Editorial Approaching the Dilemma Between Prophylactic Bilateral Mastectomy or Oophorectomy for Breast and Ovarian Cancer Prevention in Carriers of BRCA1 or BRCA2 Mutations Dimitrios H. Roukos, MD, Niki J. Agnanti, MD, Evangelos Paraskevaidis, MD, and Angelos M. Kappas, MD Despite advances in the genetics of familial breast and ovarian cancer, the clinical management of women with established mutations in BRCA1 or BRCA2 genes re- mains controversial. For women who decide for prophy- lactic surgery and not for a conservative approach, it is highly debated whether they are benefited more by a prophylactic mastectomy rather than a prophylactic oo- phorectomy. Although BRCA mutation carriers are at a substantially higher risk for developing breast cancer rather than ovarian cancer, medical decision-making is a major challenge. Penetrance estimates of breast and ovarian cancer considerably vary and substantially differ between BRCA1 and BRCA2 mutation carriers. This vari- ation is important in decision-making. Here we balance risks and benefits of these two surgical procedures re- garding cancer risk estimates, effectiveness, morbidity, and quality of life. Since the first description of breast cancer susceptibil- ity in women carrying mutations in BRCA1 or BRCA2 genes 8 years ago, important advances have been made in cancer genetics and several clinical studies with sur- gical or conservative preventive approaches have been published. But the clinical management of these women has not yet been established. Surgical prophylaxis in BRCA mutation carriers seems to offer higher protection against cancer than conservative approach, but it is as- sociated with a series of limitations and risks. 1 Clinicians are increasingly being asked to involve patients in deci- sions that ‘have no clear best choice,‘ and in which the medical science is imperfect, leaving many questions unanswered. Approximately 50% of women with BRCA1 or BRCA2 mutations elect surgical prophylaxis after medical counselling. But it remains unclear whether pro- phylactic mastectomy or prophylactic oophorectomy is more beneficial. BRCA1 and BRCA2 are tumor suppressor genes that play important roles in cellular functioning, such as DNA damage repair. Germ-line (inherited) mutations in these genes predispose to breast and ovarian cancer. Recent research on array-based methods has demonstrated dif- ferences in gene expression profiles between BRCA1- and BRCA2-associated tumors in both hereditary breast cancers 2,3 and ovarian cancers. 4 Thus, mutations in BRCA1 and BRCA2 genes lead to breast or ovarian cancer through different pathways. This subclassification of breast and ovarian cancer according to their gene expression patterns may clinically have prognostic and therapeutic value. 5 Indeed, penetrance, the probability that cancer will in fact develop in a woman with these genetic abnormalities, differs substantially between BRCA1 and BRCA2 mutation carriers and this is impor- tant for treatment decision-making. For BRCA1 mutation carriers, penetrance estimates range from a 45% to 85% lifetime risk of breast cancer and from a 16% to 63% lifetime risk of ovarian can- cer. 6 –14 For BRCA2 mutations, penetrance is estimated to range between a 26% and 85% risk of breast cancer and from a 10% to 20% risk of ovarian cancer, 7–11,13,15 and one study 12 found no statistically significant evidence of an increased risk. The data indicate a rather lower risk of ovarian cancer among BRCA2 mutation carriers and this seems important in clinical decision. However, all esti- Received October 9, 2002; accepted October 16, 2002. From the Departments of General Surgery (DHR, AMK), and of Obstetrics and Gynecology (IG, DP), Medical School of University of Ioannina, 451 10 Ioannina, Greece. Address correspondence to: Dimitrios H. Roukos, MD, P.O. Box 105 Neochoropoulo, Ioannina 455 00, Greece; Fax: 30-6510-70800; E- mail: droukos@cc.uoi.gr. Published by Lippincott Williams & Wilkins © 2002 The Society of Surgical Oncology, Inc. Annals of Surgical Oncology, 9(10):941–943 DOI: 10.1245/ASO.2002.10.010 941