Study Comparing EC-T Verses PCb in the Adjuvant Chemotherapy of Non-triple Negative Breast Cancer
Study Comparing EC-T Verses PCb in the Adjuvant Chemotherapy of Non-triple Negative Breast Cancer
This study is a randomized, single center, phase III clinical trial comparing the efficacy
 and safety of four cycles of epirubicin combined with cyclophosphamide followed by four
 cycles of docetaxel (EC*4-T*4) verses 6 cycles of weekly paclitaxel combined with carboplatin
 (PCb*6) in the adjuvant chemotherapy of non-triple negative breast cancer patients. The study
 is divided in to 2 branches: PANSY-1 and PANSY-2. PANSY-1 is a study of hormone receptor
 (HR)-positive/human epidermal growth factor receptor-2 (HER2)-negative patients with ≥4
 positive lymph node, while PANSY-2 is a study of HER2-positive patients with ≥1 positive
 lymph node.
PANSY-1 will be comparing the efficacy and safety of four cycles of epirubicin combined with
 cyclophosphamide followed by four cycles of docetaxel (EC-T) verses six cycles of paclitaxel
 combined with carboplatin (PCb).

 PANSY-2 will be comparing the efficacy and safety of four cycles of epirubicin combined with
 cyclophosphamide followed by four cycles of docetaxel with trastuzumab (EC-TH) verses six
 cycles of paclitaxel combined with carboplatin and trastuzumab (PCbH); both followed by 1
 year adjuvant trastuzumab.

 After pertuzumab became legally available in China, participants of PANSY-2 may choose to
 receive trastuzumab and pertuzumab dual targeted therapy, thus comparing the efficacy and
 safety of four cycles of epirubicin combined with cyclophosphamide followed by four cycles of
 docetaxel with trastuzumab and pertuzumab (EC-THP) verses six cycles of paclitaxel combined
 with carboplatin, trastuzumab and pertuzumab (PCbHP); both followed by 1 year adjuvant
 trastuzumab and pertuzumab.

 With the inclusion of pertuzumab in China's medical insurance in January 2020, study
 protocols were revised to include dual targeted therapy for HER2-positive participants.
Inclusion Criteria:

 1. Female patients aged 18-70 years old;

 2. Histologically confirmed unilateral invasive breast cancer (regardless of pathological
 type)

 3. Operable breast cancer at first diagnosis, without any absolute surgical
 contraindication.

 4. No gross nor microscopic residual tumor after surgery.

 5. HER2-positive with ≥ 1 positive axillary lymph node; or estrogen receptor (ER) and/or
 progesterone receptor (PR)-positive and HER2-negative with ≥ 4 positive axillary lymph
 node. HER2-positive is defined as an immunohistochemistry (IHC) status of 3+, or a
 positive in situ hybridization (Fluorescence in situ hybridization (FISH), Chromogenic
 in situ hybridization (CISH)) test. ER-positive is defined as immunohistochemistry
 showing that ≥ 1% of tumor cells were ER positive. PR-positive is defined as
 immunohistochemistry showing that ≥ 1% of tumor cells were PR positive.

 6. Preoperative examination found no evidence of metastasis in clinical examination nor
 imaging examination.

 7. No peripheral neuropathy.

 8. Karnofsky score > 70.

 9. Good postoperative recovery, at least 1 week has passed since most recent surgery.

 10. Has adequate bone marrow function: leukocyte count > 4x10ˆ9 / L, absolute neutrophil
 count > 2x10ˆ9 /L; platelet count > 100x10ˆ9 /L, hemoglobin > 9g/dL.

 11. Has adequate liver function: alanine aminotransferase (ALT) < 1.5×upper limit of
 normal (ULN), aspartate aminotransferase (AST) < 1.5×ULN, alkaline phosphatase (AKP) <
 2.5×ULN, total bilirubin (TBIL) < 1.5×ULN.

 12. Has adequate kidney function: serum creatinine < 1.5×ULN.

 13. Contraception during treatment for women of childbearing age.

 14. Has adequate cardiac function: echocardiography showed left ventricular ejection
 fraction (LVEF) > 50%.

 15. Participants voluntarily joined the study, has signed informed consent before any
 trial related activities are conducted, has good compliance and has agreed to
 follow-up.

 Exclusion Criteria:

 1. Has received previous chemotherapy for late stage disease.

 2. Has bilateral breast cancer or bilateral carcinoma in situ.

 3. Has metastatic (Stage 4) breast cancer.

 4. Has clinical T4 lesion (UICC1987) (with skin involvement, mass adhesion and fixation,
 and inflammatory breast cancer).

 5. Has received neoadjuvant therapy (include chemotherapy, targeted therapy, radiotherapy
 or endocrine therapy).

 6. Has previous history of additional malignancy(with the exception of adequately treated
 basal cell carcinoma and cervical carcinoma in situ), including contralateral breast
 cancer.

 7. Is already participating in another clinical trial.

 8. Has severe systemic disease and/or uncontrolled infection.

 9. Has insufficient cardiac function: echocardiography showed LVEF< 50%.

 10. Has suffered from severe cardiovascular and cerebrovascular diseases disease within
 the 6 months previous of randomization (such as unstable angina, chronic heart
 failure, uncontrolled hypertension with blood pressure>150/90 mmHg, myocardial
 infarction, or cerebrovascular accident.

 11. Has known allergy to chemotherapy drugs used in this study.

 12. Is pregnant, is breast feeding, or is a woman of childbearing age who cannot practice
 effective contraceptives during treatment and until 8 weeks after the end of
 treatment.

 13. Has entered the study, but pre-treatment examination showed a positive pregnancy test.

 14. Has a history of mental disorders, cognitive impairment, inability to understand the
 study protocol and side effects, inability to complete the study protocol and
 follow-up workers (systematic evaluation is required before the patient is enrolled
 into the study), or is without independent civil capacity.

 15. The researchers judged patients to be unsuitable for the study.