Hot flashes in postmenopausal women treated for breast carcinoma

1682

Hot Flashes in Postmenopausal Women Treated forBreast CarcinomaPrevalence, Severity, Correlates, Management, and Relation to Quality of Life

BACKGROUND. Research on hot flashes (HFs) after the diagnosis and treatment ofJanet S. Carpenter, R.N., Ph.D., A.O.C.N.1

Michael A. Andrykowski, Ph.D.1 breast carcinoma (BC) is scarce. To our knowledge, this research represents the

second study of HF prevalence and severity in women with BC and the first studyMatthew Cordova, M.S.1

Lauren Cunningham, M.S.1 of 1) correlates of HF prevalence and severity, 2) use of HF management strategies,

and 3) the relation between HFs and quality of life (QOL) among women with BC.Jamie Studts, M.S.1

Patrick McGrath, M.D.2 METHODS. Eligible women (n Å 136) participated in structured telephone inter-

views.Daniel Kenady, M.D.2

David Sloan, M.D.2 RESULTS. Of the 114 postmenopausal women interviewed, 65% reported HFs, with

59% of women with HFs (n Å 74) rating the symptom as severe. MultivariateRita Munn, M.D.3

analysis revealed that 1) HFs were most common in women with a high school1 Department of Behavioral Science, University education or less and those who were younger at diagnosis and 2) HFs were mostof Kentucky, Lexington, Kentucky. severe in women with a higher body mass index, those who were younger at

diagnosis, and those receiving tamoxifen. Among women with HFs, 37% were not2 Department of General Surgery, University ofKentucky, Lexington, Kentucky. using any HF management strategies and 63% expressed interest in learning more

regarding¢1 strategy. HFs marginally were related to decreased mental and physi-3 Department of Hematology/Oncology, Univer-cal QOL using the SF-12 Health Survey (P õ 0.10).sity of Kentucky, Lexington, Kentucky.CONCLUSIONS. The results of the current study significantly contribute to knowl-

edge regarding HFs in women with BC and support the need for carefully controlled

clinical trials evaluating interventions for relieving HFs in this population. Cancer

1998;82:1682–91. q 1998 American Cancer Society.

KEYWORDS: breast carcinoma, hot flash, menopause, symptom, quality of life.

Hot flashes (HFs) are the most common symptom of menopause,affecting up to 93% of postmenopausal women.1 A HF is ‘‘a tran-

sient episode of flushing, sweating, and a sensation of heat, oftenaccompanied by palpitations and a feeling of anxiety, and sometimesfollowed by chills.’’2 Although interest in HFs is increasing, researchon HFs in women after diagnosis and treatment of breast carcinoma(BC) remains scarce.3–5 Among women with BC, HFs can be 1) due

Presented in part at the 1997 Society of Behav- to the natural aging process, 2) caused by chemotherapy-inducedioral Medicine 18th Annual Scientific Session, ovarian failure, and/or 3) intensified by chemotherapy and the anties-San Francisco, CA, April 16–19, 1997, and the trogen tamoxifen citrate.3,4,6–9

19th Annual Scientific Session, New Orleans,The prevalence and severity of HFs among women with BC areLA, March 25–28, 1998.

unclear. In a survey of 190 postmenopausal women ages 40–65 yearsAddress for reprints: Janet S. Carpenter, R.N., with BC, 65% reported HFs.4 Of those reporting HFs, 29% reportedPh.D., A.O.C.N., Room 131 COMOB, Depart- mild severity, 37% reported moderate severity, and 34% reported se-ment of Behavioral Science, University of Ken- vere HFs.4 However, several limitations of this study are apparent.tucky, Lexington, KY 40536-0086.

First, the study’s definition of postmenopausal–the absence of men-ses for at least 6 months–may have allowed inclusion of pre- or peri-Received July 28, 1997; revision received No-

vember 21, 1997; accepted November 21, 1997. menopausal women. A more widely accepted and epidemiologically

q 1998 American Cancer Society

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Hot Flashes after Breast Carcinoma/Carpenter et al. 1683

based definition is the absence of menses for at least for healthy women,1,22–24 use in women with BC isquestionable due to their estrogenic activity24 and sub-12 months.10 Second, study respondents were age °

65 years.4 Although HFs are most common in the first sequent unknown effects of phytoestrogens on BC.Low doses of megestrol acetate and transdermal cloni-6 years after menopause in healthy women (around

age 50 years), the total number of years in which HFs dine have been shown to alleviate HFs in women withBC,25,26 but these medications can have significant sideare experienced is variable, with some women experi-

encing HFs in their 60s and 70s.1 In addition, tamoxi- effects and may not be acceptable to some women.25–27

