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Background:The BRCA1 and BRCA2 genes confer increased susceptibility to breast and ovarian cancer and to a spectrum of other cancers. There is controversy regarding the risk of colorectal cancer conferred by germline mutations in these two genes.Methods:We followed 7015 women with a BRCA mutation for new cases of colorectal cancer. Incidence rates in carriers were compared with population-specific incidence rates, and standardised incidence ratios (SIRs) were estimated. The expected numbers of cancers were computed by multiplying person-years at risk by the appropriate age-, sex- and country-specific incidence rates from the five countries.Results:Twenty-one incident colorectal cancer cases were observed among all mutation carriers, compared with 23.6 cases expected. The SIR for BRCA1 carriers was 0.92 (95% confidence interval (CI), 0.54-1.40, P=0.7) and for BRCA2 carriers was 0.82 (95% CI, 0.30-1.81, P=0.7). The SIR for colon cancer was 3.81 (95% CI 1.77-7.23) for women below the age of 50 years (both genes combined) and was 0.60 (95% CI 0.33-1.00) for women aged 50 years and above.Conclusion:The risk of colorectal cancer is increased in female carriers of BRCA1 mutations below the age of 50 years but not in women with BRCA2 mutations or in older women. [ABSTRACT FROM AUTHOR]

Background:Germline mutations in BRCA1 and BRCA2 predispose to pancreatic cancer. We estimated the incidence of pancreatic cancer in a cohort of female carriers of BRCA1 and BRCA2 mutation. We also estimated survival rates in pancreatic cancer cases from families with a BRCA mutation.Methods:We followed 5149 women with a mutation for new cases of pancreatic cancer. The standardised incidence ratios (SIR) for pancreatic cancer were calculated based on age group and country of residence. We also reviewed the pedigrees of 8140 pedigrees with a BRCA1 or a BRCA2 mutation for those with a case of pancreatic cancer. We recorded the year of diagnosis and the year of death for 351 identified cases.Results:Eight incident pancreatic cancer cases were identified among all mutation carriers. The SIR for BRCA1 carriers was 2.55 (95% CI=1.03-5.31, P=0.04) and for BRCA2 carriers was 2.13 (95% CI=0.36-7.03, P=0.3). The 5-year survival rate was 5% for cases from a BRCA1 family and 4% for cases from a BRCA2 family.Conclusion:The risk of pancreatic cancer is approximately doubled in female BRCA carriers. The poor survival in familial pancreatic cancer underscores the need for novel anti-tumoural strategies. [ABSTRACT FROM AUTHOR]

Genetic testing for mutations in BRCA1 and BRCA2 is available in Canada for women with a significant family history of breast cancer. For the majority of tested women, a BRCA1 or BRCA2 mutation is not found, and counselling regarding breast cancer risk is based on the review of the pedigree. In this prospective study, we estimate breast cancer risks in women with a family history of breast cancer and for whom the proband tested negative for a mutation in BRCA1 or BRCA2. Families with two or more breast cancers under the age of 50 years, or with three cases of breast cancer at any age, and who tested negative for a BRCA1 or BRCA2 mutation were identified. Follow-up information on cancer status was collected on all first-degree relatives of breast cancer cases. The standardised incidence ratios (SIRs) for breast cancer were calculated by dividing the observed numbers of breast cancer by the expected numbers of breast cancers, based on the rates in the provincial cancer registries. A total of 1492 women from 365 families were included in the analyses. The 1492 first-degree relatives of breast cancer cases contributed 9109 person-years of follow-up. Sixty-five women developed breast cancer, compared to 15.2 expected number (SIR=4.3). The SIR was highest for women under the age of 40 (SIR=14.9) years and decreased with increasing age. However, the absolute risk was higher for women between the age of 50 and 70 (1% per year) years than for women between 30 and 50 (0.4% per year) years of age. There was no elevated risk for ovarian, colon or any other form of cancer. Women with a significant family history of breast cancer (ie, two or more breast cancers under the age of 50 years, or three or more breast cancers at any age), but who test negative for BRCA mutations have approximately a four-fold risk of breast cancer. Women in these families may be candidates for tamoxifen chemoprevention and/or intensified breast screening with an MRI.British Journal of Cancer (2009) 100, 421–425. doi:10.1038/sj.bjc.6604830 www.bjcancer.com Published online 16 December 2008 [ABSTRACT FROM AUTHOR]

