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Early initiation of chemotherapy may prolong DFS for early breast cancer
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Shorter time to initiation of adjuvant chemotherapy may reduce relapse and improve outcomes in patients with rapidly proliferating early breast cancer, according results of a phase 3 study.
Earlier chemotherapy may improve OS and DFS in patients with certain subtypes of breast cancer that are rapidly proliferating and aggressive, such as triple-negative or HER-2–positive disease.
Alberto Farolfi, a medical oncologist in training at the Scientific Institute of Romagna for the Study and Treatment of Cancer in Meldola, Italy, and colleagues sought to examine the influence of time to chemotherapy on the outcome of these patients and to set a threshold value for time to chemotherapy to better define the clinical outcome.
“We demonstrated that in a population with rapidly proliferating early breast cancer, the risk of a poorer prognosis is not only related to a time to chemotherapy longer than the threshold value, but also increases as the weeks pass,” Farolfi and colleagues wrote. “Although it cannot be ascertained that longer time to chemotherapy leads directly to reduced survival, it is indeed plausible. In fact, undetectable metastases may grow, making subsequent treatment less effective.”
The researchers assessed the relationship between time to chemotherapy after surgery and DFS or OS in 921 patients with early breast cancer who had rapidly proliferating tumors and who were enrolled in a phase 3 study evaluating the use of chemotherapy with or without anthracyclines. Ninety-three percent of the patients has stage I to stage II early breast cancer.
Median follow-up was 8.75 years (range, 2 months to 15.66 years).
Median time to chemotherapy in the overall cohort was 38 days (interquartile range, 33-42). One hundred patients (10.9%) received adjuvant chemotherapy within 4 weeks, 786 (85.3%) received chemotherapy within 5 and 8 weeks, and 35 (3.8%) received chemotherapy 8 weeks after surgery.
A prolonged time to chemotherapy significantly increased the risk for relapse and death (HR = 1.15; 95% CI, 1.02-1.30).
Using a backward elimination procedure, DFS appeared significantly associated with time to chemotherapy (HR = 1.15; 95% CI, 1.02-1.29), the size of the tumor (HR = 1.44; 95% CI, 1.08-1.92) and nodal involvement (HR = 1.44; 95% CI, 1.08-1.92).
The best threshold value for longer OS was 7 weeks (P = .043). Eight-year OS was 88% (95% CI, 85-90) among patients with a time to chemotherapy of less than 7 weeks and 78% (95% CI, 68-87) for patients with a time to chemotherapy of 7 or more weeks.
“Although it is probable that early initiation of adjuvant chemotherapy is not equally important for all patients, those with more aggressive diseases, such as rapidly proliferating tumors, may be worth treating as soon as possible, as confirmed by our results on DFS,” the researchers concluded. “We have found suggestions for a possible time limit and we are planning to confirm these data in a real world population.
“However, time is a continuous variable and we should always take into consideration that risk increases over time.” – by Anthony SanFilippo
Disclosure: The researchers report no relevant financial disclosures.
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