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OBJECTIVE: Patients undergoing gynecologic cancer surgery at our centre are recommended up to 28 days of enoxaparin for extended post-operative thromboprophylaxis (EP). Baseline survey revealed 92% patient adherence, but highlighted negative effects on patient experience due to the injectable route of administration. We aimed to improve patient experience by reducing pain and bruising by 50%, increasing adherence by 5%, and reducing out-of-pocket cost after introducing apixaban as an oral alternative for EP. METHODS: In this interrupted time series quality improvement study, gynecologic cancer patients were offered a choice between apixaban (2.5 mg orally twice daily) or enoxaparin (40 mg subcutaneously once daily) at time of discharge. A multidisciplinary team informed project design, implementation, and evaluation. Process interventions included standardized orders, patient and care team education programs. Telephone survey at 1 and 6 weeks and chart audit informed outcome, process, and balancing measures. RESULTS: From August to October 2022, 127 consecutive patients were included. Apixaban was chosen by 84%. Survey response rate was 74%. Patients who chose apixaban reported significantly reduced pain, bruising, increased confidence with administration, and less negative impact of the medication (p < 0.0001 for all). Adherence was unchanged (92%). The proportion of patients paying less than $125 (apixaban cost threshold) increased from 45% to 91%. There was no difference in bleeding and no VTE events. CONCLUSIONS: Introduction of apixaban for EP was associated with significant improvement in patient-reported quality measures and reduced financial toxicity with no effect on adherence or balancing measures. Apixaban is the preferred anticoagulant for EP at our centre.
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Testes Genéticos , Mutação em Linhagem Germinativa , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/prevenção & controle , Testes Genéticos/métodos , Testes Genéticos/normas , Predisposição Genética para DoençaRESUMO
BACKGROUND: Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking. METHODS: We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion). The primary outcome was cancer recurrence in the pelvic area (pelvic recurrence) at 3 years. The prespecified noninferiority margin for the between-group difference in pelvic recurrence at 3 years was 4 percentage points. RESULTS: Among 700 patients who underwent randomization (350 in each group), the majority had tumors that were stage IB1 according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), that had squamous-cell histologic features (61.7%), and that were grade 1 or 2 (59.3%). With a median follow-up time of 4.5 years, the incidence of pelvic recurrence at 3 years was 2.17% in the radical hysterectomy group and 2.52% in the simple hysterectomy group (an absolute difference of 0.35 percentage points; 90% confidence interval, -1.62 to 2.32). Results were similar in a per-protocol analysis. The incidence of urinary incontinence was lower in the simple hysterectomy group than in the radical hysterectomy group within 4 weeks after surgery (2.4% vs. 5.5%; P = 0.048) and beyond 4 weeks (4.7% vs. 11.0%; P = 0.003). The incidence of urinary retention in the simple hysterectomy group was also lower than that in the radical hysterectomy group within 4 weeks after surgery (0.6% vs. 11.0%; P<0.001) and beyond 4 weeks (0.6% vs. 9.9%; P<0.001). CONCLUSIONS: In patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov number, NCT01658930.).
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Carcinoma de Células Escamosas , Histerectomia , Neoplasias do Colo do Útero , Feminino , Humanos , Canadá , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Histerectomia/efeitos adversos , Histerectomia/métodos , Linfonodos/patologia , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Incontinência Urinária/etiologia , Retenção Urinária/etiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVES: Optimal management of patients with stage IA p53abn endometrial cancer without myoinvasion, classified as intermediate risk in the 2020 European Society of Gynaecological Oncology, European Society for Radiotherapy and Oncology, and European Society of Pathology (ESGO-ESTRO-ESP) guidelines, and the 2022 European Society of Medical Oncology (ESMO) guidelines, is currently unclear. Practice varies from surgery alone to adjuvant radiation±chemotherapy. Our aim was to assess the risk of disease recurrence in patients with stage IA p53abn endometrial cancer without myoinvasion compared with stage IA with myoinvasion (<50%). METHODS: Stage IA p53abn endometrial cancers were identified from retrospective cohorts. Cases were segregated into stage IA with no myoinvasion, including (1) tumor restricted to a polyp, (2) residual endometrial tumor, and (3) no residual tumor in hysterectomy specimen, versus stage IA p53abn with myoinvasion (<50%), with treatment and outcomes assessed. RESULTS: There were 65 stage IA p53abn endometrial cancers with no myoinvasion (22 polyp confined, 38 residual endometrial tumor, 2 no residual in hysterectomy specimen, 3 not specified) and 97 with myoinvasion. There was no difference in survival outcomes in patients with stage IA without myoinvasion (16% of patients recurred, 19% if there was residual endometrial disease) compared with stage IA with myoinvasion (17%). The risk of recurrence was lowest in patients with stage IA p53abn endometrial cancer without myoinvasion treated with chemotherapy±radiation (8%). Most recurrences in patients with stage IA without myoinvasion were distant (89%), with no isolated vaginal vault recurrences, and all except one distant recurrence occurred in patients who had not received adjuvant chemotherapy. CONCLUSION: The recurrence rate in patients with stage IA p53abn endometrial cancer without myoinvasion was 16%, highest in the setting of residual endometrial disease (19%), and exceeding the threshold where adjuvant therapy is often considered. The high frequency of distant recurrences observed may support chemotherapy as part of the treatment regimen.
