Advancements in Breast Cancer Treatment: Highlights from the ESTRO 2023 Conference

The annual meeting of the European Society for Radiotherapy and Oncology (ESTRO) took place in Vienna from 12 to 15 May, gathering over 6000 professionals. More than 2500 abstracts on radiotherapy-related research projects were spread among 197 sessions.

May was also cancer research month and international women’s health month. Since breast cancer is the most frequently diagnosed cancer in women, we chose to summarize some of the clinical studies that we considered to have immediate clinical impact.

 

Key Points

  • For selected patients, preoperative single-dose partial breast irradiation followed by BCS is a safe treatment with acceptable oncological outcomes, mild late toxicity, satisfactory cosmetic results and quality of life at 5 years of follow-up. 
  • Moderately hypofractionated loco-regional radiotherapy for early breast cancer is non-inferior to conventional fractionated radiotherapy in terms of lymphedema risk. 
  • Concurrent administration of tamoxifen does not lead to increase in the pulmonary fibrosis in hormone positive women receiving postoperative adjuvant radiotherapy for breast cancer.
  • A dose constraint of V30Gy<10-13% to the ipsilateral lung is recommended to minimize the risk of radio-induced lung toxicity when using 3D-CRT for breast cancer, especially in patients presenting pulmonary medical history. 
  • Local recurrence risk for stage I-III breast cancer with axillary node positive and/or medially located tumors was higher for BCS compared to MRM. It was not influenced by internal mammary and medial supraclavicular nodes irradiation, but it was decreased by adjuvant systemic treatment.
  • Excellent oncological results were obtained after the second lumpectomy and multicatheter interstitial brachytherapy partial breast irradiation for the second breast tumor event. Combined score using APBI and molecular classification together with the interval between the first and the second lumpectomy appears to be an important tool for leading the decision making process.
  • HDR interstitial radiotherapy combined with surgical intervention for chest wall local recurrences after mastectomy and previous external irradiation seems to be an effective reirradiation treatment with acceptable toxicity.
  • In-consult use of a patient decision aid template increases patient-reported shared decision making. 

 

Pre-operative single-dose partial breast irradiation – a possible shift in the current treatment sequence 

Pre-operative radiotherapy is recommended for rectal cancer, esophageal cancer and for sarcomas. For breast cancer, it became a hot topic and subsequently an increased body of evidence is emerging. The multicenter ABLATIVE trial included 36 low-risk patients who were treated with preoperative partial breast irradiation followed by breast conserving surgery (BCS) in 6 or 8 months. After receiving a single fraction of 20 Gy on the GTV, 15 patients achieved pathologic complete response. The median follow-up was 5.1 years. Grade 1 breast discomfort/pain was present in  44% of patients. Grade 1 breast fibrosis developed in 83% of patients, but grade 2 was found only in 3% at 3 years and resolved at 5 years. One patient developed ipsilateral DCIS and one was diagnosed with ipsilateral lobular carcinoma. Two patients developed distant metastases. Five-year disease-free and overall survival rates were 89% and 94%, respectively. Physicians rated the cosmetic result as excellent/good in 80% of the patients at 5 years versus 97% at baseline (p=0.4) (1). 

 

What is new on postoperative irradiation for breast cancer?

More evidence for moderate hypofractionation

HypoG-01 is a UNICANCER, non-inferiority, open-label, multicenter, phase III French trial that randomized 1221 patients having surgery for T1-3, N0-3, M0 breast cancer. Breast conserving surgery was performed in about 55% of the cases and 82% of the patients received axillary clearance. Intensity modulated radiotherapy was used in approximately half of the cases and a tumor bed boost was delivered in a similar proportion. At 3 years, the use of moderate hypofractionation schedule (40 Gy/15 fractions) for loco-regional irradiation did not result in a higher risk of developing arm lymphedema, compared to the conventional fractionation radiotherapy (24.1% vs 22.6%). Shoulder range of motion impairment, loco-regional free survival, disease free survival and overall survival were not inferior, either. Together with the Danish Skagen 1 trial, this study provides level 1A evidence supporting the use of 40 Gy/15 fractions for loco-regional radiation therapy in early breast cancer (2).

Concurrent use of Tamoxifen

Breast cancer irradiation can lead to lung toxicity, but the detrimental use of concurrent Tamoxifen represents a topic of debate. A phase 3 randomized trial presented at ESTRO 2023 compared the outcomes of concurrent vs sequential Tamoxifen with radiotherapy in adjuvant treatment of breast cancer (NCT00896155). Patients included in this trial had hormone-positive tumors larger than 5 cm and received either mastectomy (MRM) or BCS, followed by 50 Gy in 25 fractions to the chest wall or whole breast and supraclavicular region, delivered with 6MV X rays or telecobalt. Lung fibrosis was evaluated at 2 years after radiotherapy using high resolution computed tomography scan, symptoms and clinical findings. RTOG ≥ Grade II toxicity was observed in more patients in the concurrent arm compared to the sequential arm but the difference was not statistically significant (12.6% vs 7.9%, p=0.25). However, a larger irradiated volume was a risk factor for developing lung fibrosis. In patients with central lung distance larger than 2 cm the risk was 22%, compared to only 5.7% for central lung distance less than 2 cm (p=0.0001). Interestingly, the lung toxicity was similar for chest wall or whole breast irradiation. Locoregional control and distant free survival were similar in both arms (3).

