Browsing by Author "Plichta, Jennifer K"
Now showing 1 - 8 of 8
- Results Per Page
- Sort Options
Item Open Access Clinical and pathological stage discordance among 433,514 breast cancer patients.(American journal of surgery, 2019-10) Plichta, Jennifer K; Thomas, Samantha M; Sergesketter, Amanda R; Greenup, Rachel A; Fayanju, Oluwadamilola M; Rosenberger, Laura H; Tamirisa, Nina; Hyslop, Terry; Hwang, E ShelleyBACKGROUND:We aim to determine clinical and pathological stage discordance rates and to evaluate factors associated with discordance. METHODS:Adults with clinical stages I-III breast cancer were identified from the National Cancer Data Base. Concordance was defined as cTN = pTN (discordance: cTN≠pTN). Multivariate logistic regression was used to identify factors associated with discordance. RESULTS:Comparing clinical and pathological stage, 23.1% were downstaged and 8.7% were upstaged. After adjustment, factors associated with downstaging (vs concordance) included grade 3 (OR 10.56, vs grade 1) and HER2-negative (OR 3.79). Factors associated with upstaging (vs concordance) were grade 3 (OR 10.56, vs grade 1), HER2-negative (OR 1.25), and lobular histology (OR 2.47, vs ductal). ER-negative status was associated with stage concordance (vs downstaged or upstaged, OR 0.52 and 0.87). CONCLUSIONS:Among breast cancer patients, nearly one-third exhibit clinical-pathological stage discordance. This high likelihood of discordance is important to consider for counseling and treatment planning.Item Open Access Concordance Between Genomic Alterations Detected by Tumor and Germline Sequencing: Results from a Tertiary Care Academic Center Molecular Tumor Board.(The oncologist, 2023-01) Green, Michelle F; Watson, Catherine H; Tait, Sarah; He, Jie; Pavlick, Dean C; Frampton, Garrett; Riedel, Jinny; Plichta, Jennifer K; Armstrong, Andrew J; Previs, Rebecca A; Kauff, Noah; Strickler, John H; Datto, Michael B; Berchuck, Andrew; Menendez, Carolyn SObjective
The majority of tumor sequencing currently performed on cancer patients does not include a matched normal control, and in cases where germline testing is performed, it is usually run independently of tumor testing. The rates of concordance between variants identified via germline and tumor testing in this context are poorly understood. We compared tumor and germline sequencing results in patients with breast, ovarian, pancreatic, and prostate cancer who were found to harbor alterations in genes associated with homologous recombination deficiency (HRD) and increased hereditary cancer risk. We then evaluated the potential for a computational somatic-germline-zygosity (SGZ) modeling algorithm to predict germline status based on tumor-only comprehensive genomic profiling (CGP) results.Methods
A retrospective chart review was performed using an academic cancer center's databases of somatic and germline sequencing tests, and concordance between tumor and germline results was assessed. SGZ modeling from tumor-only CGP was compared to germline results to assess this method's accuracy in determining germline mutation status.Results
A total of 115 patients with 146 total alterations were identified. Concordance rates between somatic and germline alterations ranged from 0% to 85.7% depending on the gene and variant classification. After correcting for differences in variant classification and filtering practices, SGZ modeling was found to have 97.2% sensitivity and 90.3% specificity for the prediction of somatic versus germline origin.Conclusions
Mutations in HRD genes identified by tumor-only sequencing are frequently germline. Providers should be aware that technical differences related to assay design, variant filtering, and variant classification can contribute to discordance between tumor-only and germline sequencing test results. In addition, SGZ modeling had high predictive power to distinguish between mutations of somatic and germline origin without the need for a matched normal control, and could potentially be considered to inform clinical decision-making.Item Open Access Germline Genetic Testing: What the Breast Surgeon Needs to Know.