A nested case-control study on radiation dose-response for cardiac events in breast cancer patients in Germany

  by Dan Baaken, Hiltrud Merzenich, Marcus Schmidt, Inga Bekes, Lukas Schwentner, Wolfgang Janni, Achim Woeckel, Manfred Mayr, Stephan Mose, Thomas Merz, Voica Ghilescu, Jona Renner, Detlef Bartkowiak, Thomas Wiegel, Maria Blettner, Heinz Schmidberger, Daniel Wollschläger 

 The Breast: Published: June 09, 2022

Background

Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT.

Methods

In a cohort of 11,982 BC patients diagnosed in 1998–2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events.

Results

Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94–1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98–1.01, P = .68).

Conclusions

Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.

 

Validation of a prognostic scoring system for postmastectomy locoregional recurrence in breast cancer

by Van der Vorst Aline, Kindts Isabelle, Laenen Annouschka, Neven Patrick, Janssen Hilde, Weltens Caroline 

The Breast: Published: April 16, 2022

Background

To date, it remains unclear which patients with breast cancer (BC) benefit from post-mastectomy radiotherapy (PMRT). Cheng et al. developed and validated a scoring system based on 4 prognostic factors for locoregional recurrence (LRR) to identify patients in need for PMRT. These factors include age, estrogen receptor status, lymphovascular status and number of affected axillary lymph nodes.

Purpose

To validate the scoring system for LRR in BC developed by Cheng et al. by using an independent BC database.

Methods and materials

We retrospectively identified 1989 BC cases, treated with mastectomy (ME) with or without PMRT at the University Hospitals Leuven between 2000 and 2007. The primary endpoint was 5-year locoregional control rate with and without PMRT, according to the LRR score.

Results

Median follow-up time was 11.4 years. After excluding patients with missing variables 1103 patients were classified using the LRR scoring system: 688 (62.38%) patients were at low risk of recurrence (LRR score 0–1), 335 (30.37%) patients were at intermediate risk of recurrence (LRR score 2–3) and 80 (7.25%) patients were at high risk of recurrence (LRR score ≥4). 5-year locoregional control rates with and without PMRT were 99.20% versus 99.21% (p = 0.43) in the low-risk group; 98.24% versus 85.74% (p < 0.0001) in the intermediate-risk group and 96.87% versus 85.71% (p = 0.10) in the high-risk group respectively.

Conclusion

Our validation of the LRR scoring system suggests it can be used to point out patients that would benefit from PMRT. We recommend further validation of this scoring system by other independent institutions before application in clinical practice

 

Geriatric assessment tool application in treatment recommendations for older women with breast cancer

  by Asma Munir, Anita Huws, Sohail Khan, Yousef Sharaiha, Simon Holt, Saira Khawaja 

 The Breast: Published: March 26, 2022

 Treatment of early breast cancer in older women is usually not guideline concordant owing to lack of routine evaluation of their potential frailty. We assessed the feasibility and impact of a self-administered geriatric assessment on the decision-making process in women aged 65 and above treated in a UK District General Hospital.

Breast Surgery Bulletin - February 2022

 

Is breast conservation superior to mastectomy in early stage triple negative breast cancer?

 

by Omran Saifi, Mohamad Chahrour, Zhuo Li, Jawad Hoballah, Joseph Panoff, Laura A. Vallow, Youssef H. Zeidan 

 

The Breast: Published:February 09, 2022

 

Purpose

Compare overall survival (OS) and breast cancer-specific survival (BCSS) outcomes of breast conservative therapy (BCT) and mastectomy in a large cohort of patients with early-stage triple negative breast cancer (TNBC), using a propensity score-based matching approach.

Methods

Surveillance, Epidemiology, and End Results (SEER) database was used to study the role of RT in early stage TNBC. Primary end points were OS and BCSS. Cox proportional hazard regression models and Kaplan-Meier plots were used to generate the desired outcomes. Propensity score matching was done to minimize bias.

