Bilateral Prophylactic Mastectomy Research Articles

Women at familial risk of breast cancer electing for prophylactic mastectomy: frequencies, procedures, and decision-making characteristics.

Some women of families at high risk of breast cancer (BC) choose prophylactic mastectomy (PM) in spite of ambiguous evidence for survival benefits. The aim of this study was to investigate counselees' characteristics, decisions on PM, and frequencies of different procedures to better understand how to tailor interventions. Eight hundred and forty-nine counselees who attended interdisciplinary consultation for genetic risk adjustment at the University Hospital Heidelberg between July 2009 and July 2011 received a tripartite questionnaire addressing sociodemographic characteristics, psychological parameters, behavioural questions, and medical data. Six hundred and twelve of the 849 counselees (72%) returned the questionnaire. Four hundred were classified as high risk of genetic BC (19.5% BRCA mutation carriers; 4% unclassified variant (UV); and 76.5% calculated as high risk by pedigree). Two hundred and thirteen out of 400 (53%) were diagnosed with BC. Fourteen out of 54 (27%) BRCA mutation carriers with BC chose contralateral PM (CPM) compared to 24/126 (14%) without a mutation but with a personal BC history (p=0.2175). Of those without BC, 12/27 (44%) mutation carriers opted for bilateral PM (BPM) compared to none without a mutation (p<0.0001). Women who received any PM (CPM and BPM) reported a higher emotional burden from partners (p=0.003) and family (p=0.008), more worries regarding children and family (p=0.003) and were associated with positive mutation status and higher heterozygous and lifetime risk (all p<0.001). Although evidence on survival benefit is unclear in several clinical situations, a relevant number of counselees opt for PM. Counselees may decide based on other reasons than survival benefit.

Cost-effectiveness of different strategies to prevent breast and ovarian cancer in German women with a BRCA 1 or 2 mutation.

Women with a BRCA1 or BRCA2 mutation are at increased risk of developing breast and/or ovarian cancer. This economic modeling study evaluated different preventive interventions for 30-year-old women with a confirmed BRCA (1 or 2) mutation. A Markov model was developed to estimate the costs and benefits [i.e., quality-adjusted life years (QALYs), and life years gained (LYG)] associated with prophylactic bilateral mastectomy (BM), prophylactic bilateral salpingo-oophorectomy (BSO), BM plus BSO, BM plus BSO at age 40, and intensified surveillance. Relevant input data was obtained from a large German database including 5902 women with BRCA 1 or 2, and from the literature. The analysis was performed from the German Statutory Health Insurance (SHI) perspective. In order to assess the robustness of the results, deterministic and probabilistic sensitivity analyses were performed. With costs of €29,434 and a gain in QALYs of 17.7 (LYG 19.9), BM plus BSO at age 30 was less expensive and more effective than the other strategies, followed by BM plus BSO at age 40. Women who were offered the surveillance strategy had the highest costs at the lowest gain in QALYs/LYS. In the probabilistic sensitivity analysis, the probability of cost-saving was 57% for BM plus BSO. At a WTP of 10,000 € per QALY, the probability of the intervention being cost-effective was 80%. From the SHI perspective, undergoing BM plus immediate BSO should be recommended to BRCA 1 or 2 mutation carriers due to its favorable comparative cost-effectiveness.

Post-mastectomy cancer recurrence with and without a continuous paravertebral block in the immediate postoperative period: a prospective multi-year follow-up pilot study of a randomized, triple-masked, placebo-controlled investigation.

