Contralateral risk reducing mastectomy in Non-BRCA-Mutated patients
-
Giuseppe Falco
, Nicola Rocco, Daniele Bordoni
, Luigi Marano , Antonello Accurso , Claudio Buccelli , Pierpaolo Di Lorenzo , Emanuele Capasso , Fabio Policino , Massimo Niola und Guglielmo Ferrari
Abstract
The use of contralateral risk reducing mastectomy (CRRM) is indicated in women affected by breast cancer, who are at high risk of developing a contralateral breast cancer, particularly women with genetic mutation of BRCA1, BRCA2 and P53. However we should consider that the genes described above account for only 20-30% of the excess familiar risk. What is contralaterally indicated when genetic assessment results negative for mutation in a young patient with unilateral breast cancer? Is it ethically correct to remove a contralateral “healthy” breast? CRRM rates continue to rise all over the world although CRRM seems not to improve overall survival in women with unilateral sporadic breast cancer. The decision to pursue CRRM as part of treatment in women who have a low-to-moderate risk of developing a secondary cancer in the contralateral breast should consider both breast cancer individual-features and patients preferences, but should be not supported by the surgeon and avoided as first approach with the exception of women highly worried about cancer. Prospective studies are needed to identify cohorts of patients most likely to benefit from CRRM.
1 Introduction
Breast cancer represent the second leading cause of cancer-related deaths in the United States [1] and the UK [2]. Although it regards predominantly older women, approximately 12% of new breast cancer cases occur in women younger than 45 years [3]. Younger age is usually related with more aggressive and less responsive tumours and consequently with lower survival rates, higher recurrence rates, and negative prognostic variables [4-6]. Therapeutic interventions include chemotherapy, hormone-therapies and surgery with or without radiotherapy. Systemic treatments impact on fertility prompting early menopause and ovarian decline [7]. Higher depression rates with effect on family life are also reported in these patients [8]. Refer to surgery could be cause of a negative body image that influence post-operative quality of life. Breast surgery includes breast conserving surgery (BCS) followed by radiation-therapy (RT) for early breast cancer or unilateral mastectomy (UM). BCS with RT and UM survival rates are equivalent [9], but preserving the breast, considering an oncoplastic technique could achieve better satisfaction levels and improve post-operative quality of life. Recently, however, numerous papers revealed a consistent growth in the use of both UM and contralateral risk reducing mastectomy (CRRM) [10,11]. CRRM consist in a so-called conservative mastectomy, the Nipple Areola Complex-Sparing Mastectomy that preserve the native breast skin and the nipple-areola complex, resulting in improved aesthetic results with local recurrence rates comparable to the traditional modified radical mastectomy [12]. The use of UM and CRRM is indicated in women affected by breast cancer, who are at high risk of developing a contralateral breast cancer (CBC), particularly women with genetic mutation of BRCA1, BRCA2 and P53. However, we should consider that the genes described above account for only 20-30% of the excess familial risk [13,14]. Consequently, the genetic etiology for the majority of families with an increased familial breast cancer risk remains unknown. Young age at diagnosis is a feature of hereditary disease and it is currently suggested that all women diagnosed with breast cancer younger than 37 should be referred for genetic assessment. But what is indicated in the contralateral breast when genetic assessment results are negative for mutation in a young patient with unilateral breast cancer? Is it ethically correct to remove a contralateral “healthy” breast?
2 Literature search
We reviewed PubMed database using the keywords “contralateral breast cancer”, “contralateral prophylactic mastectomy” and “contralateral risk reducing mastectomy”. We included only articles in English focused on contralateral mastectomy in women who presented a low-to-moderate risk of developing a secondary cancer in the contralateral breast. We considered as low-to-moderate risk patients, all women with a unilateral breast cancer in young age without a genetic mutation of BRCA1, BRCA2, P53 and without an evidence of strong familiarity for breast cancer. All papers reporting BRCA gene mutation carriers and other high-risk women have been excluded.
3 Results
Between January 1, 2005 and March 1, 2016 more than 300 papers were retrieved. Only 10% of retrieved papers addressed the impact of contralateral risk reducing mastectomy on overall survival [16-31]. Contralateral risk reducing mastectomy is estimated to reduce the risk of developing a contralateral breast cancer by approximately 94% [15]. Some studies showed a disease free survival (DSF) benefit associated with CRRM, but not an overall survival benefit [25,29].
