The symptom burden of women with a known risk of breast cancer receiving risk reducing medication

Abstract

Background:

For the estimated 10 million women in the United States who meet the high-risk criteria for breast cancer, evidence-based interventions may reduce the risk of breast cancer by 50–65 %. Even with substantial evidence supporting preventive medication for risk reduction, there is significant lack of uptake and adherence. The purpose of this study was to characterize the experience of women at high risk for breast cancer and define the content domain for a patient-reported outcomes (PRO) measure of symptom burden from breast cancer risk and risk reducing medication.

Methods:

Thirty women at high risk for breast cancer and receiving risk reducing medication participated in single qualitative interviews. Content analysis was used to identify the symptom burden. An expert panel review rated the relevance of symptoms identified in the qualitative interviews to establish the items for inclusion in a PRO symptom burden measure.

Results:

Participants had a mean age of 54.6 years; 43.3 % self-identified as Hispanic and 20.0 % self-identified as Black. Content analysis found 20 symptoms related to both risk and preventive treatment, with 8 symptoms reported by ≥ 20 % of women. All women described distress related to their risk and preventive care. Treatment-related symptoms varied based on history of risk-reducing surgery and type of endocrine therapy. Women described symptom-related interference with relationships, work, enjoyment of life, and adherence to risk reducing medication.

Conclusions:

Women with a known high risk of breast cancer and receiving preventive care experience a unique symptom burden including multiple symptoms and functional impact related to symptoms.

Introduction

Breast cancer is the most commonly diagnosed cancer in women in the United States, with an estimated 287,850 new cases of invasive breast cancer in 2022; one in eight women will be diagnosed with invasive breast cancer in the course of their lifetime [1]. The overall survival rate for women with breast cancer is 90 %, with an estimated 4 million breast cancer survivors currently living in the United States [1]. While survival rates for breast cancer are high compared to other cancers, multi-modal treatments are often required and can significantly impact quality of life and economic cost, highlighting the importance of breast cancer prevention and screening [2–6]. Implementation of robust preventive care could prevent one-half of all breast cancer cases [7].

For the estimated 10 million women in the United States who meet the high-risk criteria for breast cancer, evidence-based interventions may be implemented to reduce the risk of breast cancer by 50–65 %, including long-term risk reducing medication [7–20]. Despite the potential to reduce the risk of breast cancer by 50–65 %, risk reducing medication uptake in non-trial settings ranges from 0 % to 54.9 %, with pooled uptake estimates reported at 16.3 % [12,16,21,22]. Of those who initiate risk reducing medication, 49 % will experience medication interruptions and 40 % will not complete five years of therapy, with most discontinuations happening in the first year [16,23]. Even with substantial evidence supporting preventive medication for risk reduction, there is significant lack of uptake and adherence, especially among racial/ethnic minorities and underserved women [10,12,17,19,24–33]. Given the missed opportunity for breast cancer prevention that this represents, it is critical to characterize the experience of women receiving risk reducing medication for development of interventions focused on improving uptake and adherence.

Several patient-level barriers to compliance with prevention strategies, including risk reducing medication, impact uptake and adherence. Engaging in preventive care requires a healthy woman to navigate a complicated decision-making process involving the woman’s perception of risk, access to information about risk and prevention strategies, access to care, social support, and the financial ability to manage cost of preventive care [34]. Barriers to risk reducing medication use specifically include fear of side effects such as thrombotic events and endometrial cancer risk, bothersome symptoms, extended length of treatment, financial burden, and impact on functioning and quality of life [7,12,15, 23,24,35–42]. Risk reducing medication is associated with multiple symptoms, including arthralgias, carpal tunnel syndrome, paresthesia, joint stiffness, headache, gastrointestinal symptoms, and fatigue (more common with use of aromatase inhibitors) and vasomotor symptoms such as hot flashes, night sweats, vaginal discharge, vaginal bleeding, vaginal dryness or irritation, dyspareunia, difficulty with bladder control, leg cramps, and weight gain (more common with use of selective estrogen receptor modulators) [7,8,18,43–45]. While the range of symptoms is well documented, descriptions of the symptom experience of women receiving risk reducing medication and the associated impact on quality of life, functioning, and adherence from the patient perspective are lacking [7,8,12,20,42,46,47]. Current strategies for minimizing toxicities related to antiestrogen therapy include use of lower or intermittent dosing and alternative drug delivery methods, although strategies focused on directly addressing the symptom burden associated with these toxicities while maintaining recommended treatment are limited by a lack of evidence [16].

