With the death of Bernard Fisher, it is time to reflect on how breast cancer surgery evolved over the course of his career [1]. When Fisher became president of the National Surgical Adjunct Project in 1967, breast cancer was treated with radical mastectomy. Using the B-O6 protocol he demonstrated the equivalence of mastectomy and lumpectomy with adjuvant radiotherapy for stage II breast cancer.
The women appreciated the opportunity to treat their cancer while preserving their breast. Paradoxically, bilateral mastectomy rates are now increasing. In the USA, from 2004 to 2012, the rate of contralateral prophylactic mastectomy increased from 5% to 12% of operations for unilateral breast cancer [2].
Among mastectomized women, the rate of contralateral prophylactic mastectomy increased from less than 2% in 1998, to 28% in 2010, and 30% in 2012 [3]. Similar changes have been reported in women with ductal carcinoma in situ [4].
The reasons for the increased incidence of bilateral mastectomies are multifactorial and complex. As a framework of reference, the authors consider the following explanations:
1. Increased diagnosis of bilateral cancers due to the increasing use of magnetic resonance imaging (MRI).
2. Increased genetic testing by identifying more women with breast cancer who carry BRCA1 and BRCA2 (BRCA1/2).
3. The emergence of risk assessment models identifying women at high risk of developing contralateral breast cancer.
4. Fear of cancer recurrence and desire to avoid a second round of treatment.
5. Cancer-related distress negatively affecting quality of life.
6. Body image considerations and access to breast reconstruction
7. Surgeon preference and the influence of social networks and media
The literature for this review was identified through PubMed using the search terms “contralateral prophylactic mastectomy” and “bilateral mastectomy,” from 1995 to June 2020. The search was limited to publications written in the English language. References selected were based on factors including citations, viewing times, and relevance to the purpose of this review.
> Increased use of MRI and bilateral cancers
In the preoperative setting, the use of breast MRI helps to delineate the extent of the tumor, facilitating its complete removal. With the increased use of MRI, the detection of bilateral synchronous breast cancers increased from 1.5% in 1975 to 2.9% in 2014 [5]. Synchronous bilateral cancers are commonly treated with bilateral mastectomy [6-8]; however, the use of breast MRI has not improved surgical outcomes [9].
Preoperative breast MRI detects a contralateral breast lesion in 9.3% of women; 40% of these lesions are cancers (35% in situ , 65% invasive) and 60% are benign [10]. Some patients in whom a contralateral breast abnormality has been detected choose bilateral mastectomy over additional evaluation of the contralateral lesion.
The prospect of additional studies, biopsies, and surgical delay seem likely to be less attractive than an immediate bilateral mastectomy [11]. At Memorial Sloan Kettering Cancer Center , 38% of women with prior breast cancer choose bilateral mastectomy when they develop contralateral cancer, despite being amenable to a second lumpectomy [6]. However, bilateral breast cancers account for a small fraction of women with breast cancer who seek bilateral mastectomy.
> Genetic tests and pathogenic variants
Genetic variations are responsible for 5% to 10% of all breast cancers [12]. Women with synchronous bilateral breast cancers are candidates for genetic testing. In the international database of the Hereditary Breast Cancer Clinical Study Group, of 17,589 carriers over 20 years, 6.6% of BRCA1 carriers , and 5.4% of BRCA2 carriers , with breast cancer, presented synchronous disease bilateral.
Breast cancer patients who carry a BRCA1 or BRCA2 pathogenic variant also have a high risk of contralateral breast cancer (2% annually), and the cumulative risk is inversely correlated with age [13,14]. Among 6294 Dutch women younger than 50 years with breast cancer, the 10-year cumulative risk of contralateral breast cancer was 21% for BRCA1 carriers, 11% for BRCA2 carriers , and 5% for noncarriers [ 14].
Most BRCA1/2 carriers are unaware of their genetic variant at the time of cancer diagnosis. However, variant status affects the type of surgery performed for breast cancer [15]. At the Mayo Clinic , 83% of breast cancer patients chose bilateral mastectomy when they were aware of their BRCA pathogenic variant , compared to 29% when they were unaware [16].
BRCA1/2 carriers with early-stage breast cancer have a survival benefit 20 years after bilateral mastectomy compared with unilateral mastectomy [17]. Bilateral mastectomy has not been shown to improve survival in women with a moderate penetrance gene variant (e.g., ATM, CHEK2, CDH1, NF1 and PALB2 ) [18].
