Background
Current risk estimation models enable the identification of women who are at elevated risk for breast cancer through genetic testing for BRCA1, BRCA2, and other mutations, as well as other potential genetic susceptibilities made evident by family histories of the disease. These high-risk women face a lifetime likelihood of breast cancer of between 20% and 80% depending on family history and genetic findings, significantly greater than the average 12% risk for women in the US. A subset of high-risk women face additional stresses related to genetic findings that do not correspond to a very specific risk estimate, or have unclear clinical implications, due to limitations of existing genetic science and risk quantification.
Several risk management options are available to support women at higher than average risk of breast cancer. Most of these are significantly underused by women who may benefit in terms of reduced cancer risk and cancer-related worry. Only about half of
BRCA mutation carriers undergo the recommended prophylactic oophorectomy [
1] and fewer than 5% of the high-risk women likely to benefit from chemoprevention use it [
2,
3]. Underuse may be driven by multiple factors: lack of physician or patient information or understanding; lack of clinician confidence discussing preventive interventions or identifying women who could benefit from them; psychological or social dynamics that shape women’s preferences, deliberations, or ability to act on their decisions; and fully informed choice. Ultimately, it is women who make the choices—often with the help of health professionals and personal connections—about which prevention options to implement. These individual choices have significant impact on utilization of prevention options, breast cancer incidence, and health outcomes. Nevertheless, little is known about the processes women navigate as they make these decisions.
This article summarizes what is known and unknown about the various drivers of women’s decisions about breast cancer risk management methods. It begins with a brief overview of breast cancer prevention options for high-risk women, followed by a review of the current literature regarding decision making about these options by specific populations of women, and possible explanations for these patterns. This review also highlights important areas for future research, which could support the development of interventions that more fully empower women to make informed and values-consistent decisions and contribute to favorable health outcomes. It focuses solely on the prevention decision making of women at elevated risk of breast cancer due to identified genetic mutations or familial history. The prevention behavior of average risk women, decisions relevant after a breast cancer diagnosis, and the psychological sequelae of prevention interventions are outside the scope of this discussion.
Breast cancer prevention pathways
Women at elevated risk for breast cancer are those who either have a known predisposing genetic mutation, or have a family history of breast or related cancers sufficient to raise calculated lifetime chance of breast cancer above a certain benchmark—usually 20–25% [
4‐
13]. Studies of breast cancer patients and early population-based screening studies suggest that between 10% and 15% of women with a substantial family history likely carry
BRCA1/2 mutations [
14,
15], and about half of
BRCA mutation carriers are unaware of this status [
16,
17]. Current evidence indicates that specific mutations in other genes (
ATM,
CDH1,
CHEK2,
NBN,
NF1,
PALB2,
PTEN,
STK11, and
TP53) also confer increased breast cancer risk, and testing for these mutations is becoming increasingly available. Positive findings for these mutations are currently associated with recommendations to add magnetic resonance imaging (MRI) screenings and, for a subset of these genes, to consider prophylactic surgery, but other aspects of appropriate clinical management for these patients remain under investigation [
13,
18‐
20]. Guidelines recommend that women with a family history of breast or related cancers be screened, receive genetic counseling and testing if indicated, and receive counseling to discuss chemoprevention, risk-reducing surgery, and enhanced surveillance options if found to meet familial or genetic risk criteria [
13,
21,
22]. Four biomedical prevention options form the basis for women’s individual prevention pathways.
Bilateral prophylactic mastectomy (BPM; the surgical removal of both breasts for breast cancer risk reduction), the single most effective prevention method, reduces breast cancer risk by about 90% [
23‐
31] and breast cancer-specific mortality by upwards of 80% [
25,
26]. It may not improve overall survival, however, relative to routine mammography and MRI use, particularly for women who have had their ovaries removed [
27]. Contralateral prophylactic mastectomy (CPM; surgical removal of the nonaffected breast for women with unilateral breast cancer) has not been shown to improve survival rates, but may decrease the risk of contralateral cancers in certain high-risk women; it is considered a clinically appropriate option for breast cancer patients with known
BRCA1/2 mutations, significant family history, or high-risk histology [
32‐
38].
Prophylactic surgical removal of ovaries and fallopian tubes (bilateral prophylactic salpingo-oophorectomy; BPSO) is recommended for all
BRCA mutation carriers between the ages of 35 and 40 years (or when childbearing is complete). For this group, it reduces the risk of ovarian, fallopian tube, or peritoneal cancer by 80% [
39], likely halves the risk of breast cancer [
33,
36,
40‐
43] (but see [
44] for a counter-argument), and strongly reduces breast cancer mortality, ovarian cancer mortality, and all-cause mortality [
27,
39]. However, adverse effects include induction of menopause, as well as increased risk of cardiovascular disease, osteoporosis, and cognitive impairment. Treatment with hormone replacement therapy (HRT) is controversial due to increased breast cancer risk [
27,
45].
Two selective estrogen receptor modulators are approved for use as chemoprevention agents in the US. A 5-year course of tamoxifen by premenopausal women at elevated risk reduces their risk of breast cancer by 30% to 50%. Side effects include increased risk of endometrial cancer and venous thrombosis during the treatment period, while the protective benefits of chemoprevention last for at least 20 additional years [
23,
46‐
52]. Raloxifene (approved for postmenopausal women) is estimated to be 76% as effective as tamoxifen in reducing the risk of invasive breast cancer, with significantly lower risks of thromboembolic events and uterine cancers [
53‐
55]. Aromatase inhibitors show substantial promise as chemoprevention agents but are not yet approved for this use in the US or Europe; other potential chemoprevention agents including nonsteroidal anti-inflammatory drugs (NSAIDS), aspirin, metformin, cyclooxygenase-2 (COX-2) inhibitors, and poly-adenosine diphosphate-ribose polymerase (PARP) inhibitors have shown promise in early clinical research [
27,
53,
56‐
59].
