The majority of primary breast cancers are adenocarcinomas, and the progression and development of the tumors are variable among women.

The table below outlines the progression and staging of breast cancer.

The focus of this website is advanced, metastatic disease (stage 4), especially targeted to bone, and the prevention of skeletal complications.

Clinical manifestations that are suspicious for locally advanced malignant disease are nipple retraction or elevation; skin dimpling or retraction; heat and erythema of the breast skin; and skin edema or peau d'orange ("skin of the orange"), which is characteristic of malignant disease.

Edema may be due to invasion and obstruction of dermal lymphatics by the tumor. Ulceration of the skin with secondary infection also may be present. The presence of isolated skin nodules may indicate invasion of blood vessels and lymphatics, which often results in implantation of tumor emboli in adjacent tissues and indicates that distant metastases are likely. Clinical presentation may include, or be limited to, signs of local or distant metastatic disease.

Breast cancer metastasizes primarily to the bone, lungs, lymph nodes, liver, and brain. Women with metastatic disease usually have clinical symptoms specific to the organ involved. With metastases to bone, bone pain is the primary clinical manifestation. Involvement of the liver can produce anorexia, weight loss, and malaise. Metastases to the brain can result in neurologic symptoms and damage. Return of an earlier cancer is considered "local" if it is only in the area where it was before and "metastatic" if the cancer returns elsewhere.

A number of complications from advanced breast cancer may be either tumor-related or treatment-related. Bone metastasis is a significant tumor-related complication. Bone metastases are present in 60% to 80% of patients with metastatic breast cancer and can result in cancer-related bone complications known as skeletal-related events (SREs) (Figure 1).

Figure 1. Skeletal-related events impact quality of life and survival.
SRE=skeletal-related event.

• Bone metastases cause considerable morbidity, including severe pain, impaired mobility, symptoms of hypercalcemia, pathologic fractures, spinal cord compression, and bone marrow infiltration.¹
• Bone pain is the most common symptom associated with metastases. More than 80% of patients will experience pain, and pain is often the first indication that the tumor has metastasized to the bone.¹ Pain has a detrimental impact on patients' quality of life, interfering with daily activities and limiting patients' capabilities. This often leads to feelings of anger, fear, and depression.
• Metastatic destruction of bone reduces its load-bearing capabilities and leads to pathologic fractures.¹ The probability of developing a pathologic fracture increases with the duration of metastatic involvement. In addition, bone metastases in the vertebral body increase the risk of developing spinal cord compression, causing significant pain and discomfort.
• Moderate-to-severe hypercalcemia may cause significant health problems if left untreated, including dysfunction of the gastrointestinal tract, kidneys, and central nervous system.¹
• The necessity for pain or fracture management can significantly increase treatment costs. A study in prostate cancer has shown that up to 50% of the total treatment costs are attributable to the costs of managing SREs,² which is likely the case in breast cancer as well.
• SREs also have a negative impact on survival. The precise reason for this association is not clear, but the presence of bone lesions often occurs concomitantly with metastases in soft tissue.³ Metastasis to visceral sites eventually leads to organ failure and death and, therefore, is associated with low survival.³

Even cancer patients without metastatic bone disease are at higher risk for bone loss. This can be a result of:

• Cancer-treatment–induced bone loss (CTIBL) characterized by
  – Decreased bone mineral density^4,5
  – Increased risk of osteoporotic bone fractures^4,5
• Induction of generalized bone loss (osteopenia/osteoporosis),⁵ especially in postmenopausal women.

1.	Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80(suppl):1588-1594.
2.	Groot MT, Boeken Kruger CG, Pelger RC, Uyl-de Groot CA. Costs of prostatic cancer, metastatic to the bone, in the Netherlands. Eur Urol. 2003;43:226-232.
3.	Jacobson AF, Shapiro CL, Van den Abbeele AD, Kaplan WD. Prognostic significance of the number of bone scan abnormalities at the time of initial bone metastatic recurrence in breast carcinoma. Cancer. 2001;91:17-24.
4.	Mundy GR. The evolving role of bisphosphonates: cancer treatment-induced bone loss. Oncology. 2004;18(suppl 3):9-10.
5.	Theriault RL. Pathophysiology and implications of cancer treatment-induced bone loss. Oncology. 2004;18(suppl 3):11-15.