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Hot Flashes in Postmenopausal Women Treated for
Breast Carcinoma
Prevalence, Severity, Correlates, Management, and Relation to Quality of Life
Janet S. Carpenter, R.N., Ph.D., A.O.C.N.1
Michael A. Andrykowski, Ph.D.1
Matthew Cordova, M.S.1
Lauren Cunningham, M.S.1
Jamie Studts, M.S.1
Patrick McGrath, M.D.2
Daniel Kenady, M.D.2
David Sloan, M.D.2
Rita Munn, M.D.3
Department of Behavioral Science, University
of Kentucky, Lexington, Kentucky.
Department of General Surgery, University of
Kentucky, Lexington, Kentucky.
Department of Hematology/Oncology, University of Kentucky, Lexington, Kentucky.
BACKGROUND. Research on hot flashes (HFs) after the diagnosis and treatment of
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 study
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.
METHODS. Eligible women (n Å 136) participated in structured telephone interviews.
RESULTS. Of the 114 postmenopausal women interviewed, 65% reported HFs, with
59% of women with HFs (n Å 74) rating the symptom as severe. Multivariate
analysis revealed that 1) HFs were most common in women with a high school
education or less and those who were younger at diagnosis and 2) HFs were most
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 not
using any HF management strategies and 63% expressed interest in learning more
regarding ¢1 strategy. HFs marginally were related to decreased mental and physical QOL using the SF-12 Health Survey (P õ 0.10).
CONCLUSIONS. The results of the current study significantly contribute to knowledge 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.
Presented in part at the 1997 Society of Behavioral Medicine 18th Annual Scientific Session,
San Francisco, CA, April 16–19, 1997, and the
19th Annual Scientific Session, New Orleans,
LA, March 25–28, 1998.
Address for reprints: Janet S. Carpenter, R.N.,
Ph.D., A.O.C.N., Room 131 COMOB, Department of Behavioral Science, University of Kentucky, Lexington, KY 40536-0086.
Received July 28, 1997; revision received November 21, 1997; accepted November 21, 1997.
ot flashes (HFs) are the most common symptom of menopause,
affecting up to 93% of postmenopausal women.1 A HF is ‘‘a transient episode of flushing, sweating, and a sensation of heat, often
accompanied by palpitations and a feeling of anxiety, and sometimes
followed by chills.’’2 Although interest in HFs is increasing, research
on HFs in women after diagnosis and treatment of breast carcinoma
(BC) remains scarce.3 – 5 Among women with BC, HFs can be 1) due
to the natural aging process, 2) caused by chemotherapy-induced
ovarian failure, and/or 3) intensified by chemotherapy and the antiestrogen tamoxifen citrate.3,4,6 – 9
The prevalence and severity of HFs among women with BC are
unclear. In a survey of 190 postmenopausal women ages 40 – 65 years
with BC, 65% reported HFs.4 Of those reporting HFs, 29% reported
mild severity, 37% reported moderate severity, and 34% reported severe HFs.4 However, several limitations of this study are apparent.
First, the study’s definition of postmenopausal – the absence of menses for at least 6 months – may have allowed inclusion of pre- or perimenopausal women. A more widely accepted and epidemiologically
q 1998 American Cancer Society
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Hot Flashes after Breast Carcinoma/Carpenter et al.
based definition is the absence of menses for at least
12 months.10 Second, study respondents were age °
65 years.4 Although HFs are most common in the first
6 years after menopause in healthy women (around
age 50 years), the total number of years in which HFs
are experienced is variable, with some women experiencing HFs in their 60s and 70s.1 In addition, tamoxifen commonly is recommended for postmenopausal
women with BC.5,11 Because HFs can be a side effect
of tamoxifen,8 tamoxifen users may reexperience HFs
in their later postmenopausal years. Therefore, it is
critical to include women age ú 65 years with BC in
studies of HFs.
In women with BC, variables related to HF prevalence and severity also are unclear. One set of potential
correlates may be related to acute estrogen withdrawal.1,12 First, HF prevalence and severity are higher
among tamoxifen users in comparison with nonusers.4
Second, older age at diagnosis is related to longer time
after menopause with less likelihood of experiencing
HFs due to estrogen withdrawal. Third, women who
discontinue HRT at the time of BC diagnosis may be
more likely to experience HFs after diagnosis due to
estrogen withdrawal.5 Fourth, chemotherapy recipients may be at greater risk for HFs due to chemotherapy-induced ovarian failure and subsequent estrogen
withdrawal.6 Fifth, because estrogen withdrawal appears to be time-limited,1 women who are fewer
months postdiagnosis may be more likely to report
Other potential correlates of HFs in women with
BC include variables related to HF prevalence and severity in healthy women. Among women without BC,
HFs are more prevalent and/or more severe in those
who experience menopause prior to age 52 years, have
less than a high school education, report HFs and premenstrual tension before menopause, have an artificially induced menopause (surgically or chemically induced), and are thin and smoke (body mass index °
22.1).12 – 14 Menarche prior to age 12 years and a history
of irregular menses marginally were related to decreased HF prevalence.14 In addition, exercise may be
related to reduced HF severity.12,15
Options for managing HFs in women with BC are
severely limited. Although the benefits of hormone replacement therapy (HRT) in alleviating HFs are apparent among healthy women,2 use of HRT is controversial at best6,16,17 and traditionally contraindicated
among women with BC.18,19 Although a randomized,
prospective study of the risks and benefits of HRT currently is underway among women with BC,20 evidence
suggests some women with BC will find HRT an unacceptable alternative for managing HFs.4,21 Although
soy-based diets or herbs commonly are recommended
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for healthy women,1,22 – 24 use in women with BC is
questionable due to their estrogenic activity24 and subsequent unknown effects of phytoestrogens on BC.
