“I did not need anything else to make me feel bad”: The precarious paradox of Breast Cancer Survivors’ adherence to adjuvant endocrine therapy

doi:10.21203/rs.3.rs-1976539/v1

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Research Article

“I did not need anything else to make me feel bad”: The precarious paradox of Breast Cancer Survivors’ adherence to adjuvant endocrine therapy

https://doi.org/10.21203/rs.3.rs-1976539/v1

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Purpose

Adherence to adjuvant endocrine therapy (AET) is a critical problem in the treatment of hormone receptor-positive (HR+) breast cancer (BC). More than half of women discontinue AET prior to the end of the recommended 5-year course of therapy. The purpose of this study was to assess the feasibility of engaging women in research who prematurely discontinued AET and to describe their experiences with AET to inform future interventions.

Methods

A mixed-methods pilot study was nested within a larger observational trial of women with HR + BC (N = 594). Women who discontinued therapy were systematically identified over 24 months; quantitative surveys and in-depth interviews were conducted. Paired t-tests were used to compare the mean difference in psychosocial factors and medication-related symptoms between baseline and discontinuation time-points. In-depth open-ended interviews were audio-recorded, transcribed verbatim, and analyzed using the NVivo software program.

Results

Most women (90%) who discontinued AET during the observational period participated in the study (N = 37). Women’s ages ranged from 46 to 78 years old (m = 60.1); 62.2% were White, 29.7% were Black and the remaining women identified as being from other racial/ethnic groups. Few differences were noted between women who did and did not discontinue AET. Most women (84%) reported AET-side effects as a reason for discontinuation. Among those who discontinued, the reported vasomotor symptoms were lower at discontinuation compared to the first symptom assessment (P = 0.0047). Qualitative data suggested frustration with strategies to address symptoms, being unprepared for the intensity of symptoms, and a desire for better patient-provider communication. 69.2% of women reported that would be willing to consider restarting AET if barriers were removed.

Conclusion

Most women were willing to restart AET. Capturing women’s experiences while on treatment and their discontinuation in real-time may help women prevent discontinuation, enhance the quality of life and prevent worsening of medication-related symptoms. Interventions that integrate patients’ concerns with symptom management and enhance patient-physician communication may support AET adherence.

cancer disparities

adjuvant endocrine therapy discontinuation

breast cancer survivor

Adjuvant endocrine therapy (AET) (i.e., Tamoxifen and aromatase inhibitors (AIs)), improves outcomes in women diagnosed with estrogen-positive (ER+) breast cancer [1]. Despite proven benefits of reducing recurrence by 40% and improving mortality by 31%, adherence to the full minimum course of therapy (5 years) of AET is suboptimal [2]. Up to 54% of women discontinue AET prior to the end of the recommended 5-year course of therapy [3]. AET discontinuation is a multifaceted problem involving factors of older age, medical cost, adverse side effects and follow-up care with a provider [20–22]. Given the small body of work on AET discontinuation/persistence among breast cancer patients, there is a critical need to further examine associated factors of AET discontinuation [20–22]. For example, there are limited studies that describe examining modifiable associated factors and/or racial differences in contributing factors of AET discontinuation. To fulfill this gap in research, the purpose of this study is to provide an in-depth examination of predictors contributing to breast cancer patient’s discontinuation of recommended AET.

AET adherence behaviors are complex and information is needed from multiple sources and populations and at varying time periods during the treatment course [4]. Most studies of discontinuation have relied on either administrative data or focused on predictors of discontinuation collected prior to discontinuation with relatively limited self-reported information from patients who recently discontinued data [5]. Thus, assessment of experiences of women prescribed AET is important to anticipate barriers to treatment persistence. Data from women who stop taking AET may be useful in assessing their willingness to restart therapy and prioritizing interventions. This study employed a mixed methods approach to: 1) assess the feasibility of engaging women in research who discontinued AET; 2) describe changes of self-reported AET symptoms, quality of life, and perceived AET risks and benefits between the time women were on AET and when they discontinued and to 3) identify patient-reported priorities related to discontinuation of AET. Findings may inform future supportive care approaches to prevent premature discontinuation and/or to assist women with restarting AET.