Results

12,761 patients with T1-2N0M0 TNBC as their first malignancy were retrieved. Of these 7237 had lumpectomy with RT, and 5524 had mastectomy only. Age, race, marital status, tumor laterality, grade and stage, and receipt of chemotherapy were prognostic variables for OS and BCSS. Among 4848 matched subjects, the 5-year OS was significantly higher in patients with lumpectomy and RT (89%) compared to mastectomy alone (84.5%) (p-value <0.001). Similarly, BCSS was significantly higher in patients with lumpectomy and RT (93%) compared to mastectomy alone (91%) (p-value <0.001). On subgroup analysis, patients who are younger than 40 had similar survival outcomes after either mastectomy alone or lumpectomy with RT. However, those who are older than 60, have any grade or T stage had better survival outcomes with lumpectomy and RT.

Conclusions

Overall, lumpectomy followed by RT is associated with better OS and BCSS compared to mastectomy in T1-2N0M0 TNBC patients. Further research is needed to determine the optimal treatment strategy for specific patient subgroups.

 

 

Nomogram for the personalisation of radiotherapy treatments in breast cancer patients

by Inmaculada Beato Tortajada, Carlos Ferrer Albiach, Virginia Morillo Macias 

 

The Breast: Open Access; Published: November 08, 2021

 

Introduction

Numerous prospective studies have shown that the incorporation of genomic assays into clinical practice significantly impacts the choice of adjuvant treatments for patients with early-stage breast cancer. However, the same evidence does not exist for the treatment of locoregional recurrences.

Hypothesis and objectives

The main objective of this work was to identify the clinicopathological, molecular, and genetic parameters that allow patients to be more precisely categorised into risk groups, in order to create a locoregional recurrence riskclassification tool, the PersonalRT27.

Material and methods

To create PersonalRT27, we retrospective assessed the variables of patients with early breast cancer (stages I or II) who had undergone the OncotypeDx ® and MammaPrint ® genetic tests. These variables and factors included in the tests were categorised and weighted to obtain scores between 1 and 5 pointsto represent a lower or higher risk of relapse, respectively, based on these factors and as determined by the researchers.

Results

The mean follow-up time was 60.5 months (range 25–96 months); locoregional progression-free survival at the time of the analysis was 98.4%, and overall survival was 97.5%, of which 0.6% of the deaths had been cancer specific. The area under the curve for the PersonalRT27 was 0.76 (95% CI [0.70, 0.81]), sensitivity was 78%, and the specificity was 58.9%. We used these factors to create an inhospital web-based nomogram.

Conclusions

The PersonalRT27 is a novel tool that integrates clinical-pathological, molecular, and genetic parameters. External and independent validation will be required to implement its clinical use.

 

SABR in oligometastatic breast cancer: Current status and future directions

 

by Rachel Stewart, Michelle White, Jennifer Tan, Shankar Siva, Lama Karroum, Steven David 

 

The Breast: REVIEW ARTICLE| VOLUME 60, P223-229, DECEMBER 01, 2021

 

Oligometastatic breast cancer (OMBC) is a heterogeneous disease with intrinsic biological diversity. It is increasingly accepted in clinical practice that patients with OMBC could be treated with the expectation of long-term disease remission. Local ablative treatments, such as radiotherapy or surgery have a role in this setting. At present, patients that may benefit are characterised by low tumour burden, long disease-free interval and the capacity to completely ablate all sites of disease. In the future, biological or genomic classifiers may help predict which patients may benefit the most from local ablative treatments. This review provides an overview of the proposed classifications of oligometastatic disease and outlines the standard systemic treatment options of endocrine therapy, chemotherapy, and immunotherapy. The evidence for localized treatment with stereotactic ablative body radiotherapy (SABR) is presented. We discuss current active trials in oligometastatic cancer and discuss potential future directions for the use of SABR in the treatment of OMBC.

