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Journal of Clinical Oncology, Vol 26, No 11 (April 10), 2008: pp. 1909-1910 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.16.0275
Contralateral Prophylactic Mastectomy: Mind the GeneticsDepartments of Medical Oncology and Surgery, Medical School of the University of Ioannina, Ioannina, Greece To the Editor: In the November 20, 2007, issue of the Journal of Clinical Oncology, Tuttle et al1 delineate the current landscape in the extent of surgery for early-stage breast cancer in the United States. Despite the limitations of lack of genetic testing data, this report has important clinical implications for physicians, patients, society, health systems, and industry. The data of the Surveillance, Epidemiology and End Results database for breast cancer patients treated in the United States are clear. They show a dramatic increase in the rate of contralateral prophylactic mastectomy (CPM) among women with unilateral breast cancer. This rate was significantly increased from 4.2% in 1998 to 11.0% in 2003. In this population-based study, the rate of breast-conserving surgery was also increased from 56.1% in 1998 to 59.7% in 2003, whereas the rate of unilateral mastectomy was decreased. How can this trend be explained? Will this trend impact European and other countries with a high prevalence of breast cancer? Women who undergo unilateral surgery for early breast cancer are known to live with the fear of increased risk of developing a second primary in the contralateral breast.2 This fear led to the introduction of CPM in early 1970s, which gradually gained popularity with the increasing attention to bilateral prophylactic mastectomy in late 1990s.3,4 Tuttle at al showed that in the United States, women diagnosed with unilateral early breast cancer increasingly choose CPM to prevent contralateral breast cancer (CBC).1 However, despite its apparent popularity, there are no randomized controlled trials to support the efficiency of CPM among all patients with unilateral breast cancer, or for the subsets of patients with family history of breast cancer, regardless, the presence of germline BRCA1/2 mutations. Only in a recently published retrospective cohort study was CPM found to be associated with decreased breast cancer mortality.5 It deserves careful consideration that with the generalization of genetic testing in clinical practice, it became evident that the subset of breast cancer patients who carry BRCA1/2 mutations faces the highest risk of developing CBC, whereas it remains unknown if noncarriers of BRCA mutations with a family history of breast cancer face a true increased risk for CBC.6,7 Moreover, it has been shown that although CPM can reduce the risk of CBC in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer, it is bilateral prophylactic oophorectomy that can provide a survival benefit.7 We want to draw attention to the fact that the inclusion of genetic testing in the pretreatment diagnostic work-up of patients with breast cancer and a family history of breast/ovarian cancer allows rational decision making toward individualized surgical treatment decisions.8,9 Today, in the era of evidence based medicine, when cancer management evolves toward more personalized approaches, the option of prophylactic surgery offered to women with a family history of breast cancer should be evidence-driven and rationally guided by genetic testing, with adequately informed patients taking active roles in decision making.10,11 Molecular genetics helps tailor treatment decisions to optimize therapeutic results and minimize unnecessary harms, and this complex management should be undertaken by experienced teams.12-14 We think it is time to start rethinking the unconditional generalization of radical surgery practices such as CPM without offering patients the opportunity for genetic testing and counseling. Moreover, unbiased prospective studies are definitely needed to evaluate the CPM and precisely define which subsets of patients with inherited predisposition to breast cancer might benefit, and by which type of prophylactic surgery.8,15 AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Tuttle TM, Habermann EB, Grund EH, et al: Increasing use of contralateral prophylactic mastectomy for breast cancer patients: A trend toward more aggressive surgical treatment. J Clin Oncol 25:5203-5209, 2007 2. Hislop TG, Elwood JM, Coldman AJ, et al: Second primary cancers of the breast: Incidence and risk factors. Br J Cancer 49:79-85, 1984[Medline] 3. Leis HP: Selective, elective, prophylactic contralateral mastectomy. Cancer 28:956-961, 1971[CrossRef][Medline] 4. Hartmann LC, Schaid DJ, Woods JE, et al: Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 340:77-84, 1999 5. Herrinton LJ, Barlow WE, Yu O, et al: Efficacy of prophylactic mastectomy in women with unilateral breast cancer: A cancer research network project. J Clin Oncol 23:4275-4286, 2005 6. Pierce LJ, Levin AM, Rebbeck TR, et al: Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 24:2437-2443, 2006 7. van Sprundel TC, Schmidt MK, Rookus MA, et al: Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer 93:287-292, 2005[CrossRef][Medline] 8. Roukos DH, Briasoulis E: Individualized preventive and therapeutic management of hereditary breast ovarian cancer syndrome. Nat Clin Pract Oncol 4:578-590, 2007[CrossRef][Medline] 9. Roukos DH: Prognosis of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357:1555-1556, 2007; author reply 1556 10. Nekhlyudov L, Bower M, Herrinton LJ, et al: Women's decision-making roles regarding contralateral prophylactic mastectomy. J Natl Cancer Inst Monogr 35:55-60, 2005 11. Rolnick SJ, Altschuler A, Nekhlyudov L, et al: What women wish they knew before prophylactic mastectomy. Cancer Nurs 30:285-291, 2007[CrossRef][Medline] 12. Roukos DH: Innovative genomic-based model for personalized treatment of gastric cancer: Integrating current standards and new technologies. Expert Rev Mol Diagn 8:29-39, 2008[CrossRef][Medline] 13. Roukos DH, Murray S, Briasoulis E: Molecular genetic tools shape a roadmap towards a more accurate prognostic prediction and personalized management of cancer. Cancer Biol Ther 6:308-312, 2007[Medline] 14. Fatouros M, Baltoyiannis G, Roukos DH: The predominant role of surgery in the prevention and new trends in the surgical treatment of women with BRCA1/2 mutations. Ann Surg Oncol 15:21-33, 2008 15. Robson M, Offit K: Management of an inherited predisposition to breast cancer. N Engl J Med 357:154-162, 2007
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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