Different Strategies May Be Necessary for Single Hormone Receptor-Positive Breast Cancer

Statistically significant distinctions between survival rates of patients with single hormone receptor-positive breast cancer (BC) versus double hormone receptor-positive/double hormone receptor-negative BC were observed in this study published in JAMA Network Open.¹

These results suggest that different approaches might be necessary for patients with single hormone-receptor positive tumors to guarantee optimal treatment and maximum benefits from therapies. 

“This study represents the largest analysis to date, to our knowledge, focusing on single hormone receptor-positive BC,” the authors wrote. “We provide novel insights in the epidemiology of single hormone receptor-positive subtypes.” 

Using the SEER database, 823,399 patients with breast cancer (818,002 women and 5,397 men) diagnosed between 1990 and 2015 were identified. The percentages of estrogen receptor (ER)-positive/progesterone receptor (PR)-positive, ER-positive/PR-negative, ER-negative/PR-positive, and ER-negative/PR-negative cases were 67.2%, 12.2%, 1.6% and 19.0%, respectively. Single hormone receptor-positive subtypes showed distinct clinical characteristics when compared with double hormone receptor-positive/double hormone receptor-negative subtypes.

Multivariable Cox proportional hazards regression analysis indicated that patients with ER-positive/PR-negative (hazard ratio [HR], 1.36; 95% CI, 1.34-1.38) and ER-negative/PR-positive (HR, 1.61; 95% CI, 1.55-1.67) tumors had worse BC-specific survival (BCSS) than patients with the ER-positive/PR-positive subtype. Comparatively, patients with ER-positive/PR-negative (HR, 1.27; 95% CI, 1.24-1.29) and ER-negative/PR-positive (HR, 1.07; 95% CI, 1.03-1.11) tumors had better BCSS than those with the ER-negative/PR-negative subtype. The BCSS was statistically significantly worse in individuals with ER-negative/PR-positive tumors than in those with ER-positive/PR-negative tumors (HR, 1.18; 95% CI, 1.14-1.23).

“We propose 2 possible reasons for these changes. The incidence of the 4 subtypes may have changed over time,” the authors wrote. “Alternatively, tumors that might be detected as ER-negative and/or PR-negative may have subsequently been classified as ER-positive and/or PR positive with the development of immunohistochemical techniques.” 

ER-positive/PR-negative tumors are more common in older and postmenopausal women, and this was indicated in the present study as well; ER-positive/PR-negative tumors were most frequent in patients 60 years or older, whereas ER-negative/PR-positive tumors were most frequent in those aged 30 to 49 years. However, researchers also found statistically significant differences in sex and race among the 4 subtypes, a finding which has not been previously reported.

Furthermore, the researchers suggested that their findings indicate that adjuvant endocrine therapy should be limited to hormone receptor-positive BC, based on evidence that demonstrated that additional hormone therapy is not beneficial in patients with the ER-negative/PR-negative subtype. However, the value of single hormone receptor-positive for assessing the benefit from endocrine therapy remains unknown. Results from this study, in addition to prior assessments, suggests that the combination of endocrine therapy and chemotherapy may be a rational treatment for ER-negative/PR-positive disease. 

In an editorial written by Vasily Giannakeas, MPH, a research analyst at ICES Ontario, Giannakeas noted there is a chance that misclassification occurred in determining hormone receptor status in this study cohort.² She indicated that the idea that the ER-negative/PR-positive subtype is a real category is challenged by the decline in proportions from 4.5% to 1.0% from 1990 to 2016.

“When there is a gray zone, there is bound to be misclassification,” Giannakeas wrote. “In the case of hormone receptor status, technologies and protein expression cutoff values varied during the study period (1990-2015).”

The editorial author also suggested that it will remain a challenge to personalize treatments for patients with ER-negative/PR-cancer, given that this subtype only currently constitutes about 1% of all breast cancers. 

References:

1. Li Y, Yan D, Yin X, et al. Clinicopathological Characteristics and Breast Cancer-Specific Survival of Patients With Single Hormone Receptor-Positive Breast Cancer. JAMA Network Open. doi:10.1001/jamanetworkopen.2019.18160.

2. Giannakeas V. Single Hormone Receptor-Positive Breast Cancer – Signal or Noise? JAMA Network Open. doi:10.1001/jamanetworkopen.2019.18176.