Kelly K Hunt

• University of Texas MD Anderson Cancer Center

Importance Neoadjuvant systemic therapy (NST) has been associated with pathologic complete response (pCR) in up to 60% of breast cancers (BCs). The findings of this trial question the necessity of surgery. Objective To report preplanned 5-year efficacy outcomes evaluating radiotherapy alone without breast surgery in patients selected with image-gu...

IMPORTANCE Neoadjuvant systemic therapy (NST) has been associated with pathologic complete response (pCR) in up to 60% of breast cancers (BCs). The findings of this trial question the necessity of surgery. OBJECTIVE To report preplanned 5-year efficacy outcomes evaluating radiotherapy alone without breast surgery in patients selected with image-gui...

Purpose: To develop deep learning models for predicting the pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in patients with triple-negative breast cancer (TNBC) based on pretreatment multiparametric breast MRI and clinicopathological data. Methods: The prospective institutional review board-approved study [NCT02276443] in...

Background Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor–positive, HER2–negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for relia...

Endocrine therapy with CDK4/6 inhibitors is standard for estrogen receptor-positive, HER2−negative metastatic breast cancer (ER+/HER2− MBC), yet clinical resistance develops. Previously, we demonstrated that low doses of palbociclib activate autophagy, reversing initial G1 cell cycle arrest, while high concentrations induce off-target senescence. T...

Introduction Breast sarcomas are rare, heterogeneous malignancies often associated with prior radiation and require a multidisciplinary approach, including a comprehensive reconstruction plan. We analyzed reconstructive outcomes in a large cohort of patients with breast sarcomas and provide a contemporary treatment algorithm. Methods We retrospect...

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST‐specific biomarkers for screening patients with NF1. Genome‐wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tis...

Trials evaluating omission of axillary dissection (ALND) in patients with cN0 breast cancer with positive sentinel lymph nodes (SLNs) have excluded neoadjuvant chemotherapy (NACT). It remains unclear whether the data can be extrapolated to cN0 patients undergoing NACT. This study sought to identify factors associated with positive SLNs and addition...

Residual disease after neoadjuvant chemotherapy (NAC) is prognostic and informs adjuvant treatment. Targeted axillary dissection (TAD) following NAC has low false-negative rates, facilitating accurate axillary staging. This study evaluates the clipped node status in axillary staging utilizing TAD. Retrospective review identified cN1 breast cancer p...

The course of subclinical gastrointestinal stromal tumors (GISTs) is variable. The management of small GISTs is not well-defined. Records of patients presenting with small GISTs with documented follow-up appointment at our institution between 2016 and 2022 were identified and reviewed. Comparative univariate analysis to compare patient and tumor ch...

Background Moderately hypofractionated, preoperative radiotherapy in patients with soft tissue sarcomas (HYPORT‐STS; ClinicalTrials.gov identifier NCT03819985) investigated a radiobiologically equivalent, moderately hypofractionated course of preoperative radiotherapy (RT) 15 × 2.85 Gy in patients with soft tissue sarcoma (STS). Here, the authors r...

HER2-positive breast cancer is traditionally treated with neoadjuvant systemic therapy (NST), but optimal treatment sequencing is less clear in patients with small tumors. We investigated clinicopathologic and oncologic outcomes in early stage HER2-positive breast cancer. An institutional database was queried to identify patients with cT1–2 (≤ 3 cm...

Cyclin E is a regulatory subunit of CDK2 that mediates S phase entry and progression. Cleavage of full-length cyclin E (FL-cycE) to low molecular weight isoforms (LMW-E) dramatically alters the substrate specificity, promoting G1/S cell cycle transition and accelerating mitotic exit. Approximately 70% of triple-negative breast cancers (TNBC) expres...

Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity. A retrospective review of patient demographics,...

For localized breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), surgical resection is crucial; however, radiation therapy (RT) can be utilized as local-regional therapy if surgery is incomplete or not recommended. We present the case of a woman with BIA-ALCL who received systemic therapy and consolidation RT.

In response to growing evidence that proper performance of operative techniques during cancer surgery is associated with improved patient outcomes, the American College of Surgeons (ACS) implemented six operative standards as part of Commission on Cancer (CoC) accreditation. This study aimed to assess surgeon familiarity with these standards when f...

Optimal surgical margin width for patients with phyllodes tumors (PTs) of the breast remains debated. The aim of this study was to assess the influence of margin width on long-term local recurrence risk. This was a single-institution retrospective review of patients with confirmed PT treated from 2008–2015. Margins were defined as positive (ink on...