In addition, progesterone (megestrol acetate) mayfen commonly is recommended for postmenopausalwomen with BC.5,11 Because HFs can be a side effect have an adverse effect on tumor biology.19 Inability

to use known, efficacious HRT and limited choice ofof tamoxifen,8 tamoxifen users may reexperience HFsin their later postmenopausal years. Therefore, it is proven and acceptable treatment options suggest HFs

may represent an untreated symptom among womencritical to include women age ú 65 years with BC instudies of HFs. with BC.

Finally, research has not addressed the relationIn women with BC, variables related to HF preva-lence and severity also are unclear. One set of potential between HFs and quality of life (QOL) among women

with BC. This is an important area to study becausecorrelates may be related to acute estrogen with-drawal.1,12 First, HF prevalence and severity are higher both the prevalence and severity of symptoms may

interfere with QOL.28,29 In fact, menopausal symptoms,among tamoxifen users in comparison with nonusers.4

Second, older age at diagnosis is related to longer time including HFs, were found to be associated with lowQOL in 63 healthy women ages 45–60 years.28after menopause with less likelihood of experiencing

HFs due to estrogen withdrawal. Third, women who The current study sought to 1) determine the prev-alence and severity of HFs in outpatients previouslydiscontinue HRT at the time of BC diagnosis may be

more likely to experience HFs after diagnosis due to treated for BC, 2) identify variables associated with HFprevalence and severity, 3) examine women’s use andestrogen withdrawal.5 Fourth, chemotherapy recipi-

ents may be at greater risk for HFs due to chemother- knowledge of HF symptom management strategies,and 4) examine the relation between HFs and QOL.apy-induced ovarian failure and subsequent estrogen

withdrawal.6 Fifth, because estrogen withdrawal ap- This study improves on prior studies in several ways:1) clear definition of postmenopausal status, 2) inclu-pears to be time-limited,1 women who are fewer

months postdiagnosis may be more likely to report sion of women ageú 65 years, 3) assessment of multi-variate correlates of HF prevalence and severity, 4)HFs.

Other potential correlates of HFs in women with examination of use and knowledge of HF symptommanagement strategies, and 5) evaluation of the rela-BC include variables related to HF prevalence and se-

verity in healthy women. Among women without BC, tion between HFs and both emotional and physicalaspects of QOL.HFs are more prevalent and/or more severe in those

who experience menopause prior to age 52 years, haveless than a high school education, report HFs and pre- METHODS

Samplemenstrual tension before menopause, have an artifi-cially induced menopause (surgically or chemically in- All participants were age ¢ 18 years, had a first-time

diagnosis of BC, were at least 3 months from comple-duced), and are thin and smoke (body mass index °22.1).12–14 Menarche prior to age 12 years and a history tion of primary treatment (surgery, radiation, or che-

motherapy), were disease free, spoke and understoodof irregular menses marginally were related to de-creased HF prevalence.14 In addition, exercise may be English, and provided written informed consent.

Potential participants were recruited using tworelated to reduced HF severity.12,15

Options for managing HFs in women with BC are strategies. First, women participating in prior re-search30,31 who had agreed in writing to be contactedseverely limited. Although the benefits of hormone re-

placement therapy (HRT) in alleviating HFs are appar- for future research (n Å 50) were sent a letter describ-ing the purpose and nature of the study (to learn aboutent among healthy women,2 use of HRT is controver-

sial at best6,16,17 and traditionally contraindicated physical symptoms in women treated for BC) and aconsent form to sign and return if interested. Reasonsamong women with BC.18,19 Although a randomized,

prospective study of the risks and benefits of HRT cur- women may have declined participation were not as-sessed. Women who returned a signed consent formrently is underway among women with BC,20 evidence

suggests some women with BC will find HRT an unac- (n Å 40; 80%) were sent a questionnaire packet andinstructed to read but not complete the packet. Tele-ceptable alternative for managing HFs.4,21 Although

soy-based diets or herbs commonly are recommended phone interviews then were scheduled by study staff

