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Epirubicin 100mg/m2 on day 1 cyclophosphamide 600mg/m2 on day1 every 2 weeks for four cycles followed by docetaxel 100mg/m2 on day 1 every 3 weeks for four cycles

Docetaxel 75mg/m2 on day 1 and cyclophosphamide 600mg/m2 on day 1 every 3 weeks for four cycles followed by goserelin acetate+tamoxifen for young patients/ letrozole for postmenopausal patients

Goserelin acetate

Zhiyong Yu, PhD

Zhaoyun Liu, MD

Breast cancer is the most common female malignancy in the world, and the leading cause of cancer-associated mortalities among women. Hormone receptors (HR) including ER and PR are the main prognostic factor for breast cancer patients. Breast cancer subtype was defined by ER, PR, HER2 and Ki67 status since the definition of intrinsic subtypes for breast cancer. Breast cancer which ER are positive have less aggressive and better long-term prognoses than other breast cancer subtype. Luminal B1 was definited as ER Positive, PR positive \<20%, or Ki-67 ≥20% , and HER2-Negative. Although standard therapy to HR positive breast cancer is endocrine treatment, evidence reported that Luminal B1 breast cancers with lower PR expression are less sensitive to tamoxifen than luminal A breast cancers with higher PR expression, and the specific mechanism is not clear. We previously had a clinically analysed, and we found the Luminal B1 breast cancer had a significant proportion with 38%. Whether we need standard chemotherapy or chemotherapy based intensive endocrine therapy for those patients? In our research, we divided the patients with ER positive, PR negative, and HER-2 negative into two groups. One groups will be treated with 8 cycles of chemotherapy (EC×4-T×4). The other received 4 cycles of chemotherapy (TC×4) then will be given the intensive endocrine therapy (Goserelin acetate+Tamoxifen for young patients/Letrozole for postmenopausal patients). The primary endpoint is to assess disease-free survival (DFS) and overall survival (OS) in different regiments, the secondary endpoint is to assess the expression of female hormone levels. The correlation of the expression of female hormone levels with the clinical outcomes, so that the investigators could optimize adjuvant treatment regiment with luminal B1 breast cancer.

The trial is designed to investigative the risk and clinical benefit of chemotherapy and intensive endocrine therapy for Luminal B1 early-staged breast cancer. In this trial the investigators will randomly assign 200 primary breast cancer patients to receive four cycles of epirubicin and cyclophosphamide (EC) followed by four cycles of docetaxel(T), or four cycles of docetaxel and cyclophosphamide (TC) followed by intensive endocrine therapy (Goserelin acetate+Tamoxifen/Letrozole for young patients) . Patients with HER-2 positive was excluded. The patient's conditions will be assessed before, and after every four cycles of adjuvant chemotherapy to determine if there is any progression of the disease. The patient's conditions will be assessed every three months when they received the intensive endocrine therapy (Goserelin acetate+Tamoxifen for young patients/Letrozole for postmenopausal patients). Patients will be followed up for DFS and OS in different regiments, the secondary endpoint is to assess the expression of female hormone levels. The correlation of the expression of female hormone levels with the clinical outcomes, so that the investigators could optimize adjuvant treatment regiment with luminal B1 breast cancer.

Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer

Prospective Randomized Controlled Study on the Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer

To determine the percentage of disease-free survival (DFS) for the EC follow T arm and TC follow endocrine therapy arm separately.

To assess the association between the female hormone levels and the clinical outcomes

To determine the percentage of Overall survival (OS) for the EC follow T arm and TC follow endocrine therapy arm separately.

Zhiyong Yu

Director of the Breast Surgery Ⅰ

women candidate to receive ET and interviewed before starting treatment

women interviewed within 1 years from beginning of ET

women interviewed after more than 4 years but no more than 6 years of ET

Completion of questionnaires at the time of study entry

Completion of questionnaires

Emilia Montagna, MD

Preference studies reveal how individuals trade-off the potential benefits, harms and inconveniences of a treatment by determining the minimum benefits they judge sufficient to make the treatment worthwhile.

They are especially relevant to adjuvant therapies where individuals must weigh up modest survival benefits only realized in time by no recurrence of their cancer with side effects predominantly experienced whilst on the treatment.

Previously it was reported, for example, that over 50% of women who had adjuvant chemotherapy for early breast cancer judged a 1% improvement in 5 year survival rates sufficient to make it worthwhile.

Larger survival benefits were required for longer duration adjuvant hormonal therapy where over 50% of women required at least 5% improvement in 5 year survival rates to make it worthwhile.

The endocrine therapy is generally proposed to all patients with endocrine positive early breast cancer to reduce the risk of recurrence and death. Moreover several data support that the prolongation of hormonal therapy (i.e. 10 years of hormonal treatment) is associated with statistical improved outcome.

In order to achieve the benefit related to hormonal therapy all women have to be treated despite the fact that the data and analyses are unable to differentiate as to whether a small prolongation in survival accrues to all women treated or a few patients survive who would otherwise have died. Moreover the hormonal therapy is associated with side effects that may impact the quality of life of the patients.

Patients are more likely to accept treatment on the basis of presented relative rather than absolute risks and so the question arises as to whether unrealistic improvements in outcome are expected by patients.

The interviews with patients in the proposed trial will elicit the expected gains both in terms of survival and life years and will be able to assess the proportion of patients who considered an improvement of realistic size was sufficient to justify the treatment and the prolongation of the treatment.

Several studies showed that choices are guided by the personal attitude to react and adapt to traumatic events, individual resilience.

It is important therefore to consider also the influence of these factors on the patients' treatment preferences.

For this reason, besides the elicitation of preferences, resilience and reaction to traumatic events will be assessed thorough validated questionnaires.

Patients' Preferences for Adjuvant Endocrine Therapy in Early Breast Cancer

Evaluation of Endocrine Therapy and Patients Preferences in Early Breast Cancer - Patients' Preferences for Adjuvant Endocrine Therapy in Early Breast Cancer.

Risk reduction will be evaluated in the 40% and 20% 5 years risk scenarios

Prolonged survival time gain will be evaluated in the 5-yr and 15-yr survival scenarios

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer	NCT03373708	Breast Cancer Chemotherapy Endocrine Breas...	Epirubicin Cyclophosphamid... Docetaxel Goserelin aceta... Tamoxifen Letrozole	18 Years - 70 Years	Shandong Cancer Hospital and Institute
Patients' Preferences for Adjuvant Endocrine Therapy in Early Breast Cancer	NCT03939156	Breast Cancer Endocrine Breas...	Completion of q...	18 Years -	European Institute of Oncology

Spots Global Cancer Trial Database for endocrine breast diseases