Highlights
- •Increasingly, patients diagnosed with unilateral breast cancer request CPM.
- •Here, a multidisciplinary panel of breast cancer experts provides guidance on CPM.
- •Patients should be counselled and treated at specialist breast centres.
- •Patients need to understand competing risks for contralateral breast cancer.
- •Patients need personalised information about CPM risk:benefit and a realistic plan.
Abstract
After a diagnosis of unilateral breast cancer, increasing numbers of patients are requesting contralateral prophylactic mastectomy (CPM), the surgical removal of the healthy breast after diagnosis of unilateral breast cancer. It is important for the community of breast cancer specialists to provide meaningful guidance to women considering CPM. This manifesto discusses the issues and challenges of CPM and provides recommendations to improve oncological, surgical, physical and psychological outcomes for women presenting with unilateral breast cancer: (1) Communicate best available risks in manageable timeframes to prioritise actions; better risk stratification and implementation of risk-assessment tools combining family history, genetic and genomic information, and treatment and prognosis of the first breast cancer are required; (2) Reserve CPM for specific situations; in women not at high risk of contralateral breast cancer (CBC), ipsilateral breast-conserving surgery is the recommended option; (3) Encourage patients at low or intermediate risk of CBC to delay decisions on CPM until treatment for the primary cancer is complete, to focus on treating the existing disease first; (4) Provide patients with personalised information about the risk:benefit balance of CPM in manageable timeframes; (5) Ensure patients have an informed understanding of the competing risks for CBC and that there is a realistic plan for the patient; (6) Ensure patients understand the short- and long-term physical effects of CPM; (7) In patients considering CPM, offer psychological and surgical counselling before surgery; anxiety alone is not an indication for CPM; (8) Eliminate inequality between countries in reimbursement strategies; CPM should be reimbursed if it is considered a reasonable option resulting from multidisciplinary tumour board assessment; (9) Treat breast cancer patients at specialist breast units providing the entire patient-centred pathway.
Graphical abstract
Graphical Abstract
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Keywords
1. Introduction
Contralateral prophylactic mastectomy (CPM), also referred to as contralateral risk-reducing mastectomy, describes the surgical removal of the unaffected breast in women who developed a unilateral primary breast cancer [
[1]
]. One should realise that a CPM generally implies a bilateral mastectomy, since breast conservation of the affected breast and a CPM is illogical. While CPM is a reasonable option for patients with BRCA1/2 germline mutations or other characteristics associated with a high risk of contralateral breast cancer (CBC) [[2]
], most available guidelines and position statements discourage CPM in low-to-average-risk women with unilateral early-stage breast cancer [3
, 4
, 5
, 6
, - Bjelic-Radisic V.
- Singer C.
- Tamussino K.
- et al.
Austrian Gynecologic Oncology Working Group
Contralateral prophylactic mastectomy in women with breast cancer without a family history or genetic predisposition: consensus statement from the Austrian Gynecologic Oncology Working Group of the Austrian Society of Obstetrics and Gynecology.
Contralateral prophylactic mastectomy in women with breast cancer without a family history or genetic predisposition: consensus statement from the Austrian Gynecologic Oncology Working Group of the Austrian Society of Obstetrics and Gynecology.
Wien Klin Wochenschr. 2019; 131: 233-236
7
, 8
, - National Comprehensive Cancer Network
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Version 8.2021 – September 13, 2021.
https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
Date accessed: November 22, 2021
9
]. Nevertheless, after a diagnosis of breast cancer, CPM is frequently one of the first questions raised by patients and increasingly women are requesting (and undergoing) CPM [10
, 11
, 12
, 13
]. In one clinic in The Netherlands, as many as one in three women wish to discuss CPM, with an estimated 10%–15% of patients requesting CPM (E. Rutgers, personal communication), although there are regional and cultural variations across Europe and published estimates are scarce.The increase in CPM has become particularly apparent following media publicity of high-profile women undergoing this procedure – the so-called ‘Angelina Jolie effect’ [
[5]
,[14]
,[15]
]. However, publicity of medical issues through influential advocates can increase anxiety as well as awareness. In many situations, requests for CPM create an uneasy balance for the surgeons between respecting patients' fears and wishes and the principle of primum non nocere (first, do no harm) [16
, 17
, 18
]. Counsellors and surgeons uncomfortable with performing CPM report concerns about the use of surgery as a primary prevention tool (a special case of ‘overtreatment’), an unfavourable risk:benefit ratio and inadequate patient understanding of the anticipated risks and benefits of CPM [[17]
]. In a US-based survey, two-thirds of women undergoing CPM reported no major genetic or familial risk factors for CBC [[19]
]. Furthermore, although the use of bilateral mastectomy has increased since the 2000s, most likely attributable to increased awareness of second breast cancer risk, this has had no measurable impact on mortality rates but has led to an increase in side effects [[20]
].In this European Breast Cancer Conference (EBCC) manifesto, we consider broad societal and biomedical misunderstandings regarding CPM, the challenges of discussing pros and cons, explaining risks, providing a realistic picture and responding to patients asking (or not) for CPM, and the ways in which healthcare professionals can balance patient autonomy and respect for patients' decisions with avoidance of unnecessary or inappropriate surgery.
