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Soldera 2018
Soldera 2018
https://doi.org/10.1007/s10549-018-4894-8
EPIDEMIOLOGY
Abstract
Purpose Sexual dysfunction is reported in women with breast cancer (BC). It is unclear whether symptoms persist over time
as data comparing long-term survivors to controls are lacking. We compared sexual functioning in long-term breast cancer
survivors (BCS) to controls and determined the impact of adjuvant therapy on sexual health.
Methods A cohort of women with localized BC (1989–1996) was prospectively followed. BCS and controls (2005–2007)
completed self-reported questionnaires. Sexual health was measured with the Sexual Activity Questionnaire (SAQ). Vaso-
motor, gynecological, and bladder symptoms were scored using the Menopausal Symptom Scale. Regression analysis was
used to compare groups, with adjustment for age and secondly menopausal status.
Results BCS (n = 248, 87%) and controls (n = 159, 95%) completed the SAQ at a median time from diagnosis of 12.5 years.
BCS were older (62 vs 59 years, p = 0.0004) and more likely to be menopausal (94 vs 86%, p = 0.0025). Sexual activity did
not differ significantly between BCS and controls, but when adjusted for menopausal status, pre/peri-menopausal BCS were
less likely to be sexually active than pre/peri-controls (odds ratio OR 0.12, p = 0.012). In those sexually active, no significant
differences were noted on the SAQ Pleasure, Discomfort, and Habit scales. BCS reported worse gynecological symptoms
and pre/peri-menopausal patients had more bladder complaints (standardized effect size 0.36 p = 0.002 and 1.11, p = 0.011).
Adjuvant treatments were not significantly associated with sexual function, but BCS treated with chemotherapy reported
worse gynecological symptoms.
Conclusion Sexual health and uro-genital symptom counseling should be provided to BCS, particularly pre/peri-menopausal
patients, even at long-term follow-up.
Keywords Breast cancer · Sexual function · Chemotherapy · Endocrine therapy · Survivorship · Sexual Activity
Questionnaire
Introduction
Electronic supplementary material The online version of this Over the last decades, the number of breast cancer survi-
article (https://doi.org/10.1007/s10549-018-4894-8) contains vors (BCS) has increased [1]. Improved outcomes in this
supplementary material, which is available to authorized users. population are in part attributed to more effective adjuvant
* Sara V. Soldera therapies [2]. While increasing cure, treatments inflict sub-
[email protected] stantial symptom burden on patients. Given improvement
in outcomes, survivorship issues including long-term ther-
1
Department of Hematology and Oncology, CISSS apy-related toxicities have become increasingly important.
Montérégie Centre/Hôpital Charles‑Lemoyne, Centre Affilié
de l’Université de Sherbrooke, Greenfield Park, Canada
Sexual health in particular is now recognized as an area of
2
concern for BCS [3, 4] and an aspect of care that is often
Lunenfeld Tanenbaum Research Institute, Mount Sinai
Hospital, University Health Network, University of Toronto,
overlooked by healthcare professionnals [4].
Toronto, Canada Several studies have reported significant sexual dysfunc-
3
Applied Statistician, Markham, Canada
tion in the few years following diagnosis [5–13]. It remains
4
unclear whether this effect persists over time, as high qual-
Division of Medical Oncology and Hematology, Division
of Clinical Epidemiology, Department of Medicine,
ity long-term data are sparse and conflicting [14–16]. Dis-
Lunenfeld‑Tanenbaum Research Institute, Mount Sinai tinguishing changes in sexual health related to the normal
Hospital, University of Toronto, Toronto, Canada
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Breast Cancer Research and Treatment
aging process versus those associated with BC diagnosis sexual activity than usual, respectively (Table S3). Vaso-
and treatment is also a challenge. Sexually activity declines motor, gynaecological complaints, and bladder symptoms
and sexual complaints increase with advancing age [17]. To were evaluated based on the Menopausal Symptom Scale
date, few studies have investigated sexual function in BCS of the Breast Cancer Prevention Trial Symptom Check List
compared to healthy controls and most were limited by small in which symptoms are graded from 0 to 4 of increasing
numbers and comparison to historical data [13, 16, 18, 19]. intensity (Table S3) [31, 32]. Specific items consisted of
The impact of adjuvant treatments on sexual health remains hot flashes and night sweats (vasomotor subscale), vagi-
controversial with varying reports on the effect of chemo- nal dryness, genital irritation, and pain with intercourse
therapy and hormonal agents [5, 6, 9, 10, 14, 16, 18, 20–28]. (gynaecological subscale), difficulty with bladder control
The primary aims of this study are threefold: (1) to while laughing or crying and difficulty with bladder control
evaluate sexual health in long-term BCS compared to aged- at other times (bladder symptom subscale).
