Breast cancer is the second most commonly diagnosed cancer in women and a major cause of cancer-related mortality [1]. The majority of breast cancers are sporadic, i.e., occur in women with no family history of cancer. About 70% to 80% of breast cancers are placed in this category [2]. However, it is estimated that 5% to 10% of cases have hereditary causes and, in women under 35 years of age, this percentage ascents to 25% to 40% [2].

Although several genes have been associated with hereditary types of cancer, the majority of cases of breast and gynecological cancer (ovaries, fallopian tubes, and peritoneum) in which a family history of cancer is present are associated with mutations in BRCA 1 and BRCA 2 genes. It is estimated that 60% to 70% of hereditary cancer cases are related with mutations in these genes [3]. These genes were identified in the mid 1990 s and are classified as tumor suppressor genes BRCA 1 and BRCA 2 [4,5]. Both have high-level coding sequences, consisting of 51 exons in total, with the majority of mutations described as protein-truncating mutations, containing frameshift mutations [6].

Mutations in BRCA 1 are more associated with the basal or triple negative subtype of breast cancer with predominance of lymphocytic infiltration with histologically aggressive features [7]. Moreover, tumors associated with mutations in BRCA 2 tend to be luminal, estrogen receptor positive and progesterone receptor positive [7]. There remained controversy regarding prognosis of BRCA-associated breast cancers but Rennert et al. [8] found no differences in breast cancer–specific rates of death among Israeli women with BRCA founder mutation and noncarriers.

Germ line mutations in BRCA 1/2 are related with higher risk for breast and ovarian cancer in women, when compared to general population. However, the magnitude of risk is very wide and often contradictory, as it also depends on contextual factors (family history, ethnicity, environmental, hormonal and lifestyle factors). Results from a meta-analysis show that, in women with a BRCA1 mutation, the average cumulative risk of cancer at the age of 70 years is 57% (95% CI 47 - 66) and, for women with a BRCA 2 mutation, it is of 49% (95 CI 40% - 57%) [9]. However, Bermejo-Perez et al. [10] indicate that, in women with BRCA1 mutation, the average risk of cumulative breast cancer at the age of 70 years ranges from 51% to 95% and for BRCA 2 mutation, the risk ranges between 33% and 95%. The greater penetrance was found in families with multiple cases of cancer.

Clinically, breast cancers associated with mutations of the genes BRCA 1 and BRCA 2 seem to have an earlier onset, when compared with sporadic breast cancer. The average age of breast cancer onset is at 40 to 50 years for BRCA 1/2 mutation carriers, and at 60 to 70 years for sporadic cases [11]. BRCA 1 mutation seems to be associated with earlier onset breast cancer, when compared with BRCA 2 mutations [12].

Women at high-risk for breast cancer, such as the carriers of BRCA 1/2 mutations, are advised to take preventive measures in order to reduce risk. Currently, there are various medical and surgical options for the prevention of breast cancer, namely: intensive monitoring, chemoprevention and prophylactic surgery, which can be divided into mastectomy and oophorectomy. The National Comprehensive Cancer Network [14] has established screening and intervention guidelines (NCCN guidelines) for hereditary breast and/or ovarian cancer syndrome (associated with BRCA 1/2 mutations), which include the three afore mentioned options (http://www.nccn.org). There are other hereditary syndromes, which are less frequent, such as the Li-Fraumeni (associated with TP 53 mutations), the Cowden (associated with PTEN gene mutations), or the Peutz-Jeghers syndrome (associated with STK 11 mutations), for which the NCCN also established specific guidelines. However, these syndromes are not under the scope of this study.

The efficacy of these interventions varies, and to perform a linear meta-analysis is not a simple process. This happens because of the type of studies conducted and included in the analysis (which are difficult to operationalize as randomized-control studies), as well as because of the difficulty in defining specific criteria to evaluate the overall effectiveness of each strategy studied. Review studies show that there is a higher effectiveness of prophylactic surgery strategies compared to other strategies, in women carrying BRCA mutations [7,10,12]. Regarding prophylactic surgery, and more specifically in relation to bilateral mastectomy, there seems to be a reduction of risk for breast cancer in 85% to 100%, in carriers of BRCA mutations [7,12]. In the case of oophorectomy, it reduces the risk of ovarian cancer in 96%, and of breast cancer in 53%. Nevertheless, there are adverse events inherent to these interventions that need to be taken into account. In fact, Bermejo-Pérez and colleagues [10] found between 21% to 30% prevalence of mastectomy complications including hematomas, infections, contractions or rupture of the implant in cases of immediate reconstruction. Surgical interventions may also present additional complications with respect to psychological issues, particularly regarding body image, and mother and wife roles [10].

The surveillance strategies are based on early detection of cancer and not on prevention, which is difficult to study in comparison studies. The mammogram seems to present lower sensitivity results in women with BRCA mutation (40% to 56%) [10], but this sensitivity seems to increase (83% to 95%) with the combination of MRI [7,10].

The decision for chemoprevention is based on the assumption that oestrogen plays a major role in carcinogenesis [13-15], and based on this assumption, tamoxifen, may prevent of breast cancer and ovarian cancer [7,10, 12]. In a clinical trial, tamoxifen reduced the risk of invasive breast cancer, but significant reduction was found only in ER-Positive tumours, [16]. Although data for tamoxifen as an effective strategy to reduce breast cancer are convincing, there are important side effects such as an increase in endometrial cancer, or an increase in vascular events [16]. Other hormonal treatments are being tested as preventive measures for breast cancer, such as the aromatase inhibitors [17].

Surgical mastectomy seems to have a multivariate, complex and often ambivalent nature: recommendations are suggested on a case-by-case basis, and women always have to make the final decision, which is a difficult process. This paper aims to study the decision-making process of women carrying BRCA mutations, regarding the adoption of mastectomy as a risk reduction strategy. To pursue this aim, a descriptive systematic literature review was conducted, in order to respond to the following research questions: 1) to what extent is the decision-making for prophylactic mastectomy in women with the BRCA mutation a more relevant option than other strategies, and 2) what are the major factors influencing the decision for mastectomy? We decided to study the answers to these questions because in medical genetics consultations with women at high familial risk for breast and ovarian cancer we must recommend a prevention strategy and we are frequently confronted with very different decisions from patients regarding the same issue. Therefore, understanding the reasons for accepting or rejecting PM in high risk women has become a highly relevant topic for practical cancer care.

Research studies conducted between 2005 and 2012 were gathered using electronic databases PubMed and MEDLINE, specifying the following research terms: “BRCA mutation”, “mastectomy” and “prophylactic surgery”. A search for the cited articles in the originally found research studies and reviews was also conducted.

Table 1 presents the reference for the articles included in this review. Some of these focus on the study of the frequency of prophylactic mastectomy, comparing to other prevention strategies adopted like prophylactic oophorectomy. Other studies aim to explore the factors and processes underlying the decision-making process, either by looking for correlations between factors, either by adopting a more qualitative analysis in describing women’s perceptions.