Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial.

BACKGROUND: Concurrent chemoradiotherapy has been the standard of care for locally advanced cervical cancer for over 20 years; however, 30-40% of treated patients have recurrence or progression within 5 years. Immune checkpoint inhibition has improved outcomes for patients with PD-L1 positive metastatic or recurrent cervical cancer. We assessed the benefit of adding durvalumab, a PD-L1 antibody, with and following chemoradiotherapy for locally advanced cervical cancer. METHODS: The CALLA randomised, double-blind, phase 3 trial included 105 hospitals across 15 countries. Patients aged at least 18 years with previously untreated locally advanced cervical cancer (adenocarcinoma, squamous, or adenosquamous; International Federation of Gynaecology and Obstetrics [FIGO] 2009 stage IB2-IIB lymph node positive, stage ≥III any lymph node status) and WHO or Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) through an interactive web response system using a permuted block size of 4 to receive durvalumab (1500 mg intravenously once every 4 weeks) or placebo with and following chemoradiotherapy, for up to 24 cycles. Chemoradiotherapy included 45 Gy external beam radiotherapy at 5 fractions per week concurrent with intravenous cisplatin (40 mg/m2) or carboplatin (area under the concentration-time curve 2) once weekly for 5 weeks, followed by image-guided brachytherapy (high-dose rate, 27·5-30 Gy or low-dose/pulse-dose rate, 35-40 Gy). Randomisation was stratified by disease stage status (FIGO stage and node status) and geographical region. Chemoradiotherapy quality was continuously reviewed. The primary endpoint was progression-free survival, assessed by the investigator using Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03830866. FINDINGS: Between Feb 15, 2019, and Dec 10, 2020, 770 women were randomly assigned (385 to durvalumab and 385 to placebo; median age 49 years [IQR 41-57]). Median follow-up was 18·5 months (IQR 13·2-21·5) in the durvalumab group and 18·4 months (13·2-23·7) in the placebo group. At data cutoff, median progression-free survival had not been reached (95% CI not reached-not reached) for either group (HR 0·84; 95% CI 0·65-1·08; p=0·17); 12-month progression-free survival was 76·0% (71·3-80·0) with durvalumab and 73·3% (68·4-77·5) with placebo. The most frequently reported grade 3-4 adverse events in both groups were anaemia (76 [20%] of 385 in the durvalumab group vs 56 [15%] of 384 in the placebo group) and decreased white blood cells (39 [10%] vs 49 [13%]). Serious adverse events occurred for 106 (28%) patients who received durvalumab and 89 (23%) patients who received placebo. There were five treatment-related deaths in the durvalumab group (one case each of urinary tract infection, blood loss anaemia, and pulmonary embolism related to chemoradiotherapy only; one case of endocrine disorder related to durvalumab only; and one case of sepsis related to both durvalumab and chemoradiotherapy). There was one treatment-related death in the placebo group (pneumonia related to chemoradiotherapy). INTERPRETATION: Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Concurrent durvalumab plus chemoradiotherapy warrants further exploration in patients with high tumoral PD-L1 expression. Rigorous monitoring ensured high chemoradiotherapy compliance with advanced technology and allowed patients to receive optimal care. FUNDING: AstraZeneca.

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission.

OBJECTIVE: To investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy. METHODS: This single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics. RESULTS: Twenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6-13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%). CONCLUSIONS: Hu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy. TRIAL REGISTRATION: NCT01137071.

Quality of life of locally advanced cervical cancer patients after neoadjuvant chemotherapy followed by chemoradiation versus chemoradiation alone (CIRCE trial): a randomized phase II trial.

