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Influence of Menopausal Status on the Symptom Experience of Women Before Breast Cancer Surgery

Mazor, Melissa, PhD(c), RN; Cataldo, Janine K., PhD, RN; Lee, Kathryn, PhD, RN; Dhruva, Anand, MD; Paul, Steven M., PhD; Smoot, Betty J., PT, DPTSc, MAS; Dunn, Laura B., MD; Levine, Jon D., PhD; Mastick, Judy, MN, RN; Conley, Yvette P., PhD; Miaskowski, Christine, PhD, RN

doi: 10.1097/NCC.0000000000000545
Articles

Background Breast cancer treatments can change women's hormonal milieu and alter their symptom experience. Little is known about associations between menopausal status and menopausal symptoms in women with breast cancer before surgery.

Objective The purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between premenopausal and postmenopausal women before breast cancer surgery.

Methods A total of 312 women with breast cancer completed the Menopausal Symptoms Scale, a self-report measure that evaluated the occurrence, severity, and distress of 46 common symptoms associated with menopause. Regression analyses were used to evaluate for between-group differences in these symptoms.

Results Of the 312 patients enrolled, 37.4% (n = 116) were premenopausal, and 62.6% (n = 196) were postmenopausal. In the multivariate analysis that adjusted for 7 covariates, premenopausal patients reported higher occurrence rates for urinary frequency (P = .006) and reported lower occurrence rates for joint pain/stiffness (P = .011), difficulty falling asleep (P = .025), and vaginal dryness (P = .002). A significant interaction was found between age and menopausal status for hot flashes (P = .002), wake during the night (P = .025), and headache (P = .040).

Conclusion Regardless of menopausal status, women reported high occurrence rates for several menopausal symptoms. Associations between some symptom occurrence rates and menopausal status depended on the patients' age.

Implications for Practice As part of a preoperative symptom assessment, clinicians need to consider a woman's menopausal status and salient demographic and clinical characteristics. The identification of women with a higher symptom burden will assist with more effective management.

Author Affiliations: Schools of Nursing (Mss Mazor and Mastick and Drs Cataldo, Lee, Paul, and Miaskowski) and Medicine (Drs Dhruva, Smoot, and Levine), University of California at San Francisco; School of Medicine, Stanford University, California (Dr Dunn); and School of Nursing, University of Pittsburgh, Pennsylvania (Dr Conley).

This study was funded by grants from the National Cancer Institute (NCI; CA107091 and CA118658). Dr Christine Miaskowski is an American Cancer Society Clinical Research Professor and is funded by a K05 award from the NCI (CA168960). This project is supported by NIH/NCRR UCSF-CTSI grant number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. M.M. was funded by the American Cancer Society and a T32 grant (NR007088) from the National Institute of Nursing Research.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.cancernursingonline.com).

Correspondence: Christine Miaskowski, PhD, RN, Department of Physiological Nursing, University of California, 2 Koret Way, N631Y, San Francisco, CA 94143-0610 (chris.miaskowski@ucsf.edu).

Accepted for publication July 24, 2017.

Approximately 85% of healthy women experience at least 1 menopausal-associated symptom.1 Symptoms include vasomotor instability (eg, hot flashes, night sweats, day sweats), sleep disturbance, musculoskeletal pain, mood changes, sexual dysfunction, vaginal dryness and atrophy, cognitive complaints, headaches, and fatigue.2 Approximately 40% of healthy women report symptoms that can lead to increased distress and negatively impact their quality of life.1,3 Management of these symptoms is complex because of the increased risk for breast and endometrial cancer associated with hormone replacement therapy (HRT),4 unwanted adverse effects from pharmacologic agents, and variable efficacy of both pharmacologic and nonpharmacologic interventions.5

