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  • 1
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    Online Resource
    Meta‐analysis of agreement/concordance statistics in studies comparing self‐ vs clinician‐collected samples for HPV testing in cervical cancer screening
    Wiley ; 2022
    In:  International Journal of Cancer Vol. 151, No. 2 ( 2022-07-15), p. 308-312
    Details
    In: International Journal of Cancer, Wiley, Vol. 151, No. 2 ( 2022-07-15), p. 308-312
    Abstract: We conducted a meta‐analysis of test agreement/concordance between human papillomavirus (HPV) testing in self‐collected vs clinician‐collected samples in 26 studies (10 071 participants) updating a previous meta‐analysis on accuracy for cervical precancer. Pooled overall agreement was 88.7% (95% CI: 86.3%‐90.9%), positive agreement was 84.6% (95% CI: 79.9%‐88.7%), negative agreement was 91.7% (95% CI: 89.1%‐94.0%) and kappa was 0.72 (95% CI: 0.66‐0.78). Subgroup meta‐analyses suggested higher overall agreement for target amplification‐based DNA assays (90.4%) compared to signal amplification‐based DNA assays (86.7%; P  = .175) or RNA assays (82.3%; P   〈  .001). HPV test agreement/concordance targets may provide criteria to extend existing validations toward alternative sampling approaches and devices/storage media.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    URL: Article
    DOI: 10.1002/ijc.v151.2
    DOI: 10.1002/ijc.33967
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 2
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    Cancer Prevention in Primary Care: Perception of Importance, Recognition of Risk Factors and Prescribing Behaviors
    Elsevier BV ; 2020
    In:  The American Journal of Medicine Vol. 133, No. 6 ( 2020-06), p. 723-732
    Details
    In: The American Journal of Medicine, Elsevier BV, Vol. 133, No. 6 ( 2020-06), p. 723-732
    Type of Medium: Online Resource
    ISSN: 0002-9343
    URL: Article
    DOI: 10.1016/j.amjmed.2019.11.017
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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  • 3
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    Abstract 159: Modulating effects of resveratrol on systemic markers associated with breast cancer risk: a pilot clinical study in postmenopausal women with high adiposity.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 159-159
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 159-159
    Abstract: Resveratrol, a phytochemical produced by a restricted number of plant species in response to stress, has exerted compelling breast cancer preventive activities in preclinical studies. Resveratrol not only acted as an estrogen receptor agonist/antagonist and inhibited aromatase but also affected multiple carcinogenesis pathways and multiple targets within a pathway. Resveratrol also demonstrated beneficial effects on metabolic disturbances in rodent models for obesity. We conducted an open label, single arm pilot study of resveratrol in postmenopausal women with high body mass index (BMI ≥ 25 kg/m2), a risk factor for breast cancer. The primary objective was to determine the effect of resveratrol on serum estradiol levels with secondary endpoints being measurement of modulation of multiple systemic markers associated with breast cancer risk. Forty eligible subjects were recruited to initiate the resveratrol intervention (1 gm resveratrol daily for 12 weeks) with six withdrawn early due to adverse events. Thirty-four subjects completed 12 weeks of resveratrol intervention. We found that resveratrol intervention did not result in significant changes in serum concentrations of estradiol, estrone, and testosterone in the study cohort but significantly increased serum levels of sex steroid hormone binding globulin (10% increase from baseline, p & lt; 0.01). Resveratrol intervention resulted in a significant increase in urinary 2-hydroxyestrone (2-OHE1) levels (73% increase from baseline, p & lt; 0.01) leading to a favorable change in urinary 2-OHE1/16α-OHE1 ratio (85% increase from baseline, p & lt; 0.01). Serum leptin levels were suppressed significantly (10% decrease from baseline, p & lt; 0.01) following resveratrol intervention whereas serum adiponectin levels were not changed. The most common possibly or probably related adverse events were diarrhea, constipation, and abdominal discomfort. One participant had a possibly related serious grade 4 elevation in hepatic ALT and AST enzymes at the post-intervention visit which resolved after less than 3 months of follow-up. Aside from this event, resveratrol intervention did not result in clinically significant changes in hematology and blood chemistry. We conclude that daily 1 gm dose of resveratrol did not affect the levels of circulating sex steroid hormones in postmenopausal women with high BMI but resulted in favorable changes in serum sex steroid binding globulin and leptin levels and urinary 2-OHE1/16α-OHE1 ratio that may be associated with reduced breast cancer risk. However, the observed adverse effects advocate for the consideration of lower doses for further clinical development of resveratrol for cancer prevention. (supported by a contract, N01-CN-35158, from the National Cancer Institute, Division of Cancer Prevention) Citation Format: H-H. Sherry Chow, Linda L. Garland, Brandy M. Heckman-Stoddard, Chiu-Hsieh Hsu, Valerie D. Butler, Catherine A. Cordova, Wade M. Chew, Terri L. Cornelison. Modulating effects of resveratrol on systemic markers associated with breast cancer risk: a pilot clinical study in postmenopausal women with high adiposity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 159. doi:10.1158/1538-7445.AM2013-159