Low doses of megestrol acetate and transdermal clonidine have been shown to alleviate HFs in women with
BC,25,26 but these medications can have significant side
effects and may not be acceptable to some women.25–27
In addition, progesterone (megestrol acetate) may
have an adverse effect on tumor biology.19 Inability
to use known, efficacious HRT and limited choice of
proven and acceptable treatment options suggest HFs
may represent an untreated symptom among women
with BC.
Finally, research has not addressed the relation
between HFs and quality of life (QOL) among women
with BC. This is an important area to study because
both the prevalence and severity of symptoms may
interfere with QOL.28,29 In fact, menopausal symptoms,
including HFs, were found to be associated with low
QOL in 63 healthy women ages 45 – 60 years.28
The current study sought to 1) determine the prevalence and severity of HFs in outpatients previously
treated for BC, 2) identify variables associated with HF
prevalence and severity, 3) examine women’s use and
knowledge of HF symptom management strategies,
and 4) examine the relation between HFs and QOL.
This study improves on prior studies in several ways:
1) clear definition of postmenopausal status, 2) inclusion of women age ú 65 years, 3) assessment of multivariate correlates of HF prevalence and severity, 4)
examination of use and knowledge of HF symptom
management strategies, and 5) evaluation of the relation between HFs and both emotional and physical
aspects of QOL.
All participants were age ¢ 18 years, had a first-time
diagnosis of BC, were at least 3 months from completion of primary treatment (surgery, radiation, or chemotherapy), were disease free, spoke and understood
English, and provided written informed consent.
Potential participants were recruited using two
strategies. First, women participating in prior research30,31 who had agreed in writing to be contacted
for future research (n Å 50) were sent a letter describing the purpose and nature of the study (to learn about
physical symptoms in women treated for BC) and a
consent form to sign and return if interested. Reasons
women may have declined participation were not assessed. Women who returned a signed consent form
(n Å 40; 80%) were sent a questionnaire packet and
instructed to read but not complete the packet. Telephone interviews then were scheduled by study staff
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CANCER May 1, 1998 / Volume 82 / Number 9
at a mutually convenient time. During interviews, both
interviewer and participant had a questionnaire
packet with the interviewer recording participant responses. A total of 39 interviews were completed in
this manner.
Second, women were recruited from the University of Kentucky Comprehensive Breast Care Center.
Women returning for routine follow-up examinations
(mammograms, clinical breast examinations, etc.) sequentially were identified from patient rosters and eligible women were introduced to the study by their
physician (n Å 128). If a woman expressed interest,
further information was provided by study personnel
and written informed consent was obtained (n Å 110).
Women were given a questionnaire packet and interviews proceeded as described earlier. Because 13 participants were either unavailable for interviews or ineligible, a total of 97 women were included in the analysis
from the breast center. Thus, a total of 136 women
were interviewed successfully. Disease and treatment
data for all women were recorded from medical records.
Both standardized and study specific measures were
used. Questions adapted from the Massachusetts
Women’s Health Study were designed to assess menopausal status using the following definitions10,32: premenopausal: had a menstrual period in the last 3
months; perimenopausal: 3 – 11 months of amenorrhea or increased menstrual irregularity if still cycling;
and postmenopausal: ¢12 months of amenorrhea.
Questions assessed the time of a woman’s last menstrual cycle (number of weeks, months, or years ago)
and whether menses were regular or irregular if a
woman still was cycling.
The following demographic information was collected; birthdate, race, marital status, income, education, employment status, and height (meters) and
weight (kgs) for calculation of body mass index
(weight/height2 ).14 Disease and treatment information
extracted from medical records included date and
stage at diagnosis, types and dates of treatments (surgery, radiation, chemotherapy, or tamoxifen), and
presence of non-BC-related physical comorbidity,
such as arthritis.
Hot Flashes
The presence and severity of HFs was assessed using
three questions. Participants were asked if they had
experienced HFs in the past 2 weeks.10,33,34 If a woman
said yes, she was asked to rate severity using the following scale: 0: not at all; 1: slightly; 2: moderately; 3:
quite a bit; and 4: extremely.30 Women who stated they
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had experienced HFs in the previous 2 weeks also were
asked to indicate how bothered they were by the
symptom using a 10-point numeric rating scale anchored by the words not at all bothered (0) and extremely bothered (10). The HF prevalence and severity
question was embedded in a 30-item symptom checklist.30
HF Correlates
Menstrual history, smoking history, and exercise also
were assessed.12 – 15 Women were asked for their age
at menarche,14 whether they experienced HFs while
having regular menstrual cycles,13 and whether they
were using or had used HRT in the past. Menstrual
cycle regularity was assessed either in the present if a
women still was cycling or in the past if a woman had
stopped cycling.14 Women were asked to provide the
following information on smoking14: age started smoking, age stopped smoking, and number of cigarettes
smoked on an average day (either currently if still
smoking or in the past for prior smokers). Data were
used to classify women as current smokers14 (no vs.
yes) and to calculate pack-years using the following
formula: ([number of cigarettes smoked per day/20
cigarettes per pack] 1 number of years smoked).35
Women also were asked how many times per week
they engaged in moderate exercise, such as walking or
swimming, for ¢20 minutes.
