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. 2025 Jun 2;21(15):1929–1938. doi: 10.1080/14796694.2025.2505372

The effect of postmastectomy radiotherapy after neoadjuvant chemotherapy in patients with breast cancer: a meta-analysis

Aishan Zou a,b, Liuyi Li b, Yang Guo b, Cuiwei Zhang a,c,✉
PMCID: PMC12150640  PMID: 40452500

ABSTRACT

Background

Recent advancements in NAC efficacy have sparked considerable debate regarding the role of postmastectomy radiation therapy (PMRT) in breast cancer treatment.

Methods

A comprehensive search of PubMed, Embase, and Cochrane databases was conducted to identify all relevant studies examining the prognostic significance of PMRT in breast cancer patients. The incidence of adverse events was aggregated to determine the correlation between PMRT and patient survival outcomes.

Results

The current meta-analysis included 15 eligible studies. Patients who received PMRT numbered 42,289, while 23,199 did not receive these treatments. No significant difference was observed between PMRT and OS (pooled RR 0.93; 95% CI 0.83–1.04) or DMFS (pooled RR 1.12; 95% CI 0.99–1.28) in predicting breast cancer outcomes. PMRT was associated with improved DFS in patients with lymphovascular invasion (LVI) (pooled RR 0.33; 95% CI 0.19–0.57). The meta-analysis found no significant correlation between PMRT and OS in patients with pathological complete remission (pCR) (HR 0.86; 95% CI 0.68–1.07).

Conclusion

No significant difference was observed between PMRT and OS. While PMRT did not improve overall survival in the entire group, our subgroup analyses suggest selective benefit for non-pCR or LVI positive patients. These findings may aid in the clinical decision-making process.

KEYWORDS: Breast cancer, neoadjuvant chemotherapy, mastectomy, postmastectomy radiotherapy, meta-analysis

1. Background

Neoadjuvant chemotherapy followed by surgery is nowadays used in a significant number of patients presenting with locally advanced breast cancer. Retrospective studies remain the main source of information guiding the selective use of radiotherapy after neoadjuvant chemotherapy and mastectomy. This is one of the reasons why there are still many uncertainties regarding the indications of postmastectomy radiotherapy in this patient population [1]. A growing number of breast cancer patients are receiving NAC as preoperative treatment. The potential benefits of NAC include reduced distant metastasis, decreased disease staging, and evaluation of chemotherapy sensitivity [2–4]. NAC is recommended for patients with locally advanced operable breast cancer and is increasingly used for early-stage breast cancer. Early randomized trials have demonstrated that NAC is equivalent to adjuvant chemotherapy in terms of survival. Furthermore, these trials have shown that NAC, following a favorable response to chemotherapy, increases the rate of breast preservation and can lower the risk of local recurrence [5]. However, the role of postmastectomy radiation therapy (PMRT) in breast cancer treatment has been a subject of intense debate, particularly with recent improvements in NAC efficacy [6]. Disagreement exists regarding patient selection for PMRT after NAC. NAC modifies the visible degree of disease pathology at the time of mastectomy, sparking a discussion about which factor is most critical for radiation therapy decisions: the initial clinical burden of disease before NAC, the residual pathological burden after NAC, or the response to NAC [7].

Currently, the combined effects of NAC and PMRT on breast cancer patients remain unclear. Some studies suggest that patients who respond well to NAC may not benefit from PMRT [8]. One of the most contentious questions surrounding PMRT indications is whether adjuvant radiation is necessary for patients diagnosed with early-stage disease. Additionally, there is ongoing debate about the utility of PMRT for patients with clinically negative lymph nodes after NAC completion [1].

Some proponents argue that adjuvant radiation may not offer significant benefits for patients with pathologically negative lymph nodes post-NAC, asserting that pathological lymph node status after chemotherapy is crucial [9]. It has been demonstrated that prognosis correlates with the degree of NAC response, with patients achieving pCR having the best relative disease-free survival (DFS) [10]. Therefore, if NAC can sufficiently reduce the risk of locoregional recurrence-free survival (LRFS) following surgery, the addition of adjuvant radiation may not significantly lower the risk of breast cancer mortality [11].