matched controls, (2) to determine the impact of chemother-
apy and endocrine therapy on sexual functioning, and (3) to Statistical analysis
compare related symptoms such as gynecological, vasomo-
tor, and bladder complaints between groups to potentially Subject and treatment-related characteristics were reported
explain the source of any differences in sexual function. as frequencies or means with standard deviations (SD)
and compared using t tests and Chi square tests. Despite
matching, BCS and controls differed in terms of age and
Methods menopausal status. Given that premature menopause is a
well-documented risk of adjuvant chemotherapy in younger
Study population women and has been demonstrated to contribute to sexual
dysfunction, we adjusted only for age in our primary analy-
A cohort of women with newly diagnosed localized BC was ses and added adjustment for menopausal status in second-
recruited from three metropolitan hospitals at the University ary analyses. We compared the sexual activity of BCS and
of Toronto between 1989 and 1996 and followed prospec- controls using logistic regression with odds ratios (OR) as
tively for disease outcomes [29]. This cohort was previously summary measures. For other outcomes, we used linear
described [29]; it included English-speaking women aged regression with standardized effect sizes (StES) calculated
< 75 years with completely resected localized invasive BC as the regression-adjusted difference relative to controls,
(T1-3, N0-1, M0). Exclusion criteria included the use of divided by the SD of the controls. Age was modelled as
neoadjuvant chemotherapy, presence of serious coexisting a quadratic polynomial to allow for curved relationships.
medical conditions, and living more than 1 h from a study Adjustment for menopausal status included testing for an
site. Information regarding diagnosis, stage, pathology, and interaction between it and subject type. For adjuvant treat-
treatments and cancer outcomes was obtained from medical ment (hormone therapy, chemotherapy, both, neither), an
records. omnibus test of any difference between treatment groups and
Survivors were re-contacted from 2005 to 2007 and those controls was examined before looking at individual compari-
without distant BC recurrence or a new cancer diagnosis sons. p values ≤ 0.05 were called significant.
were enrolled in a survivorship study. Between 2007 and The research ethics committee at the Mount Sinai Hospi-
2008, a control group was recruited among women under- tal approved this study and all participants provided written
going screening mammograms at one of the three centres. informed consent.
Those with a history of invasive cancer or undiagnosed
abnormalities on screening mammogram were excluded. To
the extent possible, controls were age-frequency matched to Results
the BCS. For the current study, we included all long-term
BCS and controls who completed the Sexual Activity Ques- Patient demographics
tionnaire (SAQ) in the survivorship study.
Between 1989 and 1996, 535 women newly diagnosed
Study questionnaires with BC participated in the original cohort. Two hundred
and eighty-five survivors were enrolled into the survivor-
The SAQ [30], a validated standardized tool, was used to ship study a median of 12.5 years after diagnosis (range
assess the frequency of sexual activity and three dimen- 9.4–17.6 years, Fig. 1) [29]. Enrolled survivors were similar
sions of sexual function: pleasure (SAQ-P), discomfort to the remaining cohort except for lower body mass index
(SAQ-D), and habit (SAQ-H), with higher scores indicat- (BMI) and cancers of lower T and N stage, as expected.
ing greater pleasure, discomfort, and greater frequency of Of the participating survivors, 248 (87%) completed the
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Breast Cancer Research and Treatment
SAQ forming the group under study. 37 survivors who did for SAQ-H. Age itself explained a significant amount of the
not complete the SAQ were older on average (mean 65 vs variation in SAQ-D but not in SAQ-P or SAQ-H.