Hypofractionated versus conventional fractionated radiotherapy for breast cancer in patients with reconstructed breast: toxicity analysis

 Hypofractionated versus conventional fractionated radiotherapy for breast cancer in patients with reconstructed breast: toxicity analysis

The Breast: VOLUME  55, P37-44, FEBRUARY 01, 2021

by Dong-Yun Kim, Eonju Park, Chan Yeong Heo, Ung Sik Jin, Eun Kyu Kim, Wonshik Han, Kyung Hwan Shin, In Ah Kim

Highlights

•There was no significant difference in the occurrence of breast complications between the two fractionation regimens.

•Hypofractionated RT may be used comparable to conventional fractionated RT in reconstructed breast cancer patients.

•The prospective randomized trial would be necessary to clarify this issue.

Purpose

This study investigated whether hypofractionated adjuvant radiotherapy (RT) increased breast-related complication(s) compared to conventional fractionated RT in reconstructed breast cancer patients.

Methods

We conducted a retrospective review including 349 breast cancer patients who underwent immediate breast reconstruction following mastectomy or breast-conserving surgery (BCS) between 2009 and 2018 at two institutions. All patients were treated with adjuvant RT via either a conventional fractionated or hypofractionated regimen. We defined a major breast complication as a breast-related toxic event requiring re-operation or re-hospitalization during the follow-up period after the end of RT.

Results

The median follow-up was 32.3 months (4.8–118.5 months); 126 patients had conventional fractionated RT, and 223 patients received hypofractionated RT. In patients with mastectomy, there was no significant difference in the occurrence of any or major breast-related complications between the two fractionation regimens. In patients undergoing BCS, incidence of any breast complication showed no difference between two RT groups and no major breast complication was reported as well. Hypofractionated RT did not increase major wound problem (infection and dehiscence) compared to conventional RT. Incidence of major contracture was significantly lower in hypofractionated RT.

Conclusions

There was no significant difference in the occurrence of any or major breast-related complications between the two different fractionation regimens, even in patients with mastectomy. Hypofractionated RT may be used comparable to conventional fractionated RT in terms of breast-related complications in reconstructed breast cancer patients. The prospective randomized trial would be necessary to clarify this issue.

Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study

Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study

by Mami Ogita, Kenshiro Shiraishi, Katsuyuki Karasawa, Kenji Tokumasu, Naomi Nakajima, Tachen Chang, Jiro Kawamori, Hideomi Yamashita, Keiichi Nakagawa

The Breast: VOLUME 52, P88-94, AUGUST 01, 2020

Highlights

•Clinical outcome of adjuvant radiotherapy for SCC of the breast was evaluated.

•Breast SCC had poor prognosis and a high incidence of locoregional recurrence.

•In-field recurrence following radiotherapy occurred frequently.

•Age and lymphatic invasion were significantly associated with increased risk of recurrence.

Abstract

Background:

Because primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC.

Material and methods:

We conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated.

Results:

Between January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence.

Conclusion:

Breast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence.

Winter is over: The use of Artificial Intelligence to individualise radiation therapy for breast cancer

Winter is over: The use of Artificial Intelligence to individualise radiation therapy for breast cancer

by Philip M.P. Poortmans, Silvia Takanen, Gustavo Nader Marta, Icro Meattini, Orit Kaidar-Person 

The Breast: FULL LENGTH ARTICLE| VOLUME 49, P194-200, FEBRUARY 01, 2020

Artificial intelligence demonstrated its value for automated contouring of organs at risk and target volumes as well as for auto-planning of radiation dose distributions in terms of saving time, increasing consistency, and improving dose-volumes parameters. Future developments include incorporating dose/outcome data to optimise dose distributions with optimal coverage of the high-risk areas, while at the same time limiting doses to low-risk areas. An infinite gradient of volumes and doses to deliver spatially-adjusted radiation can be generated, allowing to avoid unnecessary radiation to organs at risk.