Although menopausal-associated symptoms co-occur in both premenopausal and postmenopausal women,6 their occurrence, severity, and distress are influenced by a healthy woman's menopausal status,7 as well as demographic, health and illness, lifestyle, and psychosocial factors (for reviews, see Woods and Mitchell1 and Gartoulla et al6). Compared with healthy postmenopausal women, healthy premenopausal women experience lower occurrence rates of vasomotor symptoms (33%–79% vs 4%–46%), vaginal dryness (25%–32% vs 3%–7%), and sleep disturbance (16%–79% vs 6%–54%) (for reviews, see Woods and Mitchell1 and Bromberger and Kravitz8). In addition, although findings are inconsistent, compared with healthy postmenopausal women, healthy premenopausal women report a lower occurrence of physical and psychological symptoms including joint/muscle aches (30%–80% vs 10%–82%),1 mood disturbance (15%–18% vs 8%–12%), depressive symptoms (28% vs 21%),8 and decreased sexual arousal (49% vs 25%).9 Although a substantial amount of research suggests that the symptom experiences of premenopausal and postmenopausal women differ, most of these studies were conducted in healthy women undergoing a natural menopausal transition.

Breast cancer treatments can change the hormonal milieu of both premenopausal and postmenopausal women and alter women's symptom experiences.10 Most research on women with breast cancer has focused on changes in their symptom experience after surgery, chemotherapy (CTX), radiation, and/or hormonal therapy.10–14 Findings from these studies suggest that between 65% and 100% of patients with breast cancer experience at least 1 treatment-induced menopausal symptom (for reviews, see Crandall et al16 and Moon et al17). These symptoms can be acute or chronic, increase distress, negatively impact quality of life, and reduce adherence with long-term hormonal therapy.15 Although some studies demonstrated differences in the symptom experience of premenopausal compared with postmenopausal women,11,13,16,17 most of these investigations were cross-sectional surveys of women with breast cancer several years after diagnosis.13,16,17 In addition, most of these studies evaluated a single symptom and/or a single dimension of the symptom experience and/or did not evaluate for the impact of menopausal status on differences in patients' symptom experiences.10,12,14,18 Therefore, little is known about differences in the multiple dimensions of the symptom experience (ie, occurrence, severity, distress) between premenopausal and postmenopausal women before breast cancer surgery.

Findings from a limited number of studies19–24 suggest that, before breast cancer surgery, a relatively high proportion of women report a number of symptoms (eg, anxiety, depression, pain, fatigue, and sleep disturbance). For example, recent work from our research team found that 28% of women reported presurgical breast pain22; 37% and 70% reported clinically meaningful levels of depression and anxiety, respectively24; and 32% and 50% reported fatigue and decrements in energy, respectively.21 Although, in the study of presurgical breast pain,22 premenopausal women were more likely to report pain before surgery, they were not evaluated for differences in additional symptoms. In another study that evaluated presurgical symptoms,23 the most common symptoms were pain (35%), fatigue (32%), sleep disturbances (26%), and depression (11%). None of the studies cited previously evaluated for differences in symptom occurrence rates between premenopausal and postmenopausal women before breast cancer surgery.

Although these findings suggest that patients experience a variety of symptoms of varying severity before breast cancer surgery, most of these studies evaluated the occurrence or severity of a single symptom, included women who were treated before surgery with hormonal therapy or CTX, and did not compare differences in women's symptom experiences by menopausal status. In fact, no studies were found that compared multiple dimensions of co-occurring symptoms in premenopausal versus postmenopausal women before breast cancer surgery. Recent work from an expert panel recommended that multiple dimensions of a patient's symptom experience be evaluated.25 An evaluation of differences in the occurrence, severity, and distress of various symptoms provides a more comprehensive picture of which symptoms are the most common versus the most severe versus the most distressing for patients. For example, although a specific symptom may have a low occurrence rate, when it occurs, it may be very severe but only mildly distressing.

If differences are found in the symptom experience of premenopausal compared with postmenopausal women before surgery, this information will help clinicians to determine the specific symptoms that need to be assessed and that may warrant intervention. In addition, this information can be used to assess the impact of subsequent treatments on the occurrence, severity, and distress associated with menopausal-related symptoms. Of note, for women with hormone-positive breast cancer, recommendations for specific types of endocrine therapy are made based on the woman's menopausal status.15 Given that tamoxifen and aromatase inhibitors have different treatment-induced symptom profiles, an evaluation of the association between menopausal status and symptoms before surgery will facilitate our understanding of the impact of specific types of endocrine therapy on patients' subsequent symptom experiences.