2. CPM prevalence and determining factors
2.1 CPM prevalence
Numerous reports in the literature describe doubling to tripling of the number of patients in North America with unilateral early-stage breast cancer undergoing CPM (Appendix Table 1), despite the lack of evidence for improved outcomes [
20
, 21
, 22
, 23
, 24
, 25
, 26
, 27
, 28
]. The increase in CPM is particularly pronounced in younger white women [[21]
,[28]
,[29]
]. Affluent non-Hispanic white women, those with private health insurance and/or those with high socioeconomic status tend to seek more aggressive preventive care [[20]
].In Europe, data are scarce and there is less evidence of an increase in CPM [
[30]
]. Studies in Italy and Switzerland detected no increase over time [[31]
,[32]
], whereas more recent studies from the UK [[33]
] and a single centre in Romania [[34]
] reported increases in CPM, particularly among those at highest cancer risk. In many European countries, for example in German university centres, CPM is discussed primarily with BRCA1/2 mutation carriers diagnosed with breast cancer, with an overall uptake rate of approximately 20% that seems to be increasing (R. Schmutzler, personal communication based on data from approximately 7000 BRCA1/2 mutation carriers). Overall, CPM uptake in some European countries is reported to be much lower than in the USA [[35]
,[36]
], but anecdotally CPM rates appear to be rising across Europe.2.2 EUROPA DONNA survey on CPM usage and reasons
In light of this manifesto and to explore CPM usage and reasons behind the decision to undergo CPM in Europe, EUROPA DONNA distributed a survey to member societies in 47 countries in October and November 2021. Of the 636 women from 30 countries who responded, 79% came from Italy, Serbia or Slovenia, 87% were aged between 35 and 65 years and 446 had breast cancer. Among the 405 women who still had one or both breasts after the first breast cancer treatment, 46% had undergone CPM and 15% were still considering it. In respondents with breast cancer, the most frequently cited reasons for considering CPM were a BRCA1/2 mutation (cited 156 times) and worries about developing breast cancer again (135 times) or dying from breast cancer (44 times). The most frequently cited reasons for not considering CPM were low risk (cited 55 times), fear of operation (45 times) or regret (38 times) and body image (39 times). Less than half of the women (47%) for whom this was applicable felt that they had sufficient discussion about the potential risks and benefits of CPM and 33% said they had insufficient discussion (20% neutral).
3. Risk of CBC and effects of CPM on mortality and CBC risk
After a diagnosis of breast cancer, fear of CBC affects many women [
[19]
,37
, 38
, 39
]. CPM may be seen as a way of reducing this worry and bringing peace of mind [[18]
,[19]
,40
, 41
, 42
]. Nevertheless, patients should be informed and understand whether CPM provides a meaningful reduction in the risk of death or, at least, of a second primary CBC. In addition, they should be fully informed about the situations in which CPM is endorsed by professionals and about other risk-reduction strategies. The utility of CPM varies considerably according to the clinical situation, genetic profile and tumour biology. Although CPM reduces the risk of CBC, the absolute benefit is low when women are at low risk of developing a second primary cancer [[43]
] or at very high risk of progression of the first breast cancer.3.1 Risk factors for CBC
Compared with women not carrying BRCA1/2 mutations, those with BRCA1/2 germline mutations are at 3- to 4-fold increased cumulative risk of CBC [
44
, 45
, 46
]. Carriers of BRCA1 germline mutations are at higher cumulative risk of CBC than those with BRCA2 germline mutations, particularly when first breast cancer occurs at a young age [[44]
,[45]
,47
, 48
, 49
, 50
, 51
]. In patients with BRCA1/2 germline mutations, CPM reduces the risk of CBC by approximately 90% [[52]
,[53]
], may improve breast cancer-specific survival and overall survival (reported hazard ratios ranging from 0.37 to 0.52) [53
, 54
, 55
] and is generally considered a reasonable option [[3]
,[56]
]. A potential role for contralateral irradiation in BRCA1/2 mutation carriers who opt for unilateral surgery rather than CPM was suggested by a comparative two-arm trial [[57]
,[58]
]. Prophylactic salpingo-oophorectomy appeared to reduce the risk of breast cancer in patients with BRCA2 but not BRCA1 mutations in a prospective cohort [[59]
].Beyond BRCA1/2 germline mutations, predictors for developing CBC include deleterious germline mutations in TP53, PALB2 and CHEK2, a family history of breast cancer and a high polygenic risk score (PRS) [
[44]
,[50]
,60
, 61
, 62
, 63
, 64
, 65
]. Additional risk factors associated with CBC include high body mass index, parity, certain characteristics of the first breast cancer (larger tumour size, lobular morphology, oestrogen receptor-negative) and prior radiotherapy at a young age, whereas adjuvant chemotherapy, adjuvant endocrine therapy and older age at diagnosis are associated with decreased CBC risk [[63]
,[66]
]. The protective effects of systemic adjuvant treatment (e.g. taxane chemotherapy, aromatase inhibitors and tamoxifen) on the unaffected as well as the affected breast are well established [[67]
,[68]
] and should be considered when estimating the overall risk of CBC.3.2 Risk of CBC and value of CPM in the general population
The risk of CBC in breast cancer survivors without clear germline genetic predisposition (family history and/or gene mutations or a high PRS) is relatively low with an annual incidence of around 0.4% and a 5-year cumulative incidence of 1.9% [
[10]
,[51]
,68
, 69
, 70
]. Annual risk does not appear to vary substantially by age at diagnosis [[10]
], so the long-term cumulative risk is substantially higher for younger women. Risk is higher in black and Hispanic than non-Hispanic white women [[10]
,[71]
] but less is known about populations of other ethnicities.In the general breast cancer population, the risk of distant metastasis and death from the first breast cancer is typically higher than the risk of developing a second primary breast cancer [
[12]
,[43]
,[72]
,[73]
]. Moreover, there is no evidence that CPM improves overall survival compared with breast-conserving surgery or unilateral mastectomy on the tumour-bearing side in the general breast cancer population [[12]
,[22]
,[24]
,[74]
]. CPM does not reduce the risk of metastatic disease from the first breast cancer (or indeed death), yet often it is challenging for patients to disentangle the risks of ipsilateral recurrence, distant recurrence and CBC [[75]
]. Although this point may be difficult to communicate to patients, it is important, particularly as multidisciplinary teams may decline requests for CPM because of the low risk of CBC versus the relatively high risk of systemic relapse [[76]
].3.3 CBC risk prediction
While these figures give a broad picture of risk factors, they provide less guidance when discussing CPM with an individual patient. Several models for assessing the risk of CBC exist, including the Manchester formula [
[5]
], CBCRisk [[77]
,[78]
], PredictCBC [[79]
], BOADICEA [80
, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm version 5.
