Letter to the Editor European Journal of Cancer Prevention 2013, 00:000–000 Proposal on Raloxifene use after prophylactic salpingo-oophorectomy in BRCA1–2: hypothesis and rationale Salvatore Gizzo, Marco Noventa, Carlo Saccardi, Pietro Litta, Donato D’Antona and Giovanni B. Nardelli, Department of Woman and Child Health, Obstetric and Gynaecologic Clinic, University of Padua, Padua, Italy Correspondence to Salvatore Gizzo, MD, Department of Woman and Child Health, Obstetric and Gynaecologic Clinic, University of Padua, Giustiniani Street 3, 35128 Padua, Italy Tel: + 39 333 5727248/ + 39 049 8213400; fax: + 39 049 8211785; e-mail: ginecologia_padova@libero.it Received 11 October 2013 Accepted 26 November 2013 I am very pleased to bring to your attention our new research project on the use of Raloxifene (RAL) as first- line therapy after surgical prophylactic oophorectomy in patients carrying the genetic mutation BRCA1–2. As is known, prophylactic salpingo-oophorectomy is the complete surgical removal of the ovaries and fallopian tubes for the prevention of ovarian/fallopian cancer. The uptake of this surgery ranges from 60 to 90% among BRCA carriers and this uptake is related to age, perception of cancer risk, and perceived benefits of surgery (Finch et al., 2012). This surgery reduces the risk of ovarian/fallopian tube cancer by 75–96% and of breast cancer by B50%, if performed before natural menopause. Recently, gynecologists and oncologists debated the adverse consequences of premature menopause linked to this surgery. It is universally accepted that bilateral salpingo-oopho- rectomy offers the greatest risk reduction for breast and ovarian cancer among BRCA mutation carriers. In any case, considering quality-adjusted life expectancy, bilat- eral salpingectomy with delayed oophorectomy could be considered as a cost-effective strategy. It may be considered as an acceptable alternative for those women unwilling to undergo bilateral salpingo- oophorectomy because of negative consequences of premature ovarian failure (Kwon et al., 2013). Many studies have evaluated the ovarian chemopreven- tion role of combined oral contraceptive use in BRCA mutation carriers. Data about their use, despite hetero- geneous and often inconsistent, suggested that the advantage in ovarian cancer protection are reduced by the potential adverse effects on breast tissue (Cibula et al., 2011). Recently, all simulation models to predict the impact of prophylactic surgery and screening on the life expectancy of BRCA1–2 mutation carriers concluded that gains in life expectancy depend on the type of BRCA mutation and the age of risk-reducing salpingo-oophorectomy as the degree of breast cancer risk reduction, because of prophylactic oophorectomy, is a key determinant of life expectancy (Sigal et al., 2012). According to the evidence that prophylactic oophorect- omy represents the mainstay for both ovarian and breast cancer prevention in the BRCA1–2 cohort of patients, it is important to not underestimate the surgical impact in terms of both short-term and particularly long-term effects, considering that most of the patients are young at risk-reducing surgery. Many studies have focused on the short-term effects linked to surgical menopause, such as quality of life, but studies on long-term health after salpingo-oophorectomy in women who carry a BRCA mutation are underway and the results have not yet been published. Studies based on short-term outcomes have reported that the overall quality of life appears to be similar before and after surgery. In fact, although vasomotor symptoms related to surgical menopause and changes in sexual functioning are common, the overall quality of life did not generally worsen as the high levels of patient satisfaction linked to the surgical choice mitigate the discomforts. The early endogenous deficiency in estrogen interferes with bone health (increasing the risk of osteopenia and osteoporosis), cardiovascular health (increasing the risk of disease with respect to natural menopause by about 4.5 times), and cognitive function (estimated hazard ratio of 1.89 for cognitive impairment or dementia in case of surgery before 49 years of age) (Finch et al., 2012). To avoid the early and long-term effects of early endogenous estrogen deficiency, many authors have proposed estrogen–progesterone therapy (EPT), at least for a short period. Particularly in case of intact breasts (high risk), there is a suspect that the administration of EPT increase the risk of breast cancer, despite the uncertainties seems to be more than the certainties. In any case, the debate on the effects of EPT on breast tissue also remain unresolved in case of previous breast cancer treated surgically and followed by prophylactic contralateral mastectomy. Letter to the Editor 1 0959-8278  c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/CEJ.0000000000000003 CE: Diana ED: Maitreyee Op: Harish CEJ EJCP061786: LWW_CEJ_EJCP061786