Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 17 ( 2023-06-10), p. 3116-3121
    Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. METHODS We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. RESULTS The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. CONCLUSION Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. GS4-08-GS4-08
    Abstract: We have previously shown in a phase 3 trial that tamoxifen 5 mg/day for 3 years decreased by 52% the incidence of recurrence of invasive breast cancer or DCIS after a median follow-up of 5.1 years in women with excised non invasive breast disease, including atypical ductal hyperplasia, DCIS or LCIS (DeCensi et al. JCO 2019; 37:1629). Toxicity was negligible with only an extra hot flash per day in the tamoxifen arm compared with the placebo arm. These findings were incorporated into the ASCO clinical practice guidelines for breast cancer risk reduction as an alternative option to standard doses and duration of tamoxifen or aromatase inhibitors in women with non-invasive disease (Visvanathan et al. JCO 2019; 37:3152). In the present study we update the findings on breast cancer recurrence after a median of 9.14 years (interquartile range, IQR, 7.16-10.73) and a total of 10.57 person years of follow up to see if the treatment effect is retained with more events and after a median of approximately 6 years from treatment cessation. We conducted a national multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. Between November 1, 2008, and March 31, 2015, 1,160 women were screened and 500 aged 75 years of age or younger were included in the study. Women with high-grade or comedo/necrotic DCIS received adjuvant radiotherapy of 50 Gy in 25 courses. The mean age was 54 years (standard deviation, 9 years), and 55% of participants were postmenopausal. The mean (SD) body mass index, kg/m2, was 25.7 (4.8) on tamoxifen and 25.3 (4.2) on placebo. Twenty percent had ADH, 11% had LCIS, and the remaining 69% had DCIS. After a median follow-up of 9.14 years, there were 22 neoplastic events (invasive breast cancer or DCIS) with tamoxifen and 37 with placebo (annual rate 11.09, 95% CI, 7-30-16.84 on T vs 19.71, 95% CI, 14.28-27.21 on P per 1,000 person-years; hazard ratio, 0.56; 95% CI, 0.33 to 0.95; P = .03), which resulted in a 5-year number needed to treat of 18. Overall, 71% of the recurrences were invasive breast cancer. The follow-up was updated with the most recent visit within 12 months in two thirds of the participants, so an update of all participants will be performed by Sept 30th with full analysis of neoplastic events, annual risk rate ratio, serious adverse events and deaths. Moreover, an updated analysis of potential effect modifiers will be conducted, including menopausal status, baseline estradiol levels, menopausal symptoms, BMI, smoking status and Ki-67 of the primary lesion. In conclusion, our findings indicate that low dose tamoxifen given for 3 years still significantly prevents recurrences from non-invasive breast cancer after a median of 6 years from treatment cessation, providing a valid prevention/interception option in this disease group. Supported by Ente Ospedaliero Ospedali Galliera, Genova, Italy, the Italian Ministry of Health (RFPS-2006-1-339898), the Italian Association for Cancer Research (IG 2008 Grant No. 5611), and the Italian League against Cancer (LILT 7-08). Citation Format: Andrea De Censi, Matteo Lazzeroni, Matteo Puntoni, Luca Boni, Aliana Guerrieri Gonzaga, Tania Buttiron Webber, Marianna Fava, Irene Maria Briata, Livia Giordano, Maria Digennaro, Laura Cortesi, Fabio Falcini, Franca Avino, Francesco Millo, Katia Cagossi, Elisa Gallerani, Alessia De Simone, Anna Cariello, Giuseppe Aprile, Maria Renne, Bernardo Bonanni. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive 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 GS4-08.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 1500-1500