Setting and Sample

This is an ancillary pilot study of participants from the Women’s Hormone Initiation and Persistence cohort study (WHIP) [7]. The purpose of this ancillary study was to assess the feasibility of recruiting and engaging participants near their time of AET discontinuation and to describe experiences of women who discontinued AET. WHIP participants were identified and recruited from integrated health care systems, teaching hospitals, and community outreach institutions (i.e., community-based oncology practices). Eligibility criteria included being within 12 months of a diagnosis of hormonal receptor (HR) positive breast cancer, ≥ 21 years old, and initiating AET within one-year post-diagnosis. Information on discontinuation patients was collected from February 2013 to July 2018. All study procedures were approved by the institutional review board of all participating sites. Additional details can be found elsewhere [8].

Measures

After consenting to participate in the study, women completed a REDCap survey either online through a secure link or with the assistance of a trained clinical research assistant. Data collected through the survey included demographics (e.g., education, race), ratings of provider communication, self-reported AET adherence, physical activity, AET-related symptom, psychosocial, and socio-cultural measures. The Functional Assessment of Cancer Therapy general and breast cancer specific scales (FACT-G and FACT-B, respectively) measured quality of life; higher scores indicate higher ratings of QOL [9, 10, 11]. Potential scores ranged from 0-135 for total Fact-G score and 0–50 for total Fact-B score.

Endocrine Symptoms (FACT-ES) scale. The FACT-ES scale includes a 23 item 5-point Likert-scale, and potential total scores ranged from 0-115. The AET symptoms are also examined through the combination of FACT-ES items into domains (e.g., vasomotor and neurological). Higher scores for this scale indicate worse symptoms. Clinical data were drawn from medical records and included body mass index (BMI), presence or absence of a recurrence, cancer staging, surgery type (e.g., lumpectomy), AET type (e.g., Tamoxifen), chemotherapy receipt, and radiation receipt. Follow-up surveys were administered at 12, 24, and 36 months. Follow-up surveys repeated collection on key measures from the baseline (e.g., AET-related symptoms) and ended at the point of discontinuation.

Discontinuation was captured from pharmacy records or from the follow-up survey. In the survey, if women reported that they had discontinued their medication, it was verified via pharmacy records. The brief discontinuation surveyed queried women about: (a) their reasons for discontinuation (women selected from multiple options including “other”); (b) with whom discontinuation was discussed (physician, family, friend, etc.); (c) their willingness to consider restarting therapy (yes vs no); (d) interest in potential intervention to support them with taking AET (yes vs. no) and open-ended responses regarding their suggestions for helping women on AET.

Procedures for In-depth Interviews

To complement data from discontinuation surveys, phase two of the pilot involved implementation of in-depth interviews with a small sample of women who prematurely discontinued AET (target recruitment goal of N = 10; 7 completed interviews) to explore survivor experiences more in-depth. In-depth interviews were elected over a focus group to individual (vs group) decision processes.

The interview guide was developed by study researchers (VBS, AHS). The opening set of questions asked the participant to describe factors about herself (e.g., residence, overall health), how long ago she was diagnosed with breast cancer, and the status of her cancer (e.g., remission, recurrence). Topics within interview guide included communication with their providers about AET, personal experiences taking AET, information seeking behaviors regarding AET, social support, perceived barriers, and decision-making in the context for AET initiation and, ultimately, early discontinuation. Interviews were conducted in-person or by phone by two study team members. All interviews were audio-recorded and transcribed verbatim by the study team. Participants received a $30 gift card upon completion.