Nevertheless, the value of PMRT remains debatable due to the small sample sizes and discrete outcomes of most published studies. Consequently, to clarify the prognostic significance of PMRT in breast cancer patients, we conducted the present quantitative meta-analysis.

2. Materials and methods

2.1. Study strategy

This review was conducted following the established protocols for meta-analyses and systematic reviews. Independent searches were performed by Liuyi Li and Aishan Zou in the Cochrane, PubMed, and Embase databases to identify all relevant literature regarding the impact of adjuvant radiation on survival in breast cancer patients. The final date for the literature search was 28 July 2023. Both MeSH terms and free-text phrases were employed to enhance search sensitivity. The key search terms included: “Neoplasm, Breast,” “Breast Tumors,” “Breast Tumor,” “Breast Carcinoma,” “Tumor, Breast,” “Tumors, Breast,” “Neoplasms, Breast,” “Breast Cancer,” “Cancer, Breast,” “Mammary Cancer,” “Cancer, Mammary,” “Malignant Neoplasm of Breast,” “Breast Malignant Neoplasm,” “Breast Malignant Neoplasms,” “Malignant Tumor of Breast,” “Breast Malignant Tumor,” “Breast Malignant Tumors,” “Cancer of Breast,” “Cancer of the Breast,” “Carcinoma, Human Mammary,” “Carcinomas, Human Mammary,” “Human Mammary Carcinomas,” “Mammary Carcinomas, Human,” “Human Mammary Carcinoma,” “Mammary Neoplasms, Human,” “Human Mammary Neoplasm,” “Human Mammary Neoplasms,” “Neoplasms, Human Mammary,” “Breast Carcinoma,” “Breast Carcinomas,” “Carcinoma, Breast,” “Carcinomas, Breast,” “neoadjuvant chemotherapy,” “Chemotherapy, Neoadjuvant,” “Neoadjuvant Chemotherapies,” “Neoadjuvant Chemotherapy Treatment,” “Chemotherapy Treatment, Neoadjuvant,” “Neoadjuvant Chemotherapy Treatments,” “Treatment, Neoadjuvant Chemotherapy,” “Adjuvant Radiotherapy,” “Adjuvant Radiotherapies,” “Radiotherapies, Adjuvant,” “Radiotherapy, Adjuvant,” “survival,” “outcome,” “prognosis,” and “prognostic.” Any conflicts were resolved through group discussion.

2.2. Inclusion and exclusion criteria

The studies deemed eligible for inclusion in this analysis had to fulfill the following criteria: (1) The cohort was classified based on the administration of postmastectomy radiation therapy (PMRT) or its absence. (2) The study investigated the association between PMRT and survival outcomes. (3) At least one study included clinical outcomes such as overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Local recurrence was defined as primary site recurrence, including anastomotic or regional lymph nodes. Distant metastasis was defined as the involvement of distant organs or lymph nodes. (4) The cases involved female patients with pathologically confirmed breast cancer. (5) The study type was randomized controlled trial or retrospective study.

The exclusion criteria were as follows: (1) Non-female breast cancer patients. (2) Patients with a history of other malignant tumors. (3) For duplicate publications, the latest and most comprehensive data were included. Studies lacking available or reliable data were excluded. (4) Laboratory articles, reviews, letters, case reports, non-English or unpublished articles, and conference abstracts. All eligible studies were meticulously screened by two researchers, and any discrepancies were resolved through discussion with a third researcher.

2.3. Data extraction

Two investigators independently extracted relevant data and reached a consensus on all items. For all eligible studies, the following information was collected: author, year of publication, region, sample size, Newcastle – Ottawa Scale (NOS) score, characteristics of the study population (including the number of patients, follow-up duration in months, and median age), endpoints, and survival analysis. The endpoints included overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). The relative risk (RR) was extracted according to the suggested methodology to evaluate the influence of PMRT on patient prognosis.

2.4. Quality assessment

The quality of all included studies was independently assessed by two researchers using the validated Newcastle – Ottawa Scale (NOS). Any disagreements were resolved through discussion with a third researcher.

