Molecular markers for prognosis after isolated postmastectomy chest wall recurrence

Abstract

Background: Local chest wall recurrence after mastectomy occurs in 10-20% of patients with operable breast carcinoma. The objective of the current study was to assess the prognostic value of molecular markers at the time of local recurrence and to compare these markers with clinical variables.

Methods: Between 1975 and 1999, the authors treated 113 patients at their institution for postmastectomy chest wall recurrences with full-course external beam radiotherapy. Patients who presented primarily with lymph node recurrences or with simultaneous distant metastasis were excluded. Follow-up from the time of chest wall recurrence was 10.13 years. All clinical and pathologic data from the original diagnosis and from the time of chest wall recurrence were entered into a computerized database. Paraffin-embedded tumor specimens from the chest wall recurrences were available for 43 patients and were constructed into tissue microarrays for immunohistochemical staining of estrogen receptor, progesterone receptor (PR), p53, HER-2/neu, and cyclin D.

Results: Overall survival after chest wall recurrence for the entire cohort was 46% at 5 years and 28% at 10 years. The distant metastasis-free survival rate was 49% at 5 years and 40% at 10 years. Local-regional control of disease was achieved in 79% of patients at 10 years. In multivariate analysis, significant factors for distant metastasis after local recurrence were time to recurrence (< 2 years from the original diagnosis to chest wall recurrence) and PR status (distant metastasis-free survival rate: 84% [PR-positive] vs. 38% [PR-negative]; P = 0.007). The only significant factor for local-regional disease progression was HER-2/neu status. Patients with positive HER-2/neu status had a local-regional progression-free rate of 59%, compared with 92% for patients with negative HER-2/neu status.

Conclusions: The prognosis for patients after local-regional recurrence of breast carcinoma is relatively poor. Longer time to local recurrence and positive PR status were associated with favorable distant metastasis-free rates and long-term survival. Positive HER-2/neu status was associated with poorer local-regional control of disease. Implications for systemic therapy and further studies are discussed.