In a portion of breast cancer diagnoses, the cancer has already spread to distant organs in the body. There may have been a rapid progression of disease or the cancer has been present but undetected. Since outcomes in women with breast cancer depend largely on treatment being started as early as possible, early diagnosis is key.

Breast self-exams, clinical physical examinations, and routine mammography may reveal breast disease that ranges from equivocal benign conditions, to those with suspicious morphology, to those that must be accepted as malignant until proved otherwise. The majority of breast cancers are associated with abnormal mammographic findings. If there is a palpable abnormality, additional diagnostic testing is required.

The diagnostic evaluation of breast lesions may be a simple one-step procedure, or it may involve a multilevel process. First, noninvasive and low-invasive diagnostic procedures are used, such as the diagnostic mammogram to target potentially suspicious lesions and the sonogram (ultrasound) to help differentiate solid or cystic lesions.

Tumor markers that are nonspecific but that may be used to monitor breast cancer patients and that are elevated in women with metastatic disease are CEA (carcinoembryonic antigen) and CA 15-3.

The final determinant in diagnosis is the biopsy.

Apart from following the progressions of the actual breast lesions, bone loss should be assessed and monitored to treat and reduce the incidence of skeletal-related events (see Skeletal Complications section).

Screening for bone mineral density (BMD) is commonly used as a quantitative measure of the calcium in bone. It is often used in healthy populations at risk for osteoporosis to predict future fracture risk. Hip BMD is the best predictor not only of hip fractures but also of fractures at other skeletal sites.

Magnetic resonance imaging (MRI) and computed tomography (CT) are used to characterize known bone lesions, often helping to differentiate between benign and malignant lesions as well as to determine the extent of bone destruction.

Dual energy x-ray absorptiometry (DEXA) can be used in the office to measure BMD at multiple skeletal sites, including the spine, proximal femur, forearm, and total body. Central DEXA of the hip and/or spine is the preferred measurement for definitive diagnosis.

Peripheral dual x-ray absorptiometry (pDXA) and single-energy x-ray absorptiometry (SXA) are techniques that measure bone density in the forearm, finger, and sometimes the heel. Quantitative computed tomography (QCT) measures trabecular and cortical bone density at several skeletal sites, but it is most commonly used to measure trabecular bone density in the spine. It is also possible to measure trabecular and cortical bone density in the periphery by pQCT (peripheral QCT). Ultrasound densitometry is used to assess bone in the heel, tibia, patella, or other peripheral sites where the bones are relatively superficial. Ultrasound measurements are generally not as precise as DXA or SXA, but these tests appear to predict fracture risk as well as other measures of bone density.¹

Bone mineral density and T-score measurements are used for bone loss based on the criteria set forth by the World Health Organization. The resulting scores give a general measure of the risk for osteoporosis. An abnormal score increases the need for intervention to manage weakened bones and prevent further impairment.

The World Health Organization has established categories of bone density based on DEXA measurement at the spine, hip, or wrist in white postmenopausal women to facilitate the diagnosis of osteoporosis. The reference to a "young normal adult" relates to optimal or peak density for a healthy 30-year-old.¹

• T-score at or above -1 means that the BMD is not more than 1 standard deviation (SD) below that of a young, normal adult, providing the definition of normal.¹
• T-score between -1 and -2.5 SD below normal is defined as low bone mass, or osteopenia.¹
• When the T-score is -2.5 SD or more below normal, the BMD is defined as osteoporosis.¹
• The presence of one or more fractures in an individual with a T-score of at or below -2.5 SD is defined as severe osteoporosis.¹

However, regardless of the score, the whole patient should be considered when developing a risk profile and designing interventions.

Bone mineral density should be monitored in cancer patients who may be at risk for bone loss subsequent to treatment effects. Especially at risk are all women over age 65 and women aged 60 to 64 with risk factors such as a family history of breast cancer, body weight less than 70 kg, or prior nontraumatic fracture. Postmenopausal women of any age receiving aromatase inhibitors should be included, as well as premenopausal women with therapy-associated premature menopause.²

Monitoring should be continued yearly after the initial examination.

From the beginning, BMD technology had very acceptable accuracy and precision errors such that diagnosis and monitoring of disease progression or regression were straightforward. However, one major drawback to BMD alone in the management of osteoporosis, especially when focused on individual patient care, is that bone turnover is generally so slow (particularly in relation to metabolic bone diseases) it may take up to 2 years to be certain with 95% confidence that any change in BMD is more than can be accounted for by method imprecision.

Chemicals in serum and urine can serve as markers for monitoring bone loss, bone reformation, and the effectiveness of therapy in patients with osteoporosis or cancer treatment-induced bone loss. Biochemical markers can measure the rate of bone loss or formation.

Markers of bone resorption: urinary markers³

• Calcium
• Hydroxyproline
• N-telopeptide
• C-telopeptide
• Pyridinoline
• Deoxypyridinoline

Markers of bone resorption: serum markers^3,4

• N-telopeptide (S-NTx)
• C-telopeptide (S-CTx)
• Bone sialoprotein (S-BSP)

Markers of bone formation: serum markers³

• Alkaline phosphatase (total and skeletal)
• Procollagen-I extension peptide
• Osteocalcin

1.	National Osteoporosis Foundation. Physician's Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2003. Available at: http://www.nof.org_vti_ bm/sktml.dll/physguide/index.htm. Accessed December 2004.
2.	Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer (ASCO special issue). J Clin Oncol. 2003;21:4042-4057.
3.	Rosen CJ, Tenchouse A. Biochemical markers of bone turnover. Postgrad Med. 1998;104.
4.	Delmas PD, Eastell R, Garnero P, et al. The use of biochemical markers of bone turnover in osteoporosis. Osteoporosis Int. 2000;(suppl 6):S2-S17.