HF Management
Women were given a list of ten HF management strategies and asked to indicate which strategies they were
using currently, which had been used in the past, and
which they might like to know more about. Women
were not asked to rate effectiveness of the strategies.
Options represented traditional and alternative therapies commonly recommended to decrease HFs including HRT, nonhormonal prescription medications (e.g.,
Bellegal-St [phenobarbital, ergotamine tartrate, and
bellafoline] [Sandoz Pharmaceuticals, East Hanover,
NJ] and clonidine), vitamins (e.g., E, B6, and C), herbal
remedies (ginseng and dong quai), diet, exercise,
behavioral methods (e.g., relaxation and paced respiration), acupuncture, and a category labeled
Quality of Life
The SF-12 Health Survey was used to assess QOL.38
The SF-12 assesses eight health concepts using a 4week recall period: physical functioning, role limitations due to physical health problems, bodily pain,
general health, vitality, social functioning, role limitations due to emotional problems, and mental health.
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Hot Flashes after Breast Carcinoma/Carpenter et al.
Both a physical and mental subscale are computed
with higher scores indicating more favorable QOL.
Sample Demographics
Of participants completing phone interviews (n Å
136), 12% were premenopausal, 4% were perimenopausal, and 84% were postmenopausal. Of the postmenopausal women (n Å 114), 49% were pre- or perimenopausal at BC diagnosis, 27% were surgically
menopausal at diagnosis, and 24% were naturally
menopausal at diagnosis. The mean time since last
menstrual period for postmenopausal women was
12.1 years (standard deviation [SD] Å 10.7 years; range,
1 – 41 years). Because the small numbers of pre- and
perimenopausal women (n Å 22) were not sufficient
for subsequent analyses, results focus on postmenopausal women only (n Å 114).
Postmenopausal women were a mean age of 58.8
years (SD Å 10.3 years; range, 36 – 83 years), primarily
white (96%), married (63%), and working full time or
parttime outside the home (42%), with a median
household income of $35,000. Mean education level
was 13.3 years (SD Å 3.3 years; range, 4 – 20 years),
with 51% of women having a °high school diploma.
The mean time after diagnosis was 39.0 months (SD
Å 24.4 months; range, 4 – 154 months) and the mean
time after completion of treatment (surgery, radiation,
or chemotherapy) was 34.9 months (SD Å 22.1
months; range, 4 – 116 months). Staging information
was incomplete for 12 women. Staging information
(according to American Joint Committee on Cancer
staging system) for the 102 participants with complete
data included: Stage 0 (11%), Stage I (34%), Stage IIA
(24%), Stage IIB (21%), Stage IIIA (5%), and Stage IIIB
(5%). Types of surgeries included unilateral modified
radical mastectomy (60%), lumpectomy with axillary
dissection (36%), and bilateral modified radical mastectomy (4%). Types of primary treatment included
surgery alone (40%), surgery and radiation (13%), surgery and chemotherapy (24%), and surgery, radiation,
and chemotherapy (23%). For the 55 women receiving
chemotherapy, the mean number of cycles received
was 5.0 (SD Å 1.7 cycles) with regimens including various combinations of cyclophosphamide, doxorubicin,
methotrexate, and 5-fluorouracil. Tamoxifen use was
reported by 54 postmenopausal women (47%) and tamoxifen was the only adjuvant therapy received for
57% of those women (n Å 31). In addition, 14% of
postmenopausal women chose to have reconstructive
surgery and 68% reported the presence of non-BCrelated physical comorbidity, such as hypertension or
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Prevalence and Severity of HFs
HF prevalence rates were examined for the entire
group of postmenopausal women and according to
the number of years since a woman’s last menstrual
period. Overall, HFs were reported by 65% of postmenopausal women with BC. Prevalence rates by years
since last menstrual period were as follows: 1 – 2 years
postmenopausal (n Å 20), 70%; 3 – 5 years postmenopausal (n Å 28), 75%; 6 – 10 years postmenopausal (n
Å 15), 73%; and ú10 years postmenopausal (n Å 50),
54%. These differences were not statistically significant
(P Å 0.21).
Severity of HFs based on the entire sample of participants (n Å 114) was as follows: none to not at all
severe, 36%; slightly, 11%; moderately, 15%; quite a
bit, 18%; and extremely, 20%. Severity of HFs among
only those women reporting HFs (n Å 74) was as follows: not at all, 1%; slightly, 16%; moderately, 23%;
quite a bit, 28%; and extremely, 31%. Among women
reporting HFs, the mean HF bother rating was 5.7 (SD
Å 3.2; median Å 5.0). HF bother ratings ranged from
1 to 10, with 23% of women reporting a bother rating
equal to 10. HF bother was rated as mild (°3) by 36%
of women, moderate (4 – 6) by 20% of women, and
severe (¢7) by 44% of women.
