Survival and Time to Surgery, Chemotherapy for Patients with Breast Cancer

The association between survival and the time to surgery and chemotherapy for patients with breast cancer is examined in two original investigations published by JAMA Oncology, along with a related editorial and an audio interview with the authors.1
In the first study, Mariana Chavez-MacGregor, M.D., M.Sc., of the University of Texas MD Anderson Cancer Center, Houston, and coauthors, analyzed data from 24,843 patients with invasive breast cancer (stages I to III) from the California Cancer Registry to examine the relationship between time to chemotherapy after surgery and overall survival and breast cancer-specific survival. The authors also identified factors associated with a delayed start of chemotherapy.
The median age of the 24,843 patients at diagnosis was 53 and the median time to chemotherapy was 46 days. In the study, 21 percent of patients started chemotherapy within fewer than 31 days; 50 percent between 31 and 60 days after surgery; 19.2 percent between 61 and 90 days; 9.8 percent in 91 or more days after surgery.
The factors associated with delays in time to chemotherapy included low socioeconomic status, breast reconstruction, nonprivate insurance, and being Hispanic or black, according to the study.
Compared with patients who received chemotherapy within 31 days of surgery, the study reports no adverse outcomes were associated with time to chemotherapy of 31 to 90 days of surgery.
However, there was increased risk of worse overall survival and worse breast cancer-specific survival among patients treated with chemotherapy 91 or more days after surgery, the results indicate. The study suggests patients with a time to chemotherapy of 91 or more days had a 34 percent increased risk of overall death and a 27 percent increased risk of death from breast cancer.
For patients with triple-negative breast cancer, 91 or more days to chemotherapy was associated with worse overall and breast cancer-specific survival, according to the study.
The authors note their study is limited by its retrospective nature, which uses historical data.
“Given the results of our analysis, we would suggest that all breast cancer patients that are candidates for adjuvant chemotherapy should receive this treatment within 91 days of surgery or 120 days from diagnosis. Administration of chemotherapy within this frame is feasible in clinical practice under most clinical scenarios, and as medical oncologists, we should make every effort not to delay the initiation of adjuvant chemotherapy. Furthermore, determinants of delay in TTC [time to chemotherapy] were sociodemographic in nature; better understanding and removing barriers to access of care in vulnerable populations should be a priority,” the study concludes.
In a second study, Richard J. Bleicher, M.D., of the Fox Chase Cancer Center, Philadelphia, and coauthors looked at the relationship between the time from diagnosis to breast cancer surgery and survival. The authors analyzed patient data from two of the largest cancer databases in the United States. Analysis between the two databases was not done, or warranted, so the authors present both analyses.
Data were analyzed for 95,544 patients (mostly women, average age 75) in the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Of the patients, 77.7 percent had surgery in 30 days or less; 18.3 percent in 31 to 60 days; 2.7 percent in 61 to 90 days; 0.7 percent in 91 to 120 days; and 0.5 percent in 121 to 180 days. The increase in death in all stages of disease for all patients and from all causes was 9 percent for each preoperative time interval increase. While overall survival was lower with each interval of delay increase, the decline was most pronounced in patients with stage I and stage II disease. The risk of death from breast cancer for each 60-day increase in time to surgery was significant for stage I disease, according to the results.
Data also were analyzed for 115,790 patients (nearly all women, average age 60) in the National Cancer Database. Of the patients, 69.5 percent of patients had surgery in 30 days or less; 24.9 percent in 31 to 60 days; 4.1 percent in 61 to 90 days; 1 percent in 91 to 120 days; and 0.5 percent in 121 to 180 days. The added risk of death from all causes for each interval increase in time to surgery was 10 percent for the entire group, and most pronounced for stage I and stage II disease.
The authors acknowledge unmeasured confounders may exist in their study.
“In conclusion, survival outcomes in early-stage breast cancer are affected by the length of the interval between diagnosis and surgery, and efforts to minimize that interval are appropriate. Although the effect on both overall and disease-specific survival remains small, consideration should be given to establishing reasonable and attainable goals for the timing of surgical interventions to afford this population a finite, but clinically relevant, survival benefit,” the study concludes.
“The articles published in this issue of JAMA Oncology increase our confidence that avoiding delays in breast cancer care is important to ensuring the best possible outcomes for our patients. … Few people like standing in line at the supermarket; if retailers can make efforts to minimize customer wait times, so we, too, can make sure that patients are seen and treated as promptly as possible,” write Eric P. Winer, M.D., of the Dana-Farber Cancer Institute, Boston, and coauthors in a related editorial2.
1. JAMA Oncol. Published online December 10, 2015. doi:10.1001/jamaoncol.2015.4508. 
2. JAMA Oncol. Published online December 10, 2015. doi:10.1001/jamaoncol.2015.4506.