Given the paucity of research on the presurgical symptom experience, the purpose of this study was to evaluate for differences in multiple dimensions (ie, occurrence, severity, distress) of the symptom experience between premenopausal and postmenopausal women before breast cancer surgery. Given the high level of co-occurring symptoms in healthy women, we hypothesized that both groups of women would report the occurrence of multiple symptoms. Second, we hypothesized that, compared with postmenopausal women, premenopausal women would report lower occurrence rates of and severity ratings for vasomotor symptoms (ie, hot flashes, night sweats, daytime sweats), vaginal dryness, and sleep disturbance.

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Methods

This study is part of a larger descriptive, longitudinal study that evaluated neuropathic pain and lymphedema in women who underwent breast cancer surgery.21,24 Patients were recruited from breast cancer centers located in a Comprehensive Cancer Center, 2 public hospitals, and 4 community practices. Eligibility criteria included adult women (≥18 years old) who were scheduled to undergo unilateral breast cancer surgery; were able to read, write, and understand English; agreed to participate; and provided written informed consent. Patients were excluded if they were scheduled for bilateral breast surgery, had distant metastases at the time of diagnosis, and/or received neoadjuvant CTX.

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Instruments

A demographic questionnaire obtained information on age, education, ethnicity, marital status, employment status, living situation, and financial status. Menopausal status was determined by the patient's response (ie, “yes/no”) to the question, “Have you gone through menopause yet (stopped having your menstrual cycle)?”. Patients were asked to indicate whether they exercised on a regular basis (yes/no). The Karnofsky Performance Status (KPS) scale was used to evaluate functional status. Patients rated their functional status using the KPS scale that ranged from 30 (“I feel severely disabled and need to be hospitalized”) to 100 (“I feel normal; I have no complaints or symptoms”). The KPS scale has well-established validity and reliability.26

The Self-Administered Comorbidity Questionnaire (SCQ) is a short and easily understood instrument that was developed to measure comorbidity in clinical and health service research settings. The questionnaire consists of 13 common medical conditions that were simplified into language that could be understood without any previous medical knowledge. Patients indicated whether they had the condition (yes/no), whether they received treatment for it (proxy for disease severity), and whether it limited their activities (indication of functional limitations). Self-Administered Comorbidity Questionnaire scores can range from 0 to 39. The SCQ has well-established validity and reliability and has been used in studies of patients with a variety of chronic conditions.27

The Menopausal Symptoms Scale (MSS), modified from the 50-item Seattle Women's Health study questionnaire, was used to evaluate the occurrence, severity, and distress of 46 symptoms commonly associated with menopause. Patients were asked to indicate whether they experienced each symptom during the past week (ie, symptom occurrence). If they experienced the symptom, they were asked to rate its severity and distress. Symptom severity was rated using a numeric rating scale (NRS) of 0 (“none”) to 10 (“intolerable”). Symptom distress was rated using an NRS of 0 (“not at all distressing”) to 10 (“very distressing”). The MSS has well-established validity and reliability.28

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Study Procedures

The study was approved by the Committee on Human Research at the University of California, San Francisco, and by the institutional review boards at each of the study sites. A clinician explained the study and determined patient's willingness to participate during her scheduled preoperative visit. After the visit, the clinician introduced the patient to the research nurse who met with the woman, determined eligibility, and obtained written informed consent before surgery. After obtaining consent, patients completed the enrolment questionnaires on an average of 4 days before surgery. Medical records were reviewed for disease and treatment information.

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Statistical Analysis

Data were analyzed using SPSS version 23 (IBM, Armonk, New York). Descriptive statistics and frequency distributions were generated on sample characteristics and symptom occurrence rates, severity scores, and distress scores. Women were categorized into the premenopausal or postmenopausal group based on self-reports of their menopausal status. Independent Student t tests, Mann-Whitney U tests, Fisher exact tests, and χ2 analyses were used to evaluate for differences in demographic and clinical characteristics between the 2 menopausal groups. Characteristics that differed significantly between the menopausal groups were considered for use as potential covariates in the logistic and linear regression analyses.