Retrospective studies have associated perioperative regional anesthesia/analgesia during mastectomy for breast cancer with a decreased incidence of cancer recurrence. However, to date, no prospective data from a randomized controlled trial have been reported. In a previous study we found that extending a single-injection paravertebral block with a multiple-day perineural local anesthetic infusion improves analgesia. This follow-up study investigates the rates of cancer recurrence for the single-injection and multiple-day infusion treatments. Patients undergoing unilateral (n=24) or bilateral mastectomy (n=36) were included in the study. All patients had been diagnosed with breast cancer or tumor in situ, except for six patients who were receiving prophylactic bilateral mastectomy and were excluded from analyses. Patients received unilateral or bilateral single-injection thoracic paravertebral block(s) corresponding to their surgical site(s) with ropivacaine and perineural catheter(s). Subsequently, patients were randomized to receive either ropivacaine 0.4% (n=30) or normal saline (n=30) via their catheter(s) until catheter removal on postoperative day 3. Cancer recurrence from the date of surgery until at least 2years post surgery was investigated via chart review. Five of the 54 (9.2%) patients experienced a cancer recurrence following mastectomy-3 of 26 (11.5%) of the patients with perineural ropivacaine and 2 of 28 (7.1%) of the patients with perineural saline. This pilot study found no evidence that extending a single-injection paravertebral block with a multi-day perineural local anesthetic infusion decreases the risk of post-mastectomy cancer recurrence. However, due to the small sample size of this investigation, further research is needed to draw definitive conclusions.

Breast cancer prevention strategies in lobular carcinoma in situ: A decision analysis.

Women diagnosed with lobular carcinoma in situ (LCIS) have a 3-fold to 10-fold increased risk of developing invasive breast cancer. The objective of this study was to evaluate the life expectancy (LE) and differences in survival offered by active surveillance, risk-reducing chemoprevention, and bilateral prophylactic mastectomy among women with LCIS. A Markov simulation model was constructed to determine average LE and quality-adjusted LE (QALE) gains for hypothetical cohorts of women diagnosed with LCIS at various ages under alternative risk-reduction strategies. Probabilities for invasive breast cancer, breast cancer-specific mortality, other-cause mortality and the effectiveness of preventive strategies were derived from published studies and from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Assuming a breast cancer incidence from 1.02% to 1.37% per year under active surveillance, a woman aged 50 years diagnosed with LCIS would have a total LE of 32.78 years and would gain 0.13 years (1.6 months) in LE by adding chemoprevention and 0.25 years (3.0 months) in LE by adding bilateral prophylactic mastectomy. After quality adjustment, chemoprevention resulted in the greatest QALE for women ages 40 to 60 years at LCIS diagnosis, whereas surveillance remained the preferred strategy for optimizing QALE among women diagnosed at age 65 years and older. In this model, among women with a diagnosis of LCIS, breast cancer prevention strategies only modestly affected overall survival, whereas chemoprevention was modeled as the preferred management strategy for optimizing invasive disease-free survival while prolonging QALE form women younger than 65 years. Cancer 2017;123:2609-17. © 2017 American Cancer Society.

Innovative practice model to optimize resource utilization and improve access to care for high-risk and BRCA+ patients

Bilateral prophylactic mastectomy (BPM) has demonstrated breast cancer risk reduction in high-risk/BRCA+ patients. However, priority of active cancers coupled with inefficient use of operating room (OR) resources presents challenges in offering BPM in a timely manner. To address these challenges, a rapid access prophylactic mastectomy and immediate reconstruction (RAPMIR) program was innovated. The purpose of this study was to evaluate RAPMIR with regards to access to care and efficiency. We retrospectively reviewed the cases of all high-risk/BRCA+ patients having had BPM between September 2012 and August 2014. Patients were divided into 2 groups: those managed through the traditional model and those managed through the RAPMIR model. RAPMIR leverages 2 concurrently running ORs with surgical oncology and plastic surgery moving between rooms to complete 3 combined BPMs with immediate reconstruction in addition to 1-2 independent cases each operative day. RAPMIR eligibility criteria included high-risk/BRCA+ status; BPM with immediate, implant-based reconstruction; and day surgery candidacy. Wait times, case volumes and patient throughput were measured and compared. There were 16 traditional patients and 13 RAPMIR patients. Mean wait time (days from referral to surgery) for RAPMIR was significantly shorter than for the traditional model (165.4 v. 309.2 d, p = 0.027). Daily patient throughput (4.3 v. 2.8), plastic surgery case volume (3.7 v. 1.6) and surgical oncology case volume (3.0 v. 2.2) were significantly greater in the RAPMIR model than the traditional model (p = 0.003, p < 0.001 and p = 0.015, respectively). A multidisciplinary model with optimized scheduling has the potential to improve access to care and optimize resource utilization.