Three team members (AS, BM, ME) coded transcripts using a phenomenological approach. Interpretive phenomenological analysis (IPA) was selected for transcript review because of its emphasis on describing a “common meaning for several individuals of their lived experiences of a concept or phenomenon”[12]. IPA most frequently draws on accounts of an average of 6 interview participants, although 3 to 15 participants is acceptable [13]. The first segments were coded by hand and later translated to NVivo. The coders convened to discuss segments identified, how they were coded, and to consider the emergence of key quotations. Within the few disagreements in coding, these were discussed and ultimately consensus was reached before continuing. Next, segments were reduced to just key statements by participants that “provide an understanding of how participants experienced the phenomenon,” in this case, early discontinuation of AET, through a process called horizontalization[12]. Next, thematic findings were emerged until saturation from the key quotations. The themes and highlighted quotes were then used to describe what the participants experienced as the textural description and the context that influenced how the participants experienced early treatment discontinuation as the structural description. The essential, invariant structure or essence of early discontinuation to AET was then discerned and described.

Statistical Methods

Patient characteristics were summarized with their percentages for categorical variables and their means and standard deviation for continuous variables. Characteristics of patients were examined at baseline and discontinuation through means and standard deviations. Differences in psychosocial factors and medication-related symptoms were compared between baseline and discontinuation with paired t-tests. Further Reasons for discontinuation were summarized with percentages.

FACT-ES symptoms were also examined at their individual level looking at each question that makes up the FACT-ES score. The individual symptoms were considered through the symptoms being present (item rating ≥ 1, “a little bit” or more severe) versus not at all (0, “not at all”). The 10 most common individual FACT-ES symptoms at baseline were plotted. Differences in the presence of individual symptoms at baseline and discontinuation were tested using Fisher’s Exact tests, and those found to significantly differ were plotted as well. A significance level of 0.05 was used for all tests in this study, and statistical analysis was performed in SAS 9.4.

Of the 41 women who discontinued during the data collection period, 37 (90%) participated in the ancillary study. On average, women had been on study for 26.7 (SD = 9.8) months prior to discontinuation. Most (62.2%) women were White and 29.7% were Black. A majority had some level of college education (94.3%) and 92% had private health insurance (Table 1). Sixty-seven percent of participants were diagnosed with stage I breast cancer, 65.2% underwent lumpectomy, 76.0% had radiation therapy, and 32.1% of patients had chemotherapy. Prior to discontinuation, most (72.4%) survivors were taking AIs.

Table 1

Characteristics of Study Participants (N = 37)
	(%)
Stage
I	67.9
II	25.0
III	7.1
AET Type
Aromatase Inhibitors (AI)	72.4
Tamoxifen	27.6
Surgery type
None	20.7
Lumpectomy	51.7
Mastectomy	27.6
Radiation
Yes	76.0
No	24.0
Chemotherapy
Yes	32.1
No	67.9
Patient Reported Outcomes	Mean (SD)
Overall HRQOL	111.3 (22.9)
AET-Symptoms	19.4 (12.4)

Table 2 displays AET-reported symptoms, quality of life and psychosocial factors for women while on treatment (i.e., baseline) and post discontinuation. The total AET-related symptoms scores ranged from 5 to 48 (mean sore = 19.4) at baseline and were lower at discontinuation (mean: 15.9 vs 19.4; p = 0.06). When consideration of differences across symptom domains, vasomotor symptoms were significantly lower at discontinuation compared to baseline (2.2 vs 3.8 p = 0.0045). Moreover, women reported lower levels at discontinuation for all three individual symptoms that comprise the vasomotor domain with average ratings for hot flashes of 1.15 versus 1.93; cold sweats 0.11 versus 0.58; and night sweats 0.94 versus 1.34.

