Publications by authors named "Hope S Rugo"

351 Publications

The clinical relevance of humoral immune responses to Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 and expression of Globo H in metastatic breast cancer.

J Immunother Cancer 2022 Jun;10(6)

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan

An international randomized phase II trial of Globo H (GH) vaccine, adagloxad simolenin/OBI-821 in 349 patients with metastatic breast cancer showed longer progression-free survival (PFS) in vaccinated patients who developed anti-Globo H (anti-GH) IgG than those who did not and the placebo group. The impacts of anti-GH IgM and GH expression on peak anti-GH IgG and clinical outcome were further evaluated. The titers of anti-GH IgG and IgM were determined by ELISA. GH expression in tumor was examined by immunohistochemical staining. Immunophenotyping was conducted by flow cytometry. Adagloxad simolenin elicited anti-GH IgM which peaked at titers ≥1:80 between weeks 5 and 13. The mean anti-GH IgG titer peaked at week 41 and decreased thereafter on the completion of vaccination. One log increase in peak IgM was associated with 10.6% decrease in the HR of disease progression (HR: 0.894, 95% CI: 0.833 to 0.960, p=0.0019). Patients with anti-GH IgM ≥1:320 within first 4 weeks after vaccination had significantly higher maximum anti-GH IgM (p<0.0001) and IgG titers (p<0.0001) than those with <1:320. Moreover, the median PFS appears to be longer for patients with anti-GH IgM ≥1:320 within first 4 weeks than those with anti-GH IgM titer <1:320 (11.1 vs 7.3 months, p=0.164), but not statistically significant. Among patients with H score ≥80 for GH expression by immunohistochemistry, the vaccination group (n=42) seemed to have better PFS than the placebo group (n=23) (HR=0.59; 95% CI: 0.32 to 1.10, p=0.10), but the difference did not reach statistical significance. In addition, peak levels of anti-GH IgM were higher in patients who had lower percentage of activated regulatory T cells (Treg cells; CD4CD45RAFoxp3) at baseline than those who had higher activated Treg cells (p=0.042). This study demonstrates that adagloxad simolenin induced both IgG and IgM antibodies against GH. Anti-GH IgM ≥1:320 within first 4 weeks or low activated Treg cells at baseline may help to select patients who are likely to produce a higher level of GH-specific IgM and IgG in the future.
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http://dx.doi.org/10.1136/jitc-2021-004312DOI Listing
June 2022

Efficacy and Safety of Initial 5 Years of Adjuvant Endocrine Therapy in Postmenopausal Hormone Receptor-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.

Front Pharmacol 2022 30;13:886954. Epub 2022 May 30.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China.

To identify the optimal initial 5 years of adjuvant endocrine therapy for hormone receptor-positive postmenopausal early breast cancer (EBC) patients. We conducted a systematic search of the PubMed, Web of Science, and EMBASE to obtain relevant studies published between January 2000 and January 2022. Randomized clinical trials assessing the efficacy and safety of initial 5 years of adjuvant endocrine therapy were included. The primary outcomes were disease-free survival and overall survival and the secondary outcome was severe adverse effects (SAEs). A Bayesian network meta-analysis was carried out to indirectly compare all regimens and the value of surface under the cumulative ranking curve (SUCRA) was used to obtain rankings. Eleven studies with 49,987 subjects were included. For DFS, exemestane (EXE) [hazard ratio (HR) 0.91, 95% confidence interval (95%CI) 0.87-0.96], anastrozole (ANA) (0.94, 0.90-0.97), letrozole (LET) (0.93, 0.89-0.97), tamoxifen (TAM) followed by EXE (0.91, 0.87-0.96), and TAM followed by ANA (0.92, 0.87-0.98) were more favorable than TAM, with TAM followed by EXE ranking as the first of SUCRA. For OS, only TAM followed by ANA showed significant superiority than TAM (HR 0.91, 95%CI 0.86-0.97) and ranked as the first of SUCRA. For SAEs, EXE (HR 1.72, 95%CI 1.04-2.98), ANA (1.58, 1.03-2.43), and LET (1.63, 1.02-2.57) showed greater associations with bone fracture than TAM. However, no significant difference in the incidences of cardiac events, thromboembolic events, and cerebrovascular events was found among all comparisons. The sequential use of aromatase inhibitors, which has the best curative effects and relatively mild side effects, may be the optimal treatment mode for hormone receptor-positive postmenopausal EBC patients. In addition, the three kinds of aromatase inhibitors achieved roughly equal efficacy, but caused different types of SAEs. [website], identifier [registration number].
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http://dx.doi.org/10.3389/fphar.2022.886954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198062PMC
May 2022

Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

J Natl Compr Canc Netw 2022 Jun;20(6):691-722

28Moffitt Cancer Center.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.
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http://dx.doi.org/10.6004/jnccn.2022.0030DOI Listing
June 2022

Sacituzumab govitecan as second-line treatment for metastatic triple-negative breast cancer-phase 3 ASCENT study subanalysis.