2.5. Statistical analysis

Review Manager 5.4 was used for statistical analysis. A summary of the quantity of adverse events in both the PMRT and non-PMRT groups was provided. Inter-study heterogeneity was evaluated using I2 statistics. For statistical significance, a p-value of less than 0.05 or an I2 value of more than 50% was required. The study initially employed a fixed-effect model, which revealed no substantial heterogeneity among the studies (p < 0.05, I2 ≤50%). Therefore, a random-effects model was selected instead. Subgroup analysis of the included studies was conducted based on similar features to investigate the origins of variability. Additionally, sensitivity analysis was performed to evaluate the impact of each study on the overall pooled results. Review Manager 5.4 was also used to assess publication bias.

3. Results

3.1. Characteristics of studies

Using the specified search strategy, the initial algorithm retrieved a total of 1,669 studies. We did not find the target literature in other sources, such as Citation Tracking, Handsearching, etc. After removing duplicates, 1,437 studies remained. The following types of studies were excluded: unrelated topics, meeting abstracts, case reports, reviews, studies with no usable data, and non-English articles. Ultimately, 15 studies meeting the inclusion criteria were included in the current meta-analysis (Figure 1).

Figure 1.

Figure 1.

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The flow diagram indicated the process of study other sources, such as citation tracking, handsearching, etc.

The main characteristics of the included studies are shown in Table 1. These studies included a minimum sample size of 39 patients and a maximum sample size of 29,270 individuals, totaling 42,289 participants. Chemotherapy was administered to each patient before surgery. Most patients received chemotherapy regimens containing taxanes and anthracyclines. PMRT was advised and prescribed by the treating physician based on clinicopathologic findings. The accrual periods of these studies varied from 2004 to 2021, with median follow-up periods ranging from 39 to 75 months. Four different types of survival outcomes were reported in the enrolled studies, including OS (n = 8) [5,12–19] in 56,737 patients, DFS (n = 4) [8,12,15,19,20] in 11,412 patients, LRFS (n = 10) [12,14,15,18,21–26] in 9,585 patients, and DMFS (n = 4) [12,14,15,21] in 7,613 patients. The results should also mention the incidence of locoregional recurrence and the respective DFS, DMFS, and OS.

Table 1.

Characteristics of studies included in the meta-analysis.

Author Year Region study design sample size median follow-up(months) PMRT NO PMRT Endpoints NOS Method
Krug et al. [8] 2019 Germany retrospective 817 51.5 676 141 DFS, LRFS 7 2
Wu [12] 2014 China retrospective 39 – 23 16 OS, DFS, LRFS, DMFS 7 1
Liu [13] 2016 USA retrospective 1560 – 903 657 OS 7 2
Miyashita et al. [14] 2019 Japan retrospective 3226 – 993 2233 OS, LRFS, DMFS 7 2
Shim et al. [15] 2014 Korea retrospective 151 57 105 46 OS, DFS, LRFS, DMFS 7 1
Haque et al. [16] 2021 USA retrospective 14690 55.6 10092 4598 OS 7 1
Ohri et al. [17] 2017 USA retrospective 29270 – 18284 10986 OS 7 1
Huang et al. [18] 2004 USA retrospective 676 PMRT 73;
NO PMRT 66		 542 134 OS, LRFS 7 1
Rusthoven et al. [19] 2016 USA retrospective 10283 39 7386 2897 OS, DFS 7 2
Nagar et al. [20] 2015 USA retrospective 161 48 118 43 DFS 7 1
Zhang et al. [21] 2020 China retrospective 4236 – 2917 1319 LRFS, DMFS 6 2
McGuire et al. [22] 2007 USA retrospective 106 62 72 34 LRFS 7 1
Garg et al. [24] 2007 USA retrospective 107 PMRT 75;
NO PMRT 63		 80 27 OS, LRFS 7 1
Chen et al. [25] 2018 China retrospective 104 64 79 25 LRFS 7 1
Nagar et al. [26] 2011 USA retrospective 162 75 119 43 LRFS 7 1
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Method 1 means to obtain the number of events directly from publications; Method 2 denotes as the number of events, corresponding P-values and Kaplan-Meier curves OS overall survival, DFS disease-free survival, LRFS local recurrence free survival,DMFS distant metastasis free survival, NOS Newcastle – Ottawa Scale.

