Radiation Therapy for Breast Cancer: Current Status and Future Perspectives

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Breast Cancer".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 31296

Special Issue Editors


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Guest Editor
Department of Oncology, Faculty of Medicine, Hebrew University, Jerusalem, Israel
Interests: breast cancer; PROMs; science of hope

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Co-Guest Editor
Sheba Medical Center, Ramat Gan, Israel
Interests: breast cancer; radiation; PBI; breast radiation in young women

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Co-Guest Editor
Israel Assuta Medical Center, Tel-Aviv, Israel
Interests: breast cancer; radiation; genetics; re-irradiation; PBI

Special Issue Information

Dear Colleagues,

Breast cancer represents the malignancy most widely treated by radiation oncologists.  As a result, it has been the subject of numerous studies and practices have evolved over time. An array of creative questions has been posed within the field of breast radiation oncology with the goals of improving cancer outcomes, decreasing treatment related toxicity, and improving quality of life for breast cancer patients and survivors.

In this Special Issue of Current Oncology, we welcome the input from leaders in the field of radiation. Contributors may wish to explore one of the topics identified by the editors (e.g., radiation dose de-escalation, boost techniques, partial breast irradiation, re-irradiation, nodal management, onco-plastics, the treatment of oligometastatic and oligoprogressive disease, incorporating bio-signatures into radiotherapeutic management, testing the limits of hypofractionation, addressing disparities in breast RT, new technologies such as proton and MR guidance, etc.) or propose alternative concepts which they deem valuable. In so doing, we hope to produce a volume which is scholarly, thought-provoking, and clinically relevant.

Dr. Benjamin W. Corn
Dr. Shira L. Galper
Prof. Dr. Merav A. Ben-David
Guest Editors

Manuscript Submission Information

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Keywords

  • breast cancer
  • radiotherapy
  • oligometastases
  • hypofractionation
  • PBI
  • re-irradiation
  • biosignatures
  • diversity

Published Papers (11 papers)

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Editorial

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3 pages, 169 KiB  
Editorial
The Coming of Age of Breast Radiotherapy
by Benjamin W. Corn, Shira Galper and Merav Ben-David
Curr. Oncol. 2023, 30(5), 5179-5181; https://doi.org/10.3390/curroncol30050392 - 19 May 2023
Viewed by 1102
Abstract
Exactly 50 years ago, the investigators of the National Surgical Adjuvant Breast and Bowel Project began to design the B-06 trial [...] Full article

