Introduction
Breast cancer (BC) is the most common cancer in women [1]. Tremendous progress has been achieved in its treatment through recent decades, improving disease-free (DFS) and overall survival (OS) [2]. Treatment of early BC is multimodal: it addresses both the local and systemic components of the disease with surgery with or without radiotherapy (RT) for the former and systemic treatments (hormone therapy, chemotherapy, targeted treatments, and immunotherapy) for the latter [3, 4]. RT is an essential modality of locoregional management because it has permitted a de-escalation of surgery in breast and axilla [5] and provides local control and OS benefits after lumpectomy and even mastectomy in higher-risk patients [6, 7].
The vast amount of published evidence on BC RT merits putting it into context, so that it is readily available for evidence-based decisions in the routine treatment of the individual cancer patient. Indeed, in modern BC RT, several evidence-based options exist. Their overview and understanding can promote quality in shared or multidisciplinary decision-making and represents the scope of this work.
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The Scientific Association of Swiss Radiation Oncology (SASRO) is the national scientific multidisciplinary society in radiation oncology. Given its mission to promote education in the discipline within Switzerland, a pilot project was initiated by the SASRO board to address this need and is presented in this manuscript.
This educational SASRO initiative aims to provide an updated, clinically relevant and comprehensive background of existing evidence on radiation oncology treatment of BC. It is not a narrative review of the literature, nor does this work aim to give specific recommendations for clinical practice, since this has already been undertaken within the work presented here. The goal of this work is to make available all the relevant information for evidence-based radiation oncology treatment of BC, so that clinicians can decide for themselves which guideline to adopt and which discussion on a grey zone they are going to adhere to in their clinical practice.
Methods
This work was undertaken through January 2023 to January 2024. The SASRO board assigned the tasks of conceptualization, methodology, and final manuscript drafting to one of its members (PT). A first draft including methodology was presented to the SASRO board at the 2023 SASRO board retreat. Upon discussion and board approval, a panel of 9 additional BC radiation oncology experts for BC treatment, representing academic, public cantonal, and private centers within Switzerland and distributed among Swiss regions (German, French and Italian speaking), was defined. An expert BC surgeon (WW) and an expert BC medical oncologist (KhZ) were included in the panel to provide insights from these relevant disciplines. The panel met four times, approximately every 3 months, and worked on the initial draft. Input from all panelists was critically discussed and integrated in the final draft based on consensus. After review, the final draft of the manuscript was approved by the panel and submitted to the SASRO board for final approval at the 2024 SASRO board retreat. This draft is to be posted on the SASRO website after publication of the present manuscript, submitted to the official journal of SASRO, Strahlentherapie Onkologie.
Breast cancer is a disease with much evidence and subtlety, and this work aimed to highlight all the available options and guidance without replacing existing guidelines. The project was defined as such by SASRO and aims to reflect the Swiss mentality of consensus and acknowledgement of possible multiple different views that can be applicable.
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The recommendations will be updated by the panel every 2 years. After completion of this pilot project, future projects of the SASRO board include undertaking this work for other tumor pathologies (e.g., head and neck and/or prostate cancer).
Results
BC RT indications
Standard recommendations for BC RT indications
include the statements that every decision on BC RT must be undertaken within a BC tumor board, preferably within a certified BC center. All patients with BC should have access to comprehensive cancer care [8]. Participating in clinical trials improves patients’ outcomes, and enrolment should be encouraged by BC tumor boards and BC radiation oncologists. Minimum requested work-up for BC diagnosis is described in the NCCN (National Comprehensive Cancer Network) and ESMO (European Society for Medical Oncology) guidelines. The most recent, essential guidelines for BC RT have been identified and are presented in Table 1. The number of radiation oncologists (ROs)/specialists out of all specialists participating in the guidelines/consensus is also illustrated.