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Neoplasias do Endométrio , Recidiva Local de Neoplasia , Feminino , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias do Endométrio/patologia , Radioterapia AdjuvanteRESUMO
Objective: Serous tubal intraepithelial carcinoma (STIC) are precursors for high grade serous carcinomas (HGSC) of tubo-ovarian origin. It is a rare entity, most commonly described in patients with a BRCA pathogenic variant (PV) undergoing risk-reducing surgery. Little is known about the risk of subsequent HGSC in patients found to have an isolated STIC without a genetic PV. The objective of this study is to report the outcomes of STIC diagnosed in patients with negative genetic testing ("average risk"). Methods: Retrospective population-based cohort study from British Columbia, Canada. Chart review of patients diagnosed with an isolated STIC from January 2012 to May 2022. Average risk patients are defined as individuals with known negative genetic testing results. Treatment and outcomes are described in the "average risk", BRCA PV, and total cohorts. Results: Twenty-nine patients with isolated STIC were identified. Ten patients had a BRCA PV, four had other variants identified (BRIP1, MLH1, BRIP1 VUS, BRCA 2 VUS), nine had no PV identified ("average risk"), and six were unknown (no genetic testing). Of the nine "average risk" patients, eight (89%) underwent surgical staging. Three (33.3%) had subsequent HGSC diagnosed 29, 70 and 86 months after STIC diagnosis. Conclusions: STIC identified in patients with negative genetic testing are at risk of subsequent HGSC. Patients developed primary peritoneal HGSC despite surgical staging. These patients should also be included in future meta-analysis to determine outcomes and optimal treatment.
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OBJECTIVES: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during another pelvic surgery for the purpose of ovarian cancer prevention. Herein, we describe the rates of OS at the time of hysterectomy and tubal sterilization between 2017 and 2020. METHODS: This study uses the Canadian Institute of Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories except for Quebec between the fiscal years 2017 and 2020. A descriptive analysis on all people aged 15 years and older who had hysterectomies or tubal sterilizations was conducted to determine the proportion of hysterectomies that included bilateral salpingectomy (OS) and the proportion of tubal sterilizations that were OS compared to tubal ligation. RESULTS: There were 174 006 people included in the study. The proportion of hysterectomies that included OS increased from 31.7% in 2017 to 39.9% by 2020. With respect to tubal sterilizations, rates of OS increased from 26.3% of all tubal sterilizations in 2017 to 42.5% in 2020. British Columbia remained the jurisdiction with the highest rates of OS, but rates increased significantly in many jurisdictions, particularly at the time of tubal sterilization. CONCLUSION: The rates of OS have continued to increase in all Canadian jurisdictions following the official Society of Obstetricians and Gynaecologists of Canada recommendation to consider OS in 2015. Assuming that all tubal ligations could have been OS and 75% of hysterectomies with ovarian conservation could have included OS, our data indicate 76 932 missed opportunities for ovarian cancer prevention.