Patient and medical barriers preclude uptake of tamoxifen preventative therapy in women with a strong family history

AimsTo assess the eligibility, uptake and impediments to tamoxifen use in high-risk women attending a risk management clinic due to family history. Patients and methodsAll patients with a germline mutation in a cancer predisposing gene or at high genetic risk (based on family history) attending a Breast and Ovarian cancer risk management clinic from February 2014 to May 2015 received both verbal and written evidence-based information on preventive therapy and were recommended to consider endocrine prevention if not contraindicated. Endocrine therapy initiation, use and cessation were captured. Patient eligibility was analysed and reasons for declining, ceasing or contraindications for medication use were recorded. ResultsDuring the study period, 237 women were seen over 305 consultations for breast surveillance and preventative therapy discussion. They comprised 38 BRCA1 and 42 BRCA2 mutation carriers, 4 with Peutz-Jegher syndrome, 153 with a strong family history. Their median age was 39.4 years. Endocrine preventative was considered and discussed with all but 19 women. Of the remaining 218, 34 chose bilateral prophylactic mastectomy, while endocrine preventative was not recommended in 50 women due to contraindications and 25 women declined treatment due to their intention to fall pregnant. In 118 patients who remained eligible, 18.6% (22) tried prevention and 9.4% (14) remained on therapy. ConclusionsPhysician-reluctance is not a dominant reason for poor uptake of endocrine prevention even by high-risk premenopausal women in a specialised risk management clinic. Many women are not eligible, and most elect for alternative options.

Society of Surgical Oncology Breast Disease Working Group Statement on Prophylactic (Risk-Reducing) Mastectomy.

Over the past several years, there has been an increasing rate of bilateral prophylactic mastectomy (BPM) and contralateral prophylactic mastectomy (CPM) surgeries. Since publication of the 2007 SSO position statement on the use of risk-reducing mastectomy, there have been significant advances in the understanding of breast cancer biology and treatment. The purpose of this manuscript is to review the current literature as a resource to facilitate a shared and informed decision-making process regarding the use of risk-reducing mastectomy.

Users' guide to the surgical literature: how to assess an article about harm in surgery.

You are a new plastic surgeon in the community and you are referred a patient interested in breast reconstruction. The patient is a 35-year-old female school teacher who had a bilateral prophylactic mastectomy 2 years earlier, as she was a BRCA gene carrier. Since she is of a petite build with very little subcutaneous tissue or extra skin in the lower abdomen, you decide that she is not a suitable candidate for an abdomen-based autologous tissue reconstruction. You recommend the technique of tissue expansion and silicone gel implants. She is concerned, however, about the possibility of anaplastic large cell lymphoma (ALCL) developing in her breasts. She read in a magazine recently that ALCL, an unusual form of breast cancer, has been occurring in patients who have breast implants. She is very concerned that she might be at risk and asks for your opinion as to whether she should proceed with the procedure or not.

Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers. Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided. Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51). Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.

Patient Satisfaction and Nipple-Areola Sensitivity After Bilateral Prophylactic Mastectomy and Immediate Implant Breast Reconstruction in a High Breast Cancer Risk Population: Nipple-Sparing Mastectomy Versus Skin-Sparing Mastectomy.

Prophylactic skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) both are associated with major risk reduction in women with high breast cancer risk. Skin-sparing mastectomy followed by nipple-areola complex (NAC) reconstruction is standard of care, but NSM is increasingly being performed. Preservation of the NAC in NSM may increase patient satisfaction. Therefore, we measured NAC sensitivity after NSM and compared patient satisfaction as well as body image after SSM with NSM. Women who underwent prophylactic bilateral SSM or NSM and immediate implant breast reconstruction between 2002 and 2012 were eligible. Patient satisfaction was assessed using the Breast-Q reconstruction questionnaire, body image using Hopwood's body image scale (BIS), and satisfaction with the (reconstructed) NAC using a study-specific questionnaire. In the NSM group, NAC sensitivity was assessed using Semmes Weinstein monofilaments with a 5-point scale and compared with NAC sensitivity in a nonoperated control group. The SSM group comprised 25 women (50 SSMs) and the NSM group 20 women (39 NSMs). Median follow-up was 65 months in the SSM group compared with 27 months in the NSM group (P < 0.01). In univariable analyses, Breast-Q scores were favorable in the SSM group compared with the NSM group with trends for higher "satisfaction with breasts" (66.2 vs 56.6; P = 0.06) and "satisfaction with outcome" (76.1 vs 61.5; P = 0.09). Mean BIS score of 7.1/30 in the SSM group and 9.3/30 in the NSM group (P = 0.35). Adjusted for follow-up, there were no significant differences in Breast-Q scores, nor in BIS scores. Interestingly, satisfaction with the (reconstructed) NAC was similar after SSM and NSM. Nipple-areola complex sensitivity was lower in the NSM group (mean score, 1.9; 95% confidence interval, 1.5-2.3) compared with the control group (mean score, 4.7; 95% confidence interval, 4.6-4.9; P < 0.01). Breast-Q scores regarding satisfaction with breasts and overall outcome were in favor of the SSM group. Residual NAC sensitivity after NSM was low. This suggests that SSM followed by NAC reconstruction is a balanced alternative to NSM. We observed no significant differences in body image and NAC-specific satisfaction between the NSM and SSM groups.