> Risk of contralateral breast cancer
In women without a genetic variant, the risk of contralateral breast cancer varies depending on age at cancer diagnosis and family history. The average risk is 0.5% annually [19]. The risk of contralateral breast cancer after ductal carcinoma in situ is similar (0.6% annually) [20].
Younger age at diagnosis is associated with a higher cumulative lifetime risk of contralateral cancer. Among 78,775 Swedish women with breast cancer, the cumulative risk of contralateral cancer (up to age 80) was 23% when diagnosed in women younger than 50 years, 17% when diagnosed between ages 50 and 59, and 12% when diagnosed between 60 and 69 years [21].
Family history affects a woman’s risk of contralateral breast cancer. Among young women with breast cancer in the Women’s Environmental Cancer and Radiation Epidemiology (WECARE ) study, the 10-year cumulative risk of contralateral breast cancer was 4.3% if there was no family history, 8.1% if a first-degree relative had breast cancer, 13.5% if the first-degree relative was diagnosed before age 40, and 14.1% if the first-degree relative had bilateral breast cancer [24 ].
The risk of contralateral breast cancer is also influenced by tumor biology, treatments received, and lifestyle factors. Increased risk is associated with lobar subtype (30%), and hormone receptor negative (40%) [25]. Endocrine therapy and chemotherapy reduce the risk [26]. Alcohol consumption, heavy smoking, and obesity all increase the risk [22,27].
In Ontario, risk-reducing surgery is offered to women with an estimated lifetime risk of developing breast cancer of 25% [77]. Combining age at diagnosis, family history, and treatments received for first cancer, few women are likely to reach that threshold. Risk prediction calculators for contralateral breast cancer are emerging, including the Manchester Tool [28], CBCRisk [29], and PredictCBC [30], but have modest accuracy [31].
The clinical factors that estimate the possibility of contralateral breast cancer are not necessarily the same factors associated with the uptake of bilateral mastectomy in women with breast cancer.
Women who choose contralateral prophylactic mastectomy tend to have large (>5 vs <2 cm), high-grade tumors, with multifocality/multicentricity, lobular subtype, hormone receptor negative, and lymph node positive [32,33,35].
Social status and access to medical care also appear to influence the pursuit of contralateral prophylactic mastectomy. Women with contralateral prophylactic mastectomy tend to be young, white, have private health insurance, and have high socioeconomic status [3,32-38].
From this review of the literature, it appears that the choice for contralateral mastectomy cannot be explained by the risk of contralateral breast cancer. Factors that are associated with distant recurrence are also associated with bilateral mastectomy.
For a woman with newly diagnosed breast cancer, the risks of ipsilateral recurrence, distant recurrence, and contralateral breast cancer can be difficult to disentangle. It may confuse one risk with another, or frame all risks into a single risk of recurrence [41]. This challenging problem may not be adequately addressed by her doctors. Among 1,295 women with breast cancer in Georgia and Los Angeles, California, only 33% said their doctors discussed the risk of recurrence "a lot" and 14% said "not at all."
> Anguish and fear of recurrence
The decision for a bilateral mastectomy is not supported by the published empirical risks of contralateral cancer or the estimated mortality benefit. Qualitative studies have highlighted fear of cancer recurrence, contralateral cancer, and death as underlying motivators of contralateral prophylactic mastectomy [39]. Two points must be considered.
- First, the risk of contralateral breast cancer is often exaggerated by the patient, possibly due to inadequate doctor-patient discussion [40,41].
- Second, women often reveal fear of death as the reason for undergoing contralateral mastectomy, despite the lack of mortality reduction.
Although contralateral prophylactic mastectomy reduces the risk of contralateral breast cancer by 95% [23], it does not improve survival [28,47,48]. Furthermore, the risk of postoperative complications, including infection, bleeding, and chronic pain, is doubled [63]. Therefore, there are important emotional and psychosocial components underlying the motivation for a contralateral prophylactic mastectomy.
Women may experience a heightened psychological reaction due to fear of a theoretical, low-probability event occurring in the future. Squires et al. [42], reported that fear anxiety influenced women with breast cancer to prefer contralateral mastectomy. Graves et al. [43], associated breast cancer-specific distress with contralateral prophylactic mastectomy.
In one study, women low in dispositional optimism were more likely to undergo contralateral prophylactic mastectomy [44]. Psychological distress may be exacerbated by feelings of terror engendered by regular screening examinations, anticipation of treatment-related adverse effects, and fears of cancer recurrence, additional treatments, and death.
