Rethinking breast cancer surveillance in women with BRCA-associated ovarian cancer in the post-solo trial era.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5565-5565
Author(s):  
Catherine S. John ◽  
Farin F. Amersi ◽  
Abigail Fong ◽  
Jessica Gillen ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Ductal Carcinoma ◽  
Brca2 Mutation ◽  
Breast Cancer Incidence ◽  
Cancer Surveillance ◽  
Advanced Stage ◽  
Free Survival ◽  
Mutation Carriers ◽  
Increased Risk

5565 Background: Patients with BRCA mutations are at increased risk of developing both breast (BC) and epithelial ovarian cancer (EOC). Optimal breast cancer surveillance guidelines for BRCA mutation carriers following EOC has not been defined due to high risk of EOC recurrence. The recent SOLO-1 trial demonstrated a survival benefit of olaparib maintenance therapy for newly diagnosed women with advanced stage EOC. Olaparib reduced the risk of disease-progression or death by 70% compared to placebo with a median progression-free survival (PFS) of 36 months. Methods: An IRB-approved, multi-institutional study retrospective chart review was performed. Patients had BRCA-associated EOC diagnosed between 1990-2015 without a history of prior BC or mastectomy. All women received combination chemotherapy for EOC. The observed breast cancer free survival was adjusted to reflect the enhanced 3-year PFS observed in olaparib-treated women from the SOLO-1 trial. Kaplan-Meier survival curves were performed. Results: 191 patients with BRCA-associated EOC were included (135 BRCA1, 55 BRCA2, 1 BRCA1 and BRCA2). Median age was 53 years. Most women had advanced stage, high-grade serous EOC (75%). The median overall survival was 7.7 years for BRCA 1, and 9.7 years for BRCA2 mutation carriers. Annual mammography and MRI were performed in 43% and 34% of women, respectively, with a median of 4 mammograms and 3 MRI per patient. 16 women (8.3%) were diagnosed with BC over a median follow up of 80 months: 7 (44%) DCIS and 9 (56%) invasive ductal carcinoma. 14 (88%) women had early stage (0-2) BC. 28 (15%) of women had risk-reducing mastectomy performed an average of 2.1 years following their EOC diagnosis. The incidence of BC increased from 5.6% to 11% at 5- and 10-years post EOC, and in the predicted model with olaparib, from 10% to 17% at 5- and 10-years, assuming olaparib does not impact breast cancer incidence. Conclusions: The risk of metachronous BC following BRCA-associated EOC increases over time. In the post SOLO trial era, BC surveillance strategies in women with EOC should be optimized to reflect improved outcome. [Table: see text]

An exploratory study to determine if BRCA1 and BRCA2 mutation carriers have higher risk of cardiac toxicity.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1585-1585 ◽  
Author(s):  
Roohi Ismail-Khan ◽  
Monique Sajjad ◽  
Weihong Sun ◽  
Hatem Hussein Soliman ◽  
Hyo S. Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Exploratory Study ◽  
Online Survey ◽  
Cardiac Toxicity ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

1585 Background: Anthracycline related cardiac toxicity (CT) is a concern in treating women with breast cancer. The prevalence of heart failure (HF) affects 2% of the population, less so in women. Patients receiving anthracycline based therapy (ABT) have a dose-dependent risk of reduction in ejection fraction. Recent work by Dr. Verma suggests that BRCA-deficient mice manifest increased levels of cardiac failure. We sought to explore the risk for CT and evaluate the association between ABT and HF in female BRCA mutation carriers. Methods: An online survey was developed to collect information about breast cancer treatment (including HF) in BRCA mutation carriers through the national BRCA patient advocacy organization FORCE via their 2011 conference and their website as well as the Moffitt-based Inherited Cancer Registry (ICARE). The prevalence of CT and HF was calculated in both BRCA 1 and 2 breast cancer patients and compared to general population risks. Data from those that received ABT was compared to published HF rates from ABT. Results: Our sample included 227 BRCA1 carriers and 164 BRCA2 carriers in whom 6.4% reported cardiac toxicity (i.e., either HF and/or CT). This included similar proportions in BRCA1 vs BRCA2 carriers (i.e., 6.6% and 6.1%, respectively). These proportions are significantly higher than the published rate of 2% (all p-values < 0.001). Specifically regarding ABT, 112 mutation carriers had doxorubicin (Adriamycin) for treatment of whom 8% reported HF, similar to the 11 who had Epirubicin (11 patients), of whom 9% reported HF. Conclusions: Our data suggests that BRCA mutation carriers may have an increased risk of CT compared to the general population. In particular, women with BRCA mutations treated with ABT also appear to have a higher risk of developing CT and/or HF. This exploratory study provides the basis upon which larger retrospective and prospective studies are currently being planned. The high percentage of CT observed in this study requires confirmation as they could inform recommendation for cardiac screening and review of the current standard for ABT use in this population.

