Clinicopathological characteristics and adjuvant treatment
A total of 2875 luminal breast cancer patients were included (Fig. 1). Clinicopathological characteristics and adjuvant treatments according to BMI groups were listed in Tables 1 and 2. The mean age of the study population was 56.41 ± 12.71 years old and 66.6% of patients were aged ≥ 50 years old. There were 919 (32.0%) patients with at least one comorbidity. Only 7.6% of patients had lymphovascular invasion. A total of 1851 (64.4%) patients had tumors ≤ 2.0 cm. Exactly 1882 (65.5%) patients presented with node negative disease. There were 1743 (60.6%) and 665 (23.1%) with grade I-II and III tumors, respectively, leaving the remaining 467 (16.2%) patients histologic grade unknown. Invasive ductal carcinoma (IDC) was diagnosed in 2407 (83.7%) patients. The proportions of patients with ER ≥ 50%, PR-positive, and Ki‑67 ≥ 14% were 91.5%, 85.2%, and 54.4% respectively. Moreover, 926 (32.2%), and 1949 (67.8%) patients had luminal A, and luminal B/HER2-negative tumors. The clinicopathological features by luminal subtype was presented in Supplementary Table S1.
Table 1
Distribution of clinicopathological characteristics in the whole population and different BMI groups
Characteristics | Whole population (N = 2875) N (%) | BMI < 28 kg/m2 (N = 2598) N (%) | BMI ≥ 28 kg/m2 (N = 277) N (%) | P value |
Age at diagnosis (year), mean ± SD | 56.41 ± 12.71 | 55.85 ± 12.72 | 61.57 ± 11.46 | < 0.001 |
Age at diagnosis (year) | | | | |
< 50 | 961 (33.4) | 917 (35.3) | 44 (15.9) | < 0.001 |
≥ 50 | 1914 (66.6) | 1681 (64.7) | 233 (84.1) | |
Menopausal status | | | | < 0.001 |
Pre/peri-menopausal | 1109 (38.6) | 1051 (40.5) | 58 (20.9) | |
Post-menopausal | 1766 (61.4) | 1547 (59.5) | 219 (79.1) | |
Comorbidities | | | | < 0.001 |
None | 1956 (68.0) | 1844 (71.0) | 112 (40.4) | |
≥ 1 | 919 (32.0) | 754 (29.0) | 165 (59.6) | |
Lymphovascular invasion | | | | 0.811 |
Negative | 2657 (92.4) | 2400 (92.4) | 257 (92.8) | |
Positive | 218 (7.6) | 198 (7.6) | 20 (7.2) | |
Pathologic tumor size | | | | 0.172 |
≤ 2cm | 1851 (64.4) | 1683 (64.8) | 168 (60.6) | |
> 2cm | 1024 (35.6) | 915 (35.2) | 109 (39.4) | |
Pathologic nodal status | | | | 0.756 |
Negative | 1882 (65.5) | 1696 (65.3) | 186 (67.1) | |
Positive | 967 (33.6) | 879 (33.8) | 88 (31.8) | |
Unknown | 26 (0.9) | 23 (0.9) | 3 (1.1) | |
Histological grade | | | | 0.465 |
I-II | 1743 (60.6) | 1568 (60.4) | 175 (63.2) | |
III | 665 (23.1) | 601 (23.1) | 64 (23.1) | |
Unknown | 467 (16.2) | 429 (16.5) | 38(13.7) | |
Histopathological type | | | | 0.297 |
Non-IDC | 468 (16.3) | 429 (16.5) | 39 (14.1) | |
IDC | 2407 (83.7) | 2169 (83.5) | 238 (85.9) | |
ER expression | | | | 0.005 |
< 50% | 244 (8.5) | 233 (9.0) | 11 (4.0) | |
≥ 50% | 2631 (91.5) | 2365 (91.0) | 266 (96.0) | |
PR status | | | | 0.005 |
Negative | 425 (14.8) | 400 (15.4) | 25 (9.0) | |
Positive | 2450 (85.2) | 2198 (84.6) | 252 (91.0) | |
Ki-67 expression | | | | 0.323 |
< 14% | 1310 (45.6) | 1176 (45.3) | 134 (48.4) | |
≥ 14% | 1565 (54.4) | 1422 (54.7) | 143 (51.6) | |
Molecular subtype | | | | 0.046 |
Luminal A | 926 (32.2) | 822 (31.6) | 104 (37.5) | |
Luminal B/HER2-negative | 1949 (67.8) | 1776 (68.4) | 173 (62.5) | |
Abbreviations: BMI, body mass index; SD, standard deviation; IDC, invasive ductal carcinoma; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2. |
Table 2