4 Discussion
As a preventive measure, CRRM in women with low-to-moderate risk of developing a secondary cancer in contralateral breast remains controversial and potential benefits and disadvantages need to be discussed. The risk of mortality from contralateral disease must always be weighed against risk of mortality from primary tumour metastases, without an overall survival benefit. Different studies in fact showed as patients prognosis is strongly related to the features of their first breast cancer [32-34]. Moreover, mastectomy does not remove all breast tissue and therefore cannot eliminate risk of breast cancer at all, even if this surgery is shown to be effective in reducing risk. Presently, we are participating in a serious paradox: “a lesser surgical procedure is always more used in patients with an invasive breast cancer thanks to the screening program that allows an early detection of small cancer while mastectomy is offered in healthy breast for cancer prevention [32]”. In addition, there is no demonstrated survival benefit [35] and CRRM may cause significant physical morbidity: complication including infection, nipple areola complex necrosis, bleeding with a reoperation rate up to 16% of patients [36]. Chronic pain and unsatisfactory aesthetic results are also been reported respectively up to 50% and 84% of the CRRM affecting irreparably post-operative quality of life [37,38]. Women should be thoroughly informed about achievable outcomes in breast reconstructive surgery when considering undergoing risk reducing procedures. On the other side, CRRM in non affected breast have potential benefits connected with the reduction of both risk of cancer and anxiety patient. Given the potential complications and no demonstration of survival benefits, CRRM could be safely omitted in patients with low-to-moderate breast cancer risk.
5 Conclusion
CRRM rates continue to rise all over the world although CRRM seems not to improve overall survival in women with unilateral sporadic breast cancer. The decision to pursue CRRM as part of treatment in women who have a low-to-moderate risk of developing a secondary cancer in the contralateral breast should consider both breast cancer individual-features and patients preferences, but should not be supported by the surgeon and avoided as first line approach with the exception of women highly worried about cancer. Prospective studies are needed to identify cohorts of patients most likely to benefit from CRRM.
Conflict of interest statement: Authors state no conflict of interest.
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© 2016 Giuseppe Falco et al.
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
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- Expression and clinical significance of LXRα and SREBP-1c in placentas of preeclampsia
- Letter to the Editor
- ARDS diagnosed by SpO2/FiO2 ratio compared with PaO2/FiO2 ratio: the role as a diagnostic tool for early enrolment into clinical trials
- Research Article
- Impact of sensory integration training on balance among stroke patients: sensory integration training on balance among stroke patients
- Review Article
- MicroRNAs as regulatory elements in psoriasis
- Review Article
- Influenza A(H1N1)pdm09 and postpandemic influenza in Lithuania
- Review Article
- Garengeot’s hernia: two case reports with CT diagnosis and literature review
- Research Article
- Concept of experimental preparation for treating dentin hypersensitivity
- Research Article
- Hydrogen water reduces NSE, IL-6, and TNF-α levels in hypoxic-ischemic encephalopathy
- Research Article
- Xanthogranuloma of the sellar region diagnosed by frozen section
- Case Report
- Laparoscopic antegrade cholecystectomy: a standard procedure?