3.2. Analysis of LRFS of patients

Calculations using the random effects model revealed a substantial correlation between PMRT and longer locoregional recurrence-free survival (LRFS) (RR 0.43; 95% CI 0.32–0.58, p ≤0.0001) Figure 2). The studies exhibited significant heterogeneity (I2 = 75%; p < 0.001). To investigate the source of this heterogeneity, we performed a subgroup analysis based on sample size (≤500 or ≥ 500), and the percentage of patients in the PMRT group who had pCR implementation or who were ypT0–2, ypN0, LVI positive, ER positive, PR positive, or HER-2 positive. Subgroup analysis revealed that for all of the aforementioned variables, PMRT was substantially linked to improved LRFS in breast cancer patients (Figure 3).

Figure 2.

Figure 2.

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Meta-analysis of the pooled RRs of LRFS for patients (RRs:Relative Risk; LRFS: locoregional relapse-free survival).

Figure 3.

Figure 3.

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Results of subgroup analysis of pooled RRs of LRFS for patients (a). Subgroup analysis stratified by sample size. (b).Subgroup analysis stratified by pCR. (c).Subgroup analysis stratified by ypT. (d).Subgroup analysis stratified by ypN. (e).Subgroup analysis stratified by LVI. (f).Subgroup analysis stratified by ER. (g).Subgroup analysis stratified by PR. (h).Subgroup analysis stratified by HER-2. （pmrt:post-mastectomy radiation Therapy; RRs: relative Risk; LRFS: locoregional relapse-free survival. LVI :lympho-vascular invasion; ER: estrogen Receptor; PR: progesterone Receptor; HER-2: human epidermal growth-factor receptor-2).

3.3. Analysis of OS, DFS, DMFS of patients

The systematic analysis showed no significant differences in overall survival (OS) (RR 0.93; 95% CI 0.83–1.04, p = 0.19), disease-free survival (DFS) (RR 0.78; 95% CI 0.52–1.16, p = 0.22), and distant metastasis-free survival (DMFS) (RR 1.12; 95% CI 0.99–1.28, p = 0.08) when PMRT was used Figure 4. We also assessed the predictive significance of PMRT in cases of low-grade ypT, pCR, ypN0, LVI, and hormone receptor positivity. The results showed that PMRT was associated with increased OS (RR 0.57; 95% CI 0.39–0.82, p < 0.001) (Figure 5) and DFS (RR 0.33; 95% CI 0.19–0.57, p < 0.001) (Figure 6) in a larger proportion of LVI positive patients.

Figure 4.

Figure 4.

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Meta-analysis of the pooled RRs of OS(a), DFS(b) and DMFS(c) for patients (a). Results of subgroup analysis of pooled OS for patients. (b). Results of subgroup analysis of pooled DFS for patients (c). Results of subgroup analysis of pooled DMFS for patients. （pmrt:post-mastectomy radiation Therapy; RRs: relative Risk; OS: overall survival; DFS: disease-free Survival; DMFS: distant metastasis free survival).

Figure 5.

Figure 5.

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Results of subgroup analysis of pooled RRs of OS for patients (a).Subgroup analysis stratified by sample size. (b). Subgroup analysis stratified by pCR. (c). Subgroup analysis stratified by ypT. (d). Subgroup analysis stratified by ypN. (e). Subgroup analysis stratified by LVI. (f). Subgroup analysis stratified by ER. (g). Subgroup analysis stratified by PR. (h). Subgroup analysis stratified by HER-2. （pmrt:post-mastectomy radiation Therapy; RRs: relative Risk; OS: overall survival; pCR: pathological complete response; LVI :lympho-vascular invasion; ER: estrogen Receptor; PR: progesterone Receptor; HER-2: human epidermal growth-factor receptor-2).

Figure 6.

Figure 6.

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Results of subgroup analysis of pooled RRs of DFS for patients (a).Subgroup analysis stratified by sample size. (b).Subgroup analysis stratified by pCR. (c).Subgroup analysis stratified by ypT. (d).Subgroup analysis stratified by ypN. (e).Subgroup analysis stratified by LVI. (f).Subgroup analysis stratified by ER. (g).Subgroup analysis stratified by HER-2. （pmrt:post-mastectomy radiation Therapy; RRs: relative Risk; DFS: disease-free Survival; pCR: pathological complete response; LVI :lympho-vascular invasion; ER: estrogen Receptor; HER-2: human epidermal growth-factor receptor-2).