Correlates of HF Prevalence and Severity
Univariate correlates of HF prevalence and severity
that were examined using Student’s t tests and chisquare analysis included sociodemographic variables
(education, body mass index, premenopausal regularity/irregularity of menstrual cycles, age at menarche,
presence of HFs while regularly menstruating, use of
HRT prior to or at the time of BC diagnosis, smoking,
and exercise) and BC specific variables (age at diagnosis, tamoxifen use, chemotherapy, and months after
diagnosis). HF severity was dichotomized as none to
mildly severe (i.e., severity rating ° 1) versus severe
(severity rating ¢ 2). The results of the Student’s t tests
are shown in Table 1. For chi-square analysis, women
with HFs were significantly more likely to have received chemotherapy (P õ 0.05) and more likely to be
tamoxifen users (P õ 0.25) in comparison with women
without HFs. Similarly, women with severe HFs were
significantly more likely to be tamoxifen users (P õ
0.01) and have received chemotherapy (P õ 0.05) in
comparison with women with none to mildly severe
Variables to be included in a subsequent multivariate analysis of HF prevalence were identified on the
basis of our univariate results. We determined that
eight variables could be supported in a subsequent
logistic regression analysis per Stokes et al.’s39 suggestion of 1 predictor variable per 5 subjects with the
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Group Differences in Prevalence and Severity of Hot Flashes Based on Demographic, Disease, and Treatment Variables
Prevalence (M [SD])
Severity (M [SD])
No HFs (n Å 40)
HFs (n Å 74)
None/mild (n Å 53)
Severe (n Å 61)
Years of education
Body mass index
Age at menarche
Smoking (pack-years)
Exercise (times per week)b
Age at BC diagnosis
Months after BC diagnosis
14.2 (3.0)
25.2 (4.3)
13.1 (1.7)
12.8 (23.7)
3.0 (2.6)
60.3 (11.49)
45.0 (30.9)
12.8 (3.4)
27.6 (6.9)
12.5 (1.6)
11.2 (20.3)
2.5 (2.4)
53.0 (8.68)
35.8 (19.6)
13.5 (3.4)
25.1 (4.4)
13.0 (1.6)
13.2 (24.0)
2.8 (2.6)
59.1 (11.8)
44.5 (28.2)
13.1 (3.2)
28.3 (7.1)
12.4 (1.6)
10.5 (19.1)
2.6 (2.4)
52.5 (7.8)
34.3 (19.6)
M: mean; SD: standard deviation; HF: hot flash; BC: breast carcinoma.
Student’s t test of difference between groups.
Weekly frequency of engaging in moderate exercise for ¢20 minutes.
P õ 0.05.
P õ 0.01.
P õ 0.25.
rarer outcome being determined (n Å 40 women without HFs; 40/5 Å 8). Based on univariate results, five
variables were eliminated as potential predictors of HF
prevalence (P values ú 0.25) from subsequent multivariate analysis40; menstrual cycle regularity, history of
HFs while cycling, use of HRT prior to or at the time
of BC diagnosis, smoking, and exercise. The remaining
7 variables included in the logistic regression analysis
and their coding scheme included: education (°high
school vs. úhigh school), body mass index (15.1 – 20,
20.1 – 25 . . . 35.1 – 40), age at menarche (°12 years vs.
ú12 years), age at diagnosis (grouped by deciles: 30s,
40s . . . 80s), tamoxifen use (no vs. yes), prior chemotherapy (no vs. yes), and months after diagnosis (õ12
months, 12 – 23.9 months . . . . 72 – 83.9 months).
The results of the logistic regression of HF prevalence are shown in Table 2. The set of 7 predictor
variables was significantly associated with HF prevalence (chi-square model Å 21.50; 7 degrees of freedom
[df]; P õ 0.01). Significant predictors (P values õ 0.05)
included education and age at diagnosis. In general, a
greater likelihood of experiencing HFs was associated
with less education and younger age at diagnosis.
Women with more than a high school education were
approximately 33% as likely to experience HFs as
women with °a high school education (odds ratio
[OR] Å 0.36). For every 10-year increase in age ú 39
years, the probability of HFs decreased by approximately 50% (OR Å 0.59).
Five variables also were eliminated from the multivariate analysis of HF severity (P values ú 0.25).40 As
stated earlier, the goal was to reduce the number of
predictor variables in the logistic regression to avoid
overspecification of the model.39 Our data suggested
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that as many as 10 parameters could be supported in
the logistic regression analysis (n Å 53 women with
none to mild HFs; 53/5 Å 10.6). Results of the logistic
regression of HF severity are shown in Table 2. The
set of 7 predictor variables was significantly associated
with HF severity (chi-square model Å 22.96; 7 df; P õ
0.01). Significant predictors included body mass index
(P õ 0.05), age at diagnosis (P õ 0.01), and tamoxifen
(P õ 0.05). In general, greater likelihood of experiencing severe HFs was associated with greater body mass
index, younger age at diagnosis, and use of tamoxifen.
The probability of severe HFs increased by a factor of
1.64 for every 5 unit increase in body mass above 20
(OR Å 1.64), decreased by approximately 50% for every
10-year increase in age ú age 39 years (OR Å 0.52),
and increased by a factor of 2.63 in women receiving
tamoxifen (OR Å 2.63).
