Metastasis patterns and prognosis in young breast cancer patients: a SEER database analysis

doi:10.21203/rs.3.rs-1434952/v1

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Metastasis patterns and prognosis in young breast cancer patients: a SEER database analysis

https://doi.org/10.21203/rs.3.rs-1434952/v1

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Background

There are few studies on young patients with metastatic breast cancer. This study aims to explore the metastasis pattern and prognosis of young patients with metastatic breast cancer.

Methods

6336 metastatic breast cancer patients diagnosed in the Surveillance, Epidemiology and End results database from 2010 to 2015 were selected. They were divided into three age groups: the younger group (≤ 40 years old), middle-aged group (41–69 years old) and older group (≥ 70 years old). χ2 test was used to compare clinicopathological characteristics. Survival differences were compared by Kaplan–Meier analysis. Cox regression models were used to determine the prognostic factors affecting survival.

Results

Finally, 494 patients (7.8%) ≤ 40 years old, 3957 patients (62.5%) 41–69 years old, and 1885 patients (29.7%) ≥ 70 years old were included. In younger group, the proportion of liver metastasis was significantly higher than that in middle-aged group and older group; the proportion of lung metastasis was significantly lower than that of the older group, but there was no significant difference with the middle-aged group. Kaplan-meier analysis showed that the younger group had the best prognosis and the older group had the worst. Youth is an independent protective factor for survival.In the young group, liver metastasis had the best prognosis among all metastatic sites, and HR-/HER2 + had the best prognosis among all molecular subtypes.

Conclusions

The disease in young metastatic breast cancer patients is more aggressive but has a better prognosis, especially in liver metastases and the HR-/HER2 + subtypes.

breast cancer

young patients

metastasis patterns

SEER

prognosis

Breast cancer is the most common cancer in women and the leading cause of cancer-related deaths among women worldwide. [1] For breast cancer, “young patients” are women diagnosed with cancer before age 40. [2] Breast cancer in women less than 40 years of age accounts for about 7% of breast cancers, making it the most common cancer diagnosed in females for the 25–39 years old age group. [3], [4] The number of patients with metastatic breast cancer under 40 years old showed a trend of stable and even accelerated growth. [5] Compared with developed countries, breast cancer in young women is a huge burden in developing countries. A disproportionate number of young women lost their life every year because of this type of cancer. [6] Moreover, young women are usually at the peak of their career when they have to deal with the sudden diagnosis of cancer. Juggling a job, the pressures of being young parents, if relevant, concerns with preexisting financial issues, and peer pressures concurrently with cancer diagnosis can affect adherence to therapies. [7] Therefore, in-depth research on breast cancer in young women is nessesary.

In metastatic breast cancer (MBC), the most common sites of metastasis include bone, brain, lung, and liver. [8] Currently, short metastasis-free interval, visceral involvement and crisis, negative hormone receptor (HR) and particularly triple negative subtype, primary endocrine resistance for luminal subtype and number of metastatic sites are recognized as poor prognostic factors. [9] However, the effect of age on prognosis remains unclear. Studies have shown that age at diagnosis is associated with breast cancer survival, but the results are conflicting. Some studies [10] [11] have shown that youth is associated with poor prognosis because tumors are more aggressive in young people. Conversely, other studies have shown that older patients have a worse prognosis than younger patients. [12, 13], [14] Therefore, the purpose of this study is to explore the metastasis pattern and prognosis of MBC patients aged ≤ 40 years.

Data collection

Data were obtained from the US Surveillance, Epidemiology, and End Results (SEER)with the username 10067-Nov2018. The data we selected came from Incidence-SEER Research Plus Data, 9 Registries, based on the November 2020 submission. Since this study used registry data, this study was exempted by the ethics committee of the Forth Hospital of Hebei Medical University. The methods were based on approved guidelines.

Study population

Patients diagnosed with advanced breast cancer from January 1, 2010 to December 31, 2015 were included in the study.Inclusion criteria: ①female patients,②age at diagnosis ≥ 18 years’old,③primary site at breast,④diagnosis between 2010 and 2015,⑤stage IV of the 7th edition of the American Joint Committee on Cancer(AJCC) staging system.Exclusion criteria:①reported only from a nursing or convalescent home, hospice, autopsy, or death certificate,②patients with unknown metastatic site.Patients were divided into three groups according to age (younger group: ≤40 years old, middle-aged group: 41–69 years old, older group: ≥70 years old).A total of 6337 patients were included.The following factors were extracted: age of diagnosis, year of diagnosis, race, TNM stage (AJCC 7th edition), molecular subtype, surgery, chemotherapy, radiotherapy, site of distant metastasis (bone, brain, liver, lung, distant lymph nodes), death events, and survival time.

