Faculty Bibliography

Pathology reports are considered the gold standard in medical research due to their comprehensive and accurate diagnostic information. Natural language processing (NLP) techniques have been developed to automate information extraction from pathology reports. However, existing studies suffer from two significant limitations. First, they typically frame their tasks as report classification, which restricts the granularity of extracted information. Second, they often fail to generalize to unseen reports due to variations in language, negation, and human error. To overcome these challenges, we propose a BERT (bidirectional encoder representations from transformers) named entity recognition (NER) system to extract key diagnostic elements from pathology reports. We also introduce four data augmentation methods to improve the robustness of our model. Trained and evaluated on 1438 annotated breast pathology reports, acquired from a large medical center in the United States, our BERT model trained with data augmentation achieves an entity F1-score of 0.916 on an internal test set, surpassing the BERT baseline (0.843). We further assessed the model's generalizability using an external validation dataset from the United Arab Emirates, where our model maintained satisfactory performance (F1-score 0.860). Our findings demonstrate that our NER systems can effectively extract fine-grained information from widely diverse medical reports, offering the potential for large-scale information extraction in a wide range of medical and AI research. We publish our code at https://github.com/nyukat/pathology_extraction.

Triple-negative breast cancers (TNBC) include diverse carcinomas with heterogeneous clinical behavior. DNA methylation is a useful tool in classifying a variety of cancers. In this study, we analyzed TNBC using DNA methylation profiling and compared the results to those of mutational analysis. DNA methylation profiling (Infinium MethylationEPIC array, Illumina) and 50-gene panel-targeted DNA sequencing were performed in 44 treatment-naïve TNBC. We identified 3 distinct DNA methylation clusters with specific clinicopathologic and molecular features. Cluster 1 (phosphoinositide 3-kinase/protein kinase B-enriched cluster; n = 9) patients were significantly older (mean age, 71 years; P = .008) with tumors that were more likely to exhibit apocrine differentiation (78%; P < .001), a lower grade (44% were grade 2), a lower proliferation index (median Ki-67, 15%; P = .002), and lower tumor-infiltrating lymphocyte fractions (median, 15%; P = .0142). Tumors carried recurrent PIK3CA and AKT1 mutations and a higher percentage of low HER-2 expression (89%; P = .033). Cluster 3 (chromosomal instability cluster; n = 28) patients were significantly younger (median age, 57 years). Tumors were of higher grade (grade 3, 93%), had a higher proliferation index (median Ki-67, 75%), and were with a high fraction of tumor-infiltrating lymphocytes (median, 30%). Ninety-one percent of the germline BRCA1/2 mutation carriers were in cluster 3, and these tumors showed the highest level of copy number alterations. Cluster 2 represented cases with intermediate clinicopathologic characteristics and no specific molecular profile (no specific molecular profile cluster; n = 7). There were no differences in relation to stage, recurrence, and survival. In conclusion, DNA methylation profiling is a promising tool to classify patients with TNBC into biologically relevant groups, which may result in better disease characterization and reveal potential targets for emerging therapies.

BACKGROUND:Screening MRI as an adjunct to mammography is recommended by the ACS for patients with a lifetime risk for breast cancer > 20%. While the benefits are clear, MRI screening is associated with an increase in false-positive results. The purpose of this study was to analyze our institutional database of high-risk patients and assess the uptake of screening MRI examinations and the results of those screenings. METHODS:Our institutional review board-approved High-Risk Breast Cancer Database was queried for patients enrolled from January 2017 to January 2023 who were at high risk for breast cancer in a comparative analysis between those who were screened versus not screened with MRIs. Variables of interest included risk factor, background, MRI screening uptake, and frequency and results of image-guided breast biopsies. RESULTS:A total of 254 of 1106 high-risk patients (23%) had MRI screening. Forty-six of 852 (5.3%) patients in the non-MRI-screened cohort and nine of 254 (3.5%) patients in the MRI-screened cohort were diagnosed with a malignant lesion after image-guided biopsy (p = 0.6). There was no significant difference between MRI and non-MRI guided biopsies in detecting breast cancer. All malignant lesions were T1 or in situ disease. The 254 patients in the MRI-screened group underwent 185 biopsies. Fifty-seven percent of MRI-guided biopsies yielded benign results. CONCLUSIONS:Although the addition of MRI screening in our high-risk cohort did not produce a significant number of additional cancer diagnoses, patients monitored in our high-risk cohort who developed breast cancer were diagnosed at very early stages of disease, underscoring the benefit of participation in the program.