Additional logistic regression analyses assessed
the potential interaction between body mass and
smoking described by Schwingl et al.14 Smoking was
added to the reduced variable models along with the
interaction term (body mass by smoking). Neither
smoking nor the interaction were significant predictors of HF prevalence or HF severity (all P values
ú 0.89).
Because the association between body mass index
and HF severity was not as expected,12,14 additional
analyses were performed. Using Pearson correlations,
body mass was found to be significantly (P õ 0.05)
associated with years of education (correlation coefficient [r] Å 00.19), number of chemotherapy cycles (r
Å 0.21), and months after diagnosis (r Å 00.25). Body
mass was not significantly associated with frequency
of weekly exercise or age at diagnosis. Using Student’s
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Hot Flashes after Breast Carcinoma/Carpenter et al.
Logistic Regression Analyses of Prevalence and Severity of Hot Flashes
95% CL
Body mass indexd
Age at menarchee
Age at diagnosisf
Months after BC diagnosisi
Model Chi-square
0.36 j
0.59 j
95% CL
1.64 j
2.63 j
OR: odds ratio; 95% CL: 95% confidence limit; BC: breast carcinoma.
Prevalence: no vs yes.
Severity: none to mild vs. severe.
Amount of education completed (°high school vs. úhigh school).
Body mass index; 15.1 to 20, 20.1 to 25, 25.1 to 30, 30.1 to 35, 35.1 to 40.
Age at menarche (°12 years vs. ú12 years).
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.
Use of tamoxifen (no vs. yes).
Chemotherapy treatment received (no vs. yes).
Months after diagnosis: õ12, 12–23.9, 24–35.9, . . . 72–83.9
P õ 0.05.
P õ 0.01.
t tests, no significant differences were found in body
mass between women based on menstrual cycle regularity (regular vs. irregular), age at menarche (°12
years vs. ú12 years), prior history of HFs (no vs. yes),
prior use of HRT (no vs. yes), smoking (no vs. yes), or
tamoxifen use (no vs. yes).
HF Management
Symptom management strategies used by women with
HFs (n Å 74) are listed in Table 3. Vitamins were the
most commonly used current strategy, whereas HRT
was the most commonly used past strategy. The mean
number of strategies currently used was 1.3 (SD Å 1.3
strategies; range, 0 – 4 strategies) and used in the past
was 0.8 (SD Å 1.0 strategies; range, 0 – 4 strategies).
The mean number of strategies women stated they
would like to know more about was 2.6 (SD Å 2.7
strategies; range, 0 – 9 strategies). In addition, 37% of
women with HFs were not using any strategies, 51%
had not used any strategies in the past, and 63%
wanted to know more about ¢1 symptom management strategy.
Student’s t tests and chi-squared analysis were
used to examine differences in demographic, disease,
and treatment variables between women with HFs
who reported currently using HF management strategies (n Å 46) and those who did not report using any
strategies (n Å 27). Women currently using HF man-
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Symptom Management Strategies Reported by Postmenopausal
Women with BC Experiencing Hot Flashes (n Å 74)
Hormone replacement therapy
Nonhormonal prescription
Behavioral methodsd
use %
Tried in the
past %
Would like to know
more about %
BC: breast carcinoma.
Bellergal-St (phenobarbital, ergotamine tartrate, and bellafoline) (Sandoz Pharmaceuticals, East Hanover, NJ) and clonidine.
Vitamins E, B6, and C.
Ginseng and dong quai.
Relaxation and paced respiration.
agement strategies reported significantly (all P values
õ 0.05) more HF bother, higher levels of education,
greater frequency of weekly exercise, and were more
likely to have received chemotherapy. No differences
between HF management groups were noted on body
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CANCER May 1, 1998 / Volume 82 / Number 9
mass index, menstrual cycle regularity, age at menarche, previous history of HFs, prior use of HRT, smoking, age at diagnosis, current use of tamoxifen, or
months after diagnosis.
Relation to QOL
Using Student’s t tests, differences in QOL were examined between 1) 40 women without HFs and 74 women
with HFs and 2) 53 women with none to mildly severe
HFs and 61 women with severe HFs. Groups differences in QOL narrowly missed our criterion for statistical significance (0.05 õ P õ 0.10). Women with HFs
tended to report poorer mental QOL (mean [M] (SD)
Å 48.4 [12.0] vs. 52.5 [11.2]; P Å 0.08) and poorer physical QOL (M [SD] Å 42.0 [11.9] vs. 46.3 [12.4]; P Å 0.07)
in comparison with women without HFs. Similarly,
women with severe HFs tended to report poorer mental QOL (M [SD] Å 48.2 [11.8] vs. 51.8 [11.7]; P Å 0.10)
and poorer physical QOL (M [SD] Å 41.7 [12.1] vs. 45.7
[12.0]; P Å 0.08) in comparison with women with less
severe HFs. In addition, HF severity marginally was
related to mental and physical QOL (r Å 00.18; P values Å 0.06).
