In the 1990s, the most common indication for high dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (AHCT) was breast cancer. Several randomized controlled trials for metastatic breast cancer (MBC), performed to address the role of HDC and AHCT, found no survival benefit over conventional therapy. A recently published meta-analysis confirmed a lack of significant survival benefit and failed to identify any subset of patients that benefited from this approach. Many trials of HDC for MBC, however, demonstrate better than expected 10–15 year progression free and overall survival occurring in 5–15% of patients. These data prompted us to evaluate the long term results of treatment with HDC and AHCT in MBC at our institution.
Two-hundred eighty five patients underwent HDC followed by AHCT for metastatic breast cancer from 1984–2000. Preparative regimens included STAMP V (cyclophosphamide [Cy], carboplatin, thiotepa [TT]), n=98; CBT (Cy, carmustine, TT), n=79; busulfan and Cy, n=54; TT, n=27; STAMP I (Cisplatin, Cy, BCNU), n=26; and BCNU, n=1. With a median follow up of 169 months (range 77–283 months) in survivors, 34 (12%) of these patients remain alive. Of the 251 patients who died, 218 (87%) died of relapsed/metastatic disease. Other causes of death included infectious or cardiopulmonary etiologies. Incidence of death from secondary malignancies was less than 1%. Her2 status was unavailable in the majority of the patients, but comparison by age (<50 and >50) and hormonal status did not demonstrate any significant differences in relapse (p=0.33 and p=0.32 respectively) or survival (p=0.13 and p=0.42). Using Cox analysis, we identified three prognostic factors for survival in multivariable analysis: number of prior chemotherapy regimens (HR 1.48 per 1 regimen increase, p<0.001); disease status, (HR 1.34, p=0.029 for partial response and HR 2.66, p=0.008 for relapsed/refractory disease); and source of hematopoietic cells (HR 2.45, p=0.012 for bone marrow compared to peripheral stem cells). Data regarding number and type of metastatic sites was not available for the entire cohort.
Of the 34 long term survivors identified, sufficient data was available on 28 patients. In this cohort, 10 patients had metastatic disease at presentation while 18 patients had recurrent metastatic disease. Of the 10 patients with primary metastatic disease, 4 patients had oligometastatic involvement of the ipsilateral supraclavicular lymph node which would now be classified as stage IIIC disease by current AJCC staging guidelines. Three patients had limited bone disease and 3 had oligometastatic disease that had been resected. Of the 18 patients with recurrent metastatic disease, 9 had local recurrence at the site of the incision or chest wall, and 6 had a single site of recurrence primarily in the lung or loco-regional lymph nodes, also classified as primarily oligometastatic disease. Most of these lesions were surgically resected. Of the remaining patients, one had recurrent lesions in the liver, one had bilateral breast recurrence, and one had recurrence in the lung with additional possible bone involvement.
This retrospective evaluation of patients who underwent HDC and AHCT for metastatic breast cancer demonstrates long term survival in a small subset of MBC patients, primarily those with primary or recurrent oligometastatic disease. Previous studies have suggested that oligometastatic breast cancer is a distinct subgroup with long-term prognosis that is superior to MBC. While the use of HDC and AHCT has largely been abandoned in the United States, several recent long term follow up studies such as this one questions its role for select populations. The use of HDC in subsets such as oligometastatic breast cancer may be beneficial, and may warrant further study; however, overall there remains no demonstrable benefit to HDC and long term survival is rare in the population of patients with metastatic disease.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.