Background: Prophylactic nipple-sparing mastectomies (NSM) have become increasingly common, although there is little long-Term data on its efficacy in prevention of breast cancer. The objective of this study was to assess the incidence of breast cancer in a cohort of patients undergoing prophylactic NSM with a median follow-up of 10 years. Methods: Patients receiving prophylactic NSM at a single institution from 2006 to 2019 were included in a retrospective nature. Patient demographics, genetic mutations, operative details, and specimen pathology were recorded, and all postoperative patient visits and documentation were screened for cancer occurrence. Descriptive statics were performed where appropriate. Results: Two hundred eighty-four prophylactic NSMs were performed on 228 patients with a median follow-up of 120.5 ± 15.7 months. Roughly, a third of patients had a known genetic mutation, with 21% BRCA1 and 12% BRCA2. The majority (73%) of prophylactic specimens had no abnormal pathology. The most commonly observed pathologies were atypical lobular hyperplasia (10%) and ductal carcinoma in situ (7%). Cancer was identified in 10% of specimens, with only one case of lymphovascular invasion. Thus far, there have been no incidences of locoregional breast cancer occurrence in this cohort. Conclusions: The long-Term breast cancer occurrence rate in this cohort of prophylactic NSM patients at the time of this study is negligible. Despite this, continued surveillance of these patients is necessary until lifetime risk of occurrence following NSM has been established.

The COVID-19 pandemic strained healthcare systems worldwide, delaying breast cancer screening and surgery. In 2019, approximately 80% of breast cancers in the U.S. were diagnosed on screening examinations, with 76.4% of eligible Medicare patients undergoing screening at least every two years. Since the start of the pandemic, many women have been reluctant to seek elective screening mammography, even with the lifting of pandemic-related restrictions in access to routine healthcare. We describe the effect of the COVID-19 pandemic on breast cancer presentation at a tertiary academic medical center greatly impacted by the pandemic.

Background and Objectives: Perioperative ketamine has been shown to reduce opioid consumption and pain after surgery. Ketamine is most often given as an infusion, but an alternative is single-dose ketamine. Single-dose ketamine at up to 1 mg/kg has been shown to reduce symptoms of depression, and a wide range of dosages has been used for pain in the emergency department. However, limited data exists on the tolerability and efficacy of a single-dose of ketamine at 0.6 mg/kg for pain when administered immediately after surgery. We conducted a pilot study of single-dose ketamine in patients undergoing mastectomy with reconstruction, hypothesizing that a single-dose of ketamine is well tolerated and can relieve postoperative pain and improve mood and recovery. Methods: This is a randomized, single-blind, placebo-controlled, two-arm parallel, single-center study. Thirty adult women undergoing mastectomy with reconstruction for oncologic indication received a single-dose of ketamine (0.6mg/kg) or placebo after surgery in the post-anesthesia care unit (PACU). Patients were followed through postoperative day (POD) 7. The primary outcome was postoperative pain measured by the Brief Pain Inventory (BPI) pain subscale on POD 1 and 2. Secondary outcomes include effects on opioid use, PROMIS fatigue and sleep, mood, Quality of Recovery-15, and the Breast Cancer Pain Questionnaire. Results: Side effects were minor and not significantly different in frequency between groups. The ketamine group reported lower scores on the BPI pain severity subscale, especially at POD 7; however, the difference was not statistically significant. There were no statistically significant differences between ketamine and placebo groups for the secondary outcomes. Conclusion: A single-dose of ketamine at 0.6mg/kg administered postoperatively in the PACU is well tolerated in women undergoing mastectomy and may confer better pain control up to one week after surgery. Future studies with larger sample sizes are necessary to adequately characterize the effect of postoperative single-dose ketamine on pain control in this population.

