Abstract
Whole breast irradiation after breast‐conserving surgery for early breast cancer has become one of the standard treatment modes for breast cancer and yields the same effect as radical surgery. Accelerated partial breast irradiation (APBI) as a substitute for whole breast irradiation for patients with early breast cancer is a hot spot in clinical research. APBI is characterised by simple high‐dose local irradiation of the tumour bed in a short time, thus improving convenience for patients and saving costs. The implementation methods of APBI mainly include brachytherapy, external beam radiation therapy, and intraoperative radiotherapy. This review provides an overview of the clinical effects and adverse reactions of the main technologies of APBI and discusses the prospects for the future development of APBI.
Keywords: accelerated partial breast irradiation, brachytherapy, breast cancer, breast conserving surgery, external beam radiation therapy, intraoperative radiotherapy
Accelerated partial breast irradiation (APBI) as a substitute for WBI for patients with early breast cancer is a hot spot in clinical research. The implementation methods of APBI mainly include brachytherapy, external beam radiation therapy, and intraoperative radiotherapy. This article provides a review of the clinical effects and adverse reactions of the main technologies of APBI and prospects for the future development of APBI.

Abbreviations
- 3D‐CRT
three‐dimensional conformal radiotherapy
- APBI
accelerated partial breast irradiation
- BCS
breast‐conserving surgery
- BCT
breast‐conserving therapy
- CI
confidence interval
- DFS
disease‐free survival
- EBRT
external beam radiation therapy
- HR
hazard ratio
- HRQoL
health‐related quality of life
- IBTR
ipsilateral breast tumour recurrence
- IMRT
intensity modulated radiotherapy
- IORT
intraoperative radiotherapy
- IQR
interquartile range
- MIBT
multicatheter interstitial brachytherapy
- OS
overall survival
- PBI
partial breast irradiation
- RT
radiotherapy
- WBI
whole breast irradiation
1. BACKGROUND
Breast cancer is the most common cancer in women. In the 1970s, the local treatment of breast cancer changed from radical surgery, including simple mastectomy or modified radical mastectomy, to breast‐conserving surgery (BCS). BCS combined with assisted whole breast irradiation (WBI), collectively known as breast‐conserving therapy (BCT), is one of the standard treatments for breast cancer. Multiple prospective randomised trials with long‐term follow‐up have shown that there is no significant difference between BCT and modified radical mastectomy regarding overall survival (OS) and disease‐free survival (DFS) [1, 2, 3].
Standard WBI typically includes daily radiation therapy for the entire breast with a dose of 45–50 Gy for 6–7 weeks. For many patients, WBI typically involves a 10–16 Gy boost to the tumour bed to further reduce local recurrence. In 2018, the American Society of Radiological Oncology (ASTRO) issued the latest WBI evidence‐based guidelines. For patients with invasive breast cancer, hypofractionated WBI is preferred, that is, approximately 40–42.5 Gy/15–16 f. For patients without a high risk of recurrence, the tumour bed supplement should be 10 Gy/4–5 f. For patients with a single high risk of recurrence with a positive margin or those with insufficient incisal margin combined with young age and other composite high risks of recurrence, a boost of higher dose fraction, 14–16 Gy/7–8 f or 12.5 Gy/5 f, can be used [4]. Multiple international randomised studies have shown that hypofractionated WBI can achieve the same local control rate, tumour‐free survival rate, and OS rate as conventional fraction modes [5, 6, 7, 8, 9], while yielding lower acute toxicity reactions and good cosmetic results [10, 11, 12]. With women's concern for breast health and the popularity of breast cancer screening, an increasing number of breast cancers are detected at an early stage, giving many women the opportunity to undergo BCS.
BCT studies have shown that most local breast cancer recurrence occurs at the site of the primary tumour [13, 14]. Pathological studies indicated that in over 90% of cases, residual microlesions are usually located within 1.5 cm of the primary tumour [15]. Combining advanced computed tomography (CT) plans and modern radiation therapy techniques, researchers hypothesise that only targeting the primary tumour for radiotherapy with 1–2 cm expansion will achieve local control similar to WBI. Therefore, the concept of APBI has been proposed, which involves using a higher single‐segmented dose (greater than 2 Gy) to provide therapeutic radiation only to the tumour bed rather than the entire breast. Compared with the 3–5‐week treatment duration of WBI, this strategy allows for treatment to be provided in a shorter time frame (1 week or less), thereby saving costs and improving resource utilisation at the treatment centre. The shorter treatment duration is also more convenient for patients. APBI may have fewer potential acute adverse reactions [16], and studies have shown that as the total treatment time decreases, tumour control may be improved. Early adopters also concluded that when only a portion of the breast was irradiated, the cosmetic results for the breast were improved, and the lungs and heart were protected.
APBI is mainly administered by brachytherapy, external beam radiation therapy (EBRT), and intraoperative radiotherapy. Modern studies of APBI begin with brachytherapy and have shown good local control and cosmetic effects on the breast [17, 18, 19]. Other options have been subsequently examined, including intraoperative radiation therapy, where a radiation source or applicator is positioned inside the surgical cavity during surgery to treat the tumour bed [20, 21]. Brachytherapy and intraoperative radiotherapy are not readily available to most patients since they need specialised equipment, physician training, and resources. Recently, APBI technology has focused on external radiotherapy [22, 23, 24, 25, 26, 27]. External radiotherapy is a noninvasive treatment technique that mainly includes three‐dimensional conformal radiotherapy (3D‐CRT) and intensity‐modulated radiotherapy (IMRT) techniques, making it the most accessible and cost‐effective method.
