Meghna S. Trivedi

Identifying Predictors of Taxane-Induced Peripheral Neuropathy Using Mass Spectrometry-Based Proteomics Technology

Major advances in early detection and therapy have significantly increased the survival of breast cancer patients. Unfortunately, most cancer therapies are known to carry a substantial risk of adverse long-term treatment-related effects. Little is known about patient susceptibility to severe side effects after chemotherapy. Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of taxanes. Recent advances in genome-wide genotyping and sequencing technologies have supported the discoveries of a number of pharmacogenetic markers that predict response to chemotherapy. However, effectively implementing these pharmacogenetic markers in the clinic remains a major challenge. On the other hand, recent advances in proteomic technologies incorporating mass spectrometry (MS) for biomarker discovery show great promise to provide clinically relevant protein biomarkers. In this study, we evaluated the association between protein content in serum exosomes and severity of CIPN. Women with early stage breast cancer receiving adjuvant taxane chemotherapy were assessed with the FACT-Ntx score and serum was collected before and after the taxane treatment. Based on the change in FACT-Ntx score from baseline to 12 month follow-up, we separated patients into two groups: those who had no change (Group 1, N = 9) and those who had a ≥20% worsening (Group 1, N = 8). MS-based proteomics technology was used to identify proteins present in serum exosomes to determine potential biomarkers. Mann–Whitney–Wilcoxon analysis was applied and maximum FDR was controlled at 20%. From the serum exosomes derived from this cohort, we identified over 700 proteins known to be in different subcellular locations and have different functions. Statistical analysis revealed a 12-protein signature that resulted in a distinct separation between baseline serum samples of both groups (q<0.2) suggesting that the baseline samples can predict subsequent neurotoxicity. These toxicity-associated biomarkers can be further validated in larger retrospective cohorts for their utility in identifying patients at high risk for CIPN.

Chemoprevention uptake among women with atypical hyperplasia and lobular and ductal carcinoma in situ

Women with atypical hyperplasia and lobular or ductal carcinoma in situ (LCIS/DCIS) are at increased risk of developing invasive breast cancer. Chemoprevention with selective estrogen receptor modulators or aromatase inhibitors can reduce breast cancer risk; however, uptake is estimated to be less than 15% in these populations. We sought to determine which factors are associated with chemoprevention uptake in a population of women with atypical hyperplasia, LCIS, and DCIS. Women diagnosed with atypical hyperplasia/LCIS/DCIS between 2007 and 2015 without a history of invasive breast cancer were identified (N = 1,719). A subset of women (n = 73) completed questionnaires on breast cancer and chemoprevention knowledge, risk perception, and behavioral intentions. Descriptive statistics were generated and univariate and multivariable log-binomial regression were used to estimate the association between sociodemographic and clinical factors and chemoprevention uptake. In our sample, 29.3% had atypical hyperplasia, 23.3% had LCIS, and 47.4% had DCIS; 29.4% used chemoprevention. Compared with women with atypical hyperplasia, LCIS [RR, 1.43; 95% confidence interval (CI), 1.16–1.76] and DCIS (RR, 1.54; 95% CI, 1.28–1.86) were significantly associated with chemoprevention uptake, as was medical oncology referral (RR, 5.79; 95% CI, 4.80–6.98). Younger women were less likely to take chemoprevention (RR, 0.61; 95% CI, 0.42–0.87), and there was a trend toward increased uptake in Hispanic compared with non-Hispanic white women. The survey data revealed a strong interest in learning about chemoprevention, but there were misperceptions in personal breast cancer risk and side effects of chemoprevention. Improving communication about breast cancer risk and chemoprevention may allow clinicians to facilitate informed decision-making about preventative therapy. Cancer Prev Res; 10(8); 434–41. ©2017 AACR.

Factors associated with false positive results on screening mammography in a population of predominantly Hispanic women

