Currently available management strategies for women who carry inherited predisposition to develop breast cancer are limited given the lack of prevention methods with proven efficacy. Furthermore, there have been no prospective, controlled trials of the breast cancer risk reduction associated with bilateral prophylactic mastectomy. Such studies are unlikely to take place due to ethical and practical considerations. Prophylactic mastectomy, whether subcutaneous or total, significantly reduces, but does not eliminate, the risk of breast cancer in high-risk individuals.
Several studies showed that breast reduction procedures substantially lower the risk of breast cancer. Recently, Brinton et al
] confirmed that the magnitude of cancer risk reduction is directly related to the amount of tissue removed during the operation. With a SCM, the nipple-areola complex is preserved and some of the underlying breast tissue remains on the skin flaps. When SCM is intended as prophylaxis against breast cancer, the surgeon's aim is to remove as much tissue as possible. It is plausible that a less thorough removal of glandular tissue may have taken place given the indication for surgery in our patient's case. It is generally agreed that the prophylactic nature of bilateral mastectomy in an unaffected BRCA1
mutation carrier calls for the most complete breast tissue removal. This viewpoint makes SCM a less desirable choice. Skin-sparing mastectomy [8
] could be seen as a partial compromise and appears to be an increasingly popular option for women at high risk. More recently, geneticists have questioned the rejection of simple SCM as a viable procedure in such women. It is argued that the magnitude of the risk reduction offered by SCM, when combined with its greater cosmetic acceptability, is sufficient to keep this option available to women [9
There are numerous reports in the literature describing the occurrence of breast cancer after SCM [10
]. Subsequently, the perception exists that SCM fails to eliminate the risk of breast cancer. Although the extent of risk reduction achieved by SCM is limited given that about 5–10% of the mammary tissue remains in situ
, it is thought to be of the order of >85% [4
]. As stated above [9
], at this level of risk reduction, SCM would have a greater effect on breast cancer rates in BRCA1/2
carriers than would total mastectomy if at least 50% of BRCA1/2
carriers chose preventive SCM. Currently, preventive bilateral total mastectomy rates are about 20% in most populations.
The first retrospective study of efficacy of prophylactic mastectomy carried out by Hartmann et al
] included 18 subjects later confirmed to be carriers of deleterious mutations in the BRCA
genes but, unfortunately, it had insufficient statistical power to detect a difference in the risk reduction between total and SCM. In this cohort, all breast cancers (n = 7) were diagnosed in women who had undergone SCM (total of 950). None were known to be BRCA1/2
mutation carriers. Of the seven cases, only one occurred in the nipple-areolar area. Not surprisingly, the majority of the high-risk women (n = 17) described in the subsequent report [3
] underwent SCM. After a median of 13.4 years of follow-up, none of the BRCA1/2
germ-line mutation carriers has developed breast cancer. The authors concluded that at least 90% risk reduction could be expected among women with confirmed BRCA
mutation status following prophylactic bilateral SCM. Meijers-Heijboer et al
] report the initial results of a prospective study of 76 women with deleterious BRCA1
mutations who chose to undergo bilateral simple mastectomy and no breast cancers were observed after a mean follow-up of 2.9 ± 1.4 years. The Prevention and Observation of Surgical End Points (PROSE
) Study Group findings [5
] support the notion that bilateral mastectomy results in approximately 90% breast cancer risk reduction. Of 105 BRCA
mutation carriers, only two women (1.9%) developed breast cancer 2.3 and 9.2 years after SCM. The first breast cancer case was diagnosed at the age of 28 years in the BRCA2
mutation carrier who presented with a palpable axillary mass at 27 months post-SCM. Subsequently, metastatic adenocarcinoma in an axillary lymph node was identified and it was most likely consistent with a primary breast cancer already present at the time of SCM. It is important that this case is not considered as a failure of SCM, and it should be therefore classified as a recurrence which would have likely taken place despite the surgery. The second breast cancer case occurred in a BRCA1
carrier at the age of 41 years.
When hereditary predisposition to breast cancer is being assessed, it is important to consider the impact of the age-related penetrance of the BRCA1
has a higher penetrance than BRCA2
in the pre-menopausal years [1
]. The benefits of preventive surgery will be proportionally greater for an older BRCA2
carrier than an older BRCA1
carrier, and therefore if a BRCA2
carrier discovers her mutation status when she is peri- or post-menopausal, the potential benefits of preventive mastectomy should not be understated, as the breast cancer risks do not significantly diminish following menopause.
In our review of the literature (see Table ), only one primary breast cancer has been reported to occur in a cohort of 207 BRCA1/2 mutation carriers who opted for preventive surgery. It could be argued that the efficacy of the bilateral total mastectomy has not been studied adequately in the high-risk individuals to prove its absolute superiority over SCM. The total number of the BRCA1 and BRCA2 carriers who have undergone this type of mastectomy is relatively small and the mean follow-up is rather short. Furthermore, the presence of a microscopic primary lesion at the time of surgery may result in subsequent recurrence that would be impossible to differentiate from a new primary breast cancer. Based on the above data, the risk-reducing effect of SCM should not be ignored when presenting prophylactic mastectomy options to women at high risk who find total mastectomy unacceptable and would not otherwise have considered surgical prevention. Nevertheless, the lack of popularity of this procedure among surgeons will likely limit its use.
Studies assessing efficacy of bilateral prophylactic mastectomy (PM) in BRCA1 and BRCA2 carriers
The existing literature on the mammographic and sonographic appearance of breast cancer in BRCA
-positive patients' reconstructed breasts is rather scanty. Pathologic studies have demonstrated that tumors in BRCA1
mutation carriers are associated with morphologic features of continuous pushing margins [13
], with a reduced potential for stromal infiltration explaining that this appearence might mimic benign-looking lesions at mammography [14
] and breast sonography as well. Indeed, sonographic criteria of the mass in our case – ovoid axis, thin pseudocapsule, posterior enhancement, and well defined margins – were in keeping with a benign nodule [15
]. In addition, according to Giovagnorio criteria [16
], the lesion described in our case, with a single vascular pole (type 2), was compatible with a benign lesion. Cconsistent with the Lamb et al
], this lesion appeared benign but was in fact a moderate to high-grade invasive cancer.