Factors Influencing Clinical Follow-Up for Individuals with a Personal History of Breast and/or Ovarian Cancer and Previous Uninformative BRCA1 and BRCA2 Testing

Ovarian cancer is one of the most common cancers of the reproductive organs. As there are no symptoms in the early stages, it is mainly detected in the advanced stages. Even then, the symptoms are non-specific and include, for example, abdominal pain, early satiety, or changes in bowel habits. Both biochemical marker levels and imaging studies are used in the initial diagnosis. However, it should be emphasized that they are not characterized by high specificity. Treatment is multistage, and usually first-line debulking surgery is used followed by platinum-based chemotherapy. Here we present a clinical case of a 56-year-old female, a carrier of a mutation in the BRCA1 gene, with a history of breast cancer and with recurrent epithelial ovarian cancer. The patient was qualified for treatment with a PARP inhibitor and is currently undergoing treatment with olaparib. In the patient’s follow up of 50 months to date, there has been no recurrence of cancer. Few side effects have been observed, and the most serious one that can be effectively treated is anemia. On the basis of the described case, the authors concluded that olaparib treatment is effective, relatively safe, and does not significantly affect daily functioning.

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Factors influencing women’s decisions to getting tested for BRCA mutation

Journal of Nursing Education and Practice ◽

10.5430/jnep.v9n3p33 ◽

2018 ◽

Vol 9 (3) ◽

pp. 33 ◽

Cited By ~ 1

Author(s):

Suha Al-Oballi Kridli ◽

Holly Austin

Keyword(s):

Ovarian Cancer ◽

Brca Mutation ◽

Genetic Mutations ◽

Inclusion Criteria ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Factors Influencing ◽

Brca1 And Brca2 Mutations ◽

Internal And External Factors

Ovarian cancer is the leading cause of death among gynecological cancers. There are many risk factors that can increase a woman’s susceptibility to breast and ovarian cancers, some of which are modifiable. However, non-modifiable risks for breast and ovarian cancer include the presence of genetic mutations (BRCA) increase the risk of these diseases. The purpose of this review was to identify factors, reported in the literature, known to affect women’s decision to get genetic testing for BRCA1 and BRCA2 mutations for hereditary breast and ovarian cancer. A total of 31 studies that met the inclusion criteria were included in this review. Several internal and external factors, influencing women’s decision to getting tested for BRCA mutations, were identified and explained. Implications for clinical practice were provided.

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P5341Predictive factors of atherosclerotic cardiovascular diseases events in HIV-HVC co-infected patients: results from hepavih ANRS co13 cohort

European Heart Journal ◽

10.1093/eurheartj/ehz746.0309 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

F Boccara ◽

B K Tan ◽

M Chalouni ◽

D Salmon Ceron ◽

A Cinaud ◽

...

Keyword(s):