[Review] Radiotherapy in the setting of breast reconstruction: types, techniques, and timing

[Review] Radiotherapy in the setting of breast reconstruction: types, techniques, and timing

Ho, AY et al

Lancet Oncology December 2017 Vol 18, 12 e742- e753

As the use of breast reconstruction and postmastectomy radiotherapy (PMRT) has increased over the past decade, the typical approach to integrating radiotherapy with breast reconstruction has provoked intense controversy in the management of breast cancer. PMRT can lead to an increased frequency of complications in the reconstructed breast. Conversely, the reconstructed breast can increase the complexity of radiotherapy delivery. How to minimise the frequency of complications without compromising oncological or cosmetic outcomes of the reconstructed breast is an important shared multidisciplinary goal for oncologists and their patients.

Breast Reconstruction and Radiation Therapy: An Update

Breast Reconstruction and Radiation Therapy: An Update

Nelson, JA. Disa, JJ.
Plastic and Reconstructive Surgery: November 2017 - Volume 140 - Issue 5S - p 60S–68S

With the indications for radiation therapy in the treatment of breast cancer continuing to expand, many patients present for reconstruction having previously had radiation or having a high likelihood of requiring radiation following mastectomy. Both situations are challenging for the plastic surgeon, with different variables impacting the surgical outcome. To date, multiple studies have been performed examining prosthetic and autologous reconstruction in this setting. The purpose of this article was to provide a general platform for understanding the literature as it relates to reconstruction and radiation through an examination of recent systematic reviews and relevant recent publications. We examined this with a focus on the timing of the radiation, and within this context, examined the data from the traditional surgical outcomes standpoint as well as from a patient-reported outcomes perspective. The data provided within will aid in patient counseling and the informed consent process.

Postoperative radiotherapy after DCIS: Useful for whom?

Postoperative radiotherapy after DCIS: Useful for whom?

Karlsson P
The Breast 
Article in Press

The number of patients with ductal carcinoma in situ (DCIS) increases with more widely used screening mammography programs. DCIS accounts for approximately 20% of all new breast cancer diagnoses in these programs and the natural course of this heterogeneous group of pre-invasive lesions is not fully known. Better definition of subgroups benefitting from radiotherapy and knowledge on the natural course of DCIS are important issues for the future management of DCIS.Four large randomized trials have studied the effects of postoperative radiotherapy after breast conserving surgery in patients with wider spectrum of DCIS and all of them have shown radiotherapy to halve the risk of ipsilateral events, however, without any significant effect on breast cancer mortality.

Should Immediate Autologous Breast Reconstruction Be Considered in Women Who Require Postmastectomy Radiation Therapy? A Prospective Analysis of Outcomes

Should Immediate Autologous Breast Reconstruction Be Considered in Women Who Require Postmastectomy Radiation Therapy? A Prospective Analysis of Outcomes

Billig, J et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1279–1288

Background: In women who require postmastectomy radiation therapy, immediate autologous breast reconstruction is often discouraged. The authors prospectively evaluated postoperative morbidity and satisfaction reported by women undergoing delayed or immediate autologous breast reconstruction in the setting of postmastectomy radiation therapy. 
Methods: Patients enrolled in the Mastectomy Reconstruction Outcomes Consortium study, who received postmastectomy radiotherapy and underwent immediate or delayed free abdominally based autologous breast reconstruction, were identified. Postoperative complications at 1 and 2 years after reconstruction were assessed. Patient-reported outcomes were evaluated using the BREAST-Q questionnaire preoperatively and at 1 and 2 years postoperatively. Bivariate analyses and mixed-effects regression models were used to compare outcomes. 
Results: A total of 175 patients met the authors’ inclusion criteria. Immediate reconstructions were performed in 108 patients and delayed reconstructions in 67 patients; 93.5 percent of immediate reconstructions were performed at a single center. Overall complication rates were similar based on reconstructive timing (25.9 percent immediate and 26.9 percent delayed at 1 year; p = 0.54). Patients with delayed reconstruction reported significantly lower prereconstruction scores (p < 0.0001) for Satisfaction with Breasts and Psychosocial and Sexual Well-being than did patients with immediate reconstruction. At 1 and 2 years postoperatively, both groups reported comparable levels of satisfaction in assessed BREAST-Q domains. 
Conclusions: From this prospective cohort, immediate autologous breast reconstruction in the setting of postmastectomy radiation therapy appears to be a safe option that may be considered in select patients and centers. Breast aesthetics and quality of life, evaluated from the patient’s perspective, were not compromised by flap exposure to radiation therapy. 

