Long-term Survival Outcomes in Patients with Locally Advanced Breast Cancer after Total Mastectomy with or without Breast Reconstruction: A Seer-based Analysis

doi:10.21203/rs.3.rs-2995216/v1

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Long-term Survival Outcomes in Patients with Locally Advanced Breast Cancer after Total Mastectomy with or without Breast Reconstruction: A Seer-based Analysis

https://doi.org/10.21203/rs.3.rs-2995216/v1

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Background: There is ongoing debate about the safety of breast reconstruction for patients with locally advanced breast cancer (LABC) who have undergone total mastectomy (TM). More and more LABC patients are undergoing breast reconstruction after TM, but its long-term survival outcomes remain unclear. This study aims to compare the survival outcomes of LABC patients who underwent breast reconstruction after TM with those who did not, based on a large sample.

Methods: We collected data for all LABC patients who underwent TM with or without breast reconstruction in the Surveillance, Epidemiology, and End Results (SEER) database. We divided patients into two groups: TM group and total mastectomy with reconstruction (TM+R) group. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) analysis was used to eliminate imbalances of baseline data between the in tow groups. Data were analyzed using chi-square tests, Kaplan-Meier methods, and univariate and multivariate cox regression analyses.

Result: We identified 39,112 eligible patients (33,169 patients received TM and 5,943 received TM+R), and 8,680 patients were matched after PSM (4,340 patients received TM and 4,340 received TM+R). Patients with middle age, white, married, lived in urban, IIB-IIIA stage, invasive ductal carcinoma(IDC), pathological grade II-III, hormone receptor positive, and undergone chemotherapy were more likely to receive breast reconstruction. After PSM, Kaplan-Meier survival analysis showed better OS and BCSS in the TM+R group versus the TM group (OS:P<0.001; BCSS: P=0.008). Multivariate cox regression analysis showed that TM+R significantly improved OS and BCSS (OS: hazard ratio (HR) 0.73, 95% CI [0.68,0.79], P<0.001; BCSS: 95% CI [0.79,0.94], P=0.001). Subgroup analysis showed that patients with old age, white, and hormone receptor positive had better OS and BCSS by TM+R compared to TM.

Conclusions: Breast reconstruction after total mastectomy is associated with better OS and BCSS in patients with LABC.

locally advanced breast cancer

breast reconstruction

total mastectomy

survival

overall survival

breast cancer-specific survival

Locally advanced breast cancer (LABC) is typically characterized as a substantial tumor in the breast, classified as clinical stage T3 or T4, which may or may not extend into the skin or chest wall. Additionally, LABC is often accompanied by extensive metastasis to the lymph nodes, while lacking any signs of distant metastases[1][2]. LABC represents approximately 5% of newly diagnosed breast cancer cases globally. However, it is noteworthy that in developing countries, the incidence of LABC is significantly higher, ranging from 20–25%[3]. Initially, total mastectomy (TM) served as the primary surgical treatment for LABC patients. However, with the advancement of systemic treatments such as chemotherapy, radiation therapy, targeted therapy, and the continuous refinement of surgical techniques in breast cancer management, an increasing number of eligible LABC patients have undergone breast reconstruction. Breast reconstruction can be accomplished through two primary methods: prosthetic implants and autologous tissue, which can also be combined if necessary. Among the autologous tissue reconstruction techniques, notable approaches include the latissimus dorsi flap, transverse rectus abdominis myocutaneous (TRAM) flap, and deep inferior epigastric perforator flap (DIEP), among others. The timing of breast reconstruction can be immediate, performed concurrently with the total mastectomy, or delayed after the mastectomy procedure[4].