PURPOSE/OBJECTIVE:Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS/METHODS:Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS:Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION/CONCLUSIONS:In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

Purpose/Objective(s): Breast re-irradiation (reRT) after repeat breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy in women presenting with low risk in-breast tumor recurrence (IBTR). However, there is limited data on optimal patient selection and safety of different fractionation regimens. This multi-institutional study reports safety and efficacy in a large cohort of women with IBTR treated with repeat BCS and reRT. Materials/Methods: Using electronic medical record search tools, we identified all patients who underwent repeat BCS followed by breast reRT from 2015-2021 at 2 institutions. Univariate logistic regression models were used to identify clinical and dosimetric factors associated with development of acute and late toxicities. All statistical tests were two-sided, and the null hypothesis was rejected for p<0.05. Kaplan Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS) and locoregional recurrence-free survival (LR-RFS).
Result(s): We identified 66 patients with an IBTR treated with repeat BCS. In the initial RT course, 55% received whole breast RT (WBI) with conventional fractionation (<=2 Gy/fraction[fx]), 29% WBI with hypofractionation (2.6-2.7 Gy/fx), 6% partial breast irradiation (PBI) ultrahypofractionation (6-8 Gy/fx) and 11% had unavailable treatment details. There was a median of 11 years between initial breast cancer and IBTR. At time of recurrence, 36% of patients had tumors located in the same quadrant as the initial cancer, 41% had invasive carcinoma with ductal carcinoma in situ (DCIS), 41% had invasive carcinoma alone, 18% had DCIS alone, 92% had tumors < 2 cm, 68% had low-intermediate grade tumors and all were clinically node negative. For reRT, 95% received PBI (57.5% 45 Gy/1.5 Gy twice daily; 27% 45 Gy/1.8 Gy daily; 10.5% hypofractionation), and 5% received WBI (45-46.8 Gy in 1.8 Gy/fx), all of whom had received PBI for the initial course. Nine patients (13%) underwent adjuvant chemotherapy and 44 (67%) adjuvant hormone therapy. Median follow-up was 16 months (range 3-60). Twenty-one patients (32%) experienced any acute >= grade 2 events, and 17 (26%) experienced any late >= grade 2 toxicities. One patient experienced grade 3 fibrosis and one patient experienced grade 3 telangiectasia at 36 months. None had grade 4 or higher late adverse events. We found no association between fractionation of reRT or cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%.
Conclusion(s): In this large multi-institutional series of patients with recurrent breast cancer, second breast conservation surgery followed by reRT was effective with no local recurrences and excellent disease control outcomes, and toxicity appears to be acceptable. Longer follow-up and more prospective study are needed to further inform patient selection and establish the efficacy and tolerability of repeat breast conservation therapy in the setting of limited, low-risk recurrence.
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INTRODUCTION/UNASSIGNED:In patients with non-palpable breast cancer, the availability of wireless localization techniques facilitates removal of the target lesion. One such technique uses a radar reflector for localization (RRL). This study evaluates the feasibility and effectiveness of RRL to guide excision of axillary lymph nodes in patients with node-positive breast cancer. METHODS/UNASSIGNED:Our Breast Cancer Database was queried for patients diagnosed with breast cancer, between 5/2017 and 10/2021, who underwent preoperative placement of a radar reflector into a biopsy proven axillary lymph node. Clinicopathologic data were reported using descriptive statistics. RESULTS/UNASSIGNED:Twenty patients underwent preoperative placement of a radar reflector into the axilla. Intraoperatively, the clip and radar reflector were successfully removed in all patients. Among the 10 patients treated with NAC, 5 patients achieved an axillary pathologic complete response (pCR) and were spared a complete axillary lymph node dissection (cALND). Among the entire cohort, RRL resulted in a 53% reduction in the number of lymph nodes removed. CONCLUSIONS/UNASSIGNED:Wireless localization of axillary lymph nodes is safe and feasible. The technique ensures excision of biopsy proven positive axillary lymph nodes and enables a targeted approach to assessing the axilla, both in the setting of NAC and upfront surgery.