Breast cancer patients whose chemotherapy is initiated more than 60 days following surgery experience worse survival outcomes, and the impact of treatment delay is greatest among patients with stage III or triple-negative breast cancer and those whose HER2-positive tumors have been treated with trastuzumab, according to findings of a large, retrospective review of patient medical records conducted by researchers at the UT MD Anderson Cancer Center in Houston, Texas. ( [published online ahead of print January 27, 2014]. J Clin Oncol. doi:10.1200/JCO.2013.49.7693).
Most adjuvant breast cancer chemotherapy begins within a few weeks of surgery; however, previous research results differ on the impact longer time to chemotherapy (TTC) might have on survival. Treatment delays also have been reported to occur more frequently among lowincome groups, racial minorities, and Medicare patients.
To further investigate on the impact of TTC overall and on specific breast cancer subtypes, in particular, researchers analyzed the records of 6827 patients diagnosed with stage I-III invasive primary breast cancer who received treatment at the cancer center between 1997 and 2011, which, the authors noted, represents one of the largest single-institution cohorts to be evaluated for breast cancer outcomes associated with TTC. Most patients (84.3%) had stage I / II disease, and 15.5% stage had stage III disease.
Patient medical records were divided into three groups based on the number of days between completion of surgery and start of chemotherapy: ≤30 days (n = 2716), 31 to 60 days (n = 2994), and ≥61 days (n = 1117). Overall survival (OS), relapse-free survival (RFS), and distant relapse-free survival (DRFS) were assessed for the study population as a whole and also according to breast cancer subtype, with a median follow-up of 59.3 months.
Investigators applied multivariable models and adjusted for confounders to estimate 5-year OS, RFS, and DRFS for all patients based on TTC and other patient characteristics. They determined that when compared with patients who had adjuvant chemotherapy ≤30 days after surgery, patients whose TTC was ≥61 days postsurgery had a 19% increased risk of death (HR = 1.19; 95% CI, 1.02-1.38).
Although TTC was not significantly linked to outcome in patients with stage I disease, the risk of distant relapse was estimated to increase by 18% in stage II patients whose chemotherapy started 31-60 days after surgery, and by 20% in the ≥61 days cohort. For patients with stage III disease who started chemotherapy ≥61 days after surgery, the risk of death was increased by 76%, the risk of relapse by 34%, and the risk of distant relapse by 36%, when compared with patients whose TTC was ≤30 days.
The impact of TTC on survival and relapse also varied according to breast cancer subtype. Patients with hormone receptor (HR)-positive tumors receiving chemotherapy ≥61 days after surgery had a 29% increased risk of death (HR = 1.29; 95% CI, 1.02-1.64). HR-positive patients who received chemotherapy 31 to 60 days after surgery were estimated to have a 15% increased risk of relapse and a 18% increased risk of distant relapse compared with patients whose TTC was ≤30 days, the researchers reported.
The magnitude of risk was more pronounced when the researchers looked at the records of patients with triple-negative breast cancer (TNBC) and those who were HER2-positive and treated with trastuzumab.
Patients with TNBC who received chemotherapy either 31 to 60 days or ≥61 days after surgery had a 74% and 54% increased risk of death, respectively, compared with the ≤30 days group, but RFS and DRFS were not impacted by TTC in these patients.
For patients whose tumors were HER2-positive but not treated with trastuzumab (n = 551), outcomes were not adversely affected by longer TTC, but a statistically significant increase in death risk was observed in the trastuzumabtreated group (n = 591) when chemotherapy was initiated ≥61 days after surgery versus ≤30 days (HR = 3.09; 95% CI, 1.49-6.39). A trend toward worse RFS and DRFS was also reported for this group.
The researchers concluded that for patients with stage II and III breast cancer, those with TNBC, and those with HER2-positive tumors, “Every effort should be made to avoid postponing the initiation of adjuvant chemotherapy. This may lead to an improvement in outcomes for these subsets of patients.”
The study performed by de Melo Gagliato et al was a large retrospective study examining the association between the initiation of adjuvant chemotherapy and survival outcomes among different breast cancer subtypes and stage of diagnosis. The authors concluded that those with a more advanced breast cancer stage at diagnosis experienced worse outcomes with delayed initiation of adjuvant chemotherapy, specifically those with stage II or III breast cancers and those with triple-negative and HER2-positive subtypes.
This study brings to light not only the importance of initiating adjuvant chemotherapy in newly diagnosed breast cancer patients, but also the possible reasons surrounding the delay of treatment. Reasons for delay of chemotherapy may include personal, work, insurance, or even organizational issues. Personal reasons may include fear or anxiety of starting chemotherapy. For these individuals, referral to counseling services, chaplaincy, or a support group may be necessary in order to allay these emotions. Insurance barriers may be overcome with the assistance of financial counselors. Organizational barriers may include wait times before being able to see a medical oncologist. A nurse case manager may be of assistance to these individuals experiencing this type of delay.
After definitive surgery, a multidisciplinary effort would be an optimum approach to care in order to assist this population of patients’ smooth transition to a medical oncologist’s care so that adjuvant chemotherapy can be started as promptly as possible.