scholarly journals Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial

2021 ◽  
pp. JCO.20.02598 ◽  
Author(s):  
Mikael Eriksson ◽  
Martin Eklund ◽  
Signe Borgquist ◽  
Roxanna Hellgren ◽  
Sara Margolin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammographic Density ◽  
Screening Program ◽  
Standard Dose ◽  
Controlled Trial ◽  
Menopausal Status ◽  
Premenopausal Women ◽  
Secondary Outcome ◽  
Double Blind ◽  
Density Reduction

PURPOSE Tamoxifen prevents breast cancer in high-risk women and reduces mortality in the adjuvant setting. Mammographic density change is a proxy for tamoxifen therapy response. We tested whether lower doses of tamoxifen were noninferior to reduce mammographic density and associated with fewer symptoms. PATIENTS AND METHODS Women, 40-74 years of age, participating in the Swedish mammography screening program were invited to the 6-month double-blind six-arm randomized placebo-controlled noninferiority dose-determination KARISMA phase II trial stratified by menopausal status (EudraCT 2016-000882-22). In all, 1,439 women were accrued with 1,230 participants accessible for intention-to-treat analysis. The primary outcome was proportion of women treated with placebo, 1, 2.5, 5, and 10 mg whose mammographic density decreased at least as much as the median reduction in the 20 mg arm. The noninferior margin was 17%. Secondary outcome was reduction of symptoms. Post hoc analyses were performed by menopausal status. Per-protocol population and full population were analyzed in sensitivity analysis. RESULTS The 1,439 participants, 566 and 873 pre- and postmenopausal women, respectively, were recruited between October 1, 2016, and September 30, 2019. The participants had noninferior mammographic density reduction following 2.5, 5, and 10 mg tamoxifen compared with the median 10.1% decrease observed in the 20 mg group, a reduction confined to premenopausal women. Severe vasomotor symptoms (hot flashes, cold sweats, and night sweats) were reduced by approximately 50% in the 2.5, 5, and 10 mg groups compared with the 20 mg group. CONCLUSION Premenopausal women showed noninferior magnitude of breast density decrease at 2.5 mg of tamoxifen, but fewer side effects compared with the standard dose of 20 mg. Future studies should test whether 2.5 mg of tamoxifen reduces the risk of primary breast cancer.

scholarly journals Adjuvant Therapy and Mammographic Density Changes in Women With Breast Cancer

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
Louise Eriksson ◽  
Wei He ◽  
Mikael Eriksson ◽  
Keith Humphreys ◽  
Jonas Bergh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammographic Density ◽  
Adjuvant Treatment ◽  
Premenopausal Women ◽  
Cancer Registries ◽  
Dense Area ◽  
Intention To Treat ◽  
Density Reduction ◽  
Treatment Information ◽  
Drug Register

Abstract Background Tamoxifen decreases mammographic density. Whether compliance affects this relationship is unclear as is the relationship between other types of adjuvant treatment and changes in mammographic density. Methods This prospective cohort study included 2490 women diagnosed with breast cancer during 2001–2015 in Sweden. Mammographic density was assessed within 3 months of diagnosis and 6–36 months post diagnosis. Logistic regression was performed to study the association between each respective adjuvant treatment and mammographic density reduction (annual dense area decrease >15%). Results Intention-to-treat analyses using treatment information from the regional cancer registries showed that tamoxifen-treated patients more frequently experienced mammographic density reductions compared with nontreated patients (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.25 to 1.99), as did chemotherapy-treated patients (OR = 1.28, 95% CI = 1.06 to 1.54). For chemotherapy, the association was mainly seen in premenopausal women. Neither aromatase inhibitors nor radiotherapy was associated with density change. Tamoxifen use based on prescription and dispensation data from the Swedish Prescribed Drug Register showed that users were more likely to have density reductions compared with nonusers (adjusted OR = 2.24, 95% CI = 1.40 to 3.59). Moreover, among tamoxifen users, tamoxifen continuers were more likely than discontinuers to experience density reductions (adjusted OR = 1.50, 95% CI = 1.04 to 2.17). Conclusions Our results indicate that adherence influences the association between tamoxifen and mammographic density reduction. We further found that chemotherapy was associated with density reductions and propose that this is largely secondary to chemotherapy-induced ovarian failure.