Table 1
Reference guidelines for early-stage primary breast cancer
Guideline | Description | Reference | ROs/specialists |
|---|---|---|---|
NCCN v 5.2023 | Decision trees for BC [14] | 4/44 | |
St Gallen | Expert consensus [15] | Curigliano G, Burstein HJ, Gnant M et al. Understanding breast cancer complexity to improve patient outcomes: The St. Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer. An Oncol 2023 34;11: 970–986 | 3/61 |
ESMO | Guideline [16] | S. Loibl, F. André, T. Bachelot et al, on behalf of the ESMO Guidelines Committee. Early Breast Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology (2024), https://doi.org/10.1016/j.annonc.2023.11.016 | 1/8 |
ASCO | Specific guideline on axilla management [17] | Brackstone M, Baldassarre FG, Perera FE et al. Management of the Axilla in Early-Stage Breast Cancer: Ontario Health (Cancer Care Ontario) and ASCO Guideline. JCO 2021 Sep 20;39(27):3056–3082 | 3/14 |
SSO-ASTRO-ASCO | Consensus on margins in DCIS [18] | Morrow M, Van Zee KJ, Solin LJ et al. Society of Surgical Oncology—American Society for Radiation Oncology—American Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery with Whole-Breast Irradiation in Ductal Carcinoma in Situ. J Clin Oncol. 2016 34:33, 4040–4046 | 4/13 |
ASCO | Guideline on post-mastectomy RT for early-stage BC [19] | Recht A, Comen EA, Fine RE et al. Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update. JCO 2016 34:36, 4431–4442 | 6/17 |
ESTRO | Recommendations on IORT [20] | Fastner G, Gaisberger C, Kaiser J et al. ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy with electrons (IOERT) in breast cancer. Radiother Oncol. 2020;149:150–157 | NA |
ESTRO | Guideline on brachytherapy [21] | Strnad V, Major T, Polgar C et al. ESTRO-ACROP guideline: Interstitial multi-catheter breast brachytherapy as Accelerated Partial Breast Irradiation alone or as boost—GEC-ESTRO Breast Cancer Working Group practical recommendations. Radiother Oncol. 2018;128(3):411–420 | NA |
ESTRO | Consensus on fractionation [22] | Meattini I, Becherini C, Boersma L, 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 Jan;23(1):e21–e31. https://doi.org/10.1016/S1470-2045(21)00539-8. PMID: 34973228 | 14/22 |
ESTRO-endorsed | Consensus on association of BC RT and drugs [23] | Meattini I, Becherini C, Caini S et al.; Consensus Panellist Group. International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations. Lancet Oncol. 2024 Feb;25(2):e73–e83. https://doi.org/10.1016/S1470-2045(23)00534-X. PMID: 38301705 | 8/19 |
ASTRO | Guideline on PBI [12] | Shaitelman SF, Anderson BM, Arthur DW, et al. Partial Breast Irradiation for Patients With Early-Stage Invasive Breast Cancer or Ductal Carcinoma In Situ: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol. 2024 Mar-Apr;14(2):112–132 | All |
Emerging disease settings include oligometastatic disease, for which appropriate imaging and treatments are clinical research priorities [9]—a setting where the optimal treatment approach remains to be defined and should be discussed in a multidisciplinary setting. Emerging indications include partial breast irradiation (PBI), representing a standard option for early, low-risk breast cancer [10], with preferred modalities being external-beam RT with CT planning or brachytherapy [11]. Intraoperative radiotherapy (IORT) remains a possible option in carefully selected patients with very-low-risk BC, such as luminal A T1a‑b N0 tumors and elderly patients with comorbidities, although most recent guidelines advise against more generalized use for low-risk patients [12]. Low-risk BC or ductal carcinoma in situ (DCIS) represents a personalized setting where adjuvant treatment trade-offs should be discussed within a shared decision-making context [13].
Grey zones in BC RT indications
have been identified and discussed. We recognized regional BC RT, which has long been a matter of debate, as a pertaining grey zone, despite the recent Oxford meta-analysis confirming small benefits of regional BC RT for distant control and BC-related mortality, with no negative impact on non-BC mortality within modern trials. The magnitude of the benefit is larger in higher-risk patients [24]. Treatment of the axilla and the associations of surgery and RT in the era of de-escalation of the latter remain challenging and are regularly addressed in multidisciplinary panels of BC specialists [25]. As this field is evolving and the object of research underway, results of ongoing trials, such as MA.39 (NCT03488693), will permit better identification of risk factors for addition or omission of regional RT by integrating biology. Of note, the indicated irradiation volumes when regional RT is performed also remain a matter of debate, as the pivotal studies, such as ACOSOG Z0011 [26], AMAROS [27], MA.20 [28], and EORTC-IMC [29], all used slightly different irradiation volumes.