A recent Delphi study identified 4 characteristics of persistent fear: worry about cancer, high levels of worry, persistent worry, and hypervigilance of bodily symptoms [45]. Peace of mind is a relief from the anxiety engendered by the assumption that women are at risk. Strategies for obtaining peace of mind include those that eliminate the risk and therefore fear of contralateral cancer, and those that reduce anxiety.
By choosing contralateral prophylactic mastectomy, women with breast cancer were reported to be “regaining control” of their breast cancer and achieving peace of mind [39,46]. Emerging longitudinal data suggest that bilateral mastectomy may alleviate these concerns to a greater or lesser extent [43].
At MD Anderson Cancer Center , Parker et al. [49] reported that women with high levels of cancer distress, cancer concern, and body image concerns were more likely to have a contralateral prophylactic mastectomy; After surgery, only the worry about cancer decreased.
Among 43 women at the University of Minnesota, those undergoing contralateral prophylactic mastectomy had a significantly lower perceived risk of contralateral cancer after surgery (5.8% vs 17.3%) [50].
In a multicenter prospective study of 1,144 breast cancer patients in the Mastectomy Reconstruction Outcomes Consortium , women who had a contralateral prophylactic mastectomy had higher baseline levels of anxiety, but after surgery, there was no substantial difference between women who received the procedure and those who did not [51].
Among 506 women with unilateral ductal carcinoma in situ , or breast cancer, at the University Health Network in Toronto, Canada, there was no significant difference in postoperative psychological well-being and cancer distress among women who had a prophylactic mastectomy. contralateral and those that do not [52]. Further research is required to determine any benefit of bilateral mastectomy on cancer-related distress.
> Improvement in the results of breast reconstruction
Between 2000 and 2010, the proportion of women with contralateral mastectomies who also underwent breast reconstruction increased from 18.7% to 46.5% [58]. Access to breast reconstruction is a determinant of contralateral prophylactic mastectomy [3,11]. The plastic surgeon aims to optimize cosmetic results and symmetry.
There is no consensus among plastic surgeons as to whether bilateral or unilateral mastectomy with reconstruction achieves better cosmesis. Women undergoing contralateral prophylactic mastectomy do not necessarily have better long-term breast satisfaction, but breast reconstruction appears to influence that relationship. Among 1176 women in the Sister Study , body image scores were worse after contralateral prophylactic mastectomy than with unilateral lumpectomy, but improved with reconstruction [53].
Among 269 women with contralateral prophylactic mastectomy at the Mayo Clinic , adverse effects after 20 years were poor body image (31%), lack of femininity (24%), and lack of sexuality (23%); performing a reconstruction also improved these statistics [54,56].
In a survey of 7,619 women with prior breast cancer, those who had a contralateral prophylactic mastectomy had equivalent (if no reconstruction) or better (if reconstruction) satisfaction after 5 years relative to women who They didn’t have it; while women who underwent breast reconstruction had better satisfaction than those who did not have reconstruction [55].
The available studies examining patient-reported outcomes after breast surgery are limited by the lack of a control group that is followed prospectively [56], non-collection of comparable preoperative data [53-56], data collection at a single time point time [53,55], or no control for reconstruction [49], resulting in conflicting data reporting both improved [54,55] and worsened [49] satisfaction after contralateral prophylactic mastectomy.
After controlling for breast reconstruction, a prospectively controlled longitudinal cohort study reported no statistically significant difference in breast satisfaction at 12 months after surgery between women who had a bilateral versus unilateral mastectomy [52].
> Doctor’s preferences
Some doctors actively encourage the operation, while others believe it should be the patient’s choice. Among 1140 breast cancer patients in the Surveillance, Epidemiology and End Results registries of Georgia and Los Angeles, California, 32.3% reported that the option of contralateral prophylactic mastectomy was not substantially discussed. Women were dissatisfied when their surgeon recommended against performing a contralateral prophylactic mastectomy without giving a reason [74].
In a survey by the American Society of Plastic Surgeons , 87% of women who responded agreed that contralateral prophylactic mastectomy does not improve overall survival [59]. Most respondents agreed that women want contralateral prophylactic mastectomy because of a falsely perceived risk of increased contralateral cancer and death. However, many surgeons justified their adherence to the woman’s decision to have a contralateral prophylactic mastectomy because they respected her autonomy.