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-159
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 4
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    1507-P: Baseline Metabolite Profiles of Incident Type 2 Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program (DPP)
    American Diabetes Association ; 2019
    In:  Diabetes Vol. 68, No. Supplement_1 ( 2019-06-01)
    Details
    In: Diabetes, American Diabetes Association, Vol. 68, No. Supplement_1 ( 2019-06-01)
    Abstract: Novel biomarkers of T2D and preventative treatment response could predict outcomes in high-risk individuals. We used Cox models to assess the association of 334 profiled metabolites in 2,019 baseline plasma samples with incident T2D after 3.2 years in a DPP substudy. We further assessed if associations out of the 334 metabolites differed by treatment (lifestyle (ILS), metformin (MET), and placebo (PLA)) and if, after stratification into concentration quartiles, the metabolite levels modified treatment effect in pair-wise treatment comparisons. We found 69 metabolites associated with incident T2D in the entire cohort (FDR-q & lt;0.05) including the novel association of cytosine, which had the lowest risk (HR of 0.77 per 1 SD, 95% CI 0.67-0.89, FDR-q 0.008). The associations of 35 metabolites differed across the three treatments (p for homogeneity & lt;0.05) and the quartiles of several of these metabolites modified treatment effects in pair-wise comparisons (Table 1). For example, individuals in higher quartiles of specific phospholipids had decreased T2D risk with ILS compared to PLA and MET, but not with MET when compared to PLA. In conclusion, we identified baseline metabolites associated with T2D risk prediction and efficacy of prevention interventions. This motivates further studies to validate interactions between biomarkers and diabetes prevention strategies. Disclosure Z. Chen: None. J. Liu: None. J. Morningstar: None. B.M. Heckman-Stoddard: None. C. Lee: None. S. Dagogo-Jack: Board Member; Self; Jana Care Inc. Consultant; Self; Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Stock/Shareholder; Self; Dance Biopharm Holdings Inc. J.F. Ferguson: None. R.F. Hamman: None. W.C. Knowler: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. L. Perreault: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. J.C. Florez: None. T. Wang: None. C.B. Clish: None. M. Temprosa: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Other Relationship; Self; Merck KGaA. R.E. Gerszten: None. DPP Research Group: None.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db19-1507-P
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 5
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    Abstract P2-02-02: Phase I trial of the safety and immunogenicity of a tri-antigen vaccine targeting HER2, IGFBP-2, and IGF-IR in patients with non-metastatic breast cancer
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 5_Supplement ( 2023-03-01), p. P2-02-02-P2-02-02
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. P2-02-02-P2-02-02
    Abstract: Background: HER2, IGFBP-2, and IGF-IR are proteins that are overexpressed in breast cancer. These three proteins, when used as immunogens, provide broad antigenic coverage to all molecular breast cancer subtypes. The proteins are also up-regulated in pre-invasive and high-risk breast lesions which are associated with progression to invasive cancer. Therefore, generating protective immunity against these antigens could have the result of preventing cancer development in high risk patients. We identified epitopes derived from these proteins, termed Th1 selective epitopes, that specifically stimulated T-helper 1 immune responses in humans and mice. The tri-antigen vaccine was effective in preventing the development of breast cancer in a transgenic mouse model of neu-expressing mammary cancer. We conducted a dose finding study of a plasmid-based vaccine encoding three extended Th1 selective epitopes derived from these antigens in breast cancer patients. Methods: Patients with non-metastatic, node positive, HER2 negative breast cancer that are in remission and defined as no evidence of disease were enrolled sequentially to one of 3 dose arms: 150, 300, and 600 mcg of the tri-antigen vaccine plasmid with 10 evaluable patients per arm (NCT02780401). Vaccines were given monthly intradermally