An observational study in Breast Cancer Invasive, sponsored by Ente Ospedaliero Ospedali Galliera. Completed at 2 sites in Italy. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-11.
Sponsored by Ente Ospedaliero Ospedali Galliera · Observational
Low-dose tamoxifen (5 mg/day for three years, BabyTam) has emerged as a safer and effective alternative to the standard regimen (20 mg/day), reducing breast cancer recurrence with fewer adverse events. The TAM-01 phase III trial demonstrated a 42% reduction in breast cancer events over ten years compared to placebo in women with ductal carcinoma in situ (DCIS) or high-risk lesions (HRL, ADH, LCIS), supporting its inclusion in clinical guidelines.
The phase III TAM-01 trial enrolled 500 women, comparing low-dose tamoxifen to placebo over three years, with a median follow-up of 9.7 years (IQR, 8.3-10.9). Results showed a significant reduction in invasive breast cancer (HR = 0.58; 95% CI: 0.35-0.95; p = 0.03) and in contralateral breast cancer, CBC (HR = 0.36; 95% CI: 0.14-0.92; p = 0.025), with no increase in serious adverse events.
Exploratory analyses suggested a greater benefit in postmenopausal women (HR = 0.30; 95% CI: 0.11-0.82), compared to premenopausal women (HR = 0.73; 95% CI: 0.30-1.76), though this interaction did not reach statistical significance (p-interaction = 0.13). However, our unpublished data indicate a remarkable reduction of CBC in premenopausal women on BabyTam.
The TAM-01 long-term follow-up study aims to extend the follow-up of TAM-01 participants, evaluating long-term outcomes, including incidence of invasive breast cancer and DCIS, with a focus on tumor laterality and menopausal status, as well as to assess other non-invasive events (LCIS, ADH, or ALH) and adverse outcomes of special interest.
We will also perform a pooled analysis of our three low-dose tamoxifen studies to increase the statistical power of our findings, with special attention to the effect according to menopausal status and site of recurrence. The primary endpoint will be the breast cancer-free interval.
The findings are expected to strengthen the evidence supporting low-dose tamoxifen as a viable prevention strategy in high-risk populations with intraepithelial neoplasia (IEN or DCIS+HRLs) or microinvasive disease.
The protocol was amended to harmonize endpoint definitions and to specify a pooled analysis combining TAM-01 with other clinical studies evaluating low-dose tamoxifen on BCFI, defined as the time from study entry to the first occurrence of any ipsilateral or contralateral invasive breast cancer (CBC), ipsilateral or contralateral DCIS, regional recurrence, or distant recurrence.
Low-dose tamoxifen (5 mg/day for three years) has emerged as a safer alternative to standard-dose tamoxifen (20 mg/day), effectively reducing the risk of breast cancer recurrence while minimizing adverse events. The TAM-01 phase III trial demonstrated that this regimen decreased subsequent breast cancer events by 42% compared to placebo after 10 years in women with ductal carcinoma in situ (DCIS) or high-risk lesions (atypical ductal hyperplasia, ADH, or lobular carcinoma in situ, LCIS), without exceeding serious adverse events and patient-reported outcomes, thus supporting its wide uptake in the medical community and NCCN guideline inclusion.
The IBIS-I trial reinforced the role of tamoxifen in breast cancer prevention, demonstrating a lasting reduction in breast cancer incidence, particularly in estrogen receptor-positive tumors, with benefits extending beyond the treatment period. Furthermore, real-world evidence indicates strong patient preference for low-dose tamoxifen due to its fewer side effects, which increases adherence in clinical practice. Additionally, studies have shown that low-dose tamoxifen can lower mammographic density, potentially improving screening sensitivity and facilitating earlier cancer detection.