Abstract Background Women who are notified they carry a BRCA1/2 mutation are presented with surgical options to reduce their risk of breast and ovarian cancer, including risk-reducing mastectomy (RRM) and risk-reducing oophorectomy (RRO). Growing evidence suggests that a sub-group of women do not make decisions about RRM and RRO immediately following genetic testing, but rather, consider these decisions years later. Women's perspectives on the timing of these decisions are not well understood. Accordingly, the purpose of this research was to describe how women construct the 'right time' to consider decisions about RRM and RRO. Methods In-depth interviews were conducted with 22 BRCA1/2 carrier women and analyzed using qualitative, constant comparative methods. Results The time that lapsed between receipt of genetic test results and receipt of RRM or RRO ranged from three months to nine years. The findings highlighted the importance of considering decisions about RRM and RRO one at a time. The women constructed the 'right time' to consider these decisions to be when: (1) decisions fit into their lives, (2) they had enough time to think about decisions, (3) they were ready emotionally to deal with the decisions and the consequences, (4) all the issues and conflicts were sorted out, (5) there were better options available, and (6) the health care system was ready for them. Conclusions These findings offer novel insights relevant to health care professionals who provide decision support to women considering RRM and RRO.

BACKGROUND: Screening mammography is associated with a small dose of radiation to the breast, and women with increased genetic risk might be particularly sensitive to the DNA-damaging effects of ionising radiation. We aimed to assess whether exposure to ionising radiation through mammography screening was associated with risk of breast cancer in BRCA1 or BRCA2 mutation carriers. METHODS: We identified 1600 cases of breast cancer and 1600 controls without breast cancer who were matched for BRCA mutation, date of birth (within 1 year), and country of residence from an international registry of BRCA1 and BRCA2 mutation carriers. We used a questionnaire to inquire about whether participants had ever had screening mammography, and, if so, the age at which they first had the procedure. RESULTS: We found no association between ever having screening mammography and risk of breast cancer (odds ratio [OR] 1.03 [95% CI 0.85-1.25], adjusted for parity, oral-contraceptive use, ethnic origin, and bilateral oophorectomy). The association was much the same for BRCA1 mutation carriers and BRCA2 mutation carriers (1.04 [0.84-1.29] vs 1.06 [0.67-1.66], respectively, adjusted for parity, oral-contraceptive use, ethnic origin, and bilateral oophorectomy). INTERPRETATION: These findings do not lend support to the idea that exposure to ionising radiation through routine screening mammography contributes substantially to the burden of breast cancer in BRCA1 and BRCA2 mutation carriers. Prospective studies are needed to confirm the results of this initial report, and, where possible, these studies should assess a more appropriate endpoint of total exposure. [ABSTRACT FROM AUTHOR]