Symptom burden is a subset of health-related quality of life (HRQOL) and refers to the combined severity of the symptoms of a disease and its treatment and the impact of those symptoms on daily functioning [48, 49]. In contrast to concepts such as quality of life or functioning, symptom burden is the concept most closely related to the physiological effects of disease and treatment, useful for monitoring the patient status and treatment decision-making in clinical care [48,49].

Management of symptom burden across the cancer trajectory depends on valid symptom measurement and patient-clinician communication about the symptom experience [50]. Substantial evidence demonstrates that cancer patients and clinicians are not engaged in efficient symptom-related communication, resulting in underreporting of symptom burden, lack of symptom management, impact on quality of life and functioning, and unnecessary treatment modifications or discontinuations [2,4,47,51–54]. To date, few studies have reported on the symptom burden related to risk reducing medication among women at high risk for breast cancer, and methods for effectively monitoring symptom burden in preventive care settings are not established.

Routine capture of patient-reported outcomes data using validated symptom burden measures provides a mechanism for supporting accurate symptom burden measurement and patient-clinician communication about symptoms [47]. Importantly, generic measures may not accurately capture the unique experience of a patient population, such as women at high risk for breast cancer [55]. While several validated measures are used to capture quality of life and functioning across the breast cancer disease- and treatment-trajectory [55–59], no measure specific to the symptom burden of women at high risk for breast cancer and receiving risk reducing medication exists. A first step in development of a measure to be used for monitoring the symptom burden experienced by women receiving risk reducing medication includes describing the content domain, or the components of the symptom experience most important to patients, through direct input from patients within the target population. Our purpose here was to describe the symptom burden experienced by women receiving preventive care for breast cancer, including risk reducing medication, to identify the content domain and support the further development of a PRO measure for use in clinical care.

Methods

This qualitative study was approved by the Institutional Review Board at The University of Texas Health Science Center at Houston (UTHealth Houston).

Setting

Participants were recruited from breast cancer high-risk specialty clinics at The University of Texas Health Science Center at Houston (UTHealth Houston) (the Memorial Hermann Oncology Clinics and UT Physicians Multispecialty Bayshore Clinic).

Participants

Patients were eligible for participation if they were (1) female, (2) ≥ 18 years of age, (3) able to speak and read English, (4) at high-risk for breast cancer, (5) currently receipt of risk reducing medication for a duration of at least one month, and (6) able to provide informed consent. High-risk for breast cancer was defined using the National Comprehensive Cancer Network Breast Cancer Screening and Diagnosis Guidelines, Version 1.2023 [60]. Patients with documented cognitive deficits were excluded from participation.

Study coordinators screened high-risk specialty clinics for eligible patients and approached potential participants either in clinic or by phone to obtain informed consent. Recruitment continued until data saturation was achieved, defined as no new themes being found in three consecutive interviews [61].

After informed consent was obtained, participants were contacted by phone for qualitative interviews. An interview guide (Table 1), was drafted by the research team with input from breast medical oncologists who, specialized in the care of women at high risk for breast cancer; the guide featured open-ended questions about the patient experience was used as a template for the interviews. Open-ended questions were written to capture not only the preventive care experiences of women at high risk for breast cancer, including what brought them to their initial screening and symptoms related to their breast cancer risk and preventive treatment, but also the burden of their identified risk on other aspects of their life, including work, finances, and overall stress level. Here we report on the symptom burden as described by study participants for the purpose of establishing the content domain for a patient-reported outcomes measure of the symptom burden of receiving risk reducing medication for breast cancer risk reduction. Interview duration varied based on depth and length of participant answers, ranging from approximately five minutes to over thirty minutes. Audio from the interviews was recorded, with participant consent, and professionally transcribed. After the interview was completed, interviewers also recorded field notes, documenting the circumstances surrounding the interview. Transcripts were later verified and, if needed, corrected by the research team.

Table 1.

Interview guide for qualitative interviews.

1.	What is it like for you to have a high risk for breast cancer?
	Potential additional probe questions if patient does not describe spontaneously:How do you feel about your breast cancer risk and your preventive care?
2.	What was it like for you when you first learned of your breast cancer risk?
	Potential additional probe questions if patient does not describe spontaneously:What first took you to the doctor to determine your risk?
3.	What symptoms have you experienced that were related to your breast cancer risk and any preventive care you may have received?
4.	What symptoms are you experiencing while receiving hormone therapy?
5.	How has having risk for breast cancer impacted your (and your family’s) day-to-day life?
	Potential additional probe questions if patient does not describe spontaneously:
	Were there any barriers to seeking care? If so, what were those barriers?
	How has having breast cancer risk affected your overalls stress level?
	How has having a breast cancer risk affected your ability to work?
	How has having a breast cancer risk affected you financially?