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1684 CANCER May 1, 1998 / Volume 82 / Number 9

at a mutually convenient time. During interviews, both had experienced HFs in the previous 2 weeks also wereasked to indicate how bothered they were by theinterviewer and participant had a questionnaire

packet with the interviewer recording participant re- symptom using a 10-point numeric rating scale an-chored by the words not at all bothered (0) and ex-sponses. A total of 39 interviews were completed in

this manner. tremely bothered (10). The HF prevalence and severityquestion was embedded in a 30-item symptom check-Second, women were recruited from the Univer-

sity of Kentucky Comprehensive Breast Care Center. list.30

Women returning for routine follow-up examinations(mammograms, clinical breast examinations, etc.) se- HF Correlatesquentially were identified from patient rosters and eli- Menstrual history, smoking history, and exercise alsogible women were introduced to the study by their were assessed.12–15 Women were asked for their agephysician (n Å 128). If a woman expressed interest, at menarche,14 whether they experienced HFs whilefurther information was provided by study personnel having regular menstrual cycles,13 and whether theyand written informed consent was obtained (n Å 110). were using or had used HRT in the past. MenstrualWomen were given a questionnaire packet and inter- cycle regularity was assessed either in the present if aviews proceeded as described earlier. Because 13 parti- women still was cycling or in the past if a woman hadcipants were either unavailable for interviews or ineli- stopped cycling.14 Women were asked to provide thegible, a total of 97 women were included in the analysis following information on smoking14: age started smok-from the breast center. Thus, a total of 136 women ing, age stopped smoking, and number of cigaretteswere interviewed successfully. Disease and treatment smoked on an average day (either currently if stilldata for all women were recorded from medical re- smoking or in the past for prior smokers). Data werecords. used to classify women as current smokers14 (no vs.

yes) and to calculate pack-years using the followingMeasures formula: ([number of cigarettes smoked per day/20Both standardized and study specific measures were cigarettes per pack] 1 number of years smoked).35

used. Questions adapted from the Massachusetts Women also were asked how many times per weekWomen’s Health Study were designed to assess meno- they engaged in moderate exercise, such as walking orpausal status using the following definitions10,32: pre- swimming, for ¢20 minutes.menopausal: had a menstrual period in the last 3months; perimenopausal: 3–11 months of amenor-

HF Managementrhea or increased menstrual irregularity if still cycling;Women were given a list of ten HF management strate-and postmenopausal: ¢12 months of amenorrhea.gies and asked to indicate which strategies they wereQuestions assessed the time of a woman’s last men-using currently, which had been used in the past, andstrual cycle (number of weeks, months, or years ago)which they might like to know more about. Womenand whether menses were regular or irregular if awere not asked to rate effectiveness of the strategies.woman still was cycling.Options represented traditional and alternative thera-The following demographic information was col-pies commonly recommended to decrease HFs includ-lected; birthdate, race, marital status, income, educa-ing HRT, nonhormonal prescription medications (e.g.,tion, employment status, and height (meters) andBellegal-St [phenobarbital, ergotamine tartrate, andweight (kgs) for calculation of body mass indexbellafoline] [Sandoz Pharmaceuticals, East Hanover,(weight/height2 ).14 Disease and treatment informationNJ] and clonidine), vitamins (e.g., E, B6, and C), herbalextracted from medical records included date andremedies (ginseng and dong quai), diet, exercise,stage at diagnosis, types and dates of treatments (sur-behavioral methods (e.g., relaxation and paced res-gery, radiation, chemotherapy, or tamoxifen), andpiration), acupuncture, and a category labeledpresence of non-BC-related physical comorbidity,other.2,18,22,24,36,37

such as arthritis.

Hot Flashes Quality of LifeThe SF-12 Health Survey was used to assess QOL.38The presence and severity of HFs was assessed using

three questions. Participants were asked if they had The SF-12 assesses eight health concepts using a 4-week recall period: physical functioning, role limita-experienced HFs in the past 2 weeks.10,33,34 If a woman

said yes, she was asked to rate severity using the fol- tions due to physical health problems, bodily pain,general health, vitality, social functioning, role limita-lowing scale: 0: not at all; 1: slightly; 2: moderately; 3:

quite a bit; and 4: extremely.30 Women who stated they tions due to emotional problems, and mental health.

