Testing In Breast Cancer Patients Research Articles

Abstract P4-06-17: Expanded panel testing in patients with breast or ovarian cancer in a rural familial cancer program

Abstract Objective: We sought to investigate our center's experience with multi-gene panel testing in breast and ovarian cancer patients from a largely rural catchment area. Our goal was to identify predictors of pathogenic variants and assess indicators for expanded genetic testing. Methods: We conducted a retrospective review of breast and ovarian cancer patients who underwent panel testing between May 2011 and April 2016. A variety of commercial gene panels were used with variant classification determined by the individual laboratory. Differences in patient demographics, age of first cancer diagnosis, number of genes tested and tumor characteristics including hormone/HER2 status, histology, differentiation, tumor size and AJCC staging classification were analyzed among pathogenic variant positive, negative, and VUS patient subsets with a chi-square test and one-way ANOVA. Results: We identified 215 patients who underwent panel testing: the average age of patients was 52.9 ± 12 with first cancer onset at 47 ± 12; 27% of patients had undergone prior single-gene testing; 7% of patients had ovarian cancer and 93% of patients had breast cancer. VUS were detected in 18.1% of patients and pathogenic variants were detected in 9.3% of patients. Of the 20 pathogenic variants identified, 1 was detected in BARD1, 2 in BRIP1, 3 in MUTYH, 5 in CHECK2, 2 in BRCA1, 2 in BRCA2, 3 in ATM, 1 in PALB2 and 1 in PMS2. In our breast cancer cohort, there was a statistical difference (p=.03) between patients with VUS, pathogenic variants and negative testing in respect to hormone and HER2 status. Most pathogenic variants (75%) were in patients who were HER2 negative, with the majority of VUS detected in patients who were hormone receptor positive (66%). Between the groups, there were no differences in histology, tumor differentiation, size or AJCC stage classification. However, individuals with pathogenic variants tended to have a younger age of first cancer diagnosis, have higher grade disease and have triple negative tumors. Conclusions: Specific tumor patterns (that is, HER2 negative or triple negative pathology) may be important indicators for genetic testing in breast cancer patients. Expanded panel testing should be considered in patients with a younger age of cancer diagnosis, higher grade disease and triple negative tumors. Citation Format: Hermel DJ, McKinnon WC, Colello L, Greenblatt MS, Wood ME. Expanded panel testing in patients with breast or ovarian cancer in a rural familial cancer program [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-17.

Abstract P4-06-14: Voice of cancer patients: Association of family history with genetic mutations in breast and ovarian cancer

Abstract There are specific guidelines for testing germline mutations in patients with breast cancer. Besides BRCA 1 and 2, germline mutations of multiple other genes are being recognized as risk factors for breast and ovarian cancers and hence more patients are being tested using multigene panels. Many patients share their experiences as freely shared messages in online forums. In this study, we use our automated system (VoCP) to analyze these messages to understand awareness of genetic testing in breast cancer patients and some factors that lead to their genetic testing. Method: We collected 15.13 million unique messages (by 987,189 users) from 37 unrestricted cancer forums that provide clinically relevant information. We built custom ontologies for genetic tests; breast, ovarian and other cancers; risk reducing mastectomy and oophorectomy; and screening. We then used VoCP that uses techniques from Big Data Science and Artificial Intelligence (e.g., deep learning, topic modeling, information retrieval, and natural language processing) to extract relevant information from these messages. Results: Out of 15.13 million, 30,074 messages from 7,838 distinct users were discussing genetic testing. Mutations that were discussed most include: · BRCA1/BRCA2 (28,130 messages); 954 patients were positive · PALB2 (218 messages); 114 were positive · CHEK2 (315 messages); 149 were positive · TP53 (180 messages); 55 were positive · BRIP1 (76 messages); 36 were positive · CDH1 (128 messages); 12 were positive · NBN (80 messages); 28 were positive · STK11 (48 messages); 2 were positive · RAD50/ RAD51C (39 messages/48 messages) Association with family history of cancer: 3,083 messages mentioned positive family history and some mentioned several cancers in their family; these messages discussed the following cancers: · Breast cancer: 2,243 massages · Ovarian cancer: 830 massages · Colon cancer: 247 messages · Pancreatic cancer: 121 massages · Prostate cancer: 206 massages · Lung cancer: 138 messages Out of 954 BRCA 1 and 2 positive patients, · 279 messages indicated their family members were tested for BRCA 1 and 2 · 156 messages indicated positive mutations were found in family members · 23 messages indicated that male members of family were also being tested Also, out of 954 BRCA 1 and 2 positive patients, · 333 mentioned opting for bilateral mastectomy and 117 talked about getting Prophylactic Bilateral Salpingo Oophorectomy · 309 messages talked about ovarian cancer once they found out that they have BRCA mutation Discussion:There is increasing awareness of genetic testing and germline mutations in addition to BRCA 1 and 2 in breast cancer. Positive family history of cancer is mentioned in 10% of patients seeking genetic testing. VoCP reliably provides meaningful insights from patients' point of view to their treatment and their concerns; it also gives insight into unmet needs where more resources and research should be focused. We plan to use VoCP for further segmenting these 30,074 messages to understand other attributes and awareness among such patients. Citation Format: Aggarwal S, Sharma R, Sharma R, Aggarwal A. Voice of cancer patients: Association of family history with genetic mutations in breast and ovarian cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-14.