Axillary dissection is the standard of care for patients with positive sentinel lymph nodes (SLNs) following neoadjuvant systemic therapy. Frozen section can provide intraoperative information regarding the need for axillary dissection during the index operation. However, there are limited data on the utility of frozen section in patients with clin...

Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer...

Inflammatory breast cancer (IBC) is rare and biologically aggressive. We sought to assess diagnostic and management strategies among the American Society of Breast Surgeons (ASBrS) membership. An anonymous survey was distributed to ASBrS members from March to May 2023. The survey included questions about respondents’ demographics and information re...

Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and af...

Importance Although most women with BRCA- associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conserva...

Background: We evaluated the activity of neoadjuvant ICB in localized resectable DDLPS (n=17) and undifferentiated pleomorphic sarcomas (UPS; n=10). DDLPS and UPS patients were randomized to neoadjuvant nivolumab or ipilimumab+nivolumab, with UPS patients receiving concurrent radiotherapy. We assessed genomic markers of early relapse (progression b...

Background: Women with a history of breast cancer (BC) more commonly have a diagnosis of other primary malignancies (OPMs) than the general population. This study sought to evaluate OPMs among patients with BC who underwent germline testing with a hereditary BC gene panel. Methods: The study identified women 18 years of age or older with a histo...

Background: Patients with unplanned excision (UPE) of trunk and extremity soft tissue sarcoma (STS) present a significant management challenge for sarcoma specialists. Oncologic re-resection has been considered standard practice after UPE with positive or uncertain margins. A strategy of active surveillance or "watch and wait" has been suggested a...

IntroductionEORTC-62092 (STRASS) was a phase 3, randomized study that compared surgery alone versus surgery plus neoadjuvant radiotherapy (RT) for retroperitoneal sarcomas. RT was not associated with improved abdominal recurrence-free survival, the primary outcome measure, although on subanalysis, there may have been benefit for well-differentiated...

Introduction: The ALTERNATE trial randomized postmenopausal women with ER Allred 6-8 HER2- breast cancer to 6 months of NET with anastrozole (A), fulvestrant (F) or the combination (A+F). Biopsies were taken preNET and after 4-weeks(wks). Patients with Ki67 values >10% at 4-wks were offered triage to neoadjuvant chemotherapy. Patients with on-treat...

Introduction: Cyclin E is an independent predictor of poor outcomes and response to treatment in breast cancer (BrCa). Expression of low-molecular-weight cyclin E (LMW-E) is associated with more aggressive disease in all BrCa subtypes. While tumor infiltrating lymphocytes (TILs) are more abundant in LMW-E+ tumors, high-TIL/LMW-E+ tumors have lower...

Background: Cyclin E, a key mediator for G1 to S transition, has unique tumor-specific deregulation in multiple malignancies including breast, ovarian, and colorectal cancers. Our group previously reported that the oncogenic roles of cyclin E are primarily a consequence of the accumulation of several truncated forms, collectively termed low-molecul...

Background: Clinically, the addition of CDK4/6 inhibitors (e.g. palbociclib) to endocrine therapy (ET) significantly delays progression of advanced hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer patients. However, most patients develop resistance and progress following long-term treatment. Thus, an ongoing clinical challenge h...

Background: Neutrophil elastase (NE), a serine protease exclusively secreted in neutrophils, is a crucial mediator of chronic inflammation and tumor progression. Studies from our group reveal that NE may be a prognostic marker of metastasis. In a cohort of 192 breast cancer patients (58% ER/PR+ve, 20%-HER-2 +ve and 22% TNBC), our results show that...

Background/Objective: Optical coherence tomography (OCT) is the optical analog of high-frequency ultrasound and produces real-time, high-resolution images up to 2 mm deep. Multi-reader studies of OCT have shown differentiation of normal parenchyma from neoplasms, including DCIS and cancers, with >85% sensitivity and specificity. Intraoperative eval...

Background: CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) delay progression and improve survival in patients with hormone receptor positive (HR+), HER2 negative metastatic breast cancer (MBC). However, most patients develop resistance to CDK4/6i leading to disease progression, thus new therapies to overcome resistance are needed. CDK4/6i...

Introduction: Sarcomas are rare, aggressive tumors that make up a higher percentage of overall cancer mortality in children and young adults. Primary management of sarcoma patients includes surgical resection with adjuvant or neoadjuvant radiation/chemotherapy. Even with aggressive multimodal treatment regimens, patients with high-grade sarcomas ex...

Introduction: Patients with luminal A and B early-stage ER+/HER2- breast cancer (BrCa) are uniformly treated with adjuvant endocrine therapy (ET) (±chemotherapy). A better understanding of drivers of ET resistance is required as subsequent lethal metastatic disease remains a major clinical problem. Therefore, there is an unmet clinical need to iden...

