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The Impact of Having a Sister Diagnosed With
Breast Cancer on Cancer-Related Distress and
Breast Cancer Risk Perception
Kelly A. Metcalfe, RN, PhD1,2; May-Lynn Quan, MD, MSc3,4; Andrea Eisen, MD5; Tulin Cil, MD, MEd2;
Ping Sun, PhD2; and Steven A. Narod, MD2
BACKGROUND: A family history of breast cancer has been shown to affect psychosocial functioning. However, the majority of
research has focused on the daughters of patients with breast cancer and families with multiple relatives with the disease. The pur-
pose of the current study was to examine cancer-related distress and breast cancer risk perception, and further examine the predic-
tors of these outcomes, in the sisters of newly diagnosed patients with breast cancer without a previous family history of the disease.
METHODS: Sisters of newly diagnosed index breast cancer patients were identified and asked to complete a study-specific question-
naire (demographics and cancer risk perception) and the Impact of Events Scale. Pathological information was abstracted from the
medical chart for the index breast cancer patients. RESULTS: A total of 205 sisters completed the questionnaires. The mean time
between breast cancer diagnosis and the sisters’ completion of the questionnaire was 9.8 months. Approximately one-half of the
women scored in the moderate or severe distress range. The most significant predictor of cancer-related distress was perceived life-
time breast cancer risk (P ¼ .04). Women with a lifetime risk of breast cancer > 20% were more than twice as likely to have moderate
or severe distress compared with those with a lifetime risk of < 20%. CONCLUSIONS: Cancer-related distress is high in the sisters of
newly diagnosed patients with breast cancer in whom there is no other family history of breast cancer. Specifically, women with a per-
ceived lifetime risk of breast cancer of > 20% experienced the highest levels of distress. Future interventions that target this group
should be considered. Cancer 2013;119:1722–8.VC 2013 American Cancer Society.
KEYWORDS: breast cancer, sisters, distress, cancer risk perception.
INTRODUCTIONAccording to the Canadian Cancer Society, approximately 22,000 women in Canada are diagnosed with breast cancerannually.1 Women diagnosed with breast cancer, as well as their relatives, experience high levels of distress after the diag-nosis. Interestingly, distress levels in relatives are comparable to those observed in the patients themselves, suggesting thata breast cancer diagnosis has significant psychosocial implications for relatives.2 Distress in relatives has been associatedwith decreased natural cytotoxic activity and elevated levels of stress hormones.3
The majority of research examining the psychosocial implications of a breast cancer diagnosis in relatives has focusedon daughters. In a qualitative study of the adult daughters of newly diagnosed patients with breast cancer, the narrativesdocumented that the mother’s cancer diagnosis subjected the daughters to a period of crisis fraught with severe emotionaldistress and life-and-death concerns.4 They also described a heightened sense of vulnerability. In a study by Mosher et alof adult daughters of women who were newly diagnosed with breast cancer, 19% of women fit the criteria for posttrau-matic stress disorder and symptom severity was associated with the mother’s stage of disease at the time of diagnosis.5
A family history of breast cancer has been shown to effect psychosocial functioning. Previous research has shownthat both cancer-related distress and overall distress are elevated in women with a family history of breast cancer.6-11 How-ever, most studies have focused on high-risk families in which multiple family members are affected with breast cancer. Tothe best of our knowledge, there has been very little research that has examined the psychosocial implications of a recentbreast cancer diagnosis in families in which this is the first diagnosis of the disease. Eight of 9 women who develop breastcancer do not have an affected mother, sister, or daughter.12 For the majority of times a woman is diagnosed with breastcancer, it is the first time that sisters now realize that they are at an increased risk of developing the disease.
DOI: 10.1002/cncr.27924, Received: June 21, 2012; Revised: October 9, 2012; Accepted: October 15, 2012, Published online February 7, 2013 in Wiley Online
Library (wileyonlinelibrary.com)
Corresponding author: Kelly A. Metcalfe, RN, PhD, Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, 155 College St, Toronto, ON M5T 1P8
Canada; Fax: (416) 978-2851; Fax: (416) 978-8222; [email protected]
1Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Ontario, Canada; 2Women’s College Research Institute, Toronto, Ontario, Canada;3Department of Surgery, University of Calgary, Foothills Medical Centre, Calgary, Alberta, Canada; 4Department of Oncology, University of Calgary, Foothills Medi-
cal Centre, Calgary, Alberta, Canada; 5Department of Medical Oncology/Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario,
Canada
We wish to acknowledge the Canadian Breast Cancer Foundation (Ontario Chapter) for funding this study.