Abstract P4-06-07: Trends and results of BRCA1/2 and multigene panel testing in newly diagnosed breast cancer patients

Abstract Background: Next-generation sequencing technology, reduced costs and public interest have fueled a surge in more expansive germline genetic testing of breast cancer patients. However, there are no population-based data on trends in use of different test types or the distribution of results. Methods: In the iCanCare study, we surveyed 7,303 women diagnosed in 2013-15 with early-stage breast cancer and reported to the Georgia and Los Angeles County SEER registries. Of 5,080 respondents (response rate 70%), 5,050 were linked to SEER clinical data and to test results from four commercial laboratories that performed nearly all germline genetic testing for breast cancer patients in the regions. We examined trends in test type (two genes, BRCA1/2 only, vs. more cancer susceptibility genes, multigene panel) and patterns of results (positive for a pathogenic mutation; variant of uncertain significance (VUS); negative) by clinical and sociodemographic subgroups. Pre-test risk of having a pathogenic mutation was categorized as higher vs. average based on patient report of age at diagnosis, family cancer history, ancestry (Ashkenazi Jewish vs. not) and breast cancer subtype (triple-negative vs. not), according to practice guidelines criteria for genetic testing. Results: The mean age was 62 years; 26%, 49% and 25% had stage 0, I, and II cancer, respectively; 78% had estrogen receptor-positive, HER2-negative disease, and 9% had triple-negative; 28% had higher pre-test risk of having a pathogenic mutation; 56% were non-Hispanic white, 18% African American, 14% Hispanic, and 10% Asian. Genetic testing use did not change over time (p=0.695), with one-quarter of patients receiving any test (either BRCA1/2 only or multigene panel) according to clinical laboratory data. However, testing included more genes over time: multigene panels comprised 19% of tests in 2013 vs. 66% in 2015 (p<0.001). Among all patients, 14% received BRCA1/2 only and 12% multigene panel testing, with no differences in test type by pre-test risk or race/ethnicity. Among all patients, 7% had a pathogenic mutation and 14% had a VUS in any gene. Patients at high pre-test risk had a lower ratio of uninformative VUS to informative pathogenic mutations (14%/10%) than average risk patients (15%/4%, p<0.001). There was a substantially higher ratio of VUS to pathogenic mutation among African Americans (22%/7%) and Asians (23%/3%) than other racial/ethnic groups (12%/8%, p<0.001). Conclusions: In a large, diverse, contemporary sample of early-stage breast cancer patients accrued from population-based registries and linked to clinical laboratory data, one-quarter had genetic testing, with multigene panels markedly replacing BRCA1/2-only tests over time. The ratio of uninformative VUS to informative pathogenic mutation results was lowest in women at high pre-test risk and highest among racial/ethnic minorities. These findings can inform genetic counseling and they emphasize the urgent need to re-classify VUS results in racial/ethnic minorities. More research is needed to determine the impact of this marked increased in multigene panel testing on patient experiences, and the impact of test results on treatment decision-making and outcomes. Citation Format: Kurian AW, Katz SJ. Trends and results of BRCA1/2 and multigene panel testing in newly diagnosed breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-07.