The TAM-01 (EudraCT number: 2007-007740-10) trial was a multicenter, phase III trial comparing 5 mg/day tamoxifen to placebo over 3 years in 500 women aged 75 years or younger with an ECOG performance status of 1 or lower, and hormone-sensitive (ER or progesterone receptor ≥ 1%) or unknown DCIS (69%) or breast intraepithelial neoplasia (ADH, 20% or LCIS, 11%). Women with high-grade or comedo/necrotic DCIS were treated with adjuvant radiotherapy at 50 Gy in 25 fractions. Participants were followed up every 6 months, undergoing annual mammography and transvaginal ultrasound for 3 years of treatment and then being seen annually for 7 years of follow-up. All breast-related events during the trial were centrally adjudicated by an expert committee. The primary endpoint was the incidence of invasive breast cancer and DCIS.
The mean (SD) age at treatment initiation was 54 (9) years, with 58% being postmenopausal women. After a median follow-up of 9.7 years (IQR, 8.3 to 10.9 years), 66 breast cancers were diagnosed (15 in situ; 51 invasive): 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years: 11.3 with tamoxifen vs. 19.5 with placebo; hazard ratio [HR] 0.58; 95% CI, 0.35 to 0.95; p = 0.03). The majority of recurrences were invasive (77%) and ipsilateral (59%). For contralateral breast cancer incidence, there were 6 events in the tamoxifen group and 16 in the placebo group (HR, 0.36; 95% CI, 0.14 to 0.92; p = 0.025). No differences were observed between the groups regarding patient-reported outcomes (menopausal symptoms) or serious adverse events during the extended follow-up period.
An exploratory analysis from TAM-01 suggested that the efficacy of low-dose tamoxifen may differ by menopausal status. Although a protective effect was observed in both groups, the reduction appeared more pronounced in postmenopausal women (HR: 0.30; 95% CI, 0.11 to 0.82) than in premenopausal women (HR: 0.73; 95% CI, 0.30 to 1.76). Although this difference did not reach statistical significance (p-interaction = 0.13), it raises important questions about the biological mechanisms underlying tamoxifen's effects and the role of estradiol levels in modulating its efficacy.
The importance of identifying the optimal dose of tamoxifen is underscored by studies demonstrating that lower doses can retain efficacy while significantly reducing adverse effects, supporting the integration of low-dose regimens into prevention strategies. Randomized trials, such as those by Eriksson et al. and Bhatia et al., have shown the potential of low-dose tamoxifen in diverse populations, including high-risk individuals and those with preinvasive breast cancer.
Recent findings from a preplanned biomarker analysis of the TAM-01 trial have provided further support for the role of low-dose tamoxifen in targeted breast cancer prevention strategies. Specifically, baseline levels of insulin-like growth factor binding protein-3 (IGFBP-3) in the top three quartiles (≥3.44 μg/mL), but not in the lowest quartile, were shown to predict greater efficacy of BabyTam compared with placebo (p-interaction = 0.006). In contrast, baseline levels of IGF-I, estradiol, or sex hormone-binding globulin (SHBG) were not predictive of BabyTam efficacy, whereas the IGF-I/IGFBP-3 molar ratio showed a borderline significant interaction (p-interaction = 0.067). This study unveils the potential of serum biomarkers, specifically IGFBP-3 and IGF-I/IGFBP-3 ratios, as predictive factors of BabyTam efficacy among individuals with DCIS or high-risk lesions. These findings hold significant implications in clinical practice, offering a means to discern patients who may derive maximal benefits from BabyTam.
The previous TAM-01 study discontinued the follow-up of enrolled patients because, under Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use, the study would have had to be migrated to the Clinical Trials Information System (CTIS) managed by the European Medicines Agency (EMA).
As the study had started in 2008, both the protocol and the entire study documentation were not compliant with the requirements of the Regulation (EU) No 536/2014. For both administrative and feasibility reasons, the migration was not possible, and the original study was therefore closed and replaced by the current version.
Based on the TAM-01 findings, this long-term follow-up study aims to compare the long-term outcomes in women who participated in the TAM-01 trial. By extending the follow-up, the study aims to compare the incidence of invasive breast cancer and DCIS, considering tumor laterality and menopausal status, as well as to assess other non-invasive events (LCIS, ADH or ALH) and adverse outcomes of special interest.
