Browsing by Author "Suman, Vera J."

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    Anastrozole has an association between degree of estrogen suppression and outcomes in early breast cancer and is a ligand for estrogen receptor α
    (American Association of Cancer Research, 2020-06-15) Ingle, James N.; Cairns, Junmei; Suman, Vera J.; Shepherd, Lois E.; Fasching, Peter A.; Hoskin, Tanya L.; Singh, Ravinder J.; Desta, Zeruesenay; Kalari, Krishna R.; Ellis, Matthew J.; Goss, Paul E.; Chen, Bingshu E.; Volz, Bernhard; Barman, Poulami; Carlson, Erin E.; Haddad, Tufia; Goetz, Matthew P.; Goodnature, Barbara; Cuellar, Matthew E.; Walters, Michael A.; Correia, Cristina; Kaufmann, Scott H.; Weinshilboum, Richard M.; Wang, Liewei; Medicine, School of Medicine
    Purpose: To determine if the degree of estrogen suppression with aromatase inhibitors (AI: anastrozole, exemestane, letrozole) is associated with efficacy in early-stage breast cancer, and to examine for differences in the mechanism of action between the three AIs. Experimental design: Matched case-control studies [247 matched sets from MA.27 (anastrozole vs. exemestane) and PreFace (letrozole) trials] were undertaken to assess whether estrone (E1) or estradiol (E2) concentrations after 6 months of adjuvant therapy were associated with risk of an early breast cancer event (EBCE). Preclinical laboratory studies included luciferase activity, cell proliferation, radio-labeled ligand estrogen receptor binding, surface plasmon resonance ligand receptor binding, and nuclear magnetic resonance assays. Results: Women with E1 ≥1.3 pg/mL and E2 ≥0.5 pg/mL after 6 months of AI treatment had a 2.2-fold increase in risk (P = 0.0005) of an EBCE, and in the anastrozole subgroup, the increase in risk of an EBCE was 3.0-fold (P = 0.001). Preclinical laboratory studies examined mechanisms of action in addition to aromatase inhibition and showed that only anastrozole could directly bind to estrogen receptor α (ERα), activate estrogen response element-dependent transcription, and stimulate growth of an aromatase-deficient CYP19A1-/- T47D breast cancer cell line. Conclusions: This matched case-control clinical study revealed that levels of estrone and estradiol above identified thresholds after 6 months of adjuvant anastrozole treatment were associated with increased risk of an EBCE. Preclinical laboratory studies revealed that anastrozole, but not exemestane or letrozole, is a ligand for ERα. These findings represent potential steps towards individualized anastrozole therapy.
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    Summary of the 2019 Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling
    (Elsevier, 2020-10) Holstein, Sarah A.; Howard, Alan; Avigan, David; Bhutani, Manisha; Cohen, Adam D.; Costa, Luciano J.; Dhodapkar, Madhav V.; Gay, Francesca; Gormley, Nicole; Green, Damian J.; Hillengass, Jens; Korde, Neha; Li, Zihai; Mailankody, Sham; Neri, Paola; Parekh, Samir; Pasquini, Marcelo C.; Puig, Noemi; Roodman, G. David; Samur, Mehmet Kemal; Shah, Nina; Shah, Urvi A.; Shi, Qian; Spencer, Andrew; Suman, Vera J.; Usmani, Saad Z.; McCarthy, Philip L.; Medicine, School of Medicine
    The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup has organized an annual workshop focused on minimal residual disease (MRD) testing and immune profiling (IP) in multiple myeloma since 2016. In 2019, the workshop took place as an American Society of Hematology (ASH) Friday Scientific Workshop entitled “Immune Profiling and Minimal Residual Disease Testing in Multiple Myeloma”. This workshop focused on four main topics: the molecular and immunological evolution of plasma cell disorders, the development of new laboratory- and imaging-based MRD assessment approaches, chimeric antigen receptor T-cell therapy research, and the statistical and regulatory issues associated with novel clinical endpoints. In this report, we provide a summary of the workshop and discuss future directions.