Impact of Multigene Panel Testing on Surgical Decision Making in Breast Cancer Patients

With the advent of multigene panel testing for breast cancer patients, germline mutations with unknown association with cancer risk, known as variants of uncertain significance (VUS), are being increasingly identified. Some studies have shown higher rates of contralateral prophylactic mastectomies (CPM) in these patients, despite lack of evidence to support this intervention. We analyzed surgical choices in patients who were identified to have VUS. A retrospective review was performed of patients with triple-negative breast cancer treated at a single institution after multigene panel tests became available (September 1, 2013 to February 28, 2017). Rates of genetic testing, results of testing, and surgical decision making were evaluated. Chi-square or Fisher's exact test was used to compare categorical variables. A p value <0.05 was considered statistically significant. There were 477 triple-negative breast cancer patients identified; 331 met established criteria for genetic testing and 226 (68.3%) underwent genetic testing (multigene panel, n= 130 and BRCA1/2 testing, n= 96). All of them received risk-appropriate genetic counseling and follow-up. Of these, 29 (12.8%) patients had pathogenic mutations in BRCA1/2 or PALB2 (Mut+), 42 (18.6%) had VUS (VUS+), and 155 (68.6%) had no mutations identified (Mut-). Variants of uncertain significance in 6 of 42 patients (14.3%) were later reclassified as normal variants. Eighty-eight percent of Mut+ patients underwent CPM compared with 20.1% of Mut- and 21.4% of VUS+ patients (p < 0.001 for both). Rates of CPM were not significantly different between VUS+ and Mut- (p= 0.37). Multigene panel testing detected pathogenic mutations in non-breast cancer-associated genes in 6 patients, with significant management implications. When combined with risk-appropriate genetic counseling, detection of VUS did not lead to excessive CPM in this cohort of triple-negative breast cancer patients. Furthermore, panel testing detected mutations in non-breast cancer-associated genes, which had significant implications on management and outcomes.

Current guidelines for BRCA testing of breast cancer patients are insufficient to detect all mutation carriers

BackgroundIdentification of BRCA mutations in breast cancer (BC) patients influences treatment and survival and may be of importance for their relatives. Testing is often restricted to women fulfilling high-risk criteria. However, there is limited knowledge of the sensitivity of such a strategy, and of the clinical aspects of BC caused by BRCA mutations in less selected BC cohorts. The aim of this report was to address these issues by evaluating the results of BRCA testing of BC patients in South-Eastern Norway.Methods1371 newly diagnosed BC patients were tested with sequencing and Multi Ligation Probe Amplification (MLPA). Prevalence of mutations was calculated, and BC characteristics among carriers and non-carriers compared. Sensitivity and specificity of common guidelines for BRCA testing to identify carriers was analyzed. Number of identified female mutation positive relatives was evaluated.ResultsA pathogenic BRCA mutation was identified in 3.1%. Carriers differed from non-carriers in terms of age at diagnosis, family history, grade, ER/PR-status, triple negativity (TNBC) and Ki67, but not in HER2 and TNM status. One mutation positive female relative was identified per mutation positive BC patient. Using age of onset below 40 or TNBC as criteria for testing identified 32-34% of carriers. Common guidelines for testing identified 45-90%, and testing all below 60 years identified 90%. Thirty-seven percent of carriers had a family history of cancer that would have qualified for predictive BRCA testing. A Variant of Uncertain Significance (VUS) was identified in 4.9%.ConclusionsMutation positive BC patients differed as a group from mutation negative. However, the commonly used guidelines for testing were insufficient to detect all mutation carriers in the BC cohort. Thirty-seven percent had a family history of cancer that would have qualified for predictive testing before they were diagnosed with BC. Based on our combined observations, we suggest it is time to discuss whether all BC patients should be offered BRCA testing, both to optimize treatment and improve survival for these women, but also to enable identification of healthy mutation carriers within their families. Health services need to be aware of referral possibility for healthy women with cancer in their family.

Abstract P3-08-05: The yield of germline genetic testing in breast cancer patients diagnosed prior to age 50