Background: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain., Methods: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047., Findings: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths., Interpretation: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy., Funding: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society., Competing Interests: Declaration of interests AN reports honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Merck. ADC reports research grants for the STAMPEDE trial from Janssen, Astellas, Novartis, Sanofi, and Clovis. CMH is an executive committee member for the British Uro-Oncology Group. CNC reports support for the present manuscript from the Canadian Cancer Trials Group; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer Corp, Knight Therapeutics, and AbbVie. CLG reports that they participate in the independent data monitoring and steering committee for the BARCODE study at the Institute of Cancer Research in London (principal investigator Ros Eeles). CB reports stock or stock options from GSK; and has been an employee at GSK since August, 2023. CCP reports consulting fees from AAA, ITM Radiopharma, Myovant, and Clarity Pharmaceuticals to his institution; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen and Bayer to his institution. FS reports grants or contracts from Janssen, Bayer, Merck, Pfizer, Astellas, Bristol Myers Squibb (BMS), Novartis, Sanofi, and AstraZeneca to his institution; consulting fees from Janssen, Bayer, Astellas, BMS, Novartis, Sanofi, AstraZeneca, Merck, and Pfizer to him; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Janssen, Bayer, Myovant, Astellas, BMS, Novartis, Sanofi, AstraZeneca, Merck, and Pfizer to him. LCB reports that their previous Institute of Cancer role was funded in part by a Biomedical Research Centre grant which was paid to the institution; the role was not connected to the RADICALS trial. MRS reports research grants and biomarker testing costs, all to institution and all active in past 36 months but on research outside of this research, from Astellas, Clovis Oncology, Janssen, Novartis, and Sanofi-Aventis; consulting fees from Eli Lilly; speaker fees at a clinical trial statistics training meeting for clinicians (no discussion of particular drugs) from Lilly Oncology, Janssen, and Eisai; and is an independent member of many independent data monitoring committees but all for academic sponsors and unpaid. NDJ is a Senior Investigator for the National Institute for Health and Care Research. NWC reports honoraria for lectures, advisory boards, and symposia from AstraZeneca, Janssen, Bayer, and Pfizer; support for travel to and attendance at a European meeting from Bayer; participation on an independent data monitoring committee for the Probio trial (Karolinska), and the trial steering committee for the Capi 28 Trial (AstraZeneca) and the STAMPEDE Trial (Medical Research Council [MRC]); and is the Joint National Clinical Lead for National Prostate Cancer Audit. PW reports an educational event payment from Astellas; conference and travel cost support from AstraZeneca and Aventis; and participation on the advisory board for Ferring and Roche. PWMC reports grants or contracts from CARO-ACURA and the Canadian Institutes of Health Research; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer and EMD Serono; and participation on a data safety monitoring board or advisory board for TerSera, AbbVie, Tolmar, and Knight Therapeutics. PMP reports participation on a data safety monitoring board or advisory board for AAA Nordic, MSD, and Pfizer Denmark. SCM reports honoraria from Janssen, Astellas, Knight Therapeutics, Amgen Pharmaceutical, AstraZeneca, AbbVie, and Bayer; and support for attending meetings or travel from TerSera and Sanofi. WRC reports consulting fees from Bayer and Janssen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Astellas, Bayer, Janssen, AAA Novartis, and Myriad Genetics; and support for attending meetings or travel from Janssen, AAA Novartis, and Bayer. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Hypertension affects 1 in 5 Canadians and is the leading cause of morbidity and mortality globally. Hypertension control is declining due to multiple factors including lack of access to primary care. Consequently, patients with hypertension frequently visit the emergency department (ED) due to high blood pressure (BP). Telehealth for Emergency-Community Continuity of Care Connectivity via Home-Telemonitoring Blood Pressure is a pilot project that implements and evaluates a comprehensive home blood pressure telemonitoring (HBPT) and physician case management protocol designed as a postdischarge management strategy to support patients with asymptomatic elevated BP as they transition from the ED to home., Objective: Our objective was to conduct a feasibility study of an HBPT program for patients with asymptomatic elevated BP discharged from the ED., Methods: Patients discharged from an urban, tertiary care hospital ED with asymptomatic elevated BP were recruited in Vancouver, British Columbia, Canada, and provided with HBPT technology for 3 months of monitoring post discharge and referred to specialist hypertension clinics. Participants monitored their BP twice in the morning and evenings and tele-transmitted readings via Bluetooth Sensor each day using an app. A monitoring clinician received these data and monitored the patient's condition daily and adjusted antihypertensive medications. Feasibility outcomes included eligibility, recruitment, adherence to monitoring, and retention rates. Secondary outcomes included proportion of those who were defined as having hypertension post-ED visits, changes in mean BP, overall BP control, medication adherence, changes to antihypertensive medications, quality of life, and end user experience at 3 months., Results: A total of 46 multiethnic patients (mean age 63, SD 17 years, 69%, n=32 women) found to have severe hypertension (mean 191, SD 23/mean 100, SD 14 mm Hg) in the ED were recruited, initiated on HBPT with hypertension specialist physician referral and followed up for 3 months. Eligibility and recruitment rates were 40% (56/139) and 88% (49/56), respectively. The proportion of participants that completed ≥80% of home BP measurements at 1 and 3 months were 67% (31/46) and 41% (19/46), respectively. The proportion of individuals who achieved home systolic BP and diastolic BP control at 3 months was 71.4% (30/42) and 85.7% (36/42) respectively. Mean home systolic and diastolic BP improved by -13/-5 mm Hg after initiation of HBPT to the end of the study. Patients were prescribed 1 additional antihypertensive medication. No differences in medication adherence from enrollment to 3 months were noted. Most patients (76%, 25/33) were highly satisfied with the HBPT program and 76% (25/33) found digital health tools easy to use., Conclusions: HBPT intervention is a feasible postdischarge management strategy and can be beneficial in supporting patients with asymptomatic elevated BP from the ED. A randomized trial is underway to evaluate the efficacy of this intervention on BP control., (©Karen C Tran, Meagan Mak, Laura M Kuyper, Jesse Bittman, Birinder Mangat, Heather Lindsay, Chad Kim Sing, Liang Xu, Hubert Wong, Martin Dawes, Nadia Khan, Kendall Ho. Originally published in JMIR Formative Research (https://formative.jmir.org), 30.01.2024.)