NPJ Breast Cancer 2022 Jun 9;8(1):72. Epub 2022 Jun 9.

International Breast Cancer Center, Quirón Group, Barcelona, Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain.

Patients with triple-negative breast cancer (TNBC) who relapse early after (neo)adjuvant chemotherapy have more aggressive disease. In the ASCENT trial, sacituzumab govitecan (SG), an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38 via a hydrolyzable linker, improved outcomes over single-agent chemotherapy of physician's choice (TPC) in metastatic TNBC (mTNBC). Of 468 patients without known baseline brain metastases, 33/235 vs 32/233 patients (both 14%) in the SG vs TPC arms, respectively, received one line of therapy in the metastatic setting and experienced disease recurrence ≤12 months after (neo)adjuvant chemotherapy. SG prolonged progression-free survival (median 5.7 vs 1.5 months [HR, 0.41; 95% CI, 0.22-0.76]) and overall survival (median 10.9 vs 4.9 months [HR, 0.51; 95% CI, 0.28-0.91]) vs TPC, with a manageable safety profile in this subgroup consistent with the overall population. In this second-line setting, as with later-line therapy, SG improved survival over conventional chemotherapy for patients with mTNBC.
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http://dx.doi.org/10.1038/s41523-022-00439-5DOI Listing
June 2022

Biomarkers for Cyclin-Dependent Kinase 4/6 Inhibitors in the Treatment of Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced/Metastatic Breast Cancer: Translation to Clinical Practice.

JCO Precis Oncol 2022 Jun;6:e2100473

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA.

Purpose: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as effective treatments for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (mBC). Dedicated research efforts have been undertaken to find predictive biomarkers of response or resistance to these therapies although no molecular biomarkers for mBC have reached the clinic so far. This review aims to summarize and evaluate the performance of biomarkers in predicting progression-free survival in phase II and III clinical trials of CDK4/6 inhibitors in HR+/HER2- mBC.

Methods: For this narrative review, a structured literature search of PubMed, Embase, and the Cochrane library (CENTRAL) was performed. Phase II or III clinical trials of a CDK4/6 inhibitor in patients with HR+/HER2- mBC reporting on at least one molecular biomarker analysis of progression-free survival were included. Publications and selected conference abstracts were included up until November 2021.

Results: Twenty-two articles reporting biomarker results of 12 clinical trials were included. Retinoblastoma protein status and cyclin E1 mRNA expression were promising baseline biomarkers, whereas circulating tumor DNA ratio on treatment relative to baseline, change in plasma thymidine kinase activity, and circulating tumor cell count were potential dynamic biomarkers of response. A number of biomarkers were unsuccessful, despite a strong mechanistic rationale, and others are still being explored.

Conclusion: Our review of clinical trials showed that there are a number of promising biomarkers at baseline and several dynamic biomarkers that might predict response to CDK4/6 inhibitors. Validation of these findings and assessment of clinical utility are crucial to make the final translation to clinical practice. Better understanding of disease heterogeneity and further elucidation of resistance mechanisms could inform future studies of rationally selected biomarkers.
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http://dx.doi.org/10.1200/PO.21.00473DOI Listing
June 2022

Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer.

N Engl J Med 2022 Jun 5. Epub 2022 Jun 5.