Abstract Young breast cancer (BC) patients are more likely to carry a mutation in a cancer predisposition gene than women diagnosed later in life. Historically young BC patients were eligible for BRCA1/2 genetic testing, but now with the advent of larger panels, more extensive germline genetic testing is available. Little is known about the yield of panel testing in young BC patients. The goal of this study is to report on the testing outcomes of referrals to a single institution cancer genetics program for women who had a diagnosis of BC at or prior to age 50. METHODS: Cases were identified from the cancer registry of a single institution. Women with invasive breast cancer or DCIS were included if their diagnosis was at or before age 50. Charts were reviewed to abstract data on age of diagnosis, type of testing offered, and results of genetic testing, as well as insurance status and family history of cancer. RESULTS: A total of 386 young BC patients were referred for genetic counseling in 2011-2015. Of those, 287 (74%) attended a genetic counseling appointment. Many of the women not attending had previously had genetic testing with an outside provider; their test results were included in the table below. Of the 287 attending a genetics consultation, most were offered genetic testing (87.1%); most of those not offered testing had either already been tested but without genetic counseling, or did not meet current NCCN or their insurer's criteria for testing. Eighteen women were offered a panel but elected to have only BRCA testing due to concerns about variants of unknown significance (VUS). Of those tested, 15.4% had a pathogenic or likely pathogenic mutation identified. Of women who had only BRCA testing, 11.7% were positive and 4.4% had a VUS. Of those who had panel testing, 16.9% were positive and 19.3% had a VUS. Percentage of women with positive tests by age at diagnosisAge at Dx30 or less31-3536-4041-4546-50Total (n=18)(n=39)(n=78)(n=109)(n=108)(n=352)BRCA1/227.8%18.0%16.7%6.4%6.5%11.1%Other genes11.1%5.1%3.8%4.6%2.8%4.3%Total yield38.9%23.1%20.5%11.0%9.3%15.4% Other genes with positive panel results included 4 x TP53 mutations, 4 x CHEK2, 2 x PALB2 and 1x each of RAD51C, RAD51D, STK11, NF1, and PTEN. The three patients who tested positive for a hereditary cancer predisposition syndrome (STK11, NF1, and PTEN positive) had clinical features of their respective syndromes. The STK11 patient was previously known to have Peutz-Jeghers syndrome, while the NF1 and PTEN patients had subtler features of Neurofibromatosis type 1 and PTEN-Hamartoma Tumor Syndrome (Cowden Syndrome) respectively. CONCLUSIONS: The yield of germline genetic testing in BC patients increases with younger age of diagnosis. Panel testing increases the yield of testing above that of BRCA1/2 alone, and enabled the formal diagnosis of a few individuals with hereditary cancer syndromes who did not have classic features of their syndromes. The VUS rate for panel testing remains significant, and some women elect to have BRCA1/2 testing only due to personal preference because of VUS rates. These data describing the yield of testing in BC patients diagnosed at a young age may be useful for genetic counseling of this patient population. Citation Format: Madlensky L, De Rosa D, Forbes K. The yield of germline genetic testing in breast cancer patients diagnosed prior to age 50 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-08-05.

Abstract P5-09-03: Associations between breast cancer subtypes and mutations in cancer predisposition genes identified by clinical genetic testing of breast cancer patients

Abstract Clinical genetic testing of individuals with a personal or family history of breast and ovarian cancer using panels for BRCA1/2 and other candidate cancer predisposition genes has become routine clinical practice. Several of the genes on hereditary cancer testing panels have been strongly associated with specific subtypes of breast cancer. In particular, individuals with germline mutations in BRCA1 predominantly develop estrogen receptor (ER)-negative and triple negative (TN) (estrogen receptor negative, progesterone receptor negative, HER2 negative) breast tumors. In contrast, CHEK2 and ATM mutations have been associated with ER-positive breast cancer. In this study, associations between mutations in panel genes and breast cancer subtypes were evaluated. A cohort of 60,000 breast cancer patients tested for germline cancer predisposing mutations using hereditary cancer gene panels was utilized. Information on personal and family cancer history, age of diagnosis, tumor pathology, and ethnicity of patients was obtained from test requisition forms or by follow up with ordering health care providers. Mutations in each gene were combined into four histological subtypes (triple negative; HER2 positive; ER-positive,HER2-positive; and ER-positive,HER2 negative). Associations for each subtype were estimated by case-control analyses comparing the frequencies of pathogenic mutations in each subtype with frequencies from non-TCGA controls from the Exome Aggregation Consortium (ExAC) database. In addition, case-case analyses were conducted to assess enrichment of gene mutations in specific breast cancer subtypes. Among the observed associations between genes and breast cancer subtypes, mutations in CHEK2 and ATM were highly enriched in luminal breast cancers and BARD1 was specifically associated with TN breast cancer. Refining the spectrum of pathological correlates with mutations in hereditary breast cancer genes will aid gene specific cancer risk management, and may accelerate the development of novel gene-specific therapeutic interventions. Citation Format: Couch FJ, Lilyquist J, Na J, Hu C, Polley EC, Shimelis H, Akinhanmi M, McFarland R, LaDuca H, Goldgar DE, Dolinsky JS. Associations between breast cancer subtypes and mutations in cancer predisposition genes identified by clinical genetic testing of breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-09-03.

