Publications by authors named "Litton J"
Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications.
View Article and Find Full Text PDFIntroduction: Prior studies of patients treated for breast cancer during pregnancy (PrBC) report mixed outcomes and are limited by substandard treatment, small cohorts, and short follow-up. This study compared survival outcomes of PrBC patients treated with chemotherapy during pregnancy with nonpregnant patients matched by age, year of diagnosis, stage, and subtype.
Methods: PrBC patients treated from 1989 to 2022 on prospective institutional protocols were eligible.
Article Synopsis
- The study investigates the effectiveness of the anti-EGFR monoclonal antibody panitumumab combined with carboplatin and paclitaxel for treating chemotherapy-resistant triple-negative breast cancer (TNBC) patients.
- It included 43 patients who had not sufficiently responded to prior doxorubicin and cyclophosphamide treatment, achieving a combined pathological complete response/residual cancer burden class I rate of 30.2%.
- The results indicate that panitumumab shows promise as part of neoadjuvant therapy for TNBC, warranting further evaluation in larger clinical trials.
Purpose: Sleep disturbances are common in patients with breast cancer, but comprehensive evaluations with patient-reported outcomes (PRO) and sleep evaluation with polysomnography (PSG) are lacking. This study describes sleep disruption using PROs and PSG to identify underlying sleep disorders.
Methods: A retrospective review of patients with breast cancer undergoing formal sleep evaluation from 4/1/2009 to 7/31/2014 was performed.
Purpose: We tested the ability of [F] fluorthanatrace (FTT), a radiolabeled analog of poly(ADP-ribose) polymerase (PARP)-1 inhibitors, to demonstrate target engagement on positron emission tomography (PET) scans from patients with newly diagnosed primary breast cancer receiving the PARP inhibitor (PARPi) talazoparib.
Methods: Seven patients with germline pathogenic variants underwent [F]FTT PET-computed tomography scanning at baseline, and five underwent repeat scanning 14 days after talazoparib initiation. Maximum uptake on PET was quantified in the primary tumor, involved nodes, contralateral pectoralis muscle, and lumbar vertebra body level 3, and compared between the two time points.
Purpose: Radiation therapy is an underinvestigated tool for priming the immune system in intact human breast cancers. We sought here to investigate if a preoperative radiation therapy boost delivered was associated with a significant change in tumor-infiltrating lymphocytes (TILs) in the tumor in estrogen receptor positive, HER2Neu nonamplified breast cancers.
Methods And Materials: A total of 20 patients were enrolled in a phase 2 clinical trial and received either 7.
Article Synopsis
- Triple-negative breast cancer (TNBC) patients often undergo neoadjuvant systemic therapy (NAST) to improve treatment outcomes.
- A study analyzed multiparametric MRI scans from 163 TNBC patients at different stages of NAST to see if radiomic models could predict the likelihood of achieving a pathologic complete response (pCR).
- The best predictive model, based on changes in MRI features after two cycles of treatment, showed a strong ability to forecast pCR with high accuracy, indicating that MRI could be useful for early treatment response assessments in TNBC.
Background: Talazoparib monotherapy in patients with germline BRCA-mutated, early-stage triple-negative breast cancer (TNBC) showed activity in the neoadjuvant setting in the phase II NEOTALA study (NCT03499353). These biomarker analyses further assessed the mutational landscape of the patients enrolled in the NEOTALA study.
Methods: Baseline tumor tissue from the NEOTALA study was tested retrospectively using FoundationOneCDx.
Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC.
View Article and Find Full Text PDFArticle Synopsis
- - A clinical trial evaluated the use of dual PD-L1/CTLA-4 checkpoint inhibition (durvalumab and tremelimumab) in 8 patients with Stage II or III HR+/HER2-negative breast cancer before they received neoadjuvant chemotherapy (NACT).
- - Patient responses varied after the immunotherapy; 3 showed significant tumor volume reduction, 3 increased, and 1 remained stable, but only 1 patient achieved a complete pathological response (pCR) at surgery.
- - The trial was halted due to toxicity issues in 3 patients and limited positive effects on the tumor microenvironment, indicating little benefit from this combined treatment approach before NACT.
Article Synopsis
- The study investigates how the PI3K pathway is altered in different subtypes of triple-negative breast cancer (TNBC), focusing on those with mesenchymal (M) and luminal androgen receptor (LAR) characteristics.
- Using tumor samples from patients undergoing neoadjuvant therapy, researchers analyzed alterations in 32 genes related to the PI3K pathway, finding significant differences in gene alterations across seven TNBC subtypes.
- Results indicated that LAR subtype had the highest incidence of pathway alterations and that these alterations may influence treatment responses, suggesting that targeted therapies could benefit patients with M and LAR TNBC.
Article Synopsis
- The study investigates the use of diffusion tensor imaging (DTI) to assess treatment response in women with triple-negative breast cancer (TNBC) undergoing neoadjuvant systemic treatment (NAST).
- Out of 86 participants, 47% achieved a pathologic complete response (pCR), and DTI parameters showed significant differences between pCR and non-pCR patients during treatment.
- Findings suggest that DTI measurements, particularly of the peritumoral region, could be valuable in predicting treatment outcomes for TNBC patients.
Article Synopsis
- A deep learning model was trained to predict how well patients with triple negative breast cancer (TNBC) respond to neoadjuvant systemic therapy (NAST) using MRI scans taken before and after treatment.
- The model showed strong predictive performance, achieving high accuracy scores (AUCs) for different testing groups, indicating it can reliably identify patients who have a pathologic complete response (pCR).
