Background/Objectives:BRCA mutation carriers and women at high risk of breast/ovarian cancer are faced with the intricate question to opt for prophylactic surgeries and/or a periodic screening. The aim of this study was therefore to identify objective and emotional factors that have an impact on the decision-making process. Methods: Ninety-five women with BRCA mutations or women at increased breast/ovarian cancer lifetime risk were counseled at our outpatient department and either opted for prophylactic surgery or periodic screening. To identify the psychological factors that could have influenced the decision-making, a standardized questionnaire was applied. Additionally, clinical data were collected and were reviewed by a personal talk. Results: Seventy-one of the patients opted for an increased surveillance only, 21 for prophylactic surgeries. Positive predictors for prophylactic surgeries were sociodemographic characteristics such as parity and objective variables such as verified mutation status. Hierarchical regression analysis revealed that the need for safety in health issues has been the only significant psychological predictor of surgery beyond the objective factors. Fear of surgical procedures, menopausal symptoms after surgery, loss of attractiveness, or fear of interferences with sexual life did not significantly affect decision-making. Conclusion: Decision-making towards prophylactic surgeries is influenced by objective but also emotional factors. Knowing that fear and anxiety also have an important impact on decision-making, distinct counselling about the procedures, the subsequent risk reduction as well as the psychological effects of prophylactic surgeries are essential.

The risk for breast cancer (BC) and ovarian cancer (OC) is associated with the number of the relatives affected [1]. Among hereditary BCs and OCs, about half of all monogenetically determined cases are due to a mutation of the two BRCA genes [2]. Women with mutations in the BRCA1 or BRCA2 gene have an estimated lifetime risk of BC of 56–84% and a lifetime risk for OC of 54% (BRCA1) or 27% (BRCA2), respectively [3, 4]. Additionally, the risk for contralateral BC is increased for women with BRCA mutations and diagnosed BC [5].

BRCA1/BRCA2 mutation carriers or women at increased lifetime risk of BC/OC are counseled about prevention guidelines and screening options for early diagnosis.

Prophylactic surgeries are considered the most effective strategies to reduce cancer incidence in mutation carriers [6]. Thereby, risk-reducing bilateral salpingo-oophorectomy (RRBSO) is even associated with significantly lower all-cause mortality in BRCA1/2 mutation carriers [6-9]. Additionally, all-cause mortality was significantly lower after contralateral prophylactic mastectomy in BRCA mutation carriers with BC [6].

Alternatively, secondary prevention options such as increased surveillance for early detection of cancer (magnetic resonance imaging in addition to annual mammography) can be offered [10]. However, studies did not detect an increase in overall-survival by annual mammography and magnetic resonance imaging screening so far [11].

Even though prophylactic surgeries have been shown to be partly associated with survival benefits for BRCA mutation carriers (without cancer diagnosis), only few decide to realize them [12]. Summarizing the data of nine countries (without Germany), Metcalfe et al. [12] have reported that 18% of the women with BRCA1 or BRCA2 mutation without BC had undergone risk-reducing mastectomy (RRM). Approximately one-half of the women with BRCA1/BRCA2 mutation opted for screening solely. In contrast, this study showed that RRBSO was widely accepted by women with BRCA1/BRCA2 mutations (57.2% RRBSO). A German cohort study reported about 12/27 (44%) mutation carriers (without BC) to opt for RRM [13].

Previous studies revealed that the acceptance of prophylactic surgeries is affected by several internal and external variables. Concerning external variables, national care access and provider recommendations seem to matter, but also the health knowledge of one’s own [14]. Internal factors comprise sociodemographic characteristics such as education or parity. These have also been shown to be positive predictors of prophylactic surgeries [15]. Beyond that, psychosocial variables such as general health perception, perceived incurability of cancer, and perceived benefits of surgery seem to have an impact on decision-making in favor of prophylactic surgery. In contrast, emotional factors such as anxiety, vulnerability, and change in body image/sexuality have been reported to hamper the decision in favor of prophylactic surgeries [15-17].

