Locally advanced breast cancer has high-risk local regional recurrence after surgery. Radiotherapy could reduce the local regional recurrence and improve disease free survival and overall survival. Regional lymph node irradiation is the important part of breast cancer radiotherapy. However, there are some controversies about regional lymph node delineation, especially the supraclavicular irradiation volume. Many studies had confirmed that posterolateral region of the supraclavicular fossa (also named Posterior neck lymph node) had a high risk involvement based on the mapping of recurrence nodes. This randomized phase III trial compares medial supraclavicular lymph node irradiation with entire supraclavicular lymph node irradiation in patients with pathologically positive axillary lymph node and high risk of recurrence after mastectomy or breast conservative surgery. It is not yet known if radiation works better with entire supraclavicular fossa than medial supraclavicular fossa.

PRIMARY OBJIECTIVE:

I. To evaluate whether entire supraclavicular lymph node irradiation is superior to medial supraclavicular lymph node irradiation in terms of disease free survival for patients with positive lymph nodes and high risk of recurrence after breast cancer surgery

SECONDARY OBJECTIVES:

I. To estimate the difference of overall survival II. to estimate the difference of ipsilateral supraclavicular node recurrence III. to estimate the difference of local regional recurrence IV. to estimate the difference of radiation related toxicities and quality of life.

Outline: Beginning 2-12 weeks after the completion of breast cancer surgery and neoadjuvant/adjuvant chemotherapy, patients are randomized to 1 of 2 treatment arms Arm I: Patients undergo breast/chest wall, undissected axillary, internal mammary node and medial supraclavicular node radiation. Conventional fractionated radiotherapy 50Gy/25Fx/5w or hypofractionated 42.5Gy/16Fx/3.5week with IMRT or VAMT technique is recommended. 3DCRT technique is not permitted.

Arm II: Patients undergo breast/chest wall, undissected axillary, internal mammary node and entire supraclavicular node radiation. Conventional fractionated radiotherapy 50Gy/25Fx/5w or hypofractionated 42.5Gy/16Fx/3.5week with IMRT or VAMT technique is recommended. 3DCRT technique is not permitted

Inclusion Criteria:

1. ECOG 0-1
2. Newly diagnosed invasive breast cancer
3. Initial clincial diagonosis stage is T1-4, N0-3a/b, M0: If neoadjuvant chemotherapy was not administered: pathological stage is T1-3N2-3a/b, M0; If neoadjuvant chemotherapy was administered：clinical stage III or pathological stage is T1-4N1-3a/bM0.
4. Underwent breast conservative surgery or Mastectomy with or without breast reconstruction with clear negative margin. At least, axillary level I and level II should be cleared with ≥10 lymph node (including the number of sentinal lymph node) . Level III dissection and internal mamamry node dissection are not required, but may be performed at the discretion of the surgeon.
5. Should receive ≥6 cycles standard neoadjuvant and/or adjuvant chemotherapy (taxane and/or anthracycline based).
6. Enrolled on the trial within 12 weeks of the later of two dates: the final breast cancer surgical procedure or administration of the last cycle of cytotoxic chemotherapy.
7. For ER and/or PR positive patients, the duration of anticipated endocrine therapy should be≥5 year ; For HER2 postive patients, the duration of anticipated herceptin should be 1 year.
8. Writtern, informed consent.

Exclusion Criteria:

1. Initinal clinical diagnosis N3c (supraclavicualr node metastasis)

2. T4 or inflamed breast cancer with no good downstage by neoadjuvant chemotherapy

3. Distant metastasis

4. Bilateral breast cancer or previously contralateral breast cancer

5. Positve sentinal lymph node with no axillary dissection

6. ECOG ≥2

7. Could not tolerate chemotherapy and anti-HER2 target treatment

8. Active infectious

9. History of radiotherapy

10. Serious medical complcation

11. Breast cancer during pregnancy and lactation

12. Had simultaneousl or previous secondary malignancies, except for skin basal cell carcinoma and cervical carcinoma in situ.

13. Inaccessibility for follow-up

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