https://www.canrisk.org/
Date accessed: September 20, 2021
81
, 82
] and BRCAPRO [[83]
]. BOADICEA and PredictCBC incorporate the effect of multiple factors including important breast cancer risk genes and PRS (PRS313, including 313 single-nucleotide polymorphisms) [[81]
,[84]
,[85]
]. However, several have limited clinical value with only moderate discrimination [[86]
,[87]
]. BRCAPRO and BOADICEA do not consider the risk reduction associated with systemic treatment and relatively little is known about molecular predictors (based on genomic profiling of the first tumour) for CBC. Better tools for CBC prediction are required.- Recommendation: Communicate the best available risks in manageable timeframes to prioritise actions; better risk stratification and implementation of risk-assessment tools combining family history, genetic and genomic information, and treatment and prognosis of the first breast cancer are required
3.4 Relevance/influence of optimal surgery for first breast cancer on CPM decision
Breast-conserving surgery is considered the standard surgical approach for early-stage breast cancer and has shown survival outcomes at least equivalent to mastectomy [
88
, 89
, 90
, 91
, 92
, 93
, 94
]. Furthermore, less extensive surgery provides better quality of life and recovery and reduces the risk of complications. In BRCA1/2 mutation carriers, breast-conserving surgery appears to offer non-inferior disease-free, disease-specific and overall survival compared with mastectomy, although the risk of locoregional recurrence is higher with breast-conserving surgery [[95]
]. If mastectomy is not considered the optimal surgical strategy for the diseased breast, it is even more difficult to justify surgical removal of both the diseased and the healthy breast.- Recommendation: Reserve CPM for specific situations; in women not at high risk of CBC, ipsilateral breast-conserving surgery is the recommended option
3.5 Non-surgical risk reduction
Alternatives to CPM include primary preventive strategies, such as chemoprophylaxis and/or endocrine therapy, which improve survival, decrease the risk of recurrence and decrease the risk of CBC [
[13]
,[96]
]. Physical exercise and weight control are also effective in reducing the likelihood of a second breast cancer [[97]
]. Strategies aiming to minimise the impact of CBC through detection at an early stage include imaging-based screening (mammography, contrast-enhanced magnetic resonance imaging or, as recently proposed in the perioperative setting by the European Commission Initiative on Breast Cancer, contrast-enhanced mammography [[98]
]), depending on the risk group concerned [European Commission Initiative on Breast Cancer. Planning surgical treatment. Available at: https://healthcare-quality.jrc.ec.europa.eu/european-breast-cancer-guidelines/surgical-planning; 2021. [Accessed 24 April 2022].
99
, 100
, 101
] and in the future, potentially liquid biopsy-based approaches [[102]
,[103]
].4. Timing of decision-making, risk perception and competing risks
Generally, over time, the risk of progression of the first tumour declines while the risk of CBC varies, depending on the specific situation. Therefore, the optimal timing of decision-making should be taken into account when considering CPM.
Decision-making must be based on the best available risk prediction. In the case of a familial predisposition, genetic testing is a prerequisite. If the decision on CPM is to be included in primary therapy planning, patients must receive their genetic results rapidly, but this is often not the case [
[104]
]. Negative BRCA1/2 genetic test results substantially reduce the likelihood of women undergoing CPM [[104]
,[105]
]. In many countries, a shortage of genetic counsellors is hindering access to genetic testing. It is therefore particularly important that, as the cost of genetic testing decreases, clinicians involved in decision-making are literate in genetics and able to communicate genetic test results and provide risk-adjusted clinical recommendations [[106]
].If a patient requests CPM at the time of diagnosis, it is important to allow discussion of the request. However, clinicians should remind patients at the time of diagnosis that the top priority is treatment of the existing diagnosed cancer. Adjuvant systemic therapy has risk-reducing effects and thus there is greater urgency to ensure the completion of adjuvant therapy for an existing primary cancer than prophylactic surgery for a cancer that does not exist. Bilateral mastectomy brings a risk of delaying the start of adjuvant therapy, e.g. due to surgical complications [
[107]
]. Treatment delays can negatively affect oncological outcomes [[43]
]. For women with high-risk breast cancer, for example, those with node-positive disease, it is best to delay a CPM decision at least until after successful adjuvant systemic and locoregional radiation treatment. In addition, communicating and balancing the risk of invasive CBC and ipsilateral recurrence is important to determine the optimal timing for CPM.Unless the patient is at high risk, decisions concerning the contralateral breast should be delayed, providing the patient is reassured that such decisions are being postponed (particularly if adjuvant therapy is indicated) rather than ignored. The Manchester guidelines recommend that in most patients, any decision about CPM is deferred until completion of primary cancer treatment if possible, to avoid making a decision when most emotionally vulnerable [
[5]
]. A change in decision is not unusual and often women decide not to proceed with CPM.After CPM, the risk of breast cancer among women with BRCA1/2 germline mutation is <1% in symptomatic carriers and around 0.2% in asymptomatic carriers after a mean cancer-free interval of 3.6 years [
[108]
]. To allow patients to make an informed decision about the competing risks of disease progression of the first tumour (e.g. whether to postpone CPM if there is a high risk of recurrence), it is important they have reliable information about the risk of recurrence (e.g. calculated by PREDICT [[109]
,Predict: breast cancer.
https://breast.predict.nhs.uk/
Date accessed: July 10, 2022
[110]
] or other appropriate risk programmes) to compare with the risk of CBC within a manageable timeframe. For example, in advanced primary breast cancer, the risk of recurrence may initially be higher than the risk of second breast cancer, but this relationship may be reversed as the recurrence-free period increases. Consequently, it is not only the decision for or against CPM that matters, but also the identification of the optimal timing for CPM. Patients (particularly those without a known mutation) lacking reliable information about risk tend to overestimate their likelihood of developing another breast cancer, including CBC, and are more receptive to negative than positive outcomes [[13]
,[18]
,[37]
,111
, 112
, 113
]. Some women will go to any length to avoid being affected by breast cancer again [[114]
] and often patients are unaware that even after CPM, there remains a risk of around 1 in 1000 for developing breast cancer [[45]
,[115]
,[116]
]. Women who are not carriers of high-risk mutations pay less attention to the potential physical and psychological harms of CPM than the perceived benefits when assessing future cancer risk management strategies [[117]
].Differentiating between competing risks represents an important part of discussions and decision-making [
[118]
]. Competing risks, including those from a broader context unrelated to breast cancer, such as age-related comorbidities, provide an important framework for discussions with patients and reimbursement authorities, as well as surveillance considerations. Put simply, the higher the risk of CBC, the more favourable the risk:benefit ratio for CPM. For example, few healthcare professionals would reject a request for CPM from a 37-year-old woman with a germline BRCA1 mutation and a T1N0 tumour, whereas most would discourage CPM for a 55-year-old woman with a T2N2 tumour and no germline alterations associated with high risk.- Recommendation: Encourage patients at low or intermediate risk of CBC to delay decisions on CPM until treatment for the primary cancer is complete, to focus on treating the existing disease first
- Recommendation: Provide patients with personalised information about the risk:benefit balance of CPM in manageable timeframes
- Recommendation: Ensure patients have an informed understanding of the competing risks for CBC and that there is a realistic plan for the patient
5. Impact of CPM
5.1 Physical impact of surgery
Although most women are aware of the risks of synthetic implants [
[119]
], including anaplastic large cell lymphoma, squamous cell carcinoma and capsular contracture [[120]
,[121]
], few patients are fully aware that bilateral nipple and skin-sparing procedures involve major surgery, and many do not appreciate the risks of surgery and the long recovery period. Compared with unilateral mastectomy, bilateral mastectomy is associated with a higher risk of complications [Food and Drugs Administration. Risks and complications of breast implants. Available at: https://www.fda.gov/medical-devices/breast-implants/risks-and-complications-breast-implants; 2022. [Accessed 18 October 2022].