Demographic and clinical characteristics (reason for identified risk, co-morbid conditions, preventive care history) were extracted from the medical record. In addition, participants completed the MD Anderson Symptom Inventory (MDASI) Breast Cancer module after completion of their interview to capture a numeric rating of individual symptom items, common to patients with breast cancer, at the time of the interview.

Participants received a $25 gift card after completion of the qualitative interview.

Measures

The MDASI-Breast is a module of the MDASI that includes 21 symptom items (13 core cancer items and 8 breast cancer-specific items) and 6 items that refer to symptom-related interference with daily functioning [62]. Patients are asked to score the severity of the individual symptom items on a scale ranging from 0–10 with 10 being the most severe the patient could imagine over the past 24 h. The 6 interference items are similarly scored, with 10 meaning symptoms interfered completely with the given aspect of functioning in the past 24 h. The MDASI-Breast includes 6 subscales: the total symptom severity, core items symptom severity, module items symptom severity, interference, WAW (interference with walking, activity, and work) and REM (interference with relationships with others, enjoyment of life, and mood).

Analysis

Descriptive statistics were used to describe the demographic and clinical characteristics of the study sample, as well as the scores for the individual symptom severity items and symptom-related interference items and subscales from the MDASI-Breast at the time of the interview. All interview transcripts were imported into MAXQDA22 (VERBI GmbH, Berlin, Germany) for descriptive exploratory content analysis. A list of identified symptoms was created by the research team (MW, JJ, DP) as the interviews were analyzed, including symptoms related to risk status and risk reducing medication. The initial list of identified symptoms was reviewed by the research team (MW, JJ, LW, TB) and symptoms were collapsed into common categories after discussion of whether the identified symptoms were symptoms and whether they were unique symptoms. The entire team agreed on the final symptom list. Participant quotes were extracted to exemplify the identified symptoms and participant descriptors were used to name the identified symptoms and further describe the content domain.

Expert panel review

Research staff screened high-risk specialty care clinics for eligible patients and potential expert panel patient participants were approached to obtain an informed consent waiver. Healthcare providers and patients were recruited by email. The panel included a total of 25 participants: 7 physicians (medical, surgical, and radiation oncologists with expertise in breast cancer preventive care) and 5 clinical nurses experienced in breast cancer preventive care, and 13 women with a high risk for breast cancer and receiving preventive care, including risk reducing medication (age range 34–87 years). The relevance of the symptoms identified in qualitative interview was rated on a scale of 1–4, with 1 meaning not relevant and 4 meaning very relevant. Mean relevance scores were calculated.

Provisional MDASI module

Those symptoms that met at last one of the following criteria were then included in a provision instrument: (1) mentioned by at least 20 % of the sample spontaneously during qualitative interview; (2) received an expert panel mean relevance score of at least 3; (3) listed as one of the core 13 symptoms included on the MDASI, which have been psycho-metrically validated as important symptoms in a broad range of cancer patients; or (4) scored as one of the 5 symptoms on the MDASI-Breast with the highest mean severity scores.

Results

Data saturation was reached on completion of 30 interviews. Participants had a mean age of 54.6 years (range 34–87 years); 44 % self-identified as Hispanic and 56 % as non-Hispanic; 77 % self-identified as White, 20 % self-identified as Black, and 3 % as Asian (Table 2). 83 % of participants were receiving a selective estrogen receptor modulator; 17 % were receiving an aromatase inhibitor. The average duration of risk reducing medication at the time of the interview was 14.0 months (range 1.1–49.3 months).

Table 2.

Participant demographic and clinical characteristics (n= 30).