Table 2

Comparison of Selected Participant Characteristics at Baseline vs. Discontinuation (N = 37)
Mean	SD	N	Mean		p-value
BMI	30.6	8.9	23	28.9	10.4	0.14
FACT G	83.5	19.1	35	80.3	17.2	0.77
FACT B	111.3	22.9	35	107.2	19.4	0.72
Physical	21.7	6.6	35	21.5	6.1	0.9
Social Quality	21.6	6.0	34	22.3	4.9	0.43
Emotional	19.9	4.8	35	17.8	3.5	0.0047**
Functional	20.2	6.0	35	18.8	6.5	0.97
Additional concerns	27.8	5.3	35	26.9	4.0	0.76
Total AET Symptoms	19.4	12.4	35	15.9	11.8	0.06
Vasomotor	3.8	3.7	35	2.2	2.7	0.0045**
Neurological	3.1	3.6	35	2.8	3.3	0.21
Gastrointestinal	4.0	3.1	35	3.3	3.2	0.56
Gynecological	6.2	4.3	35	5.2	4.1	0.14
Bone loss	0.4	0.7	22	0.2	0.6	1.00
Joint pain	2.3	1.5	35	1.9	1.5	0.26
Benefit of Tamoxifen	8.0	1.8	8	9.0	2.6	0.47
Risk of Tamoxifen	17.9	8.6	8	19.8	3.5	0.47
Benefit of AIs	3.7	1.3	20	4.9	2.1	0.086
Risk of Ais	16.0	4.6	20	13.2	4.7	0.072
Note: Paired t-tests compared the means between baseline and discontinuation: The numbers of subjects; SD: Standard deviation.** p < 0.01 ^a Sign rank test used to test for difference due to normality assumption not being met

The most common symptom at baseline for discontinuing patients was joint pain or stiffness (80.0%). Vaginal dryness (72.0%), lost interest in sex (66.7%), hot flashes (65.4%), and breast sensitivity or tenderness (65.4%) were also common symptoms at baseline (Fig. 1). Hot flashes (41.2% vs. 65.4%), night sweats (48.6% vs. 61.5%), vaginal itching or irritation (25.7% vs. 32.0%), vaginal bleeding or spotting (8.6% vs. 16.0%), and diarrhea (15.4% vs. 8.6%) where found to be less common among patients at discontinuation while headaches (34.3% vs. 30.8%) and high cholesterol (27.3% vs. 16.7%) were more common (p < .05).

No difference was found in the total FACT of FACT-ES score, or other psychosocial factors (e.g., distress). Notably, the emotional QOL was significantly higher at baseline than at discontinuation (19.9 vs. 17.8, p = 0.0047). No other significant differences were found when comparing factors at baseline and discontinuation. A trend, however, was noted that the marital/partner status changed from baseline to discontinuation with fewer women reported being married/partnered.

When queried about reasons for discontinuation, side-effects were cited most often (84%). When asked with whom they discussed their decision to discontinue, they reported doctors (96.2%), families (66.7%), and friends (74.2%). Interestingly, a majority (69.2%) of women reported that they would be willing to reconsider therapy if barriers (such as side effects) were removed. “I would consider, if possible, starting at a lower dose to see how the body responds”. Nearly thirty percent (29.6%) of women were interested in an intervention to support them with taking their AET (Table 3). One participant commented, “if the proposed intervention were some type of medication, it would be important that the medication not cause additional side effects”. Another woman stated, “If there was a way to improve side effects without having to take more meds, that would help a lot”. Another participant expressed a similar sentiment about possibly restarting AET, “If there was something to help with the side effects, the joint pain in particular. Something other than another medication”. One participant noted, “My doctor didn't even [give] me a medication to counter the side effects. Not sure if I would have taken it anyway. Then I would need another pill to counter act those side effects”. The joint pain was common among women taking AIs. For example, when discussing decisions about discontinuation, a participant shared, “If there was a formulation that didn't cause that joint pain, I would still be taking it. Had another friend who took it and had no problem. I guess I was too old for Tamoxifen. That might be the only other thing I would try. I couldn’t do it anymore. Couldn’t l live with it”. Balancing other health concerns was reported to be a concern related to staying on AET. As one woman explained she would have continued taking her medication; “If my endocrinologist and oncologist could have kept my blood sugar down”.