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Both a physical and mental subscale are computed Prevalence and Severity of HFsHF prevalence rates were examined for the entirewith higher scores indicating more favorable QOL.group of postmenopausal women and according tothe number of years since a woman’s last menstrual

RESULTS period. Overall, HFs were reported by 65% of post-Sample Demographics menopausal women with BC. Prevalence rates by yearsOf participants completing phone interviews (n Å since last menstrual period were as follows: 1–2 years136), 12% were premenopausal, 4% were perimeno- postmenopausal (n Å 20), 70%; 3–5 years postmeno-pausal, and 84% were postmenopausal. Of the post- pausal (n Å 28), 75%; 6–10 years postmenopausal (nmenopausal women (n Å 114), 49% were pre- or per- Å 15), 73%; and ú10 years postmenopausal (n Å 50),imenopausal at BC diagnosis, 27% were surgically 54%. These differences were not statistically significantmenopausal at diagnosis, and 24% were naturally (P Å 0.21).menopausal at diagnosis. The mean time since last Severity of HFs based on the entire sample of par-menstrual period for postmenopausal women was ticipants (n Å 114) was as follows: none to not at all12.1 years (standard deviation [SD]Å 10.7 years; range, severe, 36%; slightly, 11%; moderately, 15%; quite a1–41 years). Because the small numbers of pre- and bit, 18%; and extremely, 20%. Severity of HFs amongperimenopausal women (n Å 22) were not sufficient only those women reporting HFs (n Å 74) was as fol-for subsequent analyses, results focus on postmeno- lows: not at all, 1%; slightly, 16%; moderately, 23%;pausal women only (n Å 114). quite a bit, 28%; and extremely, 31%. Among women

Postmenopausal women were a mean age of 58.8 reporting HFs, the mean HF bother rating was 5.7 (SDyears (SD Å 10.3 years; range, 36–83 years), primarily Å 3.2; median Å 5.0). HF bother ratings ranged fromwhite (96%), married (63%), and working full time or 1 to 10, with 23% of women reporting a bother ratingparttime outside the home (42%), with a median equal to 10. HF bother was rated as mild (°3) by 36%household income of $35,000. Mean education level of women, moderate (4–6) by 20% of women, andwas 13.3 years (SD Å 3.3 years; range, 4–20 years), severe (¢7) by 44% of women.with 51% of women having a °high school diploma.The mean time after diagnosis was 39.0 months (SD Correlates of HF Prevalence and SeverityÅ 24.4 months; range, 4–154 months) and the mean Univariate correlates of HF prevalence and severitytime after completion of treatment (surgery, radiation, that were examined using Student’s t tests and chi-or chemotherapy) was 34.9 months (SD Å 22.1 square analysis included sociodemographic variablesmonths; range, 4–116 months). Staging information (education, body mass index, premenopausal regular-was incomplete for 12 women. Staging information ity/irregularity of menstrual cycles, age at menarche,(according to American Joint Committee on Cancer presence of HFs while regularly menstruating, use ofstaging system) for the 102 participants with complete HRT prior to or at the time of BC diagnosis, smoking,data included: Stage 0 (11%), Stage I (34%), Stage IIA and exercise) and BC specific variables (age at diagno-(24%), Stage IIB (21%), Stage IIIA (5%), and Stage IIIB sis, tamoxifen use, chemotherapy, and months after(5%). Types of surgeries included unilateral modified diagnosis). HF severity was dichotomized as none toradical mastectomy (60%), lumpectomy with axillary mildly severe (i.e., severity rating ° 1) versus severedissection (36%), and bilateral modified radical mas- (severity rating¢ 2). The results of the Student’s t teststectomy (4%). Types of primary treatment included are shown in Table 1. For chi-square analysis, womensurgery alone (40%), surgery and radiation (13%), sur- with HFs were significantly more likely to have re-gery and chemotherapy (24%), and surgery, radiation, ceived chemotherapy (P õ 0.05) and more likely to beand chemotherapy (23%). For the 55 women receiving tamoxifen users (Põ 0.25) in comparison with womenchemotherapy, the mean number of cycles received without HFs. Similarly, women with severe HFs werewas 5.0 (SDÅ 1.7 cycles) with regimens including vari- significantly more likely to be tamoxifen users (P õous combinations of cyclophosphamide, doxorubicin, 0.01) and have received chemotherapy (P õ 0.05) inmethotrexate, and 5-fluorouracil. Tamoxifen use was comparison with women with none to mildly severereported by 54 postmenopausal women (47%) and ta- HFs.moxifen was the only adjuvant therapy received for Variables to be included in a subsequent multivar-57% of those women (n Å 31). In addition, 14% of iate analysis of HF prevalence were identified on thepostmenopausal women chose to have reconstructive basis of our univariate results. We determined thatsurgery and 68% reported the presence of non-BC- eight variables could be supported in a subsequentrelated physical comorbidity, such as hypertension or logistic regression analysis per Stokes et al.’s39 sugges-

tion of 1 predictor variable per 5 subjects with thearthritis.