A high frequency of PALB2 mutations in Jamaican patients with breast cancer

Jamaica is an island nation with one of the highest breast cancer incidence rates in the Caribbean (40/100,000 per year). The contribution of cancer susceptibility gene mutations to the burden of breast cancer in Jamaica has not yet been explored. We sought to determine the prevalence of germline mutations in BRCA1, BRCA2, and PALB2 in 179 unselected Jamaican women with breast cancer. We sequenced the entire coding regions of BRCA1, BRCA2, and PALB2 for all the study subjects. Overall, 8 of 179 patients (4.5%) had a mutation in one of the three genes: one in BRCA1, two in BRCA2, and five in PALB2. These data suggest that in addition to BRCA1 and BRCA2, PALB2 should be included in genetic testing for breast cancer patients in Jamaica.

Genetic Testing and Counseling Among Patients With Newly Diagnosed Breast Cancer

Germline genetic testing of breast cancer patients is an important model of how increasingly widespread genomic sequencing can influence treatment decision-making. Testing of two breast cancer-associated genes, BRCA1/2, has been available for twenty years, but new massively parallel sequencing technology and less restrictive patent laws have made multiplex panel tests available at much lower costs.1 Yet little is known about recent patient experience with genetic testing and counseling. Genetic counselors are expert in risk assessment and communication, but because of workforce limitations, some physicians must counsel and test patients without their assistance.2 These challenges motivated this investigation of patients’ use of and perspectives on genetic counseling and testing.

1335P - Multigene panel testing for breast cancer patients at high risk for hereditary cancer

1335P - Multigene panel testing for breast cancer patients at high risk for hereditary cancer

Decision-making for Adjuvant Chemotherapy in the Absence of Genomic Testing for Breast Cancer Patients with ‘Intermediate’ Risk of Mortality at 10 Years

Purpose: Web-based prognostic and predictive tools are used to quantify the risk of relapse, death and absolute benefit of adjuvant chemotherapy. These decision aids include Adjuvant! Online and Predict. Validated genomic tests such as Oncotype DX quantify the individual risk profile using gene expression analysis. We assessed decision-making for adjuvant chemotherapy using Adjuvant! Online in the absence of genomic testing for ‘intermediate’ risk patients.

Abstract P4-14-28: XMT-1522 induces tumor regressions in pre-clinical models representing HER2-positive and HER2 low-expressing breast cancer

Abstract XMT-1522 is an anti-HER2 antibody-drug conjugate (ADC) comprised of a novel anti-HER2 antibody (HT-19) and the Dolaflexin ADC platform, which allows for conjugation of 12-15 proprietary auristatin drug payload molecules per antibody without aggregation or detrimental impact on pharmacokinetics. The HT-19 antibody binds to a novel HER2 extracellular domain epitope and does not compete for HER2 binding with trastuzumab or pertuzumab. In vitro, XMT-1522 has sub-nanomolar potency in cell lines expressing as few as 25,000 HER2 antigens per cell, and is ∼100X more potent than ado-trastuzumab emtansine (T-DM1) across a panel of 25 cell lines representing a range of tumor indications and HER2 expression levels. In the BT-474 HER2-positive breast cancer model, treatment with the HT-19 antibody alone at a single 5 mg/kg dose is inactive, while XMT-1522 ADC at a single 2 mg/kg or 5 mg/kg dose induces durable complete tumor regression, indicating that the primary mechanism of XMT-1522 is cytotoxic payload delivery, not inhibition of HER2 signaling. T-DM1 at a single 5 mg/kg dose in the same model is inactive, consistent with the significant improvement in potency of XMT-1522 compared to T-DM1. Biodistribution studies using a HER2-targeted Dolaflexin ADC in the BT-474 model demonstrate accumulation of intact ADC and released active drug payload in tumor at levels significantly higher than normal tissues. In a HER2-positive patient-derived xenograft (PDX) model, XMT-1522 induces durable complete tumor regression after a single 1 mg/kg dose, while T-DM1 at a 10 mg/kg dose achieves tumor growth delay without regression. In a HER2 1+ PDX model without HER2 gene amplification, a single 3 mg/kg dose of XMT-1522 achieves partial tumor regression where a 10 mg/kg dose of T-DM1 is inactive. Combination of XMT-1522 with trastuzumab does not block the ability of the ADC to bind HER2 or efficiently internalize, and in vivo the combination of low dose XMT-1522 with full dose trastuzumab and pertuzumab is synergistic in a HER2-driven model. The exposure achieved with XMT-1522 at well-tolerated doses in cynomolgus monkey is several fold higher than the exposure needed in mice to achieve complete tumor regressions across models representing a range of HER2 expression and tumor indications. Based on these data, XMT-1522 will soon enter clinical testing in breast cancer patients with both HER2-positive tumors and HER2 low-expressing (IHC 1+ and 2+/FISH-) tumors. Citation Format: Bergstrom DA, Bodyak N, Park PU, Yurkovetskiy A, DeVit M, Yin M, Poling L, Thomas JD, Gumerov D, Xiao D, Ter-Ovanesyan E, Qin L, Uttard A, Johnson A, Lowinger TB. XMT-1522 induces tumor regressions in pre-clinical models representing HER2-positive and HER2 low-expressing breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-28.