From the Memorial Sloan Kettering Cancer Center, New York (S.M.); Institut du Cancer de Montpellier, Université Montpellier, INSERM Unité 1194, Montpellier (W.J.), and Institut Curie, Université Paris Cité, Paris (J.-Y.P.) - both in France; Kanagawa Cancer Center, Yokohama (T.Y.), Kyushu Cancer Center, National Hospital Organization, Fukuoka (E.T.), Showa University Hospital, Tokyo (J.T.), and Tokai University School of Medicine, Isehara-shi (N.N.) - all in Japan; Yonsei Cancer Center, Yonsei University Health System (J. Sohn), Samsung Medical Center (Y.H.P.), Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University (S.-A.I.), and Asan Medical Center, University of Ulsan College of Medicine (S.-B.K.), Seoul, Kyungpook National University Chilgok Hospital, Daegu (Y.S.C.), and the National Cancer Center, Goyang-si (K.S.L.) - all in South Korea; the Department of Medical Oncology, Hospital Clínic de Barcelona (M.V., A.P.), Translational Genomics and Targeted Therapies in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (A.P.), the Department of Medicine, University of Barcelona (A.P.), the Breast Cancer Unit, Institute of Oncology (IOB)-Quirón Salud (A.P.), Institut Catala d'Oncologia l'Hospitalet-Hospital Duran i Reynals (M.G.-G.), and Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (C.S.) - all in Barcelona; the University of Texas M.D. Anderson Cancer Center, Houston (N.T.U.); Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (B.X.), Zhejiang Cancer Hospital, Hangzhou (X.W.), the First Hospital of Jilin University, Changchun (W.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou (Q.L.), West China Hospital, Sichuan University, Chengdu (T.L.), and Liaoning Cancer Hospital and Institute, Shenyang (T.S.) - all in China; the Cleveland Clinic Foundation, Cleveland (H.C.F.M.); the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco (H.S.R.); Rabin Medical Center, Petah Tikva, Tel Aviv University, Tel Aviv, Israel (R.Y.); Alexandra Regional General Hospital, Athens (F.Z.); Institut Jules Bordet, Brussels (A.G.); Queen Mary University of London, London (P.S.), and Edinburgh Cancer Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh (D.A.C.) - both in the United Kingdom; Daiichi Sankyo, Basking Ridge, NJ (D.G., L.Y., Y.W., J. Singh, P.V., G.M.); and the Breast Center, Department of Obstetrics and Gynecology, and Comprehensive Cancer Center Munich, Ludwig Maximilian University Hospital, Munich, Germany (N.H.).

Background: Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers.

Methods: We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients.

Results: Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.

Conclusions: In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).
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http://dx.doi.org/10.1056/NEJMoa2203690DOI Listing
June 2022

Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies.

Cancer Cell 2022 Jun 26;40(6):609-623.e6. Epub 2022 May 26.

Yale School of Medicine, Yale University, New Haven, CT 06510, USA.

Using pre-treatment gene expression, protein/phosphoprotein, and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond clinical hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. We assess the predictive performance of mechanism-of-action biomarkers from ∼990 patients treated with 10 regimens targeting diverse biology. We explore >11 subtyping schemas and identify treatment-subtype pairs maximizing the pathologic complete response (pCR) rate over the population. The best performing schemas incorporate Immune, DNA repair, and HER2/Luminal phenotypes. Subsequent treatment allocation increases the overall pCR rate to 63% from 51% using HR/HER2-based treatment selection. pCR gains from reclassification and improved patient selection are highest in HR subsets (>15%). As new treatments are introduced, the subtyping schema determines the minimum response needed to show efficacy. This data platform provides an unprecedented resource and supports the usage of response-based subtypes to guide future treatment prioritization.
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http://dx.doi.org/10.1016/j.ccell.2022.05.005DOI Listing
June 2022

Overall Survival With Palbociclib And Fulvestrant in Women With HR+/HER2- ABC: Updated Exploratory Analyses of PALOMA-3, a Double-Blind, Phase 3 Randomized Study.

Clin Cancer Res 2022 May 12. Epub 2022 May 12.

Breast Unit, The Royal Marsden NHS Foundation Trust, and Breast Cancer Now Research Centre, The Institute of Cancer Research, London, United Kingdom.

Purpose: To conduct an updated exploratory analysis of overall survival (OS) with a longer median follow-up of 73.3 months and evaluate the prognostic value of molecular analysis by circulating tumor DNA (ctDNA).

Patients And Methods: Patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) were randomized 2:1 to receive palbociclib (125 mg orally/d; 3/1 week schedule) and fulvestrant (500 mg intramuscularly) or placebo and fulvestrant. This OS analysis was performed when 75% of enrolled patients died (393 events in 521 randomized patients). ctDNA analysis was performed among patients who provided consent.

Results: At the data cutoff (August 17, 2020), 258 and 135 deaths occurred in the palbociclib and placebo groups, respectively. The median OS (95% CI) was 34.8 months (28.8-39.9) in the palbociclib group and 28.0 months (23.5-33.8) in the placebo group (stratified hazard ratio 0.81; 95% CI, 0.65-0.99). The 6-year OS rate (95% CI) was 19.1% (14.9-23.7) and 12.9% (8.0-19.1) in the palbociclib and placebo groups, respectively. Favorable OS with palbociclib plus fulvestrant compared with placebo plus fulvestrant was observed in most subgroups, particularly in patients with endocrine-sensitive disease, no prior chemotherapy for ABC, low circulating tumor fraction, and regardless of ESR1, PIK3CA, or TP53 mutation status. No new safety signals were identified.

Conclusions: The clinically meaningful improvement in OS associated with palbociclib plus fulvestrant was maintained with >6 years of follow-up in patients with HR+/HER2- ABC, supporting palbociclib plus fulvestrant as a standard of care in these patients.