2. APBI TECHNOLOGY
2.1. Brachytherapy
In 2023, GEC‐ESTRO published the 10‐year follow‐up results of a multicentre, phase III, noninferiority randomised trial of APBI versus WBI using multicatheter brachytherapy [17]. The study included 1184 patients with early‐stage, low‐risk invasive and ductal carcinoma in situ who underwent BCS between April 2004 and July 2009. The patients were randomly assigned to the APBI and WBI groups: 633 patients received APBI using multicatheter brachytherapy, high‐dose‐rate brachytherapy of 30.1 Gy/7 f or 32.0 Gy/8 f within 5 days, or pulsed dose‐rate brachytherapy of 50 Gy within 5 treatment days; and 551 patients received WBI with 50 Gy of radiation once a day for a total of 25 fractions within 5 weeks, with a supplemental boost of 10 Gy to the tumour bed. The primary endpoint was ipsilateral local recurrence, with a noninferiority margin (defined as the 5‐year outcome) of 3 percentage points for the difference in recurrence rates. The median follow‐up was 10.36 years (interquartile range [IQR] 9.12–11.28), with a 10‐year ipsilateral local recurrence rate of 1.58% (95% confidence interval [CI]: 0.37–2.8) in the WBI group and 3.51% (1.99–5.03) in the APBI group. The difference in the 10‐year local recurrence rate between the two groups was 1.93% (95% CI: −0.018 to 3.87; p = 0.074). Further subgroup analysis, classified by age, menopausal status, hormone receptor status, node status, histological type, tumour size and grade, and use of systemic therapy, found that only Grade 2–3 tumours and use of systemic therapy, especially anti‐hormone therapy, affected the difference in local recurrence rates between the two groups. During a follow‐up of 7.5 or 10 years, or both, adverse events, mainly Grades 1 and 2, occurred in 234 (60%) of 393 patients in the WBI group and 314 (67%) of 470 patients in the APBI group. The incidence of Grade 3 late adverse reactions associated with treatment was significantly lower in the APBI group than in the WBI group (7 of 470 patients [1%] vs. 17 of 393 patients [4%]; p = 0.021). At 10 years, fibrosis was the most prevalent Grade 3 adverse event (6 of 313 WBI patients [2%] and 3 of 375 APBI patients [1%], p = 0.56), and there were no Grade 4 adverse reactions or deaths associated with treatment [17]. The long‐term follow‐up results from this randomised phase III trial with sufficient statistical power show that postoperative APBI using multi‐catheter brachytherapy after BCS is as effective and safe as postoperative WBI for selected patients with early‐stage breast cancer. Therefore, for patients with low‐risk early‐stage breast cancer who choose BCS and postoperative radiation therapy, APBI using multi‐catheter brachytherapy should be considered as an attractive treatment option.
The Mammo Site® (Hologic Inc.) intracavitary breast brachytherapy device was developed as an alternative to single‐channel balloon‐based multicatheter interstitial brachytherapy (MIBT) and received FDA approval in 2002 to simplify the administration of APBI and make it more independent on center expertise in MIBT. A deflated balloon applicator is placed in the BCS cavity during surgery or as a second postoperative procedure. A large registration study was carried out on 1449 patients with a treatment regimen of 34 Gy divided into 10 sessions. At a follow‐up of 63 months, the 5‐year local failure rate was 3.8%. At 84 months, the aesthetic satisfaction rate was 90.6%. However, the incidence of fat necrosis and infection was higher, at 2.5% and 9.6%, respectively [19]. Wallace et al. [28] reported the findings of a prospective phase I/II trial that involved 45 patients receiving 28 Gy balloon brachytherapy with four exposures of 7 Gy each. At a median follow‐up of 11.4 months, relatively high toxicity was observed in four cases (two symptomatic) of fat necrosis and 4% [2] of rib fractures, reflecting the lower dose distribution of balloon‐based bandage brachytherapy (BAB) in accordance with the surrounding organs at risk (OARs) compared with MIBT [28].
2.2. EBRT
The RAPID multicentre, randomised, and noninferiority trial compared the effectiveness and toxicity of APBI using 3D‐CRT and WBI. A total of 2135 women ≥40 years old who had undergone BCS for ductal carcinoma in situ or breast cancer with negative lymph nodes and tumour ≤ 3 cm were randomised to the APBI and WBI groups. In the APBI group, 3D‐CRT (90%) or IMRT (10%) was used at 38.5 Gy/10 f twice daily in the segmentation mode. The WBI group was treated with segmentation mode of 50 Gy/25 f or 42.5 Gy/16 f. The median follow‐up was 8.6 years. In the APBI group, the 8‐year cumulative recurrence rate in the ipsilateral breast was 3.0% (95% CI: 1.9–4.0); in the WBI group, it was 2.8% (1.8–3.9). The HR of APBI versus WBI was 1.27 (90% CI: 0.84–1.91). The preset noninferiority criteria were met. There were no statistical differences in the treatment effects across different subgroups, stratified by age, histology, tumour size, ER status, tumour grade, adjuvant therapy, and APBI suitability. The two groups were equivalent regarding DFS, OS, and breast cancer mortality. In the APBI group, the incidence of acute radiation toxicity ≥ Grade 2 was 28%, which was lower than that in the WBI group (45%, p < 0.0001), but the incidence of late radiation toxicity ≥ Grade 2 was higher (32% vs. 13%, p < 0.0001). The proportion of adverse cosmetic effects was also higher in the APBI group than the WBI group, with an absolute difference of 17.7% at 7 years and a 95% CI of 12.9–22.3 [22]. The RAPID results indicate that APBI using 3D‐CRT technology is not inferior to WBI in avoiding ipsilateral breast recurrence. While less acute toxicity was observed, an increase in late toxicity and adverse cosmetic effects, which may be associated with twice‐daily treatment, requires caution in the use of this regimen.