Therefore, the aim of our study was to quantify the effects of (i) health- and cancer-related knowledge; (ii) internal or external factors that could influence decision-making in favor of prophylactic surgeries; and (iii) the detection of specific fears that could be in conflict with the decision in favor of prophylactic surgeries.

Inclusion criteria were identified BRCA1 and/or BRCA2 mutation or a significantly increased lifetime risk of BC/OC (>30%) without known mutations [2]. Only patients beyond 25 years of age were included. Prior to the study, all participants had an individual discussion with the physician geneticist as well as the gynecologist about the individual lifetime risk as well as prevention options including general health issues and prophylactic surgeries. The online supplementary questionnaire (for all online suppl. material, see www.karger.com/doi/10.1159) addressing the different topics of decision-making (additional material) was offered to all women after this talk in the outpatient department of gyne-cology.

Clinical information about sociodemographic characteristics and objective internal variables (mutation status/individual genetic risk, family, and personal history of BC/OC including subsequent therapies) were collected by medical reports and were reviewed in a personal talk with the patient. Additionally, reproductive history as well as general health care issues were noted.

Knowledge about Hereditary BC and OC and General Health Care

Women’s knowledge about general health and their special knowledge about hereditary BC and OC was evaluated using eight items. We assessed women’s knowledge about the effectiveness of measures against cancer and the concrete use of alternative medicines.

Women were also asked to rate their individual risk for BC/OC using a 5-point Likert scale item (very low to very high) in the online supplementary questionnaire. These subjective risk assessments were regressed in a single regression to the actual genetic risk. The residual values of this estimate serve as a z-standardized measure of a patient’s over- or underestimation of her actual cancer risk.

Motivating Factors That Suggest Prophylactic Surgery versus Intensified Screening

Four items asked about internal and external factors that could motivate women to undergo prophylactic surgery. Women were asked to rate the potential motivational impact of a possible detection of cancer, a possible recurrence of cancer in their family, and the patients’ general fear of cancer. A further question asked to what extent the patients were convinced that prophylactic sur-geries would be more effective against cancer than intensified screening.

The barriers against RRM or RRBSO were addressed in 18 subscaled items. Here, questions asking for specific fears were included (weight gain and menopausal symptoms, loss of attractiveness, rejection by the partner, disordered female identity, interferences with sex life, surgical measures). Another question assessed the belief that increased surveillance was safe enough as a cancer prevention. Questions that may refer to both mastectomy and RRBSO were asked in relation to these two surgical interventions. The two ratings were averaged.

General Health Care

Questions about general health (smoking status, medications, supplementary medicine, physical activity, nutrition) of the participants were addressed in four different items in the online supplementary questionnaire. Additionally, women’s BMI was noted.

Statistical Analysis

We carried out a hierarchical logistic regression analysis with RRM/RRBSO versus no surgery as the criterium variable. Sociodemographic and psychosocial control variables were entered as predictors in a first step. Perceived barriers and benefits of the operative and nonoperative procedures were included in the second step. Due to the small sample size only variables with significant bivariate correlations with the surgery decision were included in the model. Statistical significance was assessed at the two-sided p < 0.05 level. All analyses were conducted using SPSS 22 (IBM, 20xx).

Sociodemographic Characteristics of Patients with RRM/RRBSO

The data of 95 patients were analyzed. Three patients were excluded because it was not possible to determine whether the patient underwent surgery, resulting in a final sample of n = 92. Our sample included 23 BRCA1 mutation carriers, 12 BRCA2 mutation carriers as well as 57 patients with a significantly increased lifetime risk for BC/OC without specific detection of a mutated gene. Twenty-one out of 92 patients underwent surgery after the screening (3 RRM, 17 RRBSO, 1 RRM, and RRBSO). Table 1 describes all sociodemographic data of the patients with and without prophylactic surgery. Analyzing the age of the patients with/without prophylactic surgeries, we did not detect significant differences between the two groups. Parity was significantly higher of women with prophylactic surgeries. However, breastfeeding, smoking, physical activity, or the use of alternative medicine was not significantly more prevalent in one group. Patients with detected mutation status (BRCA1 or BRCA2 vs. high risk) opted significantly more often for RRM/RRBSO than nonmutation carriers. Previous curative/elective surgeries did not significantly influence decision-making towards prophylactic surgeries.