Distribution of treatment in the whole population and different BMI groups
Characteristics | Whole population (N = 2875) N (%) | BMI < 28 kg/m2 (N = 2598) N (%) | BMI ≥ 28 kg/m2 (N = 277) N (%) | P value |
Surgery of the breast | | | | 0.778 |
Breast-conserving surgery | 1029 (35.8) | 932 (35.9) | 97 (35.0) | |
Mastectomy | 1846 (64.2) | 1666 (64.1) | 180 (65.0) | |
Surgery of the axilla | | | | 0.499 |
SLNB | 1709 (59.4) | 1547 (59.5) | 162 (58.5) | |
ALND | 1140 (39.7) | 1029 (39.6) | 111 (40.1) | |
Unknown | 26 (0.9) | 22 (0.8) | 4 (1.4) | |
Chemotherapy | | | | 0.027 |
No | 1262 (43.9) | 1123 (43.2) | 139 (50.2) | |
Yes | 1613 (56.1) | 1475 (56.8) | 138 (49.8) | |
Radiotherapy | | | | 0.483 |
No | 1354 (47.1) | 1218 (46.9) | 136 (49.1) | |
Yes | 1521 (52.9) | 1380 (53.1) | 141 (50.9) | |
Endocrine therapy | | | | 0.154 |
No | 137 (4.8) | 119 (4.6) | 18 (6.5) | |
Yes | 2738 (95.2) | 2479 (95.3) | 259 (93.5) | |
Ovarian function suppression | | | | < 0.001 |
No | 2701 (93.9) | 2427 (93.4) | 274 (98.9) | |
Yes | 174 (6.1) | 171 (6.6) | 3 (1.1) | |
Abbreviations: BMI, body mass index; SLNB, sentinel lymph node biopsy; ALND, axillary lymph node dissection. |
Table 3
Multivariate analysis of factors associated with obesity.
Characteristics | OR (95%CI) | P value |
Age at diagnosis (year) | | 0.066 |
≥ 50 vs < 50 | 1.71 (0.97–3.02) | |
Menopausal status | | 0.741 |
Post- vs pre/peri-menopausal | 1.09 (0.65–1.84) | |
Comorbidities | | < 0.001 |
≥ 1 vs 0 | 2.83 (2.13–3.74) | |
ER expression | | 0.221 |
≥ 50% vs < 50% | 1.50 (0.78–2.88) | |
PR status | | 0.037 |
Positive vs negative | 1.63 (1.03–2.58) | |
Molecular subtype | | 0.552 |
luminal B vs luminal A | 0.92 (0.70–1.21) | |
Abbreviations: OR, odds ratio; CI, confidence interval; ; ER, estrogen receptor; PR, progesterone receptor. |
Table 4
Multivariate analysis of factors associated with RFS and OS in luminal A patients.
| RFS | | OS |
Variables | HR (95%CI) | P value | | HR (95%CI) | P value |
Age : ≥ 50 vs < 50 | 0.75 (0.31–1.84) | 0.528 | | 1.68 (0.35–8.18) | 0.520 |
BMI: obese vs non-obese | 3.48 (1.31–9.22) | 0.012 | | 4.67 (1.28–16.95) | 0.019 |
Pathologic tumor size: > 2cm vs ≤ 2cm | 2.18 (0.94–5.06) | 0.071 | | 1.21 (0.33–4.43) | 0.774 |
Pathologic nodal status: | | 0.176 | | | 0.155 |
positive vs negative | 2.08 (0.71–6.08) | 0.182 | | 2.04 (0.54–7.73) | 0.292 |
unknown vs negative | 4.73 (0.61–36.88) | 0.138 | | 7.33 (0.86–62.21) | 0.068 |
Chemotherapy: yes vs no | 1.57 (0.53–4.62) | 0.412 | | | |
Abbreviations: RFS, relapse-free survival; OS, overall survival; HR, hazard ratio; CI, confidence interval; BMI, body mass index |
In terms of surgical approach, 1029 (35.8%) patients received breast-conserving surgery (BCS) and 1709 (59.4%) patients received sentinel lymph node biopsy (SLNB). Regarding adjuvant treatment, the proportions of patients who underwent adjuvant chemotherapy, radiotherapy, endocrine therapy, and ovarian function suppression (OFS) treatment were 56.1%, 52.9%, 95.2%, and 6.1%, respectively. A total of 2738 patients received adjuvant endocrine therapy. According to the first endocrine therapy agent received, 1872 patients received AI treatment (including 118 patients who received OFS simultaneously) and 866 patients received selective estrogen receptor modulators (SERM) treatment (including 56 patients who received OFS simultaneously). A total of 174 patients received OFS.