HFs were shown to be a significant problem for a majority of women after treatment for BC. Our overall
prevalence rate is identical to the 65% prevalence rate
found in prior research on this population4 and comparable to prevalence rates found in healthy non-BC
postmenopausal women who have the option of receiving HRT.1,33,34,41 However, the 65% prevalence rate
actually may underestimate the problem of HFs in
women with BC. First, our prevalence rates by time
after menopause were higher than those reported in
Kronenberg’s1 comprehensive review. In particular,
our 54% prevalence rate among women who were ú10
years postmenopause is significantly higher than the
4 – 35% rate found in healthy non-BC samples.1 Second, although HFs decrease with time after menopause in healthy women,1 HFs do not appear to be
time-limited in women with BC. Prevalence rates for
women with BC were found to be fairly stable across
time after menopause, a phenomenon that may be
related to use of tamoxifen during the later postmenopausal years or inability to use HRT. Third, HF prevalence rates for specific subgroups of women with BC
were higher than the overall prevalence rate of 65%.
For example, 72% of tamoxifen users and 78% of chemotherapy recipients experienced HFs. Finally, HFs
were severe and bothersome for a majority of BC survivors. Although approximately 25% of 228 naturally
postmenopausal healthy women reported severe HFs,1
our results suggest more than twice as many women
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with BC (59%) will report their HFs to be severe. Data
on HF prevalence, severity, and bother are convincing
indicators of the magnitude of the HF problem in
women with BC.
Three aspects of our results reinforce the need for
carefully controlled clinical trials evaluating interventions for relieving HFs. First, prevalence, severity, and
bother data highlight the significance of the problem
of HFs in women with BC. Second, correlates of HF
prevalence and severity identified in this research define women with BC at high risk for experiencing HFs
in general and severe HFs in particular. Although correlates will be useful for developing screening criteria
for identifying women at high risk, such criteria are of
little use when proven treatments are not available.
Third, HF management responses indicate current use
of and potential interest in using alternative treatments, despite the lack of research supporting their
safety and efficacy in women with BC. Specifically,
63% of women with HFs expressed interest in learning
more regarding HF management strategies. In addition, treatments are needed for women who are told
to discontinue HRT after diagnosis of BC (40% of the
women in the current study with HFs). Because alternatives to HRT for relieving HFs cannot be recommended based on our current state of knowledge,1,23
further research is needed. Research on alternative interventions for relieving HFs is compatible with, and
not intended to replace, research evaluating use of
HRT in women with BC.20
Results pertaining to multivariate correlates of HF
prevalence (education, age at diagnosis) and severity
(age at diagnosis, tamoxifen) in our sample of women
with BC generally are consistent with prior research
and theory based on healthy non-BC samples. Lower
educational levels have been tied to earlier age at
menopause,42 which has been shown to be a risk factor
for HFs.14 In our study, lower educational levels also
were linked with a lower likelihood of using HF management strategies. Education also may be an indicator of other environmental influences, such as diet,
which may affect a woman’s general health status and
menopausal experience. In regard to age at diagnosis,
younger BC survivors may be more likely to experience
HFs and severe HFs for several reasons. Younger
women are more likely to be perimenopausal, to experience chemotherapy-induced ovarian failure, and to
be fewer years postmenopause than older women and
thus, more likely to experience HFs.1 In addition, the
association between tamoxifen and HF severity is consistent with prior research demonstrating that HFs are
a side effect of tamoxifen therapy.4,9 HFs may be due
to tamoxifen’s antiestrogen effect on vascular smooth
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Hot Flashes after Breast Carcinoma/Carpenter et al.
muscle, which is mediated through competitive binding of the drug to estrogen receptors.8
Our finding that HFs were associated with increased body mass index in women with BC is somewhat puzzling. Theory suggests that because lack of
adiposity is associated with lower levels of circulating
estrogen in healthy postmenopausal women,43,44 thinner women may experience more HFs due to more
severe estrogen withdrawal in the postmenopausal period.45 However, previous research has only partially
supported this theoretic perspective.
The mechanism through which increased body
mass index might be associated with HFs in women
with BC is unknown. Weight gain is a common side
effect of BC chemotherapy and tamoxifen.46,47 Although mechanisms for such weight gain are unclear,
one suggestion is that hormonal changes resulting
from chemotherapy and tamoxifen may lower basal
metabolic rate.46,47 It is possible that weight gain in
women with BC simply is a marker for hormonal disruptions which in turn may be related to HFs. Research is needed to explore the mechanism through
which increased body mass index might be related to
HFs. Analysis of body mass and body composition at
time of diagnosis and at varying times throughout the
survival trajectory may provide important information
for understanding this mechanism.
The finding that HFs marginally were related to
physical and mental QOL is consistent with prior research showing that HFs were associated with low
QOL in healthy women.28 Although other studies have
shown that HFs are not significantly associated with
significant mental health problems in healthy postmenopausal women,12,48 we hypothesized that HFs
would be associated with decreased QOL in our
women with BC for two reasons. First, other cancer
treatment side effects such as fatigue have been associated with decreased QOL in men and women with
cancer.49 Second, we postulated that HFs would affect
QOL negatively because of the lack of effective treatment options. Given the marginal significance of our
findings, it is possible that our QOL measure, which
was primarily a measure of functional status, was not
entirely sensitive to group differences. For women
with BC, HFs may be more of a ‘‘bother’’ than a cause
of interference with functional activity.