Study participants offered suggestions for future interventions and urged healthcare providers to; “incorporate a more holistic approach”. The paradox of medications and side effects was raised by participants. As one woman shared, she was, “not convinced the meds will work”. Not sure if the goal is to get pp [people] well vs managing symptoms”. Another suggestion for future interventions was to consider, “Exercise, nutrition, and spirituality should be more of a focus. Medication alone does not have to be the main emphasis.”

In-depth Interviews

Of the seven BC survivors who participated in the in-depth interviews. Four women identified as non-Latino Black and three identified as non-Latino White. Most were married (n = 4), college-educated (n = 4). Seven main themes were identified from transcripts: perceived risk of recurrence, unexpected side effects, patient-provider communication, Side Effects (Severity of side effects), medical decision-making, social support, and weight of the decision. Thematic findings and key statements are presented in Table 3.

Perceived risk of recurrence

a common misconception by the survivors was the complete remission of the disease after the initial surgical management, consequently, the role of AET was thought of as an unnecessary addition to the regimen

Patient # “I had a lumpectomy and then radiation and so the hormonal was just the added benefit um my chance of recurrence was fairly low, so chemo wasn’t recommended either with the one-type testing umm so I just felt like well this is what the doctor recommended so I’ll just take it.”

Patient # “I felt like I didn’t really have cancer, I mean even though technically I guess it was stage zero.”

Unexpected side effects

Survivors tended to feel as though they knew the typical AET side effects, but that either the likelihood of them experiencing the side effects was too low to affect them, or they would have liked more detailed information about potential side effects

“Well, I feel like they did tell me that [about all of the potential side effects], but I thought ‘oh it’s not going to happen to me!” (Participant #)

“I didn’t expect to have side effects, I didn’t expect for there to be issues.” (Participant #)

“I kind of wish I knew more about the side effects; you know the possible side effects.” (Participant #)

“I didn’t know to ask the questions.” (Participant #)

Side Effects (Severity of side effects)

Survivors equated the side effects as almost as difficult as cancer itself, and were distressed by their severity, such as in the quotations below

“I mean this is all real, it’s all real that this happened to me, so I am actually, instead of having the outer and inner labia now one of my inner labia is gone, the second one is almost entirely gone.” (Participant #)

“I thought I was going to need a seeing-eye dog after a while I ain’t kidding I could not see you.” (Participant #)

Patient-provider communication

Women also shared how they desired to speak with their medical provider regarding their AET decision-making experiences

“I went back to the oncologist, and like I decided to stop taking it, but just wanted to talk with him about it.” (participant #)

Medical decision-making

Survivors mentioned that they discussed AET discontinuation with their physicians; some of them took the decision of discontinuation with them, while others had already decided to stop taking AET

“I made the decision with both my oncologist that prescribed it and I do also have a gynecologist, I made the decision with both of them you know as a team to not go back on the tamoxifen.” (participant #)

“I went back to the oncologist, and like I decided to stop taking it, but just wanted to talk with him about it.” (participant #)

Social support

Survivors acknowledged the role of family and friends in encouraging them to continue AET while also supporting their decision

“I talked to my husband about it and my daughters and my best friend and they all were you know were supportive and also encouraging me to strongly consider taking the medication, because you know it was recommended by the team that I had been seeing” (participant #)

Weight of decision

Different thoughts contributed to the stress of whether to restart the treatment regimen; as it had an important role in therapy and at the same time accompanied by the burden of unwanted side effects, which can be understood from a exemplar of survivor quotations

“Even if I had a resolution to all that and the doctors were like ‘you can go back on it’, I would be afraid that it would start another domino effect, and at the exact same time I’m afraid not to be on it.” (participant #)

“Do I regret taking the medication? I can't say that I do, because I feel the benefit as far as my care, my future care, the avoidance of cancer returning outweighs, as bad as the pain was.” (participant #)

Taken together, the decision to discontinue AET was complex as demonstrated by some of the overlapping themes. Moreover, women’s decisions were influenced by their experiences with care and both internal and external forces.