A wealth of evidence from numerous studies consistently demonstrates the positive impact of breast reconstruction on both the physical and mental well-being of breast cancer patients. The procedure has been shown to effectively restore the shape of the breast, offering substantial benefits that contribute to an enhanced quality of life[5][6][7]. These findings highlight the potential benefits of breast reconstruction for LABC patients, as it offers not only aesthetic improvements but also a low incidence of surgical complications and comparable survival rates [8][9][10]. Nevertheless, it is important to acknowledge that the existing studies examining breast reconstruction in LABC patients have primarily focused on surgical safety and have been limited by small sample sizes. Consequently, the long-term survival outcomes following breast reconstruction in this patient population remain uncertain. Therefore, conducting further investigations to elucidate the prognosis of LABC patients who undergo breast reconstruction after TM holds substantial significance.

The primary objective of this study was to comprehensively compare the long-term survival outcomes between LABC patients who underwent breast reconstruction after TM and those who did not, utilizing a large sample derived from the Surveillance, Epidemiology, and End Results (SEER) database. By leveraging this extensive dataset, we sought to provide robust and reliable insights into the potential impact of breast reconstruction on the overall prognosis of LABC patients.

Data Sources and Patient Selection

We extracted comprehensive demographic, tumor-specific, and treatment information from SEER*Stat version 8.4.0.1 to conduct this study. A total of 51,720 female patients aged between 18 and 80 years, who were diagnosed with locally advanced breast cancer and treated with total mastectomy (TM) with or without breast reconstruction, were initially identified from the database for the study period spanning 1998 to 2017. Subsequently, patients were excluded if they were below 20 years of age or 80 years and above, had bilateral breast cancer, had unknown hormone receptor status, unknown tumor size or unknown histological grade, or if there was a lack of follow-up data (as shown in Fig. 1).

Following the exclusion criteria, a final cohort of 39,112 patients with locally advanced breast cancer was included for analysis. The dataset encompassed various key variables, including age, ethnicity, laterality, tumor stage, pathological grade, pathological type, estrogen receptor (ER) and progesterone receptor (PR) status, details of chemotherapy and radiotherapy, marital status, income, and geographic region.

The study cohort comprised patients diagnosed with LABC, divided into two groups: the TM group (N = 33,169) and the total mastectomy with reconstruction (TM + R) group (N = 5,943). The primary outcomes investigated in this study were overall survival (OS) and breast cancer-specific survival (BCSS). Overall survival (OS) was defined as the duration from the date of diagnosis to the event of death from any cause. Breast cancer-specific survival (BCSS) was determined as the time from the initial diagnosis to death specifically attributed to breast cancer.

Statistical Analysis

We compared the demographic characteristics, clinicopathologic characteristics and treatment information between two groups by chi-square test. We further adopted the propensity score-matching (PSM) analysis to balance the potential selection bias between the TM group and TM + R group. OS and BCSS of theses two groups were plotted using the Kaplan-Meier method and the log-rank test was performed to determine statistical significance. We calculated Cox proportional hazards models with hazard ratios (HR) with 95% confidence interval (CI) for univariate analysis and multivariate analysis to compare the effects of surgical type and the variables on OS and BCSS. The variables of interest in this study were analysed through subgroup analysis to identify patients who could benefit from breast reconstruction. A two-tailed P-value < 0.05 were considered statistically significant and were two-sided. All statistical analyses and figures were performed using SPSS Statistics 22.0.0.0 and Graphpad Prim 9.0.0(121), respectively.

A total of 39,112 patients met the inclusion and exclusion criteria and were included in this study. Among them, 5,943 patients underwent breast reconstruction, while 33,169 patients did not. Various demographic and clinical characteristics were analyzed to assess factors associated with the likelihood of receiving breast reconstruction. Based on the findings presented in Table 1, patients of middle age, whites, married status, residing in urban areas, having stage IIB-IIIA tumors, being diagnosed with invasive ductal carcinoma (IDC), having pathological grade II-III tumors, being hormone receptor positive, and having undergone chemotherapy were more likely to undergo breast reconstruction. To minimize potential confounding factors, PSM analysis was performed, resulting in a matched cohort of 8,680 patients. This cohort consisted of 4,340 patients who underwent TM and 4,340 patients who underwent total mastectomy with breast reconstruction. Importantly, after PSM, the covariates between the two groups were appropriately balanced, as indicated by non-significant differences (P > 0.05) in the matched cohort.