Table 1.

Sociodemographic characteristics of women with/without RRM or RRBSO

Sociodemographic characteristics of women with/without RRM or RRBSO
Sociodemographic characteristics of women with/without RRM or RRBSO

Psychological Variables for RRM/RRBSO

Women who opted for prophylactic surgery attributed to RRBSO more effect than women who did not undergo surgery. Beyond that, there were no significant differences in health-related knowledge.

For women who opted for prophylactic RRM/RRSO, the need for safety in health issues was a more significant reason to participate in screening than for women who did not undergo surgery (Table 2). The RRM/RRSO group also reported a greater fear of far-reaching therapeutic measures as a reason to participate in the screening compared to the non-surgery group.

Table 2.

Psychological variables (mean comparisons) of women with/without RRM or RRBSO

Psychological variables (mean comparisons) of women with/without RRM or RRBSO
Psychological variables (mean comparisons) of women with/without RRM or RRBSO

Fear to come down with cancer was the only psychological factor that was stronger in the prophylactic surgery group than in the non-surgery group. The fears of rejection by the partner, an impaired sexual life, loss of attractiveness, or a disturbed female identity did not significantly correlate with decision-making. Fear of surgical interventions or menopausal symptoms after surgery also had no significant effects.

We entered all objective and psychological variables significantly correlating with the surgery decision into a logistic regression analysis. It revealed that the need for safety in health issues was the only significant psychological predictor of surgery beyond the objective factors parity, BRCA1, and BRCA2 mutation status (Table 3).

Table 3.

Hierarchical logistic regression of objective and psychological factors predicting RRM or RRBSO

Hierarchical logistic regression of objective and psychological factors predicting RRM or RRBSO
Hierarchical logistic regression of objective and psychological factors predicting RRM or RRBSO

Despite increased awareness of prophylactic surgeries due to BRCA mutations in the public, studies revealed that the public discussion did neither improve the understanding of hereditary BC and OC in the United States of America nor the understanding of the benefits of -prophylactic surgeries for BRCA1/2 mutation carriers [17-19].

In our cohort study, we investigated the reasons for or against the uptake of RRM/RBSO or prophylactic screening of women with BRCA1/BRCA2 mutation and in those with a >30% increased lifetime risk for BC and OC.

After consultation, only 21 out of our 95 patients had undergone prophylactic surgeries. This is a smaller percentage than that reported in previous studies [13, 20]. Especially RRM were low. Older age of the participants of our study and a short follow-up period could explain these differences.

We detected that decision-making for prophylactic surgeries is influenced by objective factors such as detected BRCA1/BRCA2 mutation. These findings support previous studies that described that BRCA1/BRCA2 mutation carriers more often opted for prophylactic surgeries than women with an increased lifetime risk [1]. Thus, the objective risk information by genetic counselling seems to be of importance for decision-making [21, 22]. We hypothesized that apart from personal history, family history could also have an impact on decision-making towards prophylactic surgeries.

In a previous study, the desire to live longer for the family was also found to be a predictive factor for prophylactic surgeries [23]. In accordance to this observation, we found that parity was a significant predictive factor for the uptake of prophylactic surgeries.

As mentioned above, emotional factors have been shown to affect women’s decisions for RRM/RRBSO [23-25].