IMRT is recommended as the preferred technique for APBI in the 4th Edition of the NCCN Breast Cancer Clinical Practice Guidelines in 2023 for better dose uniformity and better protection of normal tissue than 3D‐CRT.
A randomised phase III study from Florence compared APBI using IMRT with WBI over 10 years of follow‐up. A total of 520 patients were randomly assigned to the APBI and WBI groups (n = 260/group) between 2005 and 2013, with over 90% having characteristics associated with a low risk of recurrence. The APBI group received a radiation dose of 30 Gy/5 f once every other day. The WBI group received 50 Gy/25 f, plus a tumour bed boost of 10 Gy/5 f, once a day. The median follow‐up was 10.7 years. The 10‐year cumulative recurrence rate in the ipsilateral breast was 2.5% (n = 6) in the WBI group and 3.7% (n = 0.9) in the APBI group (HR = 1.56; 95% CI: 0.55–4.37; p = 0.40). The 10‐year OS of both groups was 91.9% (HR = 0.95; 95% CI: 0.50–1.79; p = 0.86). The specific survival rate of patients with breast cancer was 96.7% in the WBI group and 97.8% in the APBI group (HR = 0.65; 95% CI: 0.21–1.99; p = 0.45). No factors such as age, hormone receptor status, nodal status, tumour size and grade, or risk group influenced the treatment effects for WBI and APBI. Acute toxicity (p = 0.0001) and late toxicity (p = 0.0001) of the APBI group were significantly reduced, and cosmetic outcomes were significantly improved as assessed by both patients (p = 0.0001) and physicians (p = 0.0001) [26]. The study reported a low 10‐year cumulative incidence of IBTR in early‐stage breast cancer patients who received external beam APBI using IMRT technology five times daily; there was no difference from that after WBI treatment. Treatment‐related acute and late toxicity and cosmetic effects were clearly favourable for APBI.
UK IMPORT LOW reported the 5‐year results from a noninferiority study of nonaccelerated partial breast irradiation (PBI) using IMRT [27]. From 2007 to 2010, 2018 female patients with tumours sized 3 cm or smaller (pT1–2) and 0–3 positive axillary lymph nodes (pN0–1) undergoing BCS were randomised into three groups in a 1:1:1 ratio: the PBI group (40 Gy/15 f), the WBI dose reduction group (36 Gy/15 f for the whole breast and 40 Gy/15 f for the tumour bed), and the WBI control group (40 Gy/15 f for the whole breast). The median follow‐up was 72.2 months, and 18 patients developed local recurrence (including 6 patients in the PBI group, three in the WBI dose reduction group, and nine in the WBI control group). The 5‐year cumulative local recurrence rates were 0.5% (95% CI: 0.2–1.4), 0.2% (95% CI: 0.02–1.2), and 1.1% (95% CI: 0.5–2.3), respectively. The 5‐year absolute difference in estimates of local recurrence was −0.73% (−0.99–0.22) in the WBI dose‐reduction group and −0.38% (−0.84 to 0.90) in the PBI group compared with the WBI control group. Both the WBI dose reduction group and the PBI group showed noninferiority compared with the WBI control group, with a critical risk greater than 2.03 (p = 0.003 and p = 0.016, respectively). Local recurrence, distant recurrence, and OS were similar among the three groups. Photographs, patients, and clinical evaluations recorded similar adverse events in the WBI dose reduction group and the PBI group, with significant reductions in adverse reactions in both groups compared with the WBI control group, including changes in breast appearance (p = 0.007 for the PBI group) and breast hardening (p = 0.002, WBI dose reduction group; p < 0.0001, PBI group) [27].
The results of the above three clinical trials showed that regardless of which external radiotherapy technique was used, the recurrence rate in the ipsilateral breast after APBI was comparable to that after WBI. Therefore, the application of EBRT in APBI was supported.
NSABP B‐39/RTOG 0413 is a multicentre, Phase III randomised controlled study using an equivalent design, with APBI using 3D‐CRT (73%) (38.5 Gy/10 f twice a day) or brachytherapy (34 Gy/10 f twice a day) and brachytherapy using single cavity (21%) or multicatheter (6%) techniques compared with WBI (50 Gy/25 f, ±10–16 Gy tumour bed boost). From 2005 to 2013, a total of 4216 women ≥ 18 years old with tumours ≤ 3 cm and 0–3 positive axillary lymph nodes were enroled. At a median follow‐up of 10.2 years, the 10‐year cumulative recurrence rate in the ipsilateral breast (primary endpoint) after APBI was 4.6% (95% CI: 3.7–5.7) and that after WBI was 3.9% (3.1–5.0); the HR was 1.22 (90% CI: 0.94–1.58), which did not meet the preset equivalence criteria. Compared with WBI, APBI resulted in a shorter relapse‐free interval (91.8% vs. 93.4%), with an HR of 1.33 (95% CI: 1.04–1.69, p = 0.02). Breast cancer mortality and OS were similar between groups. There were no variations in the treatment effects between the subgroups classified by menopausal status, intent to receive chemotherapy, disease stage, hormone receptor status, and invasive cancer risk. APBI was also advantageous in patients with invasive tumours sized 10 mm or smaller. Acute and late toxicities were not reported separately. The overall toxicity characteristics were similar, with Grade ≥ 3 toxicity slightly more common in the APBI group (10% vs. 7%) [23]. The cosmetic outcomes of the group of patients who received or did not receive chemotherapy were evaluated by the patients, the attending physician, and a photographic review. The results varied. The patient and photographic evaluations showed equivalence between the two groups. According to the doctor's evaluation, the cosmetic outcome of APBI patients at 36 months was worse than that of WBI patients [29]. However, in controlling IBTR, APBI did not meet the criteria equivalent to WBI in BCT. It may be that the trial had a broad range of inclusion criteria, resulting in a large number of heterogeneous patients and having sufficient ability to test treatment equivalence, but it was not designed to detect the equivalence of patient subgroups or the outcomes of different APBI technologies. However, for early breast cancer patients, the absolute difference in the 10‐year cumulative recurrence rate in the ipsilateral breast between the APBI and WBI groups was less than 1%, suggesting APBI may be an acceptable alternative for some female patients.
