Evaluation of Additional Sequential Boost Radiotherapy (RT) After Whole Breast Irradiation (WBI) for Patients with Early Breast Cancer (Ca)

Breast cancer (Ca) comprises the most common cancer in females and constitutes a leading cause of cancer related deaths around the globe [1,2]. Contemporary treatment protocols established by incorporation of accumulating high level evidence suggest multimodality therapy for patients suffering from breast Ca with combinations of surgery, Radiotherapy (RT) and systemic treatment. Nevertheless, there remain controversies for certain conditions such as the role of postmastectomy RT for subgroups of patients with T3N0 tumors or T1-T2 tumors with 1 to 3 positive axillary lymph nodes, and for patients receiving neoadjuvant chemotherapy before mastectomy [3-9]. Another potential focus of consideration is the role of adjuvant RT for elderly patients deemed at lower risk of recurrence with respect to hormonal receptor status, axillary nodal status, tumor size, grade, lymphovascular invasion, and surgical margin status [10-12]. These considerations primarily stem from a motivation for omission of RT when there is no substantial benefi t to improve the therapeutic ratio. Sparing of highly selected subgroups of patients from RT may have potential implications for improved Abstract


Introduction
Breast cancer (Ca) comprises the most common cancer in females and constitutes a leading cause of cancer related deaths around the globe [1,2]. These considerations primarily stem from a motivation for omission of RT when there is no substantial benefi t to improve the therapeutic ratio. Sparing of highly selected subgroups of patients from RT may have potential implications for improved Abstract Breast cancer (Ca) comprises the most common cancer in females and constitutes a leading cause of cancer related deaths around the globe. Contemporary treatment protocols established by incorporation of accumulating high level evidence suggest multimodality therapy for patients suffering from breast Ca with combinations of surgery, radiotherapy (RT) and systemic treatment. Surgical options for management of breast cancer typically include breast conserving surgery (BCS) or mastectomy. In current treatment practice, BCS is used as a viable surgical modality for breast Ca management. RT after BCS has been widely adopted for management of the vast majority of patients with breast Ca particularly to achieve improved local control as suggested by collaborative group studies and metaanalyses. Although alternative dose-fractionation schemes may be considered for management of some patients, current widely accepted practice includes the use of conventionally fractionated RT after BCS for breast Ca. Whole breast irradiation (WBI) constitutes a widely recognized breast Ca RT approach which is typically used to deliver a total dose of 45 to 50 Gy over 5 to 6 weeks in daily fractions of 1.8 to 2 Gy. Hypofractionated RT schemes have also been widely accepted as a viable alternative to conventional fractionation with satisfactory treatment outcomes. A typical location for local recurrences of breast Ca includes the primary tumor site within the tumor bed or its vicinity, which justifi es the delivery of additional boost dose focused on this area to improve local control rates particularly for patients with high-risk characteristics including younger age, large tumor size, higher grade, extensive intraductal component, close or positive surgical margins. Herein, we assess the utility of delivering an additional sequential boost RT after WBI for patients with early breast Ca in light of the literature.
Citation: Dincoglan  quality of life due to elimination of radiation induced adverse effects. Also, cumulative costs of treatment may be reduced along with the RT facility workloads. Hypofractionated RT schemes have gained widespread popularity given the patient and treatment facility convenience along with shorter treatment courses offering satisfactory therapeutic outcomes. Herein, we focus on another critical aspect of multidisciplinary breast Ca management. We assess the utility of delivering an additional sequential boost RT after Whole Breast Irradiation (WBI) for patients with early breast Ca in light of the recent advances and existing literature.

Breast Conserving Surgery (BCS) as an alternative to mastectomy
Surgical options for management of breast cancer typically include BCS or mastectomy. Several factors may have a role in selection of either BCS or mastectomy for a given patient such as patient and treatment characteristics, considerations regarding cosmesis, adverse effects, tumor control and patient preferences. Regarding the outcomes of management with these 2 surgical modalities, BCS and mastectomy were found to achieve comparable effi cacy as supported by high level evidence from randomized trials [13][14][15]. Also, there have been some other studies focusing on favorable aspects of management with BCS [16-18]. In current treatment practice, BCS is used as a viable surgical modality for breast Ca management.

Utilization of RT after BCS
There has been thorough consideration for omission of RT after BCS in selected subgoups of highly selected patients with favorable characteristics regarding the hormonal receptor status, axillary nodal status, tumor size, grade, lymphovascular invasion, and surgical margin status [10-12,19-21]. Nevertheless, RT after BCS has been widely adopted for management of the vast majority of patients with breast Ca particularly to achieve improved local control as suggested by collaborative group studies and metaanalyses [22-25].

Dose and fractionation for RT after BCS
Utility of Accelerated Partial Breast Irradiation (APBI) and hypofractionated RT schedules for breast Ca management has been investigated [26][27][28][29][30][31][32][33]. Although these alternative dosefractionation schemes may be considered for management of some patients, current widely accepted practice includes the use of conventionally fractionated RT after BCS for breast Ca. Whole Breast Irradiation (WBI) constitutes a widely recognized breast Ca RT approach which is typically used to deliver a total dose of 45 to 50 Gy over 5 to 6 weeks in daily fractions of 1.8 to 2 Gy. Nevertheless, hypofractionated RT schemes have also been widely accepted as a viable alternative to conventional fractionation with satisfactory treatment outcomes and widespread adoption. Rationale of hypofractionation stems from the moderately low alpha/beta ratio of breast tumors together with other potential favorable features of hypofractionated regimens including patient and treatment facility convenience. In the recent American Society for Radiation Oncology (ASTRO) evidence based guideline, delivery of an additional boost dose to the tumor bed is suggested for patients ≤ 50 years of age with any grade Ca [58].

Conclusion
There is growing body of evidence supporting the use of an Citation: Dincoglan