Background: Potential harms of screening mammography include false positive results, such as recall breast imaging or biopsies. Methods: We recruited women undergoing screening mammography at Columbia University Medical Center in New York, New York. They completed a questionnaire on breast cancer risk factors and permitted access to their medical records. Breast cancer risk status was determined using the Gail model and a family history screener. High risk was defined as a 5-year invasive breast cancer risk of ≥1.67% or eligible for BRCA genetic testing. False positive results were defined as recall breast imaging (BIRADS score of 0, 3, 4, or 5) and/or biopsies that did not yield breast cancer. Results: From November 2014 to October 2015, 2,361 women were enrolled and 2,019 were evaluable, of whom 76% were Hispanic and 10% non-Hispanic white. Fewer Hispanic women met high-risk criteria for breast cancer than non-Hispanic whites (18.0% vs. 68.1%), but Hispanics more frequently engaged in annual screening (71.9% vs. 60.8%). Higher breast density (heterogeneously/extremely dense vs. mostly fat/scattered fibroglandular densities) and more frequent screening (annual vs. biennial) were significantly associated with false positive results [odds ratio (OR), 1.64; 95% confidence interval (CI), 1.32–2.04 and OR, 2.18; 95% CI, 1.70–2.80, respectively]. Conclusions: We observed that women who screened more frequently or had higher breast density were at greater risk for false positive results. In addition, Hispanic women were screening more frequently despite having a lower risk of breast cancer compared with whites. Impact: Our results highlight the need for risk-stratified screening to potentially minimize the harms of screening mammography. Cancer Epidemiol Biomarkers Prev; 27(4); 446–53. ©2018 AACR.

The Impact of Mental Illness on Uptake of Genetic Counseling for Hereditary Breast Cancer and Ovarian Cancer in a Multiethnic Cohort of Breast Cancer Patients

We evaluated whether mental illness is a barrier to genetic counseling for hereditary breast and ovarian cancer (HBOC) in multiethnic breast cancer patients. We conducted a retrospective analysis of 308 women with newly diagnosed breast cancer and eligible for HBOC genetic testing seen in the breast clinic of an academic, urban medical center from 2007 to 2015. Uptake of genetic services and history of mental health disorder (MHD), defined as a psychiatric diagnosis or treatment with an antidepressant, mood stabilizer, anxiolytic, or antipsychotic medication, were ascertained by medical chart review. The mean age at breast cancer diagnosis was 56 years, with 44% non‐Hispanic whites, 37% Hispanics, and 15% non‐Hispanic blacks. Ninety‐nine (32%) women met study criteria for MHD, 73% had a genetics referral, 57% had genetic counseling, and 54% completed BRCA testing. Uptake of genetic counseling services did not differ by race/ethnicity or presence of MHD. In multivariable analysis, younger age at diagnosis, Ashkenazi Jewish heritage, and family history of breast cancer were associated with HBOC genetic counseling. A relatively high proportion of breast cancer patients eligible for HBOC genetic testing were referred to a genetic counselor and referral status did not vary by MHD or race/ethnicity.

Population‐Based Study of Attitudes toward BRCA Genetic Testing among Orthodox Jewish Women

Given the high prevalence (1 in 40) of BRCA1 and BRCA2 mutations among Ashkenazi Jews, population‐based BRCA genetic testing in this ethnic subgroup may detect more mutation carriers. We conducted a cross‐sectional survey among Orthodox Jewish women in New York City to assess breast cancer risk, genetic testing knowledge, self‐efficacy, perceived breast cancer risk and worry, religious and cultural factors affecting medical decision‐making. We used descriptive statistics and multivariable logistic regression models to identify predictors of genetic testing intention/uptake. Among evaluable respondents (n = 243, 53% response rate), median age was 25 and nearly half (43%) had a family history of breast cancer. Only 49% of the women had adequate genetic testing knowledge and 46% had accurate breast cancer risk perceptions. Five percent had already undergone BRCA genetic testing, 20% stated that they probably/definitely will get tested, 28% stated that they probably/definitely will not get tested, and 46% had not thought about it. High decision self‐efficacy, adequate genetic testing knowledge, higher breast cancer risk, and overestimation of risk were associated with genetic testing intention/uptake. Decision support tools that improve knowledge and self‐efficacy about genetic testing may facilitate population‐based BRCA testing among Orthodox Jews.

Abstract 1790: Factors associated with false positive results on screening mammography in a population of predominantly Hispanic women

Objective - High rates of screening mammography have been reported among Hispanic women in the U.S. However, a potential harm of screening is a false positive result with recall breast imaging or biopsy. Our objective was to identify factors associated with false positive results on screening mammography among a predominantly Hispanic population in New York City. Methods - We enrolled women receiving mammography at Columbia University Medical Center in New York, NY. They completed a questionnaire on breast cancer risk factors and gave consent to access their medical records for breast imaging and biopsy reports for the past 15 years. Breast cancer risk was assessed using the Gail model and eligibility for BRCA genetic testing was determined using a family history screener. High breast density was defined qualitatively as heterogeneously or extremely dense. Recall breast imaging was based upon a BIRADS score of 0, 3, 4, 5, or 6 on the screening mammogram. False positive breast biopsies were any biopsies that did not yield breast cancer. Results - From November 2014 to May 2015, 1325 women were enrolled: median age 58 years (range, 29-89); white/black/Hispanic/other (%): 10/10/76/4; 25% met high-risk criteria for breast cancer; 31% had high breast density; 71% were undergoing annual mammography; 53% had at least one recall breast imaging and 6% had at least one false positive breast biopsy. In multivariable analysis, high breast cancer risk, high breast density, and more frequent screening mammograms were associated with recall breast imaging and biopsy. Conclusions - Based upon our results, a potential strategy to reduce the false positive rates on screening mammography is to target women at high risk for breast cancer or with high breast density for screening with breast tomosynthesis, which has less false positives than digital mammography. Additionally, we may adopt less frequent breast cancer screening in average risk women to further reduce the harms of screening. Citation Format: William Ueng, Julia McGuinness, Katherine Infante, Meghna S. Trivedi, Hae Seung Yi, Raven David, Alejandro Vanegas, Jennifer Vargas, Rossy Sandoval, Rita Kukafka, Katherine D. Crew. Factors associated with false positive results on screening mammography in a population of predominantly Hispanic women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1790.