Trial Registration: ClinicalTrials.gov Identifer: NCT01942135.
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http://dx.doi.org/10.1158/1078-0432.CCR-22-0305DOI Listing
May 2022

Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial.

JAMA Oncol 2022 May 12. Epub 2022 May 12.

International Breast Cancer Center, Quironsalud Group, Barcelona, Spain.

Importance: Patients with breast cancer and brain metastases (BM) have a poor prognosis and high clinical need for novel treatments; however, historically, studies have often excluded these patients. Although the BEACON study did not meet its primary end point, treatment with etirinotecan pegol vs chemotherapy of the physician's choice for patients with advanced breast cancer demonstrated a significant improvement in overall survival (OS) for the prespecified patient subgroup with preexisting, pretreated, and nonprogressive BM.

Objective: To compare clinical outcomes in patients with BM treated with etirinotecan pegol vs chemotherapy of the physician's choice in a confirmatory trial.

Design, Setting, And Participants: This study was a phase 3, open-label, randomized clinical trial (ATTAIN) in patients with metastatic breast cancer and a history of stable pretreated BM who experienced disease progression while receiving chemotherapy in the metastatic setting. The trial took place at 47 sites in 10 countries, and patients were enrolled between March 7, 2017, and November 6, 2019.

Interventions: Patients were randomized to receive etirinotecan pegol, 145 mg/m2, every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel).

Main Outcomes And Measures: The primary end point was OS. Key secondary end points included progression-free survival, objective response rate, duration of response, and the clinical benefit rate.

Results: A total of 178 female patients (9 [5.1%] Asian, 8 [4.5%] Black or African American, and 123 [69.1] White individuals) were randomized to receive treatment with etirinotecan pegol (92 [51.7%]; median [range] age, 53 [27-79] years) or chemotherapy (86 [48.3%]; median [range] age, 52 [24-77] years). Median OS was similar in both groups (etirinotecan pegol, 7.8 months; chemotherapy, 7.5 months; hazard ratio [HR], 0.90; 95% CI, 0.61-1.33; P = .60). Median progression-free survival for non-central nervous system metastases per blinded independent central review for etirinotecan pegol vs chemotherapy was 2.8 and 1.9 months (HR, 0.72; 95% CI, 0.45-1.16; P = .18) and 3.9 vs 3.3 months, respectively, for central nervous system metastases (HR, 0.59; 95% CI, 0.33-1.05; P = .07). Safety profiles between the groups were largely comparable.

Conclusions And Relevance: The results of the ATTAIN randomized clinical trial found no statistically significant difference in outcomes between treatment with etirinotecan pegol and chemotherapy in patients with BM. However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research.

Trial Registration: ClinicalTrials.gov Identifier: NCT02915744.
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http://dx.doi.org/10.1001/jamaoncol.2022.0514DOI Listing
May 2022

Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer.

Breast Cancer Res Treat 2022 May 11. Epub 2022 May 11.

International Breast Cancer Center, Quironsalud Group, Barcelona, Spain.

Purpose: Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38 via a proprietary hydrolyzable linker. In the ASCENT study, SG improved survival versus single-agent treatment of physician's choice (TPC) in pre-treated metastatic triple-negative breast cancer (mTNBC). Hormone/HER2 receptor changes are common, particularly at relapse/metastasis. This subanalysis assessed outcomes in patients who did/did not have TNBC at initial diagnosis, before enrollment.

Methods: TNBC diagnosis was only required at study entry. Patients with mTNBC refractory/relapsing after ≥ 2 prior chemotherapies were randomized 1:1 to receive SG or TPC. Primary endpoint was progression-free survival (PFS) in patients without brain metastases.

Results: Overall, 70/235 (30%) and 76/233 (33%) patients who received SG and TPC, respectively, did not have TNBC at initial diagnosis. Clinical benefit with SG versus TPC was observed in this subset. Median PFS was 4.6 versus 2.3 months (HR 0.48; 95% CI 0.32-0.72), median overall survival was 12.4 versus 6.7 months (HR 0.44; 95% CI 0.30-0.64), and objective response rate (ORR) was 31% versus 4%; those who also received prior CDK4/6 inhibitors had ORRs of 21% versus 5%. Efficacy and safety for patients with TNBC at initial diagnosis were generally similar to those who did not present with TNBC at initial diagnosis.

Conclusion: Patients without TNBC at initial diagnosis had improved clinical outcomes and a manageable safety profile with SG, supporting SG as a treatment option for mTNBC regardless of subtype at initial diagnosis. Subtype reassessment in advanced breast cancer allows for optimal treatment. Clinical trial registration number NCT02574455, registered October 12, 2015.
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http://dx.doi.org/10.1007/s10549-022-06602-7DOI Listing
May 2022

NCCN Guidelines® Insights: Hematopoietic Growth Factors, Version 1.2022.