Statistical analysis

Overall survival (OS) was calculated from the date of diagnosis to the date of death due to any cause, the date of last follow-up, or December 31, 2015. Breast cancer specific survival (BCSS) was measured as the time from the date of diagnosis to the date of death attributed to breast cancer. The clinical characteristics of the selected patients were compared with the Pearson’s χ2 test. Survival was estimated using the Kaplan–Meier method and compared between the different metastatic groups using log-rank test. The survival curves were drawn with GraphPad Prism 7.0.0. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by univariable and multivariable Cox regression models to assess the effect of the factors associated with OS and BCSS. All statistical analyses were performed using SPSS Statistics 25.0. Statistical significance was considered at two-sided p value < 0.05.

Demographics

Overall, 6336 MBC patients were enrolled in our study from SEER database. Clinical characteristics of patients in different age groups were summarized in Table 1. Among them, 494 patients (7.8%) were diagnosed at the age of ≤ 40 years old, 3957 patients (62.5%) were at 41–69 years old, and 1885 patients (29.7%) were at ≥ 70 years old. Except for the year of diagnosis, there were significant differences among the three groups in race, T stage, N stage, molecular subtype, surgery, chemotherapy and radiotherapy. In the younger group, there were more blacks than any other race (25.9% vs. 18.6% and 12.3%, P < 0.001) and less whites (59.7% vs. 71.7% and 81.4%, P < 0.001).The younger group had larger tumor size with more stage T2 (32.2% vs. 27.1% and 26.9, P < 0.001) and T3 (19.6% vs. 15.1% and 11.8%, P < 0.001) tumors, as well as higher rate of lymph node involvement (P < 0.001). The younger group was more likely to have the more aggressive molecular subtypes -- HR+/HER2+, HR-/HER2 + and HR-/HER2- subtypes (P < 0.001), while the older group was more likely to have the HR+/HER2- subtypes. In terms of treatment, the younger group had a higher rate of receiving surgery (41.3% vs. 31.3% and 21.4%, P<0.001), chemotherapy (81.2% vs. 61.9% and 29.2%, P < 0.001), and radiotherapy (46.4% vs. 37.8% and 27.7%, P < 0.001).

Relationship between age and metastasis patterns

In the study population, bone was the most common site of metastasis (37.2%), followed by distant lymph node metastasis (7.7%), lung metastasis (8.0%), liver metastasis (6.6%), and brain metastasis (1.4%). The proportion of multiple sites metastasis was up to 39.1%, of which the most common was bone metastasis with liver metastasis, accounting for 16.1% of patients with multiple sites metastasis (n = 399). Notably, the proportion of liver only metastasis were significantly higher in the younger group (9.9%vs.6.9%vs.5.3%, P < 0.001) than in the middle-aged group and older group. The proportion of lung only metastasis in the younger group (5.7%vs.10.5%, P < 0.001) was significantly lower than that in the older group, but there was no significant difference with the middle-aged group. There was no significant difference between the three groups in brain only metastasis and distant lymph node only metastasis. Detailed results are shown in Fig. 1.