2.3. Intraoperative radiotherapy
Intraoperative radiotherapy refers to the application of local radiation therapy during the surgical process, including electron therapy, brachytherapy, and photon therapy. Two phase III clinical trials (ELIOT [21] and TARGIT‐A [20]) are large clinical studies on the application of APBI in BCS for early breast cancer.
In the ELIOT trial, 1305 female patients with breast tumours ≤ 2.5 cm in diameter who underwent BCS between 2000 and 2007 were randomised into two groups: the ELIOT group (a single dose of 21 Gy intraoperative radiotherapy with electrons to the tumour bed) (n = 651) and the WBI group (routine segmentation of 50 Gy/25 f, plus a 10 Gy tumour bed boost) (n = 654). The median follow‐up was 12.4 years, with 86 patients (7%) developing IBTR, including 70 in the ELIOT group (11%) and 16 in the WBI group (2%), with an HR of 4.62 (95% CI: 2.68–7.95, p < 0.0001). The 5‐year, 10‐year, and 15‐year IBTR incidence rates of the two groups were 4.2% versus 0.5%, 8.1% versus 1.1%, and 12.6% versus 2.4%, respectively. In stratified analysis, the risk of IBTR in the ELIOT group was higher than that in the WBI group in all subgroups, including age, histology, pathological tumour size, positive nodes, resection margins, tumour grade, oestrogen receptor status, progesterone receptor status, proliferative index (Ki‐67), HER2 status, and molecular subtype groups. However, there was no difference in mortality between the two groups (98 deaths in the ELIOT group and 95 deaths in the WBI group), with an HR of 1.03 (95% CI: 0.77–1.36, p = 0.85) [21]. The trial did not collect long‐term data on adverse reactions.
TARGIT‐A was a randomised, controlled, noninferiority clinical study including women who were eligible for breast preservation, ≥45 years of age, and with tumours ≤3.5 cm, N0–1, M0, and single focal invasive ductal carcinoma. Between 2000 and 2012, the trial involved 2298 women; 1140 patients were randomly assigned to the TARGIT‐IORT group (intraoperative tumour bed surface receiving 50 kV X‐ray beams at 20 Gy), and 1158 patients were assigned to the WBI group. A risk adaptation approach was used, and approximately 20% of patients with high‐risk features found in the final pathological examination after intraoperative APBI were given an additional WBI equivalent to 50 Gy. At a complete 5‐year follow‐up, the risk of local recurrence was 2.11% in the TARGIT‐IORT group and 0.95% in the WBI group (the difference was 1.16%, 90% CI: 0.32–1.99). The preset equivalent standards were met. The median follow‐up was 8.6 years. Local recurrence‐free survival, OS, mastectomy‐free survival, distant metastasis‐free survival, and breast cancer mortality were similar between groups. However, in the TARGIT‐IORT group, the mortality rate from other causes was significantly reduced (HR = 0.59; 95% CI: 0.40–0.86, p = 0.005) [20]. Further subgroup analysis indicated no difference in local relapse‐free survival between the TARGIT‐IORT group and the WBI group in each tumour subgroup. Unlike after WBI, the prognosis of local recurrence after TARGIT‐IORT is good [30]. The TARGIT‐A study findings support the intraoperative use of APBI instead of WBI in early‐stage breast cancer patients who meet the study enrolment criteria and are risk‐adapted.
From the results of the above two large clinical trials of intraoperative radiotherapy, it is necessary to carefully select appropriate patients for intraoperative radiotherapy, and strict screening conditions for intraoperative radiotherapy patients may be a hot spot for further research.
2.4. Other APBI technologies
Stereotactic body radiation therapy (SBRT) can accurately determine the size and position of the target area by connecting with imaging devices such as MR or CT. Lozza et al. [31] applied CyberKnife to APBI and published preliminary results in 2018, indicating that CK‐APBI is feasible and safe for the treatment of early‐stage breast cancer, with moderate acute and late toxicity and good cosmetic effects. CK‐APBI has the technical features of real‐time tracking, respiratory motion management, and millimetre‐level accuracy, maximising target coverage while protecting normal tissues from unnecessary high doses of radiation. The treatment time was approximately 60 min (35–120 min), the irradiation dose was 30 Gy/5 f, and the median number of irradiation fields was 180 (IQR: 107–213). Although CK‐APBI is highly innovative, breast tissue is more difficult to locate than brain or chest tissue because of its mobility and flexibility. The number of patients enroled thus far is small, and long‐term follow‐up data will be worth exploring.