Research

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13 pages, 1603 KiB  
Article
Increased Circulating Epithelial Tumor Cells (CETC/CTC) over the Course of Adjuvant Radiotherapy Is a Predictor of Less Favorable Outcome in Patients with Early-Stage Breast Cancer
by Matthias Mäurer, Dorothea Schott, Monika Pizon, Sonia Drozdz, Thomas Wendt, Andrea Wittig and Katharina Pachmann
Curr. Oncol. 2023, 30(1), 261-273; https://doi.org/10.3390/curroncol30010021 - 24 Dec 2022
Cited by 6 | Viewed by 2760
Abstract
Background: Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into [...] Read more.
Background: Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into lymphatic fluid or blood, circulating epithelial tumor cells (CETC/CTC), which can reach distant tissues and regrow into metastases. The purpose of this study is to determine changes in the number of CETC/CTC in the course of adjuvant RT, and to evaluate whether they are correlated to local recurrence and distant metastases in breast cancer patients. Methods: Blood from 165 patients irradiated between 2002 and 2012 was analyzed 0–6 weeks prior to and 0–6 weeks after RT using the maintrac® method, and patients were followed over a median period of 8.97 (1.16–19.09) years. Results: Patients with an increase in CETC/CTC numbers over the course of adjuvant RT had a significantly worse disease-free survival (p = 0.004) than patients with stable or decreasing CETC/CTC numbers. CETC/CTC behavior was the most important factor in predicting subsequent relapse-free survival. In particular, patients who had received neoadjuvant chemotherapy were disproportionately more likely to develop metastases when cell counts increased over the course of RT (p = 0.003; hazard ratio 4.886). Conclusions: Using the maintrac® method, CETC/CTC were detected in almost all breast cancer patients after surgery. The increase in CETC/CTC numbers over the course of RT represents a potential predictive biomarker to judge relative risk/benefit in patients with early breast cancer. The results of this study highlight the need for prospective clinical trials on CETC/CTC status as a predictive criterion and for individualization of treatment. Clinical Trial registration: The trial is registered (2 May 2019) at trials.gov under NCT03935802. Full article
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10 pages, 223 KiB  
Article
Stereotactic Body Radiation Therapy for Lung and Liver Oligometastases from Breast Cancer: Toxicity Data of a Prospective Non-Randomized Phase II Trial
by Davide Franceschini, Tiziana Comito, Anna Di Gallo, Veronica Vernier, Marco A. Marzo, Luciana Di Cristina, Beatrice Marini, Lorenzo Lo Faro, Sara Stefanini, Ruggero Spoto, Luca Dominici, Ciro Franzese and Marta Scorsetti
Curr. Oncol. 2022, 29(10), 7858-7867; https://doi.org/10.3390/curroncol29100621 - 17 Oct 2022
Cited by 7 | Viewed by 1816
Abstract
Aims: We report the mature toxicity data of a phase II non-randomized trial on the use of SBRT for lung and liver oligometastases. Methods: Oligometastatic patients from breast cancer were treated with SBRT for up to five lung and/or liver lesions. Inclusion criteria [...] Read more.
Aims: We report the mature toxicity data of a phase II non-randomized trial on the use of SBRT for lung and liver oligometastases. Methods: Oligometastatic patients from breast cancer were treated with SBRT for up to five lung and/or liver lesions. Inclusion criteria were: age > 18 years, ECOG 0–2, diagnosis of breast cancer, less than five lung/liver lesions (with a maximum diameter <5 cm), metastatic disease confined to the lungs and liver or extrapulmonary or extrahepatic disease stable or responding to systemic therapy. Various dose–fractionation schedules were used. Then, a 4D-CT scan and FDG-CTPET were acquired for simulation and fused for target definition. Results: From 2015 to 2021, 64 patients and a total of 90 lesions were irradiated. Treatment was well tolerated, with no G 3–4 toxicities. No grade ≥3 toxicities were registered and the coprimary endpoint of the study was met. Median follow-up was 19.4 months (range 2.6–73.1). Conclusions: The co-primary endpoint of this phase II trial was met, showing excellent tolerability of SBRT for lung and liver oligometastatic in breast cancer patients. Until efficacy data will mature with longer follow-up, SBRT should be regarded as an opportunity for oligometastatic breast cancer patients. Full article