Background: Radiotherapy (RT) and surgery are potential treatment options in patients with biochemical recurrence (BCR) following primary prostate cancer treatment. This study examines the value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-informed surgery and RT in patients with BCR treated without systemic therapy., Methods: This is a post-hoc subgroup analysis of a prospective clinical trial. Inclusion criteria were: histologically proven prostate cancer at initial curative-intent treatment, BCR after primary treatment with curative intent, having five or fewer lesions identified on [ 18 F]DCFPyL PET/CT, and treatment with either PET/CT-directed RT or surgery without systemic therapy. The biochemical progression-free survival after PSMA ligand PET/CT-directed RT and surgery was determined. Uni- and multivariate Cox regression analyses were performed for the association of patients' characteristics, tumor-specific variables, and PSMA PET/CT imaging results with biochemical progression at the last follow-up., Results: Fifty-eight patients (30 in surgery and 28 in radiotherapy groups) met the inclusion criteria. A total of 87 PSMA-positive lesions were detected: 16 local recurrences (18.4%), 54 regional lymph nodes (62.1%), 6 distant lymph nodes (6,8%), and 11 osseous lesions (12.7%). A total of 85.7% (24 of 28) and 70.0% (21 of 30) of patients showed a ≥ 50% decrease in prostate-specific antigen (PSA) levels after RT and surgery, respectively. At a median follow-up time of 21 months (range, 6-32 months), the median biochemical progression-free survival was 19 months (range, 4 to 23 months) in the radiotherapy group, as compared with 16.5 months (range, 4 to 28 months) in the surgery group. On multivariate Cox regression analysis, the number of PSMA positive lesions (2-5 lesions compared to one lesion), and the anatomic location of the detected lesions (distant metastasis vs. local relapse and pelvic nodal relapse) significantly correlated with biochemical progression at the last follow-up, whereas other clinical, tumor-specific, and imaging parameters did not., Conclusions: This study suggests that RT or surgery based on [ 18 F]DCFPyL PET/CT are associated with high PSA response rates. The number and site of lesions detected on the PSMA PET/CT were predictive of biochemical progression on follow-up. Further studies are needed to assess the impact of targeting these sites on patient relevant outcomes., Trial Registration: Registered September 14, 2016; NCT02899312; https://clinicaltrials.gov/ct2/show/NCT02899312., (© 2023. The Author(s).)