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TABLE 1Group Differences in Prevalence and Severity of Hot Flashes Based on Demographic, Disease, and Treatment Variables

Prevalence (M [SD]) Severity (M [SD])

Variable No HFs (n Å 40) HFs (n Å 74) t a None/mild (n Å 53) Severe (n Å 61) t a

Years of education 14.2 (3.0) 12.8 (3.4) 2.3c 13.5 (3.4) 13.1 (3.2) 0.7Body mass index 25.2 (4.3) 27.6 (6.9) 02.3c 25.1 (4.4) 28.3 (7.1) 02.9d

Age at menarche 13.1 (1.7) 12.5 (1.6) 1.9e 13.0 (1.6) 12.4 (1.6) 1.9e

Smoking (pack-years) 12.8 (23.7) 11.2 (20.3) 0.4 13.2 (24.0) 10.5 (19.1) 0.7Exercise (times per week)b 3.0 (2.6) 2.5 (2.4) 0.9 2.8 (2.6) 2.6 (2.4) 0.4Age at BC diagnosis 60.3 (11.49) 53.0 (8.68) 3.5d 59.1 (11.8) 52.5 (7.8) 3.5d

Months after BC diagnosis 45.0 (30.9) 35.8 (19.6) 1.7e 44.5 (28.2) 34.3 (19.6) 2.3c

M: mean; SD: standard deviation; HF: hot flash; BC: breast carcinoma.a Student’s t test of difference between groups.b Weekly frequency of engaging in moderate exercise for ¢20 minutes.c P õ 0.05.d P õ 0.01.e P õ 0.25.

rarer outcome being determined (n Å 40 women with- that as many as 10 parameters could be supported inthe logistic regression analysis (n Å 53 women without HFs; 40/5 Å 8). Based on univariate results, five

variables were eliminated as potential predictors of HF none to mild HFs; 53/5 Å 10.6). Results of the logisticregression of HF severity are shown in Table 2. Theprevalence (P values ú 0.25) from subsequent multi-

variate analysis40; menstrual cycle regularity, history of set of 7 predictor variables was significantly associatedwith HF severity (chi-square model Å 22.96; 7 df; P õHFs while cycling, use of HRT prior to or at the time

of BC diagnosis, smoking, and exercise. The remaining 0.01). Significant predictors included body mass index(P õ 0.05), age at diagnosis (P õ 0.01), and tamoxifen7 variables included in the logistic regression analysis

and their coding scheme included: education (°high (P õ 0.05). In general, greater likelihood of experienc-ing severe HFs was associated with greater body massschool vs. úhigh school), body mass index (15.1–20,

20.1–25 . . . 35.1–40), age at menarche (°12 years vs. index, younger age at diagnosis, and use of tamoxifen.The probability of severe HFs increased by a factor ofú12 years), age at diagnosis (grouped by deciles: 30s,

40s . . . 80s), tamoxifen use (no vs. yes), prior chemo- 1.64 for every 5 unit increase in body mass above 20(ORÅ 1.64), decreased by approximately 50% for everytherapy (no vs. yes), and months after diagnosis (õ12

months, 12–23.9 months . . . . 72–83.9 months). 10-year increase in age ú age 39 years (OR Å 0.52),and increased by a factor of 2.63 in women receivingThe results of the logistic regression of HF preva-

lence are shown in Table 2. The set of 7 predictor tamoxifen (OR Å 2.63).Additional logistic regression analyses assessedvariables was significantly associated with HF preva-

lence (chi-square model Å 21.50; 7 degrees of freedom the potential interaction between body mass andsmoking described by Schwingl et al.14 Smoking was[df]; P õ 0.01). Significant predictors (P values õ 0.05)

included education and age at diagnosis. In general, a added to the reduced variable models along with theinteraction term (body mass by smoking). Neithergreater likelihood of experiencing HFs was associated

with less education and younger age at diagnosis. smoking nor the interaction were significant pre-dictors of HF prevalence or HF severity (all P valuesWomen with more than a high school education were

approximately 33% as likely to experience HFs as ú 0.89).Because the association between body mass indexwomen with °a high school education (odds ratio