As part of the evaluation of between-group differences, menopausal symptom occurrence rates were generated for each symptom, and mean scores for severity and distress ratings were calculated for those patients who reported the symptom. Of note, the N for each symptom severity and distress rating varies based on the number of women who reported the occurrence of each symptom. For symptoms that occurred in greater than or equal to 10% of the total sample, unadjusted and adjusted logistic regression analyses were used to evaluate for between-group differences in symptom occurrence rates. Linear regression analyses were used to evaluate for between-group differences in severity and distress scores. First, menopausal status was entered into the regression analysis (unconditional model). Then, characteristics that were found to be significantly different between the 2 menopausal groups and identified as potential covariates were added into the model along with menopausal status (conditional model). Next, the interaction between age and menopausal status group was evaluated. If the “age by menopausal group” interaction was statistically significant, the relationship between age and symptom is presented separately for the 2 menopausal groups.29 A P < .05 was considered statistically significant.

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Results

Differences in Demographic Characteristics Between Premenopausal and Postmenopausal Women

Of the 312 patients with breast cancer who met the eligibility criteria for this study, 37.4% (n = 116) were premenopausal, and 62.6% (n = 196) were postmenopausal. Patients in the premenopausal group ranged in age from 29 to 57 years. Patients in the postmenopausal group ranged in age from 33 to 91 years. As shown in Table 1, compared with postmenopausal patients, premenopausal patients were significantly younger (P < .001), reported more years of education (P = .035), and were less likely to live alone (P = .015), more likely to be employed (P = .005), and more likely to report a higher total annual household income (P = .027).

Table 1

Table 1

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Differences in Clinical Characteristics Between Premenopausal and Postmenopausal Women

As shown in Table 1, compared with postmenopausal patients, premenopausal patients had a lower body mass index (BMI) (P = .022) and a lower SCQ score (P < .001). In addition, a lower percentage of premenopausal patients had high blood pressure (P < .001), diabetes (P < .001), liver disease (P = .028), osteoarthritis (P = .001), fibrocystic disease (P = .045), a previous hysterectomy (P < .001), a previous oophorectomy (P = .001), or HRT before surgery (P < .001). A higher percentage of premenopausal patients exercised on a regular basis (P = .038) and had genetic testing for BRCA1 and BRCA2 (16.5% vs 4.1%, P < .001).

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Differences in Symptom Occurrence Rates and Total Number of Symptoms Between Premenopausal and Postmenopausal Women

The occurrence rates for the 46 symptoms and the top 10 symptoms are listed in the Table, Supplemental Digital Content 1, http://links.lww.com/CN/A13, and in Table 2, respectively. No differences were found in the total number of symptoms between premenopausal (mean, 13.3 ± 7.8) and postmenopausal (mean, 12.0 ± 8.6) women (t = 1.35, P = .177). The 5 symptoms with the highest occurrence rates in premenopausal patients were anxiety (69.8%), fatigue or tiredness (62.1%), tension (57.8%), wake during the night (54.3%), and nervousness (52.6%). Except for tension, the other 4 symptoms were in the top 5 symptoms reported by postmenopausal patients. The fifth symptom in postmenopausal women was difficulty concentrating (42.9%).

Table 2

Table 2

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BIVARIATE AND MULTIVARIATE ANALYSES OF SYMPTOMS WITH HIGHER OCCURRENCE RATES IN PREMENOPAUSAL WOMEN

As shown in Table 3, in the unconditional models, premenopausal patients reported higher occurrence rates for tearful/crying spells (P = .011), painful/tender breasts (P < .001), anxiety (P = .023), lost interest in things (P < .001), anger (P = .016), tension (P = .006), lost sexual interest (P = .005), fatigue or tiredness (P = .026), and impatience (P = .027). In the multivariable analyses that adjusted for 7 covariates (ie, age, lives alone, working for pay, SCQ score, previous use of HRT, regular exercise, and BMI), premenopausal patients reported significantly higher occurrence rates for urinary frequency (P = .006).