OBJECTIVE: The CIRCE trial (NCT01973101) investigated the efficacy, safety, and quality of life of the addition of neoadjuvant chemotherapy with cisplatin and gemcitabine to standard chemoradiation for locally advanced cervical cancer (stages IIB-IVA). The impact of both treatment arms on quality of life is reported in the present study. METHODS: Patients completed the European Organization of Research and Treatment of Cancer questionnaire QLQ-C30 and CX24 before treatment and at 3, 6, 9, and 12 months after treatment. Linear mixed models were fitted to analyze differences in quality of life over time and between groups. Differences in mean quality of life scales >10 points and p<0.05 were considered clinically relevant and statistically significant, respectively. Inclusion criteria were: (1) histological diagnosis of locally advanced invasive carcinoma of the uterine cervix, International Federation of Gynecology and Obstetrics stages IIB-IVA; (2) signed informed consent to participate in the CIRCE trial; and (3) answered at least one quality of life questionnaire. Excluded were patients who did not complete any quality of life questionnaire. Relevant exclusion criteria for the CIRCE trial included Eastern Cooperative Oncology Group performance status >2 and peripheral neuropathy >2. Mann-Whitney U tests were performed to assess differences between groups in quality of life at baseline. To evaluate differences between treatment arms, linear mixed models were fitted using the transformed quality of life scores as a dependent variable and time of follow-up and study arm as factors. RESULTS: A total of 107 patients were enrolled (n=55 neoadjuvant chemotherapy arm; n=52 chemoradiation arm). Quality of life compliance rates were higher for the chemoradiation group at every assessment time (ranging from 75-86.5% in the chemoradiation arm vs 55-81.8% in the neoadjuvant chemotherapy arm). For quality of life results at baseline, no statistically significant difference between the groups was seen. For both groups, most scales showed improvements over time, except for worsening of the summary score, sexual enjoyment, peripheral neuropathy, and menopausal symptoms. For chemoradiation, body image was lower (p<0.001) and patients presented more lymphedema (p<0.001) and sexual worry (p<0.001) at 12 months compared with baseline. Comparing study arms, neoadjuvant chemotherapy showed significantly lower scores in the menopausal symptoms scale (p=0.03) and higher scores for sexual/vaginal functioning (p=0.01). At 12 months, clinical differences were seen only for body image and menopausal symptoms scale, with neoadjuvant chemotherapy presenting better body image scores and a lower burden of menopausal symptoms. CONCLUSION: After treatment for locally advanced cervical cancer, patients improved in most quality of life aspects. However, worsening was observed in sexual enjoyment, peripheral neuropathy, and menopausal symptoms. To improve patients' quality of life, efforts should be made to prevent and treat these long term effects of locally advanced cervical cancer treatment.

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness.

OBJECTIVE: Three cycles of neoadjuvant chemotherapy (NACT) followed by interval debulking (ID) surgery is an alternative for patients with advanced ovarian cancer unresectable disease. This study aimed to determine the efficacy and safety of six cycles of NACT followed by cytoreduction. METHODS: Retrospective analysis of all patients with advanced epithelial ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma treated with platinum based NACT between January 2008 and February 2012. RESULTS: Eighty-two patients underwent NACT; 78% and 18.2% had extensive stage IIIC or IV disease at diagnosis, respectively. Their median age was 60 years (41-82). On histology, serous adenocarcinoma was found in 90.2%. Patients did not receive chemotherapy after debulking surgery. 35.4% suffered grade 3/4 toxicity; the most commonly observed toxicities were hematologic and nausea. After NACT, 23.1% experienced clinical complete response, 57.4% partial response, and 12.1% disease progression. Complete resection of all macroscopic and microscopic disease (R0) was performed in 63.7%. Surgical complications were uncommon; however, four (6.2%) patients needed a second procedure due to operative complications and 18 (27.3%) needed blood transfusion after debulking. Over a median follow-up period of 19.2 months, median overall survival and chemotherapy-free interval were 37.5 months (confidence interval not reached) and 16 months, respectively. CONCLUSION: Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did not increase perioperative or postoperative complications in patients with stage IIIC/IV disease who were unsuitable for optimal PDS. The overall survival of this cohort was higher than that of those treated with ID surgery.

Frequency of Radiation Therapy-Induced Malignancies in Patients With Li-Fraumeni Syndrome and Early-Stage Breast Cancer and the Influence of Radiation Therapy Technique.