[OR] Å 0.36). For every 10-year increase in age ú 39 and HF severity was not as expected,12,14 additionalanalyses were performed. Using Pearson correlations,years, the probability of HFs decreased by approxi-

mately 50% (OR Å 0.59). body mass was found to be significantly (P õ 0.05)associated with years of education (correlation coeffi-Five variables also were eliminated from the mul-

tivariate analysis of HF severity (P values ú 0.25).40 As cient [r] Å 00.19), number of chemotherapy cycles (rÅ 0.21), and months after diagnosis (r Å 00.25). Bodystated earlier, the goal was to reduce the number of

predictor variables in the logistic regression to avoid mass was not significantly associated with frequencyof weekly exercise or age at diagnosis. Using Student’soverspecification of the model.39 Our data suggested

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TABLE 2Logistic Regression Analyses of Prevalence and Severity of Hot Flashes

Prevalencea Severityb

Variable OR 95% CL R 95% CL

Educationc 0.36 j 0.14–0.91 0.68 0.29–1.62Body mass indexd 1.35 0.83–32.79 1.64 j 1.02–2.61Age at menarchee 0.74 0.29–1.86 0.85 0.35–2.06Age at diagnosisf 0.59 j 0.36–0.95 0.52k 0.32–0.85Tamoxifeng 1.46 0.57–3.75 2.63 j 1.09–6.37Chemotherapyh 1.61 0.56–4.66 0.94 0.35–2.51Months after BC diagnosisi 0.98 0.72–1.30 0.94 0.72–1.24Model Chi-square 21.5k 22.96k

OR: odds ratio; 95% CL: 95% confidence limit; BC: breast carcinoma.a Prevalence: no vs yes.b Severity: none to mild vs. severe.c Amount of education completed (°high school vs. úhigh school).d Body mass index; 15.1 to 20, 20.1 to 25, 25.1 to 30, 30.1 to 35, 35.1 to 40.e Age at menarche (°12 years vs. ú12 years).f Age at diagnosis by decile: 30–39.9 years, 40–49.9 years, 50–59.9 years, 60–69.9 years, 70–79.9 years, 80–89.9 years.g Use of tamoxifen (no vs. yes).h Chemotherapy treatment received (no vs. yes).i Months after diagnosis: õ12, 12–23.9, 24–35.9, . . . 72–83.9j P õ 0.05.k P õ 0.01.

TABLE 3t tests, no significant differences were found in bodySymptom Management Strategies Reported by Postmenopausalmass between women based on menstrual cycle regu-Women with BC Experiencing Hot Flashes (n Å 74)larity (regular vs. irregular), age at menarche (°12

years vs. ú12 years), prior history of HFs (no vs. yes), Currently Tried in the Would like to knowprior use of HRT (no vs. yes), smoking (no vs. yes), or use % past % more about %tamoxifen use (no vs. yes).

Hormone replacement therapy 0 40 16Nonhormonal prescriptionHF Management

medicationsa 16 14 26Symptom management strategies used by women with Vitaminsb 51 10 33HFs (n Å 74) are listed in Table 3. Vitamins were the Herbsc 0 6 37

Diet 15 1 37most commonly used current strategy, whereas HRTExercise 23 3 30was the most commonly used past strategy. The meanBehavioral methodsd 14 4 40number of strategies currently used was 1.3 (SD Å 1.3Acupuncture 0 0 19

strategies; range, 0–4 strategies) and used in the past Other 8 2 26was 0.8 (SD Å 1.0 strategies; range, 0–4 strategies).

BC: breast carcinoma.The mean number of strategies women stated theya Bellergal-St (phenobarbital, ergotamine tartrate, and bellafoline) (Sandoz Pharmaceuticals, East Han-would like to know more about was 2.6 (SD Å 2.7over, NJ) and clonidine.strategies; range, 0–9 strategies). In addition, 37% of b Vitamins E, B6, and C.

women with HFs were not using any strategies, 51% c Ginseng and dong quai.had not used any strategies in the past, and 63% d Relaxation and paced respiration.

wanted to know more about ¢1 symptom manage-ment strategy.

Student’s t tests and chi-squared analysis wereused to examine differences in demographic, disease, agement strategies reported significantly (all P values

õ 0.05) more HF bother, higher levels of education,and treatment variables between women with HFswho reported currently using HF management strate- greater frequency of weekly exercise, and were more

likely to have received chemotherapy. No differencesgies (n Å 46) and those who did not report using anystrategies (n Å 27). Women currently using HF man- between HF management groups were noted on body

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mass index, menstrual cycle regularity, age at menar- with BC (59%) will report their HFs to be severe. Datache, previous history of HFs, prior use of HRT, smok- on HF prevalence, severity, and bother are convincinging, age at diagnosis, current use of tamoxifen, or indicators of the magnitude of the HF problem inmonths after diagnosis. women with BC.