Table 1

Demographic and clinical characteristics of the cohort
		≤ 40 years n(%)	41–69 years n(%)	≥ 70 years n(%)	Total n(%)	P-value
Year of diagnosis	2010	56(11.3%)	638(16.1%)	274(14.5%)	968(15.3%)	0.250
	2011	80(16.2%)	622(15.7%)	304(16.1%)	1006(15.9%)
	2012	80(16.2%)	650(16.4%)	323(17.1%)	1053(16.6%)
	2013	84(17.0%)	692(17.5%)	343(18.2%)	1119(17.7%)
	2014	92(18.6%)	675(17.1%)	317(16.8%)	1084(17.1%)
	2015	102(20.6%)	680(17.2)	324(17.2%)	1106(17.5%)
Race	White	295(59.7%)	2813(71.1%)	1535(81.4%)	4643(73.3%)	P<0.001
	Black	128(25.9%)	736(18.6%)	231(12.3%)	1095(17.3%)
	Others^a	69(14.0%)	400(10.1%)	116(6.2%)	585(9.2%)
	Unknown	2(0.4%)	8(0.2%)	3(0.2%)	13(0.2%)
T stage	T0	4(0.8%)	86(2.2%)	54(2.9%)	114(2.3%)	P<0.001
	T1	53(10.7%)	486(12.3%)	220(11.7%)	759(12.0%)
	T2	159(32.2%)	1071(27.1%)	507(26.9%)	1737(27.4%)
	T3	97(19.6%)	596(15.1%)	222(11.8%)	915(14.4%)
	T4	127(25.7%)	1183(29.9%)	527(28.0%)	1837(29.0%)
	Tx	54(10.9%)	535(13.5%)	355(18.8%)	944(14.9%)
N stage	N0	83(16.8%)	892(22.5%)	544(28.9%)	1519(24.0%)	P<0.001
	N1	229(46.4%)	1674(42.3%)	694(36.8%)	2597(41.0%)
	N2	62(12.6%)	447(11.3%)	170(9.0%)	679(10.7%)
	N3	99(20.0%)	614(15.5%)	209(11.1%)	922(14.6%)
	Nx	21(4.3%)	330(8.3%)	268(14.2%)	619(9.8%)
Molecular subtype^b	HR+/HER2-	210(42.5%)	2158(54.5%)	1055(56.0%)	3423(54.0%)	P<0.001
	HR+/HER2+	125(25.3%)	586(14.8%)	205(10.9%)	916(14.5%)
	HR-/HER2+	61(12.3%)	316(8.0%)	97(5.1%)	474(7.5%)
	HR-/HER2-	64(13.0%)	502(12.7%)	199(10.6%)	765(12.1%)
	Unknown	34(6.9%)	395(10.0%)	329(17.5%)	758(12.0%)
Surgery	Yes	204(41.3%)	1237(31.3%)	404(21.4%)	1845(29.1%)	P<0.001
Surgery	No/Unknown	290(58.7%)	2720(68.7%)	1481(78.6%)	4491(70.9%)	P<0.001
Chemotherapy	Yes	401(81.2%)	2448(61.9%)	550(29.2%)	3399(53.6%)	P<0.001
Chemotherapy	No/Unknown	93(18.8%)	1509(38.1%)	1335(70.8%)	2937(46.4%)	P<0.001
Radiation	Yes	229(46.4%)	1496(37.8%)	523(27.7%)	2248(35.5%)	P<0.001
Radiation	No/Unknown	265(53.6%)	2461(62.2%)	1362(72.3%)	4088(64.5%)	P<0.001
Total		494(7.8%)	3957(62.5%)	1885(29.7%)	6336(100%)
Notes: ^aOther races includes American Indians, Asians and Pacifc Islanders; bHR: hormone receptor, HER2: human epidermal growth receptor 2; ^cSurgery only included surgery at the primary site.

Kaplan-Meier analysis showed that the younger group had the best prognosis and the older group had the worst prognosis (Fig. 2A༆2B). The median survival was 48, 35 and 20 months in the younger group, the middle-aged group and the older group, respectively. The younger group had the best OS (HR: 0.724, 95%CI: 0.639–0.821, P < 0.001) and BCSS (HR: 0.748, 95%CI: 0.658–0.851, P < 0.001). Multivariate COX regression showed that besides age, diagnosis year, race, T stage, N stage, molecular subtype, surgery, chemotherapy, bone metastasis, brain metastasis, liver metastasis and multiple metastasis were significantly correlated with survival (P < 0.05) (Table 2).

The survival analysis of metastatic sites in different age groups showed that in the younger group, patients with liver metastasis had the best OS and BCSS, with a 5-year survival rate of 67.1% (Fig. 2C༆2D). However, in the middle-aged group and the elderly group, patients with bone metastasis only had the best OS and BCSS (Fig. 2E-2H). Patients with brain metastasis only had the worst prognosis in three age groups.

Survival analysis of different age groups showed that HR-/HER2 + subtype had the best prognosis (five-year survival rate 63.6%) in the younger group (Fig. 2I༆2J), HR+/HER2 + subtype (five-year survival rate 49.9%) in the middle-aged group (Figure K, L) and HR+/HER2- subtype (five-year survival rate 21.6%) in the older group (Fig. 2M༆2N). HR-/HER2- subtype had the worst prognosis in three age groups.

