Radiation Therapy Omission Not Advised in Early-Stage HER2+ Breast Cancer

A recent study showed that patients with stage I (T1N0) HER2-positive breast cancer who were treated without radiation therapy had a greater than 3-fold increased risk of death versus those who did, lending caution to strategies that omit radiotherapy in this setting.

At a median follow-up of 29.4 months, the overall survival rate at 2 years in the group receiving radiotherapy was 99.2% versus 88.9% in those who did not (P <.0001).

“We found that radiation omission is independently associated with an increased risk of death in patients with T1N0 HER2[-positive breast cancer] treated with lumpectomy, adjuvant chemotherapy, and anti-HER2 therapy,” wrote the study authors, who were led by Jose G. Bazan, MD. “While other selection biases that influence radiation omission likely persist, including the possibility that patients in this cohort were not compliant with systemic therapy, these data should give caution to radiation omission in T1N0 HER2[-positive breast cancer].

The data from a retrospective review of radiation omission in HER2-positive tumors using the National Cancer Database (NCDB) was performed in patients treated with lumpectomy and adjuvant therapy that included trastuzumab (Herceptin). Patients receiving neoadjuvant therapy were excluded.

In total, 6897 patients were identified, of whom 6388 received radiation therapy and 509 did not. Those who were not treated with radiation tended to be 70 years of age or older (odds ratio [OR], 3.69; 95% CI, 3.02-4.51; P <.0001), have 1 or more comorbidities (OR, 1.33; 95% CI, 1.06-1.68; P = .0154), to be Hispanic (OR, 1.49; 95% CI, 1.00-2.22; P = .049), and to live in lower income areas (OR, 1.32; 95% CI, 1.07-1.64; P = .0266). Reasons that patients did not receive radiation included treatment refusal (n = 254), it was not part of the treatment plan (n = 234), and it was contraindicated (n = 21).

Omission of radiotherapy was associated with a 3.67-fold (95% CI, 2.23-6.02; P <.0001) increased risk of death versus receipt of radiation. By multivariate analysis, patients with estrogen receptor- and progesterone receptor–negative status had a 4.2-fold increased risk of death when radiotherapy was omitted (P = .0003). In those with hormone-sensitive disease, the risk was increased 5.7-fold (P <.0001).

“Patients with hormone-sensitive disease who did receive endocrine therapy and patients with ER-/PR-[negative] disease were associated with better survival outcomes,” wrote the investigators. “While de-escalation of radiation therapy would not be considered in T1N0 ER−/PR−/HER2+ disease, the more biologically favorable group of patients with T1N0 hormone-sensitive HER2+ disease that are committed to taking endocrine therapy represents a population in which radiation de-escalation may be considered.”

By propensity-score matching, 504 of the patient set were identified who had well-balanced baseline covariates by a standard difference of <0.10. With a median follow-up of 26.5 months, the 2-year rates of OS were 97.1% with radiation versus 88.9% without (HR, 3.67; 95% CI, 2.23-6.02; P <.0001).

There were several limitations to the study, including those innate to the National Cancer Database, such as the absence of data on loco-regional recurrence and other cancer-specific survival. Lack of these details makes it unclear if increased mortality was associated with factors like recurrent disease, noncompliance, toxicities, or other comorbid aspects.

Reference

Bazan JG, Jhawar SR, Stover D, et al. De-escalation of radiation therapy in patients with stage I, node-negative, HER2-positive breast cancer. NPJ Breast Cancer. 2021;7(1):33. doi: 10.1038/s41523-021-00242-8