From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer

From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer


The Breast October 2016Volume 29, Pages 213–222
Leonardi MC et al

Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue.

Postmastectomy radiotherapy in patients with breast cancer

Postmastectomy radiotherapy in patients with breast cancer - author's reply. The Lancet, Nov 2014, Vol. 384(9957), p.1846-47

Early Breast Cancer Trialists' Collaborative Group 

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62240-6/fulltext?rss=yes#bib1

Our meta-analysis of individual patient data from trials in women given mastectomy and axillary clearance to at least level ll showed that radiotherapy reduced mortality from breast cancer by 20% in women with one to three positive lymph nodes (rate ratio [RR], irradiated vs not, 0·80, 95% CI 0·67—0·95; 2p=0·01) and by 13% in women with at least four positive lymph nodes (RR 0·87, 95% CI 0·77—0·99; 2p=0·04). Little reason of how radiotherapy works exists to think that this treatment for breast cancer has any appreciable abscopal effect and so, as Ismail Jatoi suggests, these results showed that a proportion of the deaths avoided by radiotherapy would have arisen from cells localised within the areas targeted by radiotherapy (ie, the chest wall and, for most trials, the regional lymph nodes).

Breast Journal Vol 16 Sept - Oct Supplement

A New Era in the Diagnosis and Treatment of Breast Cancer
Tabár L and Dean PB
S2-4
Abstract only


Challenges in the Interpretation of Breast Core Biopsies
Corben AD et al.
S5-9
Abstract only


Lobular Carcinoma, Not Only a Classic
Brogi E et al.
S10-4
Abstract only


Trends in the Surgical Treatment of Breast Cancer.
Morrow M
S17-9
Abstract only


Oncoplastic Surgery: The Evolution of Breast Cancer Treatment
De Lorenzi F
S20-1
Abstract only


Breast Cancer in Pregnancy.
Rovera F et al.
S22-5
Abstract only


The role of Micrometastatic Disease in Sentinel Lymph Node in Breast Cancer
Rovera F et al.
S26-8
Abstract only


Predictors of Loco-Regional Recurrence and Cancer-Related Death after Breast Cancer Surgery
Rausei S et al.
S29-33
Abstract only


Radiotherapy for Breast Cancer in the 21st Century
Powell S
S34-8
Abstract only


Capecitabine in Breast Cancer: The Issue of Cardiotoxicity During Fluoropyrimidine Treatment
Molteni LP et al
S45-8
Abstract only


The Surgical Management of Ductal Carcinoma In Situ
Kumar S and Sacchini V
S49-52
Abstract only

The Lancet Vol 376 Iss 9735 2010

Partial breast irradiation: new standard for selected patients
Azria, D. and Bourgier, C.
P71 - 72
Abstract only


Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial
Vaidya, J.S. et al.
P91 - 103
Abstract only

BMJ 2nd March 2010

Editorial
Waiting times for radiotherapy after breast cancer
Ruth H Jack and Lars Holmberg
BMJ 2010;340 c1007

Impact of interval from breast conserving surgery to radiotherapy on local recurrence in older women with breast cancer: retrospective cohort analysis
Rinaa S Punglia, Akiko M Saito, Bridget A Neville, Craig C Earle, and Jane C Weeks
BMJ 2010;340 c845