Does Time to Initiate Adjuvant Chemotherapy Affect Outcomes in HER2-Positive Breast Cancer?

Among patients with HER2-positive breast cancer, initiating adjuvant chemotherapy between 31 and 60 days from the date of surgery seems to be the ideal window, according to an analysis of a large national database, presented as a poster at the 37th Annual Miami Breast Cancer Conference.

HER2-positive breast cancer comprises approximately 20% to 30% of all breast cancer cases. Despite it being an aggressive subtype of breast cancer, survival has improved with the use of anti-HER2 agents and adjuvant chemotherapy. Studies show that the influence of delayed initiation of chemotherapy on breast cancer survival is subtype-dependent. The Centers for Medicare & Medicaid Services considers the initiation of systemic chemotherapy within 120 days to be a quality metric for patients aged <70 years with stage I-III estrogen receptor (ER)-negative and progesterone receptor (PR)-negative breast cancer. Prashanth Ashok Kumar, MBBS, Internal Medicine Resident, SUNY Upstate Medical University, Syracuse, NY, and colleagues aimed to study the effect of time to starting adjuvant chemotherapy from the date of surgery in patients with HER2-positive breast cancer. They analyzed thousands of patient records from the National Cancer Database between 2010 and 2016.

“We used the database to define a timeframe at which starting chemotherapy would be beneficial,” said Dr Kumar.

The researchers included patients aged ≥18 years with stage I-III HER2-positive breast cancer and adjuvant chemotherapy use after surgery; patients who had received neoadjuvant chemotherapy were excluded from the analysis. Approximately 80,000 patients met the inclusion criteria, and patients were further divided into 2 subgroups: HER2-positive and hormone receptor–positive (HER2-positive, ER-positive, and/or PR-positive; N = 57,380) and HER2-positive, hormone receptor–negative (HER2-positive, ER-negative, and/or PR-negative; N = 23,521).

Patients were then further divided into 5 subgroups according to the number of days elapsed between the date of surgery and initiation of chemotherapy: ≤30 days; 31-60 days; 61-90 days; 91-120 days; and >120 days.

“The most important part is the adjusted hazard ratios [HRs], the hazard being death,” Dr Kumar explained. “And head-to-head comparisons of each of these subgroups showed that the 31- to 60-day group had a better HR than all of the other groups.”

No major difference was noted regarding the effect of delayed chemotherapy on the 2 HER2-positive subgroups, despite the known variability in response to treatment in clinical practice, the investigators reported.

For HER2-positive, ER-positive, and PR-positive patients initiating chemotherapy between 31 and 60 days postsurgery, the adjusted HRs were 0.854 (vs ≤30 days), 0.81 (vs 61-90 days), 0.68 (vs 91-120 days), and 0.562 (vs >120 days). In the same subgroup, patients in the ≤30-day and 61- to 90-day groups had better outcomes compared with >120 days.

For HER2-positive hormone receptor–negative patients initiating chemotherapy between 31 and 60 days postsurgery, the adjusted HRs were 0.84 (vs ≤30 days), 0.771 (vs 61-90 days), and 0.721 (vs >120 days). Comparison between the 31- to 60-day group and the 91- to 120-day group was not significant.

Surprisingly, the study team found that patients who initiated chemotherapy <30 days after surgery did worse than the 31- to 60-day group. According to the researchers, adjuvant chemotherapy sooner than 30 days after surgery may be poorly tolerated by patients still recovering from surgery, whereas delaying beyond 60 days may lead to poor outcomes secondary to reasons like rapid growth of micrometastasis following surgery.

“We were anticipating the ≤30 days group to have the best outcome, because usually the earlier you start chemotherapy the better, so that was a little bit surprising,” said Dr Kumar. “What we can conclude is that 31 to 60 days might be considered an ideal time frame for starting adjuvant chemotherapy in HER2-positive stage I-III breast cancer.”

He noted that these results are from nonpopulation-based observational data and may be subject to confounding, so prospective studies are needed.

 

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