Post-M RT (PMRT)
another possible grey zone, especially when intermediate-risk stages, such as pT1‑2 pN1, are concerned. For these stages, especially after axillary lymph node dissection (ALND), the benefit of PMRT with modern systemic treatments can be challenged, as discussed in the ASCO guidelines on PMRT [19]—and this despite the Oxford meta-analysis that advises PMRT after ALND for any node-positive patient [7]. As surgery is de-escalated and systemic treatments evolve and improve outcomes, these indications can be debated in more modern contexts. Despite this, it must be kept in mind that improved systemic treatments will probably make BC RT even more efficient and relevant [30].
Irradiation after neoadjuvant chemotherapy (NACT)
remains another grey zone of possible de-escalation. Most recent guidelines advise the consideration of initial nodal involvement for decision-making regarding regional RT. For selected cases with cT1‑2 cN1 disease transforming into ypN0 after NACT and ALND, de-escalation of RT emerged as a potentially safe consideration after the publication of the prospective registry study RAPCHEM [31]. However, the panel noted that this is a prospective registry study, where around 80% of patients received ALND after NACT, a practice that is now being abandoned in cases of ycN0. The study is highly relevant as proof of principle but not sufficient for practice change. The recent presentation of NSAPB-51 at the San Antonio Breast Cancer Symposium (SABCS) 2023 is a practice changing phase III study showing no benefit of regional RT in patients with cT1‑3 cN1 BC converting into ypN0 [32].
Another grey zone in the field of axillary management and work-up is described in ASCO guidelines [19]. Omission of sentinel lymph node dissection (SLND) in low-risk cN0 BC becomes an evidence-based option, given the recent publication of the SOUND trial [33]. The panel recognized that this is a fast-moving field, with more data expected in the coming years.
Finally, for a detailed discussion on modern BC RT controversies, the JCO special issue on locoregional management of BC that appeared in May 2020 remains a precious resource [34]. BC RT indications as standard options recognized by the panel are presented in Table 2.
Table 2
Volumes, doses, and fractionation for breast cancer radiotherapy: indicative options
Indication | Irradiation | Irradiation doses (Gy) | Fractionation (Gy/fr) | Number of fractions |
|---|---|---|---|---|
BCS | ||||
DCIS | Low-risk DCIS: RT indication as shared decision with patient Breast +/− boost tumor bed Boost: shared decision with patient | Breast 40.5 + SIB 48 | 2.7/3.2 | 15 |
Reading | ||||
pT1pN0 Preferably: luminal A > 60y | Partial breast irradiation tumor bed | PTV 30* | 6 | 5; every other day |
pT1pN0, luminal, > 40y | HDR brachytherapy | Tumor bed + 20 mm 30.1 | 7 | In 5 days; twice daily |
Margin > 2 mm | Tumor bed + 20 mm 32 | 8 | ||
PDR brachytherapy | Tumor bed + 20 mm 50 , pulses 0.6–0.8 Gy/h | – | ||
Reading | External beam RT PBI [37] | |||
pT1‑2 pN0 | Breast +/− boost tumor bed | Breast 40.5/48 SIB | 2.7‑3.2 | 15 |
Boost: shared decision with patient after 50y | Breast 40.5 +/− boost 10.8–13.5 | 2.7 | 15 + 5 | |
Moderate hypofractionation preferable | Breast 36/partial breast 40/48 tumor bed | 2.4/2.67/3.2 | 15 | |
Elderly: extreme hypofractionation an option | Breast 42.56 + boost 10.64 | 2.66 | 16 + 4 | |
Breast 50/SIB 60 | 2 | 25 | ||
Breast 28.5 | 5.7 | 5; once weekly | ||
Breast 26 | 5.2 | 5 within a week | ||
Reading | ||||
pN1 and SLND | Breast +/− boost tumor bed | Breast 50/SIB 60 | 2–2.4 | 25 |
Boost: shared decision with patient after 50y | Regional nodes: 45–50 | 1.8–2 | 25 | |