Radio-induced lung injury for 3D conformal radiotherapy

Identifying clinical and dosimetric risk factors associated with radio-induced lung injury (RILI) was the main topic of another interesting study. Data from 1565 patients from CANTO-RT prospective longitudinal cohort, mainly treated with conformational 3D RT (96%), were analyzed retrospectively. Within the 5 first years after radiotherapy, RILI was found in 2.4% patients, but the incidence of ≥ grade 3 events was 0.1% of the total cohort. No grade 5 toxicity was reported. V30Gy was the most predictive of RILI occurrence, V30Gy < 10% having a better predictive value than V30Gy<20%. Pulmonary medical history (COPD, infectious pneumonitis or interstitial syndrome), chemotherapy use and nodal radiotherapy were associated with RILI occurrence in univariate analysis. Results of further analysis of large cohorts treated with modern radiotherapy techniques are expected (4).

 

When the cancer comes back

Internal mammary nodes irradiation – does it decrease the risk of local recurrence?

The impact of internal mammary and medial supraclavicular lymph nodes irradiation on the local recurrence was evaluated for stage I-III breast cancer patients with involved axillary nodes and/or a medially located primary tumor. The multicentre EORTC trial included 3049 patients who underwent BCS and 955 patients who underwent MRM. After a median follow-up of 15.7 years, the cumulative incidence rate of local relapse was lower after mastectomy (3.1%) and for patients who received systemic therapy. The percentage of patients who developed local relapse after chemotherapy only was 7.5%, for endocrine therapy-only was 4.7%, and for both chemo and endocrine therapy was  4.4%, compared to 10.7% without any systemic treatment. The majority of the recurrences occurred outside of the primary tumor bed for BCS, or at the level of the chest wall for patients receiving MRM (5).

Second conservative treatment for ipsilateral second breast tumor event

An analysis of data coming from the GEC-ESTRO prospective database evaluated the outcomes of a second lumpectomy followed by accelerated partial breast irradiation (APBI) by multicatheter interstitial brachytherapy.

The interval between the first and the second ipsilateral tumor event was more than five years for 86% of the patients. In a multivariate analysis, a scoring system using APBI + Molecular classifications + Time interval between the first and the second lumpectomy was the only independent prognostic factor for a third ipsilateral breast event, regional relapse and metastatic disease after the salvage treatment. After a median follow-up of 61 months, disease free survival was 89% and overall survival 91%.

Late complications were reported in 59% of the patients. Cutaneous and subcutaneous fibrosis developed in 67.9% and the rate of G≥3 late toxicity was 12.1%. However, the cosmetic outcome was evaluated as excellent for 36.8% and good for 30.3% of the patients. This option can be a suitable alternative to MRM, but it might not be so appealing for the patients who could prefer reconstruction 9 (6).

Salvage HDR brachytherapy re-irradiation for chest wall recurrences 

The local recurrence rate (LR) rate after mastectomy and post-operative irradiation can be up to 8% for node-positive breast cancer.

A retrospective analysis included 54 patients previously treated with mastectomy and EBRT who received salvage resection and interstitial HDR-IRT for a chest wall recurrence. The mean dose of previous EBRT was 52.4 Gy and for salvage HDR-IRT was 30.2 Gy, delivered in 2 daily fractions. Local recurrence after salvage occurred in 11 patients (20.4%), after a mean interval of 12.2 months. The only treatment-related toxicities were grade 1-2 in the form of skin toxicity or fibrosis (7).

Patients’ voices can be better heard within the right frame

The Danish Breast Cancer Group Radiotherapy Committee has completed a randomized multicenter trial to provide evidence in the implementation of a patient-engaging process, especially for preference-sensitive decisions. A generic, in-consult patient decision aid template has previously been developed and doctors at four radiotherapy departments were randomized to either continue usual practice or receive a 30-minutes introduction to shared decision making and use an in-consult template. 

In the cohort where the template was used, patients reported significantly more shared decision making compared to the control cohort. One third of the patients reported the maximum score for all three questions in the CollaboRATE questionnaire compared to only 17% in the control cohort (8). 

In conclusion, preoperative radiotherapy has many chances to become part of the clinical care in the future, and moderate hypofractionation for locoregional breast radiotherapy should be the standard of care in the present days. New factors for predicting the local recurrence are proposed, and new treatment approaches are validated as efficient and safe, including second BCS and re-irradiation. Patients’ role in deciding upon their treatment is increasingly recognized and encouraged.

 

References

1.https://www.estro.org/Congresses/ESTRO-2023/1427/breast/13245/pre-operativesingle-dosepartialbreastirradiation-f

2.https://www.estro.org/Congresses/ESTRO-2023/1418/late-breakingpapers/13177/hypog01-unicancerphase3trialoflocoregionalhypovsno

3.https://www.estro.org/Congresses/ESTRO-2023/1418/late-breakingpapers/13174/arandomizedtrialofconcurrentversussequentialtamoxi

4.https://www.estro.org/Congresses/ESTRO-2023/1427/breast/13247/radio-inducedlunginjury-clinicalanddosimetricriskf

5.https://www.estro.org/Congresses/ESTRO-2023/1427/breast/13248/therateandspatiallocationoflocalrecurrences-result

6.https://www.estro.org/Congresses/ESTRO-2023/1443/reirradiation/13379/2ndconservativetreatmentfor2ndbreasttumorevent-age

7.https://www.estro.org/Congresses/ESTRO-2023/1422/breast-giandpaediatrics/13205/salvagehdrinterventionalradiotherapyforchestwallre

8.https://www.estro.org/Congresses/ESTRO-2023/1418/late-breakingpapers/13173/shareddecisionmakingwithbreastcancerpatients-doesi

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