Biomarker Modulation Study of Celecoxib for Chemoprevention in Women at Increased Risk for Breast Cancer: A Phase II Pilot Study

Bayraktar, Soley; Baghaki, Sema; Wu, Jimin; Liu, Diane D.; Gutierrez‐Barrera, Angelica M.; Bevers, Therese B.; Valero, Vicente; Sneige, Nour; Arun, Banu K.

doi:10.1158/1940-6207.capr-20-0095

Cited by 4 publications

(3 citation statements)

References 52 publications

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“…We propose that clinical prevention trials evaluating the efficacy of NSAIDs for breast cancer prevention among women with BBD that incorporate correlative studies to examine interactions between inflammation and estrogen pathways in breast tissues are warranted. A recently completed phase II trial of celecoxib 400 mg twice daily for 6 months, demonstrated good tolerance with favorable modulation of selected biomarkers (42).…”

Section: Discussionmentioning

confidence: 99%

Breast Cancer Risk and Use of Nonsteroidal Anti-inflammatory Agents After a Benign Breast Biopsy

Sherman

Vierkant

Kaggal

et al. 2020

Cancer Prevention Research

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◥Over one million women in the United States receive biopsy diagnoses of benign breast disease (BBD) each year, which confer a 1.5-4.0-fold increase in breast cancer risk. Studies in the general population suggest that nonsteroidal anti-inflammatory agents (NSAID) lower breast cancer risk; however, associations among women with BBD are unknown. We assessed whether NSAID use among women diagnosed with BBD is associated with lower breast cancer risk. Participants included 3,080 women (mean age ¼ 50.3 AE 13.5 years) in the Mayo BBD surgical biopsy cohort diagnosed between January 1, 1992 and December 31, 2001 who completed breast cancer risk factor questionnaires that assessed NSAID use, and whose biopsies underwent detailed pathology review, masked to outcome. Women were followed from date of BBD biopsy to breast cancer diagnosis (main outcome) or censoring (death, prophylactic mastec-tomy, reduction mammoplasty, lobular carcinoma in situ or last contact). Median follow-up time was 16.4 AE 6.0 years. Incident breast cancer was diagnosed among 312 women over a median follow-up of 9.9 years. Regular non-aspirin NSAID use was associated with lower breast cancer risk [HR ¼ 0.63; 95% confidence interval (CI) ¼ 0.46-0.85; P ¼ 0.002] with trends of lower risk (highest tertiles of use vs. nonuse) for greater number of years used [HR ¼ 0.55; 95% CI ¼ 0.31-0.97; P trend ¼ 0.003), days used per month (HR ¼ 0.51; 95% CI ¼ 0.33-0.80; P trend ¼ 0.001) and lifetime number of doses taken (HR ¼ 0.53; 95% CI ¼ 0.31-0.89; P trend ¼ 0.003). We conclude that nonaspirin NSAID use is associated with statistically significant lower breast cancer risk after a BBD biopsy, including a dose-response effect, suggesting a potential role for NSAIDs in breast cancer prevention among patients with BBD.

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Section: Discussionmentioning

confidence: 99%

Breast Cancer Risk and Use of Nonsteroidal Anti-inflammatory Agents After a Benign Breast Biopsy

Sherman

Vierkant

Kaggal

et al. 2020

Cancer Prevention Research

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“…In other phase II trials however, celecoxib treatment (NCT00300729) or adding celecoxib to concurrent chemoradiation (NCT01503385) did not improve survival of NSCLC patients [294,295]. In a phase II trial, celecoxib induced favorable changes in serum biomarkers and cytology in women with increased risk for breast cancer [296]. Notably, the improvement of prognosis by celecoxib-based combination treatment is more prominent in patients with tumors expressing higher levels of COX-2 [297].…”

Section: Non-steroidal Anti-inflammatory Drugs (Nsaids)mentioning

confidence: 96%

Targeting inflammation as cancer therapy

Wang,

Chen,

et al. 2024

J Hematol Oncol

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Inflammation has accompanied human beings since the emergence of wounds and infections. In the past decades, numerous efforts have been undertaken to explore the potential role of inflammation in cancer, from tumor development, invasion, and metastasis to the resistance of tumors to treatment. Inflammation-targeted agents not only demonstrate the potential to suppress cancer development, but also to improve the efficacy of other therapeutic modalities. In this review, we describe the highly dynamic and complex inflammatory tumor microenvironment, with discussion on key inflammation mediators in cancer including inflammatory cells, inflammatory cytokines, and their downstream intracellular pathways. In addition, we especially address the role of inflammation in cancer development and highlight the action mechanisms of inflammation-targeted therapies in antitumor response. Finally, we summarize the results from both preclinical and clinical studies up to date to illustrate the translation potential of inflammation-targeted therapies.

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“…Initial efforts to examine this question by evaluating the effect of PGE 2 inhibition using celecoxib, a selective COX2 inhibitor, on tissue biomarkers of proliferation (Ki-67) were terminated due to toxicity concerns. Revisiting this, a recently completed study of women at increased risk for breast cancer treated with 400 mg celecoxib twice daily for 6 months using random periareolar fine-needle aspiration sampling of the breast support favorable changes in cytology but no change in tissue Ki-67 or estrogen receptor (ER) expression (19). Observational studies of NSAID use for effects on BD using mammographic measurements have also been largely null though for women followed prospectively, those who continued NSAID use were more likely to remain low density than those who discontinued use (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Sulindac, a Nonselective NSAID, Reduces Breast Density in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors

Thompson

Huang

Yang

et al. 2021

Clinical Cancer Research

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Purpose: To evaluate the effect of sulindac, a nonselective anti-inflammatory drug (NSAID), for activity to reduce breast density (BD), a risk factor for breast cancer. Experimental Design: An open-label phase II study was conducted to test the effect of 12 months' daily sulindac at 150 mg twice daily on change in percent BD in postmenopausal hormone receptor–positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by noncontrast magnetic resonance imaging (MRI) and reported as change in MRI percent BD (MRPD). A nonrandomized patient population on AI therapy (observation group) with comparable baseline BD was also followed for 12 months. Changes in tissue collagen after 6 months of sulindac treatment were explored using second-harmonic generated microscopy in a subset of women in the sulindac group who agreed to repeat breast biopsy. Results: In 43 women who completed 1 year of sulindac (86% of those accrued), relative MRPD significantly decreased by 9.8% [95% confidence interval (CI), −14.6 to −4.7] at 12 months, an absolute decrease of −1.4% (95% CI, −2.5 to −0.3). A significant decrease in mean breast tissue collagen fiber straightness (P = 0.032), an investigational biomarker of tissue inflammation, was also observed. MRPD (relative or absolute) did not change in the AI-only observation group (N = 40). Conclusions: This is the first study to indicate that the NSAID sulindac may reduce BD. Additional studies are needed to verify these findings and determine if prostaglandin E2 inhibition by NSAIDs is important for BD or collagen modulation.

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Biomarker Modulation Study of Celecoxib for Chemoprevention in Women at Increased Risk for Breast Cancer: A Phase II Pilot Study

Cited by 4 publications

References 52 publications

Breast Cancer Risk and Use of Nonsteroidal Anti-inflammatory Agents After a Benign Breast Biopsy

Breast Cancer Risk and Use of Nonsteroidal Anti-inflammatory Agents After a Benign Breast Biopsy

Targeting inflammation as cancer therapy

Sulindac, a Nonselective NSAID, Reduces Breast Density in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors

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