Effectiveness of Prophylactic Surgeries in BRCA1 or BRCA2 Mutation Carriers: A Meta-analysis and Systematic Review.

To systematically investigate the effectiveness of prophylactic surgeries (PS) implemented in women carrying BRCA1/2 mutations. The PubMed database was searched till August 2014 and 15 studies met the inclusion criteria. Fixed- or random-effects models were conducted according to study heterogeneity. We calculated the pooled relative risks (RR) for cancer risk or mortality along with 95% confidence intervals (CI). Prophylactic bilateral salpingo-oophorectomy (PBSO) and bilateral prophylactic mastectomy (BPM) were both associated with a decreased breast cancer risk in BRCA1/2 mutation carriers (RR, 0.552; 95% CI, 0.448-0.682; RR, 0.114; 95% CI, 0.041-0.317, respectively). Similar findings were observed in BRCA1 and BRCA2 mutation carriers separately. Moreover, contralateral prophylactic mastectomy (CPM) significantly decreased contralateral breast cancer incidence in BRCA1/2 mutation carriers (RR, 0.072; 95% CI, 0.035-0.148). Of note, PBSO was associated with significantly lower all-cause mortality in BRCA1/2 mutation carriers without breast cancer (HR, 0.349; 95% CI, 0.190-0.639) and those with breast cancer (HR, 0.432; 95% CI, 0.318-0.588). In addition, all-cause mortality was significantly lower for patients with CPM than those without (HR, 0.512; 95% CI, 0.368-0.714). However, BPM was not significantly associated with reduced all-cause mortality. Data were insufficient to obtain separate estimates of survival benefit with PS in BRCA1 or BRCA2 mutation carriers. BRCA1/2 mutation carriers who have been treated with PS have a substantially reduced breast cancer incidence and mortality. Clin Cancer Res; 22(15); 3971-81. ©2016 AACR.

Cirugía profiláctica en síndrome de cáncer hereditario de mama

IntroductionApproximately 5-10% of global cancer has a genetic base. Nowadays it is possible to identify those who have a genetic predisposition for breast cancer, so they can be treated in short term. ObjectivesEvaluate how useful is prophylactic surgery on Hereditary Breast cancer Syndrome. Materials and methodsThis investigation is a literature review of different research papers from electronic databases such as Scientific Electronic Library Online (SciELO), MedLine-PubMed and UpToDate. The research was made with clinical queries and MeSH terms, specially focused on Hereditary Breast cancer Syndrome. ResultsThis research shows that prophylactic bilateral mastectomy (PBM) decreases 90% risk of developing breast cancer in BRCA1 and BRCA2 carriers. On the other hand, Salpyngo-oophoferectomy (SO) technique decreases around 53% chances of breast cancer, depending on the associated mutation. ConclusionProphylactic surgery has shown an important role decreasing the risk on Hereditary Breast cancer Syndrome. So on, in cases of BRCA1 and BRCA2 carriers we suggest to perform prophylactic surgery.