Results from this study should be examined in
light of certain limitations. First, findings are based
on a relatively small, cross-sectional sample of
women from one geographic region. Although the
prevalence of HFs found in this study is identical to
a prior study of HF prevalence in women with BC4
and comparable to prevalence rates found among
naturally postmenopausal women without BC,1 large
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04-09-98 13:31:26
scale epidemiologic research is needed to provide
more accurate and stable estimates of HF prevalence
rates in women with BC. Such large scale research
also would be useful for verifying correlates of HF
prevalence and severity prior to proceeding with intervention research. Second, information regarding
HFs was limited to prevalence in the past 2 weeks
(no vs. yes), severity, and symptom bother. Additional
research is needed to obtain detailed information regarding HFs, such as daily frequency, daily pattern
(worse at night, worse during day), aggravating and
alleviating factors, and worst, least, and average intensity. Future research using a diary methodology
would be useful for obtaining detailed information
on HFs in women with BC. Third, data on HFs were
gathered solely with the use of self-reports. Although
self-reports may be the best indicator of symptom
severity,49 objective measures that document the occurrence of HFs may provide more accurate information regarding the prevalence and frequency of HFs
among women with BC. One valid and reliable objective measure of HFs is sternal skin conductance monitoring.50,51 Increases in skin conductance occurring
over a 30-second interval have been shown to correspond with self-reports of HFs. Incorporating this
type of objective measure of HFs in future research
would enable researchers to obtain detailed, reliable,
and valid information regarding prevalence, frequency, and/or daily pattern of HFs. This type of information then can be used to carefully design and
implement intervention research. Fourth, we did not
have data from a non-BC comparison group. However, we attempted to compare our findings with previous research when possible.1,4,12,14,28,33,34,41,42,48
HFs were found to be a significant problem among
women after treatment for BC. HFs were perceived to
be severe and bothersome by a majority of women
and marginally were associated with poorer mental
and physical QOL. Although many women reported
using strategies to manage their HFs and expressed
interest in learning more about alternative HF management strategies, many of these strategies have not
been examined in carefully controlled research. Future
research is needed to explore interventions for decreasing both the prevalence and severity of HFs in
women after treatment for BC. Carefully designed research is needed to provide women with BC safe and
effective alternatives for decreasing this common and
bothersome symptom.
Kronenberg F. Hot flashes: epidemiology and physiology.
Ann N Y Acad Sci 1990;592:52–86.
W: Cancer
CANCER May 1, 1998 / Volume 82 / Number 9
Kronenberg F. Hot flashes: phenomenology, quality of life, and
search for treatment options. Exp Gerontol 1994;29:319–36.
Canney PA, Hatton MQ. The prevalence of menopausal
symptoms in patients treated for breast cancer. Clin Oncol
(R Coll Radiol) 1994;6:297–9.
Couzi RJ, Helzlsouer KJ, Fetting JH. Prevalence of menopausal symptoms among women with a history of breast
cancer and attitudes toward estrogen replacement therapy.
J Clin Oncol 1995;13:2737–44.
Fenlon D. Menopause: a problem for breast cancer patients.
Eur J Cancer Care 1995;4:166–72.
Cobleigh MA, Berris RF, Bush T, Davidson NE, Robert NJ,
Sparano JA, et al. Estrogen replacement in breast cancer
survivors: a time for change. JAMA 1994;272:540–5.
Crabbe WW. The tamoxifen controversy. Oncol Nurs Forum
Love RR. Tamoxifen therapy in primary breast cancer: biology, efficacy, and side effects. J Clin Oncol 1989;7:803–15.
Love RR, Cameron L, Connell BL, Levanthal H. Symptoms
associated with tamoxifen treatment in postmenopausal
women. Arch Intern Med 1991;151:1842–7.
Brambilla DJ, McKinlay SM, Johannes CB. Defining the perimenopause for application in epidemiologic investigations.
Am J Epidemiol 1994;140:1091–5.
Early Breast Cancer Trialists’ Collaborative Group. Effects of
adjuvant tamoxifen and of cytotoxic therapy on mortality in
early breast cancer. N Engl J Med 1988;319:1681–92.
Hunter MS. Predictors of menopausal symptoms: psychosocial aspects. Baillieres Clin Endocrinol Metab 1993;7:33–45.
Hunter M. The south-east England longitudinal study of the
climacteric and postmenopause. Maturitas 1992;14:117–26.
Schwingl PJ, Hulka BS, Harlow SD. Risk factors for menopausal hot flashes. Obstet Gynecol 1994;84:29–34.
Hammar M, Berg G, Lindgren R. Does physical exercise influence the frequency of postmenopausal hot flushes? Acta
Obstet Gynecol Scand 1990;69:409–12.
Smith HO, Kammerer-Doak DN, Barbo DM, Sarto GE. Hormone replacement therapy in the menopause: a pro opinion. CA Cancer J Clin 1996;46:343–63.
Wile AG, Opfell RW, Margileth DA. Hormone replacement
therapy in previously treated breast cancer patients. Am J
Surg 1993;165:372–5.
Brzezinski A. Management of menopause in women with
breast cancer. Isr J Med Sci 1995;31(2–3):163–8.
Runowicz CD. Hormone replacement therapy in cancer survivors: a con opinion. CA Cancer J Clin 1996;46:365–73.
Vassilopoulou-Sellin R, Theriault RL. Randomized prospective trial of estrogen-replacement therapy in women with a
history of breast cancer. Monogr Natl Cancer Inst 1994;
Vassilopoulou-Sellin R, Zolinski C. Estrogen replacement
therapy in women with breast cancer: a survey of patient
attitudes. Am J Med Sci 1992;304:145–9.