Background: We evaluated measures to protect healthcare workers (HCWs) in Vancouver, Canada, where variants of concern (VOC) went from <1% VOC in February 2021 to >92% in mid-May. Canada has amongst the longest periods between vaccine doses worldwide, despite Vancouver having the highest P.1 variant rate outside Brazil., Methods: With surveillance data since the pandemic began, we tracked laboratory-confirmed SARS-CoV-2 infections, positivity rates, and vaccine uptake in all 25,558 HCWs in Vancouver Coastal Health, by occupation and subsector, and compared to the general population. Cox regression modelling adjusted for age and calendar-time calculated vaccine effectiveness (VE) against SARS-CoV-2 in fully vaccinated (≥ 7 days post-second dose), partially vaccinated infection (after 14 days) and unvaccinated HCWs; we also compared with unvaccinated community members of the same age-range., Findings: Only 3.3% of our HCWs became infected, mirroring community rates, with peak positivity of 9.1%, compared to 11.8% in the community. As vaccine coverage increased, SARS-CoV-2 infections declined significantly in HCWs, despite a surge with predominantly VOC; unvaccinated HCWs had an infection rate of 1.3/10,000 person-days compared to 0.89 for HCWs post first dose, and 0.30 for fully vaccinated HCWs. VE compared to unvaccinated HCWs was 37.2% (95% CI: 16.6-52.7%) 14 days post-first dose, 79.2% (CI: 64.6-87.8%) 7 days post-second dose; one dose provided significant protection against infection until at least day 42. Compared with community infection rates, VE after one dose was 54.7% (CI: 44.8-62.9%); and 84.8% (CI: 75.2-90.7%) when fully vaccinated., Interpretation: Rigorous droplet-contact precautions with N95s for aerosol-generating procedures are effective in preventing occupational infection in HCWs, with one dose of mRNA vaccination further reducing infection risk despite VOC and transmissibility concerns. Delaying second doses to allow more widespread vaccination against severe disease, with strict public health, occupational health and infection control measures, has been effective in protecting the healthcare workforce., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Emergency department (ED) access block, the inability to provide timely care for high acuity patients, is the leading safety concern in First World EDs. The main cause of ED access block is hospital access block with prolonged boarding of inpatients in emergency stretchers. Cumulative emergency access gap, the product of the number of arriving high acuity patients and their average delay to reach a care space, is a novel access measure that provides a facility-level estimate of total emergency care delays. Many health leaders believe these delays are too large to be solved without substantial increases in hospital capacity. Our objective was to quantify cumulative emergency access blocks (the problem) as a fraction of inpatient capacity (the potential solution) at a large sample of Canadian hospitals., Methods: In this cross-sectional study, we collated 2015 administrative data from 25 Canadian hospitals summarizing patient inflow and delays to ED care space. Cumulative access gap for high acuity patients was calculated by multiplying the number of Canadian Triage Acuity Scale (CTAS) 1-3 patients by their average delay to reach a care space. We compared cumulative ED access gap to available inpatient bed hours to estimate fractional access gap., Results: Study sites included 16 tertiary and 9 community EDs in 12 cities, representing 1.79 million patient visits. Median ED census (interquartile range) was 66,300 visits per year (58,700-80,600). High acuity patients accounted for 70.7% of visits (60.9%-79.0%). The mean (SD) cumulative ED access gap was 46,000 stretcher hours per site per year (± 19,900), which was 1.14% (± 0.45%) of inpatient capacity., Conclusion: ED access gaps are large and jeopardize care for high acuity patients, but they are small relative to hospital operating capacity. If access block were viewed as a "whole hospital" problem, capacity or efficiency improvements in the range of 1% to 3% could profoundly mitigate emergency care delays.

BRCA mutation carriers may use tamoxifen for breast cancer prevention or treatment. Hormone replacement therapy is often prescribed after surgical menopause and oral contraceptives are recommended for ovarian cancer prevention. The objective of this study was to assess the impact of these medications and other risk factors on endometrial cancer risk in BRCA carriers. Women with a BRCA1 or BRCA2 mutation were identified from a registry of mutation carriers. Cases were 83 women who had a diagnosis of endometrial cancer. Controls were 1027 matched women who did not develop endometrial cancer and who had an intact uterus. All women completed a baseline questionnaire, which included questions about ages at menarche and menopause, oral contraceptive use, hormone replacement therapy use, hysterectomy, oophorectomy, breast cancer history and tamoxifen use. We estimated the odds ratio associated with each risk factor in a multivariate analysis. No differences were found between cases and controls in terms of age at menarche, BMI, smoking, or oral contraceptive use. In a multivariate analysis, for women taking estrogen-only hormone replacement therapy, the odds ratio was 0.23 (95% CI 0.03-1.78, p = 0.16), and for women taking progesterone-only hormone replacement therapy the odds ratio was 6.91 (95% CI 0.99-98.1, p = 0.05). The adjusted odds ratio for endometrial cancer associated with a history of tamoxifen use was 3.50 (95% CI 1.51-8.10, p = 0.003). The observed increased risk of endometrial cancer associated with progesterone-only therapy merits further study.

