Title
Lotam: A Randomized, Phase III Clinical Trial Of Low-Dose Tamoxifen For Selected Patients With Molecular Low-Risk Early-Stage Breast Cancer

Description
This phase III trial compares the effect of low dose tamoxifen to usual hormonal therapy, including aromatase inhibitors, in treating post-menopausal women with hormone positive, HER2 negative early stage breast cancer. Tamoxifen is in a class of medications known as antiestrogens. It blocks the activity of estrogen (a female hormone) in the breast. This may stop the growth of some breast tumors that need estrogen to grow. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, prevent the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibitors are used as a type of hormone therapy to treat postmenopausal women with hormone-dependent breast cancer. Giving low dose tamoxifen may be more effective compared to usual hormone therapy in treating post-menopausal women with hormone-positive, HER2 negative early stage breast cancer.

Objective
PRIMARY OBJECTIVE:

I. To evaluate whether the recurrence-free interval (RFI) with low-dose tamoxifen is non-inferior to standard-of-care endocrine therapy among post-menopausal women with early-stage, low molecular risk breast cancer.

SECONDARY OBJECTIVES:

I. To compare endocrine therapy nonadherence rates between treatment arms. II. To compare the incidence of adverse events between treatment arms, including osteoporosis, fracture, endometrial carcinoma, stroke, and deep vein thrombosis.

III. To compare endocrine therapy-related patient reported symptoms between treatment arms.

IV. To compare the invasive disease-free survival between treatment arms. V. To compare the locoregional breast cancer recurrence between treatment arms. VI. To compare distant recurrence free survival between treatment arms. VII. To compare overall survival between treatment arms. VIII. To compare ductal carcinoma in situ (DCIS) incidence (ipsilateral and contralateral) between treatment arms.

IX. To evaluate the association between radiotherapy modality (no radiation, partial breast radiation, and whole breast radiation) and RFI in each arm.

X. To explore important measures of quality of life that would reasonably be expected to vary by study arm, including global quality of life and reasons for nonadherence.

XI. To compare change in mammographic density at two years between treatment arms.

XII. To conduct a within patient comparison of automated versus (vs) semi-automated mammographic density determination.

Treatment OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive standard of care endocrine therapy per physician choice with either anastrozole orally (PO), letrozole PO, exemestane PO or standard dose tamoxifen PO once daily (QD) for up to 5 years in the absence of disease progression or unacceptable toxicity. Patients may also undergo mammogram or magnetic resonance imaging (MRI), dual X-ray absorptiometry (DEXA), and blood sample collection on study.

ARM II: Patients receive low-dose tamoxifen PO every other day (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.

After completion of study treatment, patients are followed up for 10 years after registration.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Breast

Participating Institutions
UW Health Carbone Cancer Center Rockford; UW Health Eastpark Medical Center; UW Health University Hospital