- Case Report
- Maxillary fibrous dysplasia associated with McCune-Albright syndrome. A case study
- Regular Article
- Sialoendoscopy, sialography, and ultrasound: a comparison of diagnostic methods
- Research Article
- Antibody Response to Live Attenuated Vaccines in Adults in Japan
- Conference article
- Excellence and safety in surgery require excellent and safe tutoring
- Conference article
- Suggestions on how to make suboptimal kidney transplantation an ethically viable option
- Regular Article
- Ectopic pregnancy treatment by combination therapy
- Conference article
- Use of a simplified consent form to facilitate patient understanding of informed consent for laparoscopic cholecystectomy
- Regular Article
- Cusum analysis for learning curve of videothoracoscopic lobectomy
- Regular Article
- A meta-analysis of association between glutathione S-transferase M1 gene polymorphism and Parkinson’s disease susceptibility
- Conference article
- Plastination: ethical and medico-legal considerations
- Regular Article
- Investigation and control of a suspected nosocomial outbreak of pan-drug resistant Acinetobacter baumannii in an intensive care unit
- Regular Article
- Multifactorial analysis of fatigue scale among nurses in Poland
- Regular Article
- Smoking cessation for free: outcomes of a study of three Romanian clinics
- Regular Article
- Clinical efficacy and safety of tripterygium glycosides in treatment of stage IV diabetic nephropathy: A meta-analysis
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Prevention and treatment of peritoneal adhesions in patients affected by vascular diseases following surgery: a review of the literature
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Surgical treatment of recidivist lymphedema
- Special Issue on Italian Society for the Study of Vascular Anomalies
- CT and MR imaging of the thoracic aorta
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Role of FDG-PET scan in staging of pulmonary epithelioid hemangioendothelioma
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Sternal reconstruction by extracellular matrix: a rare case of phaces syndrome
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Prenatal diagnosis, 3-D virtual rendering and lung sparing surgery by ligasure device in a baby with “CCAM and intralobar pulmonary sequestration”
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Serum levels of inhibin B in adolescents after varicocelelectomy: A long term follow up
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Our experience in the treatment of Malignant Fibrous Hystiocytoma of the larynx: clinical diagnosis, therapeutic approach and review of literature
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Delayed recurrent nerve paralysis following post-traumatic aortic pseudoaneurysm
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Integrated therapeutic approach to giant solitary fibrous tumor of the pleura: report of a case and review of the literature
- Special Issue on Italian Society for the Study of Vascular Anomalies
- Celiac axis compression syndrome: laparoscopic approach in a strange case of chronic abdominal pain in 71 years old man
- Special Issue on Italian Society for the Study of Vascular Anomalies
- A rare case of persistent hypoglossal artery associated with contralateral proximal subclavian stenosis
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Contralateral risk reducing mastectomy in Non-BRCA-Mutated patients
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Professional dental and oral surgery liability in Italy: a comparative analysis of the insurance products offered to health workers
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Informed consent in robotic surgery: quality of information and patient perception
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Malfunctions of robotic system in surgery: role and responsibility of surgeon in legal point of view
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Medicolegal implications of surgical errors and complications in neck surgery: A review based on the Italian current legislation
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Iatrogenic splenic injury: review of the literature and medico-legal issues
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Donation of the body for scientific purposes in Italy: ethical and medico-legal considerations
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Cosmetic surgery: medicolegal considerations
- Focus on Medico-Legal and Ethical Topics in Surgery in Italy
- Voluntary termination of pregnancy (medical or surgical abortion): forensic medicine issues
- Review Article
- Role of Laparoscopic Splenectomy in Elderly Immune Thrombocytopenia
- Review Article
- Endoscopic diagnosis and treatment of neuroendocrine tumors of the digestive system
- Review Article
- Efficacy and safety of splenectomy in adult autoimmune hemolytic anemia
- Research Article
- Relationship between gastroesophageal reflux disease and Ph nose and salivary: proposal of a simple method outpatient in patients adults
- Case Report
- Idiopathic pleural panniculitis with recurrent pleural effusion not associated with Weber-Christian disease
- Research Article
- Morbid Obesity: treatment with Bioenterics Intragastric Balloon (BIB), psychological and nursing care: our experience
- Research Article
- Learning curve for endorectal ultrasound in young and elderly: lights and shades
- Case Report
- Uncommon primary hydatid cyst occupying the adrenal gland space, treated with laparoscopic surgical approach in an old patient
- Research Article
- Distraction techniques for face and smile aesthetic preventing ageing decay
- Research Article
- Preoperative high-intensity training in frail old patients undergoing pulmonary resection for NSCLC
- Review Article
- Descending necrotizing mediastinitis in the elderly patients
- Research Article
- Prophylactic GSV surgery in elderly candidates for hip or knee arthroplasty
- Research Article
- Diagnostic yield and safety of C-TBNA in elderly patients with lung cancer
- Research Article
- The learning curve of laparoscopic holecystectomy in general surgery resident training: old age of the patient may be a risk factor?
- Research Article
- Self-gripping mesh versus fibrin glue fixation in laparoscopic inguinal hernia repair: a randomized prospective clinical trial in young and elderly patients
- Research Article
- Anal sphincter dysfunction in multiple sclerosis: an observation manometric study