In overall cohort, the median follow-up of TM group and TM+R group were 159 months and 257 months, respectively. Our Kaplan–Meier survival analysis results showed that patients who underwent TM+R group tended to have statistically significant better OS (P<0.001; figure 2A) and BCSS (P <0.001; figure 2B). The 5-year OS rate (87.3%) and 10-year OS rate (79.1%) of TM+R group were much higher than that in TM group ( 5-year OS rate, 76.2%, 10-year OS rate, 63.9%). Similarly, the 5- and 10-yr BCSS rates were 89.1% and 82.2% in TM+R group while 81.3% and 73.4% in TM group, respectively . After PSM, TM+R group also had better OS (P<0.001; figure 3A) and BCSS (P =0.008; figure 3B) than TM group. The 5-and 10-year OS rates were 88.2% and 79.8% for TM+R group compared with 82.4% and 71.1% for TM group. The 5-and 10-year BCSS rates were 89.9% and 83.0% for patients undergoing breast reconstruction , as compared with 86.4% and 76.8% for patients without breast reconstruction after total mastectomy.

Univariate Cox regression analysis indicated that the OS (hazard ratio (HR 0.57; 95% CI 0.54-0.60, P<0.001) and BCSS (HR, 0.67; 95% CI 0.63 to 0.71, P<0.001) were better in TM+R group, and multivariate Cox regression analysis also showed that the TM+R group was associated with better OS (HR, 0.70; 95% CI 0.66-0.74, P<0.001) and BCSS (HR, 0.77; 95%CI 0.72-0.82，P<0.001). After PSM, multivariate Cox regression analysis also showed that the OS (HR, 0.73; 95% CI 0.68-0.79, P<0.001; figure 4) and BCSS (HR, 0.86; 95% CI 0.79-0.94, P=0.001; figure 5) of the TM+R group were statistically better than those in the TM group.

To investigate the potential role of the clinicopathological characteristics with surgery type, subgroup survival analysis of the OS and BCSS was performed. According to the subgroup analysis(Table 3), patients with age 40-79 year, stage IIB or IIIA, Grade I-III, HR+, IDC and invasive lobular carcinoma (ILD) were benefit for OS if patients received breast reconstruction after TM. Subsequently, the analysis results of BCSS showed that patients with age 60-79 year, stage IIIA, grade I or III, and HR+ was favorable in breast reconstruction. In addition, OS was better in patients with white or other race after breast reconstruction, but only white people had better BCSS after breast reconstruction. The same situation was observed in radiation therapy and chemotherapy.

With the progress made in neoadjuvant chemotherapy, systemic therapy, and surgical interventions, the overall survival rates of patients diagnosed with locally advanced breast cancer (LABC) have witnessed significant improvement. In the United States, a comprehensive population-based study utilizing data from SEER database revealed noteworthy advancements in the survival outcomes of LABC patients over time. According to this study, conducted over several decades, the 5-year survival rate for LABC patients in the 1990s was approximately 50%. However, by 2015, the survival rate had substantially increased, approaching 80%. These findings demonstrate a remarkable improvement in patient outcomes, indicating the positive impact of advancements in neoadjuvant chemotherapy, systemic therapy, and surgical approaches on LABC management[1]. The introduction of neoadjuvant chemotherapy has been instrumental in the down-staging of tumors in the management of LABC. This significant development has not only made breast reconstruction, utilizing either implants or autologous tissue, a routine procedure for LABC patients[11], but has also contributed to the increased prevalence and safety of breast-conserving surgery, regardless of whether the LABC presentation is non-inflammatory or inflammatory[12][13]. Researches has provided evidence that an increasing number of patients diagnosed with LABC are opting for immediate breast reconstruction, particularly following the year 2004[14]. Immediate or delayed breast reconstruction is strongly recommended for operable locally advanced breast cancer (LABC) patients due to its potential to address physical defects, alleviate psychological distress, and enhance the overall quality of life in individuals who have undergone mastectomy. Despite these benefits, the long-term survival outcomes following breast reconstruction in LABC patients remain uncertain.