Enhanced surveillance is designed to facilitate early detection and treatment of breast cancer in women at high risk. Recommendations include: 1) increasing the frequency of clinical breast examinations to biannual checks; 2) initiation of radiologic screening at younger ages, such as 5 to 10 years prior to the youngest age of breast cancer diagnosis in a woman’s family; 3) annual bilateral screening mammograms, combined with targeted ultrasound examinations as indicated; and 4) the addition of breast MRI for women with a lifetime risk of breast cancer of 20% or greater [
13,
60]. These methods substantially increase the probability of early cancer detection in high-risk women, but require sustained adherence, involve regular (and sometimes substantial) expenditures, and raise distress rates associated with false-positive tests [
61‐
66].
Lifestyle changes that reduce the risk of breast cancer in the general population are considered wise but insufficient for those with higher, familial risk [
30,
56,
67]. These include increased intake of vegetables, fruit, and fiber, increased exercise, weight management, smoking cessation, reductions in alcohol use, prolonged lactation, and minimizing exogenous hormone therapy [
56,
68].
It is likely that high-risk women commonly compare the effectiveness and consequences of methods and consider particular combinations of prevention options. There is, however, a sparse evidence base for these comparisons and combinations [
69,
70]. It is known that
BRCA mutation carriers can achieve greater risk reduction by undergoing both BPM and BPSO than either alone [
27,
71], and that prophylactic surgeries generally reduce both cancer risk and anxiety about cancer [
28]. BPSO is likely the single intervention with the best risk-benefit ratio for
BRCA mutation carriers [
72,
73]. Prophylactic surgeries may be more cost-effective than other methods, but enhanced surveillance yields the most quality-adjusted life years [
74,
75]. Given the serious ethical and practical impediments to randomized controlled trials, prospective observational studies that take into account adherence to chemoprevention and enhanced surveillance could be useful in comparing morbidity, mortality, and psychological consequences in the context of various prevention strategies across various subgroups of women [
30,
76].
Future research
Many of the most substantial gaps in the research literature have to do not with breast cancer risk reduction options themselves, but instead with how women make sense of and utilize these measures. Key gaps in existing knowledge of women’s prevention decision making are summarized in Table
1. Future research should focus on four key areas.
Table 1
Key gaps in current knowledge concerning breast cancer prevention decision making by women at elevated risk
• Which prevention options and combinations women consider viable (prevention pathways) |
• Women's reasons for low uptake of biomedical prevention interventions |
• Explicit comparisons of prevention options and their effects |
• How prevention behavior varies among subgroups of women, who differ according to: |
– Medically-defined or self-perceived level of risk |
– Geographical and cultural context |
– Race-ethnicity or socioeconomic status |
– Access to medical information or care |
• Mechanisms that account for variation in prevention choices across subgroups |
• Effects of emotions and psychological factors on women’s prevention decision making |
• Effects of spouses, children, family, and friends on decision making |
• Effects of exposure to cancer patients, support groups, or advocacy organizations on decision making |
• Effects of exposure to genetic counseling and quality of communication with other healthcare providers on decision making |
• Effects of previously unstudied factors on decision making: stigma, self-worth, desire to take control of health, personal exposure to experience of cancer |
• Interactions among various drivers of prevention choice |
• How women at elevated risk explain their own decision-making processes and needs |
• Key methods to help women attain informed and empowered decision making |
Women’s own perspectives
Prior research on women’s use of prevention interventions has been largely quantitative and deductive. This research has provided a powerful foundation for understanding women’s prevention behavior, but has also missed key dynamics such as the potential roles of financial resources, social support, and desire to control one’s health. The ability to support improved decision making will hinge on accurate understanding of women’s own perspectives, which can be illuminated by systematic qualitative research that offers women more space to articulate perspectives on their own experiences, rationales, and challenges.
Explicit comparison of prevention pathways
The ability of women to compare their options would be facilitated by research that explicitly documents the effects of various choices on physical, psychological, and social well-being. One potential outcome of such research may be improved decision aids, which have been shown to positively impact knowledge, expectations, distress, and decisions among patients facing multiple medical options with complex pros and cons [
183‐
189]. Initial steps have been made toward developing such tools for women at elevated risk (particular with respect to chemoprevention) [
185,
190‐
200], but considerable work remains to incorporate all possible prevention pathways, and to consider psychological, social, and demographic factors in the construction of decision aids [
97].
Processes of decision making
Inductive research from women’s own perspectives may illuminate previously unstudied processes important to women’s decisions, and thereby offer new potential approaches for designing prevention-supportive interventions. At a minimum, these dynamics are likely to include: psychological factors from cancer-specific distress and fear for children to the desire to take control of health; social dynamics of support from spouses, family, and friends; exposure to cancer patients, survivors, and advocacy groups; the need to bolster both information acquisition and skills-building to facilitate deliberative decision making; and interactions among the drivers of prevention choice.
Dynamics of subgroup variation
Existing research in and beyond the area of breast cancer prevention indicate that decision-making processes and prevention choices are likely influenced by the severity of medical risk, geographical context, race-ethnicity, SES, and access to medical information or care. These distinctions may have important implications for tailoring supportive interventions.
Acknowledgements
The authors would like to thank Anne Esacove and Gene Deerman for their comments on an early draft of this piece, Megan Hils for her editorial assistance, and Robert Pilarski for his assistance in verifying information related to genetic risk and testing.