The influence of the plastic surgeon should not be underestimated. At the University of California, San Diego , 90 women with breast cancer were selected for a plastic surgery consultation after establishing a preliminary surgical plan with their surgical oncologist. After that consultation, 44% of women considered or required changes in their treatment, including changing from lumpectomy to mastectomy (45%), and wanting contralateral prophylactic mastectomy (28%) [60].
The surgical oncologist also appears to influence the woman’s decision-making process. Among 2402 women surveyed with unilateral ductal carcinoma in situ or breast cancer from Georgia and Los Angeles, California, 40.9% of women at average risk had considered contralateral prophylactic mastectomy.
In that group, 39.3% reported that their surgical oncologist had recommended against contralateral prophylactic mastectomy, of whom only 1.9% underwent the procedure. Conversely, 46.8% reported not having received a recommendation from their surgeon regarding contralateral prophylactic mastectomy; of those women, 19.0% went ahead with the procedure [37]. However, the interpretation of the patient-doctor consultation was made by the patients and it was not possible to verify what the conversation really involved.
In Canada, physicians do not seem to raise the issue of contralateral prophylactic mastectomy unless the patient mentions it, or is considering a unilateral mastectomy [11,42]. Canadian physicians have reported that, if a woman had expressed a desire for contralateral prophylactic mastectomy, it was difficult for her to change her mind. Likewise, 42% of physicians were not aware of guidelines related to contralateral prophylactic mastectomy [42].
Presumably, they were unaware of societal position statements discouraging the procedure in average-risk women with unilateral breast cancer [61-63]. Clinical oncologists and radiation therapists are less likely to support contralateral mastectomy than surgeons [42]. Kantor et al. [57] found that only 33% of clinical oncologists and 28% of radiation therapists supported supporting insurance coverage for contralateral mastectomy in average-risk women, compared with 55% of surgeons. oncologists and 76% of plastic surgeons.
Nurses appear to be more positive than doctors in expressing that bilateral prophylactic mastectomy should be considered an option for women who want the procedure [42].
> Social networks and culture
There is increasing information and opinion in mainstream media and social media about women suffering from breast cancer, including several celebrities [64]. Women can post their personal experiences with breast cancer online. Surgical posts related to contralateral prophylactic mastectomy increased from 2000 to 2016, coinciding with the increased number of women choosing the procedure [65].
Between April and May 2017, 155,000 Facebook users (mostly young women) in the US posted and shared 163,200 items related to contralateral prophylactic mastectomy. The content of these publications was related to affect (feeling anxious, worried, depressed and afraid), outcomes (death and survival benefit), complications (scar, infection and pain), body image and sexuality, and risk (carrier or non- BRCA carrier and family history). Much of the information was subjective and lacked supporting evidence [66].
Women can also turn to community forums, such as breastcancer.org and breastcancernow.org , for support and advice. These circles of influence have fostered a culture in which bilateral mastectomies are discussed and seen as a rational treatment option for sporadic unilateral breast cancer, despite the lack of endorsement from any professional body.
> Financing of contralateral prophylactic mastectomies
In the US, the majority of women who have had a contralateral prophylactic mastectomy have private health insurance. In Ontario, Canada, the provincial health ministry will pay for contralateral prophylactic mastectomy in breast cancer patients. It is unclear how payer affects contralateral prophylactic mastectomy rates, but the financial burden of potentially medically unnecessary contralateral prophylactic mastectomies deserves mention.
Between 2009 and 2013, in a database of commercially insured women and women with private Medicare supplemental insurance in the US, the additional cost of contralateral prophylactic mastectomy with reconstruction for women with unilateral breast cancer was u $s 11,872 [67]. Boughey et al. [68], examined OptumLabs , a large US commercial insurance database, and found that 2-year total costs were higher for women with bilateral mastectomy than with unilateral mastectomy, with alloplastic reconstruction (in both cases). s 106,711 vs u$s 97,218; P < 0.001) and autologous (u$s 114,725 vs u$s 87,874; P < 0.001).
An analysis of the Healthcare Cost and Utilization Project National Inpatient Sample , between 2009 and 2012, found that contralateral prophylactic mastectomy resulted in an additional cost of $20,775 for women with mastectomy and reconstruction for sporadic breast cancer. [69]. Among 904 women with stage III breast cancer at MD Anderson Cancer Center , the total cost increased by $7,749 for women with contralateral prophylactic mastectomy, compared with a matched group of women without that procedure [71].
Among 101 women who had surgery for unilateral breast cancer seen at the Yale Breast Center between June and August 2017, there was no statistically significant difference in out-of-pocket costs for women who had a contralateral prophylactic mastectomy versus those who they did not carry it out [72].