Our study investigated the disparity in long-term survival outcomes between two groups of patients with LABC: those who underwent breast reconstruction following total mastectomy and those who did not. By comparing these two cohorts, we sought to shed light on the potential impact of breast reconstruction on the survival of LABC patients. Our study revealed compelling findings regarding the long-term OS and BCSS outcomes among patients with LABC who underwent breast reconstruction following TM. Our analysis demonstrated that LABC patients who underwent breast reconstruction exhibited significantly improved long-term OS and BCSS compared to those who did not undergo reconstruction. Importantly, these findings remained consistent even after adjusting for baseline characteristics. While several single-center or small sample size studies have provided preliminary evidence regarding the oncological safety of breast reconstruction in LABC patients, there remains a scarcity of data regarding the long-term survival outcomes associated with this procedure. Although these initial studies have contributed valuable insights, the limited sample sizes and single-center nature of these investigations restrict the generalizability and reliability of their findings[15][16][17][18]. In a retrospective analysis conducted by Tung-Ying Hsieh et al., data from women who underwent TRAM reconstruction immediately following unilateral modified radical mastectomy (MRM) for locally advanced breast cancer were examined. The study, which encompassed the period from January 2002 to December 2009, yielded compelling results regarding the 5-year breast cancer-specific survival rates in the MRM-TRAM and MRM groups. Remarkably, the analysis revealed that the MRM-TRAM group exhibited a significantly higher 5-year breast cancer-specific survival rate (84.6%) compared to the MRM group (61.2%) (P = 0.003) [19]. The findings of our study align with the results obtained by previous investigations. Our analysis revealed that patients with LABC who underwent breast reconstruction exhibited a notable 5-year BCSS rate of 89.1%. Notably, after conducting PSM to account for potential confounding factors, the BCSS rate increased to an impressive 89.9%. These findings demonstrate the substantial survival benefits associated with breast reconstruction in LABC patients. PSM was employed in our study to mitigate any potential imbalances in baseline characteristics between the two groups. Prior to PSM, our data revealed significant differences in clinicopathological variables between these groups. However, after implementing PSM, these differences were effectively eliminated, ensuring a more balanced comparison.Before matching, OS and BCSS rates in the TM + R group were superior to those in the TM group. Encouragingly, even after matching, we obtained consistent conclusions, further reinforcing the reliability of our research findings.

In our subgroup analysis, we meticulously examined various subgroups of patients who underwent breast reconstruction, and we observed no evidence to suggest that any particular subgroup experienced a detrimental effect on survival prognosis. Importantly, our findings revealed significant survival benefits associated with breast reconstruction, particularly among older patients, specifically those aged 60 years and above, in terms of both OS and BCSS. While breast reconstruction surgery is commonly preferred by young women diagnosed with breast cancer[20], age is not a risk factor for the safety of breast reconstruction surgery[21]. According to a comprehensive review encompassing 44 articles, it was concluded that elderly women should be proactively informed about the potential benefits of breast reconstruction, provided that adequate preoperative evaluation has been conducted and surgical safety measures are in place[22]. The survival benefit associated with breast reconstruction was evident among white individuals and those from other racial backgrounds, but not among individuals of black race. It is worth noting that this discrepancy may be attributed to the higher prevalence of smoking, diabetes, and obesity among African Americans compared to their white counterparts[23]. These factors could potentially impact the survival outcomes of black patients after breast reconstruction. Radiation therapy may be associated with adverse events of breast reconstruction surgery, such as: reconstruction failure, capsular contracture, and overall complications[24][25][26][27][28][29][30][31]. A retrospective study conducted on breast cancer patients demonstrated that radiotherapy had a positive impact on OS and BCSS in patients with N3 stage who underwent autologous breast reconstruction. However, contrasting results were observed for patients with N0 stage, where radiotherapy was associated with poorer survival outcomes[32]. In theory, it has been suggested that breast reconstruction surgery in breast cancer patients could potentially cause delays in chemotherapy administration, which could subsequently impact patient prognosis. However, several studies have investigated this concern and have found no evidence to support the notion that breast reconstruction surgery leads to chemotherapy delays or adversely affects survival outcomes[33], even in patients with LABC[34]. Hence, the impact of chemotherapy and radiotherapy on the survival outcomes of patients undergoing breast reconstruction remains inconclusive. Our study findings indicate that the receipt of chemotherapy and radiotherapy did not influence the survival benefit associated with breast reconstruction.

