Locally advanced invasive breast cancer

Epidemiology
Decreasing percentage of tumors are diagnosed at stage T3 or greater probably due to increasing mammography rates
Inflammatory breast cancer represents about 2% of all breast cancers (4,000 cases per year)
 -incidence is increasing slightly for unknown reasons
 -more common in black women (who are overall at higher risk for presenting with advanced stage disease)
 -associated with high rates of nodal involvement and metastases

Stages
T3 = 2 to 5cm breast tumor
T4a = chest wall invasion (pec muscles do not count)   T4b = skin invasion  T4c = both
T4d = inflammatory breast cancer
 -rapid progression of erythema, edema, and warmth
 -underlying mass may or may not be present
 -inflammatory disease is associated with invasion of the dermal lymphatics on pathology but this is not necessary to make the diagnosis in a patient who has bx proven breast cancer with the appropriate clinical findings
 -30% have mets at diagnosis
 -tumors tend to be ER-, high grade, highly proliferative

Neoadjuvant chemotherapy
Recommended in most LABC patients
NSABP B-18: patients with operable breast cancer assigned to AC chemo either before or after surgery
-DFS and OS were equivalent regardless of when chemo was given
-60% of patients were BCT candidates at the time of study entry
-20% of non-BCT patients were converted to BCT by the use of preoperative chemo, however a trend to increased rates of first recurrence as an in-breast tumor recurrence was noted in this group
-EORTC replicated these results

Postmastectomy radiation trials
1) Danish 82b: premenopausal T3/T4 with + nodes randomized to mastectomy + CMF +/- RT
RT improved 10-year DFS (34 vs 48%)
                and 10-year OS (45 vs 54%)
       decreased local failure (26 vs 5%)
Most common site of recurrence in patients not receiving radiation was the chest wall
Adequacy of LN dissection has been questioned

2) Danish 82c: postmenopausal T3/T4 with + nodes randomized to mastectomy + tam +/- RT
RT improved 10-year DFS (24 vs 36%)
                and 10-year OS (36 vs 45%)
        decreased local failure (35 vs 8%)
No survival benefit was seen for RT in patients with 0-3 positive nodes

3) British Columbia: premenopausal women, N+, randomized to mastectomy + CMF +/- RT
RT increased 10-year OS (37 vs 47%)
      decreased local failure (39 vs 13%)

Indications for PMRT
Absolute: Four or more positive nodes; positive margins; inflammatory carcinoma; T4 primary; ECE
Gray area: 1-3 nodes
Tiebreakers: large tumors (T3), younger patients, less than ten nodes dissected, more than 20% of nodes involved, high grade, ER-, LVSI+