for three total doses with rhu-GM-CSF (100mcg) as an adjuvant. The primary endpoint was safety through the 6-month follow-up visit and the secondary endpoints were immunogenicity, persistence of the immune response after vaccination, and assessment of potential stimulation of T-regulatory (T-reg) cells or myeloid derived suppressor cells to the overexpressed non-mutated antigens as well as determining the recommended Phase II dose. Results: Thirty-two patients were enrolled and 97% received all three vaccinations. The mean age at enrollment was 51.9 years with 61% of patients being pre-menopausal and 39% post-menopausal. The majority of patients were Stage II/III. Eighty-eight percent of patients had hormone receptor positive tumors and twelve percent were triple negative disease. The majority of adverse events (AE) ( & gt;95%) were grade 1 or 2. The most common AE were injection site reactions, flu like symptoms, fatigue, chills, myalgia, and nausea. All doses were immunogenic with the greatest magnitude antigen specific Type I immune responses seen in the low and intermediate doses. Eighty percent of patients at the 300mcg dose retained high levels of antigen specific immunity at 1 and 6 months after immunization as compared to 57% and 50% at the 100 and 600mcg doses respectively. No antigen specific Th2 cells, MDSC or T-reg were generated with vaccination. Immunizations did not upregulate PD-1 on CD4 or CD8 T-cells. Conclusions: A plasmid-based vaccine encoding extended Th1 selective epitopes derived from HER2, IGFBP-2, and IGF-IR could be administered safely and generate high levels of antigen specific interferon gamma secreting T-cells (Th1). The 300mcg dose elicited significant immune responses in the majority of patients which persisted at least 6 months after the end of immunization. A Phase II study of the vaccine given in the neoadjuvant setting to patients with HER2 positive breast cancer is ongoing (NCT04329065). Citation Format: Sasha E. Stanton, Kari B. Wisinski, William R. Gwin, Andrew Coveler, John B. Liao, Mark Burkard, Howard Bailey, KyungMann Kim, Thomas Havinghurst, Katina DeShong, Jennifer S. Childs, Eileen Dimond, Margaret Wojtowicz, Brandy M. Heckman-Stoddard, Denise Cecil, Mary Disis. Phase I trial of the safety and immunogenicity of a tri-antigen vaccine targeting HER2, IGFBP-2, and IGF-IR in patients with non-metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-02.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS22-P2-02-02
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 6
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    Abstract A23: Cancer outcomes in the diabetes prevention program outcomes study
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Prevention Research Vol. 8, No. 10_Supplement ( 2015-10-01), p. A23-A23
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 8, No. 10_Supplement ( 2015-10-01), p. A23-A23
    Abstract: Numerous observational studies have reported decreased cancer incidence and cancer-related mortality in patients with diabetes receiving standard doses of metformin. A recent meta-analysis of these studies suggested a 31% reduction in overall cancer incidence, summary relative risk (0.69; 95% confidence interval, 0.52-0.90), in subjects taking metformin as compared with other antidiabetic drugs. Separate meta-analyses of studies that adjusted for BMI or time-related bias suggested an attenuation of this signal, but still showed a significant reduction in cancer incidence. However, studies published to date are limited by the observational nature of the data and the randomized controlled trials that have been used to examine metformin's potential as an anti-cancer agent in patients with diabetes have had insufficient follow-up for cancer endpoints. These data also do not address the cancer risk in non-diabetic populations, in which the cancer preventive potential of metformin is unknown. The Diabetes Prevention Program (DPP) was a national multi-center, randomized, placebo-controlled clinical trial, which enrolled 3234 participants between 1996 and 1999, designed to investigate whether intensive lifestyle modification or treatment with metformin (850mg twice a day) delayed or prevented the onset of type 2 diabetes in a high risk population. The DPP and its follow up study, the Diabetes Prevention Program Outcomes Study (DPPOS), provide a unique opportunity to examine the role of metformin and lifestyle intervention in reducing cancer incidence in an overweight adult population with impaired glucose regulation, before the onset of diabetes. The National Cancer Institute Division of Cancer Prevention, in collaboration with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the DPPOS investigators, proposed a study to examine the hypothesis that metformin and/or lifestyle intervention can modify total cancer incidence and/or obesity-related cancer incidence (breast, colorectal, endometrium, pancreas, lower esophagus, gall-bladder, and kidney) in DPP/DPPOS participants. The DPPOS protocol and