We postulate that the observed improved survival following TM with breast reconstruction may be attributed, to psychological factors. Breast reconstruction offers significant physical and psychological benefits by restoring the body shape and enhancing the overall well-being of women with breast cancer. Previous studies have consistently demonstrated an improvement in the quality of life for breast cancer patients undergoing various types of breast reconstruction, including implant-based reconstruction, TRAM flap reconstruction, and DIEP flap reconstruction[6][35]. Researches indicates that breast cancer patients who undergo total mastectomy without breast reconstruction may experience higher levels of postoperative emotional depression and anxiety, especially among younger individuals. The absence of breast reconstruction in these patients can have a profound psychological impact, contributing to heightened distress and diminished emotional well-being[36]. Additionally, mounting evidence suggests a potential association between negative psychological stress and unfavorable outcomes in breast cancer, including increased rates of disease recurrence and reduced overall survival. Psychological stress, characterized by factors such as depression, anxiety, and chronic stress, can exert a profound impact on the physiological functioning of the body, potentially influencing the progression and outcomes of breast cancer[37][38]. The findings from the study conducted by Heneghan HM et al. revealed that patients who underwent breast reconstruction exhibited a comparable quality of life to those who underwent breast-conserving surgery. This implies that breast reconstruction can provide substantial benefits in terms of overall well-being and psychological satisfaction[39]. The decision-making process regarding breast reconstruction is deeply personal and multifaceted. While this study has shed light on several important factors, it is crucial to acknowledge that additional variables, such as insurance coverage and education level, also play a significant role in influencing the choice of surgical options[40][41][42]. Social factors play a crucial role in the decision-making process of breast cancer patients and can indirectly reflect the availability of medical resources at their disposal, which in turn may impact their survival outcomes. It is important to acknowledge that these factors are interconnected and influence each other, rather than being isolated causes. Additionally, it is vital to recognize that every patient's situation is unique, and treatment plans should be tailored to individual circumstances.

There are several limitations in this study. First, comorbidity information is not available in the SEER database, so the included cases with PSM, it is impossible to completely avoid selection bias.Second, the SEER database did not provide data on endocrine therapy and targeted therapy, which is another limitation of this study. We were unable to explore the impact of endocrine therapy and targeted therapy—very important treatment modalities—on the survival of LABC patients with or without breast reconstruction after TM. Third, the SEER database does not provide data on patient recurrence, which also did not allow us to further investigate the surgical safety of breast reconstruction in LABC patients.

Our study findings support the association between breast reconstruction after total mastectomy (TM + R) and improved overall survival (OS) and breast cancer-specific survival (BCSS) in patients with locally advanced breast cancer (LABC), when compared to total mastectomy alone (TM). These results contribute to the existing evidence regarding the oncological safety of breast reconstruction in LABC patients and can serve as a valuable reference for clinicians when making treatment decisions. However, it is important to note that our study is retrospective in nature, and as such, prospective studies are warranted to validate our findings. Further research with larger sample sizes and longer follow-up periods would provide additional insights into the long-term survival outcomes of LABC patients undergoing breast reconstruction. The evidence generated from our study adds to the growing body of knowledge in this field and highlights the potential benefits of breast reconstruction in improving patient outcomes.