+ axilla I–III, consider IV, consider IMC | – | – | 15 | |
Consider regional RT if 1–2 nodes positive, no ECE | – | – | 15 | |
Consider IMC if QE | – | – | – | |
Local RT according to ACOSOG Z0011 is an option for low-risk patients | – | – | – | |
Hypofractionation an option | Breast 36/partial breast 40/48 tumor bed | 2.4/2.67/3.2 | 15 | |
Lymph nodes 40 | 2.67 | 15 | ||
Breast and regional nodes 40.5 | 2.7 | 15 | ||
Breast and regional nodes 42.56 | 2.66 | 16 | ||
pN2/pN3 | Breast +/− boost tumor bed | Breast 50+ boost 10–16 or | 2 | 25–33 |
Boost: shared decision with patient after 50y | Breast 50+ SIB 60 | 2–2.4 | 25 | |
+ axilla III, IV, IMC | Regional nodes 50 | 2 | 25 | |
Consider boost in unresected regional disease | 55 Gy | 2.2 | 25 | |
Hypofractionation an option | Breast and regional nodes 40.5 | 2.7 | 15 | |
Breast and regional nodes 42.56 | 2.66 | 16 | ||
PMRT | ||||
pT3pN0 | Chest wall | Chest wall 50 | 2 | 25 |
Hypofractionation an option if no immediate reconstruction | Chest wall 40.5 | 2.7 | 15 | |
Chest wall 42.56 | 2.66 | 16 | ||
pT4 | Chest wall +/− boost scar | Chest wall 50 + boost 10–16 | 2 | 25–33 |
Bolus if skin invasion | – | – | – | |
Consider regional RT | – | – | – | |
Hypofractionation an option if no immediate reconstruction | Chest wall 40.5 +/− boost 10.8–13.5 | 2.7 | 15–20 | |
Chest wall 42.56 +/− boost 10.64 | 2.66 | 16–20 | ||
pN1 and SLND | Chest wall + axilla I–III, consider IV, consider IMC | Chest wall 50 | 2 | 25 |
Regional nodes 45–50 | 1.8–2 | 25 | ||
Consider IMC if QE | – | – | – | |
Hypofractionation in elderly patient if no immediate reconstruction | Chest wall and regional nodes 40.5 | 2.7 | 15 | |
Chest wall and regional nodes 42.56 | 2.66 | 16 | ||
pN2/pN3 | Chest wall + axilla III, IV, IMC | Chest wall + regional nodes 50 | 2 | 25 |
Consider boost in unresected regional disease | 55 | 2.2 | 25 | |
Hypofractionation in elderly patients | Chest wall and regional nodes 40.5 | 2.7 | 15 | |
Chest wall and regional nodes 42.56 | 2.66 | 16 | ||
BC RT technique, irradiation volumes, dosimetry, and fractionation
In terms of the BC RT technique, the panel recognized that the optimum available technique, providing coverage of targets and protection of organs at risk (OARs), including consideration of the risk of secondary cancer, should be used; 3D and/or intensity-modulated techniques are valid options in this setting. The use of deep-inspiration breath hold (DIBH) to protect the heart/lung/liver, when feasible and advantageous from a dosimetric point of view, especially for left-sided tumors, was strongly supported [40, 41]. Treatment in the prone position is an option to decrease acute toxicity for selected cases, especially in patients with voluminous breasts and the indication of whole-breast irradiation (WBI) only [42]. The use of bolus should be avoided in PMRT, unless in case of skin involvement of the disease [43].
In terms of target volume delineation, the major ESTRO-endorsed guideline is commonly used [44], with a note of the panelists to remind that these volumes are appropriate for early BC. Enlarged target volumes can be considered for locally advanced BC (LABC) [45]. An alternative atlas with enlarged target volumes was used for the RADCOMP study and can be found at the RTOG site [46]. An ESTRO-endorsed atlas for clinical volume delineation after PMRT and immediate reconstruction with implants can be considered, but clinical experience and adoption by the panelists remains limited [47]. Finally, artificial intelligence (AI) solutions for contouring, preferably not atlas based, might be useful and are commonly used by some members of the panel.