Three aspects of our results reinforce the need forRelation to QOL carefully controlled clinical trials evaluating interven-Using Student’s t tests, differences in QOL were exam- tions for relieving HFs. First, prevalence, severity, andined between 1) 40 women without HFs and 74 women bother data highlight the significance of the problemwith HFs and 2) 53 women with none to mildly severe of HFs in women with BC. Second, correlates of HFHFs and 61 women with severe HFs. Groups differ- prevalence and severity identified in this research de-ences in QOL narrowly missed our criterion for statisti- fine women with BC at high risk for experiencing HFscal significance (0.05 õ P õ 0.10). Women with HFs in general and severe HFs in particular. Although cor-tended to report poorer mental QOL (mean [M] (SD) relates will be useful for developing screening criteriaÅ 48.4 [12.0] vs. 52.5 [11.2]; PÅ 0.08) and poorer physi- for identifying women at high risk, such criteria are ofcal QOL (M [SD] Å 42.0 [11.9] vs. 46.3 [12.4]; P Å 0.07) little use when proven treatments are not available.in comparison with women without HFs. Similarly, Third, HF management responses indicate current usewomen with severe HFs tended to report poorer men- of and potential interest in using alternative treat-tal QOL (M [SD] Å 48.2 [11.8] vs. 51.8 [11.7]; P Å 0.10) ments, despite the lack of research supporting theirand poorer physical QOL (M [SD] Å 41.7 [12.1] vs. 45.7 safety and efficacy in women with BC. Specifically,[12.0]; P Å 0.08) in comparison with women with less 63% of women with HFs expressed interest in learningsevere HFs. In addition, HF severity marginally was more regarding HF management strategies. In addi-related to mental and physical QOL (r Å 00.18; P val- tion, treatments are needed for women who are toldues Å 0.06). to discontinue HRT after diagnosis of BC (40% of the

women in the current study with HFs). Because alter-DISCUSSION natives to HRT for relieving HFs cannot be recom-HFs were shown to be a significant problem for a ma-

mended based on our current state of knowledge,1,23

jority of women after treatment for BC. Our overallfurther research is needed. Research on alternative in-

prevalence rate is identical to the 65% prevalence rateterventions for relieving HFs is compatible with, and

found in prior research on this population4 and com-not intended to replace, research evaluating use of

parable to prevalence rates found in healthy non-BCHRT in women with BC.20

postmenopausal women who have the option of re-Results pertaining to multivariate correlates of HFceiving HRT.1,33,34,41 However, the 65% prevalence rate

prevalence (education, age at diagnosis) and severityactually may underestimate the problem of HFs in(age at diagnosis, tamoxifen) in our sample of womenwomen with BC. First, our prevalence rates by timewith BC generally are consistent with prior researchafter menopause were higher than those reported inand theory based on healthy non-BC samples. LowerKronenberg’s1 comprehensive review. In particular,educational levels have been tied to earlier age atour 54% prevalence rate among women who wereú10menopause,42 which has been shown to be a risk factoryears postmenopause is significantly higher than thefor HFs.14 In our study, lower educational levels also4–35% rate found in healthy non-BC samples.1 Sec-were linked with a lower likelihood of using HF man-ond, although HFs decrease with time after meno-agement strategies. Education also may be an indica-pause in healthy women,1 HFs do not appear to betor of other environmental influences, such as diet,time-limited in women with BC. Prevalence rates forwhich may affect a woman’s general health status andwomen with BC were found to be fairly stable acrossmenopausal experience. In regard to age at diagnosis,time after menopause, a phenomenon that may beyounger BC survivors may be more likely to experiencerelated to use of tamoxifen during the later postmeno-HFs and severe HFs for several reasons. Youngerpausal years or inability to use HRT. Third, HF preva-women are more likely to be perimenopausal, to expe-lence rates for specific subgroups of women with BCrience chemotherapy-induced ovarian failure, and towere higher than the overall prevalence rate of 65%.be fewer years postmenopause than older women andFor example, 72% of tamoxifen users and 78% of che-thus, more likely to experience HFs.1 In addition, themotherapy recipients experienced HFs. Finally, HFsassociation between tamoxifen and HF severity is con-were severe and bothersome for a majority of BC survi-sistent with prior research demonstrating that HFs arevors. Although approximately 25% of 228 naturallya side effect of tamoxifen therapy.4,9 HFs may be duepostmenopausal healthy women reported severe HFs,1

our results suggest more than twice as many women to tamoxifen’s antiestrogen effect on vascular smooth