122
, 123
, 124
, 125
], a higher transfusion rate [[126]
], increased risk of emergency room visits [[127]
], significantly longer hospital stays [[126]
,[128]
] and a higher risk of rehospitalisation or re-operation [[122]
]. Acute or early-onset complications of surgery include tissue/skin flap necrosis, wound dehiscence, infection, haematoma, bleeding, seroma, cellulitis and more general surgical risks, such as deep vein thrombosis and anaesthetic complications [[3]
,[129]
].In the longer term, chronic effects of surgery include loss of breast sensation, loss of sensitivity of the areola–nipple complex, possible paraesthesia, capsular contracture and pain [
[116]
,[130]
]. Patients should be made aware that breastfeeding and lactation will not be possible. CPM may also necessitate further surgery to address late complications or correct imperfections. A notable proportion of patients require unanticipated re-operation after CPM, most often related to implants [[131]
]. The risk of re-operation is modestly increased with bilateral compared with unilateral mastectomy [[126]
]. Patients should be cognisant of these risks when electing for CPM (implying bilateral mastectomy) as they may underestimate the extent of the procedure and severity of pain [[18]
]. Even among women who felt sufficiently informed about recovery expectations, many reported underestimating the challenges they would encounter after surgery [[132]
].- Recommendation: Ensure patients understand the short- and long-term physical effects of CPM
5.2 Psychological impact of CPM
Numerous studies in North America have explored reasons for women choosing to undergo CPM. There are limited available data from Europe, however, and given the differences in CPM uptake, we cannot necessarily extrapolate these findings. Unfortunately, few registries collect information on reasons for choosing CPM. In a Dutch study of women at high risk of hereditary breast cancer considering CPM, many patients cited reduction in cancer risk and anxiety about cancer returning as the reasons for undergoing CPM [
[133]
]. In our survey, 44% of women who reported having undergone CPM indicated that worry about developing breast cancer again was at least one of their considerations.Most studies from North America report that the main factors leading to the decision to undergo CPM are anxiety about recurrence [
[134]
] and a desire to reduce or eliminate CBC risk [[42]
,[135]
]. Based on the evidence presented above, however, risk reduction may be minimal or even non-existent, except for patients who carry high-risk mutations (and possibly those with a strong family history of breast cancer without known mutations).While some guidelines state that CPM may be considered to manage extreme anxiety [
[3]
], surgery may seem a rather extreme treatment option for anxiety. Moreover, worries may not be alleviated by CPM, undermining the rationale for CPM in this scenario. Interestingly, physicians with low knowledge of the risk of CBC or recurrence were more likely to consider CPM to be indicated in patients with high anxiety about recurrence than physicians with high knowledge of the risks [[136]
]. Reducing fear and anxiety may be considered a valuable endpoint, but studies evaluating the impact of CPM on psychosocial functioning and cancer-related distress provide contradictory results [- Kantor O.
- Chang C.
- Bleicher R.J.
- et al.
National Accreditation Program for Breast Centers Data Working Group
Physician knowledge of breast cancer recurrence and contralateral breast cancer risk is associated with increased recommendations for contralateral prophylactic mastectomy: a survey of physicians at NAPBC-accredited centers.
Physician knowledge of breast cancer recurrence and contralateral breast cancer risk is associated with increased recommendations for contralateral prophylactic mastectomy: a survey of physicians at NAPBC-accredited centers.
Ann Surg Oncol. 2019; 26: 3080-3088
[137]
]. Several studies suggest that fear of cancer recurrence remains moderate or high for as long as 20 years after CPM, despite being one of the most commonly cited reasons for undergoing CPM [[39]
]. CPM should not be considered as an intervention to address anxiety. A multidisciplinary approach, including psychological assessment and information on the effectiveness (or not) of CPM in terms of risk reduction, may be needed when responding to a request for the procedure. Psychological interventions may be more important than surgery to manage the fear of recurrence, providing a less invasive alternative to CPM [[138]
], and patients should receive surgical and psychological counselling and perhaps the opportunity to speak to patients who have already undergone CPM or who have chosen breast conservation and watchful waiting for the treated and contralateral breast. In addition, people typically show bias to defend previously made irreversible decisions, and therefore it is perhaps more interesting to explore topics that patients wish they had known or would communicate to others going through the same decision-making process [[139]
].The decision to undergo CPM is often prompted by a desire to attain breast symmetry [
[3]
,[13]
,[30]
,[132]
], particularly in younger and/or more educated women [[140]
]. In a recent UK survey, 30 (52%) of 58 healthcare professionals agreed that patients should be offered the choice of CPM as a means of achieving symmetry [[141]
]. However, women should be aware of other ways to address asymmetry, such as breast reduction [[11]
], which may preserve sensation and be associated with fewer surgical and wound complications [[3]
]. In addition, most women newly diagnosed with breast cancer can be treated optimally with breast conservation (including radiation therapy), typically with good cosmetic outcomes. In this clinical situation, a request for CPM would imply a bilateral mastectomy (usually skin- or nipple-sparing with reconstruction). This represents major surgery compared with the relatively minor procedure of local tumour excision with radiotherapy, which is associated with minimal side effects yet identical long-term oncological outcomes. In this setting, breast-conserving surgery (and possible contralateral breast reduction) is the safest and best way to maintain symmetry.Other explanations for choosing CPM include avoiding the anxiety, psychological burden and constant reminder of previous cancer associated with ongoing surveillance and awaiting breast cancer screening results [
[30]
,[132]
,[142]
], mistrust of surveillance to detect future cancers [[5]
,[42]
,[141]
,[143]
] and avoiding potential future chemotherapy [[141]
]. Frequent screening, anticipated side effects of treatment, and fear of cancer recurrence, further therapy and death can exacerbate psychological distress [[75]
]. It is important that physicians are sympathetic to patients' concerns and fears [[132]
]. While CPM may alleviate some of these concerns to a greater or lesser extent, cancer distress, poor psychological well-being, feelings of reduced quality of life and femininity, body image dissatisfaction and other concerns may persist [[75]
,[114]
,[124]
,[144]
,[145]
].Some women view mastectomy as a way of turning a negative life experience into an opportunity for aesthetic improvement, regaining control over their body or providing psychological and physical freedom [