    Abstract: 1500 Background: Low-dose tamoxifen (babytam) at 5 mg/day for 3 years decreases local or contralateral recurrence by 52% in women with hormone sensitive breast pre-invasive neoplasia after surgery (DeCensi et al JCO 2019). Here we report the results of exploratory analyses to assess whether the benefit of babytam varies among subgroups of patients defined by individual characteristics. Methods: Post-hoc subgroup analyses were performed according to a mixed approach based on the test for interaction and biological plausibility. Incidence of invasive breast cancer or DCIS was the primary endpoint. HRs were estimated using Cox proportional-hazards modeling. Results: Age at menopause, smoking status and Ki-67 exhibited a significant interaction with treatment. Specifically, the effect of babytam was greater in women aged 〉 50y (n = 293, HR = 0.27, 95%CI: 0.10-0.73) than in women aged ≤50y (n = 207, HR = 0.86, 0.35-2.07), p-interaction = .09. Never smokers (n = 307) had a greater benefit than former (n = 68) or current smokers (n = 97): HR = 0.28, 0.11-0.70 vs HR = 0.57, 0.09-3.45 vs HR = 1.51, 0.41-5.64, respectively (p = .05). Tumors with Ki-67 above the median level of 10% (n = 133) had a greater effect (HR = 0.27, 0.09-0.81) than Ki-67 ≤10% (n = 145, HR = 1.58, 0.45-5.60, p = .04). Weaker statistical interactions (p 〉 .1) were also found for waist circumference and hot flashes (HF) at baseline. Women with waist circumference ≥89 cm (metabolic syndrome, n = 208) had a greater effect (HR = 0.22, 0.07-0.78) than women 〈 89 cm (n = 228, HR = 0.61, 0.25-1.46). Compared with placebo and no HF, babytam effect was stronger in women with HF (HR = 0.13, 0.02-0.96) than in women on babytam and no HF (HR = 0.50, 0.24-1.03) or placebo and HF (HR = 0.72, 0.31-1.69, log-rank p-trend = .004). Additional subgroups according to obesity, family history of breast or ovarian cancer, alcohol use, extent of surgery, radiotherapy for DCIS, ER and HER2 expression, positive margins and treatment compliance showed no significant heterogeneity of treatment. Conclusions: Exploratory analyses showed a trend to a higher effect of babytam in women aged 50 or older, never smokers, women with hot flashes or abdominal obesity and tumors with Ki-67 above 10%. Our results provide insight into the efficacy of babytam towards a personalized preventive approach. Clinical trial information: NCT01357772.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 19 ( 2019-07-01), p. 1629-1637
    Abstract: Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose. PATIENTS AND METHODS We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. RESULTS Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen ( P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo. CONCLUSION Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. PD3-08-PD3-08
    Abstract: Background: We recently showed that low dose (5mg/d) tamoxifen (babytam) for 3 years can halve the incidence of new breast neoplastic events in hormone sensitive or unknown breast pre-invasive neoplasia after surgery with limited toxicity (DeCensi et al JCO 2019; 37:1629-37). Here we report the results of circulating surrogate endpoint biomarkers of breast cancer risk with special attention to the risk of ovarian stimulation observed with the full dose in premenopausal women. Methods: Five hundred women 75 years old or younger were randomized to babytam or placebo (PLA). A subgroup of 406 women consented for collection of morning fasting serum at baseline (0), 1 (1Y) and 3 years (3Y) of treatment. There was a loss of about 25% of blood sampling at 3Y. Serum IGF-I, IGFBP-3, SHBG and C-reactive Protein (CRP) were performed on all available samples. Estradiol and testosterone were determined in a subsample (n=285) to determine the extent of ovarian stimulation by babytam in premenopausal women. We used Mann-Whitney test for univariate comparisons and linear regression modeling for multivariate analyses setting changes from baseline (1Y or 3Y minus baseline values) as dependent variable and treatment arm, age, BMI and baseline biomarkers values as explanatory factors. We tested treatment*menopausal status as interaction term. COX P-H model was used to calculate hazard ratio for CRP increase. Results: At baseline, all biomarkers were evenly balanced between arms (data not shown). IGF-I decreased significantly on babytam as compared to PLA. The difference of the changes between arms was -20 ng/mL after 1Y (p & lt;0.001) and -23 after 3Y (p & lt;0.001). A treatment by menopausal status interaction was observed after 1Y (p=0.017) and 3Y (p=0.058), with a steeper decrease in postmenopausal (-25, p & lt;0.001 both after 1Y and 3Y) as compared to premenopausal women (-15, p=0.007 after 1Y and -17, p=0.009 after 3Y). IGFBP-3 increased significantly on