Prophylactic Bilateral Oophorectomy Research Articles

Incidental MRI detection of BRCA1-related solitary peritoneal carcinoma during breast screening—A case report

Background. The reported cumulative risk of developing primary peritoneal carcinoma (PPC) one to 20 years after prophylactic bilateral oophorectomy is 3.5% to 4.3%. Virtually all reported cases have been stage III or IV. Case. During MRI screening of the breasts, an incidental mass on the surface of the liver was identified in a 56-year-old BRCA1 mutation carrier who had undergone prophylactic bilateral salpingo-oophorectomy several years previously with no evidence of malignancy. After four cycles of chemotherapy a localized, grade 3 serous papillary adenocarcinoma was resected followed by further chemotherapy and radiation. She remains disease-free 3 years post-treatment. Conclusion. The literature on PPC after prophylactic oophorectomy is reviewed. To the best of our knowledge, this is the first description of an apparently localized case of BRCA related PPC outside the pelvis.

AURKAF31I Polymorphism and Breast Cancer Risk inBRCA1andBRCA2Mutation Carriers: A Consortium of Investigators of Modifiers of BRCA1/2 Study

The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.

Acceptance for preventive genetic testing and prophylactic surgery in women with a family history of breast and gynaecological cancers

The fear of family members of patients with breast or gynaecologic cancer of developing a similar disease is often high. We investigated the acceptance for genetic testing of untested women with a positive family history and their attitude for prophylactic surgery. A total of 659 women with a familial history of breast or gynaecologic cancer were asked to answer a questionnaire regarding their interest in genetic testing for breast cancer as well as for gynaecologic carcinoma and their interest in prophylactic surgery. Genetic testing is seen to be accepted by the majority of participants: 85.0 and 77.8% chose a genetic test for breast and gynaecologic cancer, respectively. Prophylactic surgery was much less chosen; prophylactic mastectomy as well as prophylactic hysterectomy or bilateral prophylactic oophorectomy was an option only for a minority of women. Genetic testing for risk assessment of healthy women with a positive family history was observed to be accepted by a majority of participants. Prophylactic surgery was an option only for a minority and was not acceptable for most of the women.

Survival patterns after oophorectomy in premenopausal women: a population-based cohort study

A statistical model of death due to ovarian cancer, breast cancer, coronary heart disease, hip fracture, and stroke has suggested that women who undergo prophylactic bilateral oophorectomy are at increased risk of death for all causes. We aimed to investigate survival patterns in a population-based sample of women who had received an oophorectomy and compare these with women who had not received an oophorectomy. From an existing cohort of all women who underwent unilateral or bilateral oophorectomy while residing in Olmsted County, MN, USA, in 1950-87, we analysed those who had received an oophorectomy for a non-cancer indication before the onset of menopause. Every member of the cohort was matched by age to a referent woman in the same population who had not undergone oophorectomy. 1293 women with unilateral oophorectomy, 1097 with bilateral oophorectomy, and 2390 referent women were eligible for the study. Women were followed up until death or the end of the study (staggered over 2001-06) by use of direct or proxy interviews, medical records in a records-linkage system, and death certificates. Overall, mortality was not increased in women who underwent bilateral oophorectomy compared with referent women. However, mortality was significantly higher in women who had received prophylactic bilateral oophorectomy before the age of 45 years than in referent women (hazard ratio 1.67 [95% CI 1.16-2.40], p=0.006). This increased mortality was seen mainly in women who had not received oestrogen up to the age of 45 years. No increased mortality was recorded in women who underwent unilateral oophorectomy in either overall or stratified analyses. Although prophylactic bilateral oophorectomy undertaken before age 45 years is associated with increased mortality, whether it is causal or merely a marker of underlying risk is uncertain.

Is the Fault in Our Steroids or in Our Selves?

Is the Fault in Our Steroids or in Our Selves?

Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a <EMPH TYPE="ITAL">BRCA1</EMPH> or <EMPH TYPE="ITAL">BRCA2</EMPH> Mutation

Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort. To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2. To estimate the reduction in risk of these cancers associated with a bilateral prophylactic salpingo-oophorectomy. Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. A total of 1828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from the date of study entry until: diagnosis of ovarian, fallopian tube, or peritoneal cancer; death; or the date of the most recent follow-up. Participants were divided into women who had undergone bilateral prophylactic oophorectomy and those who had not. The incidence of ovarian, peritoneal, and fallopian tube cancer was determined by survival analysis. The risk reduction associated with prophylactic salpingo-oophorectomy was evaluated by a time-dependent survival analysis, adjusting for covariates. After a mean follow-up of 3.5 years, 50 incident ovarian, fallopian tube, and peritoneal cancer cases were reported in the cohort. Of the 1828 women, 555 (30%) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 490 (27%) underwent the procedure after entering the study, and 783 (43%) did not undergo the procedure. There were 32 incident cancers diagnosed in women with intact ovaries (1015/100,000 per year). Eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy (217/100,000 per year). The estimated cumulative incidence of peritoneal cancer is 4.3% at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003). Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.