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muscle, which is mediated through competitive bind- scale epidemiologic research is needed to providemore accurate and stable estimates of HF prevalenceing of the drug to estrogen receptors.8

Our finding that HFs were associated with in- rates in women with BC. Such large scale researchalso would be useful for verifying correlates of HFcreased body mass index in women with BC is some-

what puzzling. Theory suggests that because lack of prevalence and severity prior to proceeding with in-tervention research. Second, information regardingadiposity is associated with lower levels of circulating

estrogen in healthy postmenopausal women,43,44 thin- HFs was limited to prevalence in the past 2 weeks(no vs. yes), severity, and symptom bother. Additionalner women may experience more HFs due to more

severe estrogen withdrawal in the postmenopausal pe- research is needed to obtain detailed information re-garding HFs, such as daily frequency, daily patternriod.45 However, previous research has only partially

supported this theoretic perspective. (worse at night, worse during day), aggravating andalleviating factors, and worst, least, and average in-The mechanism through which increased body

mass index might be associated with HFs in women tensity. Future research using a diary methodologywould be useful for obtaining detailed informationwith BC is unknown. Weight gain is a common side

effect of BC chemotherapy and tamoxifen.46,47 Al- on HFs in women with BC. Third, data on HFs weregathered solely with the use of self-reports. Althoughthough mechanisms for such weight gain are unclear,

one suggestion is that hormonal changes resulting self-reports may be the best indicator of symptomseverity,49 objective measures that document the oc-from chemotherapy and tamoxifen may lower basal

metabolic rate.46,47 It is possible that weight gain in currence of HFs may provide more accurate informa-tion regarding the prevalence and frequency of HFswomen with BC simply is a marker for hormonal dis-

ruptions which in turn may be related to HFs. Re- among women with BC. One valid and reliable objec-tive measure of HFs is sternal skin conductance mon-search is needed to explore the mechanism through

which increased body mass index might be related to itoring.50,51 Increases in skin conductance occurringover a 30-second interval have been shown to corre-HFs. Analysis of body mass and body composition at

time of diagnosis and at varying times throughout the spond with self-reports of HFs. Incorporating thistype of objective measure of HFs in future researchsurvival trajectory may provide important information

for understanding this mechanism. would enable researchers to obtain detailed, reliable,and valid information regarding prevalence, fre-The finding that HFs marginally were related to

physical and mental QOL is consistent with prior re- quency, and/or daily pattern of HFs. This type of in-formation then can be used to carefully design andsearch showing that HFs were associated with low

QOL in healthy women.28 Although other studies have implement intervention research. Fourth, we did nothave data from a non-BC comparison group. How-shown that HFs are not significantly associated with

significant mental health problems in healthy post- ever, we attempted to compare our findings with pre-vious research when possible.1,4,12,14,28,33,34,41,42,48menopausal women,12,48 we hypothesized that HFs

would be associated with decreased QOL in our HFs were found to be a significant problem amongwomen after treatment for BC. HFs were perceived towomen with BC for two reasons. First, other cancer

treatment side effects such as fatigue have been asso- be severe and bothersome by a majority of womenand marginally were associated with poorer mentalciated with decreased QOL in men and women with

cancer.49 Second, we postulated that HFs would affect and physical QOL. Although many women reportedusing strategies to manage their HFs and expressedQOL negatively because of the lack of effective treat-

ment options. Given the marginal significance of our interest in learning more about alternative HF man-agement strategies, many of these strategies have notfindings, it is possible that our QOL measure, which

was primarily a measure of functional status, was not been examined in carefully controlled research. Futureresearch is needed to explore interventions for de-entirely sensitive to group differences. For women

with BC, HFs may be more of a ‘‘bother’’ than a cause creasing both the prevalence and severity of HFs inwomen after treatment for BC. Carefully designed re-of interference with functional activity.

Results from this study should be examined in search is needed to provide women with BC safe andeffective alternatives for decreasing this common andlight of certain limitations. First, findings are based

on a relatively small, cross-sectional sample of bothersome symptom.women from one geographic region. Although theprevalence of HFs found in this study is identical to

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Hot flashes in postmenopausal women treated for breast carcinoma

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