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Abstract
Objective Breast-conserving therapy (BCT) includes breast-conserving surgery (BCS) combined with radiation therapy (RT). RT plays a crucial role in improving the prognosis of patients who undergo BCS. However, obesity is a potential risk factor for resistance to radiation. The aim of this study was to evaluate any difference in the long-term prognosis of patients with early stage breast cancer and obesity treated with BCT or total mastectomy (TM).
Design, setting and participants This was a retrospective cohort study involving 1125 patients diagnosed with early stage breast cancer and obesity at the Shanghai Cancer Center of Fudan University from 2013 to 2016.
Outcome measures Obesity in the Chinese population was defined as a body mass index ≥28 kg/m2. Surgical options included BCT and TM. The primary survival outcomes were overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS). Inverse probability of treatment weighting (IPTW) was used to control for the impact of confounding factors on prognosis.
Results The median follow-up times in the BCT group and TM group without postoperative RT were 51.1 months (IQR of 40.6–68.1 months) and 61.8 months (IQR of 46.5–76.7 months), respectively. After IPTW, the baseline data were balanced. Compared with those in the TM cohort, patients in the whole IPTW cohort in the BCT cohort had worse DFS (HR 4.280, 95% CI 2.180 to 8.400; p<0.001), RFS (HR 4.380, 95% CI 2.370 to 8.120; p<0.001) and OS (HR 3.590, 95% CI 1.620 to 7.950; p=0.002).
Conclusion In patients with early stage breast cancer and obesity, TM is associated with better survival outcomes than BCT.
- Breast tumours
- Breast surgery
- Retrospective Studies
- Obesity
Data availability statement
Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, JW, upon reasonable request. The data are not publicly available since this could compromise the privacy of the research participants.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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Strengths and limitations of this study
This was a large cohort study on the surgical approach and survival duration of patients with early stage breast cancer and obesity.
This study was based on a retrospective cohort study of Chinese patients.
It is necessary to further investigate the robustness and generalisability of the findings by conducting prospective studies and including other populations.
Introduction
In recent years, the global prevalence of obesity has rapidly increased, leading to a global epidemic.1 Over the past three decades, the number of individuals with obesity worldwide has more than doubled, with an estimated 1.9 billion overweight or obese adults.2 3 Obesity is among the top five causes of global mortality and accounts for 5% of all deaths.4 Furthermore, it is recognised as a risk factor for various malignancies, including breast cancer.5 Obesity, as measured by body mass index (BMI), is associated with poorer disease-specific survival, disease-free survival (DFS) and overall survival (OS) in patients with breast cancer.6–9 It increases the risk of local or regional breast cancer recurrence and may influence prognosis through its effects on systemic and local therapy. In patients with obesity, systemic treatment can improve local control of breast cancer, whereas ineffective systemic treatment may increase the risk of local recurrence.10 The detrimental effects of obesity on local control may lead to worse breast cancer-specific survival and/or DFS, as improved local control after radiation therapy (RT) has been shown to increase breast cancer-specific survival.10
Breast-conserving therapy (BCT), consisting of breast tumour excision and local RT, is employed for invasive breast cancer and ductal carcinoma in situ. Previous studies have shown no difference in long-term prognosis between BCT and total mastectomy (TM).11 12 Additionally, RT reduces the long-term risk of local recurrence.13 Indeed, RT has long been used to treat various malignancies, including breast cancer, and has been shown to significantly improve patient survival.14 However, resistance to RT, which is characterised by the absence of a response of some cancer cells to radiation, remains a major challenge.14 Obesity is considered a risk factor for radiation resistance and metastasis, and overall poor prognosis in patients with breast cancer.15–17 If women receiving whole-breast RT have two or more breast cancer risk factors, including obesity, the likelihood of developing regional recurrence increases by 12.6% after 5 years.18 Obesity-induced radiation resistance may arise through mechanisms involving DNA repair and adipose-derived stem cells.11 19
Therefore, RT plays a critical role in breast-conserving surgery (BCS), with obesity being a risk factor for radiation resistance. The choice between BCT and TM in patients with obesity and early stage breast cancer still needs further clarification. Accordingly, we conducted a retrospective analysis of 1125 patients with early stage breast cancer and obesity who received treatment at the Shanghai Cancer Center of Fudan University from 2013 to 2016 to compare long-term prognoses following different surgical methods.
