The purpose of this study is to see if women with bone metastases from breast cancer will benefit from the addition of doxycycline to their standard bone-targeted therapy. Participants will be asked to take 100 mg of Doxycycline orally twice a day for 12 weeks. Blood and tissue collection will further define the mechanism of the benefits if there are any.

Potential candidates for this trial must have received intravenous bisphosphonate therapy (i.e. pamidronate or zoledronic acid) or subcutaneous denosumab for at least 3 months. Baseline patient characteristics will be recorded and screening serum PTH (to rule out primary hyperparathyroidism) and vitamin D (25OH-vit D) will be recorded. In order to fulfill the study objectives, serum will be taken for CTX (fasting morning blood sample), P1NP and BSAP as well as for the optional translational studies (e.g. MMP and TIMP levels). Optional urine will be taken for NTX. Questionnaires will also be completed for symptoms (Brief pain inventory (BPI) [26] and FACT-BP [27]) and analgesic use (converted into an oral Morphine-equivalent dose). The serum, urine and questionnaire data will be collected at: baseline, weeks 4, 8, and 12. In addition, toxicity information and questions about the occurrence of skeletal related events will be performed at baseline, weeks 4, 8 and 12. At baseline and week 12 the patient will also have a bone marrow aspirate and trephine biopsy performed from the posterior iliac crest. These specimens will be used for ER, PR and Her2 analysis (by FISH) and markers of apoptosis (TUNEL) and proliferation (Ki67) and also for optional translational studies providing tumour cells are present.

Inclusion Criteria:

1. Patients with metastatic breast cancer with radiologically confirmed bone metastases.
2. On intravenous bone-targeted therapy (bisphosphonate or subcutaneous (SC) denosumab) for at least 3 months.
3. ECOG ≤ 2
4. Life expectancy >3 months.
5. No changes in the type of systemic chemotherapy, endocrine therapy or biological therapy (i.e. trastuzumab, lapatinib) 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).
6. Ability to provide informed consent and complete study evaluations.

Exclusion Criteria:

1. Prior hypersensitivity to either IV bisphosphonate therapy or SC denosumab, doxycycline or tetracyclines.
2. Patients with myasthenia gravis
3. Patients taking hepatic enzymes inducers such as phenytoin, barbiturates and carbamazepine
4. Patients with rapidly progressive non-bone metastases for whom delaying a change in systemic anti-cancer treatment in the first 4 weeks of the study could have a detrimental impact on patient outcome.
5. Women of child bearing potential who are unwilling to use acceptable methods of contraception while on study.
6. Pregnancy or lactation.
7. Clotting disorder that would preclude bone marrow aspirate and trephine biopsy. (Patients on Fragmin or Daltaperin are allowed on study)