62 years p = 0.041). One hundred and sixty-seven non-BC When adjustment was made for menopausal status, there
controls were also enrolled into the survivorship study with was a significant interaction between subject type and meno-
158 (95%) completing the SAQ. pausal status for sexual activity (p = 0.024, Fig. 3a), with
Disease and treatment related characteristics of BCS are pre/peri-menopausal BCS less likely to be sexually active
summarized in Table 1 and survivorship participant charac- than pre/peri-controls (OR = 0.12, p = 0.012) while no dif-
teristics are described in Table 2. Despite matching for age, ference in sexual activity was seen between postmenopausal
breast cancer survivors were slightly older and more likely to groups (OR = 0.78, p = 0.28). For the SAQ subscales, adjust-
be post-menopausal than controls (mean age 62 and 59 years ment for menopausal status was not significant.
p = 0.0004; 94 and 86% post-menopausal, p = 0.0025).
Menopausal symptoms
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Table 2 Characteristics of breast cancer survivors at long-term follow-up and non-breast cancer controls
Variable BCS Controls p1 BCS by adjuvant treatment
(n = 248) (n = 159)
None Horm Chemo Both Omnibus p2
(n = 84) (n = 67) (n = 71) (n = 26)
Age, year
Mean (SD) 62 (8.1) 59 (7) 0.0004 63 (8.3) 66 (8.1) 57 (5.5) 59 (6.4) < 0.0001
BMI
Mean (SD) 26 (4.6) 25 (4.5) 0.079 26 (4.7) 26 (4.2) 27 (4.8) 26 (5.3) 0.15
Menop status
Pre/peri (%) 14 (6) 23 (15) 0.0025 7 (8) 3 (4) 4 (6) 0 (0) 0.027
Post (%) 234 (94) 136 (85) 77 (92) 64 (96) 67 (94) 26 (100)
Age at menop
Mean (SD) 48 (5.2) 50 (4.8) 0.0031 50 (5.3) 49 (5.9) 46 (3.9) 46 (3.9) < 0.0001
Exogenous hormones3
Yes (%) 9 (4) 24 (18) < 0.0001 4 (5) 4 (6) 1 (2) 0 (0) 0.0002
No (%) 225 (96) 112 (82) 73 (95) 60 (94) 66 (98) 26 (100)
Employment
Full-time (%) 92 (37) 75 (47) 0.044 34 (41) 17 (25) 30 (42) 11 (42) 0.053
Other* (%) 156 (63) 84 (53) 50 (59) 50 (75) 41 (58) 15 (58)
Marital status
Other** (%) 89 (36) 50 (31) 0.36 32 (38) 26 (39) 21 (30) 10 (39) 0.62
Married (%) 159 (64) 109 (69) 52 (62) 41 (61) 50 (70) 16 (61)
Living situation
Alone (%) 54 (22) 35 (22) 21 (25) 18 (27) 11 (16) 4 (15)
Partner only (%) 106 (43) 67 (42) 0.87 42 (50) 37 (55) 20 (28) 7 (27) 0.0002
Partner/kids (%) 51 (20) 37 (23) 10 (12) 5 (8) 28 (39) 8 (31)
Other (%) 37 (15) 20 (13) 11 (13) 7 (10) 12 (17) 7 (27)
BCS breast cancer survivors, both chemotherapy and hormonal therapy, BMI body mass index, chemo chemotherapy, horm hormonal therapy,
LTFU long-term follow up, menop menopausal, SD standard deviation
*Part time/retired/unemployed
**Single/widowed/divorced
1
p value for t test or Chi square test that outcomes for BCS and controls are equal
2
p value for the omnibus test that outcomes for all four treatment groups plus the control group are equal
3
Current use of estrogen/progestin among post-menopausal subjects
chemotherapy (mean 5.8 years since diagnosis) compared initial cohort, our results are restricted to adjuvant endocrine
to community controls and established that cancer survi- treatment with tamoxifen.