Prophylaktische Chirurgie bei Brust- und Eierstockkrebsrisiko

Bilateral prophylactic mastectomy and oophorectomy are currently the most effective prevention options for female carriers of the BRCA1 or BRCA2 gene. However, especially the mastectomy procedure is very invasive and is chosen rarely among high risk women in Germany. Little is known about how women cope with this surgery and their long-term satisfaction. Face-to-face interviews were conducted with two BRCA1 mutation carriers, who had undergone prophylactic mastectomy in their twenties 9 and 16 years ago. The process of decision making and long-term satisfaction were analysed using Mayring's qualitative content analysis. Both high risk women had a significant family history of breast and ovarian cancer. They were repeatedly confronted with uncontrollable courses of disease in their relatives who died of breast cancer between the age of 20 and 30 and left small children behind. Although both women experienced different decision making and peri- and post-operative complications, both were satisfied with the decision for prophylactic surgery and showed no regret. Deciding to obtain genetic testing pushed women towards further decision making concerning prophylactic surgery in case they carry a mutation. Information about carrier status reduced uncertainty even if the result was adverse. Both high risk women experienced a decrease in cancer related anxiety which may have heightened tolerance for quality of life related impairments. Implications for counseling are described.

Value of laparoscopic assistance for vaginal hysterectomy with prophylactic bilateral oophorectomy

This study was undertaken to compare morbidity for women undergoing laparoscopy-assisted vaginal hysterectomy with bilateral oophorectomy (LAVHO) and vaginal hysterectomy with bilateral oophorectomy without laparoscopic assistance (VHO). Between April 1, 2002, and February 1, 2004, a prospective randomized study at Marseille University Hospital (La Conception) included 48 patients who underwent a hysterectomy with prophylactic bilateral oophorectomy for benign uterine conditions. These patients were allocated to 2 groups (LAVHO vs VHO). The study variables were duration of surgery and of hospitalization and surgical and postoperative complications. There was no significant difference in the duration of surgery between the LAVHO and VHO groups (100.2 +/- 27.9 vs 83.9 +/- 34.6, P = .08). The rate of complications was significantly higher in the LAVHO group (13/24 [54.1%] vs 6/24 [25%], P = .039). The overall complication rate was higher with LAVHO than VHO. It thus appears that laparoscopic assistance is not useful in performing vaginal hysterectomies with prophylactic bilateral oophorectomies in patients without other related disorders (endometriosis, adhesions, adnexal anomalies).

Cost-Effectiveness of Preventive Strategies for Women with a BRCA1 or a BRCA2 Mutation

For BRCA1 or BRCA2 mutation carriers, decision analysis indicates that prophylactic surgery or chemoprevention leads to better survival than surveillance alone. To evaluate the cost-effectiveness of the preventive strategies that are available to unaffected women carrying a single BRCA1 or BRCA2 mutation with high cancer penetrance. Markov modeling with Monte Carlo simulations and probabilistic sensitivity analyses. Breast and ovarian cancer incidence and mortality rates, preference ratings, and costs derived from the literature; the Surveillance, Epidemiology, and End Results (SEER) Program; and the Health Care Financing Administration (now the Centers for Medicare & Medicaid Services). Unaffected carriers of a single BRCA1 or BRCA2 mutation 35 to 50 years of age. Lifetime. Health policy, societal. Tamoxifen, oral contraceptives, bilateral salpingo-oophorectomy, mastectomy, both surgeries, or surveillance. Cost-effectiveness. For mutation carriers 35 years of age, both surgeries (prophylactic bilateral mastectomy and oophorectomy) had an incremental cost-effectiveness ratio over oophorectomy alone of 2352 dollars per life-year for BRCA1 and 100 dollars per life-year for BRCA2. With quality adjustment, oophorectomy dominated all other strategies for BRCA1 and had an incremental cost-effectiveness ratio of 2281 dollars per life-year for BRCA2. Older age at intervention increased the cost-effectiveness of prophylactic mastectomy for BRCA1 mutation carriers to 73,755 dollars per life-year. Varying the penetrance, mortality rates, costs, discount rates, and preferences had minimal effects on outcomes. Results are dependent on the accuracy of model assumptions. On the basis of this model, the most cost-effective strategies for BRCA mutation carriers, with and without quality adjustment, were oophorectomy alone and oophorectomy and mastectomy, respectively.