Data availability statement

The datasets generated for this study can be found in the Surveillance, Epidemiology, and End Results database (https://seer.cancer.gov/).

Funding

Joint project of Chongqing Health Commission and Science and Technology Bureau (No.2021MSXM067, receptor: Li Fan)

Acknowledgments

We would like to acknowledge the SEER registries for collecting the SEER data.

Ethics approval and consent to participate This study was exempt from the Institutional Review Board approval because SEER used nonidentifable patient information. The right to informed consent was waived due to the strictly registry-based nature of the study.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

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TABLE 1 The clinicopathological characteristics of BC patients before and after PSM.
	Before PSM			After PSM
Variables	M (n=33169)	R (n=5943)	p-value	M (n=4340)	R (n=4340)	p-value
Age			<0.001			0.585
20-39	2586( 7.7)	832( 13.9)		406 ( 9.3)	409 ( 9.4)
40-59	15799(47.6)	3685 (62.0)		2805 ( 64.6)	2828 (65.1)
60-79	14784 (44.7)	1426 (24.1)		1129 ( 26.1)	1103 (25.5)
Race			<0.001			0.985
White	24354(73.4)	4689(78.8)		3614 (83.2)	3622 (83.4)
Black	3300 (9.9)	612( 10.2)		327 (7.5)	334 (7.6)
Other	5515 (16.7)	642( 11.0)		399 ( 9.3)	384(9.0)
Laterality			0.205			0.78
Right	16308 (49.2)	2975( 50.0)		2192 ( 50.5)	2179 ( 50.2)
Left	16861 (50.8)	2968( 50.0)		2148 ( 49.5)	2161 ( 49.8)
Stage			<0.001			0.715
IIB	16000(48.2)	3175(53.4)		2546 ( 58.6)	2521 ( 58.0)
IIIA	9910 (29.8)	1877( 31.5)		1293 ( 29.7)	1327 ( 30.5)
IIIB	3572 (10.7)	360( 6.0)		174 ( 4.0)	151 (3.4)
IIIC	3687 (11.3)	531( 9.1)		327 ( 7.7)	341 ( 8.1)
Grade			<0.001			0.597
I	2782 (8.3)	662( 11.1)		347 ( 7.9)	346 ( 7.9)
II	13274 (40.0)	2745( 46.1)		2124 ( 48.9)	2100 ( 48.3)
III	16671 (50.2)	2479( 41.7)		1857 ( 42.7)	1877 ( 43.2)
IV	442 (1.5)	57( 1.1)		12 ( 0.5)	17 ( 0.6)
Tumor Size			0.527			0.891
<2cm	1490 (4.4)	329( 5.5)		141 ( 3.2)	147 ( 3.3)
2-5cm	12634 (38.0)	2108( 35.4)		1382 ( 31.8)	1377 ( 31.7)
>5cm	19045 (57.6)	3506( 59.1)		2817 ( 65.0)	2816 (65.0)
Lymph node			<0.001			0.598
Negative	3292 (9.9)	659( 11.2)		330 ( 7.7)	317( 7.3)
1-3 nodes	15128 (45.6)	3068( 51.6)		2494 ( 57.4)	2491 (57.3)
≥4 nodes	14749(44.5)	2216( 37.2)		1516 ( 34.9)	1532 (35.4)
HR Status			<0.001			0.809
HR+	25149(75.8)	4933( 83.0)		3703 ( 85.4)	3695 ( 85.1)
HR-	8020 (24.2)	1010( 17.0)		637 ( 14.6)	645 ( 14.9)
Histology			0.27			0.312
IDC	26629 (80.2)	4689( 78.8)		3632 ( 83.6)	3651 ( 84.1)
ILC	4118 (12.4)	953( 16.0)		592 ( 13.6)	596 ( 13.7)
Other	2422 (7.4)	301( 5.2)		116 ( 2.8)	93 ( 2.2)
Chemotherapy			<0.001			0.579
YES	25183 (75.9)	4873( 81.9)		3630 ( 83.7)	3649 ( 84.0)
NO/Unknown	7986 (24.1)	1070( 18.1)		710 ( 16.3)	691 (16.0)
Radiotherapy			<0.001			0.518
YES	16762 (50.5)	3189( 53.6)		2324 (53.6)	2354 (54.2)
NO/Unknown	16407 (49.5)	2754( 46.4)		2016 ( 46.4)	1986 (45.8)
Marital Status			<0.001			0.47
YES	18485 (55.7)	3740( 62.9)		2866 ( 66.0)	2834 ( 65.2)
NO/Unknown	14684 (44.3)	2203( 37.1)		1474 ( 34.0)	1506 ( 34.8)
Income			<0.001			0.52
<$70,000	17654 (53.2)	2978( 50.1)		2176 ( 50.1)	2206 ( 50.8)
≥$70,000	15515 (46.8)	2965( 49.9)		2164( 49.9)	2134( 49.2)
Region			<0.001			0.796
Urban	21972 (66.2)	4068(68.4)		3054 (70.3)	3065 ( 70.6)
Rural	11197 (33.8)	1875( 31.6)		1286 ( 29.7)	1275 ( 29.4)
M, mastectomy; R, reconstruction; HR Status, hormone receptor status; IDC, Invasive ductal carcinoma; ILC, Infiltrating lobular carcinoma.