1722 Cancer May 1, 2013
Original Article
The purpose of the current study was to examinecancer-related distress and breast cancer risk perception,and to evaluate the predictors of these outcomes, in thesisters of patients newly diagnosed with breast cancerwithout a previous family history of the disease.
MATERIALS AND METHODSAll patients who were newly diagnosed with invasive breastcancer and who received surgical treatment at 2 academichealth sciences centers in Toronto, Ontario, Canada wereidentified and approached for participation. All patientswho were interested in participation were screened for eligi-bility criteria. This included being able to read and under-stand English, age> 25 years, a diagnosis of invasive breastcancer (not in situ) within the last 6 months, having at least1 sister, and meeting family history criteria (no first-degreerelative with breast cancer). If the patient met eligibilitycriteria, a detailed family history was obtained and eligiblesisters were identified. These included sisters who couldread and understand English, were aged � 25 years, andhad had no previous personal history of cancer. The patientwas asked to contact each eligible sister and obtain consentfor the study coordinator to contact them and explain thestudy. At the time of receipt of the contact informationfrom the patient, each consenting sister was contacted anda study package was mailed to each subject for completion.
Medical Chart Review
Information concerning the patient was obtained through asystematic medical chart review (AJCC staging system).The review included recording data on patient age, the dateof surgery, the type of surgery, and pathological informa-tion (including size, lymph node status, stage, and grade).
Questionnaires
Study-Specific Questionnaire
This questionnaire was designed specifically for thecurrent study and was based on questionnaires that we haveused in previous research. Items in the questionnaireincluded demographic information (age, marital status, edu-cation, etc) and information necessary to generate breast can-cer risk estimates (including age at first period, number ofbiopsies, results of biopsies, age at first live birth, ethnicity,and previous diagnoses of ductal carcinoma in situ or lobularcarcinoma in situ). We asked women about their perceptionof their lifetime risk of breast cancer after their sister’s diag-nosis using a Likert-type scale from 0% to 100%.
Impact of Event Scale
The Impact of Event Scale (IES)13 is a self-reportmeasure that was designed to measure current subjective
distress in relation to a specific stressor. For the currentstudy, the stressor was identified as ‘‘having a sister withbreast cancer.’’ It is based on a 2- factor intrusion andavoidance model of reactions to stressful life events. Itmeasures the frequency of intrusive and avoidant phe-nomena. The scale consists of 15 items (7 intrusion itemsand 8 avoidance items). The IES allows for the calculationof a total score (with a possible range of 0-75), and sepa-rate intrusion and avoidance subscale scores. The Cron-bach alpha is .78 for intrusion and .82 for avoidance.Scores for the total IES can be divided into the subclinicalrange (0-8), mild range (9-25), moderate range (26-43),and severe range (� 44).
Breast Cancer Risk Estimation
For each woman, the breast cancer risk was calculatedwith the Tyrer-Cuzick model14 using the InternationalBreast Cancer Intervention Study (IBIS) program. Thismodel uses the Bayes theorem to calculate the breast can-cer probability and then refines the calculation by maxi-mum likelihood estimates and incorporates risk factorssuch as age at menopause and menarche, weight, height,age, use of hormone replacement therapy, and previousbenign breast biopsies. When compared with the Gail,Claus, and Ford models, the Tyrer-Cuzick model hasbeen shown to be the most consistently accurate for theprediction of breast cancer15,16 and BRCA (breast cancergene) mutation carrier status.16 Specifically, with regardto breast cancer risk in women with 1 first-degree relativewith breast cancer (consistent with those women in thecurrent study), the Tyrer-Cuzick model has been shownto be accurate in predicting breast cancer risk whereas theGail, Claus, and Ford models have all been shown tounderestimate risk in this particular subgroup ofwomen.17
Statistical Analysis
Descriptive statistics (including frequencies and means)were generated for each of the study variables. Predictorvariables were grouped and analysis of variance was usedto compare the mean perceived lifetime risk of breast can-cer between groups. The dependent variable total cancer-related distress was dichotomized into low total distress(IES total score of < 20) and high total distress (IES totalscore of � 20) based on clinical cutoff scores. Predictorsof high and low total distress were examined using logisticregression models. Statistical analyses were performedusing SAS statistical software (version 9.1.3; SAS Insti-tute, Inc, Cary, NC).