Mayer DK, Linscott E. Information for women: management
of menopausal symptoms. Oncol Nurs Forum 1995;22:1567–
Miller KL. Alternatives to estrogen for menopausal symptoms. Clin Obstet Gynecol 1992;35:884–93.
Lucerno MA, McCloskey WW. Alternatives to estrogen for
the treatment of hot flashes. Ann Pharmacother 1997;
Goldberg RM, Loprinzi CL, O’Fallon JR, Veeder MH, Miser
AW, Maillard JA, et al. Transdermal clonidine for ameliorat-
/ 7bc2$$1176
04-09-98 13:31:26
ing tamoxifen-induced hot flashes. J Clin Oncol 1994;
Loprinzi CL, Michalak JC, Quella SK, O’Fallon JR, Hatfield
AK, Nelimark RA, et al. Megestrol acetate for the prevention
of hot flashes. N Engl J Med 1994;331:347–52.
Walsh B, Schiff I. Vasomotor flushes. Menopause: Eval, Treat,
Health Concerns 1989;2:71–87.
Daly E, Gray A, Barlow D, McPherson K, Roche M, Vessey
M. Measuring the impact of menopausal symptoms on quality of life. BMJ 1993;307:836–40.
Ferrell BR. The quality of lives: 1,525 voices of cancer. Oncol
Nurs Forum 1996;23:909–16.
Andrykowski MA, Curran SL, Studts JL, Cunningham L, Carpenter J, McGrath P, et al. Psychosocial adjustment and
quality of life in women with breast cancer and benign
breast problems: a controlled comparison. J Clin Epidemiol
Carpenter JS. Self-esteem and well-being among women
with breast cancer and age-matched comparison women. J
Psychosoc Oncol 1997;15:59–80.
Avis NE, Brambilla D, McKinlay SM, Vass K. A longitudinal
analysis of the association between menopause and depression: results from the Massachusetts Women’s Health Study.
Ann Epidemiol 1994;4:214–20.
Dennerstein L, Smith AM, Morse C, Burger H, Green A, Hopper J, et al. Menopausal symptoms in Australian women.
Med J Aust 1993;159:232–6.
Hemminki E, Topo P, Kangas I. Experience and opinions of
climacterium by Finnish women. Eur J Obstet Gynecol Reprod Biol 1995;62:81–7.
Martinez ME, McPherson RS, Annegers JF, Levin B. Cigarette
smoking and alcohol consumption as risk factors for colorectal adenomatous polyps. J Natl Cancer Inst 1995;87:274–
Freedman RR, Woodward S. Behavioral treatment of menopausal hot flashes: evaluation by ambulatory monitoring.
Am J Obstet Gynecol 1992;167:436–9.
Shaver JL. Beyond hormonal therapies in menopause. Exp
Gerontol 1994;29:469–76.
Ware JE, Kosinski M, Keller SD. SF-12: how to score the SF12 physical and mental health summary scales. 2nd revised
edition. Boston: The Health Institute, 1995.
Stokes ME, Davis CS, Koch GG. Categorical data analysis
using the SAS system. Cary, NC: SAS Institute, Inc., 1995.
Hosmer DW, Lemeshow S. Applied logistic regression. New
York: John Wiley & Sons, Inc., 1989.
Koster A. Change-of-life anticipations, attitudes, and experiences among middle-aged Danish women. Health Care
Women Intl 1991;12:1–13.
Stanford JL, Hartge P, Brinton LA, Hoover RN, Brookmeyer
R. Factors influencing the age at natural menopause. J Chron
Dis 1987;40:995–1002.
Judd HL, Lucas WE, Yen SS. Serum 17B-estradiol and estrone
levels in postmenopausal women with and without endometrial cancer. J Clin Endocrinol Metab 1976;43:272–8.
Potischman N, Swanson CA, Siiteri P, Hoover RN. Reversal
of relation between body mass and endogenous estrogen
concentrations with menopausal status. J Natl Cancer Inst
Erlik Y, Meldrum DR, Judd HL. Estrogen levels in postmenopausal women with hot flashes. Obstet Gynecol 1982;59:403–
W: Cancer
Hot Flashes after Breast Carcinoma/Carpenter et al.
46. Demark-Wahnefried W, Winer EP, Rimer BK. Why women
gain weight with adjuvant chemotherapy for breast cancer.
J Clin Oncol 1993;11:1418–29.
47. Hoskin PJ, Ashley S, Yarnold JR. Weight gain after primary
surgery for breast cancer—effect of tamoxifen. Breast Cancer
Res Treat 1992;22:129–32.
48. Avis NE, McKinlay SM. The Massachusetts women’s health
study: an epidemiologic investigation of the menopause. J
Am Med Wom Assoc 1995;50(2):45–9,63.
/ 7bc2$$1176
04-09-98 13:31:26
49. Groenwald SL, Goodman M, Frogge MH, Yarbro CH. Cancer
symptom management. Boston: Jones and Bartlett, 1996.
50. Freedman RR. Laboratory and ambulatory monitoring or
menopausal hot flashes. Psychophysiology 1989; 26:573 –
51. Freedman RR, Norton D, Woodward S, Cornelissen G. Core
body temperature and circadian rhythm of hot flashes in
menopausal women. J Clin Endocrinol Metab 1995;80:2354–
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