[16]
]. However, these can be unmet expectations possibly related to the lack of in-depth information about the difference between breast augmentation only for cosmetic purposes and mastectomy for oncological reasons, a difference that should be highlighted when discussing CPM with the patients. Paradoxically, CPM may alleviate the sense of anguish at loss from the first mastectomy. It has also been suggested that a general fear of cancer recurrence is focused on the contralateral breast because this represents an easily conceptualised, operable target; removal of the contralateral breast can give the woman a sense of taking control and reclaiming peace of mind [[75]
].Personality traits such as neuroticism influence achieved body image and quality of life, illustrating the breadth of factors affecting patient-reported outcomes [
[146]
]. Some women with a good cosmetic result are very unhappy with their surgery, whereas others are content with a relatively poor cosmetic outcome. While most patients undergoing CPM expressed satisfaction with their decision and low regret, satisfaction was lower in women with surgical complications, a poor cosmetic result, a diminished sense of sexuality, diminished body image or lack of information about surveillance [[39]
,[131]
,[147]
]. A considerable proportion of patients said that surgical outcomes were worse than expected, including worse sense of sexuality or self-consciousness [[18]
], or that reconstruction after CPM did not meet their expectations, which may have been unrealistic in relation to sexuality, feeling that breasts were part of their body and risk of surgical complications [[39]
]. Women also mentioned a desire for greater detail about the actual appearance of reconstructed breasts, the incidence of multiple surgical procedures, the effect of losing all nipple sensation, and surveillance and prophylaxis options [[139]
,[147]
]. Patients with particular personality traits during discussions about breast reconstruction may benefit from early referral to psychosocial counselling or psychologist-led patient support groups. Presurgical psychological assessment should cover patients' understanding of the CPM procedure and cancer risk, the potential physical and emotional impact of surgery, informed decision-making, and past/current psychological issues (anxiety and body image) [[148]
]. Particular attention to appearance-related concerns may be important in younger, more educated women [[140]
].Psychological impact is not limited to patients. Many prejudices exist and sometimes surgeons who are anxious about the risk of CBC may encourage patients to undergo CPM. The surgeon's advice and attitude are additional important factors influencing patients' decisions regarding CPM [
[149]
]. Surgeons with a mean annual breast surgery caseload ≤10 were more likely to perform mastectomy than surgeons with higher caseloads [[150]
].- Recommendation: In patients considering CPM, offer psychological and surgical counselling before surgery; anxiety alone is not an indication for CPM
6. Reimbursement
For women in certain social or economic settings, the question of reimbursement is important when considering CPM. In some healthcare and private insurance systems, the high costs of CPM are not reimbursed even in BRCA1/2 mutation carriers, whereas in other countries, such as the US, there is sometimes a financial incentive for surgeons to recommend CPM even if not oncologically indicated. In many countries, including Austria, Croatia, Slovenia and Sweden, CPM is reimbursed if the clinician considers the procedure to be supported from a medical perspective. In Germany, an independent second opinion with comprehensive counselling from a specialised centre to secure non-directive and appropriate risk prediction and communication is recommended. It is, therefore, important to mention reimbursement when discussing CPM with the patient. In The Netherlands, particular risk profiles should trigger a discussion with the patient about CPM, and if this option is selected, it is reimbursed, whereas in Greece, CPM is not reimbursed, even if recommended by the clinician.
- Recommendation: Eliminate inequality between countries in reimbursement strategies. CPM should be reimbursed if it is considered a reasonable option resulting from multidisciplinary tumour board assessment
7. Better communication with patients
Surgeons should be aware of the impact they may have on understanding risk and regret. Surgeons can empower patients to incorporate accurate risk assessment and individual patient preferences in their decision-making [
[12]
]. In a US-based survey, the proportion of patients without high genetic risk or an identified mutation who ultimately underwent CPM was 10-fold lower in those who reported a surgeon recommendation against CPM versus those who received no recommendation for or against [[40]
]. Importantly, patients advised against CPM by their surgeon did not report substantially greater dissatisfaction with the surgical decision if there was an open discussion [[151]
]. The greatest dissatisfaction was reported if surgeons advised against CPM without discussion. According to reports in the literature, in one-third of cases, there is no substantial discussion about CPM between surgeons and their patients [[12]
,[151]
].Behavioural science suggests that patient decision-making can be improved through the language used for careful communication of low-probability events [
[113]
]. Use of appropriate language is very important when communicating losses and gains to patients. Decision aids appropriate to patients' literacy and education levels can help in providing balanced information to support an informed choice [[11]
,[152]
]. Use of absolute frequencies and diagrams (e.g. infographics, iconography) can help in communicating risk visually and objectively. Decision aids may also reassure patients who have decided to postpone their decision, perhaps because they highlight the limited benefits associated with CPM and safe alternatives [[11]
]. Patients may also refer to such resources at a later date if worries about CBC re-emerge. Information processing may be affected by the stress and emotions of a diagnosis [[153]
,[154]
]. Women involved in studies of decision aids have emphasised the need for access to these tools to support informed choice and the importance of discussing the potential downsides of CPM alongside benefits [[11]
,[155]
]. An understanding of the role of emotion in decision-making is also critical, and empathic communication may enable surgeons to help patients think about risks in the context of intense emotions [[156]
].Recent studies have highlighted differences between various specialties advising patients during their decision-making. In particular, plastic surgeons were more likely or comfortable than other surgeons and oncologists to recommend CPM [
157
, - Yao K.
- Bleicher R.
- Moran M.
- et al.
National Accreditation Program for Breast Centers Data Working Group
Differences in physician opinions about controversial issues surrounding contralateral prophylactic mastectomy (CPM): a survey of physicians from accredited breast centers in the United States.