Background: CDK4/6 inhibitors (CDK4/6i, e.g. palbociclib) in combination with endocrine therapy (ET) have proven successful in delaying progression in hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer patients; however, 60-70% will progress within 1-2 years of treatment. Thus, understanding the mechanisms of resistance...

Purpose: To evaluate prediction of response and event-free survival (EFS) following neoadjuvant endocrine therapy (NeoET) by SET2,3 index of nonproliferation gene expression related to estrogen and progesterone receptors adjusted for baseline prognosis. Experimental design: A correlative study was conducted of SET2,3 measured from gene expressio...

Background Laboratory and clinical research on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is rapidly evolving. Changes in standard of care and insights into best practice were recently presented at the 3 rd World Consensus Conference on BIA-ALCL. Objectives The aim of this manuscript is to provide practice recommendations...

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon peripheral T cell lymphoma arising in response to textured-surface breast implants. Frequently, BIA-ALCL is indolent and typically presents with peri-implant swelling after breast reconstruction or cosmetic augmentation. However, patients can present with an invasive...

Importance: Positive margins following breast-conserving surgery (BCS) are often identified on standard pathology evaluation. Intraoperative assessment of the lumpectomy cavity has the potential to reduce residual disease or reexcision rate following standard of care BCS in real time. Objective: To collect safety and initial efficacy data on the...

Background Survival benefit after resection of the breast primary for women with metastatic breast cancer reported in retrospective studies has not been uniformly confirmed by randomized controlled trials. To assess the need for dissemination of trial results by the ACS Cancer Research Program Dissemination and Implementation (ACS CRP D&I) committe...

Introduction: In response to growing evidence that proper performance of specific operative techniques during cancer surgery is associated with improved patient outcomes, the American College of Surgeons (ACS) has implemented six operative standards for Commission on Cancer (CoC) accreditation. The purpose of this study was to assess surgeons’ fami...

Background: Lymph node metastases (LNMs) are rare in patients with soft tissue sarcoma (STS), and there is limited evidence to guide clinical management. We describe our experience with sentinel lymph node biopsy (SLNB) and lymphadenectomy in STS patients. Methods: A single-center, retrospective review was performed for patients with STS treated...

Background: Nonpalpable breast lesions require precise preoperative localization to facilitate negative margins with breast-conserving therapy. The traditional use of wires has several challenges including patient discomfort, wire migration, and coordination of schedules between radiology and the operating room. Radioactive seed localization overc...

Background: Sarculator is an online validated nomogram that predicts overall survival of patients with resected, primary extremity sarcomas. However, its ability to accurately predict outcomes in US patients with sarcoma is unknown. Patients and methods: Patients from the National Cancer Data Base (NCDB) (2006-2016) with resected stage I-III pri...

Clinical practice guidelines in oncology have typically focused on workup, disease staging, and medical management. Although recommendations for surgical care have been included in these guidelines, those recommendations have primarily addressed issues such as the role of surgery or the incorporation of surgery into multidisciplinary treatment stra...

Low Molecular Weight Cyclin E (LMW-E) are the tumor specific, oncogenic forms of cyclin E that are post translationally generated by neutrophil elastase (NE) mediated cleavage of the 50 KDa full-length cyclin E1 (FL-cycE, encoded by CCNE1 gene). While FL-cycE localizes mainly to the cell nucleus, LMW-E lack the N-terminus nuclear localization signa...

PURPOSE: Cyclin-dependent kinase 4/6 inhibitor (CDKi) therapy combined with endocrinetherapy is considered standard of care for patients with advanced hormone receptor (HR)-positive, HER2-negative breast cancer (BC). The Breast Medical Oncology Database at MDAnderson Cancer Center (MDACC) was analyzed to assess effectiveness of CDKi+palbociclib. PA...

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that frequently harbor genetic alterations in polycomb repressor complex 2 (PRC2) components—SUZ12 and EED. Here, we show that PRC2 loss confers a dedifferentiated early neural-crest phenotype which is exclusive to PRC2-mutant MPNSTs and not a feature of neurofibromas. Neura...

Background Inflammatory breast cancer (IBC) is a rare breast malignancy with poor outcomes compared with non-IBC. Age-related differences in tumor biology, treatment, and clinical outcomes have been described in non-IBC. This study evaluated age-related differences in IBC.Methods From an institutional prospective database, patients with an IBC diag...

Background Neoadjuvant systemic therapy (NST) is standard for locally advanced breast cancer and is now frequently considered for those with early-stage and node-positive disease. We aimed to evaluate the treatment course and outcomes in patients with disease progression during NST.Methods Patients diagnosed with unilateral stage I–III breast cance...

Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between brea...

