw. 2019;17(7):784–794. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Seow H, Sussman J, Martelli-Reid L, Pond G, Bainbridge D. Do high symptom scores trigger clinical actions? An audit after implementing electronic symptom screening. J Oncol Pract. 2012;8(6):e142–148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Sikorskii A, Wyatt G, Tamkus D, Victorson D, Rahbar MH, Ahn S. Concordance between patient reports of cancer-related symptoms and medical records documentation. J Pain Symptom Manage. 2012;44(3):362–372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Hershman DL, Unger JM, Greenlee H, et al. Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA. 2018;320(2):167–176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Henry NL, Unger JM, Schott AF, et al. Randomized, Multicenter, Placebo-Controlled Clinical Trial of Duloxetine Versus Placebo for Aromatase Inhibitor-Associated Arthralgias in Early-Stage Breast Cancer: SWOG S1202. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018;36(4):326–332. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Irwin ML, Cartmel B, Gross CP, et al. Randomized exercise trial of aromatase inhibitor- induced arthralgia in breast cancer survivors. J Clin Oncol. 2015;33(10):1104–1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Yen TWF, Laud PW, McGinley EL, Pezzin LE, Nattinger AB. Prevalence and scope of advanced practice provider oncology care among Medicare beneficiaries with breast cancer. Breast Cancer Res Treat. 2019. [DOI] [PubMed] [Google Scholar]
- 31.Briot K, Tubiana-Hulin M, Bastit L, Kloos I, Roux C. Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone- receptor-positive breast cancer: the ATOLL (articular tolerance of letrozole) study. Breast Cancer Res Treat. 2010;120(1):127–134. [DOI] [PubMed] [Google Scholar]
- 32.Henry NL, Azzouz F, Desta Z, et al. Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol. 2012;30(9):936–942. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Reese JB, Shelby RA, Keefe FJ, Porter LS, Abernethy AP. Sexual concerns in cancer patients: a comparison of GI and breast cancer patients. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2010;18(9):1179–1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Gilbert E, Perz J, Ussher JM. Talking about sex with health professionals: the experience of people with cancer and their partners. European Journal of Cancer Care. 2016;25(2):280–293. [DOI] [PubMed] [Google Scholar]
- 35.Schover LR, Baum GP, Fuson LA, Brewster A, Melhem-Bertrandt A. Sexual problems during the first 2 years of adjuvant treatment with aromatase inhibitors. The journal of sexual medicine. 2014;11(12):3102–3111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Dorfman CS, Arthur SS, Kimmick GG, et al. Partner status moderates the relationships between sexual problems and self-efficacy for managing sexual problems and psychosocial quality-of-life for postmenopausal breast cancer survivors taking adjuvant endocrine therapy. Menopause. 2019;26(8):823–832. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Reese JB, Sorice K, Beach MC, et al. Patient-provider communication about sexual concerns in cancer: a systematic review. J Cancer Surviv. 2017;11(2):175–188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Flynn KE, Whicker D, Lin L, Cusatis R, Nyitray A, Weinfurt KP. Sexual Orientation and Patient-Provider Communication About Sexual Problems or Concerns Among US Adults. J Gen Intern Med. 2019;34(11):2505–2511. [DOI] [PMC free article] [PubMed] [Google Scholar]