Study Attempts to Define Gains From Chemo for HR-Positive, HER2-Positive Breast Cancer

Compared with tumors smaller than 8 mm among patients with hormone receptor (HR)-positive, ERBB2-positive (formerly HER2-positive) breast cancer, tumors between 8 and 10 mm benefited more from postoperative chemotherapy, suggest study results recently published in JAMA Network Open.

Hormonal therapy also benefitted these patients, and together with chemotherapy, reduces their survival hazard by 47%.

Because the current National Comprehensive Cancer Network guideline does not provide concrete direction on treatments for smaller tumors (stage T1a and T1b), which have not been studied in depth in randomized trials, it recommends leaving “the consideration of chemotherapy for tumors 1 cm [10 mm] or smaller at the discretion of clinicians,” the authors wrote.

Women with these smaller tumors have a typical 5-year recurrence rate of 5% to 25%, with or without adjuvant therapy, they noted. Hoping to add to the guidance on optimal treatment options for smaller tumors in HR-positive, ERBB2-positive breast cancer, the team consulted the US National Cancer Database for cases diagnosed between 2010 and 2015. Treatment consisted of hormone therapy with or without chemotherapy.

They conducted an observational cohort study on the data they extracted, which they analyzed from November 2019 through January 2020. There were 10,065 patients in the overall population, of whom 5346 received chemotherapy and 4719 did not. Their median (interquartile range [IQR]) age was 59 (IQR, 51-67) years, and the median (IQR) follow-up was 41.8 (IQR, 24.3-62.6) months.

Overall, there was a 31% (hazard ratio [HR], 0.69; 95% CI, 0.52-0.90; P = .006) improvement in survival with chemotherapy. Broken down by tumor size, risk of death rose 7% (HR, 1.07; 95% CI, 1.03-1.12; P = .002) with each concordant 1-mm increase in tumor size.

Using Cox multivariable analysis on tumors between 2 and 9 mm, the authors determined that 8 mm was a statistically significant cutoff (P for interaction = .01). For tumors below that size, overall survival from chemotherapy did not improve (HR, 1.00; 95% CI, 0.70-1.43; P = .99); however, for tumors between 8 and 10 mm, it did (HR, 0.53; 95% CI, 0.36-0.78; P = .001).

The Kaplan-Meier method was also used for a matched-pair analysis between 1641 patients with tumors smaller than 8 mm and 648 patients with 8- to 10-mm tumors. The larger tumors were overwhelmingly shown to benefit from chemotherapy versus the smaller tumors:

• 8- to 10-mm tumors: HR, 0.48 (95% CI, 0.27-0.85; P = .01)
• Tumors smaller than 8 mm: HR, 0.88 (95% CI, 0.58-1.34; P = .55)

“To our knowledge, this is the first report to suggest that there is an association between improved survival and adjuvant chemoendocrine therapy specifically for HR-positive, ERBB2-positive tumors 8 mm to 10 mm compared with those smaller than 8 mm,” they concluded. “It is evident that tumors 10 mm and smaller represent a heterogeneous group whose treatment should be tailored to improve the risk-to-benefit ratio of systemic therapy.”

Reference

Ma SJ, Oladeru OT, Singh AK. Association of survival With chemoendocrine therapy in women with small, hormone receptor—positive, ERBB2-positive, node-negative breast cancer. JAMA Netw Open. 2020;3(4):e202507. doi:10.1001/jamanetworkopen.2020.2507