Table 3

Table 3

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BIVARIATE AND MULTIVARIATE ANALYSES OF SYMPTOMS WITH HIGHER OCCURRENCE RATES IN POSTMENOPAUSAL WOMEN

In the unconditional models (Table 3), postmenopausal patients reported higher occurrence rates for joint pain/stiffness (P = .011), vaginal dryness (P = .002), and daytime sweats (P = .023). In the multivariable analyses that adjusted for 7 covariates (ie, age, lives alone, working for pay, SCQ score, previous use of HRT, regular exercise, and BMI), postmenopausal patients reported significantly higher occurrence rates for difficulty falling asleep (P = .025) and vaginal dryness (P = .002).

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SYMPTOMS WITH INTERACTION EFFECTS

As shown in Table 4, in the multivariate analyses that included 3 symptoms (ie, hot flashes, wake during the night, and headache) for which significant interactions were found between age and menopausal status, the differences in symptom occurrence rates between premenopausal and postmenopausal patients depended on their age. In the premenopausal group, as age increased, patients were significantly more likely to report hot flashes (P = .033). In the postmenopausal group, as age increased, patients were significantly less likely to report hot flashes (P = .003), wake during the night (P = .008), and headaches (P = .009).

Table 4

Table 4

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Differences in Symptom Severity Scores Between Premenopausal and Postmenopausal Women

The severity scores for the 46 symptoms and for the 10 symptoms with the highest mean severity scores are listed in the Table, Supplemental Digital Content 1, http://links.lww.com/CN/A13, and in Table 2, respectively. For premenopausal patients, the 5 symptoms with the highest severity scores were alcohol cravings, anxiety, difficulty falling asleep, indigestion, and loss of appetite. For postmenopausal patients, the 5 symptoms with the highest severity scores were lost sexual interest, vaginal dryness, difficulty falling asleep, wake during the night, and anxiety.

In the bivariate and multivariate analyses for symptoms that occurred in greater than or equal to 10% of the sample, none of the severity scores were significantly different between the premenopausal and postmenopausal patients.

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Differences in Symptom Distress Scores Between Premenopausal and Postmenopausal Women

The distress scores for the 46 symptoms and for the 10 symptoms with the highest mean distress scores are listed in the Table, Supplemental Digital Content 1, http://links.lww.com/CN/A13, and in Table 2, respectively. For premenopausal patients, the 5 symptoms with the highest distress scores were difficulty falling asleep, weight gain, constipation, swollen hands/feet, and anxiety. For postmenopausal patients, the 5 symptoms with the highest distress scores were weight gain, panic feelings, anxiety, cramps, and difficulty falling asleep.

In the bivariate and multivariate analyses for symptoms that occurred in greater than or equal to 10% of the sample, none of the distress scores were significantly different between the premenopausal and postmenopausal patients.

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Discussion

This study is the first to describe differences in multiple dimensions of the symptom experience between premenopausal and postmenopausal women before breast cancer surgery. Similar to the literature on menopausal symptoms in healthy midlife women,1 our first hypothesis was supported. Regardless of menopausal status, most of the women experienced multiple co-occurring symptoms. In addition, our second a priori hypothesis was partially supported. After accounting for multiple covariates, premenopausal women reported lower occurrence rates for hot flashes, vaginal dryness, wake during the night, and difficulty falling asleep. However, none of the symptom severity or distress scores differed between the 2 groups. Of note, instructions on the MSS did not explicitly ask women to report only those symptoms that they attributed to menopausal changes. Therefore, the symptom scores may be related to a variety of causes (eg, menopausal status, the cancer diagnosis and its treatment, and/or other comorbid conditions).30 Consequently, the remainder of the discussion will compare our findings with those of studies of healthy midlife women and women before breast cancer surgery.

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Symptom Occurrence

Regardless of menopausal status, but consistent with previous reports of women recently diagnosed with breast cancer,23,31 anxiety, wake during the night, fatigue, and nervousness were the 4 most common symptoms reported before surgery. However, with the exception of wake during the night, these symptoms are not the most common ones reported by healthy women. For example, in a study of healthy women between the ages of 45 and 65 years,32 hot flashes (26%), night sweats (17%), insomnia (16%), and vaginal dryness (13%) were the most common symptoms.