Introduction: The early COVID-19 pandemic rapidly transformed healthcare and medical education. We sought to evaluate the professional and personal impact of the pandemic on 2019-2020 Breast Surgical Oncology (BSO) fellows in Society of Surgical Oncology approved programs to capture the experience and direct future changes. Methods: From July 15...

The goal of multidisciplinary breast cancer treatment is to optimize therapeutic effectiveness while minimizing acute and long-term toxic effects. The treatment of breast cancer is becoming more individualized. Multidisciplinary care improves patient outcomes, increases guideline-concordant care, and should be considered standard of care for the tr...

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a distinctive type of T-cell lymphoma that arises around textured-surface breast implants. In a subset of patients, this disease can involve surrounding tissues, spread to regional lymph nodes, and rarely metastasize to distant sites. The aim of this study was to assess sequential p...

580 Background: Patients (pts) in Cohort A of the American College of Surgeons Oncology Group Z1031 (Alliance) trial of NET for cStage II-III breast cancer were randomized to anastrozole [ANA], letrozole [LET] or exemestane [EXE] for 16-18 weeks (wks). In Cohort B, pts chose between ANA and LET and switched to chemotherapy or surgery if a tumor bio...

1067 Background: Endocrine therapy with a CDK4/6 inhibitor is standard of care for patients (pts) with estrogen-receptor-positive (ER+), HER2-negative MBC, yet resistance ultimately develops. We have shown that low doses of palbociclib activates autophagy, which reverses initial G1 cell cycle arrest. High concentrations of palbociclib induce senesc...

Salivary gland cancers (SGCs) are rare yet aggressive malignancies with significant histological heterogeneity, which has made prediction of prognosis and development of targeted therapies challenging. In majority of patients, local recurrence and/or distant metastasis are common and systemic treatments have minimal impact on survival. Therefore, i...

Purpose There are few prospective data on predictors of patient-reported outcomes (PROs) after whole breast irradiation (WBI) plus a boost. We sought to characterize longitudinal PROs and cosmesis in a randomized trial comparing conventionally fractionated (CF) vs hypofractionated (HF) WBI. Methods From 2011 to 2014, women age ≥40 years with Tis-T...

Objective: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes. Summary of background data: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo di...

The identification of biomarker-driven targeted therapies for patients with triple negative breast cancer (TNBC) remains a major clinical challenge, due to a lack of specific targets. Here, we show that cyclin E, a major regulator of G1 to S transition, is deregulated in TNBC and is associated with mutations in DNA repair genes (e.g., BRCA1/2). Bre...

Importance Neurofibromatosis type 1 (NF1) is a complex genetic disorder that is associated with not only neurofibromas, but also an increased susceptibility to other neoplasms. Objective To evaluate the prevalence of neoplasia and outcomes among patients with NF1. Design, Setting, and Participants This cohort study was conducted among patients wi...

We surveyed breast providers from a national oncology cooperative group to evaluate axillary management recommendations for patients with 1–2 positive sentinel lymph nodes (+SLNs) with scenarios not explicitly included in the Z0011 trial. These scenarios included patients underrepresented (premenopausal, HER2+/triple‐negative tumors, and invasive l...

Background: NET is offered to postmenopausal patients (pts) with clinical stage 2/3 ER+/HER2- BC to promote breast-conserving surgery. Also limited surgical accessibility during the COVID19 pandemic has increased NET utility. Inability to identify ET-resistant disease at diagnosis risks disease progression (PD) and delays more effective treatments....

Background: Ki67 values >10% 2-4 weeks (wks) after starting neoadjuvant ET (NET) indicates persistent cell proliferation, resistance to ET, and is associated with increased risk of recurrence. The ACOSOG Z1031 trial suggested that these tumors are also relatively chemotherapy (chemo) resistant with a low pathologic complete response (pCR) rate to N...

p>Background: Over the last decade, patients with early-stage breast cancer have been undergoing total mastectomy (TM) with increasing frequency. Our center reported that local recurrence rates with breast conserving therapy (BCT) declined throughout the 27-year period: from 7.1% for patients treated during 1970–1984 to 1.3% for patients treated du...

Importance There is currently no guidance on how to approach surveillance mammography for older breast cancer survivors, particularly when life expectancy is limited. Objective To develop expert consensus guidelines that facilitate tailored decision-making for routine surveillance mammography for breast cancer survivors 75 years or older. Evidenc...

Background Most minorities receive cancer care at minority-serving hospitals (MSHs) that have been associated with disparate treatment between Black and White patients.Objective Our aim was to examine the uptake of clinical trials that have changed axillary management in breast cancer patients at MSH and non-MSH cancer centers.Methods The National...

Background Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to imp...