Viral Load ◽

Sustained Viral Response ◽

Biological Data ◽

Personal History ◽

Hiv Viral Load ◽

Factors Associated ◽

Coronary Syndrome ◽

Increased Risk ◽

History Of

Abstract Introduction Several studies highlighted an increased risk of cardiovascular disease (CVD) in HIV-HCV co-infected patients without clearly identifying specific virologic factors associated with atherosclerotic CVD (ASCVD) events. Purpose Hence, we analyzed data collection from the French nationwide ANRS CO13 HEPAVIH cohort to determine the incidence of ASCVD events in HIV-HCV co-infected patients and the predictive factors associated with its occurrence. Methods The French multicenter nationwide ANRS CO13 HEPAVIH clinic-based cohort collected prospective clinical and biological data from HIV-HCV co-infected patients followed-up in 28 different university hospitals between December 2005 to November 2016. Participants with at least one year of follow-up were included. Primary outcome was the occurrence of major ASCVD events (cardiovascular death, acute coronary syndrome, coronary revascularization and stroke). Secondary outcomes were total ASCVD events including major ASCVD events and minor ASCVD events (peripheral arterial disease [PAD]). Incidence rates were estimated using Aalen-Johansen method and factors associated with ASCVD identified with Cox proportional hazards models. Results A total of 1213 patients were included: median age 45.4 years [42.1–49.0], 70.3% men, current smoking 70.2%, overweight 19.5%, liver cirrhosis 18.9%, chronic alcohol consumption 7.8%, diabetes mellitus (5.9%), personal history of CVD 2.7%, and statins use 4.1%. After a median follow-up of 5.1 years [3.9–7.0], 44 participants experienced at least one ASCVD event (26 major ASCVD event, and 20 a minor event). Incidences for total, major and minor ASCVD events were of 6.98 [5.19; 9.38], 4.01 [2.78; 6.00], and 3.17 [2.05; 4.92] per 1000 person-years, respectively. Personal history of CVD (Hazard Ratio (HR)=13.94 [4.25–45.66]), high total cholesterol (HR=1.63 [1.24–2.15]), low HDL cholesterol (HR=0.08 [0.02–0.34]) and undetectable HIV viral load (HR=0.41 [0.18–0.96]) were identified as independent factors associated with major ASCVD events while cirrhosis status, liver fibrosis and HCV sustained viral response were not. Cumulative incidence of CV events Conclusion HIV-HCV co-infected patients experience a high incidence of ASCVD events both coronary and peripheral artery diseases. Traditional CV risk factors are the main determinants of ASCVD whereas undetectable HIV viral load seems to be protective. Management of cholesterol abnormalities and controlling viral load are essential to modify this high cardiovascular risk. Acknowledgement/Funding Agence Natoinale de Recherche sur le SIDA et les Hépatites virales

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Impact of hereditary multigene panel testing for cancer survivors.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.3_suppl.261 ◽

2016 ◽

Vol 34 (3_suppl) ◽

pp. 261-261

Author(s):

Nimmi S. Kapoor ◽

Jennifer Swisher ◽

Rachel E. McFarland ◽

Mychael Patrick ◽

Lisa D. Curcio

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Survivors ◽

Gene Mutation ◽

Gene Panel ◽

Personal History ◽

Panel Testing ◽

Pathogenic Mutations ◽

Gene Panel Testing ◽

History Of

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

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Natural history of mucinous ovarian cancer in Ireland.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17056 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17056-e17056

Author(s):

Darren Cowzer ◽

Emily O'Donovan ◽

Therese Brown ◽

Noreen Gleeson ◽

David James Gallagher

Keyword(s):

Ovarian Cancer ◽

Mismatch Repair ◽

Treatment Protocols ◽

Gastrointestinal Malignancy ◽

Patient Demographics ◽

History Of ◽

Mismatch Repair Proteins ◽

Cancer Treatment Protocols ◽

Carcinoma Of The Ovary

e17056 Background: Mucinous ovarian neoplasmscan arise as benign, borderline or malignant disease. Primary mucinous epithelial ovarian carcinoma (mEOC) represents 3% of invasive EOC. Differentiating primary from metastatic mucinous ovarian cancer is challenging. Systemic management of mucinous ovarian cancer increasingly follow GI cancer treatment protocols. We examined retrospective data at our institution to investigate incidence, management and site of origin of mEOC. Methods: 1,333 ovarian malignancies either diagnosed at or referred to St James Hospital, Dublin (from 2000 – 2016) were evaluated. The diagnosis was based on reported pathology. Patient demographics and investigations were retrospectively analyzed. Tumours were graded according to FIGO criteria. Results: Between 1/1/2000 and 9/12/2016 1,333 primary ovarian malignancies were diagnosed at our institution. 48 (3.6%) of these were mucinous adenocarcinoma and a further 5 (0.38%) were endometriod carcinoma of the ovary with mucinous differentiation. The average age at diagnosis was 48 (range 19-77 years). The majority of cases (87.5%) were stage I (IA 23, IB 2, IC 17, II 0, IIIA 1, IIIB 1, IIIC 3, IV 1) Staging CT thorax, abdomen and pelvis was completed in 44/48 cases and 24/48 (50%) patients underwent endoscopic evaluation of the uper or lower GI tract: 11 (22.9%) patients had both upper and lower GI endoscopy, 8 (16.7%) underwent OGD only and 5 (10.4%) had colonoscopy only. Gastrointestinal malignancy was not diagnosed in any of the patients. A total of 3 patients had immunohistochemistry for mismatch repair proteins performed, all of which demonstrated normal staining. All patients underwent surgical resection, 14 (29.2%) received adjuvant chemotherapy. 12 (25%) patients have died with a median OS of 11.5 months (range 7-108 months). Median follow up is 20.5 months (range 1-85 months) Conclusions: The incidence of mEOC in our population is 3.6%. The majority of patients diagnosed with mEOC over a 16 year period are still alive without evidence of disease, suggesting the diagnosis were ovarian in origin rather than metastatic. Immunohistochemistry for mismatch repair proteins is ongoing and will be presented at the meeting.