Table 2

Univariate and multivariate analysis of the overall survival (OS) and breast cancer-specific survival (BCSS) of the study population
		Univariate analysis				Multivariate analysis
		OS		BCSS		OS		BCSS
		HRs(95%CI)	P-value	HRs(95%CI)	P-value	HRs(95%CI)	P-value	HRs(95%CI)	P-value
Age	≤ 40 years	0.692(0.612–0.784)	P<0.001	0.721(0.635–0.819)	P<0.001	0.724(0.639–0.821)	P<0.001	0.748(0.658–0.851)	P<0.001
	41–69 years	1		1		1		1
	≥ 70 years	1.596(1.500-1.698)	P<0.001	1.457(1.362–1.558)	P<0.001	1.525(1.428–1.629)	P<0.001	1.411(1.314–1.514)	P<0.001
Year of diagnosis	2010	1		1		1		1
	2011	1.031(0.935–1.137)	0.535	1.030(0.928–1.143)	0.581	1.064(0.965–1.174)	0.213	1.060(0.954–1.177)	0.277
	2012	1.025(0.929–1.131)	0.627	1.054(0.949–1.169)	0.326	1.043(0.945–1.151)	0.406	1.070(0.964–1.188)	0.206
	2013	0.953(0.863–1.052)	0.341	0.958(0.862–1.065)	0.424	0.910(0.824–1.006)	0.065	0.914(0.822–1.017)	0.098
	2014	0.977(0.881–1.082)	0.652	0.978(0.876–1.091)	0.685	0.963(0.868–1.067)	0.469	0.960(0.860–1.071)	0.465
	2015	0.893(0.801–0.994)	0.039	0.910(0.811–1.020)	0.104	0.890(0.798–0.992)	0.035	0.902(0.804–1.012)	0.902
Race	White	1		1		1		1
	Black	1.277(1.184–1.377)	P<0.001	1.271(1.173–1.377)	P<0.001	1.287(1.191–1.389)	P<0.001	1.257(1.158–1.364)	P<0.001
	Others	0.919(0.827–1.021)	0.117	0.932(0.834–1.041)	0.213	0.986(0.887–1.096)	0.796	0.983(0.879–1.099)	0.761
	Unknown	0.817(0.367–1.820)	0.621	0.614(0.230–1.636)	0.329	0.653(0.293–1.458)	0.299	0.493(0.184–1.316)	0.158
T stage	T0	1		1		1		1
	T1	0.740(0.601–0.912)	0.005	0.773(0.617–0.968)	0.025	0.973(0.787–1.203)	0.802	1.004(0.799–1.262)	0.971
	T2	0.824(0.677–1.004)	0.055	0.861(0.696–1.065)	0.169	1.158(0.947–1.418)	0.153	1.182(0.950–1.470)	0.134
	T3	0.893(0.729–1.095)	0.277	0.938(0.753–1.168)	0.566	1.214(0.985–1.496)	0.069	1.229(0.981–1.540)	0.073
	T4	1.130(0.929–1.374)	0.222	1.178(0.954–1.456)	0.129	1.408(1.151–1.722)	P<0.001	1.417(1.140–1.762)	0.002
	Tx	1.180(0.965–1.444)	0.107	1.210(0.972–1.505)	0.087	1.157(0.944–1.419)	0.160	1.184(0.950–1.476)	0.134
N stage	N0	1		1		1		1
	N1	0.943(0.875–1.016)	0.125	0.997(0.921–1.080)	0.950	0.984(0.910–1.063)	0.676	1.033(0.950–1.123)	0.448
	N2	0.919(0.825–1.023)	0.122	0.975(0.870–1.092)	0.658	1.097(0.978–1.228)	0.106	1.164(1.033–1.311)	0.013