consent were modified to allow collection of data to support the inclusion of cancer incidence as an endpoint of interest in the study. Participants complete a cancer risk questionnaire that includes family history of cancer, cancer screening activities, and use of aspirin and NSAIDs including dose and frequency. The participants who previously reported a cancer diagnosis, through the SAE reporting process and/or an annual questionnaire, or during a subsequent follow-up visit, are asked to provide physician information to obtain medical records for case adjudication. This protocol will allow for the examination of the effect of metformin and lifestyle intervention on cancer incidence in an initially pre-diabetic population potentially through a median of 20 years of follow-up. Data from this study will compare incidence of total and obesity-related cancers between the original treatment groups; assess cancer (total and obesity-related) incidence by metformin exposure across all treatment groups, using a “met-years” variable, and explore subgroups to investigate effect modification by sex, age group, race/ethnicity, diabetes status, or weight loss at 1 year or mean weight loss since study baseline. Citation Format: Brandy M. Heckman-Stoddard, Jill P. Crandall, Sharon L. Edelstein, Richard F. Hamman, Philip C. Prorok, Anne Ryan, Dana Dabelea, Helen P. Hazuda, Edward Horton, Mary A. Hoskin, Susan Jeffries, William C. Knowler, Kieren J. Mather, Susana M. Shapiro, Farzana L. Walcott, Leslie G. Ford. Cancer outcomes in the diabetes prevention program outcomes study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; N ew Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A23.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6215.PREV-14-A23
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 7
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    Use of Biomarker Modulation in Normal Mammary Epithelium as a Correlate for Efficacy of Chemopreventive Agents Against Chemically Induced Cancers
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Prevention Research Vol. 13, No. 3 ( 2020-03-01), p. 283-290
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 13, No. 3 ( 2020-03-01), p. 283-290
    Abstract: In both estrogen receptor/progesterone receptor–positive (ER+/PR+) human breast cancer and in ER+/PR+ cancers in the methylnitrosourea (MNU)-induced rat model, short-term modulation of proliferation in early cancers predicts preventive/therapeutic efficacy. We determined the effects of known effective/ineffective chemopreventive agents on proliferative index (PI) in both rat mammary epithelium and small cancers. Female Sprague-Dawley rats were treated with MNU at 50 days of age. Five days later, the rats were treated with the individual compounds for a period of 14 days. At that time, normal mammary tissue from the inguinal gland area was surgically removed. After removal, the rats remained on the agents for an additional 5 months. This cancer prevention study confirmed our prior results of striking efficacy with tamoxifen, vorozole, Targretin, and gefitinib, and no efficacy with metformin, naproxen, and Lipitor. Employing a separate group of rats, the effects of short-term (7 days) drug exposure on small palpable cancers were examined. The PI in both small mammary cancers and in normal epithelium from control rats was & gt;12%. In agreement with the cancer multiplicity data, tamoxifen, vorozole, gefitinib, and Targretin all strongly inhibited proliferation ( & gt;65%; P & lt; 0.025) in the normal mammary epithelium. The ineffective agents metformin, naproxen, and Lipitor minimally affected PI. In the small cancers, tamoxifen, vorozole, and Targretin all reduced the PI, while metformin and Lipitor failed to do so. Thus, short-term changes in the PI in either normal mammary epithelium or small cancers correlated with long-term preventive efficacy in the MNU-induced rat model.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-19-0318
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 8
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    A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Prevention Research Vol. 12, No. 12 ( 2019-12-01), p. 903-912
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 12, No. 12 ( 2019-12-01), p. 903-912