Review

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12 pages, 544 KiB  
Review
Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?
by Ezra Hahn, Danielle Rodin, Rinku Sutradhar, Sharon Nofech-Mozes, Sabina Trebinjac, Lawrence Frank Paszat and Eileen Rakovitch
Curr. Oncol. 2023, 30(6), 5795-5806; https://doi.org/10.3390/curroncol30060433 - 13 Jun 2023
Cited by 3 | Viewed by 1827
Abstract
Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce [...] Read more.
Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS—Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one—the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial—incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research. Full article
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10 pages, 1352 KiB  
Review
The Potential of Proton Therapy for Locally Advanced Breast Cancer: Clinical and Technical Considerations
by N. Lalani, S. Alqarni and R. B. Jimenez
Curr. Oncol. 2023, 30(3), 2869-2878; https://doi.org/10.3390/curroncol30030219 - 28 Feb 2023
Cited by 2 | Viewed by 2420
Abstract
Proton therapy is a promising therapeutic modality with unique physical properties that allow for abrupt dose fall-off distal to the target of interest, thereby sparing nearby organs at risk. A number of studies have identified the utility of proton radiation in mitigating treatment [...] Read more.
Proton therapy is a promising therapeutic modality with unique physical properties that allow for abrupt dose fall-off distal to the target of interest, thereby sparing nearby organs at risk. A number of studies have identified the utility of proton radiation in mitigating treatment related sequelae for patients with locally advanced breast cancers. Thus, in the following review, we highlight clinical and technical considerations for proton radiotherapy delivery in patients with locally advanced breast cancer. Full article
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14 pages, 2552 KiB  
Review
Stereotactic Radiation for Oligometastatic and Oligoprogressive Stage IV Breast Cancer: A Case-Based Review
by Gary M. Freedman, Joshua A. Jones and Neil K. Taunk
Curr. Oncol. 2023, 30(2), 2510-2523; https://doi.org/10.3390/curroncol30020192 - 18 Feb 2023
Cited by 3 | Viewed by 2822
Abstract
For decades, the distant progression of breast cancer has been the purview of systemic therapy alone or with low to moderate-dose radiation therapy intended for the palliation of symptomatic metastases. However, for decades there have been anecdotes of long-term disease-free survival with more [...] Read more.
For decades, the distant progression of breast cancer has been the purview of systemic therapy alone or with low to moderate-dose radiation therapy intended for the palliation of symptomatic metastases. However, for decades there have been anecdotes of long-term disease-free survival with more aggressive local treatment of one or more metastases. The hypothesis of oligometastases is that the treatment of a clinically limited number of distant metastases can change the natural history of stage IV breast cancer. The advance in the technology of stereotactic body radiation (SBRT) has made it more possible to offer a non-invasive, yet potentially disease-modifying, metastases-directed ablative treatment in place of surgery or a palliative radiation regimen. Although there are promising local control and survival outcomes in phase I/II trials, there is still a lack of phase III evidence of ablative SBRT results showing any change in the natural history of metastatic breast cancer. Limited oligometastases may call for an ablative approach with SBRT when definitive long-term local control is needed for the best palliation against symptomatic progression in challenging locations. Some oligometastases that have progression on a certain systemic regimen, while others remain stable or in remission, may also be treated with SBRT in the hopes of prolonging the use of that regimen. Whether SBRT should represent the standard management for stage IV breast cancer of a limited number or of limited progression requires confirmation by phase III data. This review will discuss the data from key clinical trials as it applies to decision making in typical clinical cases considered for potentially ablative SBRT for oligometastases or oligoprogression. Full article
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13 pages, 484 KiB  
Review
Different Re-Irradiation Techniques after Breast-Conserving Surgery for Recurrent or New Primary Breast Cancer
by Camille Hardy Abeloos, Juhi M. Purswani, Paulina Galavis, Allison McCarthy, Christine Hitchen, J. Isabelle Choi and Naamit K. Gerber
Curr. Oncol. 2023, 30(1), 1151-1163; https://doi.org/10.3390/curroncol30010088 - 13 Jan 2023
Cited by 4 | Viewed by 4824
Abstract
Breast re-irradiation (reRT) after breast-conserving surgery (BCS) using external beam radiation is an increasingly used salvage approach for women presenting with recurrent or new primary breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. There is [...] Read more.
Breast re-irradiation (reRT) after breast-conserving surgery (BCS) using external beam radiation is an increasingly used salvage approach for women presenting with recurrent or new primary breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. There is also limited data on efficacy and safety of external beam hypofractionation and accelerated partial-breast irradiation (APBI) regimens. This paper reviews existing retrospective and prospective data for breast reRT after BCS, APBI reRT outcomes and delivery at our institution and the need for a randomized controlled trial using shorter courses of radiation to better define patient selection for different reRT fractionation regimens. Full article
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9 pages, 248 KiB  
Review
Optimizing Adjuvant Treatment Recommendations for Older Women with Biologically Favorable Breast Cancer: Short-Course Radiation or Long-Course Endocrine Therapy?
by Susan G. R. McDuff and Rachel C. Blitzblau
Curr. Oncol. 2023, 30(1), 392-400; https://doi.org/10.3390/curroncol30010032 - 27 Dec 2022
Cited by 7 | Viewed by 3046
Abstract
Omission of radiotherapy among older women taking 5 years of adjuvant endocrine therapy following breast conserving surgery for early-stage, hormone sensitive breast cancers is well-studied. However, endocrine therapy toxicities are significant, and many women have difficulty tolerating endocrine therapy, particularly elderly patients with [...] Read more.
Omission of radiotherapy among older women taking 5 years of adjuvant endocrine therapy following breast conserving surgery for early-stage, hormone sensitive breast cancers is well-studied. However, endocrine therapy toxicities are significant, and many women have difficulty tolerating endocrine therapy, particularly elderly patients with comorbidities. Omission of endocrine therapy among women receiving adjuvant radiation is less well-studied, but available randomized and non-randomized data suggest that this approach may confer equivalent local control and survival for select patients. Herein we review available randomized and non-randomized outcome data for women treated with radiation monotherapy and emphasize the need for future prospective, randomized studies of endocrine therapy omission. Full article
12 pages, 241 KiB  
Review
Radiation in Early-Stage Breast Cancer: Moving beyond an All or Nothing Approach
by Juhi M. Purswani, Camille Hardy-Abeloos, Carmen A. Perez, Maryann J. Kwa, Manjeet Chadha and Naamit K. Gerber
Curr. Oncol. 2023, 30(1), 184-195; https://doi.org/10.3390/curroncol30010015 - 23 Dec 2022
Cited by 3 | Viewed by 2549
Abstract
Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an [...] Read more.
Radiotherapy omission is increasingly considered for selected patients with early-stage breast cancer. However, with emerging data on the safety and efficacy of radiotherapy de-escalation with partial breast irradiation and accelerated treatment regimens for low-risk breast cancer, it is necessary to move beyond an all-or-nothing approach. Here, we review existing data for radiotherapy omission, including the use of age, tumor subtype, and multigene profiling assays for selecting low-risk patients for whom omission is a reasonable strategy. We review data for de-escalated radiotherapy, including partial breast irradiation and acceleration of treatment time, emphasizing these regimens’ decreasing biological and financial toxicities. Lastly, we review evidence of omission of endocrine therapy. We emphasize ongoing research to define patient selection, treatment delivery, and toxicity outcomes for de-escalated adjuvant therapies better and highlight future directions. Full article
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21 pages, 338 KiB  
Review
Preoperative Radio(Chemo)Therapy in Breast Cancer: Time to Switch the Perspective?
by Angel Montero and Raquel Ciérvide
Curr. Oncol. 2022, 29(12), 9767-9787; https://doi.org/10.3390/curroncol29120768 - 12 Dec 2022
Cited by 9 | Viewed by 3431
Abstract
Aim: Radiation therapy represents, together with surgery and systemic treatment, the triad on which the current management of patients with breast cancer is based, achieving high control and survival rates. In recent years we have witnessed a (r)evolution in the conception of breast [...] Read more.
Aim: Radiation therapy represents, together with surgery and systemic treatment, the triad on which the current management of patients with breast cancer is based, achieving high control and survival rates. In recent years we have witnessed a (r)evolution in the conception of breast cancer treatment. The classic scheme of surgery followed by systemic treatment and radiotherapy is being subverted and it is becoming more and more frequent to propose the primary administration of systemic treatment before surgery, seeking to maximize its effect and favoring not only the performance of more conservative surgeries but also, in selected cases, increasing the rates of disease-free survival and overall survival. Radiotherapy is also evolving toward a change in perspective: considering preoperative primary administration of radiotherapy may be useful in selected groups. Advances in radiobiological knowledge, together with technological improvements that are constantly being incorporated into clinical practice, support the administration of increasingly reliable, precise, and effective radiotherapy, as well as its safe combination with antitumor drugs or immunotherapy in the primary preoperative context. In this paper, we present a narrative review of the usefulness of preoperative radiotherapy for breast cancer patients and the possibilities for its combination with other therapies. Full article