Differences in physician opinions about controversial issues surrounding contralateral prophylactic mastectomy (CPM): a survey of physicians from accredited breast centers in the United States.
Cancer Med. 2020; 9: 3088-3096
158
, 159
], emphasising the need for oncological awareness among plastic surgeons influencing patient decision-making, and the need for active involvement of plastic surgeons in the shared decision-making process [[160]
]. Similarly, in a survey of members of the German Cancer Society, one-third of respondents communicated bilateral mastectomy or CPM as an option for non-BRCA1/2 mutation carriers who were healthy women or had unilateral breast cancer, respectively [[106]
].- Recommendation: Treat breast cancer patients at specialist breast units providing the entire patient-centred pathway
8. Conclusion: shared decision-making
An urgent priority for the medical and surgical community is to overturn misconceptions about the potential benefits and harms of CPM for the management of unilateral breast cancer. Supporting patient autonomy may lead to excessive surgery if the patient is misinformed, so it is important that shared decision-making involves actively ensuring that patients have accurate knowledge rather than deferring to misinformed wishes [
[40]
]. Careful discussion about the risks of recurrence, CBC, mortality, surgical complications and sequelae, and psychological outcomes is critical to ensure patients are empowered to make an informed decision. Importantly, risk estimates should be given in absolute numbers and for manageable periods of time [[106]
]. In this context, it is particularly important to weigh the risk of recurrence of the already diagnosed breast cancer against the risk of new disease. The principle of autonomy should not prevail over ethical principles [[16]
], and respecting autonomy when a treatment decision is based on risk overestimation is debatable [[75]
].Patients should have realistic expectations about CPM. Patients require time to consider and discuss options based on thorough knowledge and understanding of the risks [
[12]
,[113]
,[161]
,[162]
]. Even among highly educated women, awareness and understanding of risk leave much room for improvement [[111]
], and tools to help communicate risk may be helpful [[163]
]. Investing time in educating patients is essential, given that higher levels of breast cancer knowledge are associated with decreased likelihood of choosing CPM [European Commission Initiative on Breast Cancer. Inviting and informing women about screening. Available at: https://healthcare-quality.jrc.ec.europa.eu/european-breast-cancer-guidelines/Invitation-to-screening-and-decision-aid; 2021. [Accessed 9 January 2022].
[164]
]. It may take several consultations to fully inform the patient about potential outcomes, the risks of surgery and the lack of impact on fear of recurrence [[39]
], and a discussion guide based on that recommended by the American Society of Breast Surgeons [[4]
] may be helpful (Table 1). Of note, the Manchester guidelines include a ‘cooling-off period’ as an important step within the shared decision-making process [[5]
].Table 1CPM discussion guide for patients considering CPM for unilateral breast cancer who are not at high risk of CBC (reproduced from the American Society of Breast Surgeons guideline [
[4]
]).| CPM is not 100% protective against cancer forming in your other breast |
| CPM will not improve your cure rate for your known cancer |
| CPM will not reduce your risk of cancer returning from your known cancer |
| CPM will not reduce your need for other cancer treatments for your known cancer (adjuvant therapy), if indicated |
| The risk of surgical complications at the surgical site (such as bleeding, infection, healing complications and chronic pain) is approximately twice as high when CPM is performed |
| CPM results in permanent numbness of the chest wall (and nipple if preserved) |
| CPM with reconstruction will result in an increased number of operations |
| Complications from CPM may delay treatment of your known cancer, including chemotherapy and radiation that may be recommended after surgery |
| CPM may be associated with negative impact on physical, emotional and sexual well-being. Approximately 10% of women regret their decision to undergo CPM |
| Breastfeeding will not be possible after CPM |
| Women who undergo CPM will not need mammograms or routine breast imaging for cancer screening after surgery |
CPM, contralateral prophylactic mastectomy.
By working as a multidisciplinary team involving oncologists, surgeons, clinical geneticists, radiologists, radiation therapy specialists, clinical psychologists, breast care nurses and reconstructive nurses in a specialist breast cancer centre, the steps described above may help to stem the tide of CPM.
9. Pros and cons summary
For certain women with genetic characteristics or family history, CPM offers a meaningful reduction in the risk of CBC and death from breast cancer and the balance of benefit versus risk favours CPM. However, for a large proportion of women, fear, exaggerated perception of risk, lack of awareness of negative outcomes of CPM, and inadequate discussion and counselling are leading women to undergo CPM despite the cons outweighing the pros. Multidisciplinary teams are critical in helping women to understand competing risks, explaining pros and cons, and working together to provide the best possible oncological, physical and psychological outcomes for women diagnosed with unilateral breast cancer.
Funding
This work was supported by the European Breast Cancer Council, which funded medical writing support provided by Jennifer Kelly. No grant number is applicable. BW is supported in part by Breast Cancer Research Foundation, Cycle for Survival, and NIH/NCI P50 CA247749 01 grants; and a Cancer Center Support Grant of the NIH/NCI (P30CA008748; MSK).
Conflict of interest statement
ITR reports honoraria from Sirius and MSD (nothing related to this manuscript). FS reports ad hoc membership of scientific advisory board for Bayer Healthcare and research/grant support from General Electric Healthcare and Bracco Imaging, all outside the submitted work. BW reports a research grant by Repare Therapeutics, outside the scope of this manuscript. MKS, JEK, AB, DAC, JdB, DFE, BVO, FP, RS, TS and EJTR declare no conflict of interest.