	N3	0.980(0.891–1.079)	0.685	1.017(0.918–1.127)	0.745	1.086(0.978–1.205)	0.124	1.123(1.005–1.256)	0.041
	Nx	1.398()	P<0.001	1.393(1.244–1.560)	P<0.001	1.140(1.021–1.273)	0.020	1.141(1.012–1.285)	0.030
Molecular subtype	HR+/HER2-	0.651(0.596–0.771)	P<0.001	0.657(0.598–0.723)	P<0.001	0.721(0.657–0.792)	P<0.001	0.714(0.645–0.789)	P<0.001
	HR+/HER2+	0.438()	P<0.001	0.446(0.394–0.506)	P<0.001	0.526(0.464–0.596)	P<0.001	0.512(0.448–0.585)	P<0.001
	HR-/HER2+	0.547(0.476–0.630)	P<0.001	0.593(0.513–0.687)	P<0.001	0.699(0.602–0.813)	P<0.001	0.714(0.610–0.836)	P<0.001
	HR-/HER2-	1.580(1.416–1.763)	P<0.001	1.663(1.481–1.867)	P<0.001	2.196(1.946–2.477)	P<0.001	2.236(1.968–2.541)	P<0.001
	Unknown	1		1		1		1
Surgery	Yes	0.541(0.506–0.579)	P<0.001	0.539(0.501–0.579)	P<0.001	0.609(0.564–0.657)	P<0.001	0.590(0.544–0.639)	P<0.001
Surgery	No/Unknown	1		1		1		1
Chemotherapy	Yes	0.698(0.659–0.740)	P<0.001	0.742(0.698–0.789)	P<0.001	0.722(0.674–0.775)	P<0.001	0.741(0.689–0.798)	P<0.001
Chemotherapy	No/Unknown	1		1		1		1
Radiation	Yes	0.888(0.836–0.944)	P<0.001	0.929(0.871–0.991)	0.024	0.977(0.916–1.043)	0.492	1.019(0.951–1.092)	0.594
Radiation	No/Unknown	1		1		1		1
Bone metastasis	Yes	1.056(0.991–1.125)	0.094	1.059 (0.990–1.133)	0.095	1.095(1.003–1.196)	0.042	1.100(1.002–1.206)	0.045
Bone metastasis	No/Unknown	1		1		1		1
Brain metastasis	Yes	2.192(1.983–2.423)	P<0.001	2.297(2.069–2.550)	P<0.001	1.962(1.751-2.200)	P<0.001	1.553(1.420–1.699)	P<0.001
Brain metastasis	No/Unknown	1		1		1		1
Liver metastasis	Yes	1.446(1.356–1.543)	P<0.001	1.506(1.407–1.612)	P<0.001	1.537(1.410–1.674)	P<0.001	1.553(1.420–1.699)	P<0.001
Liver metastasis	No/Unknown	1		1		1		1
Lung metastasis	Yes	1.334(1.254–1.419)	P<0.001	1.371(1.285–1.464)	P<0.001	1.058(0.972–1.151)	0.196	1.082(0.990–1.182)	0.084
Lung metastasis	No/Unknown	1		1		1		1
Distant lymph nodes metastasis	Yes	1.023(0.957–1.094)	0.501	1.025(0.955-1.100)	0.496	0.948(0.869–1.034)	0.225	0.927(0.846–1.015)	0.102
Distant lymph nodes metastasis	No/Unknown	1		1		1		1
Multiple sites metastasis	Yes	1.577(1.487–1.672)	P<0.001	1.645(1.546–1.750)	P<0.001	1.198(1.073–1.337)	P<0.001	1.218(1.085–1.367)	P<0.001
Multiple sites metastasis	No/Unknown	1		1		1		1
Notes: OS: overall survival; BCSS: cancer-specific survival; HRs: hazard ratios; CI: confidence interval.