Genomic testing in breast cancer patients affects medical costs

Genomic testing in breast cancer patients affects medical costs

Implementation of gene expression testing for breast cancer patients within the Veterans Health Administration.

e17511 Background: The number of Veterans diagnosed and treated for breast cancer within the Veterans Health Administration is increasing. The VA Central Cancer Registry (VACCR) reported 504 and 62...

Abstract P4-15-22: The ASCO/CAP guideline update for HER2 testing increases the number of breast cancer patients eligible for HER2-targeted therapy

Abstract Background: The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) published, in Nov/2013, the interpretive guidelines for HER2 testing of breast cancer patients. This aimed to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer. The former version of these criteria was written in 2007. Objectives: to compare the HER2 immunohistochemical (IHC) analysis using the 2007 versus 2013 algorithms in a cohort of breast cancer cases diagnosed in a single institution in Southern Brazil. The cases were previously classified as HER2 1+ or 2+, using the 2007 criteria. Methods: the sample included 100 invasive breast cancer cases. The HercepTest (Dako, Denmark) was used for determination of HER2 expression. The HER2 testing was analyzed independently by two pathologists. The FISH analysis was done using a HER2/D17Z1 probe set. Preliminary Results: The HER2 IHC interpretation changed in 11/69 (15.9%) cases: 8.7% negative or equivocal cases by the 2007 guidelines were positive by the 2013 classification and 7.2% of HER2 1+ cases became equivocal (p&amp;lt;0.001; x2 test). The FISH analyses are ongoing. Conclusion: The 2013 ASCO/CAP guidelines resulted in less negative cases and in more equivocal (requiring reflex testing) and positive tests. Applying the ASCO/CAP 2013 guidelines resulted in a significantly increase of breast cancer patients eligible for HER2-targeted therapies. Citation Format: Juliana Giacomazzi, Carolina R Hartmann, Diego D Paskulin, Luis Fernando Rivero, Maira Caleffi, Alessandro C Pasqualotto, Marcia S Graudenz, Daniela D Rosa. The ASCO/CAP guideline update for HER2 testing increases the number of breast cancer patients eligible for HER2-targeted therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-22.

Abstract 1358: Are physician recommendations for BRCA 1/2 testing among breast cancer patients appropriate? A population based study.

Abstract Purpose: To evaluate the rates and predictors of physician recommendation for BRCA 1/2 testing in breast cancer patients. Patients and Methods: Women aged 18-64 diagnosed with invasive breast cancer in 2007 in Pennsylvania completed a survey on family history of cancer, physician treatment recommendations, and BRCA 1/2 testing (N=2258). Based on age at diagnosis and family history, women were categorized as high, moderate, or low risk for BRCA 1/2 mutations. Multivariate logistic regression was used to assess the odds of physician recommendation for BRCA 1/2 testing by risk group, age at diagnosis, demographics, and tumor characteristics. Results: Nearly 25% of participants were at high risk for carrying a BRCA 1/2 mutation based on age at breast cancer diagnosis and family history of breast and/or ovarian cancer. Physician recommendations for BRCA 1/2 testing were strongly associated with risk of carrying a BRCA 1/2 mutation, with 53% of women at high risk reporting a testing recommendation compared to 9% of women at low risk. In addition, physician recommendations were strongly correlated with use of testing in all risk groups. Among women at high risk of mutation, lack of a recommendation for BRCA 1/2 testing was more common among women who were older, had lower income, and were employed. Conclusion: Although BRCA 1/2 testing recommendations appear to be appropriately correlated with mutation risk among women with breast cancer, a significant proportion of breast cancer patients who meet criteria for BRCA 1/2 testing may not be receiving recommendations for such testing from their providers. Citation Format: Anne Marie McCarthy, Mirar Bristol Demeter, Tracey Fredricks, Kaijun Liao, Judy A. Shea, Peter Groeneveld, Susan M. Domchek, Katrina Armstrong. Are physician recommendations for BRCA 1/2 testing among breast cancer patients appropriate? A population based study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1358. doi:10.1158/1538-7445.AM2013-1358