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OBJECTIVES: The landscape of early-stage endometrial cancer treatment has changed dramatically over the last decade. The aim of this study is to provide a real-world view of the impact sentinel lymph node (SLN) biopsy has had on both clinical practice and patient outcomes. We describe detection and recurrence rates, as well as our experience in managing low volume lymph node disease. METHODS: We conducted an international, multicenter retrospective cohort study of 1012 patients with apparent early-stage endometrial cancer. Eligible patients underwent primary surgical staging and SLN biopsy in one of three large academic tertiary cancer centers in Canada or the Republic of Korea between 2015 and 2019. Demographic, surgical, clinicopathologic and recurrence data were collected through chart review. RESULTS: A total of 1012 patients were included. Overall SLN detection rate for all tracer types was 94.1% and recurrence rate was 5.3%. Higher FIGO stage (III vs. I/II) was associated with failed bilateral mapping (OR 2.27, 95%CI 1.14-4.52). We identified seven patients with micrometastases and 12 with isolated tumor cells, of which only one patient with micrometastases recurred at 17 months. Recurrence rates based on risk groups were 2.1%, 5.3%, 8.1%, and 9.9% for low, intermediate, high-intermediate, and high risk, respectively. CONCLUSION: SLN biopsy is safe and feasible. Detection rates are high, regardless of which tracer type is used and recurrence rates are low, especially in low and intermediate risk disease. Patients with low volume metastases appear to have low risk of recurrence, but replication of our findings by large prospective studies are needed to elucidate their clinical importance.
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Neoplasias do Endométrio , Linfonodo Sentinela , Feminino , Humanos , Biópsia de Linfonodo Sentinela , Linfonodos/patologia , Estudos Retrospectivos , Micrometástase de Neoplasia/patologia , Excisão de Linfonodo , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/patologia , Estadiamento de Neoplasias , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologiaRESUMO
Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches. This was a retrospective cohort study of surgically treated cervical cancer at 11 Canadian institutions from 2007 to 2017. Cases initially treated with cervical conization and subsequent hysterectomy, with no residual disease on hysterectomy specimen were included. They were subdivided according to minimally invasive (laparoscopic/robotic (MIS) or laparoscopically assisted vaginal/vaginal hysterectomy (LVH)), or abdominal (AH). Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Within the total cohort, 238/1696 (14%) had no residual disease on hysterectomy specimen (122 MIS, 103 AH, and 13 VLH). The majority of cases in the cohort were FIGO 2018 stage IB1 (43.7%) and underwent a radical hysterectomy (81.9%). There was no statistical difference between stage, histology, and radical vs simple hysterectomy between the abdominal and minimally invasive groups. There were no significant differences in RFS (5-year: MIS/LVH 97.7%, AH 95.8%, p = 0.23) or OS (5-year: MIS/VLH 98.9%, AH 97.4%, p = 0.10), although event-rates were low. There were only two recurrences. In this large study including only patients with no residual cervical cancer on hysterectomy specimen, no significant differences in survival were seen by surgical approach. This may be due to the small number of events or due to no actual difference between the groups. Further studies are warranted.
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Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Canadá , HisterectomiaRESUMO
Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is the gold standard preventative option for BRCA mutation carriers at high risk for ovarian and breast cancer. However, when performed at the recommended ages of 35-45 years, RRBSO induces immediate premature surgical menopause, along with the accompanying adverse psychosocial, cardiovascular, bone, and cognitive health consequences. While these health consequences have been thoroughly studied in the general population, little is known about the long-term health outcomes in the BRCA population. Hormone replacement therapy (HRT) until the average age of natural menopause can help mitigate these health risks, yet the initiation of HRT is a complex decision among BRCA carriers due to concern of increasing the already high risk of breast cancer in these people. This review summarizes the current research on long-term non-cancer risks in BRCA carriers following RRBSO-induced premature surgical menopause, and highlights the existing evidence in support of HRT use in this population.