Methods
Data sources and study design
In this study, which was conducted at the Shanghai Cancer Center of Fudan University, a total of 18 700 patients were recruited between 2013 and 2016. The patient population had a BMI ranging from 12.9 kg/m2 to 39.13 kg/m2. Of the entire cohort, 1125 patients were early stage breast cancer with obesity, accounting for 6% of the overall population. To be included in this study, the patients met specific inclusion criteria, including primary breast cancer without metastasis, clinical stage T1–2N0M0, and no prior neoadjuvant therapy, such as chemotherapy, RT, or endocrine therapy. Furthermore, they did not have serious complications arising from conditions such as hypertension, diabetes mellitus or other underlying diseases.
All patients underwent diagnostic mammography and ultrasonography to identify any additional calcifications or masses. To be eligible for BCS, the surgical margins had to be negative. In cases in which positive margins were observed, wider resection ensured that the distance between the margin and the lesion was ≥5 mm. Patients eligible for BCS had singular or limited localised lesions that could be completely excised according to predetermined criteria. In addition, all patients who underwent BCS expressed a strong desire to preserve their breasts and agreed to postoperative RT. Patients with multicentric lesions, nipple involvement (such as Paget’s disease of the nipple), active connective tissue disease with poor radiotherapy tolerance, or unwillingness to receive RT for personal or economic reasons are typically recommended to undergo TM.
Laboratory data
Immunohistochemistry (IHC) was performed on tumour samples using an IHC staining module that specifically targeted oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The IHC results were evaluated by a breast pathologist and further reviewed by senior experts. Clinical and pathological staging was performed according to the guidelines outlined in the American Joint Committee on Cancer Staging Manual, eighth edition.20 HER2 positivity was determined based on IHC or fluorescence in situ hybridisation positivity. oestrogen receptor and PR were considered positive when expressed in 1% or more of the cells of a section; Ki67 was classified as high if 14% or more of the cells of a section stained positive.
Ethics and consent
This research complied with the Declaration of Helsinki. All patients provided informed consent when the database was constructed.
Definition of patients with obesity
According to the WHO, BMI for adults is 18.5 kg/m2<BMI≤24.9 kg/m2 for normal weight, 25 kg/m2≤BMI≤29.9 kg/m2 for overweight, and≥30 kg/m2 for obese. The standard was based on data from European and American populations.21 Due to the differences in skeletal, height and muscle development between Asians and Europeans and Americans, reference standards for overweight and obesity boundary values suitable for the Chinese population have been proposed as follows: 18.5 kg/m2≤BMI<24 kg/m2 for normal weight, 24 kg/m2≤BMI<28 kg/m2 for overweight, and a BMI≥28 kg/m2 for obese. In this study, with reference to the Chinese BMI obese population standard, BMI≥28 kg/m2 was defined as obese.22
Study endpoints
OS, DFS and recurrence-free survival (RFS) were the endpoints of this study. OS was defined as the time from the end of the diagnosis process to death from any cause. RFS was defined as the time from the end of the diagnosis process to tumour recurrence or the development of a new primary breast tumour. Finally, DFS was defined as the time from end of the diagnosis process to the time of tumour recurrence, metastasis or death from any cause.
Data integration and statistical methods
Descriptive statistics or columns are used to summarise patient demographic and baseline characteristics. Differences in clinicopathological characteristics between groups were assessed using the χ2 test or Fisher’s exact test.
