Bone metastasis occurs in 49% of patients with cancer of the breast. Although the diagnosis is currently made by x-rays and scintiscanning, there are no accurate indicators for the evaluation of the early response to therapy. Moreover, the mechanism of action of radiotracers has not been totally elucidated. Urinary excretion of total hydroxyproline (HYPRO) is elevated in metastatic bone disease and its level may suggest the degree of skeletal involvement. HYPRO is excreted as dialyzable and non-dialyzable forms; the former represents breakdown of mature collagen and the latter is an index of synthesis of new collagen. Since bone matrix is the largest store of collagen, changes in these two forms of HYPRO are good indicators of the degree of bone resorption and formation. It is, therefore, likely that serial determination of dialyzable and non-dialyzable HYPRO could be an important tool in the evaluation of the therapeutic response in patients with cancer of the breast with skeletal metastasis. The aims of this proposal are to determine: 1) If serial measurements of dialyzable and non-dialyzable HYPRO is a more reliable index for the development of osteolytic metastatic neoplasia than serial bone scanning. 2) If the response of skeletal metastasis to multi-drug chemotherapy and/or x-ray therapy is reflected in the ratio of dialyzable/non-dialyzable urinary HYPRO. 3) If metastatic osteoblastic neoplasia can be differentiated from osteolytic metastasis by the ratio of dialyzable/ non-dialyzable urinary HYPRO. 4) If the immediate effects of multi-drug chemotherapy on bone scintigrams and total and non-dialyzable HYPRO excretion.