Browsing by Author "Armstrong, Deborah K."

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    Changes in breast density and circulating estrogens in postmenopausal women receiving adjuvant anastrozole
    (AACR, 2011-12) Prowell, Tatiana M.; Blackford, Amanda L.; Byrne, Celia; Khouri, Nagi F.; Dowsett, Mitchell; Folkerd, Elizabeth; Tarpinian, Karineh S.; Powers, Pendleton P.; Wright, Laurie A.; Donehower, Michele G.; Jeter, Stacie C.; Armstrong, Deborah K.; Emens, Leisha A.; Fetting, John H.; Wolff, Antonio C.; Garrett-Mayer, Elizabeth; Skaar, Todd C.; Davidson, Nancy E.; Stearns, Vered
    Factors associated with an increased risk of breast cancer include prior breast cancer, high circulating estrogens, and increased breast density. Adjuvant aromatase inhibitors are associated with a reduction in incidence of contralateral breast cancer. We conducted a prospective, single-arm, single-institution study to determine whether use of anastrozole is associated with changes in contralateral breast density and circulating estrogens. Eligible patients included postmenopausal women with hormone receptor-positive early-stage breast cancer who had completed local therapy, had an intact contralateral breast, and were recommended an aromatase inhibitor as their only systemic therapy. Participants received anastrozole 1 mg daily for 12 months on study. We assessed contralateral breast density and serum estrogens at baseline, 6, and 12 months. The primary endpoint was change in contralateral percent breast density from baseline to 12 months. Secondary endpoints included change in serum estrone sulfate from baseline to 12 months. Fifty-four patients were accrued. At 12 months, compared with baseline, there was a nonstatistically significant reduction in breast density (mean change: -16%, 95% CI: -30 to 2, P = 0.08) and a significant reduction in estrone sulfate (mean change: -93%, 95% CI: -94 to -91, P < 0.001). Eighteen women achieved 20% or greater relative reduction in contralateral percent density at 12 months compared with baseline; however, no measured patient or disease characteristics distinguished these women from the overall population. Large trials are required to provide additional data on the relationship between aromatase inhibitors and breast density and, more importantly, whether observed changes in breast density correlate with meaningful disease-specific outcomes.
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    A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian CancerA Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer
    (American Association for Cancer Research, 2020-03-01) Oza, Amit M.; Matulonis, Ursula A.; Secord, Angeles Alvarez; Nemunaitis, John; Roman, Lynda D.; Blagden, Sarah P.; Banerjee, Susana; McGuire, William P.; Ghamande, Sharad; Birrer, Michael J.; Fleming, Gini F.; Markham, Merry Jennifer; Hirte, Hal W.; Provencher, Diane M.; Basu, Bristi; Kristeleit, Rebecca; Armstrong, Deborah K.; Schwartz, Benjamin; Braly, Patricia; Hall, Geoff D.; Nephew, Kenneth P.; Jueliger, Simone; Oganesian, Aram; Naim, Sue; Hao, Yong; Keer, Harold; Azab, Mohammad; Matei, Daniela; Anatomy and Cell Biology, School of Medicine
    PURPOSE: Platinum resistance in ovarian cancer (OC) is associated with epigenetic modifications. Hypomethylating agents (HMAs) have been studied as carboplatin re-sensitizing agents in OC. This randomized phase 2 trial compared guadecitabine, a second generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant OC. PATIENTS AND METHODS: Patients received either G+C (guadecitabine 30 mg/m2 SC once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.