To account for selection bias and potential confounding factors between groups, a propensity model was constructed using the inverse probability of treatment weighting (IPTW) approach. The weight of each patient was determined based on the inverse probability of belonging to the TM group compared with the BCS group, aiming to achieve a balance in observed characteristics, such as menopausal status, tumour grade, pathological T stage, pathological N stage and PR status.
Survival curves were constructed using the Kaplan‒Meier (KM) method, and the log-rank test was used to compare survival between groups. HRs with 95% CIs were estimated using Cox proportional hazards regression analysis.
The R programming language (V.4.1.3) was employed for data analysis and graphical plotting. A value of p<0.05 was considered to indicate statistical significance for all statistical analyses.
Results
Clinical baseline information of patients with obesity in the TM and BCS groups
The study flow chart of our investigation is presented in online supplemental figure 1. Patients were divided into two groups according to the surgical intervention they received: the TM group and the BCS group. In the TM group, 885 patients had a median BMI of 29.0 (IQR 28.0–30.0) kg/m2 and a median follow-up time of 61.1 (IQR 46.2–77.7) months. In the BCS group, 240 patients had a median BMI of 29.0 (IQR 28.0–30.3) kg/m2 and a median follow-up time of 50.7 (IQR 40.9–66.9) months. Among the patients who underwent TM treatment, 185 received RT. A total of 176 patients who underwent BCS completed postoperative RT. The specific indications for radiotherapy and the corresponding strategies were evaluated by a radiation oncologist for a more standardised approach. However, 35 patients refused RT due to external or uncontrollable factors, and no records were available for 34 patients.
Supplemental material
Online supplemental table 1 displays the clinical and pathological characteristics of the patients with obesity before and after IPTW. Before IPTW, a greater percentage of premenopausal patients were in the BCS group (36.2% vs 29.5%, p=0.045), had a grade 1 tumour (54.6% vs 53.9%, p<0.001), had a pathological T1 stage (67.1% vs 52.8%, p<0.001), had a pathological N0 stage (82.1% vs 69.3%, p<0.001), and were PR positive (73.8% vs 66.9%, p=0.043) than in the TM group. After IPTW, menopausal status, tumour grade, pathological T stage, pathological N stage and PR status were balanced between the groups (all p>0.050) (online supplemental table 1).
Survival analyses of patients with obesity in the TM and BCS groups
In the TM group, there were 34 deaths (4.0%) and 36 cases of local recurrence or distant metastasis (4.2%). In the BCS group, 15 patients died (6.3%), and 21 patients experienced local recurrence or distant metastasis (8.8%). The 3-year, 5-year and 7-year DFS rates of the TM group were 98.3%, 95.5 and 91.7%, respectively, and 96.9%, 88.8% and 79.4% in the BCS group, respectively (figure 1A). The 3-year, 5-year and 7-year RFS rates in the TM group were 99.2%, 97.5% and 94.0%, respectively; in the BCS group, they were 97.8%, 91.3% and 81.7%, respectively (figure 1B). The 3-year, 5-year and 7-year OS rates of the TM group were 98.4%, 96.9% and 95.4%, respectively; they were 97.4%, 93.0% and 88.6% in the BCS group, respectively (figure 1C). Therefore, patients in the TM group had superior outcomes to those in the BCS group in terms of DFS, RFS and OS.
Kaplan‒Meier (KM) curves of (A) DFS, (B) RFS and (C) OS in patients with obesity who underwent different surgical approaches before and after IPTW. BCS, breast-conserving surgery; DFS, disease-free survival; IPTW, inverse probability of treatment weighting; OS, overall survival; RFS, relapse-free survival; TM, total mastectomy.
After IPTW, the TM group still exhibited significantly better DFS, RFS and OS than did the BCS group (p<0.001, p<0.001 and p=0.009, respectively) (figure 1A–1C).