Proton radiotherapy uses proton beams instead of classical photon or X‐ray beams. Because of the presence of the Bragg peak, high‐dose radiation will sharply decrease after reaching the endpoint, reducing the radiation impact on distal normal tissues. Therefore, important distal organs such as the lung and heart can be protected during breast irradiation [32]. A Phase II trial using proton APBI used a split dose of 34 Gy/10 f twice a day. The midterm results showed a local control rate and survival rate of 100% at 1 and 2 years [33]. However, proton radiotherapy is currently expensive, and its promotion and application require further exploration.
3. SELECTION OF A SUITABLE POPULATION
At present, most studies choose early‐stage breast cancer patients with a low risk of recurrence. In 2009, ASTRO issued a consensus for the first time [34], dividing patients into three groups: patients in the “suitable” group can receive APBI without participating in clinical trials; patients in the “need to be cautious” group should be cautious when receiving APBI without participating in clinical trials; and patients in the “unsuitable” group who receive APBI without participating in clinical trials are generally not considered to have a guarantee of efficacy. The 2016 ASTRO Consensus defined patients who are BRCA‐negative, age ≥50 years, and meet one of the following criteria as “suitable” for APBI: invasive ductal carcinoma, primary tumour ≤2 cm (pT1), negative margin width ≥2 mm, no vascular invasion, and ER‐positive; or low/moderate nuclear grade, DCIS detected by screening, with primary tumour ≤2.5 cm and negative margin width ≥3 mm [35]. In 2018, a new interpretation of the guidelines was published [36], which answered the question of population selection for APBI and which patients can receive IORT.
With the publication of the findings from the two randomised clinical trials of IORT with ELIOT (21) and TARGIT‐A (20), new recommendations were made in the guidelines: (1) patients who strictly meet the requirements of the “suitable” group can receive intra‐operative electron therapy; and (2) intra‐operative photon therapy can only be applied in clinical trials [36].
4. FUTURE DIRECTIONS
For patients with low‐risk breast cancer, APBI is an appropriate treatment to lower the risk of IBTR after BCS. The latest large studies have demonstrated the tolerability and effectiveness of APBI. To date, trials have shown that multicatheter brachytherapy, or EBRT, appears to be the most effective. The exploration of reducing the number of fractions in the postoperative PBI setting may have reached a plateau. The typical regimen is a five‐fraction schedule, which may be a suitable compromise in terms of effectiveness, safety, and health‐related quality of life (HRQoL) [37]. The negative results of most intraoperative single‐fraction PBI trials have been considered [20, 21, 38, 39, 40]. The potential benefits of preoperative PBI open a new frontier [41], despite concerns about the optimal dose, fractionation, and technique [42, 43, 44, 45, 46, 47]. Postoperative PBI thus remains the gold standard of care.
Adjuvant endocrine therapy alone, without breast irradiation, is another significant treatment‐downgrading strategy being researched for low‐risk breast cancer. This approach has been encouraged for patients with hormone receptor positivity, pT1N0, and an age of 70 years or older who are scheduled for adjuvant endocrine therapy [48, 49]. Several cohort studies and randomised trials are currently evaluating patients ≥50 years old (NCT01791829, NCT02653755, NCT02400190, NCT02889874, and NCT04134598) [50, 51].
Meattini et al. [52] proposed a potential personalised RT algorithm for early‐stage, low‐risk breast cancer on the basis of genome data. Currently, international recommendations in favour of PBI over WBI are based on clinicopathological risk factors [35, 53]. Because genome‐based predictive relapse scores provide the risk of local recurrence and distant metastasis, combining them with clinicopathological risk factors can further improve the optimal local treatment strategy. Regarding treatment optimisation, the degradation or enhancement of RT can be tested on the basis of genomic scores, regardless of clinicopathological characteristics. Clinical trials are urgently required to explore these hypotheses. Without impacting oncologic outcomes, more individualised RT and selective endocrine therapy may improve cost‐effectiveness and patient HRQoL.
AUTHOR CONTRIBUTIONS
Dandan Song: Writing—original draft (equal); writing—review & editing (equal). Honghong Zhang: Writing—original draft (equal); writing—review & editing (equal). Chengbo Ren: Conceptualization (supporting); writing—review & editing (supporting). Ning Zhan: Writing—review & editing (supporting). Liangxi Xie: Conceptualization (lead); writing—review & editing (equal). Wenjia Xie: Conceptualization (lead); writing—review & editing (equal).
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
ETHICS STATEMENT
Not applicable.
INFORMED CONSENT
Not applicable.
ACKNOWLEDGMENTS
None.
Song D, Zhang H, Ren C, Zhan N, Xie L, Xie W. Accelerated partial breast irradiation: current evidence and future developments. Cancer Innov. 2024;3:e106. 10.1002/cai2.106
Dandan Song and Honghong Zhang contributed equally to this study and shared the first authorship.
Contributor Information
Liangxi Xie, Email: xwj7203@163.com.
Wenjia Xie, Email: lxxie@xah.xmu.edu.cn.
DATA AVAILABILITY STATEMENT
Data sharing is not applicable—no new data generated.