babytam, without effect modification by menopausal status. The difference between arms was +0.26 ug/mL after 1Y (p=0.006) and +0.19 after 3Y (p=0.024). SHBG increased markedly on babytam, irrespective of menopausal status. The difference between arms from 0 to 1Y and 3Y was 24 nMol/L (p & lt;0.001). CRP levels followed a trend towards a decrease with babytam (-0.172 mg/dL, p=0.057 after 1Y and -0.091, p=0.108 after 3Y), without effect modification by menopausal status. There was no significant increase in serum estradiol after 1Y with babytam overall (+12 pg/mL, p=0.106), but a trend to an interaction with menopausal status (p=0.079): +17 (p=0.361) in premenopausal women versus +3 (p=0.284) in postmenopausal women. Similarly, there was no overall effect of babytam on testosterone after 1Y (-0.008 ng/mL, p=0.518), but a significant effect modification by menopausal status (p=0.001), showing an increase of +0.056 (p=0.006) in premenopausal women, and a decrease of -0.045 (p=0.006) in postmenopausal women. Irrespective of treatment, the increase in CRP at 3Y was significantly higher in women who experienced recurrence compared to women who did not (Mann-Whitney p=0.009). An increase in CRP was associated with a HR of 2.9 (95% CI, 1.0-8.3, p=0.05) as compared to women with a decreased or stable CRP levels. Conclusions: Babytam for 3 years exhibits a favorable effect on sex hormones and IGFs with only a slight increase of estradiol in premenopausal women which is far below that observed with 20 mg and is well compensated by a significant increase in SHBG. These findings further support the use of babytam as an effective and safe treatment for high risk individuals. ClinicalTrials.gov Identifier: NCT01357772. Supported by the Italian Ministry of Health (RFPS-2006-339898), the Italian Association for Cancer Research (IG 2008 Grant No 5611) and the Italian League against Cancer (LILT 7-08). Citation Format: Harriet Johansson, Matteo Puntoni, Debora Macis, Valentina Aristarco, Aliana Guerrieri-Gonzaga, Davide Serrano, Silvia Caviglia, Laura Cortesi, Cristiana Taverniti, Antonio Ponti, Maria Grazia Pacquola, Marcella Gulisano, Fabio Falcini, Maria Digennaro, Anna Carriello, Katia Cagossi, Graziella Pinotti, Tania Buttiron Webber, Matteo Lazzeroni, Bernardo Bonanni, Luca Boni, Andrea DeCensi. Effects of low dose tamoxifen on circulating risk biomarkers in a phase III trial in breast pre-invasive disease [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-08.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 13 ( 2021-07-01), p. 3576-3583
    Abstract: Low-dose tamoxifen halved recurrence after surgery in a phase III trial in breast noninvasive disease without increasing adverse events. We explored the effect of low-dose tamoxifen in clinically relevant subgroups, including menopausal status, estradiol levels, smoking, body mass index, and proliferation of baseline lesion. Patients and Methods: Incidence of invasive breast cancer or ductal carcinoma in situ was the primary endpoint. HRs and interaction terms were estimated using Cox models. Results: A favorable HR and 95% confidence interval (CI) could be demonstrated for postmenopausal status (HR = 0.30; 95% CI, 0.11–0.82 vs. HR = 0.73; 95% CI, 0.30–1.76 in premenopausal women; Pinteraction = 0.13), women with estradiol less than 15.8 pg/mL, presence of menopausal symptoms at baseline, and never smoking (Pinteraction = 0.07), although the interaction P value was & gt;0.05 for all characteristics. Efficacy was similar in all body mass index categories. Tumors with Ki-67 above the median level of 10% had a greater benefit (HR = 0.27; 95% CI, 0.09–0.81) than those with Ki-67 ≤10% (HR = 1.58; 95% CI, 0.45–5.60; Pinteraction = 0.04). Conclusions: The efficacy of low-dose tamoxifen seems to be greater in postmenopausal women and in women with lower estradiol levels. Benefits appear to be larger also in women with menopausal symptoms, never smokers, and tumors with Ki-67 & gt;10%. Our results by menopausal status provide important insight into low-dose tamoxifen personalized treatment, although caution is necessary given their exploratory nature. Observation of an improved response in tumors with Ki-67 & gt;10% is consistent but the use of the marker in this setting is investigational. See related commentary by Fabian, p. 3510
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages