Pinpointing Independent Prognostic Factors Related to Treatment Modality in Breast Cancer

August 22, 2020
Hannah Slater

Researchers indicated that these study findings could set a basis to pinpoint independent prognostic factors related to a treatment modality in patients with breast cancer and provide clarity for the assessment of surrogate markers for overall survival.

In a study published in JAMA Network Open, prognostic factors were correlated with specific treatment and weighted by the outcome category with regard to untreated patients within biological and clinical circumstances.

Given this finding, researchers indicated that clinical and molecular measurements in the context of treatment should be viewed as the treatment-associated prognostic factors for overall survival (OS) as well as recurrence-free survival (RFS).

“We anticipate that the knowledge derived from this study could set a basis to pinpoint independent prognostic factors related to a treatment modality and provide clarity for the evaluation of surrogate markers for OS,” the authors wrote.

The prognostic study assessed 956 patients diagnosed with invasive breast cancer from hospital centers across 4 different regions of the US who participated in the accreditation program of the Commission on Cancer of the American College of Surgeons from 1985 to 1997. The primary outcome was analysis of OS and RFS in patients who underwent chemotherapy, radiotherapy, or endocrine therapy alone compared with those who received no systemic or locoregional therapy.

Of the total cohort, age (adjusted hazard ratio [AHR], 2.24; 95% CI, 1.27-3.94; P = .01) and high grade (AHR, 2.05; 95% CI, 1.09-3.86; P = .02), in addition to nodal status and tumor size, were independently associated with OS and RFS, respectively, in untreated patients. Moreover, p53 status (AHR, 2.11; 95% CI, 1.07-4.18; P = .03) and estrogen receptor (ER) status (AHR, 0.46; 95% CI, 0.23-0.92; P = .03) were associated with higher and lower risks of death, respectively, whereas nodal status (AHR, 1.13; 95% CI, 1.06-1.20; P < .005), high grade (AHR, 4.01; 95% CI, 1.51-10.70; P = .01), and ERBB2 positivity (AHR, 2.67; 95%CI, 1.25-5.70; P = .01) were associated with the risk of recurrence after endocrine therapy.

“The data indicate that the role of ER in favorable prognosis was largely ascribed to the endocrine therapy, relative to other types of treatment and nontherapy,” the authors wrote.

Even further, tumor size (AHR for OS, 2.76 [95% CI, 1.79-4.31; P < .005]; AHR for RFS, 2.27 [95% CI, 1.23-4.18; P = .01]) and ERBB2 status (AHR for OS, 5.35 [95% CI, 1.31-21.98; P = .02]; AHR for RFS, 6.05 [95% CI, 1.48-24.78; P = .01]) were independently associated with radiotherapy outcomes, and nodal status was significantly associated with chemotherapy outcomes (AHR for OS, 1.06 [95% CI, 1.02-1.09; P < .005]; AHR for RFS, 1.05 [95% CI, 1.01-1.09; P = .01]).

“Significantly, the number of positive nodes had the greatest value among the molecular and clinical measurements after chemotherapy and was an independent prognostic factor for OS and RFS in the Cox multivariable proportional hazards regression models,” the authors wrote. “Age, larger tumor size, and ERBB2 positivity demonstrated nonsignificant trends toward poor chemotherapy outcomes. The data were in agreement with other chemotherapy data.”

Notably, there was a lack of randomization in this study. However, the researchers indicated that current guidelines do not allow a group without treatment, except node-negative breast tumor that is 0.5 cm or smaller, and/or homogeneous therapy in patients with certain patient and tumor characteristics.

“These findings shed light on the precision assessment of clinical prognostic tools in the management of breast cancer and perhaps in other diseases,” the authors concluded.


Nguyen D, Yu J, Reinhold WC, Yang SX. Association of Independent Prognostic Factors and Treatment Modality With Survival and Recurrence Outcomes in Breast Cancer. JAMA Network Open. doi: 10.1001/jamanetworkopen.2020.7213