Publications by authors named "Rita Nanda"

Importance: Triple-negative breast cancer (TNBC) disproportionately affects Black women. Immunotherapy improves outcomes in early-stage TNBC (esTNBC) and metastatic TNBC (mTNBC). However, racial and ethnic disparities in immunotherapy receipt and its potential association with oncologic outcomes are unknown.

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Purpose: Glucocorticoid receptor (GR) activity may mediate chemoresistance in advanced triple-negative breast cancer (TNBC). Preclinical studies demonstrate that GR antagonism can augment the effect of taxanes in TNBC models. We hypothesized that pretreatment with mifepristone, a potent GR antagonist, would enhance nab-paclitaxel efficacy in advanced TNBC.

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Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have improved the efficacy of endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) and are now used in both early-stage and metastatic disease. Recent case reports suggest that pseudo-serum creatinine (Scr) elevations are likely a class effect of CDK4/6i.

Methods: This single-center retrospective analysis included patients aged ≥18 years who received at least one dose of palbociclib, ribociclib, or abemaciclib for the treatment of HR+/HER2- BC in the early or advanced setting.

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Article Synopsis
  • In early-stage triple-negative breast cancer (TNBC), high glucocorticoid receptor (GR) expression is linked to poor outcomes, potentially due to an immunosuppressed tumor microenvironment.
  • A study of 47 patients showed that high GR expression correlated with increased levels of immunosuppressive FOXP3+ regulatory T cells and BATF3+ immune cells, but not significantly with CD8+ T cell infiltration.
  • The findings suggest that high GR expression may contribute to a more immunosuppressed state in TNBC, which could explain worse prognoses for patients with GR-positive tumors.
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Purpose: The MammaPrint (MP) prognostic assay categorizes breast cancers into high- and low-risk subgroups, and the high-risk group can be further subdivided into high-1 (MP-H1), and very high-risk high-2 (MP-H2). The aim of this analysis was to assess clinical and molecular differences between the hormone receptor-positive (HR+)/HER2-negative MP-H1, -H2, and triple-negative (TN) MP-H1 and -H2 cancers.

Experimental Design: Pretreatment gene expression data from 742 HER2-negative breast cancers enrolled in the I-SPY2 neoadjuvant trial were used.

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Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR).

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Protein activity state, rather than protein or mRNA abundance, is a biologically regulated and relevant input to many processes in signaling, differentiation, development, and diseases such as cancer. While there are numerous methods to detect and quantify mRNA and protein abundance in biological samples, there are no general approaches to detect and quantify endogenous protein activity with single-cell resolution. Here, we report the development of a chemoproteomic platform, single-cell activity-dependent proximity ligation, which uses automated, microfluidics-based single-cell capture and nanoliter volume manipulations to convert the interactions of family-wide chemical activity probes with native protein targets into multiplexed, amplifiable oligonucleotide barcodes.

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Article Synopsis
  • The CREATE-X trial showed that adjuvant capecitabine can improve survival for high-risk triple-negative breast cancer patients, but the standard dose is often hard to tolerate for many in the US.
  • A retrospective study at the University of Chicago Medicine evaluated the safety and tolerability of capecitabine in 67 TNBC patients, looking specifically at their relative dose intensity (RDI) and side effects over eight treatment cycles.
  • Results indicated that the average RDI was significantly lower than in the CREATE-X trial, with hand-foot syndrome, diarrhea, and fatigue being the most common side effects; the study found no major differences in tolerability based on age, race, BMI, or initial dosage.
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Article Synopsis
  • - The study aimed to understand MRI imaging patterns in breast cancer patients undergoing neoadjuvant immunotherapy, particularly focusing on responses to various combinations of chemotherapy and immunotherapy in the I-SPY2 clinical trial.
  • - Out of 43 patients analyzed, 44.4% receiving the chemo-immunotherapy experienced increased lymphadenopathy in the first 12 weeks, significantly higher compared to just 6.3% in the control group, with most cases linked to the SD-101 and pembrolizumab treatment.
  • - Despite observing increased lymphadenopathy in some patients, this was not associated with a higher incidence of positive lymph nodes at surgery, even as breast tumor sizes decreased over time.
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Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer.

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Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes.

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Background: Given increased neoadjuvant therapy use in early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer, we sought to quantify likelihood of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) or endocrine therapy (NET) as a function of ER%/PR%/Ki-67%, 21-gene recurrence scores (RS), or 70-gene risk groups.

Methods: We analyzed the 2010-2020 National Cancer Database. Surgery was categorized as "mastectomy/BCS.

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Background: Since the COVID-19 pandemic began, we have seen rapid growth in telemedicine use. However, telehealth care and services are not equally distributed, and not all patients with breast cancer have equal access across US regions. There are notable gaps in existing literature regarding the influence of neighborhood-level socioeconomic status on telemedicine use in patients with breast cancer and oncology services offered through telehealth versus in-person visits.

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Purpose: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

Methods: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1.

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Purpose: Patients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and limited treatment options. Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies (≥ 1 in the metastatic setting) based on the ASCENT study (NCT02574455). The current study describes real-world SG use and outcomes in patients with mTNBC in the United States.

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Purpose: Integrative medicine (IM) has received the American Society of Clinical Oncology's endorsement for managing cancer treatment-related side effects. Little is known about racial differences in familiarity, interest, and use of IM among patients with breast cancer.

Methods: Patients with breast cancer enrolled in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort were surveyed regarding familiarity, interest, and use of acupuncture, massage, meditation, music therapy, and yoga.

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Article Synopsis
  • Triple-negative breast cancer (TNBC) is a serious and aggressive type of breast cancer with a high chance of returning and a generally poor outlook for patients.
  • Recent advancements in understanding TNBC's variability have shown that some cases may respond well to immunotherapy, prompting research into this treatment approach for both early and advanced stages of the disease.
  • The review highlights the biological reasons for using immunotherapy in TNBC, summarizes key trial findings that support its approval, and discusses the need for identifying biomarkers and developing new treatment combinations to enhance patient outcomes.
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Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint).

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Integrative medicine (IM) has received ASCO endorsement for managing cancer treatment-related side effects. Little is known about racial differences in familiarity, interest, and use of IM among breast cancer patients. Breast cancer patients enrolled in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort were surveyed regarding familiarity, interest, and use of IM: acupuncture, massage, meditation, music therapy, and yoga.

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Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes.

Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race.

Design, Setting, And Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer.

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Background: Guidelines recommend the use of genomic assays such as OncotypeDx to aid in decisions regarding the use of chemotherapy for hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer. The RSClin prognostic tool integrates OncotypeDx and clinicopathologic features to predict distant recurrence and chemotherapy benefit, but further validation is needed before broad clinical adoption.

Methods: This study included patients from the National Cancer Data Base (NCDB) who were diagnosed with stage I-III HR+/HER2- breast cancer from 2010 to 2020 and received adjuvant endocrine therapy with or without chemotherapy.

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Article Synopsis
  • Trebananib is a peptibody that stops angiopoietin-1 and -2 from activating Tie2 receptors, which helps inhibit cancer growth, and it was tested alongside paclitaxel in the I-SPY2 breast cancer trial.* -
  • The trial involved patients with high-risk, early-stage breast cancer being randomly assigned to receive either trebananib with paclitaxel or a control, with the main goal being to evaluate the pathologic complete response (pCR) rate.* -
  • Although trebananib did not meet the criteria to advance for further testing, it showed promising pCR rates and improved 3-year event-free survival without significantly increasing side effects, highlighting potential biomarkers
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Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint).

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