Abstract
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. 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. 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. 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. 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]). 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.
Highlights
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancerrelated death for women in the United States
Age 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 overall survival (OS) and recurrence-free survival (RFS), respectively, in untreated patients. 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
Tumor size (AHR for OS, 2.76 [95% CI, 1.79-4.31; P < .005]; Adjusted hazard ratio (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])
Summary
Current guidelines by the National Comprehensive Cancer Network and American Society of Clinical Oncology recommend management with endocrine therapy, ERBB2- (formerly HER2-) (OMIM 164870) directed therapy, radiotherapy, and cytotoxic chemotherapy or a combination for patients with invasive breast cancer.[1] The choice of treatment modality depends on patient and tumor characteristics, expression of hormone receptors (HR; including estrogen receptor α [ER] or progesterone receptor [PR]), and ERBB2 status as well as genomic test results such as the Oncotype DX breast recurrence score.[2] Endocrine therapy with a duration of 5 to 10 years is a standard of care for HR-positive disease, which accounts for approximately 70% of all breast cancers.[3,4,5] Radiotherapy applies to all individuals who underwent breast-conserving surgery and may be used for patients with a tumor larger than 5 cm or with node-positive disease after mastectomy. Chemotherapy is recommended for patients with ERBB2-positive and HR-negative tumors, node-positive disease, and high Oncotype recurrence scores in HR-positive and ERBB2-negative breast cancer.[3,6]
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