J Natl Compr Canc Netw 2022 05;20(5):436-442

Dana-Farber/Brigham and Women's Cancer Center.

The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.
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http://dx.doi.org/10.6004/jnccn.2022.0026DOI Listing
May 2022

Longitudinal Trajectories of Memory Performance in Patients with Early-Stage Breast Cancer.

J Oncol 2022 16;2022:5899728. Epub 2022 Apr 16.

New Mexico Highlands University, Department of Psychology, Las Vegas, NM, USA.

Background: While breast cancer and its treatments may affect cognition, the longitudinal trajectories of cognition among those receiving differing cancer treatment types remain poorly understood. Prior research suggests hippocampal-prefrontal cortex network integrity may influence cognition, although how this network predicts performance over time remains unclear.

Methods: We conducted a prospective trial including 69 patients with early-stage breast cancer receiving adjuvant therapy and 12 controls. Longitudinal cognitive testing was conducted at four visits: pretreatment-baseline, 6-7 months, 14-15 months, and 23-24 months. Cognitive composite scores of episodic memory, executive functioning, and processing speed were assessed at each timepoint. Baseline structural MRI was obtained in a subset of these participants, and hippocampal and prefrontal cortex regional volumes were extracted.

Results: Longitudinal linear mixed modeling revealed significant group by time interactions on memory performance, controlling for age and education. Post hoc analyses revealed this effect was driven by patients treated with chemotherapy or chemotherapy plus hormone therapy, who demonstrated the least improvement in memory scores over time. Treatment group did not significantly influence the relationship between time and processing speed or executive functioning. Neither pretreatment hippocampal nor prefrontal volume differed between groups, and there were no significant group by time by baseline regional volume effects on cognition.

Conclusion: Patients with early-stage breast cancer treated with chemotherapy or chemotherapy plus hormone therapy benefit less from practice effects seen in healthy controls on memory tests. Loss of longitudinal practice effect may be a new and clinically relevant measure for capturing patients' experience of cognitive difficulties after treatment.
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http://dx.doi.org/10.1155/2022/5899728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034940PMC
April 2022

Emerging treatment strategies for metastatic triple-negative breast cancer.

Ther Adv Med Oncol 2022 7;14:17588359221086916. Epub 2022 Apr 7.

Director, Breast Oncology and Clinical Trials Education, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1600 Divisadero St., Box 1710, San Francisco, CA 94115, USA.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is often associated with an aggressive phenotype and a poor prognosis. Cytotoxic chemotherapy remains the mainstay of treatment for most patients with metastatic TNBC (mTNBC), but duration of response is often short and median overall survival is only 12-18 months. Therefore, it is critical to identify novel treatment strategies to improve outcomes for these patients. In this review article, we discuss recent advances in treatment strategies for patients with mTNBC including the use of immune checkpoint inhibitors, targeted therapies, and antibody-drug conjugates. For each topic, we summarize important preclinical and clinical data, discuss implications for clinical practice, and highlight future research directions.
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http://dx.doi.org/10.1177/17588359221086916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9003656PMC
April 2022

The role of percutaneous vertebral augmentation in patients with metastatic breast cancer: Literature review including report of two cases.

Breast 2022 Jun 2;63:149-156. Epub 2022 Apr 2.

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Electronic address:

Patients with metastatic breast cancer are at high risk for developing vertebral compression fractures due to underlying bone metastases and bone density loss. Vertebral augmentation techniques including percutaneous vertebroplasty and percutaneous balloon kyphoplasty are techniques used to stabilize compression fractures and improve pain. However, rare complications from these interventions have been observed, including spinal cord compression, nerve root compression, venous cement embolism, and pulmonary cement embolism. These complications pose unique potential challenges for patients with cancer who may already have decreased lung function and potential for venous thromboembolism. In this review, we first describe the role of percutaneous vertebral augmentations in patients with metastatic cancer, with a particular focus on patients with breast cancer. Then, we describe complications of vertebral augmentation in two patients with metastatic breast cancer including long-term symptomatic and radiographic follow-up.
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http://dx.doi.org/10.1016/j.breast.2022.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991318PMC
June 2022

Immunotherapy in Breast Cancer and the Potential Role of Liquid Biopsy.

Front Oncol 2022 15;12:802579. Epub 2022 Mar 15.

Division of Hematology Oncology, University of California San Francisco, San Francisco, CA, United States.

Liquid biopsy biomarkers, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are noninvasive diagnostics that could complement predictive and prognostic tools currently used in the clinic. Recent trials of immunotherapy have shown promise in improving outcomes in a subset of breast cancer patients. Biomarkers could improve the efficacy of immune checkpoint inhibitors by identifying patients whose cancers are more likely to respond to immunotherapy. In this review, we discuss the current applications of liquid biopsy and emerging technologies for evaluation of immunotherapy response and outcomes in breast cancer. We also provide an overview of the status of immunotherapy in breast cancer.
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http://dx.doi.org/10.3389/fonc.2022.802579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964955PMC
March 2022

Evaluation of the Pathways for Survivors Program to Address Breast Cancer Survivorship-Associated Distress: Survey Study.

JMIR Cancer 2022 Feb 25;8(1):e31756. Epub 2022 Feb 25.

Department of Medicine, University of California San Francisco, San Francisco, CA, United States.

Background: Patients with breast cancer frequently experience escalation of anxiety after completing curative treatment.

Objective: This study evaluated the acceptability and psychological impact of a 1-day workshop to emphasize behavioral strategies involving intention and self-efficacy.

Methods: Breast cancer survivors who attended a 1-day Pathways for Survivors workshop provided feedback and completed electronic quality of life (QOL) questionnaires at baseline, 1 and 6 weeks, and 6 months after the workshop. Attendees' baseline QOL scores were compared to follow-up (FUP) scores. Scores from patients receiving routine FUP care were also compiled as a reference population.

Results: In total, 77 patients attended 1 of 9 workshops. The mean satisfaction score was 9.7 out of 10 for the workshop and 9.96 out of 10 for the moderator. Participants' baseline mean Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scores were 57.8 (SD 6.9) and 55.3 (SD 7.5), respectively, which were significantly higher than those of patients receiving routine FUP care (49.1, SD 8.3 and 47.3 SD 8.0, respectively). PROMIS anxiety and depression scores decreased, and the Happiness Index Profile (HIP-10) score-measuring intention and resiliency-increased significantly at 1- and 6-week FUPs.

Conclusions: The Pathways for Survivors program was favorably received. Anxiety and depression decreased significantly at 1- and 6-weeks after the workshop and remained below baseline at 6 months. Increased HIP-10 scores suggest that patients acquired and implemented skills from the workshop. A 1-day workshop led by a lay moderator significantly improved several psychological measures, suggesting that it may be a useful and time-efficient strategy to improve QOL in breast cancer survivors. We are investigating whether an abbreviated "booster" of the intervention at a later date could further improve and maintain QOL gains.
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http://dx.doi.org/10.2196/31756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917438PMC
February 2022

Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial.

NPJ Breast Cancer 2022 Feb 16;8(1):18. Epub 2022 Feb 16.

The University of Chicago, Chicago, IL, USA.

The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1. In this analysis, the incidence of grade 3-4 left ventricular systolic dysfunction (LVSD) in T-DM1 or trastuzumab plus paclitaxel arms were respectively 0.8 and 1.8%. In addition, three (0.8%) patients in the T-DM1 arm and six (5.3%) patients in the adjuvant paclitaxel with trastuzumab (TH) arm experienced a significant asymptomatic left ventricular ejection fraction (LVEF) decline that per-protocol required holding T-DM1 or trastuzumab. All patients with available follow-up data experienced full resolution of cardiac symptoms and LVEF normalization. Furthermore, we performed an exploratory analysis to assess the relationship between age, baseline LVEF, and body mass index with cardiac outcomes. No significant association between these baseline characteristics and the incidence of significant asymptomatic LVEF decline or symptomatic LVSD was identified. The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed.Clinical Trial Registration: ClinicalTrials.gov, NCT01853748.
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http://dx.doi.org/10.1038/s41523-022-00385-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850608PMC
February 2022

Risk-Based Screening for Cancer in Patients With Dermatomyositis: Toward a More Individualized Approach.

JAMA Dermatol 2022 03;158(3):244-247

Department of Dermatology, University of California, San Francisco.

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http://dx.doi.org/10.1001/jamadermatol.2021.5841DOI Listing
March 2022

Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer.

Clin Cancer Res 2022 04;28(7):1383-1390

Banner MD Anderson Cancer Center at Banner Gateway Medical Center, Gilbert, Arizona.

Purpose: PARP inhibitors (PARPi) have demonstrated efficacy in tumors with germline breast cancer susceptibility genes (gBRCA) 1 and 2 mutations, but further factors influencing response to PARPi are poorly understood.

Experimental Design: Breast cancer tumor tissue from patients with gBRCA1/2 mutations from the phase III EMBRACA trial of the PARPi talazoparib versus chemotherapy was sequenced using FoundationOne CDx.