We will also perform a pooled analysis of our three low-dose tamoxifen studies to increase the statistical power of our findings, with particular attention to the effect by menopausal status and site of recurrence. The primary endpoint will be the breast cancer-free interval.
The results of this study are expected to provide a robust evidence base for the incorporation of low-dose tamoxifen into routine clinical practice and to address personalized preventive strategies in high-risk populations.
285 studies on the registry are indexed under Carcinoma, Intraductal, Noninfiltrating; 54 are open to participants now.
This study's planned enrollment of 1,545 is above the median of 201 across 59 observational studies indexed under Carcinoma, Intraductal, Noninfiltrating.
Browse Carcinoma, Intraductal, Noninfiltrating studies →Ente Ospedaliero Ospedali Galliera is the lead sponsor of 19 studies on the registry; 6 are open to participants now.
Compared within Carcinoma, Intraductal, Noninfiltrating, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Breast Neoplasms. The counts are of registry records indexed under each term, refreshed daily. How we classify →
The study population will consist of all women previously enrolled in the TAM-01 study (EudraCT number: 2007-007740-10), and in the IEO-S007 trial and the prospective cohort study.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All women received one tablet of tamoxifen 5 mg per day for 3 years during the TAM-01 phase III trial.
Drug: Tamoxifen (Nolvadex)
All women received one tablet of placebo per day for 3 years during the TAM-01 phase III trial.
Drug: Tamoxifen (Nolvadex) placebo
5 mg per day for 3 years during TAM-01 phase III trial
Tamoxifen (Nolvadex) placebo per day for 3 years during TAM-01 phase III trial.
Incidence of invasive breast cancer and breast cancer-free interval
The primary objective is to compare the incidence of invasive breast cancer and ductal carcinoma in situ in a long-term follow-up of the TAM-01 study and to compare the breast cancer-free interval among the three low-dose tamoxifen studies.
Time frame: Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.
Incidence of invasive breast cancer and ductal carcinoma in situ (DCIS) considering tumor laterality and menopausal status
To compare the incidence of invasive breast cancer and DCIS by tumor site (ipsilateral or contralateral) and menopausal status.
Time frame: Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.
Incidence of other non-invasive events
The incidence of other non-invasive events, such as lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH).
Time frame: Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.
Overall Survival and Breast Cancer Survival (OS)
Overall Survival and Breast Cancer Survival (OS)
Time frame: Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.
Adverse Events
The incidence of adverse events, including endometrial cancer, deep vein thrombosis or pulmonary embolism, other neoplasms, coronary heart disease, bone fracture and cataract. These events will be expressed as the number of events and percentage (%) within each treatment arm, allowing for a direct comparison between the two groups.
Time frame: Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.
Biomarkers evaluation
Association between biomarker levels (particularly IGFBP-3) and clinical outcomes, aimed at assessing their prognostic and/or predictive value in the context of long-term follow-up.
Time frame: Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually.
Exploratory Endpoint: Correlation between biomarkers
Correlation between biomarkers collected at baseline, at year one, at the end of treatment and two years after treatment completion and long-term clinical outcomes
Time frame: Each patient will be followed for a total period of 20 years from the date of randomization in the TAM-01 trial, with data collected and updated annually
Plan to share: Yes
Supporting information: Study protocol, Statistical analysis plan
Ran from Jul 1996 to primary completion in Mar 2026, 356 months.
Of 28 non-industry observational studies under Carcinoma, Intraductal, Noninfiltrating, half reached primary completion within 60 months of starting (the median), counting those still running; a quarter within 35 and three quarters within 86. This study's 356 months is above that.
Counting every sponsor, half of 30 studies reached it within 60 months; a quarter within 46 and three quarters within 86.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 1996. You cannot join it, but the record below documents what was studied.
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Carcinoma, Intraductal, Noninfiltrating →
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