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BACKGROUND: More research is needed that compares the outcomes between those who underwent a hysterectomy for endometriosis with conservation of one or both ovaries and those who underwent a hysterectomy with bilateral salpingo-oophorectomy. OBJECTIVE: This study aimed to compare the rate and types of reoperations (primary outcome) and use of other pain-related health services (secondary outcomes) among people who underwent a hysterectomy with conservation of both ovaries, those who underwent a hysterectomy with unilateral salpingo-oophorectomy, and those who underwent a hysterectomy with bilateral salpingo-oophorectomy. STUDY DESIGN: This was a population-based, retrospective cohort study of 4489 patients aged 19 to 50 years in British Columbia, Canada, who underwent a hysterectomy for endometriosis between 2001 and 2016. Index surgeries were classified as hysterectomy alone (conservation of both ovaries), hysterectomy with unilateral salpingo-oophorectomy, or hysterectomy with bilateral salpingo-oophorectomy. Reoperation rate was the primary outcome. Secondary outcomes (measured at 3-12 months and 1-5 years after hysterectomy) included physician visits for endometriosis and pelvic pain, prescriptions filled for opioids, and use of hormonal suppression medications and hormone replacement therapy. RESULTS: Reoperation rates were low across all groups, with 89.5% of all patients remaining reoperation free by the end of follow-up (median of 10 years; interquartile range, 6.1-14.3 years). Patients who underwent a hysterectomy alone were more likely to undergo at least 1 reoperation when compared with those who underwent a hysterectomy with bilateral salpingo-oophorectomy (13% vs 5%; P<.0001), most commonly an oophorectomy or adhesiolysis. When oophorectomy as reoperation was removed in a sensitivity analysis, this difference was partially attenuated (6% of hysterectomy alone group vs 3% of hysterectomy with bilateral salpingo-oophorectomy group undergoing at least 1 reoperation). All groups were very similar in terms of rates of physician visits for endometriosis or pelvic pain and the number of days of opioid prescriptions filled. Furthermore, the rate of hormonal suppression medication use was similar among the groups, whereas the rate of prescriptions filled for hormone replacement therapy after hysterectomy with bilateral salpingo-oophorectomy was 60.6% of patients who filled at least 1 prescription at 3 to 12 months after index surgery. CONCLUSION: Patients who underwent a hysterectomy with bilateral salpingo-oophorectomy had a lower reoperation rate than those who underwent a hysterectomy with conservation of one or both ovaries. However, there was little difference between the groups for the secondary outcomes measured, including physician visits for endometriosis and pelvic pain, opioid use, and use of hormonal suppression medications, suggesting that persistent pelvic pain after hysterectomy for endometriosis may not differ substantively based on ovarian conservation status. One limitation was the inability to stratify patients by stage of endometriosis or to determine the impact of endometriosis stage or the presence of adnexal disease or deep endometriosis on the outcomes. Moreover, hormone replacement therapy prescriptions was not filled by about 40% of patients after hysterectomy with bilateral salpingo-oophorectomy, which may have significant health consequences for these individuals undergoing premature surgical menopause. Therefore, strong consideration should be given to ovarian conservation at the time of hysterectomy for endometriosis.
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Endometriose , Feminino , Humanos , Endometriose/cirurgia , Estudos Retrospectivos , Analgésicos Opioides , Ovariectomia , Histerectomia , Dor Pélvica/etiologia , Dor Pélvica/cirurgia , Colúmbia BritânicaRESUMO
PURPOSE: In 2020, ASCO recommended that all women with epithelial ovarian cancer have germline testing for BRCA1/2 mutations, and those without a germline pathogenic variant (PV) should have somatic tumor testing to determine eligibility for a poly (ADP-ribose) polymerase inhibitor. Consequently, the majority of patients with ovarian cancer will have both germline testing and somatic testing. An alternate strategy is tumor testing first and then germline testing if there is a PV in the tumor and/or significant family history. The objective was to conduct a cost-effectiveness analysis comparing the two testing strategies. METHODS: The Markov model compared the costs (US dollars) and benefits of two testing strategies for newly diagnosed ovarian cancer: (1) ASCO strategy and (2) tumor testing triage for germline testing. Data were applied from SOLO-1, and costs were from wholesale acquisition prices, Medicare, and published sources. Sensitivity analyses accounted for uncertainty around various parameters. Monte Carlo simulation estimated the number tested and identified with germline and somatic BRCA PV for olaparib maintenance treatment annually in the US population. RESULTS: The ASCO strategy was more effective but more costly than tumor testing triage in identifying patients for olaparib, with an incremental cost-effectiveness ratio of $281,296 US dollars per progression-free life year gained. Assuming 10,000 eligible patients with ovarian cancer annually, Monte Carlo simulation yielded comparable numbers of patients with BRCA PV in the germline and tumor with the ASCO and tumor testing triage strategies (2,080 v 2,062, respectively), but substantially higher number of patients tested using the ASCO strategy (8,052 v 3,076). CONCLUSION: The ASCO strategy may identify more BRCA PVs but is not cost-effective. Tumor testing in epithelial ovarian cancer as triage for germline testing is the favored strategy in this health care system.
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Antineoplásicos , Neoplasias Ovarianas , Idoso , Feminino , Humanos , Difosfato de Adenosina/uso terapêutico , Proteína BRCA1/genética , Carcinoma Epitelial do Ovário/diagnóstico , Células Germinativas/patologia , Mutação em Linhagem Germinativa/genética , Medicare , Neoplasias Ovarianas/diagnóstico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Ribose/uso terapêutico , Estados UnidosRESUMO
Individuals with proven hereditary cancer syndrome (HCS) such as BRCA1 and BRCA2 have elevated rates of ovarian, breast, and other cancers. If these high-risk people can be identified before a cancer is diagnosed, risk-reducing interventions are highly effective and can be lifesaving. Despite this evidence, the vast majority of Canadians with HCS are unaware of their risk. In response to this unmet opportunity for prevention, the British Columbia Gynecologic Cancer Initiative convened a research summit "Gynecologic Cancer Prevention: Thinking Big, Thinking Differently" in Vancouver, Canada on 26 November 2021. The aim of the conference was to explore how hereditary cancer prevention via population-based genetic testing could decrease morbidity and mortality from gynecologic cancer. The summit invited local, national, and international experts to (1) discuss how genetic testing could be more broadly implemented in a Canadian system, (2) identify key research priorities in this topic and (3) outline the core essential elements required for such a program to be successful. This report summarizes the findings from this research summit, describes the current state of hereditary genetic programs in Canada, and outlines incremental steps that can be taken to improve prevention for high-risk Canadians now while developing an organized population-based hereditary cancer strategy.
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Predisposição Genética para Doença , Neoplasias dos Genitais Femininos , Colúmbia Britânica , Feminino , Testes Genéticos , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/prevenção & controle , Humanos , RiscoRESUMO
BACKGROUND: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during hysterectomy for benign indications or instead of tubal ligation, for the purpose of preventing ovarian cancer. We determined rates of OS at the time of hysterectomy and tubal sterilization and examined how they changed over the study period. METHODS: Using data from the Canadian Institute for Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories (except Quebec) between the fiscal years 2011 and 2016, we conducted a descriptive analysis of all patients aged 15 years or older who underwent hysterectomy or tubal sterilization. We excluded those with diagnostic codes for any gynecologic cancer and those who underwent unilateral salpingectomy. We examined the proportion who had OS during their hysterectomy and compared the proportion of tubal sterilizations that were OS with the proportion that were tubal ligations. RESULTS: A total of 318 528 participants were included in the study (mean age 42.5 yr). The proportion of hysterectomies that included OS increased from 15.4% in 2011 to 35.5% by 2016. With respect to tubal sterilization, the rate of OS increased from 6.5% of all tubal sterilizations in 2011 to 22.0% in 2016. There was considerable variation across jurisdictions in 2016, with British Columbia having the highest rates (53.2% of all hysterectomies and 74.0% of tubal sterilizations involved OS). INTERPRETATION: The rates of OS increased between 2011 and 2016, but there was considerable variation across the included jurisdictions. Our study indicates room for rates of OS to increase across many of the included jurisdictions.
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Neoplasias Ovarianas , Esterilização Tubária , Adulto , Colúmbia Britânica , Feminino , Humanos , Histerectomia/métodos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/cirurgia , Salpingectomia/métodos , Esterilização Tubária/métodosRESUMO
OBJECTIVE: Examine the risks of fractures and osteoporosis after risk-reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA1/2 mutations. METHODS: In this retrospective population-based study in British Columbia, Canada, between 1996 to 2017, we compared risks of osteoporosis and fractures among women with BRCA1/2 mutations who underwent RRBSO before the age of 50 (n=329) with two age-matched groups without known mutations: 1) women who underwent bilateral oophorectomy (BO) (n=3,290); 2) women with intact ovaries who had hysterectomy or salpingectomy (n=3,290). Secondary outcomes were: having dual-energy X-ray absorptiometry (DEXA) scan, and bisphosphonates use. RESULTS: The mean age at RRBSO was 42.4 years (range, 26-49) and the median follow-up for women with BRCA1/2 mutations was 6.9 years (range, 1.1-19.9). There was no increased hazard of fractures for women with BRCA1/2 mutations (adjusted hazard ratio [aHR]=0.80; 95% confidence interval [CI]=0.56-1.14 compared to women who had BO; aHR=1.02; 95% CI=0.65-1.61 compared to women with intact ovaries). Among women who had DEXA-scan, those with BRCA1/2 mutations had higher risk of osteoporosis (aHR=1.60; 95% CI=1.00-2.54 compared to women who had BO; aHR=2.49; 95% CI=1.44-4.28 compared to women with intact ovaries). Women with BRCA1/2 mutations were more likely to get DEXA-scan than either control groups, but only 46% of them were screened. Of the women with BRCA1/2 mutations diagnosed with osteoporosis, 36% received bisphosphonates. CONCLUSION: Women with BRCA1/2 mutations had higher risk of osteoporosis after RRBSO, but were not at increased risk of fractures during our follow-up. Low rates of DEXA-scan and bisphosphonates use indicate we can improve prevention of bone loss.
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Neoplasias da Mama , Osteoporose , Neoplasias Ovarianas , Adulto , Proteína BRCA1/genética , Densidade Óssea/genética , Neoplasias da Mama/genética , Difosfonatos , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Pessoa de Meia-Idade , Mutação , Osteoporose/epidemiologia , Osteoporose/genética , Neoplasias Ovarianas/genética , Ovariectomia/efeitos adversos , Estudos Retrospectivos , Salpingo-Ooforectomia/efeitos adversosRESUMO
Importance: Opportunistic salpingectomy (OS), which is the removal of fallopian tubes during hysterectomy or instead of tubal ligation without removal of ovaries, is recommended to prevent ovarian cancer, particularly serous ovarian cancer. However, the effectiveness of OS is still undetermined. Objective: To examine observed vs expected rates of ovarian cancer among individuals who have undergone OS. Design, Setting, and Participants: This is a population-based, retrospective cohort study of all individuals in British Columbia, Canada, who underwent OS or a control surgery (hysterectomy alone or tubal ligation) between 2008 and 2017, with follow-up until December 31, 2017. Those with any gynecological cancer diagnosed before or within 6 months of their procedure were excluded. Data analysis was performed from April to August 2021. Exposures: Removal of both fallopian tubes at the time of hysterectomy or instead of tubal ligation while leaving ovaries intact. Main Outcomes and Measures: An ovarian cancer diagnosis listed in the British Columbia Cancer Registry. Age-specific rates of epithelial and serous ovarian cancer in the control group were combined with the specific follow-up time in the OS group to calculate expected numbers (and 95% CIs) of ovarian cancers in the OS group. These were compared with observed numbers. Age-adjusted expected and observed numbers of breast and colorectal cancers were also examined in the OS group. Results: There were 25â¯889 individuals who underwent OS (mean [SD] age, 40.2 [7.1] years; median [IQR] follow-up, 3.2 [1.6-5.1] years) and 32â¯080 who underwent hysterectomy alone or tubal ligation (mean [SD] age, 38.2 [7.9] years; median [IQR] follow-up, 7.3 [4.6-8.7] years). There were no serous ovarian cancers in the OS group and 5 or fewer epithelial ovarian cancers. The age-adjusted expected number was 5.27 (95% CI, 1.78-19.29) serous cancers and 8.68 (95% CI, 3.36-26.58) epithelial ovarian cancers. Age-adjusted expected vs observed numbers of breast cancers (22.1 expected vs 23 observed) and colorectal cancers (9.35 expected vs 8 observed) were not significantly different. Conclusions and Relevance: In this cohort study, the OS group had significantly fewer serous and epithelial ovarian cancers than were expected according to the rate at which they arose in the control group. These findings suggest that OS is associated with reduced ovarian cancer risk.
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Carcinoma Epitelial do Ovário/prevenção & controle , Salpingectomia/métodos , Adulto , Colúmbia Britânica/epidemiologia , Carcinoma Epitelial do Ovário/epidemiologia , Feminino , Humanos , Histerectomia , Estudos RetrospectivosRESUMO
Next-generation sequencing assays are capable of identifying cancer patients eligible for targeted therapies and can also detect germline variants associated with increased cancer susceptibility. However, these capabilities have yet to be routinely harmonized in a single assay because of challenges with accurately identifying germline variants from tumor-only data. We have developed the Oncology and Hereditary Cancer Program targeted capture panel, which uses tumor tissue to simultaneously screen for both clinically actionable solid tumor variants and germline variants across 45 genes. Validation using 14 tumor specimens, composed of patient samples and cell lines analyzed in triplicate, demonstrated high coverage with sensitive and specific identification of single-nucleotide variants and small insertions and deletions. Average coverage across all targets remained >2000× in 198 additional patient tumor samples. Analysis of 55 formalin-fixed, paraffin-embedded tumor samples for the detection of known germline variants within a subset of cancer-predisposition genes, including one multiexon deletion, yielded a 100% detection rate, demonstrating that germline variants can be reliably detected in tumor samples using a single panel. Combining targetable somatic and actionable germline variants into a single tumor tissue assay represents a streamlined approach that can inform treatment for patients with advanced cancers as well as identify those with potential germline variants who are eligible for confirmatory testing, but would not otherwise have been identified.
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Predisposição Genética para Doença/genética , Células Germinativas , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias/diagnóstico , Neoplasias/genética , Alelos , Estudos de Coortes , Variações do Número de Cópias de DNA , Confiabilidade dos Dados , Feminino , Testes Genéticos/métodos , Humanos , Mutação INDEL , Polimorfismo de Nucleotídeo Único , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Examine the risk of cardiovascular disease (CVD) following risk reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA mutations. METHODS: In this retrospective population-based study in British Columbia, Canada, between 1996 and 2017, we compared the risk of CVD among women with known BRCA mutations who underwent RRBSO before the age of 50 (n = 360) with two groups of age-matched women without known BRCA mutations: 1) women who underwent bilateral oophorectomy (BO) for benign conditions (n = 3600); and, 2) women with intact ovaries who had hysterectomy or salpingectomy (n = 3600). Our primary outcome was CVD (a composite (any of) myocardial infarction, heart failure, and/or cerebrovascular disease). Secondary outcomes included a diagnostic code for predisposing conditions (hypertension, dyslipidemia, and/or diabetes mellitus), and use of cardioprotective medications (statins and/or beta-blockers). RESULTS: We report no significant increased risk for CVD between women with BRCA mutations and women who underwent BO (aHR = 1.08, 95%CI: 0.72-1.62), but women with BRCA mutations were less likely to be diagnosed with predisposing conditions (aHR = 0.69, 95%CI: 0.55-0.85). Compared to women without BRCA mutations with intact ovaries who underwent hysterectomy or salpingectomy, women with BRCA mutations had significantly increased risk for CVD (aHR = 1.82, 95%CI: 1.18-2.79) and were less likely to be diagnosed with predisposing conditions (aHR = 0.78, 95%CI: 0.62-0.97) and to fill cardioprotective medications (aHR = 0.88, 95%CI: 0.64-1.22). CONCLUSION: Our results suggest an opportunity for improved prevention of CVD in women with BRCA mutations after prophylactic oophorectomy. Despite the observed lower prevalence of predisposing conditions for CVD and lesser use of cardioprotective medications, this population did not have a lower rate of CVD.
Assuntos
Doenças Cardiovasculares/epidemiologia , Salpingo-Ooforectomia/estatística & dados numéricos , Adulto , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Salpingo-Ooforectomia/efeitos adversosRESUMO
BACKGROUND: Minimally invasive surgery (MIS) is a standard surgical approach for comprehensive surgical staging in women with endometrial cancer. As rates and complexity of MIS are steadily increasing, it is important to identify potential risk factors which may be associated with this approach. This study evaluates the impact of local factors on the risk of disease recurrence. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) who underwent MIS between 2012 and 2016 at eight Canadian centers. Data was collected from medical records. The 75th percentile was calculated for estimated uterine volume and weight. All recurrences were categorized into two groups; intra-abdominal vs. extra-abdominal. To search for significant covariates associated with recurrence-free survival a Cox proportional hazard model was performed. RESULTS: A total of 758 patients were included in the study. Intra-uterine manipulator was used in 497 (35.8%) of patients. Vaginal lacerations were documented in 9.1%. Median follow-up was 30.5 months (interquartile range 20-47). There were 157 who had disease recurrence (20.71%), including 92 (12.14%) intra-abdominal and 60 (7.92%) extra-abdominal only recurrences. In univariate analysis myometrial invasion, LVI, stage, uterine volume and weight > 75th percentile and chemotherapy were associated with increased risk of intra-abdominal recurrence. In multivariable analysis only stage, and specimen weight > 75th percentile (OR 2.207, CI 1.123-4.337) remained significant. Uterine volume, and weight were not associated with increased risk of extra-abdominal recurrences. CONCLUSION: For patients diagnosed with HGEC undergoing MIS, extracting a large uterus is associated with a significantly increased risk for intra-abdominal recurrence.