Age (years)		Mean 54.6 Frequency	SD 9.09 Percentage
Race
	White/Caucasian	23	76.7
	Black/African American	6	20.0
	Asian	1	3.33
Ethnicity
	Not Hispanic/Latino	17	56.7
	Hispanic/Latino	13	43.3
Marital Status
	Married	20	66.7
	Single	4	13.3
	Divorced	4	13.3
	Widowed	2	6.67
Employment Status
	Employed outside the home, full-time	18	60.0
	Retired	6	20.0
	Homemaker	3	10.0
	Employed outside the home, part-time	2	6.67
	Disabled due to illness	1	3.33
Education (years)
	16 (college graduate)	13	43.3
	14	8	26.7
	17 (graduate or professional training)	4	13.3
	12 (high school diploma)	3	1.00
	13	1	3.33
	15	1	3.33
Risk assessment
	Family history of breast cancer	19	63.3
	Previous hormone use	13	43.3
	Genetic predisposition	3	10.0
	Dense breast	15	50.0
	History of DCIS	9	30.0
	History of LCIS	5	16.7
	History of atypical hyperplasia	15	50.0
History of Breast Surgery
	Lumpectomy	14	46.7
	Simple Mastectomy	1	3.3
Current Endocrine/Hormonal Therapy
	Tamoxifen (Nolvadex, Soltamox)	20	66.7
	Raloxifene (Evista)	5	16.7
	Anastrozole (Arimidex)	4	13.3
	Exemestane (Aromasin)	1	3.33

At the time of the interview, women reported multiple symptoms, with the most severe being fatigue (mean severity 3.77, SD 2.91), sleep disturbance (mean severity 2.90, SD 2.47), problems with memory (mean severity 2.48, SD 2.07), drowsiness (mean severity 2.23, SD 2.14), and decrease in sexual interest or activity (mean severity 2.09, SD 2.38) (Table 3).

Table 3.

Mean MDASI-Breast item and subscale scores for study participants at the time of the interview (n = 30).

		Mean	SD
Symptom item
	Fatigue (tiredness)	3.77	2.91
	Disturbed sleep	2.90	2.47
	Difficulty remembering things	2.48	2.07
	Drowsy (sleepy)	2.23	2.14
	Decrease in sexual interest or activity	2.09	2.38
	Dry mouth	1.90	2.19
	Constipation	1.81	2.07
	Distress	1.74	2.01
	Hot flashes or sweating	1.74	2.05
	Sadness	1.58	2.01
	Pain	1.55	2.10
	Vaginal dryness	1.35	1.68
	Breast changes	1.23	1.64
	Shortness of breath	1.19	1.61
	Numbness or tingling	1.13	1.45
	Problem with lack of appetite	1.10	1.59
	Fingernail or toenail changes	0.74	1.16
	Skin changes	0.74	1.16
	Nausea	0.52	0.84
	Vomiting	0.45	0.76
	Arm swelling	0.37	0.57
Interference item
	Work	2.57	2.60
	Activity	2.29	2.30
	Walking	2.13	2.49
	Mood	1.81	2.00
	Relationships with other people	1.77	1.91
	Enjoyment of life	1.45	1.72
Composite Scores
	Total symptom	1.55	1.23
	Core symptom	1.75	1.77
	Module symptom	1.29	1.47
	Interference	1.99	1.83
	WAW	2.30	2.25
	REM	1.68	1.74

MDASI-Breast, MD Anderson Symptom Inventory Breast Cancer module; SD, standard deviation, WAW, interference items walking, general activity, and work; REM, interference items relationships with others, enjoyment of life, and mood.

Content analysis found 20 symptoms related to both risk status and risk reducing medication, with 8 symptoms reported by ≥ 20 % of women. All women described distress related to their risk, with 23 % of women describing sadness related to their risk. In addition, 33 % of women reported distress related to the impact of their own risk on their family, primarily on their children. Women (27 %) described breast changes that were present when their risk was identified, such as a lump or pain. Treatment-related symptoms varied based on type of endocrine therapy received and history of risk-reducing surgery; they included sleep disturbance (13 % of women), pain (33 %), hot flashes/night sweats (33 %), fatigue (20 %), and joint stiffness or soreness (23 %).

Quotes illustrating the symptom descriptions for those described by at least 20 % of informants are included in Table 4. In addition, women shared ways in which symptoms impacted daily functioning, work, relationships, and ability to enjoy life. The development process and final list of symptoms that met criteria for inclusion in a provisional measure of symptom burden are included in Table 5. Although vaginal dryness did not meet the criteria for inclusion on the measure, because literature review revealed it as a relevant symptom for women receiving antiestrogen therapy, it was included on the provisional measure. Fig. 1 presents the conceptual model for the symptom burden of breast cancer prevention.

Table 4.

Examples of informant quotes for common symptoms.