PURPOSE: Breast cancer (BC) is the most common malignancy in female patients with Li-Fraumeni syndrome (LFS), a condition associated with an increased risk of various malignancies, including radiation therapy (RT)-induced malignancies (RIM) within previously irradiated areas. Our study aimed to assess the incidence of RIM in patients with LFS and early-stage BC treated with adjuvant RT, including the effect of RT dose and technique. METHODS AND MATERIALS: We examined patients with a germline pathogenic/likely pathogenic TP53 variant diagnosed with early-stage BC and monitored by a hereditary cancer team at a single cancer center. The study endpoints included RIM frequency, the association of RIM with the dose and type of RT (2-dimensional [2D] RT, 3-dimensional [3D] RT, and intensity modulated RT [IMRT]), and BC recurrence. RESULTS: We analyzed 48 patients with a median age of 39 years (range, 21-62). The majority (71%) had the TP53 R337H variant, and 87% were unaware of their LFS diagnosis at the time of BC treatment. Treatment modalities included mastectomy (62%), (neo)adjuvant chemotherapy (66%), and RT (62%), with RT being more common after breast-conserving surgery (87% vs 46% with mastectomy, P = .010). Among the 30 patients treated with RT, 10% developed RIM in the irradiated field, consisting of 3 soft tissue malignancies. RT dose (≤40.8 or >40.8 Gy) did not influence RIM occurrence, but the type of RT did. RIM was observed in 100% of cases with 2D RT (2/2), 50% with IMRT (1/2), and 0% with 3D RT (0/16) (P = .004). CONCLUSIONS: Our study underscores a concerning rate of RIM after adjuvant RT, emphasizing the importance of a thorough risk-benefit evaluation before recommending RT, with preference for its avoidance if possible. Although subgroup sizes were limited, the risk of RIM appeared to be influenced by the RT technique, with higher rates observed with 2D RT and IMRT compared with 3D RT. Early TP53 testing is essential to guide the BC treatment plan.

Economic Modelling of Screen-and-Treat Strategies for Brazilian Women at Risk of Hereditary Breast and Ovarian Cancer.

BACKGROUND: Clinical evidence supports the use of genetic counselling and BRCA1/2 testing for women at risk for hereditary breast and ovarian cancer. Currently, screen-and-treat strategies are not reimbursed in the Brazilian Unified Healthcare System (SUS). The aim of this modelling study was to evaluate the cost effectiveness of a gene-based screen-and-treat strategy for BRCA1/2 in women with a high familial risk followed by preventive interventions compared with no screening. METHODS: Adopting the SUS perspective, a Markov model with a lifelong time horizon was developed for a cohort of healthy women aged 30 years that fulfilled the criteria for BRCA1/2 testing according to the National Comprehensive Cancer Network (NCCN) guideline. For women who tested positive, preventive options included intensified surveillance, risk-reducing bilateral mastectomy and bilateral salpingo-oophorectomy. The Markov model comprised the health states 'well', 'breast cancer', 'death' and two post-cancer states. Outcomes were the incremental costs per quality-adjusted life-year (QALY) and the incremental costs per life-year gained (LYG). Data were mainly obtained by a literature review. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of the results. RESULTS: In the base case, the screen-and-treat strategy resulted in additional costs of 3515 Brazilian reais (R$) (US$1698) and a gain of 0.145 QALYs, compared with no screening. The incremental cost-effectiveness ratio (ICER) was R$24,263 (US$21,724) per QALY and R$27,258 (US$24,405) per LYG. Applying deterministic sensitivity analyses, the ICER was most sensitive to the probability of a positive test result and the discount rate. In the probabilistic sensitivity analysis, a willingness to pay of R$25,000 per QALY gained for the screen-and-treat strategy resulted in a probability of cost effectiveness of 80%. CONCLUSION: Although there is no rigorous cost-effectiveness threshold in Brazil, the result of this cost-effectiveness analysis may support the inclusion of BRCA1/2 testing for women at high-risk of cancer in the SUS. The ICER calculated for the provision of genetic testing for BRCA1/2 approximates the cost-effectiveness threshold proposed by the World Health Organization (WHO) for low- and middle-income countries.