scholarly journals Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

2016 ◽  
Vol 115 (10) ◽  
pp. 1174-1178 ◽  
Author(s):  
Leendert H Zaaijer ◽  
Helena C van Doorn ◽  
Marian J E Mourits ◽  
Marc van Beurden ◽  
Joanne A de Hullu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Mutation Carriers

Breast cancer surveillance following ovarian cancer in BRCA mutation carriers

2020 ◽  
Vol 156 (3) ◽  
pp. e14
Author(s):  
I. Cass ◽  
C. John ◽  
J. Gillen ◽  
K.M. Moore ◽  
C. Walsh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca Mutation ◽  
Cancer Surveillance ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

Oral Contraceptives and Breast Cancer Risk in the International BRCA1/2 Carrier Cohort Study: A Report From EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group

2007 ◽  
Vol 25 (25) ◽  
pp. 3831-3836 ◽  
Author(s):  
Richard M. Brohet ◽  
David E. Goldgar ◽  
Douglas F. Easton ◽  
Antonis C. Antoniou ◽  
Nadine Andrieu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Oral Contraceptives ◽  
Brca2 Mutation ◽  
Gonadal Hormones ◽  
Full Term ◽  
Term Pregnancy ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Increased Risk

Purpose Earlier studies have shown that endogenous gonadal hormones play an important role in the etiology of breast cancer among BRCA1/2 mutation carriers. So far, little is known about the safety of exogenous hormonal use in mutation carriers. In this study, we examined the association between oral contraceptive use and risk of breast cancer among BRCA1/2 carriers. Patients and Methods In the International BRCA1/2 Carrier Cohort study (IBCCS), a retrospective cohort of 1,593 BRCA1/2 mutation carriers was analyzed with a weighted Cox regression analysis. Results We found an increased risk of breast cancer for BRCA1/2 mutation carriers who ever used oral contraceptives (adjusted hazard ratio [HR] = 1.47; 95% CI, 1.16 to 1.87). HRs did not vary according to time since stopping use, age at start, or calendar year at start. However, a longer duration of use, especially before first full-term pregnancy, was associated with an increased risk of breast cancer for both BRCA1 and BRCA2 mutation carriers (4 or more years of use before first full-term pregnancy: HR = 1.49 [95% CI, 1.05 to 2.11] for BRCA1 carriers and HR = 2.58 [95% CI, 1.21 to 5.49] for BRCA2 carriers). Conclusion No evidence was found among BRCA1/2 mutation carriers that current use of oral contraceptives is associated with risk of breast cancer more strongly than is past use, as is found in the general population. However, duration of use, especially before first full-term pregnancy, may be associated with an increasing risk of breast cancer among both BRCA1 and BRCA2 mutation carriers.

scholarly journals Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

2012 ◽  
Vol 21 (4) ◽  
pp. 645-657 ◽  
Author(s):  
Fergus J. Couch ◽  
Mia M. Gaudet ◽  
Antonis C. Antoniou ◽  
Susan J. Ramus ◽  
Karoline B. Kuchenbaecker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Brca2 Mutation ◽  
Ovarian Cancer Risk ◽  
Common Variants ◽  
Brca1 And Brca2 ◽  
Mutation Carriers

scholarly journals Update on chemoprevention in BRCA1 and BRCA2 mutation carriers

2005 ◽  
Vol 8 (9) ◽  
Author(s):  
M. Stumacher ◽  
S. M. Domchek
Keyword(s):  
Breast Cancer ◽  
Prophylactic Mastectomy ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Breast Cancers ◽  
Brca1 And Brca2 ◽  
Prophylactic Oophorectomy ◽  
Estrogen Exposure ◽  
Mutation Carriers ◽  
Increased Risk

Chemoprevention with tamoxifen and oophorectomy are thought to be effective in decreasing the incidence of breast cancer in women at increased risk for the disease. There is mounting data supporting the idea that hormonal interventions that reduce estrogen exposure to breast epithelium, such as prophylactic oophorectomy and tamoxifen, are effective in breast cancer prevention in both BRCA1 and BRCA2 mutations carriers. Several recent studies directly address the protective effect of tamoxifen and oophorectomy in BRCA mutation carriers and suggest that these endocrine manipulations decrease the risk of primary and secondary breast cancers. Ongoing studies aim to better define the effect of tamoxifen in these very high-risk women and determining whether factors, such as earlier age of use or prior prophylactic oophorectomy, impact tamoxifen's effect. Based on existing data, we recommend that women with deleterious mutations in BRCA1 or BRCA2 be informed of the beneficial effect of oophorectomy on breast cancer risk and that women who choose breast cancer screening instead of prophylactic mastectomy be offered tamoxifen as a prevention option.