Acknowledgements
The authors thank EUROPA DONNA for circulating the questionnaires, Pat Vanhove for organisational support, and the European Breast Cancer Council.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
- Multimedia component 1
References
- Risk-reducing mastectomy.JAMA. 2021; 325: 1781-1782
- Prophylactic surgery: for whom, when and how?.Breast Care (Basel). 2017; 12: 379-384
- Contralateral prophylactic mastectomy (CPM) consensus statement from the American Society of Breast Surgeons: data on CPM outcomes and risks.Ann Surg Oncol. 2016; 23: 3100-3105
- Contralateral prophylactic mastectomy consensus statement from the American Society of Breast Surgeons: additional considerations and a framework for shared decision making.Ann Surg Oncol. 2016; 23: 3106-3111
- The Manchester guidelines for contralateral risk-reducing mastectomy.World J Surg Oncol. 2015; 13: 237
- Contralateral prophylactic mastectomy in women with breast cancer without a family history or genetic predisposition: consensus statement from the Austrian Gynecologic Oncology Working Group of the Austrian Society of Obstetrics and Gynecology.Wien Klin Wochenschr. 2019; 131: 233-236
- Choosing Wisely®.(Available at:)
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Version 8.2021 – September 13, 2021.(Available at:)https://www.nccn.org/professionals/physician_gls/pdf/breast.pdfDate accessed: November 22, 2021
- Indications for contralateral prophylactic mastectomy: a consensus statement using modified Delphi methodology.Ann Surg. 2018; 267: 271-279
- The risk of contralateral breast cancer: a SEER-based analysis.Br J Cancer. 2021; 125: 601-610
- The implementation of a decision aid for women with early-stage breast cancer considering contralateral prophylactic mastectomy: a pilot study.Patient Educ Couns. 2022; 105: 74-80
- Contralateral prophylactic mastectomy: a narrative review of the evidence and acceptability.Breast. 2021; 56: 61-69
- Contralateral risk-reducing mastectomy in sporadic breast cancer.Lancet Oncol. 2013; 14: e262-e269
- The Angelina Jolie effect: how high celebrity profile can have a major impact on provision of cancer related services.Breast Cancer Res. 2014; 16: 442
- Trends in use of risk-reducing mastectomy in a context of celebrity decisions and media coverage: an observational study in the United States and Australia.Health Serv Res. 2018; 53: 2682-2695
- Comment répondre aux demandes de mastectomie prophylactique controlatérale après un cancer du sein hors prédisposition génétique? Perspectives éthiques et cliniques.Psycho-Oncologie. 2019; 13: 129-135
- Surgeons' perspectives of contralateral prophylactic mastectomy.Ann Surg Oncol. 2016; 23: 2779-2787
- Perceptions, knowledge, and satisfaction with contralateral prophylactic mastectomy among young women with breast cancer: a cross-sectional survey.Ann Intern Med. 2013; 159: 373-381
- Social and clinical determinants of contralateral prophylactic mastectomy.JAMA Surg. 2014; 149: 582-589
- Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998-2011.JAMA. 2014; 312: 902-994
- Contralateral prophylactic mastectomy and survival: report from the National Cancer Data Base, 1998-2002.Breast Cancer Res Treat. 2013; 142: 465-476
- Growing use of contralateral prophylactic mastectomy despite no improvement in long-term survival for invasive breast cancer.Ann Surg. 2017; 265: 581-589
- State variation in the receipt of a contralateral prophylactic mastectomy among women who received a diagnosis of invasive unilateral early-stage breast cancer in the United States, 2004-2012.JAMA Surg. 2017; 152: 648-657
- Contralateral prophylactic mastectomy provides no survival benefit in young women with estrogen receptor-negative breast cancer.Ann Surg Oncol. 2014; 21: 3231-3239
- Canada follows the US in the rise of bilateral mastectomies for unilateral breast cancer: a 23-year population cohort study.Breast Cancer Res Treat. 2021; 185: 517-525
- Trend and survival benefit of contralateral prophylactic mastectomy among men with stage I-III unilateral breast cancer in the USA, 1998-2016.Breast Cancer Res Treat. 2021; 190: 503-515
- Trends in contralateral prophylactic mastectomy utilization for small unilateral breast cancer.J Surg Res. 2021; 262: 71-84
- Variation in contralateral prophylactic mastectomy rates according to racial groups in young women with breast cancer, 1998 to 2011: a report from the National Cancer Database.J Am Coll Surg. 2015; 221: 187-196
- Increasing rates of contralateral prophylactic mastectomy among patients with ductal carcinoma in situ.J Clin Oncol. 2009; 27: 1362-1367
- Mastectomy for risk reduction or symmetry in women without high risk gene mutation: a review.Int J Surg. 2018; 50: 60-64
- Increasing rates of contralateral prophylactic mastectomy – a trend made in USA?.Eur J Surg Oncol. 2012; 38: 296-301
- Mastectomy patterns, but not rates, are changing in the treatment of early breast cancer. Experience of a single European institution on 2315 consecutive patients.Breast. 2018; 39: 1-7
- The Angelina Jolie effect: contralateral risk-reducing mastectomy trends in patients at increased risk of breast cancer.Sci Rep. 2021; 11: 2847
- Contralateral prophylactic mastectomy in patients with breast cancer.Chirurgia (Bucur). 2021; 116: 73-83
- Predictors of contralateral prophylactic mastectomy in women with a BRCA1 or BRCA2 mutation: the Hereditary Breast Cancer Clinical Study Group.J Clin Oncol. 2008; 26: 1093-1097
- International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation.Br J Cancer. 2019; 121: 15-21
- Perceptions of contralateral breast cancer: an overestimation of risk.Ann Surg Oncol. 2011; 18: 3129-3136
- Fear of recurrence and perceived survival benefit are primary motivators for choosing mastectomy over breast-conservation therapy regardless of age.Ann Surg Oncol. 2012; 19: 3246-3250
- Contralateral prophylactic mastectomy for unilateral breast cancer in women at average risk: systematic review of patient reported outcomes.Psychooncology. 2020; 29: 960-973
- Contralateral prophylactic mastectomy decisions in a population-based sample of patients with early-stage breast cancer.JAMA Surg. 2017; 152: 274-282
- Surgical decision-making surrounding contralateral prophylactic mastectomy: comparison of treatment goals, preferences, and psychosocial outcomes from a multicenter survey of breast cancer patients.Ann Surg Oncol. 2021; 28: 8752-8765
- Emotion and contralateral prophylactic mastectomy: a prospective study into surgical decision-making.Psychooncology. 2022; 31: 1711-1718
- Contralateral prophylactic mastectomy in breast cancer: what to discuss with patients.Expert Rev Anticancer Ther. 2020; 20: 159-166
- The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study.Breast Cancer Res. 2012; 14: R156