3.4. Sensitivity analysis and publication bias

To investigate the effect of individual studies on the overall results, sensitivity analysis was employed. For locoregional recurrence-free survival (LRFS), sensitivity analysis revealed that the study by Miyashita et al. had a significant impact on the results, indicating that it may be a major source of heterogeneity. Nonetheless, the pooled relative risk (RR) and 95% confidence intervals (CI) following the removal of this study demonstrated the robustness of our findings, as all pooled RR and 95% CI values remained below the null hypothesis of 1. Review Manager was used to create a funnel plot for LRFS to identify publication bias. There was no discernible publication bias among the studies included in the analysis (Figure 7).

Figure 7.

Figure 7.

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Funnel plot of meta-analysis for publication bias (a). LRFS; (b). DFS; (c). OS; (d). DMFS. (RRs:Relative Risk; LRFS: locoregional relapse-free survival; OS: overall survival; DMFS: distant metastasis free survival.

3.5. Analysis of irradiation site and dose in pmrt group

Four studies discussed the site and dose of PMRT irradiation. In Krug’s study, detailed reports were provided for 318 patients (46.4%) who received radiation therapy (RT). Of these, 313 (98.7%) received chest wall radiation therapy. Among the 318 patients, 243 (76.7%) received regional lymph node irradiation, including 237 (74.5%) who received supraclavicular/infraclavicular lymph node irradiation and 49 (18.2%) who received internal mammary (parasternal) lymph node irradiation (58 axillary lymph nodes). Additionally, 72 patients (22.6%) received enhanced irradiation of the mastectomy scar [23].

In Chen’s study, PMRT was performed in 79 patients (76%) using an external beam irradiation of 46–50 Gy with fractions of 1.8–2.0 Gy to the chest wall and/or regional lymph nodes, typically including the internal breast and supraclavicular areas. Axillary lymph nodes were not included in the routine PMRT area. The chest wall was treated with a tangent beam of cobalt-60 or 4–6 MeV photons. The region junction was treated with a pre-photon field matching the tangential field design [25].

In Shim’s study, PMRT was administered to the chest wall and regional lymph node basin (axilla and supraclavicular fossa, with or without internal mammary chains). Only 7 patients (4.6%) did not receive supraclavicular fossa irradiation, while 57 patients (37.8%) received internal mammary irradiation. The total radiotherapy dose for the chest wall, supraclavicular lymph nodes, and internal mammary lymph nodes was 45–50 Gy. The standard schedule included a daily dose of 1.8–2.0 Gy. The chest wall was treated with a photon tangential field or reverse hockey stick (photon-electron field). The supraclavicular fossa was treated with an anteroposterior oblique photon field [15].

In Miyashita’s study, 593 (59.7%) of 993 patients in the PMRT group had radiation fields that included local lymph node fields, supraclavicular fossa/subclavian fossa, and internal mammary lymph nodes. However, data on outcome indicators for different exposure sites and doses were not available [14].

4. Discussion

The use of adjuvant radiotherapy (RT) in the treatment of breast cancer has been the focus of much discussion in recent years due to advancements in the neoadjuvant chemotherapy (NACT) prescription process. One of the more contentious questions regarding adjuvant radiation is whether it is necessary for patients with early-stage disease at the time of diagnosis. Adjuvant radiation is not well studied for patients who have clinically negative lymph nodes following NACT completion. The carefully considered concept put forth by Marks and Prosnitz supports the notion that positive axillary lymph node metastases before chemotherapy is a critical factor. It also serves as a reminder that women are at higher risk of dying from breast cancer if radiation therapy is reduced based on chemotherapy response [27]. The primary concern of suboptimal local cancer treatment, as highlighted by Marks and Prosnitz, is that it will result in lower rates of breast cancer survival.

In retrospective studies of NACT, it is generally believed that locoregional radiation therapy (LRRT) has some effect when pathological complete response (pCR) is not achieved, but the benefit of pCR in patients is controversial. Postoperative radiation did not impair local control in 30 individuals with pathologically complete remission of stage II breast cancer. Whether radiation was administered or not, there was no evidence of local recurrence. However, the number of patients in these studies is limited.