Abstract PR01: Knowledge, attitudes, and uptake of breast cancer chemoprevention in a multi-ethnic cohort of high-risk women

Background: Chemoprevention with anti-estrogens, such as tamoxifen, raloxifene, and aromatase inhibitors, has been shown to reduce breast cancer incidence in high-risk women; however, uptake remains low ( Methods: We enrolled high-risk women and those with newly diagnosed ductal carcinoma in situ (DCIS), who were seen for an initial consultation by medical oncology at Columbia University Medical Center. Women eligible for chemoprevention with anti-estrogens had a 5-year breast cancer risk ≥1.67% or lifetime risk ≥20% according to the Gail or Tyrer-Cuzick models, lobular carcinoma in situ (LCIS), DCIS, or BRCA mutation. Patients completed a baseline questionnaire collecting information on health literacy, numeracy, breast cancer knowledge, perceived breast cancer risk, reasons for taking preventive actions, and attitudes toward chemoprevention using validated measures. Demographic and clinical data, including chemoprevention uptake and type of anti-estrogen, were collected from medical chart review. Results: From August 2012 to July 2014, 69 women were enrolled and 45 were evaluable. Among evaluable women, median age was 51.5 years (range, 31.8-76.4); 51% were pre-menopausal; race/ethnicity, white/Hispanic/black/Asian/other (%): 49/24/16/9/2; risk category, elevated breast cancer risk/LCIS/DCIS/BRCA mutation (%): 49/18/29/4. Mean health literacy score was 0.74 (score range 0-4, lower scores indicate higher literacy) and 31% met criteria for low numeracy. At baseline, only 49% demonstrated good breast cancer knowledge and 45% perceived themselves to be at higher risk for breast cancer than the general population. Excluding women with DCIS, median lifetime breast cancer risk according to the Gail or Tyrer-Cuzick models was 29.2% (range, 10.3-92) and 42% had accurate risk perceptions (perceived risk within 10% of estimated lifetime risk). The most common reasons for wanting to take preventive action to lower breast cancer risk included to live longer (98%), to improve health (91%), and to do it for family (87%). Twenty-nine (64%) women had previously heard of a prescription medicine to prevent breast cancer, but only 34% had ever thought about taking an anti-estrogen for prevention. The most common concerns about side effects with tamoxifen were blood clots (47%) and uterine cancer (40%); with raloxifene, blood clots (77%); and with aromatase inhibitors, osteoporosis (59%) and arthritis symptoms (36%). Thirty (68%) women felt like they had enough information following the initial visit with the medical oncologist to decide whether or not to take chemoprevention. Overall, 22 (49%) started an anti-estrogen: 54% tamoxifen, 14% raloxifene, and 32% an aromatase inhibitor. The chemoprevention uptake rate was 69% for DCIS and 41% for the other risk categories combined. Conclusions: In a multi-ethnic cohort of high-risk women, less than half demonstrated sufficient breast cancer knowledge and had accurate breast cancer risk perceptions. After consultation with a medical oncologist, over two-thirds felt they had sufficient information for chemoprevention decision-making. Our chemoprevention uptake rate was relatively high compared to the published literature, which may reflect the highly select women referred to a breast center and the comfort level of medical oncologists in prescribing anti-estrogens. Citation Format: Meghna S. Trivedi, Laura Reimers, Katherine Infante, Dawn L. Hershman, Matthew Maurer, Kevin Kalinsky, Stephanie Aguilar, Rossy Sandoval, Maria C. Alvarez, Rita Kukafka, Katherine D. Crew. Knowledge, attitudes, and uptake of breast cancer chemoprevention in a multi-ethnic cohort of high-risk women. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PR01.