Analysis Reveals Ideal Time Period to Begin Adjuvant Chemotherapy for HER2-Positive Breast Cancer

An analysis conducted using the National Cancer Database (NCDB) found that 31 to 60 days appears to be an ideal time period to begin adjuvant chemotherapy in HER2-positive breast cancer patients.

The findings were presented at the 37th Annual Miami Breast Cancer Conference, held from March 5-8, 2020 in Miami, Florida. 

“So, there are a lot of studies which have actually looked into the ideal timeframe of starting adjuvant chemotherapy after surgery, but still the results remain inconclusive. In clinical practice, chemotherapy is usually started 4-6 weeks after surgery, but we do not have a definite set point at which chemotherapy needs to be started,” said Prashanth Ashok Kumar, MD, MBBS. 

Researchers selected patients aged older than 18 years with stage I-III, HER2-positive breast cancer who received adjuvant chemotherapy from the NCDB database. Those receiving neoadjuvant therapy were excluded from the study. Overall, 80,901 patients met the inclusion criteria for the study; 57,380 HER2-positive, ER-positive, and/or PR-positive patients and 23,521 HER2-positive, ER-negative, PR-negative patients. The participants were then divided into 5 groups based on the time elapsed from the date of primary surgery to the start of adjuvant chemotherapy (≤30, 31-60, 61-90, 91-120, and >120 days). 

Though several HR comparisons within the subgroups were not found to be significant, the 31-60 days group appeared to have a better outcome within both subgroups. In the HER2-positive, ER-positive, and/or PR-positive 31-60 days group, the hazard ratio was 85.4%, 81.1%, 68% and 56.2% of the ≤30, 61-90, 91-120, and >120 days groups, respectively. In the HER2-positive, ER-negative, PR-negative 31-60 days group, the hazard ratio was 84%, 77.1%, 72.1% of the ≤30, 61-90, and >120 days groups, respectively. 

“We were actually expecting the ≤30 days group to have the best outcome, because we’ve established that starting chemotherapy earlier is always better, so this was a little bit surprising for us,” said Kumar. 

No major differences were observed in relation to the effect of delayed adjuvant chemotherapy on the two HER2 subgroups, despite the known variability in response to treatment in clinical practice. 

Additionally, the analysis indicated that those in the ≤30 days groups did worse than the 31-60 days group. Furthermore, the researchers suggested that starting adjuvant chemotherapy after ≤30 days might lead to patients not tolerating the treatment well, whereas delaying beyond 60 days could lead to poor outcomes secondary to reasons like rapid growth of micro metastasis following surgery. 

“Starting it too early, patients may not tolerate well because they are just recovering from surgery, whereas starting it too late, the cancer gets ahead of us and the survival benefit may not be as much,” Kumar explained. 

The authors noted that the results are from non-population based observational data, and therefore may be subject to confounding which is not always adjusted by the multivariate model. 

Kumar also indicated that they have begun similar analysis in other types of breast cancer, such as triple negative hormone positive breast cancer, though these analyses could eventually lead to studies being conducted in the neoadjuvant chemotherapy setting. 

Reference:

Kumar PA, Wang D, Huang D, Sivapiragasam A. Does Time to Initiate Adjuvant Chemotherapy affect outcome in HER2 positive Breast Cancer Patients, A National Cancer Database Analysis. Presented at the 37th Annual Miami Breast Cancer Conference held from May 5-8, 2020 in Miami, Florida. Poster 60.