Abstract 514: Effect of radiation therapy on breast epithelial cells in BRCA1/2 mutation carriers

Abstract Women carrying BRCA1 and BRCA2 mutations have significantly elevated risk of developing breast and ovarian cancers. BRCA1-associated breast cancer likely originates from progenitors of the luminal epithelial lineage. Recent studies indicate that radiation therapy (RT) for BRCA1 cancer patients is associated with lower incidence of developing subsequent ipsilateral breast cancer. In the current study, we analyzed tumor-free breast tissue procured via prophylactic bilateral mastectomy from three BRCA1 and one BRCA2 mutation carriers, who had been previously treated with RT for unilateral breast cancers. Freshly isolated breast cells from the irradiated and non-irradiated breasts of the same individuals were subjected to flow cytometry, using established cell-surface markers. Two out of the three BRCA1 carriers and the BRCA2 carrier exhibited significantly diminished luminal cell population in the irradiated breast versus the non-irradiated side. The remaining BRCA1 carrier showed similar cell abundance between the two sides. Our finding suggests that prior RT could result in preferential depletion of the luminal epithelial compartment and thus reduced incidence of BRCA1-associated breast cancer. Further investigation may inform development of RT-based preventive approaches aimed at specifically decimating the source of BRCA1-associated tumors. Citation Format: Huai-Chin Chiang, Richard Elledge, Paula Larson, Ismail Jatoi, Rong Li, Yanfen Hu. Effect of radiation therapy on breast epithelial cells in BRCA1/2 mutation carriers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 514.

BRCA1/2 associated cancer susceptibility: a clinical overview

AbstractThe most frequently identified genetic cause of breast cancer is the germline mutation ofBRCA1and 2 genes. The carriers of these mutations are at high risk for breast and ovarian cancers and increased risk for pancreatic and prostate cancers. Personal and family history are routinely used to identify individuals at risk for carrying such mutations. Genetic counselling is required to guide them through genetic testing and risk management. Positive testing corresponds to a deleterious mutation, whereas negative testing is considered as uninformative; variants of unknown clinical significance are also classified as uninformative.The most effective risk reduction strategy involves bilateral prophylactic mastectomy and bilateral salpingo-oophorectomy, eliminating 90% of breast and 97% of ovarian cancer risks, respectively. Before and until such surgery, surveillance with physical examination, mammography and magnetic resonance mammography, starting at 25–30 years of age, are recommended for the early diagnosis of breast cancer; semi-annual surveillance with physical examination, transvaginal ultrasound and serum CA-125 is recommended for women who have not had prophylactic surgery. Carriers diagnosed with breast cancer run a high risk for a new breast primary and this information should be used accordingly. PARP inhibitors is a new class of antineoplastic agents, already approved for advancedBRCA1/2mutant (germline or somatic) ovarian cancer.Multigene panel testing may follow a negativeBRCAgenetic test, often identifying other genetic causes of cancer, expanding its role in oncology. Further adoption of PARP inhibitors, refinement in estimation of BRCA-associated cancer risks and wider population testing, through NGS technology, may become available in the near future.

What is new in the surgical management and prevention of breast cancer?

Breast cancer is the most common malignancy in Australian women. As most women now survive breast cancer, improving quality-of-life outcomes is increasingly important and major changes are occurring in breast surgery to meet this challenge. Use of neoadjuvant chemotherapy results in lower mastectomy rates, broader surgical options and less surgical morbidity. Oncoplastic breast surgery (OBS) facilitates less frequent need for mastectomy, better aesthetic outcomes and improved quality of life. Immediate breast reconstruction (IBR) improves quality of life and can be considered in a large proportion of women requiring mastectomy; however, Australia's rate of IBR is low compared with similar countries. Breast cancer risk reduction can be achieved with lifestyle modifications and, in women at high risk, chemoprevention with selective oestrogen receptor modulators or aromatase inhibitors. Bilateral prophylactic mastectomy is an option for BRCA gene mutation carriers or those women otherwise established to have a high level of risk. Contralateral prophylactic mastectomy (CPM) is increasingly performed at the time of initial breast cancer management, largely driven by patient preference. However, CPM does not improve survival and has similar rates of complications as therapeutic mastectomy. It should be cautiously considered, with full discussion of risks and benefits. Breast Surgeons of Australia and New Zealand (BreastSurgANZ) coordinates training of most new breast surgeons and is fostering a broader range of multidisciplinary oncology, OBS and IBR skills in its members. The BreastSurgANZ Quality Audit monitors the quality of care provided by members. Training breast surgeons now have access to a Graduate Certificate in Surgery (Breast Surgery) to broaden their knowledge base.