Symptom	Informant quote
Distress	“It’s scary. Terrifying. I mean, I have a daughter and who wants to go through [breast cancer] and have a teenage daughter that needs her mom. It’s scary to know that there is a possibility.” 47-year-old female
Pain	“Every morning it takes me a while to stand and walk. I have to stand up and stand there for a minute, and I move real slow. It takes a few minutes for me to be able to move in a decent manner. And I’m in pain every morning when I get up.” 62-year-old female
Hot flashes	“Hot flashes come just like out of nowhere, and especially at night when I’m sweating from the inside out. Even if I try to cool down and everything, my body feels the same way.” 34-year-old female
Breast changes	“I have the lumps still, which I don’t know if that’s scar tissue or what. I have puckering on one side so they’re kind of deformed-looking right now.” 44-year-old female
Sadness	“It’s just so depressing because you can see the difference from where I was before taking the Tamoxifen and after. And it’s just a little bit depressing, but I guess that’s the price you pay for preventing breast cancer.” 45-year-old female
Fatigue (tiredness)	“I used to - I couldn’t sit still and now, I can’t move, and it makes me more depressed because I don’t feel like I have the energy to get up and go and do.” 66-year-old female

Table 5.

MDASI-Breast Prevention Development Summary of Symptom Items.

Symptom item included in provisional MDASI-Breast prevention	N mentioned in qualitative interviews	% mentioned in qualitative interviews	Expert panel mean	Core item	Top 5 symptom severity on MDASI-Breast
Distress (upset)b, c	30	100.0 %	2.54	X
Hot flashesa, c	10	33.3 %	2.48
Paina, c	10	33.3 %	2.36	X
Breast changesb, c	8	26.7 %	2.12
Sadnessb, c	7	23.3 %	2.44	X
Vaginal discharge or bleedinga, c	7	23.3 %	1.87
Joint stiffness or sorenessa, c	7	23.3 %	2.60
Fatigue (tiredness)a, c	6	20.0 %	2.84	X	X
Disturbed sleepa, c	4	13.3 %	2.68	X	X
Vaginal drynessa	4	13.3 %	2.04
Decrease in sexual interest or activitya, c	3	10.0 %	2.52		X
Difficulty remembering thingsa, c	2	6.0 %	2.28	X	X
Nauseaa, c	2	6.0 %	1.92	X
Numbness or tinglinga, c	1	3.3 %	2.04	X
Problem with lack of appetitec	-	-	2.12	X
Shortness of breathc	-	-	2.00	X
Dry mouthc	-	-	2.08	X
Vomitingc	-	-	1.92	X
Drowsy (sleepy)c	-	-	2.28	X	X
Symptom item not included in provisional MDASI-Breast Prevention
Hair changesa	4	13.3 %	2.04
Headachea	3	10.0 %	2.00
Rash or skin changesa	2	6.0 %	2.08
Itchinga	2	6.0 %	1.92
Dizzinessc	1	3.3 %	1.96
Racing heartbeatc	1	3.3 %	2.08
Eye problemsc	1	3.3 %	1.79

^aTreatment-related symptom;

^bRisk- and treatment-related symptom;

^cMeets one or more criteria for inclusion in the provisional MDASI module

Abbreviations: MDASI, MD Anderson Symptom Inventory

Fig. 1.

Conceptual model for symptom burden of breast cancer prevention.

Discussion

Women at high risk for breast cancer and receiving preventive care experience a unique symptom burden that includes multiple symptoms and functional symptom impacts. Participants in our interviews described symptoms included in the core MDASI measure and additional symptoms specific to the unique experience of receiving preventive care for breast cancer. Included in the provisional MDASI-Breast Prevention measure are 13 symptoms found on the core MDASI and six symptoms specific to this unique population: hot flashes, breast changes, vaginal discharge or bleeding, decrease in sexual interest or activity, vaginal dryness, and joint stiffness or soreness.

Participants described 20 symptoms related to both risk of breast cancer and preventive treatment for breast cancer, with eight symptoms reported by at least 20 % of participants. Breast changes, distress, and sadness were described as both risk- and treatment-related symptoms. Breast changes were commonly described as being present at the time of risk identification and included lumps and breast pain, but were also described as a result of risk-reducing surgery. Importantly, symptoms related to impact on mental health were commonly described, with all women describing distress related to their risk and/or preventive care and 23.3 % of women describing sadness. Some aspects of distress among women at high risk for breast cancer have been explored, including financial distress, grief and trauma related to earlier loss of a family member to breast cancer, worry about a breast cancer diagnosis, and anxiety surrounding follow-up appointments and enhanced screening protocols. Additional research is needed to understand the reasons for distress and outcomes related to distress to support development of targeted interventions [63–67]. For example, in further analysis, 33.3 % of women described experiencing distress related to the impact of their own risk on their family, primarily the impact on their daughters and/or granddaughters. While the experience of worrying about a cancer diagnosis among women with a familial history of breast cancer is well-documented, there are limited descriptions of worry related to the impact of risk on their daughters and/or granddaughters [68–70].