scholarly journals Mammographic density as an image-based biomarker of therapy response in neoadjuvant-treated breast cancer patients

2020 ◽  
Author(s):  
Ida Skarping ◽  
Daniel Förnvik ◽  
Uffe Heide-Jørgensen ◽  
Hanna Sartor ◽  
Per Hall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammographic Density ◽  
Breast Imaging ◽  
Menopausal Status ◽  
Therapy Response ◽  
Predictive Biomarkers ◽  
Premenopausal Women ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Multicenter Studies

Abstract Purpose Personalized cancer treatment requires predictive biomarkers, including image-based biomarkers. Breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT) are in a clinically vulnerable situation with the tumor present. This study investigated whether mammographic density (MD), assessed pre-NACT, is predictive of pathological complete response (pCR). Methods A total of 495 BC patients receiving NACT in Sweden 2005–2019 were included, merged from two different cohorts. Cohort 1 was retrospectively collected (n = 295) and cohort 2 was prospectively collected (n = 200). Mammograms were scored for MD pre-NACT according to the Breast Imaging-Reporting and Data System (BI-RADS), 5th Edition. The association between MD and accomplishing pCR post-NACT was analyzed using logistic regression models—for the whole cohort, stratified by menopausal status, and in different St. Gallen surrogate subtypes. Results In comparison to patients with low MD (BI-RADS a), the multivariable-adjusted odds ratio (OR) of accomplishing pCR following NACT was on a descending scale: 0.62 (95% confidence interval (CI) 0.24–1.57), 0.38 (95% CI 0.14–1.02), and 0.32 (95% CI 0.09–1.08) for BI-RADS b, c, and d, respectively. For premenopausal patients selectively, the corresponding point estimates were lower, although wider CIs: 0.31 (95% CI 0.06–1.62), 0.24 (95% CI 0.04–1.27), and 0.13 (95% CI 0.02–0.88). Subgroup analyses based on BC subtypes resulted in imprecise estimates, i.e., wide CIs. Conclusions It seemed as though patients with higher MD at baseline were less likely to reach pCR after NACT—a finding more pronounced in premenopausal women. Larger multicenter studies are needed to enable analyses and interpretation for different BC subtypes.

scholarly journals Randomized Double-Blind 2 × 2 Trial of Low-Dose Tamoxifen and Fenretinide for Breast Cancer Prevention in High-Risk Premenopausal Women

2009 ◽  
Vol 27 (23) ◽  
pp. 3749-3756 ◽  
Author(s):  
Andrea Decensi ◽  
Chris Robertson ◽  
Aliana Guerrieri-Gonzaga ◽  
Davide Serrano ◽  
Massimiliano Cazzaniga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Neoplasms ◽  
Mammographic Density ◽  
Low Dose ◽  
Endometrial Thickness ◽  
Premenopausal Women ◽  
Intraepithelial Neoplasia ◽  
Premenopausal Breast Cancer ◽  
Double Blind ◽  
Igf I