Knowing about the increased risk of developing cancer induces multiple worries: the one that matters most is the fact to develop cancer. Consistent with other studies, we found that the fear of getting cancer and of the burden associated with the treatment after cancer diagnosis are important predictive factors for choosing prophylactic surgeries [16, 20, 25, 26]. Especially, anxiety for BC seems to matter for the uptake of RRM [21, 22, 27]. Those women who chose RRBSO also had the perception of the preventive effect of this procedure. However, if all these factors are included simultaneously within a logistic regression analysis, the need for safety in health issues (as a reason for participating in the screening) remains the only psychological predictor of the decision for prophylactic surgery.

Despite the already high cancer risk in these persons, there is still substantial variability with regard to the health safety need, and predominantly those with a high safety need choose the rational decision of prophylactic surgery. This result shows that there is still a great need for counselling, so that all persons with an increased cancer risk see this as a real danger.

Previous studies reported that women worry that RRM/RRBSO can be followed by negative change in the body image and changes in sexual attractiveness, especially for women who have operative complications [28]. However, loosing attractiveness, rejection of the partner, or interferences with sexual life did not affect decision-making in our study. Additionally, worries about menopausal complaints or about the surgeries themselves did not affect decision-making in our study. These differences could be due to the older age of the investigated group herein.

Strengths and Limitations

The strength of our study is that we had a relatively homogenous collective concerning demographic characteristics (age, BMI, etc.) that is representative for the German Consortium for Hereditary Breast and Ovarian Cancer. However, the study has some limitations. The sample size is relatively small, and few women of younger age were included, which explains some differences to other studies. Previous studies demonstrated that the uptake of prophylactic surgeries is dependent on time [1]. Thus, RRBSO was likely to occur 2 years after genetic testing in women between 35 and 45 years [1]. Due to the design of our study, we were not able to demonstrate the dependence of decision-making on time of all our patients as the time of their genetic counselling varied.

Additionally, the short follow-up could be one reason for the low rate of prophylactic surgeries. Even though cultural or religious background was not specially assessed, we did not find significant differences in health-related issues in the group opting for/against prophylactic surgeries.

The risk of developing BC or OC is also modified by lifestyle factors such as smoking [29, 30], obesity [31, 32] or physical activity [33]. It is known that penetrance of BRCA1/BRCA2 is also dependent on these risk factors [30, 34, 35]. Thus, smoking was associated with increased BC risk in BRCA2 mutation carriers [30]. However, patients included in our study – who already had a counseling about risk factors and modifiers – had a high probability of following a healthy lifestyle. Indeed, we showed that 81% were physically active, and 80% denied smoking, which shows that most of the patients were aware of the effects. This may have led to a reduction of lifestyle effects on decision-taking for or against surgery.

Predictive factors to opt for prophylactic surgeries among women with BRCA1/BRCA2 mutation/high family risk of BC OC are verified mutation status, parity, a higher need for safety in health issues, and fear of getting cancer/therapeutic measures after cancer diagnosis. As prophylactic surgeries have been shown to reduce cancer incidence and – at least for RRBSO even mortality – in contrast to periodic screening, providing more information about the benefits and reducing fear is necessary. During counselling, psychological aspects that could affect women after prophylactic surgeries should also be addressed.

The subjects of our study have given their written informed consent. The study protocol has also been approved by the research institute’s committee on human research.

Ninety-five study participants were recruited between January and August 2012 from the outpatient department of the University of Würzburg participating in the German Consortium for Hereditary Breast and Ovarian Cancer. The study was approved by the institutional review board of the hospital.

The authors have no conflicts of interest to declare.

R.S. provided the study design, did the data analysis, and interpreted the results. C.P. collected the data and also participated in the data analysis. S.H. participated in the data collection. U.K. and A.W. checked the design of the study and revised the study for intellectual content. S.S. drafted the manuscript, analyzed, and interpreted the results. All authors have read and have approved the final manuscript.