vors reported higher scores (greater dysfunction) on the
vasomotor and sexual domains of the Menopause-Specific
Quality of Life Questionnaire (MenQOL). Of note, the Conclusion
MenQOL sexual domain explores sexual desire, vaginal
dryness, and avoidance of intimacy. Long-term sexual health was similar in post-menopausal
There are several limitations to our study. Information BCS and controls with similar decline in sexual activity with
regarding sexual function prior to BC diagnosis and treat- increasing age, however, pre or peri-menopausal patients
ment is lacking. Additionally, despite age matching, BCS report lower rates of sexual activity and greater bladder
and controls differed in terms of age and menopausal status. symptoms. Adjuvant chemotherapy is associated with more
This difference was addressed by adjusting data according to frequent gynecological symptoms over a decade after BC
these two important variables. Several questions also remain diagnosis. BCS should, therefore, be counseled about sexual
unanswered. Median age in our sample (62 years) limited function and gynecological symptoms during routine medi-
the study of sexual health in younger BCS. Furthermore, as cal visits, particularly those who remain pre/peri-menopau-
aromatase inhibitors were not widely used at the time of our sal at long-term follow up. Interventions aimed at improving
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Breast Cancer Research and Treatment
Red: BC survivor
0.2
Black: Control
0.0
40 50 60 70 80
Age
(b) SAQ Pleasure factor SAQ Discomfort factor SAQ Habit factor
N = 207 N = 207 N = 207
3.0
6
2.0
4
10
Red: BC survivor
1.0
2
Black: Control
5
0.0
0
40 50 60 70 80 40 50 60 70 80 40 50 60 70 80
(c) BCPT Gynecological symptom scale BCPT Bladder symptom scale BCPT Vasomotor symptom scale
N = 407 N = 407 N = 407
4
Red: BC survivor
2
Black: Control
1
1
0
40 50 60 70 80 40 50 60 70 80 40 50 60 70 80
Fig. 2 Sexual activity (a) and function (b) in breast cancer survivors and non-breast cancer controls as per the Sexual Activity Questionnaire
(SAQ), and vasomotor, gynecological, and bladder symptoms (c) as per the BCPT Symptom Check List
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(a) Probability of being sexually active (b) BCPT Bladder symptom scale
N = 407 N = 407
Interaction P = 0.024 Interaction P = 0.049
4
1.0
Pre/peri Pre/peri
0.8
Post Post
3
BC survivor BC survivor
Control Control
0.6
2
0.4
1
0.2
0.0
0
40 50 60 70 80 40 50 60 70 80
Age Age
Fig. 3 Sexual activity (a) and the BCPT bladder symptom scale (b) in breast cancer survivors and non-breast cancer controls, after adjustment
for age and menopausal status including an interaction between subject type and menopausal status
uro-gynecological health could further improve sexual func- 2. Early Breast Cancer Trialists’ Collaborative Group (2005) Effects
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recurrence and 15-year survival: an overview of the randomised
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Funding This work was supported by The Breast Cancer Research 3. Carter J, Stabile C, Seidel B et al (2015) Baseline characteristics
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of the study, the collection, analysis, and interpretation of the data, the 23:2255–2265
manuscript writing, or the decision to submit for publication. 4. Scanlon M, Blaes A, Geller M et al (2012) Patient satisfac-
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Hospital approved this study. All procedures performed in studies lems in younger women after breast cancer surgery. J Clin Oncol
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