Effect of Short-Term Hormone Replacement Therapy on Breast Cancer Risk Reduction After Bilateral Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group

Bilateral prophylactic oophorectomy (BPO) is widely used for cancer risk reduction in women with BRCA1/2 mutations. Many premenopausal women choose to take hormone replacement therapy (HRT) after undergoing BPO to abrogate immediate symptoms of surgically-induced menopause. Thus, we evaluated whether the breast cancer risk reduction conferred by BPO in BRCA1/2 mutation carriers is altered by use of post-BPO HRT. We identified a prospective cohort of 462 women with disease-associated germline BRCA1/2 mutations at 13 medical centers to evaluate breast cancer risk after BPO with and without HRT. We determined the incidence of breast cancer in 155 women who had undergone BPO and in 307 women who had not undergone BPO on whom we had complete information on HRT use. Postoperative follow-up was 3.6 years. Consistent with previous reports, BPO was significantly associated with breast cancer risk reduction overall (hazard ratio [HR] = 0.40; 95%CI, 0.18 to 0.92). Using mutation carriers without BPO or HRT as the referent group, HRT of any type after BPO did not significantly alter the reduction in breast cancer risk associated with BPO (HR = 0.37; 95% CI, 0.14 to 0.96). Short-term HRT use does not negate the protective effect of BPO on subsequent breast cancer risk in BRCA1/2 mutation carriers.

CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer

Objectives. The main objective of screening is to identify cases of ovarian cancer in early stages. However, screening of women in the general population is ineffective due to a failure of detecting early-stage disease and high false positive rates of CA125 and transvaginal ultrasound (TVU) monitoring. The purpose of this study is to evaluate ovarian cancer screening by means of pelvic examination, serum CA125 and TVU in a consecutive series of high-risk women. Methods. Clinical data were collected from 132 BRCA1, 20 BRCA2 germ line mutation carriers, 72 members of hereditary breast and ovarian cancer (HBOC) families and 88 breast cancer patients from a hereditary breast cancer (HBC) family, seen between January 1996 and December 2002. Results. Among 10 women with an elevated CA125 level and a positive TVU, three screening carcinomas (one FIGO stage IC, one stage IIIB and one stage IV) and one interval carcinoma (stage IV) were detected. Five occult ovarian/fallopian tube carcinomas (two stage IA, one stage IC, one stage IIIB and one stage IV) after bilateral prophylactic (salpingo-) oophorectomy (BP(S)O) have been found in 152 women. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the combination of CA125 and TVU were the highest (40%, 99%, 40% and 99%) followed by CA125 alone (50%, 96%, 13% and 99%), pelvic exam (40%, 98%, 21% and 99%) and TVU, separately (40%, 90%, 6% and 99%). Conclusion. By combining CA125 with TVU results, a PPV of 40% was achieved. However, the diagnostic tools appear to be only sensitive in detecting ovarian cancer at an advanced stage, while three of four tumors with early-stage disease in this series had normal screening tests prior to the diagnosis.

Should Prophylactic Oophorectomy Be Performed During Hysterectomy

More than half of all hysterectomies for benign disease (i.e., >300,000 yearly in the U.S.) are accompanied by prophylactic bilateral oophorectomy, and

Psychosexual health 5 years after hysterectomy: population-based comparison with endometrial ablation for dysfunctional uterine bleeding.