Symptoms related to preventive care varied depending on the individual experience with risk-reducing surgery or risk reducing medication, and included hot flashes, pain, vaginal discharge or bleeding, joint stiffness or soreness, fatigue, disturbed sleep, vaginal dryness, decrease in sexual interest or activity, difficult remembering things, nausea, and numbness or tingling. Treatment-related symptoms varied based on type of endocrine therapy received and history of risk-reducing surgery. The presence of the symptoms identified in our interviews among those receiving hormone therapy for breast cancer risk is well-supported in the existing literature [7,8,18,43–45], although our findings highlight the relevance of these symptoms to the patient experience.

Symptom-related interference with general activities, relationships with others, ability to work, mood, enjoyment of life, and treatment adherence was described, consistent with findings from previous work [7,8,12,20,42]. In our study, women in our sample described the impact of both risk- and treatment-related symptoms on their relationships. For example, vaginal dryness and decreases in sexual interest or activity resulting from risk reducing medication were often described as interfering with personal relationships and distress related to risk for breast cancer was often described as interfering with relationships with sisters, daughters, and granddaughters. Difficulty with remembering things and fatigue related to preventive care, and distress related to breast cancer risk, interfered with ability to work. The combination of multiple symptoms was described as impacting enjoyment of life and inability to adhere to recommended treatment protocols for risk reducing medication. The impact of symptoms on adherence is documented in the literature, although additional work is needed to establish which symptoms drive non-adherence and how the timing and severity of individual symptoms relate to non-adherence [8,12,20].

Findings of this study offer the foundation for development of a PRO measure of the symptom burden experienced by women at high risk for breast cancer receiving preventive care. While valid and reliable PRO measures of symptom burden and other domains of quality of life and functioning are available for use in clinical practice and in research, no measure specific to the symptom burden experienced by women in the preventive care setting exists [55–59]. Our findings describe the content domain for a measure that was derived from qualitative interviews with individuals experiencing high risk for breast cancer and preventive care and expert panel opinion.

Limitations

While sampling continued through data saturation and our sample is diverse in age, race, ethnicity, marital status, education status, and preventive care regimen, our sample size is limited and may not be representative of the entire population of women at high risk for breast cancer. Our participants were receiving specialized breast cancer preventive care by a breast medical oncologist, with expertise in breast cancer prevention, which may have provided unique resources for supportive care and patient education. We did not capture symptom management nor dose adjustments or medication changes in the presence of medication side effects in this study. Additional research is needed to better understand symptom management, including medication modifications, and supportive care in prevention settings. The symptom burden described here should be verified in other specialty care settings and among women receiving preventive care in primary care settings.

Conclusions

Women engaging in preventive care for a known risk of breast cancer report multiple symptoms related to both risk and preventive care. Participants describe impact on daily functioning related to symptoms, including interference with relationships, work, mood, enjoyment of life and adherence to recommended treatment. Clinicians should be aware that women at high risk for breast cancer receiving preventive care experience multiple symptoms related to their risk and preventive treatment that interfere with daily activities and well-being. Given this impact, frequent assessment of symptoms and management of symptoms may present an opportunity to improve patient-clinician symptom-related communication, mitigate interference with daily functioning and improve adherence to recommended treatment, in particular to risk reducing medication.

A PRO measure specific to this symptom burden provides a mechanism for valid and reliable measurement and communication about symptoms most relevant to this unique population [46,47]. This study provides initial evidence of the relevant symptom burden and the content domain for a PRO measure to be used in clinical care in research in this population. Next steps include longitudinal studies to capture the symptom burden over time and establish the psychometric properties of the PRO measure. Research is needed to identify and establish methods for routinely capturing the symptom burden, including automation of PRO assessment using technology and the electronic health record and study symptom management strategies. Given that all participants in our sample reported experiencing distress related to their risk, interventions targeting patient education, management of anxiety, and helping patients navigate the impact of their risk on their relatives are needed. Finally, additional work is needed to determine risk factors for more severe symptoms among women at high risk for breast cancer, which could suggest targets for enhanced symptom monitoring and intervention. Identification of risk factors through longitudinal modeling and machine learning techniques may allow for incorporation of artificial intelligence methods for identifying women at risk for severe symptoms in the prevention setting and intervention in the presence of symptoms.