Although the most common symptoms reported by healthy women did have similar occurrence rates in our sample, it is not surprising that anxiety, sleep problems, and fatigue would occur in most of our patients before surgery. A breast cancer diagnosis and a pending surgery are associated with high levels of distress and uncertainty, which can have a negative impact on mood and sleep.31

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DIFFERENCES IN SYMPTOM OCCURRENCE BY MENOPAUSAL STATUS

One of the major strengths of this study is that statistically significant and clinically meaningful covariates (ie, age, lives alone, working for pay, SCQ score, previous HRT, regular exercise, BMI) were controlled for in our analyses of differences in symptom occurrence rates between the 2 menopausal groups. After controlling for these covariates, only 1 symptom (ie, urinary frequency) occurred more frequently in premenopausal women. After controlling for these covariates, of the 2 symptoms that occurred more frequently in postmenopausal women (ie, difficulty falling asleep and vaginal dryness), only difficulty falling asleep was influenced by age.

The overall occurrence rate for urinary frequency (17%) was consistent with previous reports of urinary symptoms (ie, 14%33 to 57%34) in midlife women. Compared with premenopausal women, postmenopausal women had a 74.6% decrease in the odds of reporting urinary frequency. In addition, regardless of menopausal status, an increased occurrence of urinary frequency was associated with previous HRT use and a higher level of comorbidity. Previous findings regarding an association between menopausal status and urinary frequency are inconsistent. Whereas some studies of midlife women found that urinary frequency was more common in postmenopausal women,1,2 others reported findings that were similar to our study.33,35 For example, in 1 study that evaluated bladder symptoms in a sample of midlife women,35 after controlling for age, a higher percentage of women in the late reproductive stage reported a higher prevalence of daytime urinary frequency than women in the menopausal transition. Inconsistencies may result from differences in the measurement of bladder symptoms (eg, urinary urgency36 vs frequency), methods of analysis (eg, not controlling for covariates2), and individual factors that can impact occurrence rates for urinary frequency (eg, other comorbid conditions) (for a review, see Cardozo and Robinson36). Given that previous studies of presurgical symptoms in women with breast cancer23,31 did not evaluate for urinary frequency, our findings warrant confirmation in future studies.

Regardless of menopausal status, the overall occurrence rate for difficulty falling asleep was 39.4%. This occurrence rate is consistent with previous studies of midlife women (31%–45%)33,37 and of women before breast cancer surgery (25%–88%).23,31 However, after adjusting for covariates, postmenopausal women were 2.3 times more likely to report the occurrence of this symptom. In addition, regardless of menopausal status, women who were younger and reported a higher level of comorbidity were more likely to report difficulty falling asleep. Given that difficulty falling asleep may be associated with additional symptom burden and may worsen during treatment,19 patients need to be assessed for the etiology of this symptom and managed appropriately.

Although only 13.1% of the women in our study reported vaginal dryness, postmenopausal women were 6.8 times more likely to report this symptom. Of note, vaginal dryness was not associated with any of the covariates that were evaluated. Our findings are consistent with previous reports in healthy premenopausal and postmenopausal women that found similar occurrence rates and odds ratios (7% vs 21%; odds ratio, 2.57 [2.12–3.12, P < .001]38; and 7% vs 16% [P < .01]2) for vaginal dryness. Because the occurrence of vaginal dryness may increase in women with breast cancer who are placed on antiestrogen therapy after surgery and its associated impact on sexual function,12 this symptom warrants ongoing assessment and management.