The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations., (© 2014 UICC.)

Importance: Women who carry a germline mutation in either the BRCA1 or BRCA2 gene face a lifetime risk of breast cancer of up to 70%, and once they receive a diagnosis of breast cancer, they face high risks of both second primary breast and ovarian cancers. Preventive bilateral salpingo-oophorectomy is recommended to women with a BRCA mutation at age 35 years or thereafter to prevent breast and ovarian cancer, but it is unclear whether oophorectomy has an impact on survival in women with BRCA-associated breast cancer., Objective: To estimate the impact of oophorectomy on survival in women with breast cancer with a BRCA1 or BRCA2 mutation., Design, Setting, and Participants: Retrospective analysis of patients selected by pedigree review of families who received counseling at 1 of 12 participating clinical genetics centers. Patients were 676 women with stage I or II breast cancer and a BRCA1 or BRCA2 mutation who were observed for up to 20 years after receiving a diagnosis between 1975 and 2008. Survival experience was compared for women who did and who did not undergo oophorectomy., Main Outcomes and Measures: In all analyses, the primary end point was death due to breast cancer., Results: Of the 676 women, 345 underwent oophorectomy after the diagnosis of breast cancer and 331 retained both ovaries. The 20-year survival for the entire patient cohort was 77.4%. The adjusted hazard ratio for death attributed to breast cancer in women who underwent oophorectomy was 0.38 (95% CI, 0.19-0.77; P = .007) for BRCA1 carriers and 0.57 (95% CI, 0.23-1.43; P = .23) for BRCA2 carriers. The hazard ratio for breast cancer-specific mortality was 0.76 (95% CI, 0.32-1.78; P = .53) for women with estrogen receptor-positive breast cancer and 0.07 (95% CI, 0.01-0.51; P = .009) for women with estrogen receptor-negative breast cancer., Conclusions and Relevance: Oophorectomy is associated with a decrease in mortality in women with breast cancer and a BRCA1 mutation. Women with estrogen receptor-negative breast cancer and a BRCA1 mutation should undergo oophorectomy shortly after diagnosis.

Women with a genetic predisposition to breast cancer may be at increased risk of cancer after exposure to ionizing radiation. It is unclear whether mammography screening increases the risk of breast cancer among BRCA1 and BRCA2 carriers. We identified 2,346 women with a BRCA1 (n = 1844) or BRCA2 (n = 502) mutation and no breast cancer, and we reviewed their history of mammography exposure. These women were followed for an average of 5.3 years and were observed for new breast cancer diagnoses. At study entry, 1808 women (77.1 %) reported ever having had a mammogram; of these, 204 women (11.2 %) reported having had a mammogram before age 30. We estimated the hazard ratios for the development of invasive breast cancer, conditional on the number of prior mammograms and on the age at first mammogram. Hazard ratios were estimated and stratified by gene (BRCA1 or BRCA2), relative to women with no exposure. We observed no significant association between prior mammography exposure and breast cancer risk for BRCA1 carriers (HR 0.79; 95 % CI 0.53-1.19; P = 0.26) or for BRCA2 carriers (HR 0.90; 95 % CI 0.35-2.34; P = 0.83). An early age at first mammogram (<30 years) did not increase breast cancer risk among BRCA1 carriers (HR 0.75; 95 % CI 0.41-1.37; P = 0.35) or among BRCA2 carriers (HR 0.69; 95 % CI 0.19-2.48; P = 0.57). Exposure to mammography in women with BRCA1 and BRCA2 mutations is not associated with an increased risk of breast cancer.

Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80 %. Tamoxifen treatment of the first cancer has been associated with a reduction in the risk of a subsequent contralateral cancer. We studied 1,504 women with a known BRCA1 or BRCA2 mutation, 411 women with bilateral breast cancer (cases) and 1,093 women with unilateral breast cancer (controls) in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of first breast cancer as the cases. For each woman who used tamoxifen, the starting and stopping dates were abstracted and the duration of tamoxifen use was calculated. Three hundred and thirty-one women had used tamoxifen (22 %); of these 84 (25 %) had completed four or more years of tamoxifen, the remainder stopped prematurely or were current users. For women with up to 1 year of tamoxifen use, the odds ratio for contralateral breast cancer was 0.37 (95 % CI 0.20-0.69; p = 0.001) compared to women with no tamoxifen use. Among women with 1-4 years of tamoxifen use the odds ratio was 0.53 (95 % CI 0.32-0.87; p = 0.01). Among women with four or more years of tamoxifen use the odds ratio was 0.83 (95 % CI 0.44-1.55; p = 0.55). Short-term use of tamoxifen for chemoprevention in BRCA1 and BRCA2 mutation carriers may be as effective as a conventional 5-year course of treatment.

Purpose: The purposes of this study were to estimate the reduction in risk of ovarian, fallopian tube, or peritoneal cancer in women with a BRCA1 or BRCA2 mutation after oophorectomy, by age of oophorectomy; to estimate the impact of prophylactic oophorectomy on all-cause mortality; and to estimate 5-year survival associated with clinically detected ovarian, occult, and peritoneal cancers diagnosed in the cohort., Patients and Methods: Women with a BRCA1 or BRCA2 mutation were identified from an international registry; 5,783 women completed a baseline questionnaire and ≥ one follow-up questionnaires. Women were observed until either diagnosis of ovarian, fallopian tube, or peritoneal cancer, death, or date of most recent follow-up. Hazard ratios (HRs) for cancer incidence and all-cause mortality associated with oophorectomy were evaluated using time-dependent survival analyses., Results: After an average follow-up period of 5.6 years, 186 women developed either ovarian (n = 132), fallopian (n = 22), or peritoneal (n = 32) cancer, of whom 68 have died. HR for ovarian, fallopian, or peritoneal cancer associated with bilateral oophorectomy was 0.20 (95% CI, 0.13 to 0.30; P < .001). Among women who had no history of cancer at baseline, HR for all-cause mortality to age 70 years associated with an oophorectomy was 0.23 (95% CI, 0.13 to 0.39; P < .001)., Conclusion: Preventive oophorectomy was associated with an 80% reduction in the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers and a 77% reduction in all-cause mortality., (© 2014 by American Society of Clinical Oncology.)

Purpose: In this program of research, we sought to expand our understanding of how cancer patients' communication needs and preferences change across the course of their illness trajectory. To address known limitations in the empirical knowledge base, we designed a study capitalizing on representative patient reports as they occurred within time and across experience obtaining care for this disease., Methods: We used a longitudinal cohort design informed by interpretive description methodology to follow 125 patients over a multi-year period as they reflected on their ongoing experiences with cancer care communication., Results: In relation to each phase of their cancer care trajectory, patients identified tension points and contextual challenges impinging on what they felt constituted helpful and unhelpful patient-provider communication., Conclusions: Findings from this study create a dynamic portrait of how we can better inform communication approaches and interventions through interpretations of population knowledge and individual experience.

It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.

Background: Communication in cancer care is a recognized problem for patients. Research to date has provided limited relevant knowledge toward solving this problem., Objective: Our research program aims to understand helpful and unhelpful communication from the patient perspective and to document changes in patient needs and priorities over time. In this analysis, we focus on patient perceptions of poor communication., Methods: Using a qualitative longitudinal approach informed by interpretive description methodology, we are following a cohort of adult cancer patients across their cancer journey. We used constant comparative analysis of repeated interviews to examine thematic patterns in their perceptions and interpret both commonalities and diversities., Results: Patient accounts reveal 3 types of poor communication. "Ordinary misses" are everyday missteps for which maturation and socialization may be an adequate solution. "Systemic misunderstandings" are assumptive gaps between patients and professionals, which may be addressed through qualitative research. "Repeat offenders" are a subset of clinicians whose communication patterns become a particular source of patient distress., Conclusions: This typology offers a novel way to conceptualize the problem of poor communication in cancer care toward more effective solutions for the communication problem. Managing the communication of a problematic subset of clinicians will likely require strategic interventions at the level of organizational culture and models of care., Implications for Practice: Nurses can play a meaningful role in detecting and buffering sources of poor communication in the practice context. Addressing poor communication may be a further reason to advocate for interprofessional team-based care models.