In terms of tumor bed delineation, surgical clips are strongly advised for boost delineation and PBI, especially in the context of oncoplasty. PBI target volume delineation strongly depends on the technique used. For both WBI and PBI, peer review of volumes and/or dosimetry is strongly advised.
In terms of BC RT fractionation, multiple fractionation regimens are supported by high-level evidence. A recent ESTRO-endorsed consensus was published on appropriate fractionation options [22]. Given the heterogeneity of fractionation regimens adopted in Switzerland and the specific availability of resources in the country, the panel decided to provide a comprehensive table of all available studies on fractionation regimens tested (Table 3).
Table 3
Overview of major phase III fractionation studies
Study Publication year | Age | Disease stage | No. patients | Surgery type (BCS/M) | RT regimen (no. factions × dose/fraction [Gy/fr]) | FU (years) | Endpoint | Conclusion |
|---|---|---|---|---|---|---|---|---|
Royal Marsden [48] 2006 | < 75 years | pT1-3a pN0‑1 M0 | 1410 | BCS | 25 × 2 vs. 13 × 3.3 vs. 13 × 3 | 9.7 | Late change in breast appearance | α/β late change in breast = 3.6 α/β breast induration = 3.1 α/β breast cancer = 4 |
START A [49] 2008 | Any 5% < 40 years | pT1-3a pN0‑1 M0 | 2236 | BCS: 84% M: 16% | 25 × 2 vs. 13 × 3.2 in 5 weeks vs. 13 × 3 in 5 weeks | 5.1 | LR Late normal tissue effects QoL | Winner: 13 × 3.2 in 5 weeks |
START B [50] 2008 | Any 5% < 40 years | pT1-3a pN0‑1 M0 | 2215 | BCS: 92% M: 8% | 25 × 2 vs. 15 × 2.67 | 6 | LR Late normal tissue effects QoL | Winner: 15 × 2.67 |
Canadian [51] 2010 | Any 25%< 50 years | pT1‑2 pN0 M0 | 1234 | BCS | 25 × 2 vs. 16 × 2.66 | 10 | LR | Non-inferiority 16 × 2.66 |
IMPORT LOW [52] 2017 | > 50 years | pT1‑2 pN0‑1 M0 T < 3 cm | 2018 | BCS | 15 × 2.67 WBI vs. 15 × 2.4 WBI + 15 × 2.67 PBI vs. 15 × 2.67 PBI | 6 | LR | Non-inferiority 15 × 2.4 WBI + 15 × 2.67 PBI vs. 15 × 2.67 PBI |
Chinese [53] 2019 | 18–75 years 51%< 50 years | pT3-4pN2‑3 M0 | 820 | M | 25 × 2 vs. 15 × 2.9 | 4.9 | LRR | Non-inferiority 15 × 2.9 |
Chinese [54] 2020 | 18–70 years 40%< 45 years | pT1-2pN0‑3 M0 | 734 | BCS | 25 × 2 + 5 × 2 boost vs. 15 × 2.9 + 3 × 2.9 boost | 6.1 | 5‑year LRR | Non-inferiority 15 × 2.9 + 3 × 2.9 boost |
FAST [38] 2020 | ≥ 50 years | pT1‑2 pN0 M0 | 915 | BCS | 25 × 2 vs. 5 × 6 once weekly vs. 5 × 5.7 once weekly | 10 | Change in photographic appearance at 2 and 5 years | Winner: 5 × 5.7 once weekly |
DBCG Hypo [55] 2020 | > 40 years | pT1‑2 pN0 pM0 and DCIS (13%) | 1854 | BCS | 25 × 2 vs. 15 × 2.67 | 7.26 | 3‑year Gr 2–3 breast induration with non-inferiority LR | Non-inferiority 15 × 2.67 |
FAST FORWARD [56] 2020 | > 18 years 1% < 40 years | pT1-3a pN0‑1 M0 | 4096 | BCS 93% M 7% Regional substudy:11% patients/no IMC | 15 × 2.67 vs. 5 × 5.4 vs. 5 × 5.2 | 5.95 | LR | Non-inferiority 5 × 5.2 |
BIG 3‑07/TROG 07.01 [35] 2022 | > 18 years | Non-low-risk DCIS | 1608 | BCS | 25 × 2 vs. 16 × 2.66 R boost vs no boost (8 × 2) | 6.6 | Time to LR | Winner: 16 × 2.66 Boost: reduced LR but increased Gr 2 toxicity |
SKAGEN Unpublished Offerssen VB, ESTRO 2022 | > 18 years | pT1‑3 pN0‑3 M0 Regional nodes RT | 2879 | BCS: 52% M: 48% | 25 × 2 WBI +/− SIB 25 × 2.28/25 × 2.52 15 × 2.67 WBI +/−SIB 15 × 3.05/15 × 3.48 SIB: 16% | 2 | 3‑year lymphedema | Non-inferiority 15 × 2.67 WBI +/− SIB 15 × 3.05/15 × 3.48 |
HypoG01: UNICANCER Unpublished Rivera S, ESTRO 2023 | > 18 years | pT1‑3 pN0‑3 M0 Regional nodes RT | 1265 | BCS: 55% M: 45% ALND: 82.8% | 25 × 2 15 × 2.67 Boost or SIB: 48.8% | 3.1 | 3‑year lymphedema | Non-inferiority 15 × 2.67 |