TABLE 2.The 5-year and 10-year OS and BCSS rates of LABC patients.
The entire cohort before PSM
	M (n=33169)	R (n=5943)		M (n=33169)	R (n=5943)
5-year OS	25280(76.2%)	5192(87.3%)	5-year BCSS	26985(81.3%)	5296(89.1%)
10-year OS	21213(63.9%)	4702(79.1%)	10-year BCSS	24369(73.4%)	4888(82.2%)
The entire cohort after PSM
	M (n=4340)	R (n=4340)		M (n=4340)	R (n=4340)
5-year OS	3579(82.4%)	3830(88.2%)	5-year BCSS	3751(86.4%)	3904(89.9%)
10-year OS	3090(71.1%)	3467(79.8%)	10-year BCSS	3421(78.8%)	3604(83.0%)
M, mastectomy; R, reconstruction;OS, overall survival; BCSS, breast cancer specific survival.

TABLE 3. Subgroup analysis of overall survival and breast cancer specific survival in propensity score matched cohort [n = 8680].
Variables		OS		BCSS
Variables		HR[95%CI]	P value	HR[95%CI]	P value
Age
20-39	M	1 [Reference]		1 [Reference]
20-39	R	0.89 [0.7-1.14]	0.38	0.91 [0.7-1.18]	0.49
40-59	M	1 [Reference]		1 [Reference]
40-59	R	0.85 [0.77-0.94]	<0.05	0.92 [0.83-1.03]	0.18
60-79	M	1 [Reference]		1 [Reference]
60-79	R	0.57 [0.5-0.66]	<0.05	0.76 [0.62-0.91]	<0.05
Race
White	M	1 [Reference]		1 [Reference]
White	R	0.75 [0.69-0.82]	<0.05	0.89 [0.81-0.99]	0.03
Black	M	1 [Reference]		1 [Reference]
Black	R	0.73 [0.52-1.01]	0.05	0.8 [0.56-1.14]	0.22
Other	M	1 [Reference]		1 [Reference]
Other	R	0.73 [0.57-0.93]	0.01	0.81 [0.61-1.08]	0.15
Stage
IIB	M	1 [Reference]		1 [Reference]
IIB	R	0.73 [0.65-0.81]	<0.05	0.92 [0.81-1.05]	0.25
IIIA	M	1 [Reference]		1 [Reference]
IIIA	R	0.72 [0.63-0.83]	<0.05	0.8 [0.68-0.94]	<0.05
IIIB	M	1 [Reference]		1 [Reference]
IIIB	R	0.94 [0.68-1.3]	0.74	1.07 [0.75-1.52]	0.69
IIIC	M	1 [Reference]		1 [Reference]
IIIC	R	0.85 [0.68-1.08]	0.19	0.85 [0.66-1.09]	0.20
Grade
I	M	1 [Reference]		1 [Reference]
I	R	0.44 [0.3-0.64]	<0.05	0.52 [0.32-0.85]	0.01
II	M	1 [Reference]		1 [Reference]
II	R	0.75 [0.67-0.85]	<0.05	0.94 [0.81-1.09]	0.45
III	M	1 [Reference]		1 [Reference]