Standardized Assessment of the HER2 Status in Breast Cancer by Immunohistochemistry

Immunohistochemistry (IHC) is widely used in surgical pathology, but it has been plagued by problems with reproducibility and lack of standardization resulting in poor concordance between laboratories. In particular, inaccuracy of routine human epidermal growth factor receptor 2 (HER2) testing in breast cancer patients has been a major issue. In 2006 this led the American Society of Clinical Oncologists (ASCO) and College of American Pathologists (CAP) to charge an expert panel with developing recommendations for HER2 testing. After subsequent publication and adoption of these guideline recommendations through dissemination of best practices, variation in clinical practice is expected to diminish and result in improved accuracy. In this article, we review the role of genomic HER2 alterations in the development and treatment of breast cancer, highlight the importance of accurate and reproducible HER2 testing, and discuss practical approaches to standardize HER2 testing by IHC. Pre-analytic and analytic variables are addressed, and a practical algorithm for test interpretation is introduced. * IHC : immunohistochemistry HER2 : human epidermal growth factor receptor 2 ASCO : American Society of Clinical Oncologists CAP : College of American Pathologists ER : estrogen receptor FISH : fluorescence in situ hybridization PR : progesterone receptor H&E : hematoxylin and eosin staining

BRCA testing of breast cancer patients: medical specialists' referral patterns, knowledge and attitudes to genetic testing

This study explores knowledge about hereditary breast cancer, attitudes about BRCA testing and referral pattern to a family cancer clinic among medical specialists. A total of 92 questionnaires were completed by surgeons (38), medical oncologists (29), radiation oncologists (13) and radiologists (12). The response rate was 51%. A substantial (11-56%) proportion of medical specialists do not refer patients who meet current criteria for BRCA testing. Although questions on inheritance were less well answered, overall knowledge was good. They had a positive attitude, but were concerned about the distress DNA testing might cause to family members. The majority (75%) stated that the best time for referral is after adjuvant therapy or during follow-up, but another important determinant was the patient's wish or need (12%). Further studies are needed to gain insight into the actual referral process, while ongoing training of medical specialists about genetic aspects of breast cancer is also necessary.

BRCA1/2 Mutation Testing in Breast Cancer Patients: A Prospective Study on the Psychological Impact of Being Approached for Genetic Counseling During Adjuvant Radiotherapy

BRCA1/2 Mutation Testing in Breast Cancer Patients: A Prospective Study on the Psychological Impact of Being Approached for Genetic Counseling During Adjuvant Radiotherapy

BRCA1/2 mutation testing in breast cancer patients: a prospective study of the long-term psychological impact of approach during adjuvant radiotherapy

This study assessed psychological distress during the first year after diagnosis in breast cancer patients approached for genetic counseling at the start of adjuvant radiotherapy and identified those vulnerable to long-term high distress. Of the approached patients some chose to receive a DNA test result (n = 58), some were approached but did not fulfill criteria for referral (n = 118) and some declined counseling and/or testing (n = 44). The comparative group consisted of patients not eligible for genetic counseling (n = 182) and was therefore not approached. Patients actively approached for genetic counseling showed no more long-term distress than patients not eligible for such counseling. There were no differences between the subgroups of approached patients. Predictors for long-term high distress or an increase in distress over time were pre-existing high distress and a low quality of life, having children, and having no family members with breast cancer. It is concluded that breast cancer patients can be systematically screened and approached for genetic counseling during adjuvant radiotherapy without imposing extra psychological burden. Patients vulnerable to long-term high distress already displayed high distress shortly after diagnosis with no influence of their medical treatment on their level of distress at long-term.