Risk-reducing salpingo-oophorectomy and breast cancer incidence among BRCA-mutation carriers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10548-10548
Author(s):  
Tamar Perri ◽  
Shani Naor-Ravel ◽  
Perry Eliassi-Revivo ◽  
Dror Lifshitz ◽  
Eitan Friedman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Breast Cancer Incidence ◽  
Mutation Carriers ◽  
Age At Surgery ◽  
Significant Difference ◽  
Brca Mutation Carriers ◽  
Risk Reducing

10548 Background: Uncertainty exists with regard to the role of bilateral salpingo-oophorectomy in altering the risk of breast cancer in BRCA-mutation carriers. Methods: Included were 1645 healthy Jewish Israeli BRCA1/2 -mutation carriers from a single center without prophylactic mastectomy. Carriers with and without risk-reducing bilateral salpingo-oophorectomy (RRBSO) were matched according to BRCA-mutation type (BRCA1 vs. BRCA2) and year of birth (±1 year). Hormonal and reproductive variables were compared and incidence of breast cancer recorded. Association between RRBSO and breast cancer was studied. Results: Seventy-seven and 50 matched-pairs had BRCA1 and BRCA2 mutation respectively. Fifty-two carriers had breast cancer, 21 in RRBSO-group and 31 in no- RRBSO group, with no statistically significant difference. When analysing each mutation group separately, stratified by age at surgery, no association between RRBSO and breast cancer incidence was found among BRCA1-mutation carriers. However, in BRCA2 mutation carriers, RRBSO was associated with a statistically significant decreased overall incidence of breast cancer, HR = 0.2 (confidence interval 0.44-0.913, p = 0.038). Breast cancer incidence was lower after 5, 10,15 and 20 years in BRCA2-mutation carriers with RRBSO compared to no-RRBSO. Age at menarche, age at surgery, parity and oral contraceptive use were not significant risk factors for breast cancer. Hormone replacement therapy was used by 62 mutation carriers, 52 in the RRBSO group and 10 in the no-RRBSO group, and its use did not alter breast cancer risk (p = 0.463). Conclusions: According to our findings, RRBSO is associated with a reduced risk of breast cancer only in BRCA2 mutation carriers, regardless of HRT use.

Heterozygous germline ATM mutations in breast cancer: A single academic center experience.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1537-1537
Author(s):  
Anish S Konde ◽  
Kristina Ivan ◽  
Jeannie Klavanian ◽  
Tara Rangarajan ◽  
Ishmael A. Jaiyesimi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Diagnosis ◽  
Ductal Carcinoma ◽  
Bilateral Mastectomy ◽  
Her2 Status ◽  
Breast Cancers ◽  
Primary Malignancy ◽  
Mutation Carriers ◽  
Increased Risk

1537 Background: Heterozygous germline ATM mutation carriers have an increased risk of developing breast, pancreas, and other cancers. The clinical and pathologic characteristics of ATM-associated breast cancers have not been well defined. Methods: Patients who underwent multigene panel testing (MGPT) between 2013-2019 and identified to harbor ATM mutations were included in the study. We evaluated demographics, pathology, and surgical management of our ATM mutation carriers with breast cancer. Results: At total of 319 individuals were identified to have variants in ATM, of which 114 were pathogenic/likely pathogenic. The majority of patients were female (82%) and Caucasian (88%). A total of 56 patients (49%) had a personal cancer diagnosis, the most common of which was breast cancer (n = 39). Nine individuals had more than one primary malignancy. The mean age at breast cancer diagnosis was 52, with a range of 25-82. The majority of patients had invasive ductal carcinoma (74%), grade 2 or 3 (90%), and ER and /or PR positive (87%). Of those with known HER2 status, 24% were positive. Thirty-nine percent of patients were lymph node positive, and 42% had lymphovascular invasion. The most common stage at diagnosis was 2 (53%). Of the 39 mutation carriers with breast cancer, 16 (42%) received radiation therapy, and 16 underwent bilateral mastectomy. Of 114 ATM positive patients, there were 55 distinct variants. Sixteen (14%) individuals had a mutation in additional cancer predisposition genes. One variant, c.5015delG, was identified in ten patients in a large, consanguineous Iraqi family with an extensive history of pancreatic and other cancers. Eight individuals were identified to have the known high-penetrance variant, c.7271T > G. Conclusions: Our study describes the clinical and pathological characteristics of ATM mutations carriers with breast cancer. The majority of patients had intermediate to high grade disease, hormone receptor positive, with a suggestion of a higher rate of HER2 positivity and lymph node involvement. Additional studies are needed to elucidate the unique characteristics of ATM-associated breast cancer, which may have implications for personalized management.

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