(Annals of surgical oncology, 2019-07) Plichta, Jennifer K; Sebastian, Molly L; Smith, Linda A; Menendez, Carolyn S; Johnson, Anita T; Bays, Sussan M; Euhus, David M; Clifford, Edward J; Jalali, Mena; Kurtzman, Scott H; Taylor, Walton A; Hughes, Kevin SPURPOSE:The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice. METHODS:A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop guideline recommendations. RESULTS:Clinical and educational guidelines were prepared to outline the essential knowledge for breast surgeons to perform germline genetic testing and to incorporate the findings into their practice, which have been approved by the ASBrS Board of Directors. RECOMMENDATIONS:Thousands of women in the USA would potentially benefit from genetic testing for BRCA1, BRCA2, and other breast cancer genes that markedly increase their risk of developing breast cancer. As genetic testing is now becoming more widely available, women should be made aware of these tests and consider testing. Breast surgeons are well positioned to help facilitate this process. The areas where surgeons need to be knowledgeable include: (1) identification of patients for initial breast cancer-related genetic testing, (2) identification of patients who tested negative in the past but now need updated testing, (3) initial cancer genetic testing, (4) retesting of patients who need their genetic testing updated, (5) cancer genetic test interpretation, posttest counseling and management, (6) management of variants of uncertain significance, (7) cascade genetic testing, (8) interpretation of genetic tests other than clinical cancer panels and the counseling and management required, and (9) interpretation of somatic genetic tests and the counseling and management required.Item Open Access Impact of HER2-low status for patients with early-stage breast cancer and non-pCR after neoadjuvant chemotherapy: a National Cancer Database Analysis.(Breast cancer research and treatment, 2023-12) Li, Huiyue; Plichta, Jennifer K; Li, Kan; Jin, Yizi; Thomas, Samantha M; Ma, Fei; Tang, Li; Wei, Qingyi; He, You-Wen; Chen, Qichen; Guo, Yuanyuan; Liu, Yueping; Zhang, Jian; Luo, ShengPurpose
To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting.Methods
We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses.Results
For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44].Conclusion
In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.Item Open Access Implications of missing data on reported breast cancer mortality(Breast Cancer Research and Treatment) Plichta, Jennifer K; Rushing, Christel N; Lewis, Holly C; Rooney, Marguerite M; Blazer, Dan G; Thomas, Samantha M; Hwang, E Shelley; Greenup, Rachel AItem Open Access Nodal Response to Neoadjuvant Chemotherapy Predicts Receipt of Radiation Therapy after Breast Cancer Diagnosis.(International journal of radiation oncology, biology, physics, 2019-10-31) Fayanju, Oluwadamilola M; Ren, Yi; Suneja, Gita; Thomas, Samantha M; Greenup, Rachel A; Plichta, Jennifer K; Rosenberger, Laura H; Force, Jeremy; Hyslop, Terry; Hwang, E ShelleyBACKGROUND:Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved overall survival (OS) in breast-cancer patients, but it is unclear how post-NACT response influences radiotherapy administration in patients presenting with node-positive disease. We sought to determine whether nodal pCR is associated with likelihood of receiving nodal radiation and whether radiotherapy among patients experiencing nodal pCR is associated with improved OS. METHODS:cN1 female breast cancer patients diagnosed 2010-2015 who were ypN0 (i.e., nodal pCR, n=12,341) or ypN1 (i.e., residual disease, n=13,668) post-NACT were identified in the National Cancer Database. Multivariate logistic regression was used to identify factors associated with receiving radiotherapy. Cox proportional hazards modeling was used to estimate the association between radiotherapy and adjusted OS. RESULTS:26,009 patients were included. 