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DIFFERENCES IN OCCURRENCE OF SYMPTOMS WITH INTERACTION EFFECTS

As shown in Table 4, after controlling for covariates, 3 symptoms (ie, hot flashes, wake during the night, and headaches) exhibited significant interaction effects between menopausal status and age. In our study, 8.6% and 35.2% of premenopausal and postmenopausal women, respectively, reported the occurrence of hot flashes. Compared with occurrence rates reported by healthy women (6%–37% for premenopausal and 22%–79% for postmenopausal), our percentages are on the lower end of these ranges.1 These findings may be partially explained by the fact that our study included a wider age range than previous studies of midlife women.1,6

Of note, in premenopausal women (age range, 29–57 years), for every 5-year increase in age, they were 1.8 times more likely to report the occurrence of hot flashes. In contrast, for every 5-year increase in age, postmenopausal women (age range, 33–91 years) were 24% less likely to report the occurrence of hot flashes. These trends are similar to previous reports in healthy women.39 For example, as women reached their final menstrual period, the occurrences of both hot flashes and sweats increase, whereas they decrease as women progress through menopause. In addition, as postmenopausal women age, they report fewer hot flashes.40

Although occurrence rates for wake during the night were relatively similar between premenopausal (54.3%) and postmenopausal (61.2%) women, a significant interaction was found between menopausal status and age. Specifically, whereas age did not influence the occurrence of this symptom in premenopausal women, for every 5-year increase in age in postmenopausal women, the occurrence rates for nighttime awakenings decreased by 20%.

Compared with healthy women, the occurrence rates for nighttime awakenings in both groups were higher (ie, 31% for premenopausal women vs 43% for postmenopausal women37). However, they are consistent with previous reports of sleep disturbance in women before breast cancer surgery (25%–88%).23,31,41 Whereas none of the studies of women with breast cancer evaluated for the effect of menopausal status or the interaction of age and menopausal status,23,31,41,42 in the studies of healthy women,3,7 the findings regarding the association between menopausal status and sleep disturbance are inconsistent (for a review, see Kravitz and Joffe37). The higher occurrence rates for nighttime awakenings in this study may be related to the co-occurrence of additional symptoms (eg, anxiety, vasomotor instability).3,23 In addition, differences may be related to the instruments used to assess symptoms. However, given its high occurrence rate in women with and without breast cancer, this symptom warrants ongoing assessment and management.

Consistent with previous studies of healthy women (for a review, see Ripa et al43), a higher percentage of premenopausal women reported headaches (29.3% vs 18.4%). In addition, an interaction effect was found between menopausal status and age. Whereas age did not influence the occurrence of headaches in premenopausal women, for every 5-year increase in age, postmenopausal women were 26% less likely to report the occurrence of headaches. These age-associated differences are similar to previous reports.43,44 However, many of the previous studies of healthy women evaluated for the occurrence of migraines (for a review, see Ripa et al43). No studies were found that reported the occurrence or etiology of headaches in women before breast cancer surgery. However, given that it occurred in more than 25% of our total sample, the cause of these headaches warrants evaluation in future studies.

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Symptom Severity

Although we hypothesized that premenopausal women would report lower severity scores for vasomotor symptoms than postmenopausal women, no between-group differences were identified. Our findings are not consistent with previous reports of healthy midlife women.1,45 Findings from previous studies suggest that postmenopausal women report more severe hot flashes, daytime sweats, and night sweats,33,46 as well as psychosocial, physical, and sexual symptoms.46 These inconsistent findings may be related to differences in sample characteristics (ie, age, cancer diagnosis) and/or in the methods used to assess symptom severity. In our study, severity was rated using an NRS of 0 to 10. In contrast, in several of the large midlife women cohort studies, severity was rated on 3- or 4-point categorical scales.1,6,45

Of note, regardless of menopausal status, these women reported an average of 12.4 (±8.3) symptoms. It should be noted that the ranking of the 5 most severe symptoms differed by menopausal group. For premenopausal women, the unique symptoms were alcohol cravings, indigestion, and loss of appetite. For postmenopausal women, the unique symptoms were lost sexual interest, vaginal dryness, and wake during the night. All women reported anxiety and difficulty falling asleep among the top 5 most severe symptoms. Given these differences in the rank order of the most severe symptoms, menopausal status needs to be taken into consideration during the preoperative assessment of these patients. That said, regardless of menopausal status, the 10 most severe symptoms were in the moderate range (4.1–5.2 on a 0–10 NRS). In fact, for the entire sample, using a cutoff score of 4.0 or greater, which is considered a moderate level of severity,47 17 of the 46 symptoms (37%) were in the moderate to severe range. Given these findings, a comprehensive assessment of multiple dimensions of the symptom experience is warranted before surgery.

