Low Dose Tamoxifen for Breast Cancer

(LoTam Trial)

Recruiting at 653 trial locations

Overseen By Jack Beranek

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must be taking: Endocrine therapy

Must not be taking: Hormone replacement

Disqualifiers: Premenopausal, Endometrial pathology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

1156 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a low dose of tamoxifen, a drug that blocks estrogen in the breast, is more effective than standard hormone therapies for early-stage breast cancer. It targets post-menopausal women with hormone-positive, HER2-negative breast cancer, meaning their cancer grows with the help of hormones but not the HER2 protein. Ideal candidates have undergone breast cancer surgery and meet specific criteria, such as having a small tumor size and no lymph node involvement. Participants will receive either low-dose tamoxifen or one of the usual hormone therapies. The trial aims to determine if the low dose is equally effective with potentially fewer side effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any endocrine therapy for breast cancer prevention or osteoporosis, including tamoxifen or hormone replacement therapy, when you start the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that low-dose tamoxifen is generally easy for patients to handle. One study found that patients taking lower doses of tamoxifen experienced fewer side effects than those on the standard dose. Common side effects of tamoxifen include hot flashes, fatigue, and an increased risk of blood clots. However, the lower dose appears to lessen these effects.

Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, are commonly used in hormone therapy for breast cancer. They may cause side effects like joint pain and bone thinning, but extensive research has deemed them safe.

This trial compares low-dose tamoxifen to these standard treatments. Prospective participants should discuss with their doctor to understand what to expect and to monitor any potential side effects.

Why do researchers think this study treatment might be promising?

Researchers are excited about low-dose tamoxifen for breast cancer because it offers potential benefits with fewer side effects compared to standard endocrine therapies. Unlike the typical daily doses of tamoxifen or other options like anastrozole, letrozole, or exemestane, this treatment uses a lower dose administered every other day. This approach may reduce the risk of side effects commonly associated with hormone therapies while still effectively managing the disease. By maintaining efficacy with a gentler impact on the body, low-dose tamoxifen could improve the quality of life for patients undergoing long-term treatment.

What evidence suggests that low dose tamoxifen might be an effective treatment for early stage breast cancer?

This trial will compare low-dose tamoxifen with standard endocrine therapies. Research has shown that a low dose of tamoxifen can help prevent the recurrence of breast cancer. In one study, women who took low-dose tamoxifen had a 52% lower chance of developing invasive breast cancer or ductal carcinoma in situ, compared to those who did not take it. Another study found that this lower dose reduced the risk of cancer returning by 52% and lowered the chance of new breast cancer developing in the other breast by 75%. Tamoxifen blocks estrogen in the breast, which can stop some tumors from growing. These findings suggest that low-dose tamoxifen could be a strong option for reducing breast cancer risks in post-menopausal women. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for post-menopausal women with hormone-positive, HER2 negative early stage breast cancer. Participants must have a specific type of invasive breast cancer that's estrogen receptor positive and not spread to lymph nodes. Tumors should be small (≤3cm) and surgically removed with clear margins. Women who've had certain high-risk scores on cancer recurrence tests or evidence of lymph node involvement can't join.

Inclusion Criteria

My breast cancer is classified as low risk by the MammaPrint test.

My breast cancer recurrence risk score is 40 or less.

My breast cancer is estrogen receptor positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low-dose tamoxifen or standard-of-care endocrine therapy for up to 5 years

5 years

Regular visits for mammogram or MRI, DEXA, and blood sample collection

Follow-up

Participants are monitored for recurrence-free interval, adverse events, and overall survival

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Tamoxifen

Trial Overview The LoTam Trial is testing the effectiveness of low dose tamoxifen against usual hormonal therapies like anastrozole, letrozole, and exemestane in treating early stage breast cancer. The study aims to see if tamoxifen, which blocks estrogen in the breast, could be more effective than aromatase inhibitors that prevent formation of estradiol.

How Is the Trial Designed?

Group I: Arm II (low dose tamoxifen) Experimental Treatment 6 Interventions

Patients receive low-dose tamoxifen PO QOD for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or MRI, DEXA, and blood sample collection on study.

Group II: Arm I (anastrozole, letrozole, exemestane, tamoxifen) Active Control 9 Interventions

Patients receive standard of care endocrine therapy per physician choice with either anastrozole PO, letrozole PO, exemestane PO or standard dose tamoxifen PO QD for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or MRI, DEXA, and blood sample collection on study.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 282 prostate cancer patients, tamoxifen at a dose of 20 mg daily significantly reduced the incidence of breast events caused by bicalutamide treatment, with only 8.8% of patients experiencing these events compared to 96.7% in the placebo group at 6 months.

The use of tamoxifen did not negatively impact prostate-specific antigen (PSA) suppression, indicating that it effectively manages breast side effects without compromising cancer control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study. Fradet, Y., Egerdie, B., Andersen, M., et al.[2014]

Tamoxifen is widely used by 7 million women for breast cancer treatment and has been shown to significantly improve patient survival with minimal adverse effects.

While there is a slightly increased risk of endometrial cancer at the 20 mg/d dosage, this risk is considered minimal, and routine monitoring primarily involves clinical examinations rather than systematic endometrial testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Monitoring women on tamoxifen ]. Lansac, J., Diouf, A.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36917758/

A 10-Year Follow-Up of TAM-01 Study Conclusion: Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526820924003707

Low Dose Tamoxifen for Breast Cancer Prevention At a median follow up of 5 years, women taking low dose tamoxifen had an approximately 52% reduction in risk of invasive breast cancer or DCIS over placebo.

3. academic.oup.com academic.oup.com/jnci/advance-article/doi/10.1093/jnci/djaf250/8244295

Effect of low-dose tamoxifen on benign gynecological and ... After a median follow-up of 5.1 years, low-dose tamoxifen led to a 52% reduction in recurrence risk and a 75% decrease in contralateral breast events.6 Extended ...

4. nature.com nature.com/articles/s41523-025-00745-8

Window-of-opportunity trials to screen effective agents and ... Tamoxifen at 5 mg daily offers a significant benefit in preventing local and contralateral recurrences in women with IEN. According to these ...

5. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-025-02059-w

Medications to reduce breast cancer risk: a network meta ... The NMA showed that tamoxifen and AIs reduce the risk of breast cancer in women at above-average risk and suggested that AIs could be more ...