1.
Lalloo
F
,
Evans
DG
.
Familial breast cancer
.
Clin Genet
.
2012
Aug
;
82
(
2
):
105
14
.
[PubMed]
0009-9163
2.
Meindl
A
,
Ditsch
N
,
Kast
K
,
Rhiem
K
,
Schmutzler
RK
.
Hereditary breast and ovarian cancer: new genes, new treatments, new concepts
.
Dtsch Arztebl Int
.
2011
May
;
108
(
19
):
323
30
.
[PubMed]
1866-0452
3.
Kauff
ND
,
Domchek
SM
,
Friebel
TM
,
Robson
ME
,
Lee
J
,
Garber
JE
, et al
Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study
.
J Clin Oncol
.
2008
Mar
;
26
(
8
):
1331
7
.
[PubMed]
0732-183X
4.
Rebbeck
TR
,
Kauff
ND
,
Domchek
SM
.
Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers
.
J Natl Cancer Inst
.
2009
Jan
;
101
(
2
):
80
7
.
[PubMed]
0027-8874
5.
Kuchenbaecker
KB
,
Hopper
JL
,
Barnes
DR
,
Phillips
KA
,
Mooij
TM
,
Roos-Blom
MJ
, et al;
BRCA1 and BRCA2 Cohort Consortium
.
Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
.
JAMA
.
2017
Jun
;
317
(
23
):
2402
16
.
[PubMed]
0098-7484
6.
Li
X
,
You
R
,
Wang
X
,
Liu
C
,
Xu
Z
,
Zhou
J
, et al
Effectiveness of Prophylactic Surgeries in BRCA1 or BRCA2 Mutation Carriers: A Meta-analysis and Systematic Review
.
Clin Cancer Res
.
2016
Aug
;
22
(
15
):
3971
81
.
[PubMed]
1078-0432
7.
Domchek
SM
,
Friebel
TM
,
Neuhausen
SL
,
Wagner
T
,
Evans
G
,
Isaacs
C
, et al
Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study
.
Lancet Oncol
.
2006
Mar
;
7
(
3
):
223
9
.
[PubMed]
1470-2045
8.
Domchek
SM
,
Friebel
TM
,
Singer
CF
,
Evans
DG
,
Lynch
HT
,
Isaacs
C
, et al
Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality
.
JAMA
.
2010
Sep
;
304
(
9
):
967
75
.
[PubMed]
0098-7484
9.
Eleje
GU
,
Eke
AC
,
Ezebialu
IU
,
Ikechebelu
JI
,
Ugwu
EO
,
Okonkwo
OO
.
Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations
.
Cochrane Database Syst Rev
.
2018
Aug
;
8
:
CD012464
.
[PubMed]
1469-493X
10.
Singh
,
K.
, et al
,
Impact of family history on choosing risk-reducing surgery among BRCA mutation carriers.
Am J Obstet Gynecol,
2013
. 208(4): p. 329 e1-6.
11.
Saadatmand
S
,
Obdeijn
IM
,
Rutgers
EJ
,
Oosterwijk
JC
,
Tollenaar
RA
,
Woldringh
GH
, et al
Survival benefit in women with BRCA1 mutation or familial risk in the MRI screening study (MRISC)
.
Int J Cancer
.
2015
Oct
;
137
(
7
):
1729
38
.
[PubMed]
0020-7136
12.
Metcalfe
KA
,
Birenbaum-Carmeli
D
,
Lubinski
J
,
Gronwald
J
,
Lynch
H
,
Moller
P
, et al;
Hereditary Breast Cancer Clinical Study Group
.
International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers
.
Int J Cancer
.
2008
May
;
122
(
9
):
2017
22
.
[PubMed]
0020-7136
13.
Schott
S
,
Vetter
L
,
Keller
M
,
Bruckner
T
,
Golatta
M
,
Eismann
S
, et al
Women at familial risk of breast cancer electing for prophylactic mastectomy: frequencies, procedures, and decision-making characteristics
.
Arch Gynecol Obstet
.
2017
Jun
;
295
(
6
):
1451
8
.
