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Breast cancer
Staging and prognostic factors

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	Breast Cancer
	- Introduction - Causes - Clinical Picture - Screening - Diagnosis - Pathology - Staging - Treatment

Staging techniques -
Bone metastasis
(80%)

1. Bone scan

The bone scan can detect an abnormality prior to the radiograph becoming abnormal. Abnormal areas of accumulation are seen related to osteoblastic activity. Purely lytic lesions such as multiple myeloma may be missed on the bone scan.

Benefits

• Bone scans are quite sensitive (70%) for the detection of metastatic disease, but the specificity is lower than the sensitivity (60%), hence the need for correlation with plain radiographs and CT.

The poor specificity is because any process involving bone will result in increased bone turnover and an abnormality on the bone scan. Thus, inflammatory, traumatic, and metabolic abnormalities will result in increased areas of localization on the bone scan.

2. Bone X-ray

Compared with other imaging techniques, radiography is relatively insensitive in detecting bone metastases, especially subtle lesions.

Benefits

• Can detect lesions that are 2 cm or larger. Metastases to bone become apparent on radiographs only after the loss of more than 50% of the bone mineral content at the site of disease.

• Useful in confirmation of lesions that are detected by bone scan.

3. CT scan of bone lesion

CT scans of the bone is useful in detection of metastasis or confirmation of bone lesions detected by bone scan.

Benefits

• More sensitive than radiography in the detection of metastatic lesions and is useful for confirmation of the results obtained by scintigraphy (bone scans), especially in sacral lesions - specificity 90%.

4. MRI of the bone

Benefits

• Whole body MRI has been reported to be superior to bone scans in detection of bone metastasis. Sensitivity is 80% and specificity is >90%.

5. PET scan for bone lesions

Benefits

• FDG PET has the highest sensitivity in detecting bone metastasis: 90%. Its specificity approaches 100%.

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Pulmonary metastasis (25%)

1. Chest x-ray

A chest radiograph in two planes is indicated on a regular basis to screen for metastatic disease in the follow-up of patients with primary tumors that preferentially spread to the lungs.

Benefits

• Sensitivity and specificity for chest radiography were 50 and 90%, respectively for nodules >5mm.
• It more accurately detects a 1-cm nodules 1cm or greater.

2. Chest CT

When metastatic nodules are identified, helical computed tomography (CT) of the chest  should be performed to assess their number and characteristics. 

Benefits

• A high-resolution CT scan can identify nodules 3 mm in diameter.

• CT has an overall sensitivity 62% in detecting pulmonary nodules (all sizes). However it underestimated the extent of the disease in 25%, and overestimated the extent of the disease in 14%.

• Sensitivity is increased to 95% for intrapulmonary nodules ≥ 6 mm and 100% for intrapulmonary nodules > 10 mm.

The limitations of CT scan in this study were mainly associated with pleural-based nodules and intrapulmonary nodules < 6 mm.

Liver metastasis (20%)

1. Ultrasonography of the liver

Ultrasonography is inexpensive and readily available, but its value compared to single-slice helical CT (SSCT), MSCT, and MRI is limited as a consequence of reduced sensitivity and specificity. In general, the US appearance of liver metastases is nonspecific.

Benefits

• Sensitivity is operator dependent. It is valuable, inexpensive, quick, and portable, and it can depict lesions as small as 1 cm with a sensitivity approaching 80%.

• The specificity of US in detecting liver metastases is poor, and its overall false-negative rate is 50%. However, the presence of multiple hepatic nodules of different sizes within the liver is nearly always due to metastases.

2. Abdominal CT

CT is the most sensitive technique for the detection of liver metastases.

Benefits

• Contrast-enhanced scans offer a high degree of sensitivity, as high as 80-90%. The specificity is 99%.

Brain metastasis (15%)

Screening for brain metastasis is not routinely done in breast cancer and is only done for those with symptoms suggestive of brain involvement.

1. CT scan of the brain

CT scan of the brain is currently the method of choice in screening for brain metastasis. Patients with multiple lesions are even more likely to have metastatic disease. Prior to definitive therapy, patients with a single metastasis by contrast-enhanced CT should undergo a contrasted MRI examination, if available.

Benefits

• 92% sensitivity, 99% specificity

2. MRI of the brain

Gadolinium-enhanced MRI is superior to contrast-enhanced CT in the diagnosis of brain metastases. It is particularly useful in patients shown to have a single metastasis by contrast-enhanced CT prior to definitive therapy.

3. FDG-PET for brain lesions

FDG-PET is not considered superior to CT or MRI in the initial evaluation of suspected brain metastases.

Benefits

• Sensitivity of 90% but low specificity. Neoplasm, inflammation, vascularity, or trauma may cause the abnormal uptake.

Staging of breast cancer

• The TNM staging system for breast cancer

Prognosis (Risk factors for recurrence)

The challenge for the clinician is to determine which patients have the highest risk of recurrence and, thus, are most likely to benefit from adjuvant therapy. In this chapter, we will detail the prognostic factors that affect whether adjuvant therapy is indicated and then describe the various adjuvant treatments that are available.

Memory Aid for breast cancer prognostic factors:

(HrGAT - Hormone receptor, Grade, Age, Tumor)

HER-2/neu oncogene: Overexpression of the HER-2/neu oncogene reflects an increase in the proliferative activity of a tumor. Overexpression has been demonstrated in 15% to 30% of patients with breast cancer and has been found by most investigators to be associated with shorter survival.

Ploidy and S-phase fraction: The degree of cellular proliferation in breast cancer specimens has shown a strong correlation with outcome. DNA ploidy is the DNA content and number. S-phase fraction is the fraction of cells actively cycling or synthesizing DNA. Aneuploid (those with abnormal DNA content and number) tumors with a high percentage of cells in S-phase are more likely to recur than are tumors with a low S-phase fraction.

Prognostic factors currently under investigation

• Angiogenesis markers
• Histologic subtype
• Lymphatic invasion
• Epidermal growth factor receptor
• Ki-67
• pS2
• Stress response proteins
• Type IV collagenases
• nm23
• p53
• Plasminogen activators

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