We report a population-based comparison of psychosexual health 5 years after contrasting amounts of surgical treatments for heavy periods [dysfunctional uterine bleeding (DUB)]. Women's fears about sexual function after hysterectomy might not be unfounded. The psychosexual problems may return and/or develop with time. The removal of ovaries at the time of hysterectomy is associated with greater deterioration of self-reported sexual function. Surgical menopause significantly impairs sexual wellbeing. We failed to observe uniform beneficial effects of hormone replacement therapy (HRT) on reported psychosexual health. To compare self-reported bothersome sexual function; loss of interest in sex, difficulty in becoming sexually excited and vaginal dryness 5 years after surgical management of DUB [transcervical endometrial resection/ablation (TCRE) or subtotal and total hysterectomy, with and without prophylactic bilateral oophorectomy (BO)]. Prospective cohort study up to 5 years post-surgery for DUB, TCRE or hysterectomy, with or without BO. Over 400 NHS and private hospitals in England, Northern Ireland and Wales. Of 11,325 women who responded to the 5-year questionnaire, over 9500 (84%) were valid cases, and over 8900 (94%) did complete the questions relating to psychosexual function. Most were between the ages of 39 and 45 years, married or cohabiting. Self-reported experience of bother, recorded as 'some', 'severe' and 'extreme', to questions on (1) libido loss, (2) difficulty with sexual arousal, and (3) vaginal dryness during the past 4 weeks, 5 years after surgery. Five years after surgery for DUB, the crude and adjusted prevalence of psychosexual problems was higher after hysterectomy than after TCRE. Amongst the women with concurrent BO, the age- and HRT-adjusted odds ratios for extreme psychosexual problems were increased by 80% (libido loss), 82% (difficult sex arousal) and 69% (vaginal dryness) compared with TCRE. Five years after hysterectomy more women reported having bothersome psychosexual function than did the women who had a less invasive operation. Hormone therapy, although related to surgical method, did not reduce this long-term detrimental effect. The odds were particularly high amongst women with concurrent BO. Women should be advised that they might be at higher risk of psychosexual problems following hysterectomy, compared with a less invasive procedure.

Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers

The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer is unknown. We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stages I–IIIa. In all, 79 women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last, that is, on average 5 years after diagnosis of the first breast cancer. One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (P<0.001). Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5 years follow-up, overall survival was 94% for the CPM group vs 77% for the surveillance group (P=0.03), but this was unexpectedly mostly due to higher mortality related with first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant. Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer-specific survival. The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far.

Impact of BRCA mutation test results in members of hereditary breast ovarian cancer (HBOC) families

1014 Background: Disclosure of BRCA mutation results may cause distress and in turn affect patient’s behavior, work and decision on cancer screening and management. Methods: Members (n=898) from 84 HBOC families who received their result and genetic counseling provided responses to their BRCA mutation test result. Findings from 395 responders (78 with breast cancer and a BRCA mutation; 20 with cancer but without a mutation; 90 without cancer but with a BRCA mutation, and 207 without cancer and without a mutation) were analyzed by Kruskal-Wallis, Dunn and Fisher’s exact tests. Results: Mutation-carriers regardless of their cancer status gave statistically higher emotionally laden scores than comparable non-carriers without cancer. Following mutation disclosure, 23% (36/154) underwent prophylactic bilateral mastectomy as compared to 5.5% (36/660) before mutation test disclosure (p<0.001). After mutation disclosure 51.5% (88/171) underwent prophylactic bilateral oophorectomy as compared to 26% (171/660) before mutation disclosure (p<0.001). No non-mutation carriers (n=352) chose prophylactic surgery after result disclosure. Alteration in screening behavior based upon BRCA mutation results are depicted in the table. A significant higher percentage of BRCA positive individuals who did not have annual ovarian ultrasounds before their result disclosure chose to do so after result disclosure as compared to their BRCA negative counterparts (p< 0.005). Similar findings were seen for annual CA-125 blood tests (p<0.001). Conclusion: These data harbor an important clinical translation as reflected by alterations in screening behavior and surgical prophylaxis in response to genetic counseling and BRCA mutation findings. No significant financial relationships to disclose.

Is family history related to preventive health behaviors and medical management in breast cancer patients?

Women diagnosed with breast cancer who also have a family history of the disease are at increased risk of developing additional primary breast or ovarian cancers. We investigated whether a relationship exists between family history and health behaviors in a cross-sectional study of breast cancer survivors. Participants in the Women's Healthy Eating and Living (WHEL) Study (a randomized trial designed to test the effect of a plant-based diet on breast cancer recurrence) completed baseline questionnaires about their family history and health behaviors. Medical records and self-reports provided treatment data. Participants were defined as having a family history (FH+) if they met specific family history criteria (n=195), and were compared with women having no family history (FH-) of breast cancer (n=1736). The mean age of breast cancer diagnosis was 51.2 years for both groups, but FH+ women were more likely to be diagnosed before age 40. FH+ and FH- women had similar dietary patterns, alcohol intake, exercise patterns, body mass index and smoking histories. However, FH+ women were more likely to have undergone prophylactic contralateral mastectomy (OR=3.6, 95% CI=2.2 - 6.2) and bilateral oophorectomy (OR=1.6; 95% CI=1.0 - 2.3) following diagnosis, adjusted for age and time since diagnosis. The FH+ and FH- groups had similar patterns of use of anti-estrogen medications and frequency of medical follow-up. Breast cancer survivors with a strong family history of breast cancer are more likely to undergo surgical preventive measures to reduce their risk of additional cancer, but do not report undertaking more preventive lifestyle behaviors compared to breast cancer survivors without a family history.