Factors affecting the prognosis of the population with obesity
After IPTW, the results of multivariate analysis showed that HER2 status (positive vs negative: HR 0.350, 95% CI 0.150 to 0.820, p=0.015) and surgical procedure (BCS vs TM: HR 3.390, 95% CI 2.090 to 5.520, p<0.001) were independent predictive factors for DFS (online supplemental table 2). As indicated in online supplemental table 3, HER2 status (positive vs negative: HR 0.270, 95% CI 0.120 to 0.590, p=0.001), adjuvant hormonal therapy (yes vs no: HR=0.290, 95% CI 0.180 to 0.490, p<0.001) and surgical procedure (BCS vs TM: HR=4.440, 95% CI 2.630 to 7.520, p<0.001) were independent predictive factors for RFS. Furthermore, as shown in online supplemental table 4, menopausal status (postmenopausal vs premenopausal: HR 4.400, 95% CI 1.730 to 11.200, p=0.002), pathological T stage (T2 vs T1: HR 3.090, 95% CI 1.520 to 6.270, p=0.002) and surgical procedure (BCS vs TM: HR 2.860, 95% CI 1.410 to 5.790, p=0.004) were independent predictive factors for OS.
Survival analyses of patients with obesity in the BCS group, BCS+RT group, and TM group without postoperative RT
To explore prognostic differences between patients with obesity treated with BCS or TM, we further performed survival prognostic analyses on three groups of 700 patients treated with TM without postoperative RT, 35 patients treated with BCS but not receiving RT due to external factors, and 176 treated with BCS and receiving postoperative RT. In the TM group, 700 patients had a median BMI of 29.0 (IQR 28.0–30.0) kg/m2 and a median follow-up time of 61.8 (IQR 46.5–76.7) months. In the BCS group, 35 patients had a median BMI of 29.0 (IQR 28.0–31.0) kg/m2 and a median follow-up time of 52.1 (IQR 45.1–61.9) months. In the BCS+RT group, 176 patients had a median BMI of 29.0 (IQR 28.0–30.0) kg/m2 and a median follow-up time of 51.1 (IQR 40.6–68.1) months.
Online supplemental table 5 lists the baseline characteristics of these patients. Compared with those in the TM group and the BCS group without postoperative RT, a greater percentage of patients in the BCS+RT group were under 60 years old, were premenopausal, had a tumour grade of 1 and received adjuvant chemotherapy.
In the TM group, there were 20 deaths (2.9%) and 21 cases of local recurrence or distant metastasis (3.0%). In the BCS group, three patients died (8.6%), and four experienced local recurrence or distant metastasis (11.4%). In the BCS+RT group, there were 11 deaths (6.3%) and 15 cases of local recurrence or distant metastasis (8.5%). Survival analysis demonstrated that the TM group had better 3-year, 5-year and 7-year DFS rates (98.7%, 96.3% and 93.0%, respectively) than the BCS without RT group (97.1%, 76.1%, 76.1%) and the BCS with RT group (96.4%, 92.0%, 79.7%) (figure 2A). Moreover, the TM group had higher 3-year, 5-year and 7-year RFS rates (99.4%, 98.2% and 94.8%, respectively) than the BCS without RT group (97.1%, 79.2%, 79.2%) and the BCS with RT group (97.6%, 94.0%, 81.4%) (figure 2B). Additionally, the 3-year, 5-year and 7-year OS rates were higher (98.7%, 97.5% and 96.8%, respectively) than those of the BCS without RT group (97.1%, 86.5%, 86.5%) and the BCS with RT group (97.0%, 93.9%, 88.2%) (figure 2C). These findings suggest that adding adjuvant RT in combination with BCS can improve DFS, RFS and OS. Furthermore, the prognosis of BCS patients with obesity, even after the addition of postoperative RT, remains lower than that of patients who undergo TM without postoperative RT.
Kaplan‒Meier (KM) curves of (A) DFS, (B) RFS and (C) OS in patients with obesity who underwent different surgical approaches BCS, breast-conserving surgery; DFS, disease-free survival; OS, overall survival; RT, radiation therapy; RFS, relapse-free survival; TM, total mastectomy.