REFERENCES
- 1. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty‐year follow‐up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–1241. 10.1056/NEJMoa022152 [DOI] [PubMed] [Google Scholar]
- 2. Litière S, Werutsky G, Fentiman IS, Rutgers E, Christiaens MR, van Limbergen E, et al. Breast conserving therapy versus mastectomy for stage I‐II breast cancer: 20 year follow‐up of the EORTC 10801 phase 3 randomised trial. Lancet Oncol. 2012;13(4):412–419. 10.1016/S1470-2045(12)70042-6 [DOI] [PubMed] [Google Scholar]
- 3. Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty‐year follow‐up of a randomized study comparing breast‐conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347(16):1227–1232. 10.1056/NEJMoa020989 [DOI] [PubMed] [Google Scholar]
- 4. Smith BD, Bellon JR, Blitzblau R, Freedman G, Haffty B, Hahn C, et al. Radiation therapy for the whole breast: executive summary of an American Society for Radiation Oncology (ASTRO) evidence‐based guideline. Pract Radiat Oncol. 2018;8(3):145–152. 10.1016/j.prro.2018.01.012. [DOI] [PubMed] [Google Scholar]
- 5. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long‐term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362(6):513–520. 10.1056/NEJMoa0906260 [DOI] [PubMed] [Google Scholar]
- 6. Rock K, Ng S, Murray L, Su J, Fyles A, Koch CA. Local control in young women with early‐stage breast cancer treated with hypofractionated whole breast irradiation. The Breast. 2018;41:89–92. 10.1016/j.breast.2018.07.002 [DOI] [PubMed] [Google Scholar]
- 7. de Rose F, de Santis MC, Meduri B, Franzese C, Franceschini D, Franco P, et al. Comparing hypofractionated and conventionally fractionated whole breast irradiation for patients with ductal carcinoma in situ after breast conservation: a propensity score‐matched analysis from a national multicenter cohort (COBCG‐02 study). J Cancer Res Clin Oncol. 2021;147(7):2069–2077. 10.1007/s00432-020-03483-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Chuang WK, Cheng SHC, Hung CF, Huang TT, Jen CW, Yen JH, et al. Comparison between the use of hypofractionated and conventionally fractionated radiotherapy in early breast cancer: a single‐center real‐world study in Taiwan. J Formos Med Assoc. 2022;121(8):1588–1595. 10.1016/j.jfma.2022.01.015 [DOI] [PubMed] [Google Scholar]
- 9. Valle LF, Agarwal S, Bickel KE, Herchek HA, Nalepinski DC, Kapadia NS. Hypofractionated whole breast radiotherapy in breast conservation for early‐stage breast cancer: a systematic review and meta‐analysis of randomized trials. Breast Cancer Res Treat. 2017;162(3):409–417. 10.1007/s10549-017-4118-7 [DOI] [PubMed] [Google Scholar]
- 10. Weng JK, Lei X, Schlembach P, Bloom ES, Shaitelman SF, Arzu IY, et al. Five‐year longitudinal analysis of patient‐reported outcomes and cosmesis in a randomized trial of conventionally fractionated versus hypofractionated whole‐breast irradiation. Int J Radiat Oncol Biol Phys. 2021;111(2):360–370. 10.1016/j.ijrobp.2021.05.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Patel AK, Ling DC, Richman AH, Champ CE, Huq MS, Heron DE, et al. Hypofractionated whole‐breast irradiation in large‐breasted women‐is there a dosimetric predictor for acute skin toxicities? Int J Radiat Oncol Biol Phys. 2019;103(1):71–77. 10.1016/j.ijrobp.2018.08.024 [DOI] [PubMed] [Google Scholar]
- 12. Shaitelman SF, Schlembach PJ, Arzu I, Ballo M, Bloom ES, Buchholz D, et al. Acute and short‐term toxic effects of conventionally fractionated vs hypofractionated whole‐breast irradiation: a randomized clinical trial. JAMA Oncol. 2015;1(7):931–941. 10.1001/jamaoncol.2015.2666 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Veronesi U, Marubini E, Mariani L, Galimberti V, Luini A, Veronesi P, et al. Radiotherapy after breast‐conserving surgery in small breast carcinoma: long‐term results of a randomized trial. Ann Oncol. 2001;12(7):997–1003. 10.1023/a:1011136326943 [DOI] [PubMed] [Google Scholar]
- 14. Freedman GM, Fowble BL. Local recurrence after mastectomy or breast‐conserving surgery and radiation. Oncology (Williston Park). 2000;14(11):1561–1581 [PubMed] [Google Scholar]; discussion 1581–2, 1582–4.
- 15. Vicini FA, Kestin LL, Goldstein NS. Defining the clinical target volume for patients with early‐stage breast cancer treated with lumpectomy and accelerated partial breast irradiation: a pathologic analysis. Int J Radiat Oncol Biol Phys. 2004;60(3):722–730. 10.1016/j.ijrobp.2004.04.012 [DOI] [PubMed] [Google Scholar]
- 16. Pérez M, Schootman M, Hall LE, Jeffe DB. Accelerated partial breast irradiation compared with whole breast radiation therapy: a breast cancer cohort study measuring change in radiation side‐effects severity and quality of life. Breast Cancer Res Treat. 2017;162(2):329–342. 10.1007/s10549-017-4121-z [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Strnad V, Polgár C, Ott OJ, Hildebrandt G, Kauer‐Dorner D, Knauerhase H, et al. Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole‐breast irradiation with boost for early breast cancer: 10‐year results of a GEC‐ESTRO randomised, phase 3, non‐inferiority trial. Lancet Oncol. 2023;24(3):262–272. 10.1016/S1470-2045(23)00018-9 [DOI] [PubMed] [Google Scholar]
