Adjuvant Endocrine Therapy Boosts Survival in Small, HR+, ERBB2- Breast Cancer

Anurag Singh, MD

Adjuvant endocrine therapy was found to be associated with improved overall survival (OS) in patients with hormone receptor (HR)–positive, ERBB2-negative (previously HER2 or HER2/neu), node-negative breast cancer with small but invasive tumors, according to results from a large cohort study published in JAMA Network Open.¹

Results showed that on Cox multivariable analysis, patients who received adjuvant endocrine therapy experienced an improvement in OS (HR, 0.69; 95% CI, 0.63-0.76; P < .001). In 7,544 matched pairs, a comparable improvement in OS was reported (HR, 0.76; 95% CI, 0.66-0.88; P < .001). Moreover, no statistically significant interaction between endocrine therapy and baseline characteristics like age, comorbidity score, or tumor grade were reported.

Following the exclusion of 1659 patients (3.9%) who had a survival of less than 6 months, adjuvant endocrine treatment was still found to be associated with OS improvement (HR, 0.74; 95% CI, 0.67-0.81; P< .001).

“To our knowledge, this is the largest cohort study to evaluate the OS outcome of endocrine therapy for pT1aN0 breast cancer using a national registry database,” wrote the authors of the study. “The survival benefit identified in our study supports the National Comprehensive Cancer Network (NCCN)’s recommendation of adjuvant endocrine therapy in this cohort and is consistent with favorable outcomes previously described.”

Although small, invasive tumors measuring less than 1 cm are found in approximately 1 of 5 breast cancer cases, HR-positive, ERBB2-negative, node-negative breast cancer, pT1a tumors has previously been underrepresented in prospective trials, according to the study authors. As no strong prospective evidence is available, the NCCN advises that adjuvant endocrine therapy be considered for patients with pT1aNO disease without the routine use of a multigene assay.

For the cohort study, investigators set out to evaluate the association between OS and endocrine therapy in this specific patient population. Using the National Cancer Database, investigators examined data from 42,708 patients who were diagnosed with HR-positive, ERBB2-negative, small, T1a breast tumors between January 2010 and December 2015.

The majority, or 86.6%, of those evaluated were white with a median age of 63 years. Of those who met the criteria for inclusion in the analysis, 73.8% of patients (n = 31,509) had received endocrine therapy, while 26.2% (n = 11,199) had not. Follow-up was done until December 2016, and then the analysis was conducted between January 2020 and March 2020.

The primary end point of the trial was OS. Investigators utilized the Kaplan-Meier method, conducted a Cox multivariable analysis, and an interaction analysis to examine survival outcomes in these patients. On Cox multivariable analysis, investigators adjusted for facility type, facility volume, age, race, income, insurance, Charlson-Deyo comorbidity score, year of diagnosis, surgery, radiation, number of lymph nodes examined, and hospital readmission.

Additional results showed that of a total of 11,199 patients who received treatment without endocrine therapy, 31.2% (n = 3,492) who were recommended therapy by a clinician refused treatment. Comparable data were reported with regard to those who refused treatment, favoring endocrine treatment (HR, 0.80; 95% CI, 0.69-0.94; P = .007).

Moreover, the significant risk of relapse from these tumors supports the use of hormone therapy in combination with radiation, according to the study authors, as hormone therapy was not found to have a negative impact on any other therapy that the patient was receiving at the same time.

“Those patients who may benefit from hormone therapy should be given clear information about this possible course of treatment and about its potential long-term toxicities,” Anurag Singh, MD, a professor of oncology; director of Radiation Research, Department of Radiation Medicine; and co-leader of the Cell Stress Biophysical Therapy Program, of Roswell Park Comprehensive Cancer Center, added in a press release.² The [adverse] effects of endocrine treatments can impact quality of life significantly, sometimes for several years, so they’re not the right option for everyone.”

Results from this study further build on recent data published by the same team in August 2020, which utilized a de-identified large national cancer registry the examine the link between survival and endocrine therapy. Again, results illustrated an association with improved OS following treatment and adjuvant endocrine therapy (HR, 0.81; 95% CI, 0.67‐0.98; P = 0.03) in patients who had been diagnosed with HR‐positive, HER2‐negative, pT1‐2N0, non–high‐grade breast cancer.³

Limitations of the study included unavailable variables like performance status, toxicity profiles, and tumor recurrences; these variables could have potentially resulted in unmeasured confounding even with matching, according to the study authors. However, the risk of relapse from these tumors supports the use of adjuvant treatment in this patient population, they concluded.

References

1. Ma SJ, Oladeru OT, Singh AK, et al. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3(8):e2013973. doi:10.1001/jamanetworkopen.2020.13973
2. New study suggests role for hormone therapy to treat even small, T1a breast cancers. News release. Roswell Park Comprehensive Cancer Center. August 24, 2020. Accessed August 25, 2020. https://bit.ly/3lpIrZk
3. Oladeru OT, Singh AK, Ma SJ. Association of endocrine therapy with overall survival in women with hormone receptor‐positive, HER2‐negative, node‐negative breast cancer of favorable histology. The Breast Journal. 2020;00:1-5. doi:10.1111/tbj.13995