High-Risk and Metastatic Breast Cancer: The Basics

There are different ways of describing the diagnostic criteria for high-risk and metastatic breast cancer. The widely used American Joint Committee on Cancer (AJCC) staging system is the accepted method for grouping patients with similar prognoses at first diagnosis. This “TNM” system (for tumor, nodes, metastases) takes into account the tumor size, the status of lymph nodes, and the presence of distant metastasis. Combined with menopausal status, estrogen-receptor (ER) status, tumor grade, and other pathology variables, this classification helps the physician and patient in selecting appropriate treatment. In general, those diagnosed at Stage I with small, localized breast cancers, are least likely to suffer a metastatic recurrence. Those diagnosed at Stage II, with larger tumors and/or invasion of the axillary lymph nodes are at higher risk of recurrence.

More than half of cancers diagnosed at Stage I and II do not recur, but this of course depends upon histology of the tumor as well as the adjuvant treatments selected. A recent text on breast cancer estimates the relapse rate for patients diagnosed with Stage I breast cancer to be 20– 30 percent, for Stage II 40–60 percent, and for Stage III, greater than 90 percent. About 75 percent of recurrences will occur within five years of diagnosis;7 however, more recent figures indicate that widespread adjuvant therapy has pushed back the time of relapse for those who do recur.

With adjuvant tamoxifen, 82 percent of 60-year-old women with estrogen-receptor positive, node negative, grade 2 invasive ductal carcinoma of a centimeter or less will be disease-free at 10 years. With adjuvant Cytoxan and Adriamycin, 71 percent of 45-year-old women with ER-negative grade 3 tumors will be disease free in 10 years, but if one to three lymph nodes are additionally involved, the 10 year disease-free survival drops to 57 percent.8 As many as 10–20 percent of tumors treated with lumpectomy and radiation will recur in the breast, and of these, one-tenth to one-fifth may be harbingers of distant metastatic disease.9 The figures are similar for regional recurrence following mastectomy.

Breast cancer that has spread significantly beyond the breast at first diagnosis is described as either “locally advanced” (Stage IIIA or B) or as “distant” metastatic disease (Stage IV). Those diagnosed at Stage III have some combination of the following characteristics: tumors larger than 5 cm, tumors of any size that have grown extensions to the chest wall or the skin, tumors of any size that have spread to axillary nodes that are fixed to each other or to surrounding tissue, or that has spread to internal mammary nodes.10

A relatively rare subtype of breast cancer that is unusually aggressive and fast growing, inflammatory breast cancer, is also classified as Stage IIIB. Although it may not have spread beyond the breast, inflammatory breast cancer is more likely to recur than other tumor types. A recent analysis found the 5- and 10-year overall survival rate for inflammatory breast cancer to be 56 percent and 35 percent.11 In a study of 178 patients with inflammatory breast cancer, disease-free survival was 28 percent at 15 years with combined-modality treatment.12

While it has not risen to the level of evidence required for a prognostic indicator, research suggests that tumors that overexpress the growth-promoting protein made by the HER2 gene, present in 25–30 percent of invasive breast cancer tumors, tend to behave aggressively and be more likely to recur.

In general, prognosis can be said to worsen as the cancer more extensively invades surrounding tissue and lymph nodes, although it may not always be clear when the cancer has spread through direct extension into the tissue, or through the lymphatic or blood stream—factors that also affect prognosis.