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Symptom Distress

Similar to symptom severity, no between-group differences in symptom distress scores were identified. In 1 study that evaluated distress in women with newly diagnosed breast cancer,31 younger women reported higher pretreatment distress. However, the effect of menopausal status was not evaluated.31 In another study,48 midlife breast cancer survivors reported higher levels of distress associated with hot flashes than age-matched controls. However, comparisons were not made between premenopausal and postmenopausal women in either group. In 1 study of healthy midlife women that compared premenopausal and early perimenopausal women,49 postmenopausal women reported more bothersome vasomotor symptoms. Because of the fact that distress and/or bother is often used interchangeably with frequency33 or severity/interference,50 comparisons are difficult.

Similar to severity, the rankings for the 5 most distressing symptoms differed by menopausal status (Table 2). For premenopausal women, the unique symptoms were constipation and swollen hands/feet. The symptoms unique to postmenopausal women were panic feelings and cramps. All women reported difficulty falling asleep, weight gain, and anxiety among the top 5 most distressing symptoms before surgery. Despite some overlap in symptom distress, these findings suggest that the most distressing symptoms vary depending on menopausal status and should be considered in the pretreatment assessment of these patients. In addition, regardless of menopausal status, the 10 most distressing symptoms were in the moderate range (4.2–5.0 on a 0–10 NRS). In fact, 14 of the 46 symptoms (30%) were “somewhat” to “very distressing.” These outcomes suggest that, although symptoms may not be reported as commonly occurring and/or severe, they may be highly distressing to the individual and vice versa.

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Limitations

Several study limitations need to be acknowledged. Patients' self-report of menopausal status was used to create the 2 groups. Although the criterion standard for determining menopausal status includes an assessment of changes in the regularity of the menstrual cycle, hormonal levels, and symptoms,51 previous studies support the validity and reliability of self-report.52,53 In addition, for some of the symptoms, after controlling for age, menopausal status accounted for variations between younger and older premenopausal and postmenopausal women (ie, interaction effects). One of the primary reasons for refusal to enroll was feeling overwhelmed with the cancer experience. Therefore, our findings may underestimate the symptom experiences of these patients. Finally, most women in this study were white and well educated, which limits the generalizability of our findings.

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Implications for Clinical Practice and Research

Findings from our study suggest that, regardless of menopausal status, most women experience multiple co-occurring, moderately severe, and distressing symptoms. In addition, similar to studies of healthy midlife women,2,7,45,49 our findings support the interrelationships among symptoms, menopausal status, and additional patient characteristics (eg, age, comorbidities, previous use of HRT). Therefore, as part of a preoperative symptom assessment, clinicians need to consider a woman's menopausal status and salient demographic and clinical characteristics. These findings highlight the importance of assessment and education before surgery. Moreover, given that many of these symptoms were “psychological” or “mood related” (eg, anxiety, tearful/crying spells), referrals to mental health specialists and/or social workers are warranted. In addition, given that many of these menopausal-related symptoms may have a negative impact on women's well-being and adherence to long-term endocrine therapy, effective symptom management before surgery may help manage expectations of symptom burden over time. These findings may assist clinicians to individualize patient assessments based on their menopausal status.

Given that breast cancer treatment impacts women's hormonal milieu, studies are needed to evaluate for changes over time in their symptom experience. Moreover, additional research is warranted on the interrelationships between multiple co-occurring symptoms (ie, symptom clusters) in these women. Studies of symptom clusters need to evaluate for differences in the number and types of clusters based on which dimension of the symptom experience is used in the analysis and whether symptom clusters change over time.25 Identification of symptom clusters may help to determine shared mechanisms and/or etiologies for the symptoms within the cluster, which in turn may direct symptom management interventions.

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References

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Keywords:

Breast cancer; Distress; Postmenopausal; Premenopausal; Severity; Surgery; Symptoms

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