Two important changes have occurred over the last decade in the definition of locally advanced breast cancer.  First, T3N0 lesions have now been categorized as Stage IIB disease, reflecting their more favorable prognosis compared with other Stage III breast cancers. Second, the N3 category no onger includes positive supraclavicular lymph nodes. This finding is now considered indicative of Stage IV disease.

Numerous older series, however, have included patients with positive supraclavicular lymph nodes, as they were previously categorized as N3, Stage IIIB disease. Therefore, the reporting and analysis of the results of patients who have locally advanced breast cancer is complicated by the fact that many series include patients with a wide variety of presentations.

Locally advanced breast cancer may be considered as three groups of conditions. Patients with 1) operable noninflammatory (T3N1) breast cancer; 2) those with inoperable noninflammatory (T4a,b,c, any N2, any N3) breast cancer; and 3) those with inflammatory breast cancer (any T4d).

All patients with locally advanced breast cancer have a high local tumor burden and a high likelihood of systemic metastases. Therefore, aggressive systemic chemotherapy plays a central role in their management.  Both ocal-regional radiation therapy and mastectomy, when possible, are useful n securing local control. Most patients with Stage III breast cancer will receive chemotherapy as their first therapeutic maneuver.

This permits the earliest treatment of micrometastatic disease, assessment of response to therapy and, in many cases, conversion of inoperable or nearly inoperable disease to operable disease. For operable noninflammatory (T3N1) lesions, surgery as the primary therapeutic modality is perfectly reasonable. In this situation, mastectomy is customary. Comprehensive chest-wall radiation is indicated or all patients with this stage breast cancer. Investigators have looked at utilizing neoadjuvant chemotherapy to assess response and to permit breast conservation.

In this situation, postoperative radiation therapy to 60 Gy to the entire breast has been utilized.

For inoperable noninflammatory lesions, neoadjuvant chemotherapy is considered the standard of care. In patients who have attained a suitable response to therapy, mastectomy is then added. There is no established role or breast-conservation therapy in this group. Completion of adjuvant chemotherapy followed by chest-wall radiation is standard practice. Alternatively, patients who are not candidates for chemotherapy may do well with hormonal management and may achieve a dramatic result. Radiation therapy alone as the local management for this entity has been reported, and reasonable local control may be anticipated.

With such a high tumor burden, however, significantly higher doses of radiation are indicated. Doses up to 80Gy have been used in this setting with good results in terms of local control. Naturally, cosmesis in this situation would be anticipated to be very poor, with dense fibrosis, atrophic skin changes and contraction of the breast tissue being common.

For patients with N2 disease, radiation alone is undesirable. Unfortunately, the tolerance of the brachial plexus will not permit adequate treatment of significant volumes of gross disease in the regions of the axilla or supraclavicular fossa. Therefore, the use of systemic agents as the initial management of this group of patients is highly desirable. If a good response is obtained, a mastectomy is performed and followed by comprehensive chest-wall radiation.

In the case of inflammatory breast cancer, neoadjuvant chemotherapy is considered the standard of care.  Among patients who have an excellent response, which is quite common, mastectomy is added. Chemotherapy is then completed and comprehensive chest-wall radiation is added. This previously dire condition is now associated with approximately a 50% survival among patients who respond well to neoadjuvant chemotherapy.

Karen D. Schupak
American College of Physicians

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