43.9% (n=5,423) of ypN0 and 55.3% (n=7,556) of ypN1 patients received nodal radiation. Rates of nodal radiation remained the same over time among ypN0 patients (trend test p=0.29) but increased among ypN1 patients from 49% in 2010 to 59% in 2015 (trend test p<0.001). After adjusting for covariates, nodal pCR (vs no stage change) was associated with decreased likelihood of nodal radiation after mastectomy (∼20% decrease) and lumpectomy (∼30% decrease, both p<0.01). After mastectomy, nodal (vs no) radiation conferred no significant survival benefit in ypN0 patients but approached significance for ypN1 patients (hazard ratio [HR] 0.83, 95% CI 0.69-0.99, p=0.04, overall p-value=0.11). After lumpectomy, nodal radiation was associated with improved adjusted OS for ypN0 (HR 0.38, 95% CI 0.22-0.66) and ypN1 patients (HR 0.44, 95% CI 0.30-0.66, both p<0.001), but this improvement was not significantly greater than that associated with breast-only radiation. CONCLUSIONS:ypN0 patients were less likely to receive nodal radiation than ypN1 patients, suggesting that selective omission already occurs and, in the context of limited survival data, could potentially be appropriate for select patients.Item Open Access The impact of chemotherapy sequence on survival in node-positive invasive lobular carcinoma.(Journal of surgical oncology, 2019-08) Tamirisa, Nina; Williamson, Hannah V; Thomas, Samantha M; Westbrook, Kelly E; Greenup, Rachel A; Plichta, Jennifer K; Rosenberger, Laura H; Hyslop, Terry; Hwang, Eun-Sil Shelley; Fayanju, Oluwadamilola MBACKGROUND AND OBJECTIVES:We sought to evaluate the impact of chemotherapy sequence on survival by comparing node-positive invasive lobular carcinoma (ILC) patients who received neoadjuvant (NACT) and adjuvant (ACT) chemotherapy. METHODS:cT1-4c, cN1-3 ILC patients in the National Cancer Data Base (2004-2013) who underwent surgery and chemotherapy were divided into NACT and ACT cohorts. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS:Five thousand five hundred fifty-one (35.6%) of 15 573 ILC patients treated with chemotherapy received NACT. NACT patients had similar rates of pT3/4 disease (26.6% vs 26.2%), nodal involvement (median 3 vs 4), and number of lymph nodes examined (median 13 vs 14) but higher rates of mastectomy (81.8% vs 74.5%, P < 0.001) vs ACT patients. 3.4% of NACT patients experienced pathologic complete response (pCR). Unadjusted 10-year OS was worse for NACT vs ACT patients (65.1% vs 54.4%, log-rank P < 0.001). After adjustment for known covariates, NACT continued to be associated with worse OS (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.25-1.52). CONCLUSIONS:In node-positive ILC, NACT yielded low rates of pCR, was not associated with lower rates of mastectomy or less extensive axillary surgery, and was associated with worse survival vs ACT, suggesting limited benefit for these patients.Item Open Access The Influence of Age on the Histopathology and Prognosis of Atypical Breast Lesions.(The Journal of surgical research, 2019-09) Sergesketter, Amanda R; Thomas, Samantha M; Fayanju, Oluwadamilola M; Menendez, Carolyn S; Rosenberger, Laura H; Greenup, Rachel A; Hyslop, Terry; Parrilla Castellar, Edgardo R; Hwang, E Shelley; Plichta, Jennifer KBACKGROUND:Although several prognostic variables and risk factors for breast cancer are age-related, the association between age and risk of cancer with breast atypia is controversial. This study aimed to compare the type of breast atypia and risk of underlying or subsequent breast cancer by age. METHODS:Adult women with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ) at a single institution from 2008 to 2017 were stratified by age at initial diagnosis: <50 y, 50-70 y, and >70 y. Regression modeling was used to estimate the association of age with risk of underlying carcinoma or subsequent cancer diagnosis. RESULTS:A total of 530 patients with atypia were identified: 31.1% < 50 y (n = 165), 58.1% 50-70 y (n = 308), and 10.8% > 70 y (n = 57). The proportion of women with atypical ductal hyperplasia steadily increased with age, compared with atypical lobular proliferations (P = 0.04). Of those with atypia on needle biopsy, the overall rate of underlying carcinoma was 17.5%. After adjustment, older age was associated with a greater risk of underlying carcinoma (odds ratio: 1.028, 95% confidence interval: 1.003-1.053; P = 0.03). Of those confirmed to have atypia on surgical excision, the overall rate of a subsequent cancer diagnosis was 15.7%. Age was not associated with a long-term risk for breast cancer (P = 0.48) or the time to a subsequent diagnosis of carcinoma (log-rank P = 0.41). CONCLUSIONS:Although atypia diagnosed on needle biopsy may be sufficient to warrant surgical excision, older women may be at a greater risk for an underlying carcinoma, albeit the long-term risk for malignancy associated with atypia does not appear to be affected by age.