Using the Surveillance, Epidemiology and End Results (SEER) cancer registry, we recently reported that the rate of contralateral prophylactic mastectomy (CPM) for stage I–III unilateral breast cancer increased by 150% from 1998 to 2003 in the United States.[1] We found that the CPM rate increased through the end of our study period with no diminution in the incline of the curve. Based on 2003 data, we estimate that about 10,000 breast cancer patients with unilateral breast cancer undergo CPM in the United States each year. In our study, young patient age, non-Hispanic white race, lobular histology, and previous cancer diagnosis were associated with significantly higher CPM rates.
Since the majority of patients with unilateral breast cancer will not develop cancer in the opposite breast, CPM is unnecessary for preventing contralateral breast cancer in most patients. Moreover, since the risk of systemic metastases often exceeds the risk of contralateral breast cancer, most patients will not experience any survival benefit from CPM. Still, many women choose CPM despite potential risks, complications, and irreversibility of the operation. Presently, controversy exists about whether physicians or patients should initiate the discussion of CPM and whether physicians should actively discourage patients who desire CPM. For the purposes of this article, this author contends that physicians should initiate the discussion regarding CPM and should not discourage appropriately selected patients who desire CPM.
Risk of Contralateral Breast Cancer
For women with unilateral breast cancer, the annual risk of clinically detected metachronous contralateral breast cancer is about 0.7%.[2-6] This risk is constant and shows no trend of either increasing or decreasing with follow-up. In contrast, the peak hazard of systemic recurrence of unilateral breast cancer is 1 to 2 years after treatment; the risk decreases consistently after 2 to 5 years.[7] Thus, occurrence of contralateral breast cancer is clinically more significant for patients who are likely to survive for a long time.
Some breast cancer patients have an increased risk of developing contralateral breast cancer. Multiple studies have reported that young age at the time of diagnosis of the first breast cancer is associated with a significantly increased risk.[3,5,8] Patients with at least one first-degree relative with breast cancer also have an increased risk of contralateral breast cancer.[8] Moreover, patients with unilateral breast cancer who also have BRCA1 or BRCA2 genetic mutations have a markedly increased risk of developing contralateral breast cancer.[9,10] Verhoog et al reported that contralateral breast cancer was four to five times more frequent in patients with BRCA1 mutations compared with a sporadic group of breast cancer patients.[10] Survivors of Hodgkin's disease treated with mantle radiation have a significantly increased risk of bilateral breast cancer.[11] Invasive lobular carcinoma is associated with an increased risk of contralateral breast cancer as compared with other histologic types.[2,8,12] Multicentric unilateral breast cancer is also associated with a significantly increased risk of contralateral breast cancer.[2]
Benefits of CPM
Several studies have demonstrated the effectiveness of CPM in preventing contralateral breast cancer.[13-17] In a study of 745 breast cancer patients with a family history of breast cancer, McDonnell et al reported that CPM reduced the incidence of contralateral breast cancer by more than 90%.[14] In a retrospective study of 239 patients, Goldflam et al reported that only 1 (0.4%) contralateral breast cancer developed after CPM.[17] In a cohort of patients with unilateral breast cancer and BRCA1 or BRCA2 mutations, van Sprundel et al reported that CPM reduced the risk of contralateral breast cancer by 91%.[16]
Clearly, CPM is an effective strategy to reduce the risk of contralateral breast cancer, a desired outcome to avoid further breast cancer treatment and anxiety. However, the effectiveness of CPM in preventing breast cancer mortality is not as clear. A recent Cochrane review of eight studies included 1,708 patients who underwent CPM; the authors concluded that CPM decreased the incidence of contralateral breast cancer, but was not associated with any survival improvement.[18] Yet, in a retrospective cohort study of 1,072 patients from the Cancer Research Network, Herrinton et al reported that CPM was associated with a significant decrease in the breast cancer mortality rate (hazard ratio [HR] = 0.57; 95% confidence interval [CI] = 0.45–0.72) and overall mortality rate (HR = 0.6; 95% CI = 0.5-0.72).[15] In this study, women who underwent CPM were less likely to die from non–breast cancer-related causes, thus emphasizing the selection bias that healthier patients undergo CPM more frequently.
In a retrospective case-control study, Peralta et al reported that CPM was associated with a significantly increased disease-free survival rate (CPM, 55%; no CPM, 28%; P = .01), but not an increased overall survival rate (CPM, 64%; no CPM, 49%; P = .26).[13] Finally, using a Markov state transition model, Schrag et al estimated that a 30-year old patient with early-stage breast cancer and a BRCA mutation would gain an additional 0.6 to 2.1 years in life expectancy after CPM.[19]
Complications of CPM
Despite the potential benefits of CPM, the surgery is not risk-free. Severe complications after CPM may potentially delay recommended chemotherapy or radiation therapy after surgery. In a series of 239 patients undergoing CPM (most received immediate reconstruction), Goldflam et al reported a 16.3% complication rate (ipsilateral breast, 8.4%; contralateral breast, 6.3%; both breasts, 1.7%).[17] Barton et al reported that the most common complications after bilateral prophylactic mastectomy were pain (35%), infection (17%), and seroma (17%).[20]
The performance of CPM generally doubles the complication rate for patients undergoing mastectomy. However, life-threatening side effects are very rare. Bilateral mastectomy with immediate breast reconstruction usually requires about 5 hours of surgery; even without complications, patients are typically hospitalized 2 to 3 days after surgery.
CPM Operations
In the past, many CPMs were subcutaneous mastectomies that left behind a substantial amount of breast tissue. Total mastectomy, including removal of the nipple-areolar complex, is recommended for prophylactic surgery today. Skin-sparing total mastectomies are oncologically equivalent procedures that preserve the skin envelope and improve the cosmetic outcomes in conjunction with reconstructive breast surgery. Some investigators have also performed nipple- and areolar-sparing mastectomies in highly selected patients.[21,22] Improvements of mastectomy and reconstruction techniques in recent years probably account for some of the increased use of CPM in the United States. Nevertheless, no mastectomy can remove all breast tissue and completely eliminate the risk of breast cancer.