- Impact of age at primary breast cancer on contralateral breast cancer risk in BRCA1/2 mutation carriers.J Clin Oncol. 2016; 34: 409-418
- Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.JAMA. 2017; 317: 2402-2416
- Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.J Clin Oncol. 2004; 22: 2328-2335
- Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer.Br J Cancer. 2000; 83: 384-386
- EMBRACE. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE.J Natl Cancer Inst. 2013; 105: 812-822
- Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers.J Clin Oncol. 2009; 27: 5887-5892
- German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance.Int J Cancer. 2020; 146: 999-1009
- Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers.Br J Cancer. 2005; 93: 287-292
- Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis.Int J Cancer. 2015; 136: 668-677
- Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis.BMJ. 2014; 348: g226
- Contralateral mastectomy improves survival in women with BRCA1/2-associated breast cancer.Breast Cancer Res Treat. 2013; 140: 135-142
- Breast cancer genetics and indications for prophylactic mastectomy.Surg Clin North Am. 2018; 98: 677-685
- Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer.Ann Oncol. 2019; 30: 412-417
- Nonsurgical options for risk reduction of contralateral breast cancer in BRCA mutation carriers with early-stage breast cancer.J Clin Oncol. 2022; JCO2201609
- Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.Breast Cancer Res. 2020; 22: 8
- The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.Genet Med. 2021; 23: 1726-1737
- Clinical implications of germline mutations in breast cancer: TP53.Breast Cancer Res Treat. 2018; 167: 417-423
- A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes.Cancer. 2017; 123: 1721-1730
- Risk factors for metachronous contralateral breast cancer: a systematic review and meta-analysis.Breast. 2019; 44: 1-14
- CHEK2∗1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer.J Clin Oncol. 2012; 30: 4308-4316
- Breast cancer polygenic risk score and contralateral breast cancer risk.Am J Hum Genet. 2020; 107: 837-848
- The impact of lifestyle and reproductive factors on the risk of a second new primary cancer in the contralateral breast: a systematic review and meta-analysis.Cancer Causes Control. 2020; 31: 403-416
- Tamoxifen for early breast cancer: an overview of the randomised trials.Lancet. 1998; 351: 1451-1467
- The influence of adjuvant systemic regimens on contralateral breast cancer risk and receptor subtype.J Natl Cancer Inst. 2019; 111: 709-718
- New malignancies following breast cancer.in: Curtis R.E. Freedman D.M. Ron E. New malignancies among cancer survivors: SEER Cancer Registries, 1973-2000. National Cancer Institute, NIH publication 05-5302, Bethesda, MD2006: 181-206
- Patterns of occurrence and outcomes of contralateral breast cancer: analysis of SEER data.J Clin Med. 2018; 7: 133
- Race, ethnicity and risk of second primary contralateral breast cancer in the United States.Int J Cancer. 2021; 148: 2748-2758
- Inflammatory breast cancer: high risk of contralateral breast cancer compared to comparably staged non-inflammatory breast cancer.Breast Cancer Res Treat. 2011; 129: 117-124
- Current knowledge on contralateral prophylactic mastectomy among women with sporadic breast cancer.Oncologist. 2011; 16: 935-941
- Risk-reducing mastectomy for the prevention of primary breast cancer.Cochrane Database Syst Rev. 2018; 4: CD002748
- Bilateral mastectomy in women with unilateral breast cancer: a review.JAMA Surg. 2021; 156: 569-576
- A multidisciplinary team approach minimises prophylactic mastectomy rates.Eur J Surg Oncol. 2015; 41: 1005-1012
- A model for individualized risk prediction of contralateral breast cancer.Breast Cancer Res Treat. 2017; 161: 153-160
- Validation of a personalized risk prediction model for contralateral breast cancer.Breast Cancer Res Treat. 2018; 170: 415-423
- Prediction and clinical utility of a contralateral breast cancer risk model.Breast Cancer Res. 2019; 21: 144
- Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm version 5.(Available at:)https://www.canrisk.org/Date accessed: September 20, 2021
- BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors.Genet Med. 2019; 21 (Erratum in: Genet Med. 2019;21(6):1462): 1708-1718
- CanRisk Tool–a web interface for the prediction of breast and ovarian cancer risk and the likelihood of carrying genetic pathogenic variants.Cancer Epidemiol Biomarkers Prev. 2021; 30: 469-473
- Assessing the added value of breast tumor markers in genetic risk prediction model BRCAPRO.Breast Cancer Res Treat. 2012; 133: 347-355
- Polygenic risk scores for prediction of breast cancer and breast cancer subtypes.Am J Hum Genet. 2019; 104: 21-34
Giardiello D, Hooning MJ, Hauptmannet M, et al. PredictCBC-2.0: a contralateral breast cancer risk prediction model developed and validated in ∼200,000 patients. Unpublished results.
- Prediction of contralateral breast cancer: external validation of risk calculators in 20 international cohorts.Breast Cancer Res Treat. 2020; 181: 423-434
- Performance of breast cancer risk-assessment models in a large mammography cohort.J Natl Cancer Inst. 2020; 112: 489-497
- Overall survival according to type of surgery in young (≤40 years) early breast cancer patients: a systematic meta-analysis comparing breast-conserving surgery versus mastectomy.Breast. 2015; 24: 175-181
- Early-stage young breast cancer patients: impact of local treatment on survival.Int J Radiat Oncol Biol Phys. 2011; 81: e553-e559
- Survival after lumpectomy and mastectomy for early stage invasive breast cancer: the effect of age and hormone receptor status.Cancer. 2013; 119: 1402-1411
- Breast conserving therapy and mastectomy revisited: breast cancer-specific survival and the influence of prognostic factors in 129,692 patients.Int J Cancer. 2018; 142: 165-175
- Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2019; 30 (Erratum in: Ann Oncol. 2019;30(10):1674. Erratum in: Ann Oncol. 2021;32(2):284): 1194-1220
- Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.N Engl J Med. 2002; 347: 1233-1241
- 10-year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study.Lancet Oncol. 2016; 17: 1158-1170
- Combined breast conservation therapy versus mastectomy for BRCA mutation carriers – a systematic review and meta-analysis.Breast. 2021; 56: 26-34
- Outcome without any adjuvant systemic treatment in stage I ER+/HER2- breast cancer patients included in the MINDACT trial.Ann Oncol. 2022; 33: 310-320
- Contralateral risk reducing mastectomy in patients with sporadic breast cancer. Benefits and hazards.Eur J Surg Oncol. 2016; 42: 913-918
European Commission Initiative on Breast Cancer. Planning surgical treatment. Available at: https://healthcare-quality.jrc.ec.europa.eu/european-breast-cancer-guidelines/surgical-planning; 2021. [Accessed 24 April 2022].