Nisreen Elsayegh

Predictive factors for BRCA1/BRCA2 mutations in women with ductal carcinoma in situ

It is unclear whether women with ductal carcinoma in situ (DCIS), like their counterparts with invasive breast cancer, warrant genetic risk assessment and testing on the basis of high‐risk variables. The authors of this report identified predictive factors for mutations in the breast cancer‐susceptibility genes BRCA1 and BRCA2 in women who were diagnosed with DCIS.

Predictors that influence election of contralateral prophylactic mastectomy among women with ductal carcinoma in situ who are BRCA-negative

The authors retrospectively examined the contralateral prophylactic mastectomy (CPM) rate among 100 women with ductal carcinoma in situ who are BRCA negative. Of 100 women with ductal carcinoma in situ, 31 elected contralateral prophylactic mastectomy (CPM). Factors associated with increased likelihood of undergoing contralateral prophylactic mastectomy (CPM) among this cohort were: family history of ovarian cancer, marital status, reconstruction, mastectomy of the affected breast, and tamoxifen use.

Evaluation of BRCAPRO risk assessment model in patients with ductal carcinoma in situ who underwent clinical BRCA genetic testing

The authors retrospectively aimed to determine which of the following three scenarios, related to DCIS entry into BRCAPRO, predicted BRCA mutation status more accurately: (1) DCIS as an invasive breast cancer (IBC) entered using the actual age of diagnosis, (2) DCIS as IBC entered with 10 years added to the actual age of diagnosis, and (3) DCIS entered as no cancer. Of the 85 DCIS patients included in the study, 19% (n = 16) tested positive for a BRCA mutation, and 81% (n = 69) tested negative. DCIS patients who tested positive for a BRCA mutation had a higher BRCAPRO risk estimation (34.61%) than patients who tested negative (11.4%) when DCIS was entered at the actual age of diagnosis. When DCIS was entered with 10 years added to the actual age at diagnosis, the BRCAPRO estimate was still higher amongst BRCA positive patients (25.4%) than BRCA negative patients (7.1%). When DCIS was entered as no cancer, the BRCAPRO estimate remained higher among BRCA positive patients (2.56%) than BRCA negative patents (1.98%). In terms of accuracy of BRCA positivity, there was no statistically significant difference between DCIS at age at diagnosis, DCIS at 10 years later than age at diagnosis, and DCIS entered as no cancer (AUC = 0.77, 0.784, 0.75, respectively: p = 0.60). Our results indicate that regardless of entry approach into BRCAPRO, there were no significant differences in predicting BRCA mutation in patients with DCIS.

Service Delivery Model and Experiences in a Cancer Genetics Clinic for an Underserved Population

This report describes a genetics clinic for hereditary breast and ovarian cancer (HBOC) in an underserved population. Genetic counseling was provided to 151 patients, and 131 underwent BRCA genetic testing. This was a unique, group-based establishment of an HBOC genetics clinic, which to our knowledge had not previously been reported.

Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer

Although multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non‐BRCA mutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows: BRCA carriers (42.3%), non‐BRCA carriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non‐BRCA carriers and BRCA carriers (P = 0.6205). Among non‐BRCA carriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM between BRCA carriers and non‐BRCA carriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non‐BRCA carriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election among BRCA carriers, non‐BRCA carries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non‐BRCA genes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes.

Abstract P5-13-03: Factors associated with prophylactic mastectomy among BRCA-positive patients with no personal history of breast cancer

Background: The rate of prophylactic mastectomy (PM) has recently increased1. A deleterious mutation in the BRCA1 or BRCA 2 genes is among the major reasons why patients pursue PM 2, 3. Women with BRCA1 or BRCA2 gene mutations have up to an 87% risk to develop an invasive breast cancer (BC), and up to 45% risk for ovarian cancer (OC)2, 3. Most studies evaluating predictors of PM in BRCA mutation carriers are performed among women with breast cancer; however, accurate predictors for PM among unaffected BRCA mutation carriers are less defined. In a single institution study we aimed to evaluate predictors of PM among BRCA carriers with no personal history of breast cancer. Method: One hundred seventy seven women with no personal history of BC, who tested positive for a BRCA1 or BRCA 2 germline mutation, were included in the study. Patients’ characteristics were obtained from a prospectively maintained research database under an IRB approved protocol at UT MD Anderson Cancer Center. Univariate analyses using chi-square and logistic regression analysis were used to determine predictive factors associated with PM. The patient characteristics examined included age, martial and educational status, bilateral salphingo-oophorectomy (BSO), family history of 1st and 2nd degree relatives with breast (BC) and ovarian cancer (OC), race, and BRCA genetic test result. Results: Out of the 177 BRCA1 and BRCA 2 positive patients, 51 (29%) elected for PM. The average age for the cohort was 44 years (range 23-91). The majority were Caucasian (81%), and married (72%) with a college degree (64%). One hundred sixty-four (92%) patients had 1st and 2nd degree relatives with BC, 93 (53%) had 1st and 2nd degree relatives with OC, and 85 (48%) had undergone BSO. A logistic regression model was run to identify factors associated with undergoing PM, including family history of OC, family history of BC, BSO and age. Patients with a family history of OC were 2.5 times more likely than those without to have had a PM (p = 0.0125), and patients who had a BSO were 0.137 times less likely to have had a PM (p <.0001). Only 12 patients did not have a family history of BC and none of those patients had a PM, so an Odds Ratio could not be calculated. However, it was determined through the Fishers exact test that patients with a family history of BC were more likely to undergo a PM (p = 0.0198). Conclusion: The rate of PM in our cohort was slightly lower than expected. Factors associated with PM included a family history of BC and OC. Interestingly, having had a BSO was associated with lower likelihood of undergoing PM (menopausal status will be further evaluated); possibly due to the knowledge that BSO reduces breast cancer risk. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-13-03.