According to our research, PMRT may positively affect patients’ survival outcomes, with overall survival (OS) showing a relative risk (RR) of 0.83 (95% CI 0.76–0.91), if a smaller percentage of patients in the PMRT group achieved pCR. However, the small number of included studies makes it difficult to assess this precisely. Here, we present a current comprehensive meta-analysis that systematically investigates how PMRT affects breast cancer patients’ chances of survival. We reviewed 15 studies and found no significant association between PMRT and OS (RR 0.93; 95% CI 0.83–1.04, p = 0.19), disease-free survival (DFS) (RR 0.78; 95% CI 0.52–1.16, p = 0.22), and distant metastasis-free survival (DMFS) (RR 1.12; 95% CI 0.99–1.28, p = 0.08) according to our systematic analysis. However, PMRT was significantly correlated with improved locoregional recurrence-free survival (LRFS) (RR 0.43; 95% CI 0.38–0.54, p < 0.0001).

We performed a subgroup analysis to investigate the sources of the significant heterogeneity in these studies. Subgroup analysis showed that ypT stage affected the prognostic significance in LRFS (RR 0.46, 95% CI 0.28–0.78 vs RR 0.75, 95% CI 0.48–1.18). This implies that heterogeneity might originate from these distinctions. Important parameters reflecting tumor progression include DFS, OS, LRFS, and DMFS. Furthermore, further research is required to examine the connection between PMRT and tumor progression, as the number of studies evaluating the relationship between PMRT with DFS, OS, and DMFS is limited.

For patients with locally advanced breast cancer (LABC), including clinical stages III (cT3–4 or cN2–3) and some stages IIb (T3N0 or T2N1), neoadjuvant chemotherapy (NAC) is the accepted standard of therapy in contemporary clinical practice. In recent years, patients with operable early-stage I-II breast cancer, particularly those with triple-negative or HER2-positive subtypes, have also been treated with NAC in addition to those with LABC [28]. Multivariate analysis identified estrogen receptor, progesterone receptor, and baseline lymph node status as significant prognostic factors for locoregional recurrence (LRR). Adjuvant radiotherapy did not improve outcomes for patients with cT1/2 stage tumors but did improve outcomes for those with cT3/4 stage tumors. Currently, there is insufficient evidence to support conventional radiotherapy or regional lymph node radiotherapy after radical mastectomy in cN+ pCR or ypN0 patients. Consequently, adjuvant radiation therapy should be seriously considered in these patients, particularly if additional risk factors are present [29]. Our meta-analysis suggests that patients with lower ypN and ypT classifications constituted a larger portion of the postmastectomy radiotherapy (PMRT) group, indicating that PMRT may not significantly affect survival outcomes. Le Scodan et al. evaluated the effect of radiotherapy after mastectomy in clinical patients with stage II and III breast cancer without lymph node involvement following preoperative anthracycline chemotherapy. With a median follow-up of 91.4 months (range 11.6 to 218 months), the study examined the outcomes of 134 patients treated at the Rene Huguenin Cancer Center (Saint-Cloud, France) between 1990 and 2004. Stage II breast cancer accounted for 62% of cases, stage III for 37%, and 58% of patients received postmastectomy radiotherapy. Radiotherapy was associated with improved local relapse-free survival (LRFS; calibrated hazard ratio 0.37, 95% CI 0.09 ~ 1.61; p = 0.18) after controlling for variations in patient and tumor characteristics. In clinical patients with stage II breast cancer who responded well to chemotherapy, radiotherapy following mastectomy was not associated with improvements in locoregional control, consistent with findings from MD Anderson [30]. Retrospective evidence suggests that patients presenting with clinical T3-T4 lesions, clinical N2-N3 lesions, and lymph node-positive breast cancer after resection may benefit from radiotherapy following mastectomy and neoadjuvant chemotherapy to improve locoregional control. The response to neoadjuvant chemotherapy may also help in selecting which women should receive radiation therapy following breast resection, as it predicts the probability of locoregional recurrence.

