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receiving a treatment of tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy

Tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy

Tamoxifen Oral Product

Zhongyu Yuan

Background: Endocrine therapy is an effective and safe treatment for hormone receptor positive breast cancer. Unfortunately , endocrine treatment resistance occurs and there is an urgent need for treatment alternative. Laboratory researches and clinical case reports indicate that hormone receptor-high expressed breast cancer patients may potentially benefit from high-dose Tamoxifen or high-dose Tamoxifen plus chemotherapy , providing a new option for treatment strategy.

Aim: To explore the efficacy and safety of high-dose Tamoxifen to standard hormone receptor-high expressed endocrine therapy resisted breast cancer.

Methods: Eligible patients will be treated with tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy. Blood and tumor samples will be obtained from the patients.Evaluate curative effect every 3 months.

Primary endpoint: progression-free survival (PFS). Secondary endpoints: objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and safety.

Exploratory endpointsincluded the efficacy predictive value of the 18F-FES SUVmax.

Efficacy of High Dose Tamoxifen to Advanced Hormone Receptor-High Expressed Breast Cancer

Efficacy and Safety of High Dose Tamoxifen to Advanced Hormone Receptor-High Expressed Endocrine Therapy Resisted Breast Cancer

Sun Yat-sen University

professer

receiving a treatment of tamoxifen 100 mg/d

Treatment Arm

receiving a treatment of tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy

Tamoxifen Oral Product: Tamoxifen 100 mg/d or high-dose Tamoxifen(100 mg/d ) plus chemotherapy

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

China

Region of Enrollment

Progression-free Survival (PFS)

Overall Study

Tamoxifen 20mg b.i.d - Participants will be treated for 14 days.

Tamoxifen 10mg b.i.d - Participants will be treated for 14 days.

Experimental arm will have tamoxifen 40mg and active comparator arm will have tamoxifen 20mg for 14 days.

Paired biopsies (before and after tamoxifen therapy) will be required for the assessment of Ki-67.

Assessment of Ki-67

The surgery date should be fixed before randomization. The surgery is to be performed within 1 day after the last dose of study treatment.

Surgery

Hyeong-Gon Moon

MORE-T trial is designed to investigate the effect of Tamoxifen 40mg (vs. Tamoxifen 20mg) for 2wks in presurgical setting.

The greater reduction in Ki-67 might be observed in Tamoxifen 40mg arm compared to the Tamoxifen 20mg arm.

Open Label, Phase 2, Randomized with 1:1 allocation

Tamoxifen

* Selective estrogen receptor modulator
* It has been the main endocrine treatment for decades
* Tamoxifen is a major endocrine treatment option, particularly for women who still have a significant ovarian estrogenic activity that cannot be controlled by aromatase inhibitors.
* The prospective clinical trials have shown that tamoxifen 20mg has comparable efficacy against tamoxifen 40mg with fewer toxicities in breast cancer patients. However, most of the trials comparing tamoxifen 20mg and 40mg were done in postmenopausal women.
* Previous studies have suggested that the higher dose of tamoxifen can induce higher serum levels of the drugs, and increasing tamoxifen dose up to 40mg can induce clinical responses in tumors resistant to 20mg of tamoxifen. A recent prospective trial demonstrated that increasing the dose of tamoxifen from 20 mg to 40 mg can compensate for the reduced endoxifen level in intermediate or poor metabolizer tamoxifen metabolizers based on CYP2D6 genotyping.

Ki-67

* Ki-67 antigen, a nuclear antigen, and marker of cell proliferation, is expressed during all cell-cycle phases except for G0, with levels peaking during mitosis.
* Reduction in Ki67 expression is reported to correlate with treatment response to endocrine therapy in ER+ breast cancer, and Ki-67 in short-term neoadjuvant studies has been shown to predict outcome in long-term adjuvant trials.

As the investigators have a higher proportion of young aged, premenopausal breast cancer patients in Korea, the investigators had an opportunity to examine the prognostic impact of young age in breast cancer recurrences and survivals. The institutional database and the Korean nationwide breast cancer registry data have all shown that the poor prognostic effect of a young age was exclusively seen in women with hormone receptor-positive breast cancers, and the effect was potentially due to the resistance to the tamoxifen. As therapeutic options diversify, studies on factors predictive of sensitivity to various endocrine therapies are needed to help select the appropriate treatment for young premenopausal breast cancer patients.

Higher Dose Preoperative taMOxifen in Premenopausal bREast Cancer Patients

Higher Dose taMOxifen in Premenopausal bREast Cancer Patients: a preoperaTive Window Trial (MORE-T Trial)

Change in Ki67 (percentage of positive tumor cells tested by immunohistochemistry \[IHC\] - digital Image Analysis ) after a 14-day treatment period compared to baseline.

Change in Ki67 (percentage of positive tumor cells tested by immunohistochemistry \[IHC\]) after a 14-day treatment period compared to baseline according to CYP2D6 genotyping.

The proportion of participants with relative decrease from baseline of Ki-67 (% positive tumor cells) ≥50%.

The PEPI score (ranged 0 to 12, lower score mean a better outcome) is the sum of the risk points of the pathological tumor (pT) stage, the pathological node (pN) stage, Ki67 levels and ER status (Allred score).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Efficacy of High Dose Tamoxifen to Advanced Hormone Receptor-High Expressed Breast Cancer	NCT03045653	Breast Cancer M...	Tamoxifen Oral ...	18 Years - 70 Years	Sun Yat-sen University
Higher Dose Preoperative taMOxifen in Premenopausal bREast Cancer Patients	NCT04997941	Premenopausal B... Hormone Recepto...	Tamoxifen Oral ... Assessment of K... Surgery	20 Years - 48 Years	Seoul National University Hospital

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