    Abstract: 9cUAB30 is a synthetic analogue of 9-cis retinoic acid with chemoprevention activity in cell lines and animal models. The purpose of this phase I placebo-controlled, double-blinded, dose escalation study of 9cUAB30 was to evaluate its safety, pharmacokinetics, and determine a dose for future phase II studies. Participants received a single dose of study drug (placebo or 9cUAB30) on day 1 followed by a 6-day drug-free period and then 28 days of continuous daily dosing starting on day 8. Fifty-three healthy volunteers were enrolled into five dose cohorts (20, 40, 80, 160, and 240 mg). Participants were randomized within each dose level to receive either 9cUAB30 (n = 8) or placebo (n = 2). 9cUAB30 was well tolerated, with no dose limiting toxicities reported and no evidence of persistent elevations in serum triglycerides or cholesterol. Treatment-emergent grade 3 hypertension occurred in 1 of 8 participants at the 20 mg dose level and in 2 of 8 at the 240 mg dose level, all considered unlikely related to study agent; no other grade 3 adverse events were observed. The AUC increased, as expected, between day 1 (single dose) and day 36 (steady state). Pharmacokinetics were linear in dose escalation through 160 mg. 9cUAB30 administered by daily oral dosing has a favorable safety and pharmacokinetic profile. On the basis of the observed safety profile and lack of linearity in pharmacokinetics at doses greater than 160 mg, the recommended phase II dose with the current formulation is 160 mg once daily.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-19-0310
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 9
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    Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Prevention Research Vol. 16, No. 1 ( 2023-01-04), p. 47-55
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 16, No. 1 ( 2023-01-04), p. 47-55
    Abstract: Agents that can reduce the incidence of hormone receptor negative breast cancer are currently lacking. Rexinoids such as bexarotene significantly reduced mammary tumor development in preclinical mouse models. Oral bexarotene in BRCA mutation carriers significantly decreased cyclin D1 in breast cells, suggesting biological activity on breast tissue. This study evaluated topical bexarotene 1% gel applied to one unaffected breast in women at high risk for breast cancer for 4 weeks to assess safety and toxicity. Secondary objectives included assessment of bexarotene concentrations in the plasma and breast tissue. In the dose escalation phase, women were assigned to one of three different dose levels: 10 mg (1 mL) every other day, 10 mg (1 mL) daily, 20 mg (2 mL) daily. Dose-limiting toxicity (DLT) was defined as a grade 2 skin adverse event for at least 6 days or any grade 3 or 4 adverse event related to study drug. A total of 14 women were enrolled with 10 participants at the every other day dose level and 4 participants at daily dosing. Two skin DLTs were experienced at daily dosing and therefore further enrollment was discontinued per protocol. An additional 10 participants were enrolled at the MTD as part of the dose expansion phase. These individuals tolerated the treatment with minimal adverse events. Maculopapular rash at the treatment site was the most common adverse event related to study drug and resolved within a few days of discontinuation. Bexarotene was detectable in breast tissue at the 10 mg daily every other day dose. Prevention Relevance: Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-22-0210
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 10
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    Clinical Trial of Acolbifene in Premenopausal Women at High Risk for Breast Cancer
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Prevention Research Vol. 8, No. 12 ( 2015-12-01), p. 1146-1155
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 8, No. 12 ( 2015-12-01), p. 1146-1155
    Abstract: The purpose of this study was to assess the feasibility of using the selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women. To do so, we assessed change in proliferation in benign breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) as a primary endpoint, along with changes in other risk biomarkers and objective and subjective side effects as secondary endpoints. Twenty-five women with cytologic hyperplasia ± atypia and ≥2% of breast epithelial cells staining positive for Ki-67, received 20 mg acolbifene daily for 6–8 months, and then had benign breast tissue and blood risk biomarkers reassessed. Ki-67 decreased from a median of 4.6% [interquartile range (IQR), 3.1%–8.5%] at baseline to 1.4% (IQR, 0.6%–3.5%) after acolbifene (P & lt; 0.001; Wilcoxon signed-rank test), despite increases in bioavailable estradiol. There were also significant decreases in expression (RT-qPCR) of estrogen-inducible genes that code for pS2, ERα, and progesterone receptor (P ≤ 0.026). There was no significant change in serum IGF1, IGFBP3, IGF1:IGFBP3 ratio, or mammographic breast density. Subjective side effects were minimal with no significant increase in hot flashes, muscle cramps, arthralgias, or fatigue. Objective measures showed a clinically insignificant decrease in lumbar spine bone density (DEXA) and an increase in ovarian cysts but no change in endometrial thickness (sonography). In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen-inducible gene expression but minimal side effects, suggesting a phase IIB placebo-controlled trial evaluating it further for breast cancer prevention. Cancer Prev Res; 8(12); 1146–55. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-15-0109
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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