[PubMed]
0932-0067
14.
Gavaruzzi
T
,
Tasso
A
,
Franiuk
M
,
Varesco
L
,
Lotto
L
.
A Psychological Perspective on Factors Predicting Prophylactic Salpingo-Oophorectomy in a Sample of Italian Women from the General Population. Results from a Hypothetical Study in the Context of BRCA Mutations
.
J Genet Couns
.
2017
Oct
;
26
(
5
):
1144
52
.
[PubMed]
1059-7700
15.
Frost
MH
,
Slezak
JM
,
Tran
NV
,
Williams
CI
,
Johnson
JL
,
Woods
JE
, et al
Satisfaction after contralateral prophylactic mastectomy: the significance of mastectomy type, reconstructive complications, and body appearance
.
J Clin Oncol
.
2005
Nov
;
23
(
31
):
7849
56
.
[PubMed]
0732-183X
16.
Glassey
R
,
O’Connor
M
,
Ives
A
,
Saunders
C
,
Hardcastle
SJ
;
kConFab Investigators
.
Influences on decision-making for young women undergoing bilateral prophylactic mastectomy
.
Patient Educ Couns
.
2018
Feb
;
101
(
2
):
318
23
.
[PubMed]
0738-3991
17.
Stuckey
AR
,
Onstad
MA
.
Hereditary breast cancer: an update on risk assessment and genetic testing in 2015
.
Am J Obstet Gynecol
.
2015
Aug
;
213
(
2
):
161
5
.
[PubMed]
0002-9378
18.
Goel
NS
.
Angelina’s choice
.
South Asian J Cancer
.
2013
Oct
;
2
(
4
):
285
7
.
[PubMed]
2278-330X
19.
Borzekowski
DL
,
Guan
Y
,
Smith
KC
,
Erby
LH
,
Roter
DL
.
The Angelina effect: immediate reach, grasp, and impact of going public
.
Genet Med
.
2014
Jul
;
16
(
7
):
516
21
.
[PubMed]
1098-3600
20.
Madalinska
JB
,
van Beurden
M
,
Bleiker
EM
,
Valdimarsdottir
HB
,
Lubsen-Brandsma
L
,
Massuger
LF
, et al
Predictors of prophylactic bilateral salpingo-oophorectomy compared with gynecologic screening use in BRCA1/2 mutation carriers
.
J Clin Oncol
.
2007
Jan
;
25
(
3
):
301
7
.
[PubMed]
0732-183X
21.
Meiser
B
,
Butow
P
,
Barratt
A
,
Friedlander
M
,
Gattas
M
,
Kirk
J
, et al
Attitudes toward prophylactic oophorectomy and screening utilization in women at increased risk of developing hereditary breast/ovarian cancer
.
Gynecol Oncol
.
1999
Oct
;
75
(
1
):
122
9
.
[PubMed]
0090-8258
22.
van Dijk
S
,
Otten
W
,
Zoeteweij
MW
,
Timmermans
DR
,
van Asperen
CJ
,
Breuning
MH
, et al
Genetic counselling and the intention to undergo prophylactic mastectomy: effects of a breast cancer risk assessment
.
Br J Cancer
.
2003
Jun
;
88
(
11
):
1675
81
.
[PubMed]
0007-0920
23.
Lloyd
SM
,
Watson
M
,
Oaker
G
,
Sacks
N
,
Querci della Rovere
U
,
Gui
G
.
Understanding the experience of prophylactic bilateral mastectomy: a qualitative study of ten women
.
Psychooncology
.
2000
Nov-Dec
;
9
(
6
):
473
85
.
[PubMed]
1057-9249
24.
van Driel
CM
,
Oosterwijk
JC
,
Meijers-Heijboer
EJ
,
van Asperen
CJ
,
Zeijlmans van Emmichoven
IA
,
de Vries
J
, et al
Psychological factors associated with the intention to choose for risk-reducing mastectomy in family cancer clinic attendees
.
Breast
.
2016