Association of clinicopathological characteristics and obesity
The median BMI of the whole population was 23.15 (21.30-25.39) kg/m2: 2598 (90.37%) with BMI < 28 kg/m2 and the rest 277 (9.63%) with BMI ≥ 28 kg/m2. Univariate analysis found that age, menopausal status, comorbidities, ER expression, PR positivity, and luminal subtypes were significantly different between two BMI groups (all P < 0.05, Table 1). Lymphovascular invasion, tumor size, node involvement, grade 3 tumors, histologic type, and Ki-67 percentage were not different between the non-obese and obese patients (P > 0.05).
Multivariate analysis demonstrated that only comorbidities and PR positivity were independently associated with obesity (Table 2). Obese patients were more likely to be diagnosed with concomitant comorbidities [odds ratio (OR) 2.83, 95%CI 2.13–3.74, P < 0.001] and slightly more PR-positive tumors (OR 1.63, 95%CI 1.03–2.58, P = 0.037). It also revealed the trend for obese patients to be older than non-obese patients (OR 1.71, 95%CI 0.97–3.02, P = 0.066).
Obesity and clinical outcomes
After a median follow-up of 50 (range 4-127) months, 170 RFS events and 75 deaths have recorded. The 5-year RFS and OS were 88.2% and 93.6% in the whole population. There was no significant difference between non-obese and obese patients in terms of RFS (5-year RFS 88.0% vs 90.3%, P = 0.839) and OS (5-year OS 93.6% vs 93.4%, P = 0.140) (Fig. 2A-2B, Supplementary Table S2).
Exploratory analysis was then done to evaluate prognosis difference according to different clinicopathological subtypes between the obese and non-obese BMI groups (Fig. 2C-2F). Luminal subtypes interacted with obesity in prognosis prediction (interact P = 0.022 for RFS, interact P = 0.056 for OS). In patients with luminal A disease, a significant RFS (5-year RFS: 94.6% vs 91.1%, P = 0.015) and OS (5-year OS: 98.5% vs 90.2 %, P = 0.005) difference was found between the non-obese and obese groups. Multivariate analysis demonstrated that obese patients had a worse prognosis compared to non-obese patients, with an adjusted HR of 3.48 (95%CI 1.31–9.22) for RFS and 4.67 (95%CI 1.28–16.95) for OS. However, in the luminal B subtype, obesity didn’t impact patient’s prognosis in terms of RFS (RFS: HR 0.78, 95%CI 0.41–1.49, P = 0.454) or OS (HR 1.17, 95%CI 0.50–2.74, P = 0.727) (Supplementary Table S3-S4).
Association of obesity and prognosis according to endocrine treatment
Kaplan–Meier curves of RFS and OS according to obesity status in patients treated with SERM or AI were listed in Fig. 4. There was no interaction between obesity and endocrine treatment modality in predicting RFS (interact P = 0.381) and OS (interact P = 0.888). In the subgroup of patients on SERM treatment (with or without OFS), the obese patients showed no significant differences in 5-year RFS (87.0% vs 85.3%, P = 0.625) or 5-year OS (90.9% vs 95.9%, P = 0.703) compared with the non-obese (Fig. 4A-4B). Regarding patients receiving AI treatment (with or without OFS), there was no difference in OS or RFS between obese and non-obese patients (5-year RFS: 92.2% vs 90.1%, P = 0.680, Fig. 4C; 5-year OS: 94.9% vs 92.9%, P = 0.253; Fig. 4D). Patients receiving OFS showed similar RFS and OS between the two BMI groups (data not shown).