This study underscored the importance of supporting women prescribed AET. Further, given the high participation rate (90%), it appears feasible to engaged women in research even after they discontinued AET. While early discontinuation is hypothesized to be associated with AET-symptoms, most studies do not include patient-reported information. Not surprisingly, few interventions have been developed to address discontinuation– particularly with insight from patients who discontinued therapy [24, 26, 27]. Uniquely, this study focused on understanding perspectives of women who discontinued therapy and found that it was feasible to recruit this population for adherence-related research. Study findings underscore the critical nature of AET-related side effects and its impact on discontinuation as well as the role of patient-provider communication on women’s knowledge of symptoms and potential methods for symptom management.

The Paradox of Adherence and Symptom Relief

Though data are lacking in clinical practice, approximately 20% of women on AET report symptoms while on medication [23, 24, 25]. Furthermore, not all women discontinue due to symptoms suggesting that symptom management approaches and other factors either buffer or exacerbate the symptom burden and/or severity experience. Sheppard and colleagues (cite the poster at AACR) found that % of women on AET reported AET-related symptoms. A study by Bellet and colleagues reported an array of symptoms including hot flashes, depression, osteoporosis, joint pain, and outcomes related to sexual function [28]. There is also growing evidence showing a variation of symptoms overtime such as bone fractures that occur after discontinuing aromatase inhibitors. [29] Better adherence may lead to worse symptoms as suggested by the finding that in this study that AET-related symptoms were lower at discontinuation than at baseline when women were on their medication. This important finding suggests that may women discontinued AET in search of relief of these symptoms. It should be noted that women seeking relief may not be willing to take additional medications as suggested by women in the qualitative portion of the study.

Therapeutic relationships are central to supporting patients undergoing AET. Patient-provider relationships were important to women in the study particularly as a need to discuss methods to manage their treatment-related side effects. Many women reported talking to their providers about their decisions to stop taking AET; in some cases, the providers recommended that women discontinue their AET. While clinicians commonly recognize the burden and effects of AET symptoms, limited efforts have been developed that seek enhance patient-provider communication in this area [15]. Training physicians and/or other members of the medical team on communication with the patients may enhance symptom management and reduce non-adherence and discontinuation rates [16]. As some side effects may be unresolvable such as those described by participants of our study and by Wheeler et al [16], upfront conversations about potential side effects prior to AET initiation may have been helpful. Additionally, there may be some women for whom discontinuing therapy is appropriate such as women with a breast cancer recurrence or for whom symptoms represent serious toxicities (e.g., venous thrombo-embolism) [30]

A substantial proportion of women in this study reported that they would consider restarting therapy if interventions were available. This is important given that restarting therapy appears to confer beneficial outcomes. Hurtado-de-Mendoza and colleagues examined the impact of discontinuing and then restarting AET in a population-based cohort using data from Swedish breast cancer survivors. They found that disease-free survival was significantly improved in treatment restarters versus non-restarters (adjusted hazard ratio, 0.61; P = 0.006) [17]. The fact that patients who had already discontinued AET were willing to consider restarting therapy is promising. Based on systematic reviews, none of the interventions focused on women who discontinued therapy. Women who discontinue therapy may require interventions and other approaches that focus on self-care and symptom management that can prepare them upfront for symptoms and perhaps reduce discontinuation.

There are several strengths of this study such as the mixed methods approach, a focus on women who discontinued therapy, use of validated AET symptom and quality of life scales. There are some limitations that should be acknowledged. First, the sample size is modest which likely impacted statistical power and the ability to conduct multivariable analysis. Because this was a pilot descriptive study, analyses were appropriate and can be used to inform a larger observational trial. Second, women were not followed for the complete five years of therapy which may have included a wider number of perspectives of women who discontinued, while we used validated and commonly used measures of symptoms, we recognize that there was no inclusion of observations of symptoms nor could we detect what providers evaluations were of reported symptoms.