Outcomes in women who received neoadjuvant chemotherapy and mastectomy but did not receive postmastectomy radiotherapy have shown that locoregional recurrence (LRR) rates are sufficiently high (at least 15%) in breast cancer patients with positive lymph nodes at the time of resection to support the use of postmastectomy radiotherapy [31]. Late T stage at presentation, advanced combined clinical stage at presentation, larger tumor size after chemotherapy, and an increased number of positive lymph nodes after chemotherapy are predictors of LRR. Subgroup analysis found that clinical stage IIb or higher at presentation, pathologically involved lymph nodes after neoadjuvant chemotherapy, and pathologically free lymph nodes at clinical stage T3 or T4 were associated with sufficiently high locoregional risk (15%) to consider radiotherapy of the chest wall and draining lymph vessels following mastectomy to lower this risk[29]. Regardless of the patient’s response to neoadjuvant chemotherapy, MD Anderson continues to evaluate postmastectomy radiation therapy for patients with T3 node-negative breast cancer, despite differences in clinical data [32]. Among 107 patients younger than 35 years who received neoadjuvant chemotherapy and mastectomy, radiotherapy after mastectomy was associated with a lower 5-year LRR (12% vs. 37%, p = 0.001) and improved survival (67% vs. 48%, p = 0.001) compared with patients who did not receive radiotherapy, despite having more advanced disease features. The authors concluded that, particularly for patients with stage IIb or higher, young age is a significant consideration when evaluating postmastectomy radiotherapy [24]. Compared to other similar researches, our study conducted more subgroup analyses. These analyses provide guidance for patients with different hormone receptor statuses or other varying conditions, making the findings more comprehensive and specific. We rigorously evaluated specific confounders/biases, such as’ treatment adherence “or” long-term outcomes’ and differentiation of focus – unlike recent meta-analyses that focused primarily on pathological grading, our work also took into account different patient characteristics, such as LVI positivity, hormone receptors, age, etc.

The present meta-analysis does, however, have some limitations. Firstly, the proportion of patients with different stages may introduce bias into the results. Secondly, certain hazard ratios (HRs) were not readily available from the publications, leading to potential inaccuracies when calculating them through survival curves. Thirdly, bias in meta-analyses may result from variations in study sample sizes and paper quality. Fourthly, all the studies included assessed radiotherapy retrospectively. Since patients at lower risk are more likely to receive radiation therapy in clinical practice, the data we included do not rule out the possibility of selection bias. The patients we analyzed who received radiation therapy had already been potentially screened before radiation therapy. In other words, the patients we analyzed may be low-risk patients after screening. Lastly, our search strategy, while comprehensive across core biomedical databases, did not incorporate gray literature or secondary databases such as Scopus, which may warrant consideration in future updates. While our search identified RCTs addressing aspects of our topic, their number remained insufficient to perform a meaningful subgroup analysis or maintain methodological homogeneity across study designs. We agree that incorporating RCT data could strengthen the validity of future investigations. Should additional high-quality RCTs emerge, we would gladly incorporate them in an updated analysis. Therefore, it is critically necessary to conduct large-scale, multicenter, and high-quality investigations to confirm our findings. The sample size involved in this study was limited and may not be sufficiently representative of the broader population. Potential confounders such as socioeconomic status were not accounted for in the analysis, which also limits this study.

5. Conclusion

No significant difference was observed between PMRT and OS. Therefore, according to our study, in general, PMRT may not have a prognostic effect in patients who achieve pcr or who significantly degrade after neoadjuvant chemotherapy, but larger prospective clinical trials are needed to prove it. While PMRT did not improve overall survival in the entire group, our subgroup analyses suggest selective benefit for non-pCR or LVI positive patients. The meta-analysis revealed that postmastectomy radiation therapy (PMRT) may be beneficial for patients with breast cancer who did not achieve pathological complete remission (pCR) or who tested positive for lymphovascular invasion (LVI). These findings may aid in the clinical decision-making process.

