Contralateral prophylactic mastectomy: are we overtreating patients?

Abstract

Patients with unilateral breast cancer are at increased risk for developing cancer in the contralateral breast. As a result, some patients choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. Several studies have reported that the CPM rates have markedly increased in recent years in the United States. In this article, we will discuss recent CPM trends, potential reasons patients choose CPM, outcomes after CPM, and alternative strategies for managing the increased risk of contralateral breast cancer among survivors of unilateral breast cancer. In addition, we will try to determine if women undergoing CPM are adequately informed about their decision.

Keywords::

• breast
• contralateral
• overtreatment
• prophylactic
• risk perceptions

Contralateral prophylactic mastectomy trends

Contralateral prophylactic mastectomy (CPM) is the removal of the normal intact breast among women with unilateral breast cancer. The Surveillance Epidemiology and End Results (SEER) registry began coding CPM in 1998. At that time, the proportion of patients who underwent CPM in the USA was very low [1]. However, the CPM rate among all surgically treated patients with invasive breast cancer increased 150% from 1998 to 2003 in the USA. Among mastectomy patients, the CPM rate increased 162% from 1998 to 2003. These trends were observed for all cancer stages and continued to increase at the end of the study period with no plateau. Importantly, there were no new studies or publications, either before or during the study period, which suggested that CPM would be beneficial for patients with invasive breast cancer. Similar findings were observed in the SEER database among patients with ductal carcinoma in situ [2].

Other studies using different databases have confirmed these findings. Using the American College of Surgeons' National Cancer Data Base, Yao et al. reported similar increases in CPM rates from 1998 to 2007; by 2007, the rates were still increasing with no plateau effect [3]. In a study using the NY State Cancer Registry, McLaughlin et al. reported that CPM use more than doubled from 1995 to 2005 [4]. Single-institutional studies have also demonstrated marked increases in CPM rates [5–7].

By contrast, similar trends have not been observed in Europe. In a single-center study from Switzerland, Güth et al. reported that the CPM rates at an academic surgery center did not increase from 1995 to 2009 [8]. The authors concluded that the increased use of CPM was a ‘trend made in the USA’. Another study supports this viewpoint. In an international registry of women with unilateral breast cancer and BRCA mutation, Metcalfe et al. reported that 49% of women in the USA underwent CPM [9]. By contrast, the CPM rates from Europe and Israel were only about 10% or less.

Various patient, tumor and treatment factors are significantly associated with CPM rates. Younger women are much more likely to receive CPM [1,3]. White race, higher education level, private health insurance and family history of breast cancer have also been associated with higher CPM rates [1,3,5,7]. In the SEER study, the presence of infiltrating lobular histology was one of the strongest predictors of CPM [1]. Yet, population-based studies indicate that the risk of contralateral breast cancer is not significantly increased for infiltrating lobular histology as compared with infiltrating ductal histology [10]. Multicentric breast cancer has also been associated with higher CPM rates [11]. BRCA testing is significantly associated with CPM, even among patients who do not have BRCA mutations. In one single-center study, the CPM rate was 40% among those patients who tested negative for mutations [12]. Several studies have reported that preoperative MRI is associated with CPM [5,7,11]. Patients treated at comprehensive cancer programs or teaching facilities are more likely to receive CPM [3].

Reasons for increased CPM rates

This trend toward more aggressive breast cancer surgery is curious and counterintuitive in the modern era of minimally invasive surgery. Many factors probably contribute to increased CPM use. Public awareness of genetic breast cancer and increased BRCA testing may partially explain these observations. Improvements in mastectomy (including skin-sparing and nipple-sparing mastectomy) and reconstruction techniques and access to breast reconstruction probably contribute to increased CPM rates. Moreover, symmetric reconstruction is often easier to achieve after bilateral mastectomy as compared with unilateral mastectomy. Additionally, the native and reconstructed breast age differently, so symmetric outcomes may diminish over time.