Purpose Tamoxifen and fenretinide are active in reducing premenopausal breast cancer risk and work synergistically in preclinical models. The authors assessed their combination in a two-by-two biomarker trial. Patients and Methods A total of 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), or intraepithelial neoplasia (IEN, n = 160), or 5-year Gail risk ≥ 1.3% (n = 54) were randomly allocated to either tamoxifen 5 mg/d, fenretinide 200 mg/d, their combination, or placebo. We report data for plasma insulin-like growth factor I (IGF-I), mammographic density, uterine effects, and breast neoplastic events after 5.5 years. Results During the 2-year intervention, tamoxifen significantly lowered IGF-I and mammographic density by 12% and 20%, respectively, fenretinide by 4% and 10% (not significantly), their combination by 20% and 22%, with no evidence for a synergistic interaction. Tamoxifen increased endometrial thickness principally in women becoming postmenopausal, whereas fenretinide decreased endometrial thickness significantly. The annual rate of breast neoplasms (n = 48) was 3.5% ± 1.0%, 2.1% ± 0.8%, 4.7% ± 1.3%, and 5.2% ± 1.3% in the tamoxifen, fenretinide, combination, and placebo arms, respectively, with hazard ratios (HRs) of 0.70 (95% CI, 0.32 to 1.52), 0.38 (95% CI, 0.15 to 0.90), and 0.96 (95% CI, 0.46 to 1.99) relative to placebo (tamoxifen × fenretinide adverse interaction P = .03). There was no clear association with tumor receptor type. Baseline IGF-I and mammographic density did not predict breast neoplastic events, nor did change in mammographic density. Conclusion Despite favorable effects on plasma IGF-I levels and mammographic density, the combination of low-dose tamoxifen plus fenretinide did not reduce breast neoplastic events compared to placebo, whereas both single agents, particularly fenretinide, showed numerical reduction in annual odds of breast neoplasms. Further follow-up is indicated.

Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial

2021 ◽  
Vol 58 (7) ◽  
pp. 617-623
Author(s):  
Ramachandran Rameshkumar ◽  
Ponnarmeni Satheesh ◽  
Puneet Jain ◽  
Jagadeesh Anbazhagan ◽  
Shilpa Abraham ◽  
...  
Keyword(s):  
Diabetic Ketoacidosis ◽  
Low Dose ◽  
Standard Dose ◽  
Controlled Trial ◽  
Double Blind

scholarly journals Methotrimeprazine versus haloperidol in palliative care patients with cancer-related nausea: a randomised, double-blind controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e029942 ◽  
Author(s):  
Janet Rea Hardy ◽  
Helen Skerman ◽  
Jennifer Philip ◽  
Phillip Good ◽  
David C Currow ◽  
...  
Keyword(s):  
Palliative Care ◽  
Outcome Measures ◽  
Controlled Trial ◽  
Response Rates ◽  
Complete Response ◽  
Response To Treatment ◽  
Secondary Outcome ◽  
Double Blind ◽  
Intention To Treat ◽  
Point Reduction

ObjectivesMethotrimeprazine is commonly used for the management of nausea but never tested formally against other drugs used in this setting. The aim was to demonstrate superior antiemetic efficacy.DesignDouble-blind, randomised, controlled trial of methotrimeprazine versus haloperidol.Setting11 palliative care sites in Australia.ParticipantsParticipants were >18 years, had cancer, an average nausea score of ≥3/10 and able to tolerate oral medications. Ineligible patients had acute nausea related to treatment, nausea for which a specific antiemetic was indicated, were about to undergo a procedure or had received either of the study drugs or a change in glucocorticoid dose within the previous 48 hours.InterventionsBased on previous studies, haloperidol was used as the control. Participants were randomised to encapsulated methotrimeprazine 6·25 mg or haloperidol 1·5 mg one time or two times per day and assessed every 24 hours for 72 hours.Main outcome measuresA ≥two-point reduction in nausea score at 72 hours from baseline. Secondary outcome measures were as follows: complete response at 72 hours (end nausea score less than 3), response at 24 and 48 hours, vomiting episodes, use of rescue antiemetics, harms and global impression of change.ResultsResponse to treatment at 72 hours was 75% (44/59) in the haloperidol (H) arm and 63% (36/57) in the methotrimeprazine (M) arm with no difference between groups (intention-to-treat analysis). Complete response rates were 56% (H) and 51% (M). In theper protocolanalysis, there was no difference in response rates: (85% (44/52) (H) and 74% (36/49) (M). Completeper protocolresponse rates were 64% (H) and 59% (M). Toxicity worse than baseline was minimal with a trend towards greater sedation in the methotrimeprazine arm.ConclusionThis study did not demonstrate any difference in response rate between methotrimeprazine and haloperidol in the control of nausea.Trial registration numberACTRN 12615000177550.

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