- 18. Polgár C, Fodor J, Major T, Sulyok Z, Kásler M. Breast‐conserving therapy with partial or whole breast irradiation: ten‐year results of the Budapest randomized trial. Radiother Oncol. 2013;108(2):197–202. 10.1016/j.radonc.2013.05.008 [DOI] [PubMed] [Google Scholar]
- 19. Shah C, Badiyan S, Ben Wilkinson J, Vicini F, Beitsch P, Keisch M, et al. Treatment efficacy with accelerated partial breast irradiation (APBI): final analysis of the American society of breast surgeons MammoSite® breast brachytherapy registry trial. Ann Surg Oncol. 2013;20(10):3279–3285. 10.1245/s10434-013-3158-4 [DOI] [PubMed] [Google Scholar]
- 20. Vaidya JS, Bulsara M, Baum M, Wenz F, Massarut S, Pigorsch S, et al. Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT‐IORT) for early breast cancer: TARGIT‐a randomised clinical trial. BMJ. 2020;370:m2836. 10.1136/bmj.m2836 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Orecchia R, Veronesi U, Maisonneuve P, Galimberti VE, Lazzari R, Veronesi P, et al. Intraoperative irradiation for early breast cancer (ELIOT): long‐term recurrence and survival outcomes from a single‐centre, randomised, phase 3 equivalence trial. Lancet Oncol. 2021;22(5):597–608. 10.1016/S1470-2045(21)00080-2 [DOI] [PubMed] [Google Scholar]
- 22. Whelan TJ, Julian JA, Berrang TS, Kim DH, Germain I, Nichol AM, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node‐negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019;394(10215):2165–2172. 10.1016/S0140-6736(19)32515-2 [DOI] [PubMed] [Google Scholar]
- 23. Vicini FA, Cecchini RS, White JR, Arthur DW, Julian TB, Rabinovitch RA, et al. Long‐term primary results of accelerated partial breast irradiation after breast‐conserving surgery for early‐stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. 2019;394(10215):2155–2164. 10.1016/S0140-6736(19)32514-0 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, et al. Accelerated partial breast irradiation using intensity‐modulated radiotherapy versus whole breast irradiation: 5‐year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. 2015;51(4):451–463. 10.1016/j.ejca.2014.12.013 [DOI] [PubMed] [Google Scholar]
- 25. Rodríguez N, Sanz X, Dengra J, Foro P, Membrive I, Reig A, et al. Five‐year outcomes, cosmesis, and toxicity with 3‐dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2013;87(5):1051–1057. 10.1016/j.ijrobp.2013.08.046 [DOI] [PubMed] [Google Scholar]
- 26. Meattini I, Marrazzo L, Saieva C, Desideri I, Scotti V, Simontacchi G, et al. Accelerated partial‐breast irradiation compared with whole‐breast irradiation for early breast cancer: long‐term results of the randomized phase III APBI‐IMRT‐florence trial. J Clin Oncol. 2020;38(35):4175–4183. 10.1200/JCO.20.00650 [DOI] [PubMed] [Google Scholar]
- 27. Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A, et al. Partial‐breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5‐year results from a multicentre, randomised, controlled, phase 3, non‐inferiority trial. Lancet. 2017;390(10099):1048–1060. 10.1016/S0140-6736(17)31145-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Wallace M, Martinez A, Mitchell C, Chen PY, Ghilezan M, Benitez P, et al. Phase I/II study evaluating early tolerance in breast cancer patients undergoing accelerated partial breast irradiation treated with the mammosite balloon breast brachytherapy catheter using a 2‐day dose schedule. Int J Radiat Oncol Biol Phys. 2010;77(2):531–536. 10.1016/j.ijrobp.2009.05.043 [DOI] [PubMed] [Google Scholar]
- 29. White JR, Winter K, Cecchini RS, Vicini FA, Arthur DW, Kuske RR, et al. Cosmetic outcome from post lumpectomy whole breast irradiation (WBI) versus partial breast irradiation (PBI) on the NRG oncology/NSABP B39‐RTOG 0413 phase III clinical trial. Int J Radiat Oncol Biol Phys. 2019;105(1):S3–S4. 10.1016/j.ijrobp.2019.06.384 [DOI] [Google Scholar]
- 30. Vaidya JS, Bulsara M, Baum M, Wenz F, Massarut S, Pigorsch S, et al. New clinical and biological insights from the international TARGIT‐a randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer. Br J Cancer. 2021;125(3):380–389. 10.1038/s41416-021-01440-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Lozza L, Fariselli L, Sandri M, Rampa M, Pinzi V, de Santis MC, et al. Partial breast irradiation with CyberKnife after breast conserving surgery: a pilot study in early breast cancer. Radiat Oncol. 2018;13(1):49. 10.1186/s13014-018-0991-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. Vanderwaeren L, Dok R, Verstrepen K, Nuyts S. Clinical progress in proton radiotherapy: biological unknowns. Cancers. 2021;13(4):604. 10.3390/cancers13040604 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Pasalic D, Strom EA, Allen PK, Williamson TD, Poenisch F, Amos RA, et al. Proton accelerated partial breast irradiation: clinical outcomes at a planned interim analysis of a prospective phase 2 trial. Int J Radiat Oncol Biol Phys. 2021;109(2):441–448. 10.1016/j.ijrobp.2020.09.009 [DOI] [PubMed] [Google Scholar]
- 34. Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, et al. Accelerated partial breast irradiation consensus statement from the American society for radiation oncology (ASTRO). Int J Radiat Oncol Biol Phys. 2009;74(4):987–1001. 10.1016/j.ijrobp.2009.02.031 [DOI] [PubMed] [Google Scholar]
- 35. Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, et al. Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence‐based consensus statement. Pract Radiat Oncol. 2017;7(2):73–79. 10.1016/j.prro.2016.09.007 [DOI] [PubMed] [Google Scholar]