Clinical Implications

Women in this study reported on the salience of preserving a good quality of life throughout survivorship. Although optimal AET adherence improves outcomes, it may unfortunately diminish quality of life due to side effects and ultimately lead to discontinuation. Studies have examined nonclinical or non-pharmacological interventions to relieve some AET-related symptoms. Examples of interventions include cessation of smoking, caffeine, spicy foods, alcohol, wearing tight clothing (fabric), and cosmetic spray (mists)¹⁸. Clinical options can be classified as pharmacological or clinical practice interventions. Studies initiated by pharmacological companies found selective serotonin reuptake inhibitors such as Paroxetine and Venlafaxine to significantly decrease the frequency of hot flashes after four weeks of their use [19]. Future work is needed to understand methods to effectively implement side effect management interventions in care settings and to test these interventions’ impact on quality of life.

AET discontinuation remains a problem in the treatment of women with HR + breast cancer. Treatment side effects and their association with quality of life offer potential mechanisms to target interventions that may ultimately improve outcomes. Further, based on suggestions provided by participants, multilevel interventions are warranted. Given the role of patient-provider communication on adherence patterns, future interventions must not focus solely on the patient but must be implemented in the context of cancer care delivery. More data are needed from diverse subgroups and their experiences with AET. Given disparities noted in survival for women with HR + BC and differential patterns of AET adherence across certain subgroups (race/ethnicity, insurance status, etc.). The qualitative part of the study provides more information to explain the AET discontinuation and understand the reasons behind the scenes from a breast cancer patient’s perspective, alongside with quantitative part. This is considered a strong point compared to the few previous studies that have been conducted among African American women. Since many patients appear interested in learning how to restart AET, it will be important for multidisciplinary team approaches to identify strategies that will not give women, “one more thing to make them feel bad”.

Ethics approval and consent to participate: The study was approved by Virginia Commonwealth University, Institute Review Board (IRB).

Consent for publication: We (Authors), the undersigned, give our consent for the publication, we do not have any identifiable details, which can include a photograph(s) and/or videos and/or case history and/or details within the text (“names”) to be published in the above Journal

Availability of data and materials: Data is available on request due to privacy/ethical restrictions. The data supporting this study's findings are available on request from the corresponding author. The data are not publicly available due to their containing information that could compromise the privacy of research participants

Competing interests: The Author(s) declare(s) that there is no conflict of interest.”

Authors' contributions:

VS the main PI completed the research question, hypothesis, and review and participated in all sections.
AN is the graduate research assistant (Ph.D. student) who completed the background and part of the method and discussion also review the file.
AS worked on results, discussion and review the file
MB worked on results ( Qualt data)
ME worked on results ( Qual data)
DB worked on results (biostatistician)
YC worked on the method and participated in data collection (Lab manager)
MW worked on references and background.
AM co-PI method and review file.

All authors reviewed the manuscript at least once and send their approval.

Funding and Acknowledgment: The authors would like to thank the women who participated in this study by sharing invaluable information. This research was funded by the National Cancer Institute R01CA154848. It was also supported in part by the NIH-NCI Cancer Center Support Grant P30 CA016059 the CTSA Award No. UL1TR002649 from the National Center for Advancing Translational Sciences, NIH-NCI 2T32CA093423, and NCI Center to Reduce Cancer Health Disparities, Award No. P30CA177558-05S3.This project was also supported by Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS) by Federal Funds; the National Center for Advancing Translational Sciences (NCATS); and the National Institutes of Health (NIH), through the Clinical and Translational Science Awards Program (CTSA) (KL2TR001432). The study identification number from National clinical trial (NCT) is 02992730.

Authors' information (optional): NA

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“I did not need anything else to make me feel bad”: The precarious paradox of Breast Cancer Survivors’ adherence to adjuvant endocrine therapy

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Procedures for In-depth Interviews

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In-depth Interviews

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The Paradox of Adherence and Symptom Relief

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