Outcomes and Prognostic Factors in a Large Cohort of Hospitalized Cancer Patients With COVID-19.

PURPOSE: Patients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19. METHODS: All consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes. RESULTS: Five hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST. CONCLUSION: A high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.

Management of cervical cancer patients during the COVID-19 pandemic: a challenge for developing countries.

During the COVID-19 pandemic, health services worldwide are going through important adaptations to assist patients infected with COVID-19, at the same time as continuing to provide assistance to other potentially life-threatening diseases. Although patients with cancer may be at increased risk for severe events related to COVID-19 infection, their oncologic treatments frequently cannot be delayed for long periods without jeopardising oncologic outcomes. Considering this, a careful consideration for treatment management of different malignancies is required. Cervical cancer is concentrated mainly in low-middle income countries (LMICs), which face particular challenges during the COVID-19 pandemic due to the scarcity of health resources in many places. Although cervical cancer is the fourth cause of cancer death among women, it receives little attention from international Oncology societies and scientific research studies. In this review paper, we discuss the cervical cancer landscape and provide specialists recommendations for its management during the COVID-19 pandemic, particularly focused on LMICs' reality.

The prognostic role of microRNA in epithelial ovarian cancer: a systematic review of literature with an overall survival meta-analysis.

Objective: To accomplish a systematic review of literature with overall survival meta-analysis about the role of microRNA in epithelial ovarian cancer as prognostic and predictive factor to chemotherapy response. Methods: A search was conducted in the PubMed database, using the keywords "microRNA" and "ovarian cancer" or "miRNA" and "ovarian cancer". Original articles published before 02/02/2019 that had as main subject microRNA (miRNA) and ovarian cancer were included. We considered for inclusion only studies that associated microRNA to chemotherapy-related diagnosis, prognosis, or response in ovarian cancer. Results: The literature search returned 1,482 articles, 497 of which fulfilled inclusion criteria, yielding 350 miRNAs. The status of each miRNA was assessed in serum and tissue of ovarian cancer, benign tumors, and healthy tissue. The status of up-/downregulation of miRNAs was related to prognostic features (overall survival and disease-free survival) and response predictive features such as platinum and paclitaxel sensitivity/resistance. The miRNAs that had been cited three or more times were selected for prognostic and response predictive features analysis. Twelve miRNAs fulfilled all these criteria and were included in the overall survival meta-analysis. Conclusions: miRNAs affect virtually all mechanisms of carcinogenesis, working as either oncogenes or tumor suppressor genes. In this systematic review we identified miRNAs that may be related to prognosis, diagnosis, and chemotherapy sensitivity. The 12 miRNAs identified here should be included in future studies for validation.

Adjuvant Carboplatin and Paclitaxel Chemotherapy Followed by Radiotherapy in High-Risk Endometrial Cancer: A Retrospective Analysis.

PURPOSE: The best adjuvant treatment in high-risk endometrial cancer remains unclear. Although adjuvant chemotherapy seems to improve overall survival (OS) in locally advanced disease, the role of adding radiotherapy is not certain. We evaluated the outcomes of patients with high-risk endometrial cancer treated with adjuvant chemotherapy followed by radiotherapy. PATIENTS AND METHODS: We performed a retrospective analysis of patients with high-risk endometrial cancer (endometrioid histology stages III to IVA or carcinosarcoma, clear cell, or serous histology stages I to IVA) treated with adjuvant carboplatin and paclitaxel, followed by radiotherapy, from 2010 to 2017 at a Brazilian cancer center. The Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed using the Cox proportional hazards model. RESULTS: One hundred forty-six consecutive patients were evaluated. The OS rates were 86.2% at 3 years and 75.4% at 5 years. OS was significantly affected by pelvic lymphadenectomy ( P = .001) and positive peritoneal cytology ( P < .001). Three- and 5-year disease-free survival (DFS) rates were 78.3% and 69.5%, respectively. The initial site of recurrence was limited to the pelvis in 4.1% of patients, within the abdomen in 1.3%, and extra-abdominal in 11.6%. Patients with grade 1 or 2 endometrioid carcinoma had better prognosis than patients with endometrioid carcinoma grade 3 or nonendometrioid histology (3-year DFS, 93.67% v 68.5%, respectively; P = .0017). CONCLUSION: Adjuvant carboplatin and paclitaxel, followed by radiotherapy, is effective in high-risk endometrial cancer and associated with low rates of pelvic recurrence, which might be explained by the addition of radiotherapy. The high-risk group is heterogeneous, and the benefit of adjuvant treatment in patients with grade 1 or 2 endometrioid carcinoma is less clear.