P4-10-06: Evaluation of BRCAPro Risk Assessment Model in Patients with Ductal Carcinoma In Situ.

Background: The BRCAPRo model is used to predict a patient9s likelihood to possess a BRCA1 or BRCA2 gene mutation based upon personal and family history. Ductal carcinoma in situ (DCIS) is considered a non-invasive condition which can progress to an invasive breast cancer if left untreated. Currently, DCIS is not specifically accounted for in the BRCAPro model, thereby causing DCIS to be weighted in the same manner as an invasive breast cancer diagnosis. Historically, a diagnosis of DCIS has been entered as having developed into an invasive breast cancer ten years later. However, there are no standard guidelines of how DCIS should be entered. We sought to determine if there were any differences in how DCIS was treated in the BRCAPro model to predict the more effective method in calculating the BRCAPro. Methods: Women with pure DCIS, who were referred for genetic counseling and underwent genetic testing, were included in the study. The likelihood of carrying a BRCA mutation was calculated using the BRCAPRO model (Version 5.1). Patient characteristics which were entered into the BRCAPro model include: tumor markers (estrogen receptor-ER and progesterone receptor-PR), history of oophorectomy prior to diagnosis, family history of 1st and 2nd degree relatives with breast and ovarian cancer, race and Ashkenazi Jewish ancestry. Each patient9s BRCAPro risk estimate was calculated and compared by entering DCIS at the presenting age of diagnosis and by adding 10 years to the age of diagnosis. Descriptive statistics and a student9s t-test were used to compare BRCAPro estimates between the two groups. Results: Ninety-five patients with pure DCIS underwent genetic counseling and testing. The average age of DCIS diagnosis was 45 years (range 26–65). Of the 95 DCIS patients included in the study 21% (n=20) tested positive for a BRCA gene mutation (8 BRCA1 and 12 BRCA2), 77% (n=74) test negative and 0.01% (n=1) had a variant of uncertain significance. Overall, DCIS patients who tested positive for a BRCA mutation had a higher BRCAPro (40%) than patients who tested negative (12%) when presenting age of diagnosis was assessed. When 10 years was added, the BRCAPro estimate was still higher amongst BRCA positive patients (28%) than BRCA negative patients (8%). The mean BRCAPro probability when DCIS was entered at presenting age of diagnosis was 18% (0.1−95.4) versus 12% (0.1−89.9) when calculated 10 years later. Conclusion: In our cohort there was no significant difference in BRCAPro probability whether DCIS was entered at the presenting age of diagnosis or 10 years later (p=0.1). However, future studies are needed to determine the most effective method to incorporate DCIS into the BRCAPro model in order to determine those individuals who may or may not be at increase risk to possess a BRCA gene mutation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-06.

P2-13-04: Testing Women with Invasive Lobular Breast Cancer for BRCA Mutations.

Background: Infiltrating lobular carcinoma (ILC) is the second most common type of invasive breast cancer behind infiltrating ductal carcinoma (IDC). ILC makes up approximately eight percent of all invasive lesions. In addition, the mixed ductal and lobular carcinoma histology makes up approximately seven percent of all invasive diagnoses. There are several biologic differences that are demonstrated by ILC compared to other common pathologies. They are more frequently bilateral and multicentric. They tend to be seen in women slightly older than the average age of diagnosis and are usually ER positive. It is also known that individuals with a genetic predisposition have an increased risk to develop breast cancers. Women with a mutation in their CDH1 gene have up to a 39% chance to develop ILC. The majority of hereditary breast cancer is caused by germ line mutations in the BRCA1 and BRCA2 genes. Women with a mutation in their BRCA1 or BRCA2 gene have up to an 87% risk to develop an invasive breast cancer, however, the presence of ILC in this population has not been well defined. Therefore, the aim of this study is to evaluate the rate of germline BRCA mutations in a cohort of patients both with pure ILC, as well as mixed ILC/IDC. Methods: A retrospective chart review revealed one hundred and sixty nine women with ILC and mixed ILC/IDC who underwent genetic testing for mutations in the BRCA1 and BRCA2 genes through the Clinical Cancer Genetics Program at M. D. Anderson Cancer Center. Women are referred for genetic testing using referral guidelines based on the NCCN guidelines, this usually involves a personal history of early onset breast cancer and/or a family history of breast and/or ovarian cancer. Results: Out of the 169 patients, 19 (11.24%) were found to have a germline mutation in their BRCA1 or BRCA2 gene. A significant majority (73.7%) of these patients were BRCA2 positive. Five women tested for a variant of uncertain significance. The average age of diagnosis for the cohort was 55.6 years (range 30–87); while the average age of diagnosis for a positive patient was 49.4 years (range 30–72). Of the 62 women with pure ILC, 5 (8.06%) were positive for a BRCA gene mutation. Historically, out of all the patients with breast cancer referred and tested through the Clinical Cancer Genetics Program, approximately 15% test positive, and research shows that in the general population, 7–10% of breast cancer patients will test positive. Conclusions: while the positivity rates between the cohorts are not statistically significant, we have shown that patients with a BRCA mutation can develop ILC in addition to the more commonly seen IDC. We suggest that patients continue to be referred for genetic counseling according to the NCCN guidelines, regardless of the pathology of their tumor. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-04.