Contralateral prophylactic mastectomy, therefore, may be viewed by the lay woman as an acceptable treatment for unilateral breast cancer, because it is financially covered. Although the cost to patients is low, there are increased costs to the healthcare system, including management of complications, additional breast-related procedures, and loss of productivity [70].
| Conclusions |
Rates of bilateral mastectomy continue to increase in women with unilateral breast cancer, and that increase may represent a new normal.
The increased use of MRI for breast cancer staging and increased genetic testing at the time of diagnosis have marginally increased the number of women who are candidates for bilateral mastectomy, based on clinical indications. Risk prediction models are unlikely to have increased the number of women who are seen as having an objectively higher risk of contralateral breast cancer.
Most bilateral mastectomies are performed in women with unilateral breast cancer who are not at special risk for contralateral cancer. Based on this review, it seems unlikely that the number of contralateral prophylactic mastectomies being performed can be separated into groups, according to the different reasons why women choose the surgery, and count the number in each group, as many studies have made. Rather, several changes in society and in the provision of health services can act simultaneously and synergistically.
First, understanding cancer recurrence involves looking at 3 different risk estimates. It is a challenge for the patient and the doctor to deconstruct the risks of all 3: an ipsilateral recurrence, a distant recurrence and a contralateral cancer [41].
The anxiety generated by the general fear of cancer recurrence is focused on the contralateral cancer, because it is easier to conceptualize and provides a ready target on which to act, with the woman - therefore - taking control and ensuring your peace of mind. The higher the risk of distant recurrence, the more likely the patient will want to undergo a contralateral prophylactic mastectomy.
Second, women with breast cancer who are considering bilateral mastectomy can feel supported by their surgeons and the breast cancer survivor community. Many surgeons are willing to defer to the patient’s wishes in order to respect her autonomy. Medical and radiation oncologists are hesitant to support the operation, but surgeons are the gatekeepers.
There are guidelines written by professional bodies that advise against the operation in routine care, but surgeons may not be aware of these guidelines, or may not be influenced by their content. To the best of the authors of this work, there is also no policy that establishes that the guidelines must be followed to ensure good clinical practice. In Canada and the US, breast surgery and reconstruction are covered by public and private insurance, and most women have their expenses covered.
The authors believe that a second set of enabling factors is the emergence of a membership of breast cancer survivors, which is tacitly generated through online communities and social media. The patient will probably find like-minded women who will support her decision either way. Previously, these discussions tended to be within the private and confidential domain of the doctor-patient relationship. Information from the Internet and social circles is unlikely to be used to dissuade a woman from her chosen course, but rather to empower her to discuss her option with her doctors.
As clinicians and researchers, the authors of this work tend to focus on survival as the relevant end goal, while the patient prioritizes anxiety, fear, and quality of life. If medically unnecessary contralateral prophylactic mastectomy is to be reduced, in line with the Choosing Wisely recommendations [3], transformative social change is needed that addresses enabling factors at the patient, clinician, cultural, and systems levels.
Although funding structures are unlikely to change, education of doctors and patients can be improved. As part of the doctor-patient relationship, the authors recommend that surgeons explore a woman’s individual concerns and her reasons for wanting a preventive contralateral mastectomy.
A team-based approach is desirable. A personalized assessment of contralateral breast cancer risk can be used to distinguish between locoregional, contralateral, and distant recurrence. It may be helpful to inform the patient of the expected benefit from contralateral prophylactic mastectomy, as well as the anticipated costs and potential surgical complications [75,76].
There is emerging evidence that such discussion may reduce the number of bilateral mastectomies [37]. Emotional and psychosocial factors leading to contralateral mastectomy must also be addressed, as these may be barriers to change. All of these interventions are topics of future research.
Patient autonomy is the individual’s ability to make a decision uninfluenced. It can be argued that the decision for bilateral prophylactic mastectomy is not rational and has arisen from an overestimation of the true level of risk. However, respecting the patient’s autonomy, when a treatment decision seems irrational, is open to debate. Nor should one do harm, but rather act in a way that benefits the patient.
Surgeons may wish to optimize cosmetic results and/or reduce fear and anxiety, which are valuable end goals.
The literature is unclear on whether psychosocial functioning is improved, and cancer-related distress reduced, with contralateral prophylactic mastectomy; more research is needed. Physicians should consider these ethical principles when adhering to or rejecting a woman’s desire to undergo a contralateral prophylactic mastectomy.
