Study of Exemestane After Anastrozole or Letrozole Treatment of Postmenopausal Women With Hormone Responsive Breast Cancer
Study of Exemestane After Anastrozole or Letrozole Treatment of Postmenopausal Women With Hormone Responsive Breast Cancer
The purpose of this study is to compare the rate of disease free survival (DFS) and distant
 disease free survival (DDFS) at 5 years in postmenopausal women with hormone receptor and
 lymph node positive breast cancer randomized between anastrozole/letrozole 5 years and
 anastrozole/letrozole 2-3 years switching to exemestane 3-2 years.
Inclusion Criteria:

 1. Provision of written informed consent.

 2. Patient muse be female.

 3. Patient must have undergone primary breast cancer surgery with institutional standard
 axillary dissection such as the following:

 -  A total mastectomy with institutional standard axillary nodal dissection.

 -  Lumpectomy or a quadrantectomy with institutional standard axillary dissection
 with breast radiotherapy (may be deferred until chemotherapy is completed) in
 accordance with breast preservation.

 -  Treatment of the breast cancer following diagnosis may have included any of the
 following; post-lumpectomy/quadrantectomy regional radiotherapy, post-mastectomy
 locoregional radiotherapy, postoperative chemotherapy, and trastuzumab.

 4. The tumor must have been pathologic primary invasive carcinoma by core needle or open
 biopsy.

 5. The beginning of endocrine therapy (letrozole or anastrozole) must be no more than 6
 weeks from the end day of chemotherapy or radiotherapy.

 6. The date of randomization must be no less than 2 years of letrozole and no more than 3
 years letrozole treatment.

 7. Positive node is defined as defined as the presence of at least micro metastasis
 greater than 0.2 mm according to the AJCC Breast Staging Criteria Edition 6.

 8. Patients who have had neoadjuvant chemotherapy are eligible. Positive lymph node
 involvement can be defined either prior of neoadjuvant chemotherapy or at the time of
 surgery following their neoadjuvant therapy. Lymph node positivity would be defined as
 the following:

 -  Pre-neoadjuvant chemotherapy lymph node assessment must include identification of
 a histological positive axillary, internal mammary or supraclavicular determined
 by one of the following: FNA of lymph node or sentinel lymph node evaluation, or
 complete or limited axillary dissection.

 -  For patients that have completed their neoadjuvant chemotherapy, without prior
 documentation of a positive lymph node, lymph node positivity must be
 demonstrated at the time of their primary surgery as defined by either:

 -  Either sentinel lymph node or primary axillary dissection identifying a
 positive lymph node is acceptable as per standard institutional practice
 guidelines.

 -  Histological evidence of a N1-N3c lymph node involvement identified at the
 time of primary breast surgery following neoadjuvant chemotherapy.

 9. Presence of occult axillary lymph node with no evidence of primary breast tumor must
 be confirmed pathologically primary breast invasive carcinoma or DCIS with
 microinvasive. And the measurement of ER, PR and HER2 must be performed on the initial
 lymph nodes or breast tumors.

 10. Bilateral, synchronous breast cancer is allowed provided at least one of the primary
 tumors meets the eligibility criteria.

 11. Hormone receptor-positive tumors, defined as any detectable estrogen or progesterone
 receptor expression by institutional standards.Patients who are PR positive and ER
 negative are eligible for the trial. Tumor slides should be submitted for central
 evaluation of hormone receptor status as per Section.

 12. HER2 status must be known, Tumor slides should be submitted for central evaluation of
 hormone receptor status as per Section.

 13. Physical and laboratory examination as per standard institutional practice,should be
 obtained at the time of definitive surgery to demonstrate there is no evidence of
 metastatic or recurrent disease.

 14. Patients must be postmenopausal at the time of initial diagnosis. For study purposes,
 postmenopausal is defined as:

 -  Prior bilateral oophorectomy.

 -  Age ≥ 60 y.

 -  Age < 60 amenorrheic for 12 or more months and has postmenopausal levels of FSH
 and LH per local institutional standards

 -  If received adjuvant chemotherapy or tamoxifen and age < 60 y, the levels of FSH
 and LH must reached postmenopausal levels.

 -  If received adjuvant chemotherapy or LHRH antagonist and amenorrheic, the levels
 of FSH and LH must reached postmenopausal levels and be confirmed at least twice.

 15. Patients must have an WHO performance status of o or all per-disease performance
 without restriction, 1=restricted in physically strenuous activity but ambulatory.

 16. WBC > 3.0*10^9/L and platelets > 100*10^9/L.

 17. AST/SGOT or ALT/SGPT < 3 times ULN.

 18. Cr ≤ 2 times ULN. 19 Can swallow pills.

 Exclusion Criteria:

 1. Presence of metastatic disease.

 2. Previous diagnosis of metachronous bilateral breast cancer.

 3. Previous or concomitant other (non-breast cancer) malignance within the previous 5
 years except in situ carcinoma of the cervix or curatively treated basal and squamous
 cell.

 4. Presence of other non-malignant disease which may prevent prolonged follow-up.

 5. Received neoadjuvant endocrine therapy.

 6. Adjuvant SERMs therapy (Tamoxifen or Toremifene) for more than 6 months before
 randomization.

 7. Breast cancer chemoprevention with anti-estrogens if less than 18 months between
 stopping and diagnosis of breast cancer.

 8. Severe hepatic dysfunction defined as Child-Pugh grade C.

 9. Severe cardiac dysfunction defined above NYHA grade III.

 10. Presence of occult axillary lymph node with no evidence of primary breast tumor
 pathologically or DCIS with microinvasive. And the measurement of ER, PR and HER2 are
 not obtained.

 11. Uncontrolled psychological diseases.