Abstract P2-09-09: Risk-reducing surgery and cancer-related distress among female BRCA1 and BRCA2 mutation carriers

Abstract Background: Distress levels among female BRCA1 and BRCA2 mutation carriers can be similar to levels reported among breast cancer patients. However, there is a lack of data on long-term psychosocial functioning, and it is not known if uptake of risk-reducing surgery influences long-term cancer related distress in women with a BRCA mutation who are unaffected with cancer. The objective of this study was to evaluate long-term cancer-related distress in women with a BRCA mutation, and to evaluate predictors of distress, including uptake of cancer risk reducing surgery. Methods: Female BRCA1 or BRCA2 mutation carriers, ages 25-55, and without cancer were eligible to complete the survey online. A validated instrument, Impact of Events Scale (IES)-Revised (Horowitz 1979, Weis &amp; Marmar 1995; 0-80 overall scale), was used to assess current levels of cancer risk-related psychological distress. Respondents were recruited through the Facing Our Risk of Cancer Empowered (FORCE) advocacy organization, which includes women at high risk of breast cancer. This interim analysis is part of a larger multi-center patient preference study of BRCA mutation carriers designed to assess women's willingness to adopt hypothetical treatments to prevent breast cancer. Linear regression was used to evaluate predictors of IES distress levels. Results: Between January and April 2015, 259 women completed the survey. The mean age of the participants was 41 years, and the mean time since receipt of genetic test results was 3.5 years (range 0-16; median 2 years). One hundred thirty-six (52%) women elected for prophylactic bilateral mastectomy (PBM), 139 (54%) elected for bilateral salpingo oophorectomy (BSO) (93 [36%] women had both surgeries), and 77 (30%) had not undergone risk-reducing surgery. The mean total IES score was 15.1 (range 0-72; median 11). Overall, 54 (21%) women reported moderate or severe cancer-related distress, and those who had undergone risk-reducing surgery reported lower perceived risk of developing breast cancer. Results to date indicate that shorter time since notification of mutation status, not having PBM (with or without BSO) (table), and not completing post-secondary education were independent predictors of higher IES distress scores. IES severityNo prophylactic surgeryPBM onlyBSO onlyPBM and BSOn (%)77434693Subclinical27 (35)23 (54)16 (35)44 (47)Mild26 (34)13 (30)21 (46)35 (38)Moderate18 (23)5 (12)6 (13)11 (12)Severe6 (8)2 (5)3 (6)3 (3) Conclusions: This study measured cancer-related distress in a large population of women with BRCA mutations who participate in the FORCE online support community. Higher levels of distress were associated with not having PBM and more recent genetic test disclosure. These findings are specific to a more informed community of women with high levels of understanding of cancer risk than may be seen in the clinical setting. Citation Format: Liede A, Fairchild A, Friedman S, Amelio J, Hallett DC, Mansfield CA, Metcalfe KA. Risk-reducing surgery and cancer-related distress among female BRCA1 and BRCA2 mutation carriers. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-09.

Impact of hereditary multigene panel testing for cancer survivors.