Several studies have reported that preoperative breast MRI is associated with higher CPM rates [5,7]. The proposed explanation is that MRI findings introduce concern about the opposite breast. For example, a patient is diagnosed with a unilateral breast cancer, and clinical breast examination and mammography of the contralateral breast are normal. The patient is an ideal candidate for breast-conserving treatment. However, an MRI is obtained that demonstrates an occult indeterminate lesion in the contralateral breast. Next, the patient undergoes a second-look (targeted) ultrasound to characterize this MRI finding. The ultrasound imaging is normal, so she gets called back again for an MRI-guided biopsy, which is negative for cancer. However, the patient decides to have bilateral mastectomy to avoid this stressful scenario again. Preoperative breast MRI probably contributes to increased CPM rates, but the initial observed CPM trends in the USA preceded the widespread use of breast MRI [1,3].

Another possible explanation for the increased CPM rates is that some patients may considerably overestimate their risk of contralateral breast cancer. Previous studies have reported that women with early breast cancer markedly overestimate their risk of recurrence [13]. In a recent survey of 350 mastectomy patients, Han et al. reported that the most common reason for CPM was worry about contralateral breast cancer [14].

The annual rates of metachronous contralateral breast cancer for women with unilateral breast cancer are fairly constant [10]. The Early Breast Cancer Trialists' Collaborative Group recently updated their meta-analyses and reported that the annual rate of contralateral breast cancer was about 0.4% for patients with estrogen receptor-positive breast cancer treated with tamoxifen; the annual rate of contralateral breast cancer was about 0.5% for patients with estrogen receptor-negative breast cancer [15]. All age, tumor and treatment subgroups had rates <0.7%/year. Thus, the 10-year cumulative risk of contralateral breast cancer is about 4–5%. In fact, the risk of contralateral breast cancer may be even lower for patients diagnosed today. Nichols et al. reported that the rates of metachronous contralateral breast cancer have significantly decreased since 1985, largely because of adjuvant systemic therapies [16].

Abbott et al. recently published the results of a prospective single-center study designed to determine patients' perceived risk of contralateral breast cancer [17]. Patients completed a standardized survey prior to surgical consultation and were asked to estimate their risk of contralateral breast cancer. Patients substantially overestimated their 10-year cumulative risk of contralateral breast cancer, with a mean perceived risk of 31.4%. Also, an increased perceived risk of contralateral breast cancer was significantly associated with measurements of psychological distress. In another survey study of young women (age ≤40 years) who underwent CPM, Rosenberg et al. also concluded that many women overestimate their actual risk of developing contralateral breast cancer [18].

Moreover, some patients may overestimate the oncologic benefits of CPM. In the survey study by Rosenberg et al., 94% of women cited ‘desire to improve my survival/extend my life’ as an extremely or very important reason for CPM [18]. Similarly, 85% of women cited ‘desire to prevent breast cancer from spreading to other places in my body’ as another reason for CPM. In another survey study of women who underwent CPM, Altschuler et al. recorded comments such as ‘I do not worry about recurrence’, and ‘I am free of worries about breast cancer’ [19]. Such observations highlight a potential overconfidence and a false sense of security to women who undergo CPM.

Outcomes after CPM

Several studies have demonstrated that CPM is effective in reducing the risk of contralateral breast cancer (relative risk reduction about 90%) [20,21]. However, the effectiveness of CPM in reducing breast cancer mortality is not as clear. The only plausible way that CPM improves breast cancer survival is by reducing the risk of a potentially fatal contralateral breast cancer. A recent survival analysis of the SEER database included patients with unilateral breast cancer diagnosed between 1998 and 2003 [22]. The authors concluded that CPM is associated with a small improvement (4.8%) in 5-year breast cancer-specific survival rates for young women with early-stage estrogen receptor-negative breast cancer. However, the cumulative incidence of contralateral breast cancer was <1% in this study; so, the apparent survival benefit is most likely due to selection bias. In a retrospective single-center study, Boughey et al. reported that CPM was associated with improved overall survival and disease-free survival rates [23]. However, a recent Cochrane review of published CPM studies concluded that ‘there is insufficient evidence that CPM improves survival’ [24].