- This technology could lead to more personalized treatment strategies for TNBC patients by allowing early identification of those likely to benefit from NAST based on MRI data.
Article Synopsis
- Early prediction of response to neoadjuvant systemic therapy (NAST) in patients with triple-negative breast cancer (TNBC) can help tailor treatments and prevent unnecessary side effects from ineffective therapies.
- The study analyzed 163 TNBC patients using dynamic contrast-enhanced MRI to identify radiomic features that could indicate treatment response, focusing on areas around and within the tumors at different treatment stages.
- Results showed promising predictive capabilities with certain radiomic features, as well as multivariate models, demonstrating significant accuracy in distinguishing between patients who achieved pathologic complete response (pCR) and those who did not, potentially enhancing early, non-invasive treatment assessments.
Article Synopsis
- Accurate tumor segmentation is essential for analyzing tumors in quantitative imaging studies, particularly for triple-negative breast cancer.
- A new automated deep learning model was developed that uses a comprehensive set of dynamic contrast-enhanced MRI images taken at different stages of treatment.
- This advanced model achieved a high Dice similarity coefficient of 93% and sensitivity of 96%, demonstrating its effectiveness in producing precise tumor measurements for clinical use.
Objective: Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed.
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- Recent research focuses on the phosphoinositide 3-kinase pathway in breast cancer, highlighting the role of PTEN as a crucial component.
- The study aimed to investigate PTEN expression changes in triple-negative breast cancer (TNBC) patients and assess if next-generation sequencing (NGS) could effectively identify PTEN loss, serving as an alternative to traditional immunohistochemistry (IHC).
- Findings revealed inconsistencies in PTEN expression between pretreatment and post-treatment samples, with some tumors showing intratumoral heterogeneity and overlapping copy numbers, suggesting that testing multiple specimens may be necessary for accurate assessment in clinical trials.
Article Synopsis
- The study aimed to evaluate if a radiomics model using synthetic MRI (SyMRI) can predict responses to neoadjuvant systemic therapy (NAST) in women with triple-negative breast cancer (TNBC).
- It involved 181 women who underwent SyMRI scans at the start and mid-treatment, analyzing tumor features extracted from the imaging to identify differences between patients who achieved pathologic complete response (pCR) and those who did not.
- Results indicated that the radiomic features from mid-treatment scans were better at predicting pCR, with the model achieving an area under the receiver operating characteristic curve (AUC) of up to 0.78 in training and 0.72 in testing cohorts, suggesting potential usefulness
Article Synopsis
- High stromal tumor-infiltrating lymphocytes (sTILs) positively correlate with improved pathologic complete response (pCR) in triple-negative breast cancer (TNBC), suggesting their potential as a predictive marker for treatment outcomes.
- A study involving 408 TNBC patients assessed various clinical and biomarker features, identifying thresholds for sTILs and Ki-67 to predict pCR, resulting in specific groups of patients likely benefiting from treatment de-escalation.
- The research demonstrated that combining high sTILs with high Ki-67 significantly increased the accuracy of predicting pCR rates, indicating a promising approach for refining patient selection in neoadjuvant clinical trials.
Article Synopsis
- The STEEP 2.0 criteria, updated in 2021, established standardized definitions for adjuvant breast cancer end points and emphasized the importance of defining neoadjuvant clinical trial end points separately.
- A specialized working group, NeoSTEEP, focused on neoadjuvant systemic therapy end points, considering various factors like cancer subtypes, imaging, and FDA regulations.
- The group recommended defining pathologic complete response (pCR) as no residual invasive cancer present and suggested additional methodologies for evaluating treatment efficacy, including unique end points for hormone receptor-positive cases.
Background: The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC.
Patients And Methods: Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.
Article Synopsis
- Neoadjuvant anti-PD-(L)1 therapy, specifically atezolizumab combined with nab-paclitaxel, shows improved pathological complete response (pCR) rates in patients with treatment-resistant triple-negative breast cancer (TNBC).
- A clinical study included 37 patients who had minimal or no response to prior chemotherapy, and found a pCR/RCB-I rate of 46%, significantly higher than the historical rate of 5%.
- The study concluded that an adaptive approach using neoadjuvant immunotherapy based on initial response should be further investigated in randomized trials, as it suggests a promising method for treating high-risk TNBC patients.
Article Synopsis
- The ENGAGE-1 study tested the monoclonal antibody GSK3174998 alone or with pembrolizumab in patients with advanced solid tumors to evaluate safety, tolerability, and clinical activity.
- Adverse events were reported in 51% of patients receiving GSK3174998 alone and 64% in those receiving it with pembrolizumab, with fatigue being the most common.
- Limited clinical activity was observed, and specific immune cell changes in the tumor microenvironment may explain some treatment responses; however, the overall efficacy did not exceed expectations based on pembrolizumab alone.
Article Synopsis
- Early assessment of neoadjuvant systemic therapy (NAST) response is important for triple-negative breast cancer (TNBC) patients to prevent harmful side effects from ineffective treatments.
- The study evaluated functional tumor volumes (FTVs) using dynamic contrast-enhanced (DCE) MRI after the 2nd and 4th cycles of NAST in 100 patients, finding FTVs at these points could indicate treatment response.
- Results showed that 49% of patients achieved a pathologic complete response (pCR), with FTV at the 4th cycle having the best predictive accuracy (AUC = 0.84), while baseline FTV did not distinguish between pCR and non-pCR.