Dec
;
30
:
66
72
.
[PubMed]
0960-9776
25.
Fang
CY
,
Miller
SM
,
Malick
J
,
Babb
J
,
Hurley
KE
,
Engstrom
PF
, et al
Psychosocial correlates of intention to undergo prophylactic oophorectomy among women with a family history of ovarian cancer
.
Prev Med
.
2003
Nov
;
37
(
5
):
424
31
.
[PubMed]
0091-7435
26.
Lodder
LN
,
Frets
PG
,
Trijsburg
RW
,
Meijers-Heijboer
EJ
,
Klijn
JG
,
Seynaeve
C
, et al
One year follow-up of women opting for presymptomatic testing for BRCA1 and BRCA2: emotional impact of the test outcome and decisions on risk management (surveillance or prophylactic surgery)
.
Breast Cancer Res Treat
.
2002
May
;
73
(
2
):
97
112
.
[PubMed]
0167-6806
27.
Hatcher
MB
,
Fallowfield
L
,
A’Hern
R
.
The psychosocial impact of bilateral prophylactic mastectomy: prospective study using questionnaires and semistructured interviews
.
BMJ
.
2001
Jan
;
322
(
7278
):
76
.
[PubMed]
0959-8138
28.
Hopwood
P
,
Lee
A
,
Shenton
A
,
Baildam
A
,
Brain
A
,
Lalloo
F
, et al
Clinical follow-up after bilateral risk reducing (‘prophylactic’) mastectomy: mental health and body image outcomes
.
Psychooncology
.
2000
Nov-Dec
;
9
(
6
):
462
72
.
[PubMed]
1057-9249
29.
Croghan
IT
,
Pruthi
S
,
Hays
JT
,
Cha
S
,
Johnson
RE
,
Kosel
M
, et al
The role of smoking in breast cancer development: an analysis of a Mayo Clinic cohort
.
Breast J
.
2009
Sep-Oct
;
15
(
5
):
489
95
.
[PubMed]
1075-122X
30.
Friebel
TM
,
Domchek
SM
,
Rebbeck
TR
.
Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis
.
J Natl Cancer Inst
.
2014
Jun
;
106
(
6
):
dju091
.
[PubMed]
0027-8874
31.
Park
J
,
Morley
TS
,
Kim
M
,
Clegg
DJ
,
Scherer
PE
.
Obesity and cancer—mechanisms underlying tumour progression and recurrence
.
Nat Rev Endocrinol
.
2014
Aug
;
10
(
8
):
455
65
.
[PubMed]
1759-5029
32.
Rose
DP
,
Gracheck
PJ
,
Vona-Davis
L
.
The Interactions of Obesity, Inflammation and Insulin Resistance in Breast Cancer
.
Cancers (Basel)
.
2015
Oct
;
7
(
4
):
2147
68
.
[PubMed]
2072-6694
33.
Lahart
IM
,
Metsios
GS
,
Nevill
AM
,
Carmichael
AR
.
Physical activity, risk of death and recurrence in breast cancer survivors: A systematic review and meta-analysis of epidemiological studies
.
Acta Oncol
.
2015
May
;
54
(
5
):
635
54
.
[PubMed]
0284-186X
34.
Bissonauth
V
,
Shatenstein
B
,
Fafard
E
,
Maugard
C
,
Robidoux
A
,
Narod
S
, et al
Weight History, Smoking, Physical Activity and Breast Cancer Risk among French-Canadian Women Non-Carriers of More Frequent BRCA1/2 Mutations
.
J Cancer Epidemiol
.
2009
;
2009
:
748367
.
[PubMed]
1687-8558
35.
Guinan
EM
,
Hussey
J
,
McGarrigle
SA
,
Healy
LA
,
O’Sullivan
JN
,
Bennett
K
, et al
A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers
.
BMC Cancer
.
2013
Mar
;
13
(
1
):
138
.
[PubMed]
1471-2407
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