- 36. Kirby AM. Updated ASTRO guidelines on accelerated partial breast irradiation (APBI): to whom can we offer APBI outside a clinical trial? Br J Radiol. 2018;91(1085):20170565. 10.1259/bjr.20170565 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Wright JL, Bellon JR. Is the time right for five‐fraction partial breast irradiation? J Clin Oncol. 2020;38(35):4135–4137. 10.1200/JCO.20.01397 [DOI] [PubMed] [Google Scholar]
- 38. Vaidya JS, Bulsara M, Saunders C, Flyger H, Tobias JS, Corica T, et al. Effect of delayed targeted intraoperative radiotherapy vs whole‐breast radiotherapy on local recurrence and survival: long‐term results from the TARGIT‐a randomized clinical trial in early breast cancer. JAMA Oncol. 2020;6(7):e200249. 10.1001/jamaoncol.2020.0249 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Marta GN, Meattini I. Partial breast irradiation with intraoperative radiotherapy in the ELIOT trial. Lancet Oncol. 2021;22(7):e297. 10.1016/S1470-2045(21)00260-6 [DOI] [PubMed] [Google Scholar]
- 40. Bentzen SM, Haviland JS, Yarnold JR. Targeted intraoperative radiotherapy for early breast cancer. JAMA Oncol. 2020;6(10):1636. 10.1001/jamaoncol.2020.2716 [DOI] [PubMed] [Google Scholar]
- 41. Corradini S, Krug D, Meattini I, Matuschek C, Bölke E, Francolini G, et al. Preoperative radiotherapy: a paradigm shift in the treatment of breast cancer? A review of literature. Crit Rev Oncol Hematol. 2019;141:102–111. 10.1016/j.critrevonc.2019.06.003 [DOI] [PubMed] [Google Scholar]
- 42. Bosma SCJ, Hoogstraat M, van der Leij F, de Maaker M, Wesseling J, Lips E, et al. Response to preoperative radiation therapy in relation to gene expression patterns in breast cancer patients. Int J Radiat Oncol Biol Phys. 2020;106(1):174–181. 10.1016/j.ijrobp.2019.09.002 [DOI] [PubMed] [Google Scholar]
- 43. Bosma SCJ, Leij F, Vreeswijk S, Maaker M, Wesseling J, Vijver M, et al. Five‐year results of the preoperative accelerated partial breast irradiation (PAPBI) trial. Int J Radiat Oncol Biol Phys. 2020;106(5):958–967. 10.1016/j.ijrobp.2019.12.037 [DOI] [PubMed] [Google Scholar]
- 44. Horton JK, Blitzblau RC, Yoo S, Geradts J, Chang Z, Baker JA, et al. Preoperative single‐fraction partial breast radiation therapy: a novel phase 1, dose‐escalation protocol with radiation response biomarkers. Int J Radiat Oncol Biol Phys. 2015;92(4):846–855. 10.1016/j.ijrobp.2015.03.007 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Nichols E, Kesmodel SB, Bellavance E, Drogula C, Tkaczuk K, Cohen RJ, et al. Preoperative accelerated partial breast irradiation for early‐stage breast cancer: preliminary results of a prospective, phase 2 trial. Int J Radiat Oncol Biol Phys. 2017;97(4):747–753. 10.1016/j.ijrobp.2016.11.030 [DOI] [PubMed] [Google Scholar]
- 46. Vasmel JE, Vreuls CPH, Manson QF, Charaghvandi RK, van Gorp J, van Leeuwen AMG, et al. Tumor‐infiltrating lymphocytes in low‐risk patients with breast cancer treated with single‐dose preoperative partial breast irradiation. Int J Radiat Oncol Biol Phys. 2021;109(5):1325–1331. 10.1016/j.ijrobp.2020.12.009 [DOI] [PubMed] [Google Scholar]
- 47. Meattini I, Francolini G, Di Cataldo V, Visani L, Becherini C, Scoccimarro E, et al. Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894. Clin Transl Radiat Oncol. 2022;37:94–100. 10.1016/j.ctro.2022.09.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48. Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM. Breast‐conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol. 2015;16(3):266–273. 10.1016/S1470-2045(14)71221-5 [DOI] [PubMed] [Google Scholar]
- 49. Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long‐term follow‐up of CALGB 9343. J Clin Oncol. 2013;31(19):2382–2387. 10.1200/JCO.2012.45.2615 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50. Whelan TJ, Smith S, Nielsen TO, Parpia S, Fyles AW, Bane A, et al. LUMINA: a prospective trial omitting radiotherapy (RT) following breast conserving surgery (BCS) in T1N0 luminal A breast cancer (BC). J Clin Oncol. 2022;40(17_suppl):LBA501. 10.1200/jco.2022.40.17_suppl.lba501 [DOI] [Google Scholar]
- 51. Meattini I, Poortmans PMP, Marrazzo L, Desideri I, Brain E, Hamaker M, et al. Exclusive endocrine therapy or partial breast irradiation for women aged ≥70 years with luminal a‐like early stage breast cancer (NCT04134598 ‐ Europa): proof of concept of a randomized controlled trial comparing health related quality of life by patient reported outcome measures. J Geriatr Oncol. 2021;12(2):182–189. 10.1016/j.jgo.2020.07.013 [DOI] [PubMed] [Google Scholar]
- 52. Meattini I, Kim K, Livi L. Accelerated partial breast irradiation: florence phase 3 trial experience and future perspectives. Am J Clin Oncol. 2023;46(1):10–15. 10.1097/COC.0000000000000968 [DOI] [PubMed] [Google Scholar]
- 53. Meattini I, Becherini C, Boersma L, Kaidar‐Person O, Marta GN, Montero A, et al. European Society for Radiotherapy and Oncology Advisory Committee in radiation oncology practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer. Lancet Oncol. 2022;23(1):e21–e31. 10.1016/S1470-2045(21)00539-8 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data sharing is not applicable—no new data generated.