Breast Cancer and Ovarian Cancer Genetics

Breast and ovarian cancers are the second and fifth leading causes of cancer death, respectively, among women in the United States. Individuals with breast cancer have a 20--30% chance of having at least one relative with the disease. However, only 5--10% of the cases are a direct result of germline mutations in highly penetrable genes, such as BRCA1 and BRCA2 (BRCA1/2) as well as genes TP53 and PTEN. Since 1996, genetic testing for these mutations has been clinically available. A strategy for the management of women at increased familial risk of breast and ovarian cancers is described, which includes genetic assessment, chemoprevention, radiologic screening, and clinical and self-examination. Genetic testing should occur within a cancer genetic clinic after genetic counseling. A blood sample allows determination of the presence of the BRCA1 and BRCA2 genes, the TP53 gene, the PTEN gene, and the ATM gene. Tumor examination has identified a growth factor receptor gene, human epidermal growth factor receptor (HER-2). With regard to diet and lifestyle, women at increased risk of breast cancer could be advised to reduce dietary fat, avoid obesity, decrease alcohol consumption, and take regular exercise. Although chemoprotection is a valuable consideration, it is important to emphasize that the use of Tamoxifen in BRCA1 and BRCA2 mutation carriers is not established, nor is the optimum duration of benefit. An overview of the main outcomes of the current published studies confirms a 38% decrease in breast cancer incidence with Tamoxifen but recommends its use be restricted to women at high risk of breast cancer and low risk for potential side effects. The role of bilateral risk-reducing mastectomy or prophylactic mastectomy has been controversial for several reasons, including the psychosocial significance of the breast in Western cultures, the wide acceptance of breast conservation in surgery for early breast cancer, and the previous lack of data on its efficacy. The surgical procedure should aim to remove substantially all at-risk breast tissue. However, there is a balance between reduction of cancer risk and cosmetic outcome. Bilateral prophylactic oophorectomy can significantly decrease ovarian cancer risk in women who carry BCRA1 mutations. Oophorectomy lowers the risk of breast cancer, even in women who have previously used hormone replacement therapy. There are no published randomized controlled trials examining the effectiveness of mammographic screening in women under 50 years of age with a family history of breast cancer. However, the published studies do suggest that mammographic screening of a high-risk group of women under 50 years of age may detect cancer at a rate equivalent to that seen in women 10 years older with normal risk. Other initial studies also support MRI as having a greater sensitivity than mammography in high-risk women. Breast clinical and self-examination is often advocated, but its effectiveness is unproved, and only one randomized study has been undertaken in women at risk. On the basis of this study as well as one nonrandomized study, it can be concluded that clinical examination as well as mammography are essential in detecting breast cancer. under 50 years of age with a family history of breast cancer. However, the published studies do suggest that mammographic screening of a high-risk group of women under 50 years of age may detect cancer at a rate equivalent to that seen in women 10 years older with normal risk. Other initial studies also support MRI as having a greater sensitivity than mammography in high-risk women. Breast clinical and self-examination is often advocated, but its effectiveness is unproved, and only one randomized study has been undertaken in women at risk. On the basis of this study as well as one nonrandomized study, it can be concluded that clinical examination as well as mammography are essential in detecting breast cancer.

Additional salpingectomy after previous prophylactic oophorectomy in high-risk women: sense or nonsense?

Objectives Since BRCA1/2 germ line mutation carriers are also at a higher risk of developing fallopian tube carcinoma, resection of the fallopian tubes is currently included at the time of risk reducing surgery. In this study, we comment on the need of additional bilateral prophylactic salpingectomy (BPS) following previous bilateral prophylactic oophorectomy (BPO) in women at high risk of ovarian cancer. Methods Retrospectively, the medical files of 42 high-risk women, who had undergone BPO only, were reviewed. Results In our center, risk-reducing surgery consisted of BPO only for 42 women. Twenty-seven women received an informative letter in which counseling for additional BPS was offered. In total, 15 women opted for additional BPS. Surgery was performed with a mean interval of 65 months (range 6–101) in 10 BRCA1 carriers, one BRCA2 carrier, one BRCA1 and 2 carrier, and three women with non-informative test results. The procedure was readily done by laparoscopy in 13 women and two needed a laparotomy. No post-operative complications had occurred. Histopathological examination revealed no malignancy. Conclusions We believe that additional risk reduction of cancer necessitates BPS in BRCA1/2 carriers after previous BPO. BPS after previous BPO was easily performed. Today, physicians should include resection of the fallopian tube at prophylactic surgery in high-risk women and should consider additional BPS in women who have undergone BPO only.