Survival analyses of patients with obesity in the BCS+RT group and TM group without postoperative RT
We performed subgroup analysis to further explore the value of BCS with RT versus TM for determining the prognosis of patients with obesity. Table 1 describes differences in baseline characteristics between the BCS+RT group and TM group without postoperative RT. Before IPTW, we observed that among patients undergoing BCS treatment, there were higher proportions of individuals younger than 60 years old, premenopausal status, tumour grade 1, pathological stage T1, ER−/PR−/HER2− subtype, and ER+ or PR+/HER2+ subtype compared with the TM group. However, the effect of these potential confounders was neutralised after IPTW (all p>0.05), suggesting that the groups were balanced in terms of these characteristics.
Clinical and pathological characteristics of patients with obesity in the BCS+RT group and TM group without postoperative RT
Survival analysis revealed that the 3-year, 5-year and 7-year DFS rates in the TM group were 98.7%, 96.3% and 93.0%, respectively, which were better than those in the BCS+RT group (96.4%, 92.0% and 79.7%, respectively) (figure 3A). The 3-year, 5-year and 7-year RFS rates in the TM group were also greater than those in the BCS+RT group (99.4%, 98.2% and 94.8%, respectively) (97.6%, 94.0%, 81.4%) (figure 3B). Furthermore, the 3-year, 5-year and 7-year OS rates in the TM group were 98.7%, 97.5% and 96.8%, respectively, which were superior to those in the BCS+RT group (97.0%, 93.9%, 88.2%) (figure 3C).
Kaplan‒Meier (KM) curves of (A) DFS, (B) RFS and (C) OS in the BCS+RT group and TM group without postoperative RT before and after IPTW. BCS, breast-conserving surgery; DFS, disease-free survival; IPTW, inverse probability of treatment weighting; OS, overall survival; RFS, relapse-free survival; RT, radiation therapy; TM, total mastectomy.
Prognostic factors of patients with obesity in the BCS+RT group and TM group without postoperative RT
After IPTW, multivariate analysis revealed several key factors that predicted different outcomes.
For DFS, pathological T stage (T2 vs T1: HR 2.520, 95% CI 1.200 to 5.280, p=0.014), Ki67% (>14 vs ≤14: HR 3.420, 95% CI 1.270 to 9.250, p=0.015) and surgery (BCS with RT vs TM: HR 4.280, 95% CI 2.180 to 8.400, p<0.001) were identified as independent predictors (table 2).
IPTW-adjusted univariate and multivariate analyses of the association between the DFS rate and clinical factors of patients with obesity in the BCS+RT group and TM group without postoperative RT
In addition, Ki67% (>14 vs ≤14: HR 2.960, 95% CI 1.010 to 8.730, p=0.049) and surgery type (BCS with RT vs TM: HR 4.380, 95% CI 2.370 to 8.120; p<0.001) were found to be independent factors for predicting RFS (online supplemental table 6).
Furthermore, menopausal status (postmenopausal vs premenopausal: HR 7.790, 95% CI 2.420 to 25.080, p=0.001), tumour grade (2–3 vs 1: HR 3.360, 95% CI 1.030 to 10.990, p=0.045), pathological T stage (T2 vs T1: HR 2.990, 95% CI 1.130 to 7.920, p=0.028), and surgery type (BCS with RT vs TM: HR 3.590, 95% CI 1.620 to 7.950, p=0.002) were independent predictors of OS (online supplemental table 7).
Prognostic factors in patients without obesity
We further selected the overweight population (24 kg/m2≤BMI<28 kg/m2) and the population with normal weight (18.5 kg/m2≤BMI<24 kg/m2) from the patients with early stage breast cancer for analysis, in order to investigate the relationships between surgical methods, clinical pathological factors and prognosis. The baseline data for the population with normal weight and the population with overweight can be found in online supplemental tables 8 and 9. After IPTW, the results of the multivariate analysis show that the surgical method is not an independent factor influencing DFS (online supplemental tables 10 and 11), RFS (online supplemental tables 12 and 13) or OS (online supplemental tables 14 and 15), regardless of whether it is in the population with normal weight or the overweight population.