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Characteristics of probands with mutations predisposing to gynecologic cancers enrolled in a facilitated cascade testing protocol.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13682 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13682-e13682

Author(s):

Kristina Hwang ◽

Katherine Baumann ◽

Allison Brodsky ◽

Kathleen Lutz ◽

Deanna Gerber ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Diagnosis ◽

Genetic Mutation ◽

Personal History ◽

Gynecologic Cancers ◽

Cascade Testing ◽

Pathogenic Mutations ◽

History Of ◽

Mutation Identification ◽

History Of Cancer

e13682 Background: We sought to evaluate the feasibility of obtaining genetic testing (GT) for first- or second-degree (1°, 2°) family members of a proband known to have actionable germline mutation associated with endometrial and/or ovarian cancer through a coordinated referral system. Here we characterize the initial probands and discuss the time frame of their enrollment in facilitated cascade testing (CT). Methods: Patients with pathogenic mutations associated with gynecologic cancers were determined from cancer genetics and gynecologic oncology clinics. Consenting patients completed a RedCap survey on personal cancer history and history of GT. They were then asked to contact 1° and/or 2° relatives regarding their GT results. Relatives were advised to contact our team. Relatives who consented to the study were referred for GT and contacted for follow up to ascertain whether they received GT and/or took action to reduce cancer risk. Results: From 3/2019- 1/2020, this study has accrued 39 probands. The median age was 39 years (range: 25-68). The most commonly expressed gene mutations were BRCA1 or BRCA2 (87.18%, n=34). Other mutations included BRIP1, MLH1, MSH2, MSH6, and PMS2. The majority (62%) of probands had no personal history of cancer. Among those who had a history of cancer (n=15), 80% had breast and/or ovarian cancer, and 80% reported their genetic mutation was discovered at or after the time of their cancer diagnosis. Median age at time of enrollment in CT was 49 years (range: 29-66) for patients with a history of cancer and 32 years (range: 25- 68) for those without, (p=0.009). Among all probands, the median time between mutation identification and enrollment in CT was 2 years (range=0 to 11). There was no significant difference in time between mutation identification and enrollment in CT when comparing those with and without cancer histories (p=0.5). Conclusions: These results suggest that patients with pathogenic mutations predisposing to gynecologic cancer are willing to undergo CT even if they have no personal history of cancer. Patients with a history of cancer tend to be older at time of enrollment in CT, likely because most discover their genetic mutation at or after the time of cancer diagnosis. With an average of 2 years elapsed between time of mutation identification and enrollment in CT, there is need for expansion of CT accessibility. Increased education and awareness among patients and providers in identifying those who may benefit from CT, screening, and risk reducing surgery to prevent cancer is needed.

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Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: ROSiA Single-Arm Phase 3B Study

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000836 ◽

2016 ◽

Vol 27 (1) ◽

pp. 50-58 ◽

Cited By ~ 29

Author(s):

Amit M. Oza ◽

Frédéric Selle ◽

Irina Davidenko ◽

Jacob Korach ◽

Cesar Mendiola ◽

...

