Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised Phase II Feasibility Study Investigating the Biological Effects of the Addition of Zoledronic Acid to Neoadjuvant Combination Chemotherapy on Invasive Breast Cancer
Brief Summary: There is clear preclinical in vitro and in vivo evidence of sequence dependent synergy between chemotherapy agents and zoledronic acid. The aim of the study is to investigate if the synergistic increase in tumour cell apoptosis observed in preclinical studies occurs in patients. The hypothesis for this study is that there may be anti-tumour benefits of the sequential application of chemotherapy agents followed by zoledronic acid in patients with invasive breast cancer.


Options:
A: Inclusion Criteria:

* Newly diagnosed primary invasive ductal or invasive lobular breast adenocarcinoma
* Tumor classified as clinically large T2 (2-5 cm), T3, T4 or any T with N1, N2
* Prior malignancies: limited to curatively treated basal or squamous carcinoma of the skin or history of previous malignancies, treated and now \> 5 years disease free
* \>= 18 years of age
* Normal left ventricular function by echocardiogram or radioventriculogram
* Karnofsky Performance \>= 70

Exclusion Criteria:

* No evidence of distant metastasis present by CT, Bone scan, or physical exam
* If the bone scan or CT scans demonstrate indeterminate lesions, the nature of these lesions may be further clarified by additional testing such as PET or MRI
* No current treatment with Zometa or other bisphosphonates
* No serious functional disorders of the liver or kidneys:
* Serum Creatinine \<=2
* ALT/AST/ALK Phos \<= 1.5 x upper limit of institutional normal.
* Bili \<= 1.5 x upper limit of institutional normal.
* Currently not pregnant
B: DISEASE CHARACTERISTICS:

* Diagnosis of primary breast cancer, meeting 1 of the following staging criteria:

  * Stage II
  * Stage III
  * T stage ≥ T1
* Receiving OR scheduled to receive chemotherapy and/or endocrine therapy

  * For patients receiving neoadjuvant therapy

    * Tumor \> 5 cm (T3), features of locally advanced disease (T4), OR biopsy-proven lymph node involvement (N1)
    * Scheduled to proceed to definitive surgery and/or radical radiotherapy with curative intent within 6 months of starting neoadjuvant therapy
    * No more than 30 days between initiation of neoadjuvant therapy and start of study drug
  * For patients receiving adjuvant therapy

    * Must have undergone complete primary tumor resection and treatment of axillary lymph nodes\*
    * Must have lymph node involvement
    * No prior neoadjuvant therapy\*\*
    * No more than 60 days since prior definitive surgery NOTE: \*Patients whose treatment plan includes further primary tumor resection and/or treatment of the axillary lymph nodes (e.g., clearance or radiotherapy) with curative intent after completion of chemotherapy are eligible provided the treatment is completed within 9 months of study entry

NOTE: \*\*Preoperative endocrine therapy with a duration of \< 30 days is not considered prior neoadjuvant therapy

* No evidence of recurrent or metastatic disease
* No history of breast cancer, except ductal carcinoma in situ or lobular carcinoma in situ
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age

* 18 and over

Sex

* Female

Menopausal status

* Premenopausal or postmenopausal

Performance status

* Karnofsky 80-100% OR
* ECOG 0-1

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Creatinine ≤ 1.5 times upper limit of normal

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No active dental problems, including dental abscess or infection of the jaw bone (e.g., maxilla or mandible)
* No prior or current diagnosis of osteonecrosis of the jaw
* No other malignancy within the past 5 years (including prior contralateral breast cancer) except nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
* No history of disease with influence on bone metabolism, including any of the following:

  * Paget's disease of the bone
  * Primary hyperparathyroidism
  * Osteoporosis requiring treatment or likely to require treatment within the next 6 months
* No other severe physical or psychological disease that would preclude study compliance
* No known hypersensitivity to bisphosphonates

PRIOR CONCURRENT THERAPY:

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* See Disease Characteristics

Radiotherapy

* See Disease Characteristics

Surgery

* See Disease Characteristics
* More than 4 weeks since prior and no concurrent dental or jaw surgery (e.g., extractions or implants)

  * Dental fillings, teeth scaling and polishing, or minor gingival surgery within the past 4 weeks are allowed

Other

* More than 1 year since prior bisphosphonates
* More than 30 days since prior investigational drugs
* No concurrent investigational drugs (i.e., not locally approved for any indication)
C: Inclusion Criteria:

1. Metastatic breast cancer to the bone with radiologically confirmed bone metastases
2. High-risk of subsequent SRE as reflected through either: elevated serum CTX (\> 400ng/L) and/or bone pain (using BPI) and/or prior SRE while on bisphosphonate therapy and/or progressive bone metastasis (by imaging)
3. On pamidronate therapy for at least 3 months
4. ECOG ≤ 2 and life expectancy \> 3 months
5. Serum creatinine ≤ 2.0 × ULN (zoledronic acid or pamidronate to be renal dosed as per institution standard)
6. No changes in systemic treatment in the 4 weeks prior to study entry or anticipated changes in the 4 weeks after entering the study. Markers of bone formation can be affected by a change in systemic therapies
7. Ability to take calcium and Vitamin D as per Health Canada recommended daily doses for the duration of the study
8. Ability to provide informed consent and complete study evaluations.

Exclusion Criteria:

1. Patients with acute symptomatic pathological fractures or acute spinal cord compression until such time as the appropriate management (surgery and/or radiotherapy) has been completed
2. Acute hypercalcemia (\>3.5 mmol/L)
3. Hypersensitivity to any bisphosphonate
4. Patients with rapidly progressive non-bone metastases for whom delaying a change in systemic anti-cancer treatment for the 1 month biochemical marker evaluation period could have a detrimental impact on patient outcome.
5. Renal dysfunction (≥ 2x creatinine of the upper limit of normal )
6. Pregnancy or lactation
7. Patients with dental abscesses or patients potentially requiring tooth extraction while on study
D: Inclusion Criteria:

* Women with histological diagnosis of invasive breast cancer requiring neoadjuvant chemotherapy
* T2 tumour or above
* WHO Performance status of 0,1 or 2
* Must consent to or have undergone a core biopsy for diagnosis of breast cancer AND consent to undergo an additional core biopsy prior to the second cycle of chemotherapy (Day 5 +/- Day 21)
* Written informed consent

Exclusion Criteria:

* Previous chemotherapy or radiotherapy to treated breast
* Evidence of metastatic disease or recurrent breast cancer or previous malignancy (some exceptions)
* Calculated creatinine clearance \< 40mls/min
* Prior treatment with bisphosphonates in last year or known contraindications to bisphosphonate therapy
* Concurrent tamoxifen or aromatase inhibitor medication
* Pregnant or lactating women
* Cardiac dysfunction that precludes use of anthracycline chemotherapy
* Unwilling to have extra interim biopsy

Answer: D