Despite the results of retrospective or cancer registry studies, CPM is not likely to improve breast cancer survival rates for patients who do not have BRCA mutations. For these patients, the 10-year cumulative risk of contralateral breast cancer is about 4–5%; most metachronous contralateral breast cancers are stage I or IIA, with a 10-year mortality rate of about 10–20%. Thus, the 20-year mortality rate from a contralateral breast cancer is about 1% or less. In addition, many patients die from systemic metastases from their known ipsilateral breast cancer or from other causes during 20-year follow-up. Finally, CPM does not prevent all contralateral breast cancers. Thus, CPM will not decrease breast cancer mortality rates for most breast cancer patients without BRCA mutations.

Contralateral prophylactic mastectomy is an irreversible procedure and is not risk free. Severe complications after CPM may potentially delay recommended adjuvant therapy and may require additional surgical procedures and subsequent loss of reconstruction. The overall complication rate after bilateral mastectomy and reconstruction is about 15–20% [21]. About half of the complications are secondary to the prophylactic mastectomy. Even without complications, these operations are long (often 5–6 h) and require 2–3 days of inpatient hospital care, drainage catheters and 3- to 4-week overall recovery.

Despite potential risks and complications, most patients are satisfied with their decision to undergo CPM. The greatest reported benefit contributing to patient satisfaction is a reduction in breast cancer-related concerns. Frost et al. reported that 83% of patients were either satisfied or very satisfied with their decision to undergo CPM at a mean of 10 years after surgery [25]. Some women have negative psychosocial outcomes following CPM, most often related to high levels of psychological distress, sexual function and body image or poor cosmetic outcome [19]. Montgomery et al. reported that the most common reasons for regret after CPM were a poor cosmetic outcome and diminished sense of sexuality [26].

Alternatives to CPM

Patients with unilateral breast cancer have options that are less drastic than CPM. Surveillance with clinical breast examination, mammography and potentially breast MRI may detect cancers at earlier stages. Prospective randomized trials have demonstrated that tamoxifen, given as adjuvant therapy for estrogen receptor-positive breast cancer, significantly reduces the rate of contralateral breast cancer [15,27]. Aromatase inhibitors may reduce the risk of contralateral breast cancer as much as, or even more than, tamoxifen [28]. The Arimidex, Tamoxifen Alone or in Combination trial demonstrated that anastrozole was superior to tamoxifen in preventing contralateral breast cancer in postmenopausal women. Ovarian ablation and cytotoxic chemotherapy also reduce the risk of contralateral breast cancer [29].

Conclusion

Increasingly, more patients in the USA with invasive breast cancer and ductal carcinoma in situ undergo CPM to prevent contralateral breast cancer. Patient, tumor and treatment factors are associated with increased use. Indeed, CPM does reduce the risk of contralateral breast cancer, but does not impact breast cancer survival rates. Controversy exists about whether the physician or patient should initiate the discussion of CPM. If a patient appropriately chooses breast-conserving surgery, then CPM is not a relevant treatment. For patients who undergo mastectomy, CPM may be a reasonable option, particularly if a patient has a BRCA mutation, strong family history, is obese or if imaging of the contralateral breast is difficult.

However, an increasing number of studies suggest that many breast cancer patients are not making informed decisions. For example, several recent studies have demonstrated that many patients substantially overestimate the risk of contralateral breast cancer and overestimate the oncologic benefits of CPM. The apparent discordance between patient perceptions and realistic expectations provides a teachable opportunity for physicians treating newly diagnosed breast cancer patients. In the study by Rosenberg et al., women identified physicians as the most important sources of information regarding CPM [18]. The development and implementation of decision aids are critically important to provide patients with accurate and easily understood information. Specifically, physicians should effectively communicate the actual risk of contralateral breast cancer, the potential complications of CPM, the likelihood of distant metastases from the index breast cancer and alternatives to CPM. Perhaps, with improved patient education, the CPM trends in the USA will plateau or be reversed.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.