Results: In the evaluable intent-to-treat population, 96.1% (296/308) had ≥1 tumor BRCA (tBRCA) mutation and there was strong concordance (95.3%) between tBRCA and gBRCA mutational status. Genetic/genomic characteristics including BRCA loss of heterozygosity (LOH; identified in 82.6% of evaluable patients), DNA damage response (DDR) gene mutational burden, and tumor homologous recombination deficiency [assessed by genomic LOH (gLOH)] demonstrated no association with talazoparib efficacy.

Conclusions: Overall, BRCA LOH status, DDR gene mutational burden, and gLOH were not associated with talazoparib efficacy; however, these conclusions are qualified by population heterogeneity and low patient numbers in some subgroups. Further investigation in larger patient populations is warranted.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-2080DOI Listing
April 2022

A multidisciplinary approach to optimizing care of patients treated with alpelisib.

Breast 2022 Feb 27;61:156-167. Epub 2021 Dec 27.

Baylor University Medical Center Texas Oncology, US Oncology, Dallas, TX, USA. Electronic address:

Purpose: The oral, α-specific phosphatidylinositol-3-kinase (PI3Kα) inhibitor alpelisib is the first PI3K inhibitor approved for the treatment of advanced breast cancer. As alpelisib is a relatively new therapeutic option, specific guidance and a multidisciplinary approach are needed to provide optimal patient care. The primary objective of this manuscript is to provide comprehensive guidance on minimizing and managing adverse events (AEs) for patients with advanced breast cancer who are receiving alpelisib.

Methods: Clinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs.

Results: The most common AEs associated with alpelisib in the phase 3 SOLAR-1 trial were hyperglycemia and rash (which are considered on-target effects of PI3Kα inhibition) and gastrointestinal AEs, including diarrhea, nausea, and decreased appetite. These AEs require regular monitoring, early recognition, and prompt initiation of appropriate treatment. In addition, there are effective strategies to reduce the onset and severity of frequently observed AEs-in particular, onset of hyperglycemia and rash may be reduced by lifestyle changes (such as reduced intake of carbohydrates and regular exercise) and antihistamine prophylaxis, respectively. To reduce risk of severe hyperglycemia, it is essential to achieve adequate glycemic control prior to initiation of alpelisib treatment.

Conclusion: Overall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach.
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http://dx.doi.org/10.1016/j.breast.2021.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749445PMC
February 2022

Role of Fcγ receptors in HER2-targeted breast cancer therapy.

J Immunother Cancer 2022 01;10(1)

Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA

Several therapeutic monoclonal antibodies (mAbs), including those targeting epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), and CD20, mediate fragment crystallizable gamma receptor (FcγR)-dependent activities as part of their mechanism of action. These activities include induction of antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), which are innate immune mechanisms of cancer cell elimination. FcγRs are distinguished by their affinity for the Fc fragment, cell distribution, and type of immune response they induce. Activating FcγRIIIa (CD16A) on natural killer cells plays a crucial role in mediating ADCC, and activating FcγRIIa (CD32A) and FcγRIIIa on macrophages are important for mediating ADCP. Polymorphisms in FcγRIIIa and FcγRIIa generate variants that bind to the Fc portion of antibodies with different affinities. This results in differential FcγR-mediated activities associated with differential therapeutic outcomes across multiple clinical settings, from early stage to metastatic disease, in patients with HER2+ breast cancer treated with the anti-HER2 mAb trastuzumab. Trastuzumab has, nonetheless, revolutionized HER2+ breast cancer treatment, and several HER2-directed mAbs have been developed using Fc glyco-engineering or Fc protein-engineering to enhance FcγR-mediated functions. An example of an approved anti-HER2 Fc-engineered chimeric mAb is margetuximab, which targets the same epitope as trastuzumab, but features five amino acid substitutions in the IgG 1 Fc domain that were deliberately introduced to increase binding to activating FcγRIIIa and decrease binding to inhibitory FcγRIIb (CD32B). Margetuximab enhances Fc-dependent ADCC in vitro more potently than the combination of pertuzumab (another approved mAb directed against an alternate HER2 epitope) and trastuzumab. Margetuximab administration also enhances HER2-specific B cell and T cell-mediated responses ex vivo in samples from patients treated with prior lines of HER2 antibody-based therapies. Stemming from these observations, a worthwhile future goal in the treatment of HER2+ breast cancer is to promote combinatorial approaches that better eradicate HER2+ cancer cells via enhanced immunological mechanisms.
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http://dx.doi.org/10.1136/jitc-2021-003171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739678PMC
January 2022

Harmonizing PD-L1 testing in metastatic triple negative breast cancer.

Expert Opin Biol Ther 2022 03 29;22(3):345-348. Epub 2021 Dec 29.

European Institute of Oncology, IRCCS, Milan, Italy.

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http://dx.doi.org/10.1080/14712598.2022.2021180DOI Listing
March 2022

Reconceptualizing Risk-Benefit Assessment of Novel Cancer Therapies to Expand Global Access and Reduce Worldwide Mortality.

JAMA Oncol 2022 02;8(2):203-204

Abramson Cancer Center, University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.1001/jamaoncol.2021.5945DOI Listing
February 2022

Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03).

J Clin Oncol 2022 01 7;40(3):282-293. Epub 2021 Dec 7.

ABCSG, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria.

Purpose: Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor-positive breast cancer has not been confirmed.

Patients And Methods: In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer-free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival.

Results: Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial.

Conclusion: At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor-positive breast cancer.
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http://dx.doi.org/10.1200/JCO.21.02554DOI Listing
January 2022

NCCN Guidelines® Insights: Breast Cancer, Version 4.2021.

J Natl Compr Canc Netw 2021 05 1;19(5):484-493. Epub 2021 May 1.

26Research Advocacy Network.

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer-focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor-positive, HER2-negative breast cancer.
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http://dx.doi.org/10.6004/jnccn.2021.0023DOI Listing
May 2021

Matched cohort study of germline BRCA mutation carriers with triple negative breast cancer in brightness.

NPJ Breast Cancer 2021 Nov 11;7(1):142. Epub 2021 Nov 11.

Department of Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.

In the BrighTNess trial, carboplatin added to neoadjuvant chemotherapy (NAC) was associated with increased pathologic complete response (pCR) rates in patients with stage II/III triple-negative breast cancer (TNBC). In this matched cohort study, cases with a germline BRCA1/2 mutation (gBRCA; n = 75) were matched 1:2 with non-gBRCA controls (n = 150) by treatment arm, lymph node status, and age to evaluate pCR rates and association of benefit from platinum/PARP inhibitors with validated RNA expression-based immune, proliferation, and genomic instability scores among gBRCA with the addition of carboplatin ± veliparib to NAC. Among the well-matched cohorts, odds of pCR were not higher in gBRCA cancers who received standard NAC with carboplatin (OR 0.24, 95% CI [0.04-1.24], p = 0.09) or with carboplatin/veliparib (OR 0.44, 95% CI [0.10-1.84], p = 0.26) compared to non-gBRCA cancers. Higher PAM50 proliferation, GeparSixto immune, and CIN70 genomic instability scores were each associated with higher pCR rate in the overall cohort, but not specifically in gBRCA cases. In this study, gBRCA carriers did not have higher odds of pCR than non-gBRCA controls when carboplatin ± veliparib was added to NAC, and showed no significant differences in molecular, immune, chromosomal instability, or proliferation gene expression metrics.
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http://dx.doi.org/10.1038/s41523-021-00349-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586340PMC
November 2021

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2 breast cancer in the adaptively randomized I-SPY2 trial.

Nat Commun 2021 11 5;12(1):6428. Epub 2021 Nov 5.

Georgetown University, Washington, DC, USA.

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2 breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2 tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.
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http://dx.doi.org/10.1038/s41467-021-26019-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571284PMC
November 2021

Expert Discussion: Predictive Markers.

Breast Care (Basel) 2021 Oct 29;16(5):552-557. Epub 2021 Sep 29.

Medical Oncology Department, Centre Léon-Bérard, Lyon, France.

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http://dx.doi.org/10.1159/000519562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543338PMC
October 2021

Decreased enrollment in breast cancer trials by histologic subtype: does invasive lobular carcinoma resist RECIST?

NPJ Breast Cancer 2021 Oct 25;7(1):139. Epub 2021 Oct 25.

University of California, San Francisco, Department of Surgery, San Francisco, CA, USA.

Enrollment in metastatic breast cancer trials usually requires measurable lesions, but patients with invasive lobular carcinoma (ILC) tend to form diffuse disease. We found that the proportion of patients with metastatic ILC enrolled in clinical trials at our institution was significantly lower than that of patients with invasive ductal carcinoma (IDC). Possible links between requiring measurable disease and decreased enrollment of ILC patients require further study to ensure equitable trial access.
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http://dx.doi.org/10.1038/s41523-021-00348-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547221PMC
October 2021

Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer.

NPJ Breast Cancer 2021 Oct 5;7(1):131. Epub 2021 Oct 5.

University of California San Francisco, 550 16th Street, 6464, San Francisco, CA, 94158, USA.

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY's prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.
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http://dx.doi.org/10.1038/s41523-021-00337-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492731PMC
October 2021
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