Survival analyses of the BCS+RT group and TM group in the total population
We finally plotted KM curves for patients undergoing BCS+RT and TM in different BMI populations, as shown in figure 4. The results showed that patients with obesity who underwent BCS+RT treatment had the lowest prognostic outcomes, regardless of whether it was in terms of OS, DFS or RFS. In addition, ignoring the BMI factor, we further compared the survival benefits of BCS+RT treatment and TM treatment in the overall population. The results showed that there was no significant difference in the long-term survival benefits of patients between the two surgical methods (online supplemental figure 2).
Kaplan‒Meier (KM) curves of (A) DFS, (B) RFS and (C) OS in the BCS+RT group and TM group among patients with different BMI levels. BCS, breast-conserving surgery; BMI, body mass index; DFS, disease-free survival; OS, overall survival; RFS, relapse-free survival; RT, radiation therapy; TM, total mastectomy.
Discussion
Our study revealed that patients with early stage breast cancer and obesity who underwent TM achieved better DFS, RFS and OS than those who underwent BCS. Further analyses showed that BCS combined with RT was superior to BCS alone, but its prognosis was still inferior to that of TM. Furthermore, when comparing the prognostic differences between different surgical methods in the overall population, the results found no significant difference in long-term prognosis between TM and BCS plus RT if the distribution of BMI in the overall population is not considered. Additionally, when comparing the effects of different surgical methods on prognosis in the normal BMI and overweight populations, the results also found no significant prognostic difference between the different surgical approaches.
Current research concludes that there are no significant differences in long-term survival outcomes between the BCS+RT and TM treatment methods in early stage breast cancer. For instance, the results of two meta-analyses on the prognostic differences between the BCS+RT and TM treatment methods in early stage breast cancer showed no statistically significant differences in long-term prognostic outcomes such as OS, local recurrence rate and DFS rate between the BCS+RT and TM groups.23 24 This is consistent with our research conclusions in the overall population.
However, to date, there has been little research focusing on obese patients with breast cancer, especially the long-term prognostic differences between the BCS+RT and TM treatment methods in the Chinese population. Our study found that in obese patients with breast cancer in China, the prognosis of the BCS+RT group is worse than that of the TM group. Further subgroup analysis found that radiotherapy resistance may be the reason why the treatment outcomes for patients with obesity undergoing BCS surgery are worse than those undergoing TM.
Rapiti et al reported that BCS is associated with worse prognosis than TM in patients with breast cancer but that BCS+RT is associated with better prognosis than TM.25 Similar conclusions were reached by Guidolin et al, suggesting that adjuvant RT has a protective effect on recurrence and survival in patients with early stage breast cancer.26 These findings suggest that RT may be a key factor influencing the long-term prognosis of patients treated with both surgical modalities. Moreover, obesity itself is a definitive adverse prognostic factor for early stage breast cancer.27–29 Numerous studies have shown that obesity often leads to resistance to chemotherapy, endocrine therapy and RT.30–35 Additionally, the influence of obesity on the pharmacokinetics and pharmacodynamics of anticancer drugs is multifaceted and variable. First, obesity can directly or indirectly affect the pharmacokinetics of small molecules and complex drugs (such as antibodies and antibody–drug conjugates) and alter metabolism of drugs in the liver and their elimination through the kidneys, thereby changing drug exposure in the blood, tissues and particularly in tumours.36 Furthermore, obesity potentially impacts drug exposure by modifying the function and phenotype of the innate immune system.37 Previous studies have found that BMI is a significant factor affecting the pharmacokinetics of drugs such as doxorubicin, cyclophosphamide, trastuzumab, tamoxifen and anastrozole.38–42 As a result, the effects of obesity on pharmacokinetics might alter the efficacy and toxicity of anticancer drugs, making it a critical factor in determining prognosis. Although the causal mechanism by which obesity affects prognosis has yet to be determined, it is believed to be related to the biology of the disease or to poorer treatment outcomes in