Sisters of Women with Breast Cancer/Metcalfe et al
Cancer May 1, 2013 1723
RESULTS
Demographics
In total, 2084 women with breast cancer (index breastcancer patients) were identified, 1873 of whom were sub-sequently found to be ineligible (348 women had a familyhistory of breast cancer; 145 women had a language bar-rier; 323 women had a breast cancer recurrence; 16women were too young or had sisters who were too youngto participate; 84 women had sisters who were residingout of the country; 200 women did not have a sister; 143women had noninvasive breast cancer; 507 women werediagnosed with breast cancer before March 2007 or afterAugust 2010; 21 women had other reasons for not partici-pating, including patients who were adopted, those whohad just received their diagnosis and were overwhelmed,and those who were not well enough to participate in thestudy; and 86 women refused participation). Of the 211remaining patients with breast cancer, 152 agreed to par-ticipate and 236 sisters were identified and contactedabout their participation. A total of 213 of the 236 sistersagreed to participate, and of these 213 sisters, 205(96.2%) (from 147 families) completed the question-naires. The mean age of the sisters was 50.1 years (range,24 years-78 years). Characteristics of the sisters are pre-sented in Table 1. One hundred fifty-six of the womenidentified themselves as white, 138 women had at least a
college education, and 124 were married or in a common-law relationship.
The index breast cancer patients were diagnosedwith breast cancer between March 2007 and August2010. Their characteristics are presented in Table 1. Themean time between breast cancer diagnosis and comple-tion of the sisters’ questionnaire was 9.8 months (range, 0months-41 months). A total of 153 sisters (74.6%) com-pleted the questionnaires within 12 months of the breastcancer diagnosis.
Breast Cancer Risk
Sisters were asked about their perceived lifetime risk ofbreast cancer after the diagnosis of the index breast cancerpatient. The mean self-reported current breast cancer riskafter diagnosis of the patient was 34.6% (range, 0%-100%). Age of the sister and model-generated (IBIS)breast cancer risk were found to significantly predict cur-rent perceived breast cancer risk (Table 2). Women aged< 50 years had a higher perceived lifetime risk of breast
TABLE 1. Characteristics of Patients With BreastCancer and Their Sisters
Characteristic No. (%)
Patients With Breast Cancer
Mean age at diagnosis (range), y 50.1 (24-78)
Stage
I 43 (21.0%)
II 82 (40.0%)
III 50 (24.4%)
IV 11 (5.4%)
Unknown 19 (9.3%)
Sisters
Martial status
Single 40 (19.5%)
Divorced/separated 29 (14.1%)
Widowed 9 (4.4%)
Married/common law 124 (60.5)
Other 3 (1.5)
Ethnicity
White 156 (76.1%)
Black 9 (4.4%)
Other 40 (19.5%)
Children
Yes 154 (75.1%)
No 48 (23.4%)
Missing data 3 (1.5%)
TABLE 2. Predictors of Perceived Breast CancerRisk
Factors
Variables(Frequencies)
N¼205
Mean PerceivedBC Risk (Range)
N¼130 Pa
Sister Age, y
20-49 (92) 39.5 (0-100) .02
50-80 (113) 30.6 (0-100)
Marital status
Single, divorced, or
separated (81)
32.4 (0-100) .42
Married (124) 35.8 (0-100)
Education
High school or less (67) 34.6 (0-80) .99
College or above (138) 34.6 (0-100)
Model-generated
lifetime BC risk
�10 (38) 23.3 (0-50) .0008
>10 (154) 36.5 (0-100)
Children
Yes (154) 34.9 (0-100) .52
No (48) 32.0 (0-80)
Patient Age at diagnosis, y
20-49 (112) 37.8 (0-100) .09
50-80 (90) 31.2 (0-100)
Stage
I (43) 31.9 (0-70) .80
II (82) 34.0 (0-100)
III (50) 31.9 (0-80)
IV (11) 40.0 (20-50)
Time since BC diagnosis
<12 mo (146) 36.2 (0-100) .32
12-24 mo (33) 29.1 (0-70)
>24 mo (18) 30.0 (10-50)
BC, breast cancer.ap-values were obtained from ANOVA to see differences of means of per-
ceived BC risk between different groups of each variable
Original Article
1724 Cancer May 1, 2013
cancer (39.5%) compared with those aged �50 years(30.6%) (P¼ .02). Those women with a higher (� 10%)model-generated lifetime breast cancer risk estimatedtheir current lifetime risk of breast cancer to be higherthan those with a lower lifetime risk of breast cancer (<10%) (P ¼ .0008). Factors associated with the indexbreast cancer patient (including age at diagnosis, stage ofbreast cancer, and time since diagnosis) were not predic-tive of the perceived risk of breast cancer in the sisters.
The lifetime breast cancer risk for each sister wasestimated with the Tyrer-Cuzick model using the IBISprogram. All 205 pedigrees, as reported by the breast can-cer patients, were entered into the IBIS program. Themean model-generated lifetime risk of breast cancer was16.6% (range, 3%-61.9%). The risk estimates generatedby the model were then compared with the sisters’ currentsubjective risk estimates. There was no significant correla-tion between the women’s current perceived lifetime riskof breast cancer and the risk estimates generated by themodel (correlation coefficient [r], 0.14; P¼ .13). The ma-jority of women (77.2%) overestimated their risk of devel-oping breast cancer. The average degree of overestimationwas 2.08 times. The degree of overestimation of one’s life-time risk of breast cancer was found to be correlated withthe total level of cancer-related distress (Pearson r, 0.25;P ¼ .005). A sister’s current perceived lifetime risk ofbreast cancer was correlated with her total level of cancer-related distress (Pearson r, 0.30; P¼ .0006).
Cancer-Related Distress
The mean level of total cancer-related distress (as meas-ured by the IES) was 25.6 (range, 0-73). The mean scorefor the intrusion scale was 14.5 (range, 0-35) and themean score for the avoidance scale was 11.1 (range, 0-38).Thirty-four women scored in the subclinical range (0-8),67 women scored in the mild range (9-25), 79 womenscored in the moderate range (26-43), and 25 womenscored in the severe range (� 44). A total of 103 women(50.4%) scored in the moderate or severe distress range.In the univariate analysis (Table 3), sister factors (includ-ing age, marital status, current perceived breast cancerrisk, and model-generated breast cancer risk) and indexbreast cancer patient factors (including age at diagnosisand stage of breast cancer) were found to be predictive ofcancer-related distress. In the multivariate analysis (Table4), the only significant predictor of cancer-related distresswas current perceived lifetime risk of breast cancer (P ¼.04), with sisters with a perceived lifetime risk of breastcancer of> 20% being more than twice as likely to experi-
ence high levels of cancer-related distress compared withwomen with a perceived lifetime risk< 20%.
DISCUSSIONIn the current study, we report that sisters of patientsnewly diagnosed with breast cancer experience high levelsof cancer-related distress and have elevated perceptions ofpersonal breast cancer risk. All of the sisters included inthe current study had no other family history of breastcancer other than the sister who was recently diagnosed.This was their first experience with a first-degree or sec-ond-degree relative being diagnosed with and treated forinvasive breast cancer.
In the current study, more than one-half of thesisters scored in the moderate-to-severe distress ranges asmeasured by the IES. The mean levels of cancer-relateddistress in this group of sisters of patients newly diagnosedwith breast cancer can be compared with other popula-tions. We have previously reported on unselected Jewishwomen who received positive BRCA1 (breast cancer 1,
TABLE 3. Predictors of Cancer-Related Distress
Factors
Variables(Frequencies)
N¼205
Mean TotalIES (Range)
N¼205 Pa
Sister Age, y
20-49 (92) 30.0 (0-69) .0002
50-80 (113) 22.1 (0-73)
Marital status
Single, divorced, or separated (81) 23.1 (0-55) .05
Married (124) 27.3 (0-73)
Education
High school or less (67) 28.0 (0-69) .12
College or above (138) 24.3 (0-73)
Perceived lifetime BC risk
�20 (52) 18.4 (0-50) <.0001
>20 (78) 30.4 (3-73)
Model-generated lifetime BC risk
�10 (38) 17.9 (0-73) .0002
>10 (154) 28.0 (0-69)
Children
Yes (154) 25.1 (0-73) .49
No (48) 26.8 (0-55)
Patient Age at diagnosis, y
20-49 (112) 29.1 (0-69) .0003
50-80 (90) 21.3 (0-73)
Stage
I (43) 21.4 (0-55) .04
II (82) 26.3 (0-69)
III (50) 24.8 (0-59)
IV (11) 35.6 (9-73)
Time since BC diagnosis
<12 mo (146) 26.3 (0-73) .48
12-24 mo (33) 23.9 (0-55)
>24 mo (18) 22.4 (0-55)
Abbreviations: BC, breast cancer; IES, Impact of Event Scale.ap-values were obtained from ANOVA to see differences of means of total
IES between different groups of each variable
Sisters of Women with Breast Cancer/Metcalfe et al
Cancer May 1, 2013 1725
early onset) and BRCA2 (breast cancer type 2 susceptibil-ity protein) genetic test results and, as a result, had a life-time risk of breast cancer that approached 80%.18 In thecurrent study, the lifetime risk of breast cancer in the sis-ters was estimated to be 14.5%. Although there was anextreme difference in lifetime risks of breast cancerbetween the 2 groups, the mean levels of cancer-relateddistress were almost identical (25.3 in the Jewish BRCAmutation carriers and 25.6 in the current study). In otherstudies of BRCA1 and BRCA2mutation carriers, the levelsof distress reported have generally been lower. Schwartz etal reported on the 6-month psychological outcomes of 93relatives undergoing genetic testing for BRCA1 andBRCA2.19 The relatives without a cancer diagnosis with apositive genetic test result had a mean score of 15.
Cancer-related distress has also been measured inwomen with breast cancer. Koopman et al reported amean total IES score of 24.2 in women at the time of a
breast cancer diagnosis.20 In a Danish study of 3343women at 3 months after a breast cancer diagnosis, themean total IES score was 20.1, and decreased to 16.2 at15 months after diagnosis.21 Changes in distress scoresover time have been demonstrated in other studies, andalthough we did not observe a significant lowering of totalIES scores by time since the sister’s breast cancer diagno-sis, there were few women in the current study who had amean time since their sister’s diagnosis of > 12 months.However, it may be that the year after a sister’s breast can-cer diagnosis is the most distressing and relatives mayrequire psychosocial support during this time.
Although there has been a considerable amount ofresearch conducted examining the effects of a breast can-cer diagnosis on relatives (mostly daughters and spouses),a study by van Dooren et al reported that having a sisterwith breast cancer was more distressing than having expe-rienced breast cancer in the mother.22 The study included
TABLE 4. Association Between Level of Cancer-Related Distress (High Versus Low) and Sister and BreastCancer Patient Variables
Factor
Variables(Frequencies)
N¼205Univariate
ORa (95% CI) PMultivariateORb (95% CI) P
Sister Age, y
�60 (45) 1 .0008 1 .73
41-60 (129) 3.59 (1.17-7.57) .003 1.27 (0.33-4.83) .83
�40 (31) 4.35 (1.64-11.6) 1.20 (0.24-5.87)
Marital status
Single, divorced, or separated (81) 1 0.14
Married (124) 1.52 (0.86-2.67)
Education
High school or less (67) 1 .37
College or above (138) 0.77(0.43-1.38)
Model-generated lifetime BC risk
�10 (38) 1 .0003 1 .27
>10 (154) 4.41 (1.96-9.95) 2.18 (0.54-8.82)
Children
No (48) 1 .19
Yes (154) 0.64 (0.33-1.24)
Perceived lifetime BC risk
�20 (52) 1 .003 1 .04
>20 (78) 3.02 (1.46-6.28) 2.35 (1.04-5.30)
Patient Age at diagnosis, y
50-80 (90) 1 .001 1 .09
20-49 (112) 2.54 (1.44-4.50) 1.91(0.91-3.99)
Stage
I (43) 1 .27
II (82) 1.53 (0.72-3.24) .17
III (50) 1.80 (0.79-4.10) .16
IV (11) 2.68 (0.68-10.6)
Time since BC diagnosis
<12 mo (146) 1 .12 1 .14
12-24 mo (33) 0.54 (0.25-1.17) .21 0.53 (0.23-1.23) .59
>24 mo (18) 0.53 (0.20-1.44) 0.74 (0.24-2.25)
Abbreviations: 95% CI, 95% confidence interval; BC, breast cancer; OR, odds ratio.a OR is related to higher total distress (�26) versus lower total distress (<26).bMultivariate analyses included all variables found to be significant on univariate analyses in addition to time since BC diagnosis.