Palliative Care in the Global Setting: ASCO Resource-Stratified Practice Guideline.

Purpose The purpose of this new resource-stratified guideline is to provide expert guidance to clinicians and policymakers on implementing palliative care of patients with cancer and their caregivers in resource-constrained settings and is intended to complement the Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update of 2016. Methods ASCO convened a multidisciplinary, multinational panel of experts in medical oncology, family medicine, radiation oncology, hematology/oncology, palliative and/or hospice care, pain and/or symptom management, patient advocacy, public health, and health economics. Guideline development involved a systematic literature review, a modified ADAPTE process, and a formal consensus-based process with the Expert Panel and additional experts (consensus ratings group). Results The systematic review included 48 full-text publications regarding palliative care in resource-constrained settings, along with cost-effectiveness analyses; the evidence for many clinical questions was limited. These provided indirect evidence to inform the formal consensus process, which resulted in agreement of ≥ 75% (by consensus ratings group including Expert Panel). Recommendations The recommendations help define the models of care, staffing requirements, and roles and training needs of team members in a variety of resource settings for palliative care. Recommendations also outline the standards for provision of psychosocial support, spiritual care, and opioid analgesics, which can be particularly challenging and often overlooked in resource-constrained settings. Additional information is available at www.asco.org/resource-stratified-guidelines . It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Bringing a humanistic approach to cancer clinical trials.

In this article, we describe some practical aspects that promote the humanisation of clinical research. Actions are not limited to improving the communication skills of medical staff but also include maintenance of care continuity, accessible written information, and application of theoretic models such as shared decision-making and management of stress in decision-making under uncertainty. We believe that a comprehensive strategy will increase patients' motivation to participate in and adhere to clinical research.

Predictability of BRCA1/2 mutation status in patients with ovarian cancer: How to select women for genetic testing in middle-income countries.

OBJECTIVES: To evaluate the accuracy of algorithms for predicting BRCA1/2 germ-line mutation carrier probability, and to identify factors that could improve their performance among Brazilian women with ovarian cancer (OC). STUDY DESIGN: In this cross-sectional study, we enrolled patients (unselected for family history of cancer) undergoing treatment or follow-up for OC in a single centre in Brazil. Clinical and demographic data, including family history of cancer, were obtained. Blood samples were collected for genetic testing. MAIN OUTCOME MEASURES: The entire coding sequence of BRCA1 and BRCA2 was evaluated for mutations. Mutation carrier probability was calculated using BOADICEA, BRCAPRO, Myriad and the Manchester score. Sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curves (AUC) were calculated for each algorithm. Logistic regression was used to detect additional factors associated with BRCA1/2 status, and these were added to the algorithms before recalculating the AUCs. RESULTS: BRCA1/2 mutations were identified in 19 of the 100 included patients. BOADICEA outperformed other algorithms (sensitivity, 73.7%; specificity, 87.7%; AUC, 0.87, with a threshold of a 10% risk of mutation). Later menarche was associated with the presence of a BRCA1/2 mutation. Although adding age at menarche resulted in a larger AUC for all models, this increase was significant only for the Myriad algorithm. CONCLUSION: A BOADICEA risk evaluation of 10% or more most accurately predicted BRCA1/2 status, and the inclusion of age at menarche tended to improve the performance of all algorithms. Using these tools could reduce the number of tests, but at the expense of missing a significant proportion of mutation carriers.