Keyword(s):

Ovarian Cancer ◽

Adverse Events ◽

Single Agent ◽

Clinical Signs ◽

Progression Free Survival ◽

Gynecology And Obstetrics ◽

Common Grade ◽

History Of ◽

Grade 3

ObjectiveThe aim of this study was to assess the safety and efficacy of extending bevacizumab therapy beyond 15 months in nonprogressive ovarian cancer.Patients and MethodsIn this multinational prospective single-arm study (ClinicalTrials.gov NCT01239732), eligible patients had International Federation of Gynecology and Obstetrics stage IIB to IV or grade 3 stage I to IIA ovarian cancer without clinical signs or symptoms of gastrointestinal obstruction or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the preceding 6 months. Prior neoadjuvant chemotherapy was permitted. After debulking surgery, patients received bevacizumab 15 (or 7.5) mg/kg every 3 weeks (q3w) with 4 to 8 cycles of paclitaxel (investigator’s choice of 175 mg/m2 q3w or 80 mg/m2 weekly) plus carboplatin AUC 5 to 6 q3w. Single-agent bevacizumab was continued until progression or for up to 24 months. The primary end point was safety.ResultsBetween December 2010 and May 2012, 1021 patients from 35 countries began study treatment. Bevacizumab was administered at 15 mg/kg in 89% of patients and for more than 15 months in 53%. Median follow-up duration was 32 months (range, 1–50 months). The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%). The most common grade 3 or higher-grade adverse events were neutropenia (27%) and hypertension (25%). Bevacizumab was discontinued because of proteinuria in 5% of patients and hypertension in 3%. Median progression-free survival (PFS) was 25.5 months (95% confidence interval, 23.7–27.6 months).ConclusionExtended bevacizumab demonstrated increased incidences of proteinuria and hypertension compared with 12 or 15 months of bevacizumab in previous trials, but these rarely led to bevacizumab discontinuation. Median PFS is the longest reported for frontline bevacizumab-containing therapy. The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safety.

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A state by state analysis of BRCA1 and BRCA2 testing in patients with ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2015.01.446 ◽

2015 ◽

Vol 137 ◽

pp. 178

Author(s):

T.J. Herzog ◽

J. Saam ◽

C. Arnell ◽

R.J. Wenstrup

Keyword(s):

Ovarian Cancer ◽

Brca1 And Brca2 ◽

Brca1 And Brca2 Testing ◽

State Analysis

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Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant

Cancer Research and Treatment ◽

10.4143/crt.2019.351 ◽

2020 ◽

Vol 52 (3) ◽

pp. 680-688

Author(s):

Hyung Seok Park ◽

Jai Min Ryu ◽

Ji Soo Park ◽

Seock-Ah Im ◽

So-Youn Jung ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Triple Negative ◽

Cumulative Risk ◽

Pathogenic Mutation ◽

Personal History ◽

Clinicopathologic Characteristics ◽

Significant Difference ◽

History Of ◽

Risk Reducing

PurposeRecent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data.Materials and MethodsThe data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study.ResultsThe median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations.ConclusionL1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

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Effects of BRCA Germline Mutations on Triple-Negative Breast Cancer Prognosis

Journal of Oncology ◽

10.1155/2020/8545643 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Katarzyna Pogoda ◽

Anna Niwińska ◽

Elżbieta Sarnowska ◽

Dorota Nowakowska ◽

Agnieszka Jagiełło-Gruszfeld ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Prognosis ◽

Entire Group ◽

Prognostic Impact ◽

Breast Cancer Patients ◽

Mutation Carriers ◽

Significant Difference ◽

History Of

Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I: 47% vs 24.5% in noncarriers), but there was no significant difference in the regional nodal status (58.5–63% with cN0). Contralateral breast cancer developed in 26.5% of BRCA1/2 mutation carriers and in 14% of noncarriers. Other primary cancers were also slightly more common in BRCA1/2 mutation carriers (16.5% vs 9.5%). The performed analysis did not show any significant differences between the groups in recurrence-free survival (p=0.312). There was no significant difference between patients with or without BRCA1/2 mutation as regards overall survival (p=0.649) and the risk of TNBC death (p=0.333). The survival from detection of metastases was similar in two groups (p=0.865). Our study demonstrated that the BRCA1 mutation does not affect TNBC patients’ outcomes.

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