Prophylactic oophorectomy in BRCA1/2 carriers

1012 Background: Women who carry a BRCA1 or BRCA2 mutation are at increased risk for breast and ovarian cancer. Bilateral prophylactic oophorectomy (BPO) has been shown to decrease the risk of ovarian cancer by 85–96%, and the risk of breast cancer by 50%. Therefore, for mutation carriers, prophylactic oophorectomy is recommended after completion of childbearing. Recent studies have found disparate rates of BPO among BRCA1/2 carriers, ranging from 27 to 60%. We conducted a review to determine the rate of BPO use among our BRCA1/2 carrier population. Methods: Clinical charts were reviewed to evaluate the use of BPO among our population of BRCA1/2 carriers. Participants included female BRCA1/BRCA2 carriers registered at the Cancer Risk Clinic. Women with a history of ovarian cancer, therapeutic oophorectomy and metastatic breast cancer at the time of genetic testing were excluded. Results: 80 BRCA1 or BRCA2 carriers in the Cancer Risk Clinic between January 1996 and December 2003 were included. The age at genetic testing ranged from 25 to 71 years old, and 75% were older than 35 at the time of genetic testing. 69 (86%) women were Caucasian, 9 (11%) were African-American and 2 (3%) were Hispanic. 55 (69%) were BRCA1 carriers and 25 (31%) were BRCA2 carriers. All participants received genetic counseling regarding risk reduction options including surveillance, prophylactic surgeries and chemoprevention. 9 (11%) women had a BPO prior to genetic testing, based on family history alone. An additional 32 women (40%) had undergone BPO at the time of analysis. 21 (66%) of these women had a BPO within 12 months of receiving their test results. 29 (53%) of the BRCA1 carriers and 12 (48%) of the BRCA2 carriers underwent BPO. Of the 9 African-American carriers 3 (33%) had a BPO, while neither of the 2 Hispanic carriers underwent BPO. Conclusions: Over 50% of our BRCA1 and BRCA2 carriers underwent bilateral prophylactic oophorectomy due to a family history suggestive of hereditary breast and ovarian cancer or genetic testing revealing a BRCA1/2 mutation. BPO is an acceptable method of risk reduction. Extended follow-up is necessary, as one-third of women delayed their decision to have BPO over one year after test disclosure. No significant financial relationships to disclose.

Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations: a critical review of the literature.

The purpose of our study was to review the evidence for the efficacy of surveillance for early detection, bilateral prophylactic mastectomy, prophylactic oophorectomy and chemoprevention in preventing breast cancer and improving survival of BRCA1 or BRCA2 carriers. A critical review of journal articles published between 1998 and 2004 identified by searches of MEDLINE, PubMed and references of retrieved articles was undertaken. None of the current evidence is based on randomized studies. The efficacy of surveillance for early detection of breast cancer among BRCA1 or BRCA2 carriers is not yet established. Screening with clinical breast examination and mammography showed lower sensitivity in BRCA1 or BRCA2 carriers than in the general population. Screening with MRI might offer higher sensitivity rates than mammography. Prophylactic mastectomy was shown to significantly reduce the risk of breast cancer by 89.5-100%. However, of all strategies reviewed, mastectomy was the least acceptable to women at high risk. Tamoxifen use was associated with breast cancer prevention among BRCA2 carriers (RR=0.38, 95%CI: 0.06-1.56). In BRCA1 or BRCA2 carriers with breast cancer, tamoxifen use was associated with the prevention of secondary breast cancer (OR= 0.50, 95% CI: 0.28-0.89). Prophylactic oophorectomy was associated with hazard ratios for breast cancer of 0.47 (95%CI:0.29-0.77) and 0.32 (95%CI: 0.08-1.20), in retrospective and short follow-up prospective cohort studies, respectively. There is a pressing need for more studies in order to determine which of the 4 strategies alone, or in combination, is the most effective for the prevention of breast cancer and for the improvement of survival of BRCA mutation carriers.