Other

17 pages, 1320 KiB  
Systematic Review
Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-Analysis
by Yasmin Korzets, Dina Levitas, Ahuva Grubstein, Benjamin W. Corn, Eitan Amir and Hadar Goldvaser
Curr. Oncol. 2022, 29(9), 6657-6673; https://doi.org/10.3390/curroncol29090523 - 17 Sep 2022
Cited by 3 | Viewed by 2618
Abstract
Background: Existing data on adding internal mammary nodal irradiation (IMNI) to the regional nodal fields are inconsistent. Methods: Randomized trials investigating the addition of IMNI to standard adjuvant radiation were identified. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall-survival [...] Read more.
Background: Existing data on adding internal mammary nodal irradiation (IMNI) to the regional nodal fields are inconsistent. Methods: Randomized trials investigating the addition of IMNI to standard adjuvant radiation were identified. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall-survival (OS), breast cancer specific-survival (BCSS), and disease-free survival (DFS) as well as distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer, and cardiovascular morbidity and mortality were also extracted. Results: Analysis included five trials comprising 10,994 patients, predominantly with higher risk, lymph node positive disease. Compared to the control group, IMNI was associated with significant improvement in OS (HR = 0.91, p = 0.004), BCSS (HR = 0.84, p < 0.001), DFS (HR = 0.89, p= 0.01), and DMFS (HR = 0.89, p = 0.02). IMNI was also associated with reduced odds for regional (OR = 0.58, p < 0.001) and loco-regional recurrence (OR = 0.85, p = 0.04). The odds for cardiotoxicity were not statistically significantly higher (OR = 1.23, p = 0.07). There were comparable odds for cardiovascular mortality (OR = 1.00, p = 1.00), non-breast cancer mortality (OR = 1.05, p = 0.74), secondary cancer (OR = 0.95, p = 0.51), and contra-lateral breast cancer (OR = 1.07, 95% 0.77–1.51, p = 0.68). Conclusions: Compared to the control group, the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness. Full article
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