III	R	0.78 [0.7-0.87]	<0.05	0.86 [0.76-0.97]	0.01
IV	M	1 [Reference]		1 [Reference]
IV	R	0.64 [0.19-2.1]	0.46	1.91 [0.37-9.86]	0.43
HR status
HR+	M	1 [Reference]		1 [Reference]
HR+	R	0.72 [0.66-0.79]	<0.05	0.87 [0.78-0.96]	<0.05
HR-	M	1 [Reference]		1 [Reference]
HR-	R	0.88 [0.74-1.05]	0.17	0.92 [0.76-1.12]	0.44
Histology
IDC	M	1 [Reference]		1 [Reference]
IDC	R	0.75 [0.69-0.82]	<0.05	0.88 [0.8-0.97]	0.14
ILC	M	1 [Reference]		1 [Reference]
ILC	R	0.73 [0.58-0.92]	0.01	0.83 [0.62-1.1]	0.20
Other	M	1 [Reference]		1 [Reference]
Other	R	0.93 [0.62-1.4]	0.75	1.1 [0.69-1.77]	0.67
Chemotherapy
YES	M	1 [Reference]		1 [Reference]
YES	R	0.79 [0.73-0.87]	<0.05	0.89 [0.8-0.98]	0.01
NO/Unknown	M	1 [Reference]		1 [Reference]
NO/Unknown	R	0.58 [0.48-0.71]	<0.05	0.85 [0.66-1.09]	0.22
Radiotherapy
YES	M	1 [Reference]		1 [Reference]
YES	R	0.81 [0.73-0.9]	<0.05	0.9 [0.8-1.02]	0.10
NO/Unknown	M	1 [Reference]		1 [Reference]
NO/Unknown	R	0.69 [0.62-0.78]	<0.05	0.86 [0.75-0.98]	0.03
Marital status
YES	M	1 [Reference]		1 [Reference]
YES	R	0.83[0.75-0.92]	<0.05	0.98 [0.88-1.10]	<0.05
NO/Unknown	M	1 [Reference]		1 [Reference]
NO/Unknown	R	0.63[0.55-0.71]	<0.05	0.72 [0.62-0.84]	<0.05
Income
<$70,000	M	1 [Reference]		1 [Reference]
<$70,000	R	0.74[0.66-0.83]	<0.05	0.90[0.79-1.02]	<0.05
≥$70,000	M	1 [Reference]		1 [Reference]
≥$70,000	R	0.76[0.68-0.85]	<0.05	0.86[0.76-0.98]	<0.05
M, mastectomy; R, reconstruction; HR Status, hormone receptor status; IDC,Invasive ductal carcinoma;ILC, Infiltrating lobular carcinoma;OS, overall survival; BCSS, breast cancer specific survival.

No competing interests reported.

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Long-term Survival Outcomes in Patients with Locally Advanced Breast Cancer after Total Mastectomy with or without Breast Reconstruction: A Seer-based Analysis

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