Original Article
1726 Cancer May 1, 2013
105 sisters of women with breast cancer, with the majority(71%) diagnosed > 3 years previously, and 42% havingdied of the disease. This suggests that although distress ishigh in the first year, as we have described, it remains adistressing experience for an extended period of time.
In the current study, the only significant predictorof cancer-related distress in a sister of a newly diagnosedpatient with breast cancer was their perceived lifetime riskof breast cancer. Women with a perceived lifetime risk ofbreast cancer >20% were more than twice as likely toexperience moderate or severe levels of cancer-related dis-tress compared with those with a perceived lifetime risk ofbreast cancer of < 20%. Interestingly, the index breastcancer factors, including age at breast cancer diagnosis,stage of breast cancer, and time since breast cancer diagno-sis, were not found to be predictors of distress in the sister.This suggests that it is the perceived personal risk of breastcancer driving distress, rather than the prognosis relatedto the index breast cancer.
It has been shown in high-risk women that long-term distress is significantly predicted by baseline levels ofdistress.23 The authors argued that this finding may reflectthat specific personal characteristics are responsible forincreased levels of distress and underlies the importance ofidentifying vulnerable women at an early stage. Cancer-related distress appears to play an important role in thedevelopment and maintenance of anxiety and depressionin those women at an increased risk of developing breastcancer.9,10 Greater than one-half of the women in the cur-rent study had moderate or severe levels of distress at thetime of a sister’s breast cancer diagnosis. To decrease therisk of long-term distress in these women, future interven-tions should be considered.
Many women overestimate their breast cancer risk.These include women with and without a family historyof breast cancer.6,24-29 Breast cancer risk perception inwomen at high risk of developing the disease is accuratelyreported by 9% to 57% of women.6,24-29 In the currentstudy, the women overestimated their lifetime risk ofbreast cancer by 2.4 times on average. This overestimationwas found to be highly correlated with the total level ofcancer-related distress. This suggests that future interven-tions should be targeted toward helping women to have amore accurate perception of their cancer risk, which maylead to lower levels of cancer-related distress.
There are limitations to the current study. Subjectswere recruited from 2 academic health centers, which maynot be representative of the population studied. In addi-tion, although we attempted to contact all sisters within 1year of a breast cancer diagnosis in the index case, 25% of
the sisters were enrolled after 1 year. However, in ouranalyses, time since breast cancer diagnosis was not foundto be predictive of cancer-related distress in the sister.
The results of the current study suggest that cancer-related distress is high in sisters of newly diagnosedpatients with breast cancer in whom there is no other fam-ily history of the disease. Specifically, women with a per-ceived lifetime risk of breast cancer of> 20% experiencedthe highest levels of distress. Future interventions that tar-get this group should be considered.
FUNDING SUPPORTSupported by the Canadian Breast Cancer Foundation (OntarioChapter).
CONFLICT OF INTEREST DISCLOSURESDr. Metcalfe is supported by the Canadian Institutes of HealthResearch and the Ontario Women’s Health Council.
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Original Article
1728 Cancer May 1, 2013
