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    Original Investigation
    July 9, 2020

    Association of Independent Prognostic Factors and Treatment Modality With Survival and Recurrence Outcomes in Breast Cancer

    Author Affiliations
    • 1National Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland
    • 2DSC, Inc, Reston, Virginia
    • 3currently affiliated with Bellese Technologies, LLC, Owings Mills, Maryland
    • 4Laboratory of Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland
    JAMA Netw Open. 2020;3(7):e207213. doi:10.1001/jamanetworkopen.2020.7213
    Key Points español 中文 (chinese)

    Question  Is the performance of clinical and molecular factors associated with distinct treatment and clinical outcome types in breast cancer?

    Findings  This prognostic study of 956 women with breast cancer analyzed overall and recurrence-free survival in patients undergoing homogeneous therapies and found a complete and partial deviation in the identification of independent prognostic factors from outcomes of untreated patients. Independent prognostic factors were differential in the context of endocrine therapy and largely concordant for radiotherapy and chemotherapy (but partly divergent from nontherapy) between survival and recurrence outcomes.

    Meaning  Performance of the independent clinical and molecular factors was weighted by treatment modality and the nature of clinical end points.


    Importance  It is not well understood whether prognostic factors in breast cancer are affected by specific treatment and vary by clinical outcome type compared with untreated patients.

    Objective  To identify independent clinical and molecular measurements associated with overall survival (OS) and recurrence-free survival (RFS) by homogeneous treatment in women with breast cancer.

    Design, Setting, and Participants  This prognostic study included 956 patients diagnosed with invasive breast cancer from hospital centers across 4 geographical regions of the United States who participated in the accreditation program of the Commission on Cancer of the American College of Surgeons from 1985 to 1997. The duration of follow-up ranged from 1 to 282 months. The study analysis was conducted from June 10, 2019, to March 18, 2020.

    Main Outcomes and Measures  Analysis of OS and RFS in patients who underwent chemotherapy, radiotherapy, or endocrine therapy alone compared with no systemic or locoregional therapy. Cox proportional hazards regression models were used to estimate independent performance and 95% CI of age, tumor size, number of positive nodes (nodal status), tumor grades 2 and 3, p53 status, estrogen receptor (ER) status, and ERBB2 (formerly HER2) status.

    Results  Among 956 participants, median age was 61 (range, 25-96) years. 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. p53 status (AHR, 2.11; 95% CI, 1.07-4.18; P = .03) and 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. 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]).

    Conclusions and Relevance  In this study, independent prognostic factors were associated with specific treatment and weighted by the outcome category with reference to untreated patients within biological and clinical contexts.