Abstract
PurposeA center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients.Patients and methodsLuminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status.ResultsAmong 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P=0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P<0.05). Compared to non-overweight patients, obese ones presented significantly higher ER, PR, CEGP1, Ki67, CCNB1 and GSTM1 (all P<0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P=0.001). RS was associated with DFS in non-overweight (P=0.046), but not in overweight (P=0.558) or obese (P=0.114) population.ConclusionsRS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.
Highlights
Breast cancer is the most frequent malignancy reported in women worldwide [1]
Baseline Characteristics Stratified by Body Mass Index Status
1876 Luminal-like breast cancer patients were enrolled in the current study (Supplementary Figure S1)
Summary
Breast cancer is the most frequent malignancy reported in women worldwide [1]. About 70% of breast cancer patients are of Luminal-like, human epidermal growth factor 2 (HER2)negative subtype, which is characterized by the expression of hormone receptor (HR), and the absence of HER2 amplification [2]. In addition to traditional tumor anatomic, biologic features, genetic factors have been integrated to guide treatment decisions as well as predict disease outcomes in these patients. The Oncotype Dx is the most common multigene panel to predict chemotherapy benefit and prognosis for HR-positive, HER2-negative, node-negative patients, based on the findings of the prospective TAILORx trial [3, 4]. Our RS panel has previously been validated in both node-negative [5] and node-positive [6] patients with two large cohorts of Chinese patients. Increased RS was associated with poor differentiation, PR-negative or highproliferation characteristics in Chinese early breast cancer patients, as indicated in our former work [5], which was comparable to the findings for Oncotype Dx in NSABP B-14 study population [4]. With the help of RS testing, selective low RS patients can be spared from adjuvant chemotherapy, while chemotherapy is recommended for high RS patients
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