The total number of young breast cancers is relatively small, but the incidence of distant metastasis is increasing. The incidence of MBC among young women increased from 1.53 per 100,000 to 2.90 per 100,000 from 1976 to 2009, with the trend showing no slowing down, indicating increasing epidemiological and clinical significance.[5] However, there are few studies on young women with MBC. Our study divided MBC patients into three age groups in a large population-based SEER data to evaluate the effect of age on metastasis patterns and the effect of age, metastasis sites, and molecular subtype on prognosis.

Our study showed that young MBC patients had larger tumors, higher rates of lymph node involvement, and more aggressive molecular types, consistent with previous studies. The largest study to date involving 200,000 breast cancer patients was conducted by Gnerlichetal with 15,000 breast cancer patients aged < 40 years at diagnosis, found that younger women were more likely to be diagnosed with larger tumors, lymph node involvement, poorly differentiated tumors, and ER-tumors.[15] In addition, a California Cancer Registry study [37] including 5600 women aged < 40 years at diagnosis reported a statistically significant HER2-higher expression in the younger women.[16] The results of these studies demonstrate the aggressiveness of breast cancer in young patients. In addition, the screening is poor in young women due to the low incidence of breast cancer, which leads to more severe disease at the time of diagnosis.[13]

The metastasis patterns in different age groups remains controversial. A study of 14,403 patients based on the ESME database found that MBC patients aged < 40 years were more likely to have visceral metastasis than bone metastasis.[12] Chen et al found that MBC patients aged < 50 years were more likely to have distant lymph node metastasis, multiple sites metastasis, and less likely to have lung metastasis.[17] A study of 6,640 patients showed that MBC patients aged < 40 years were more likely to have brain and liver metastasis than patients aged ≥ 40 years.[18] Our study found that MBC patients aged ≤ 40 years had a higher risk of liver metastasis, while the risk of lung metastasis was lower. This may be due to more HER2 + and triple-negetive subtypes in young patients. Previous studies have shown that HER2 + subtype is associated with liver metastasis.[19, 20] HER2 + and triple-negetive subtypes were more likely to have visceral metastasis than bone metastasis.[21] However, the underlying molecular mechanisms need further research.

Multivariate COX regression showed that the OS and BCSS of the younger group were better than those of the middle-aged group and the older group, and youth was an independent protective factor of prognosis. This is contrary to previous studies reported that young age at diagnosis is associated with poor prognosis in breast cancer. There are many reasons for this. First, our study confirmed that younger patients were more likely to receive treatment (surgery, chemotherapy, radiotherapy), consistent with previous studies [17]. Besides conventional systemic treatment, many studies have demonstrated the benefits of local treatment for MBC [22、23]. Second, there were more Her2 + subtypes in young patients. Studies have found that the improvement of OS in MBC patients is mainly driven by the HER2 + subgroup [24]. In fact, new HER2-targeted therapies were released in 2013 (namely pertuzumab and T-DM1), which were associated with major OS benefits in clinical trials [25–27]. In a real-world study of patients with HER2 + MBC, younger patients were more likely to receive PH + taxane than older patients, and older patients were more likely to receive regimens with H without P or hormone therapy. It turned out younger patients have better BCSS than older patients[28]. This also suggests that there may be undertreatment in elderly patients to some extent.

Kaplan-Meier analysis showed interesting results. In the younger group, patients with liver only metastasis, not bone only metastasis, had the best prognosis. This may be due to the fact that 59.2% of patients with liver metastasis were HER2 + subtypes in the younger group of our study, and younger patients received more chemotherapy and anti-HER2 therapy than older patients, bringing survival benefits. SwatiSakhuja et al. [29] found that HR-/HER2 + and HR+/HER2 + subtypes had the best survival in patients with liver metastasis. Ji et al. [19] also reached the same conclusion. Similarly, HER2 + subtype in the younger group also showed a survival advantage in our study. This suggests that even in metastatic HER2 + breast cancer, anti-HER2 therapy also result in considerable and long-lasting improvements in survival.[30]

There are some limitations to this study. This study was retrospective and not as convincing as prospective studies. The SEER database does not provide information on targeted therapy or endocrine therapy, which may affect survival outcomes. In addition, the SEER database only provided HER2 information after 2010, resulting in insufficient follow-up of some patients. Despite these limitations, this study elucidates the metastasis patterns and prognostic characteristics based on metastasis sites and molecular subtype in young MBC patients. These findings may provide a basis for precision treatment of young MBC patients.

Acknowledgements

We deeply appreciate Yunjiang Liu and JinzhaoLiu for their kind suggestions and generous help in data analysis.

Funding

This work has no funding.

Availability of data and materials

Data are available on request from the authors.

Ethics approval and consent to participate

Since this study used registry data, this study was exempted by the ethics committee of the Forth Hospital of Hebei Medical University.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable

Author Contributions

WZ, JL and YL designed the study. XZ, CY, MC and SZ extracted and analyzed the data. WZ and JL wrote and edited the manuscript. The authors were ranked according to their contributions.

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No competing interests reported.

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Metastasis patterns and prognosis in young breast cancer patients: a SEER database analysis

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