IMPORT HIGH [57] 2023 | Min 45 years | pT1-3pN0-3a M0 | 2617 | BCS | 15 × 2.67 WBI + 8 × 2 boost TB 15 × 2.4 WBI +15 × 2.67 PBI + 15 × 3.2 TB vs. 15 × 2.4 WBI + 15 × 2.67 PBI + 15 × 3.53 TB | 6.2 | LR | Dose escalation not advantageous |
GEC-ESTRO interstitial brachytherapy [11] | > 40 years | pT1 (89%), pT2 (11%) DCIS 4% | 1328 | BCS | 25 × 2 WBI + 5 × 2 boost vs. Tumor bed + 20 mm 30.1 Gy HDR Tumor bed + 20 mm 32 Gy HDR Tumor bed + 20 mm 50 Gy, pulses 0.6–0.8 Gy/h, PDR | 10.36 | LR | Non-inferiority APBI |
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Specific topics
The panel wished to address specific topics that are often debated in multidisciplinary tumor boards.
One such topic is the omission of RT in low-risk BC in elderly patients, which was recognized as an option in patients receiving adjuvant endocrine therapy, with recent relevant literature [58‐60] discussed in the New England Journal of Medicine [61, 62]. However, when endocrine therapy is not considered, BC RT can be a valuable option, as discussed by Naoum [97] or Ward and colleagues [63]. An ongoing study, EUROPA (NCT04134598) [64], will ultimately address the trade-off in quality of life between a few fractions of PBI versus 5 years of endocrine therapy, as discussed in the New England Journal of Medicine [61, 62]. However, when endocrine therapy is not considered or feasible, BC RT can be a valuable option, as discussed by Naoum [97] or Ward and colleagues [63].
BC RT in the context of autoimmune disease is another specific topic for which evidence is very scarce. Modern literature suggests that BC RT toxicity is acceptable and might be slightly increased in patients with autoimmune disease as compared to those without, especially when their autoimmune disease is active, with some recent evidence emerging on the use of hypofractionation [65] or [66] hypofractionation/PBI in this context.
BC RT in the setting of patients with a genetic predisposition to cancer has been identified as another specific topic, meriting review of the evidence. The only absolute contraindication for BC RT remains the Li-Fraumeni syndrome, which is associated with a high risk of secondary malignancies after RT [67‐69]. For patients with BC who are BRCA mutation carriers, BC RT is as safe as in the general population [70‐72].
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The combination of BC RT with new drugs established in the adjuvant disease setting is an emerging specific topic of major importance, treated in several recent comprehensive reviews [73], the most recent being ESTRO endorsed [23]. As far as BC RT and the current adjuvant anti-HER‑2 targeted therapies are concerned, their combination concurrently with BC RT seems to be safe, especially with new irradiation techniques sparing the heart [74, 75]. Regarding the concomitant use of BC RT and T‑DM1, a slight increase in pneumonitis has been noted in the adjuvant setting, with overall safety being considered acceptable, but with caution needed when irradiating intracranial sites in the metastatic setting [76]. Regarding the concurrent use of BC RT and trastuzumab deruxtecan, it is advised not to combine them concomitantly in the adjuvant setting [75]. Immunotherapy with pembrolizumab and atezolizumab can be given concomitantly with adjuvant BC RT, although few studies are available on this and mainly concern the metastatic setting [77].