261 Background: Recently, genetic testing for hereditary cancer syndromes has seen numerous advances in testing spectrum, capability, and efficiency. This may have important implications for cancer survivors and their families. The purpose of this study is to evaluate the impact of reflex genetic testing with newer multi-gene panels on patients with prior negative BRCA1/2 tests. Methods: Data was collected retrospectively from patients who underwent multi-gene panel testing at one of three sites from a single institution between 8/2013-6/2015. Those with a personal history of breast or ovarian cancer and a prior negative BRCA1/2 test were included. Results: Of 914 patients who underwent multi-gene panel tests, 187 met study inclusion criteria. Ten patients (5.3%) were found to carry 11 pathogenic mutations, including 6 patients with mutations in CHEK2, 2 patients with mutations in PTEN, and 1 patient each with mutations in the following genes: BARD1, NF1, and RAD51C. One patient had two pathogenic mutations identified—CHEK2 and BARD1. Of 10 patients with mutations, 9 had a personal history of breast cancer diagnosed at a median age of 43 (range 35-52) and 1 had ovarian cancer diagnosed at age 65. A majority of mutation carriers underwent panel testing years after their cancer diagnosis (median 6 years, range 0.5-32 years) and none with delayed testing had undergone prophylactic contralateral mastectomy prior to the discovery of their gene mutation. All patients with mutations had a family history of at least one cancer, with most having a variety of cancer diagnoses in multiple relatives. Positive panel testing results altered clinical management in most patients, including addition of breast MRI, colonoscopy, or thyroid ultrasound depending on the gene mutation. After discovery of a PTEN mutation 19 years after her initial cancer treatment, one woman underwent bilateral prophylactic mastectomy and was found to have occult ductal carcinoma in situ. Conclusions: Cancer survivorship must incorporate advances in technology that may be beneficial even years after treatment has ended. Multi-gene panel testing can be applied in survivorship settings as a useful tool to guide screening recommendations.

Celebrity Influence and Identification: A Test of the Angelina Effect

Angelina Jolie's announcement that she is a BRCA1 carrier and has had a prophylactic bilateral mastectomy was met with widespread support as well as speculation about its possible impact on the public. These speculations were the subject of a Time magazine cover story titled “The Angelina Effect” (Kluger et al., 2013). Although there is anecdotal evidence to support this hypothesized Angelina effect, empirical tests are lacking. To explore possible links between Angelina's announcement and public health, we surveyed 356 adults immediately after the announcement. Guided by a model of celebrity influence, the survey assessed participants’ demographics and health history, identification and parasocial interaction with Jolie, and genetic testing intentions. Results supported the model's predictions and provided preliminary evidence of an Angelina effect.

Primary peritoneal cancer in BRCA carriers after prophylactic bilateral salpingo-oophorectomy.

The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. Primary peritoneal cancer is an aggressive malignancy which, due to the absence of a specific screening test, cannot be diagnosed in its early stages. As a risk-reducing option, prophylactic bilateral salpingo-oophorectomy and mastectomy are often proposed in BRCA gene carriers. The effectiveness of a preventive surgical treatment is, however, unclear in the development of peritoneal cancer. An extensive electronic search was performed in PubMed, Scopus, and Cochrane databases. The total number of patients who underwent prophylactic bilateral salpingo-oophorectomy was 1,830, of whom 28 presented with peritoneal cancer (1.53%). The age of the included patients ranged from 48 to 61 years. BRCA-1 was present in 9 out of 28 patients and BRCA-2 in 2 patients, while the type of BRCA was unclear in 17 patients. Salpingo-oophorectomy was performed in 23 out of 28 patients, while oophorectomy was carried out in 5 patients. The interval from initial risk-reducing surgical treatment to the presentation of peritoneal cancer ranged from 12 to 84 months. Modification of the follow-up guidelines and increase in healthcare providers' awareness may reduce the risk of peritoneal cancer.

Prophylactic Bilateral Nipple-sparing Mastectomy and a Staged Breast Reconstruction Technique: Preliminary Results.

More high-risk women with breast cancer are identified using genetic testing at a younger age. These young women often opt for prophylactic surgery. Most patients are reluctant for extra donor-site scars besides infections and necrosis. In order to reduce these risks, a two-stage breast reconstruction technique is used for high-risk women with large or ptotic breasts. We presume that this procedure will reduce the risk of skin envelope and nipple–areola complex (NAC) necrosis to less than 1%. In the first stage, an inferior pedicle reduction is performed to obtain large volume reduction with maximal safety for the NAC. The ptosis, skin excess, and malpositioning of the NAC are corrected safely at this stage. In the second stage, the skin-sparing mastectomy is performed with or without nipple sparing. During this procedure, the areola is never removed. A bilateral breast reconstruction is then performed with an immediate subpectoral prothesis or delayed with the use of a subpectoral tissue expander. In this way, we aim to meet the patient’s wish to undergo bilateral risk reducing mastectomy in breasts that need ptosis correction without donor-site scarring. This article describes the procedure and reports the preliminary data.