Funding Statement

The present study was funded by the Undergraduate Training Programs for Innovation and Entrepreneurship of the Affiliated Hospital of Southwest Medical University [the grant number is No. S202310632203] and the Luzhou Scientific Grant [the grant number is No. 2024LZXNYDJ036]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Article highlights

  • Marks and Prosnitz supports the notion that positive axillary lymph node metastases before chemotherapy is a critical factor. It also serves as a reminder that women are at higher risk of dying from breast cancer if radiation therapy is reduced based on chemotherapy response. The primary concern of suboptimal local cancer treatment, as highlighted by Marks and Prosnitz, is that it will result in lower rates of breast cancer survival.

  • According to our research, we found no significant difference was observed between PMRT and OS or DMFS in predicting breast cancer outcomes. We reviewed 15 studies and found no significant association between PMRT and OS (RR 0.93; 95% CI 0.83–1.04, p = 0.19), disease-free survival (DFS) (RR 0.78; 95% CI 0.52–1.16, p = 0.22), and distant metastasis-free survival (DMFS) (RR 1.12; 95% CI 0.99–1.28, p = 0.08) according to our systematic analysis.

  • PMRT was significantly correlated with improved locoregional recurrence-free survival (LRFS) (RR 0.43; 95% CI 0.38–0.54, p < 0.0001). Calculations using the random effects model revealed a substantial correlation between PMRT and longer locoregional recurrence-free survival (LRFS) (RR 0.43; 95% CI 0.32–0.58, p ≤0.0001) (Figure 2). The studies exhibited significant heterogeneity (I2 = 75%; p < 0.001). Subgroup analysis revealed that for all of the aforementioned variables, PMRT was substantially linked to improved LRFS in breast cancer patients (Figure 3).

  • We performed a subgroup analysis to investigate the sources of the significant heterogeneity in these studies. Subgroup analysis showed that ypT stage affected the prognostic significance in LRFS (RR 0.46, 95% CI 0.28–0.78 vs RR 0.75, 95% CI 0.48–1.18). This implies that heterogeneity might originate from these distinctions. Important parameters reflecting tumor progression include DFS, OS, LRFS, and DMFS.

  • The systematic analysis showed no significant differences in overall survival (OS) (RR 0.93; 95% CI 0.83–1.04, p = 0.19), disease-free survival (DFS) (RR 0.78; 95% CI 0.52–1.16, p = 0.22), and distant metastasis-free survival (DMFS) (RR 1.12; 95% CI 0.99–1.28, p = 0.08) when PMRT was used (Figure 4).

  • We also assessed the predictive significance of PMRT in cases of low-grade ypT, pCR, ypN0, LVI, and hormone receptor positivity. The results showed that PMRT was associated with increased OS (RR 0.57; 95% CI 0.39–0.82, p < 0.001) |(Figure 5)and DFS (RR 0.33; 95% CI 0.19–0.57, p < 0.001) (Figure 6) in a larger proportion of LVI positive patients.

  • Our meta-analysis suggests that patients with lower ypN and ypT classifications constituted a larger portion of the postmastectomy radiotherapy (PMRT) group, indicating that PMRT may not significantly affect survival outcomes.

  • Compared to other similar researches, our study conducted more subgroup analyses. These analyses provide guidance for patients with different hormone receptor statuses or other varying conditions, making the findings more comprehensive and specific.

  • We rigorously evaluated specific confounders/biases, such as’ treatment adherence “or” long-term outcomes’ and differentiation of focus – unlike recent meta-analyses that focused primarily on pathological grading, our work also took into account different patient characteristics, such as LVI positivity, hormone receptors, age, etc.

Author contributions

Cuiwei Zhang and Liuyi Li designed the project. Aishan Zou and Liuyi Li conducted separate searches to find all pertinent literature and screened all eligible studies. All authors assessed the quality of all included studies, extracted relevant data independently and reached a consensus on all items. Aishan Zou and Yang Guo were responsible for manuscript writing. Cuiwei Zhang took responsibility and provided financial support for the project. All authors were aware of this manuscript.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Data availability statement

The data underlying this article are available in [PubMed], at https://pubmed.ncbi.nlm.nih.gov; [Embase], at https://www.embase.com; [Cochrane Library], at https://www.cochranelibrary.com/library.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data underlying this article are available in [PubMed], at https://pubmed.ncbi.nlm.nih.gov; [Embase], at https://www.embase.com; [Cochrane Library], at https://www.cochranelibrary.com/library.

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