Regarding combinations of BC RT and CDK4/6 inhibitors, in the absence of sufficient data, caution is needed in the adjuvant setting. Concomitant administration seems to be safe in the metastatic setting [78]. The combination with olaparib in high-risk TNBC is based on preliminary evidence that is reassuring [79]. In the pivotal phase III OlympiA trial, BC RT and olaparib were administered sequentially [80] and it should be stated that the recent ESTRO consensus recommends against concurrent use [23]. The combination of BC RT and capecitabine in the setting of advanced BC has been tested in a phase II study [81], while in the adjuvant setting, capecitabine is provided after the completion of adjuvant BC RT, as per the CREATE.X study [82]. The combination of stereotactic body RT (SBRT) and drugs in the oligometastatic setting was the object of a literature review and an expert consensus within the OligoCare consortium [83].
Re-irradiation for local recurrence has been discussed as another specific topic [84‐86]. Indeed, breast preservation with partial breast re-irradiation is emerging as an option for selected patients with late low-risk local recurrence after initial breast-conserving surgery and adjuvant WBI [87, 88]. Brachytherapy has been the most commonly used technique for partial breast re-irradiation, with good oncological outcomes and tolerance [89, 90]. For chest wall recurrences and the need to re-irradiate in the adjuvant or definitive setting, combination with hyperthermia is an interesting option, available in a number of centers in Switzerland today, which should be considered [91, 92]. A recent resource on re-irradiation globally was published as an ESTRO-EORTC expert consensus [93].
Finally, integrative medicine tools are being incorporated in international guidelines, such as the ASCO, and these resources can be of use to the clinician [94‐96].
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Access to clinical studies in Switzerland
The panel also advised to include a list of all resources for open studies in Switzerland. These can be found on the websites of the Swiss Group for Clinical Cancer Research (SAKK; https://www.sakk.ch/en/trials); the European Organization for Research and Treatment of Cancer (EORTC; https://www.eortc.org/clinical-trials-database/); the International Breast Cancer Study Group (IBCSG; https://www.ibcsg.org/en/patients-professionals/clinical-trials/open-trials), which is specific for clinical and translational research in BC; and the European Thoracic Oncology Platform (ETOP; https://www.etop-eu.org/index.php?option=com_content&view=category&id=408&Itemid=195), which is specific for clinical and translational research in lung cancer.
Conclusion
As part of a pilot project initiated by the SASRO board, we completed a comprehensive overview with a brief discussion of the most recent and clinically relevant evidence for BC RT clinical care. This tool could contribute to quality improvement of radiation oncology decision-making within a multidisciplinary setting and could additionally be used for teaching purposes within the radiation oncology community. The present work is evidence based but has permitted integration of BC experts’ views, mainly radiation oncologists but also a BC surgeon and a medical oncologist, all around Switzerland, reflecting modern clinical care in radiation oncology in the BC setting in the country.
Acknowledgements
The following SASRO board members are acknowledged for their support in initiating and discussing this project: Prof. Oliver Riesterer, SASRO President; Prof. Jean Bourhis, SASRO Past President; Dr. Brigitta Baumert PhD, MBA, SASRO Vice President; PD Dr Stephanie Tanadini-Lang, SASRO Treasurer; and the SASRO board members (in alphabetical order): Dr. Jenny Bertholet, Dr. Veljko Grilj, PhD., BSc Frank Grozema, BSc Stephano Leva, PD Dr. Michaela Medova, BSc Ina Nilo, and Dr. Elena Riggenbach. Ms. Sylvia Fortunato is acknowledged for administrative support.
Funding
This work did not receive any funding and was solely supported by SASRO and individual efforts.
Conflict of interest
P.G. Tsoutsou, A.-L. Eberhardt, G. Gruber, G. Henke, W. Jeannerret-Sozzi, C. Linsenmeier, K. Lössl, M.-C. Valli, W.P. Weber, K. Zaugg, K. Zaman, and D. Zwahlen declare that they have no competing interests.
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