patients with obesity.30 While RT reduces the risk of recurrence after BCS for breast cancer, its potential protective effects may diminish in patients with obesity. RT resistance significantly increases the risk of local recurrence, thus affecting the long-term survival of patients. However, the specific mechanisms of RT resistance in breast cancer remain unclear. Sabol et al discovered that adipose-derived stem cells altered by obesity promote radiation resistance in oestrogen receptor-positive breast cancer through paracrine signalling.11 Su et al reported that ionising radiation induces DNA double-strand breaks (DSBs) and enhances Serpin Family E Member 1 (SERPINE1) expression in cancer cells in an Ataxia Telangiectasia Mutated/Ataxia Telangiectasia and Rad3-Related (ATM/ATR)-dependent manner, which promotes nuclear localisation of SERPINE1 and facilitates DSB repair. The link between obesity and RT resistance in triple-negative breast cancer has been revealed, with SERPINE1 identified as a key factor mediating RT resistance in obesity-associated tumours.19
Therefore, the superior prognosis of patients who undergo TM compared with BCT is likely attributed to differences in RT resistance among patients with obesity. Considering the above conclusions, patients with early stage breast cancer and obesity who show RT resistance may benefit more from TM or breast reconstruction surgery. Nevertheless, clinical application of these findings requires validation through large-scale randomised experiments.
One of the strengths of this study is that we adopted measures to balance potential confounding factors. The baseline characteristics of patients in subgroups, such as age, pT stage, pN stage and PR status, were somewhat heterogeneous. Regardless, we confirmed the prognostic differences between different surgical methods using IPTW without compromising the sample size. This approach helps to reduce confounding bias or covariate imbalance.
Our study has several limitations. First, this was a retrospective study with a relatively small sample size and was conducted at a single centre. Second, our data lacked information on obesity-related complications such as diabetes and hypertension. We did not conduct subgroup analysis on additional dimensions, such as cholesterol level, which may provide a more refined definition of obesity. Patients with obesity often have comorbidities such as diabetes and hypertension, which may influence treatment choices and prognoses. Additionally, patients with diabetes prefer TM to BCS, but diabetes itself does not seem to influence the choice of RT among patients who undergo BCS.43 Third, whether the impact of obesity on the pharmacokinetics of drugs will affect the conclusions of this study is still worth further exploration. Finally, this study used BMI standards for the Asian population to define obesity, which may limit the generalisability of the results. No similar studies have been performed in Asia, and further exploration through randomised experiments or retrospective analyses in other regions is needed.
Conclusion
In patients with early stage breast cancer and obesity, TM is associated with better survival outcomes than BCT.
Data availability statement
Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, JW, upon reasonable request. The data are not publicly available since this could compromise the privacy of the research participants.
Ethics statements
Patient consent for publication
Ethics approval
This research was granted approval by the Ethics Committee of Shanghai Cancer Center, Fudan University (Shanghai, China; ID: 050432-4-1911D, 1905202–7), and complied with the Declaration of Helsinki.
References
Footnotes
LL and JP contributed equally.
Contributors LL and JP: Conceptualisation, data curation, formal analysis, methodology, validation, writing—original draft. YY, QZ, SZ and MC: Investigation, resources, writing—review and editing. JW and WY: Conceptualisation, funding acquisition, investigation, resources, supervision, writing—original draft. The work reported in the article has been performed by the authors, unless clearly specified in the text. LL and JP contributed equally. JW is the guarantor.
Funding This study was funded by the Academic Leaders of Shanghai Science and Technology Commission (18XD1401300) and the Youth Program of the National Natural Science Foundation of China (82002797), the Changsha Natural Science Fundation (kq2208336), the Hunan Provincial Natural Science Fundation (2023JJ40831; 2023JJ60441), and the Scientific ResearchLaunch Project for new employees of the Second Xiangya Hospital of Central South University (2022- 086).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.