Study of Bone Mineral Density in Postmenopausal Women After Treatment for Breast Cancer
Study of Bone Mineral Density in Postmenopausal Women After Treatment for Breast Cancer
Bone Mineral Density (BMD) as measured by X-ray shows the amount of calcium in the bone. Low
 BMD may reflect osteoporosis, a condition where there is an increased risk of fracture. Women
 who have gone through menopause have a higher risk of getting osteoporosis because they lose
 calcium from their bones much faster than younger women. Women with breast cancer may have an
 additional risk for getting osteoporosis because of the effects of their treatment with
 chemotherapy. The purpose of this study is to see what levels of BMD post-menopausal women
 with breast cancer have, and to see if the level of BMD changes during a women's treatment
 after her surgery. This trial studies changes in BMD and markers of bone activity in women
 receiving treatment for early stage breast cancer.
Breast cancer patients may be at increased risk for osteoporosis secondary to cancer
 treatment. The hypothesis of this study is that adjuvant chemotherapy increases the risk of
 osteoporosis in postmenopausal women. The objective of this pilot study is to describe the
 effects of chemotherapy on bone mineral density and serum markers of bone metabolism.

 There is limited data on the change in bone mineral density due to chemotherapy in
 postmenopausal women. This prospective study will gather data on the effects of systemic
 breast cancer therapy on bone mineral density in postmenopausal women receiving adjuvant care
 for early stage (0, I, II or III) breast cancer. Postmenopausal women are the focus of this
 study because: (1) they are the largest subgroup of women with breast cancer (2) they are
 expected to have a rate of BMD loss unless disturbed by disease or medications, unlike the
 pre and perimenopausal women whose BMD is dramatically affected by changes in hormonal status
 (3) this group of patients is at greatest risk for acute osteoporotic fractures.
Inclusion Criteria:

 -  Documented histologically or cytologically proven diagnosis of breast cancer

 -  Non-metastatic breast cancer tumor with the diagnosis of Tis, T1-T4, N0-3, M0 (Stage
 0, I, II or III breast cancer) by the American Joint Committee on Cancer revised
 tumor-nodal-metastases staging system (Singletary, JCO 2002). DCIS is allowed, but
 LCIS (only) is not. Adjuvant care is administered as clinically indicated. Adjuvant
 treatment decisions are not stipulated in this trial.

 -  Postmenopausal as defined by last menstrual cycle occurring more than 5 years
 previously. Women who have had a hysterectomy without bilateral oophorectomy will be
 considered postmenopausal if greater than 55 years of age. Women who have had a
 bilateral oophorectomy more than 5 years previously will be considered postmenopausal.

 -  Chemotherapy Arm: Patients about to begin adjuvant, or neoadjuvant, treatment with
 Doxorubicin (60mg/m2), Cyclophosphamide (600mg/m2) followed by Paclitaxel (175mg/m2)
 (AC-T) or Doxorubicin (60mg/m2) for 4 cycles followed by Paclitaxel (175mg/m2) for 4
 cycles followed by Cyclophosphamide (600mg/m2) for 4 cycles (A-T-C) administered in
 the dose dense regimen every 2 weeks with growth

 -  factor support. The patient may enter this trial within 3 months of initiating
 adjuvant chemotherapy.

 -  Observation Arm: Patients begin adjuvant follow up with expectant monitoring (no
 systemic therapy). The patient may enter this trial within 2 months of initiating
 adjuvant care.

 -  Signed informed consent

 -  Assessment of the complete blood count and complete biochemical profile must indicate
 absolute neutrophil count >1000/ul, hemoglobin > 9 g/dl and platelets >100,000/ul and
 the bilirubin, liver transaminases (AST/ALT) and serum creatinine must be within 2.5
 times the institutional upper level of normal at the time of enrollment into the
 study.

 Exclusion Criteria:

 -  Any metabolic bone disease (including Paget's disease of the bone) other than
 postmenopausal osteoporosis or osteopenia.

 -  Use of systemic gonadal hormonal medications or supplements within the past 24 months.
 Topical vaginal estrogens such as "Estring" or other vaginal estrogenic compounds not
 associated with systemic absorption are allowed.

 -  Prior use of tamoxifen or raloxifene is permitted if the medication was discontinued
 more then 24 months prior to the diagnosis of breast cancer. No adjuvant antiestrogen,
 antineoplastic, therapies are permitted on study.

 -  Chronic use of systemic steroids (equivalent of prednisone 5mg daily for more then 3
 months) for disease process other than breast cancer chemotherapy premedications or
 antiemetics. Inhaled steroids are allowed, as is the occasional use of low to moderate
 dose short pulse steroids.

 -  History of rheumatoid arthritis, ankylosing spondylitis, hyperparathyroidism, renal
 osteodystrophy, moderate to severe inflammatory or autoimmune diseases or newly
 diagnosed thyroid condition requiring titration of medications (stable dose and minor
 dose modifications of thyroid medications are acceptable). Other exclusionary comorbid
 conditions include thalassemia, moderate to severe malabsorptive syndromes and HIV.
 Patients diagnosed with the above conditions or similar comorbid and/or inflammatory
 diseases associated with changes in BMD either from the disease process or the therapy
 of such condition(s) during the course of the study will be removed from the study at
 the point of diagnosis.

 -  Lobular carcinoma in situ (LCIS) or Stage IV breast cancer and patients with a
 concurrently active second malignancy other then adequately treated non-melanoma skin
 cancers or in situ cervical cancer. Patients with non-mammary malignancies, or prior
 breast cancer, must have been disease free for at least 5 years.

 -  Participation in other clinical trials that are measuring BMD as a study parameter

 -  Patients with conditions that are expected to distort BMD reading and make DEXA
 results unreliable such as bilateral prosthetic hips, extensive degenerative joint
 disease, or severe calcification of the aorta.

 -  Patients with concurrent medical or psychiatric conditions, which at the judgment of
 the consenting investigator, would prevent them from understanding and complying with
 this clinical trial.