Introduction
Traditionally, patients undergoing breast-conserving surgery (BCS) receive standard whole breast irradiation (WBI) (1–3). However, patients with early-stage breast cancer are a heterogeneous group, with a variable risk and pattern of recurrence. Accordingly, alternative treatment options besides conventional WBI should be available. Based on findings that most recurrences after BCS for early breast cancer usually occur within or near the original tumor bed, partial breast irradiation (PBI) has become the focus of many cancer centers. Moreover, various centers have investigated the indications for BCS without radiotherapy (BCS only) (4,5). Thus, BCS and WBI, BCS and PBI or BCS only jointly constitute the individualized treatment strategy for early-stage breast cancer.
PBI is still in the clinical research stage. No consensus has been reached on numerous issues, such as indications, target area identification and fractionation methods. The aim of this study was to examine the use of PBI with a conventional fractionated three-dimensional conformal modality. Since the target volume was the only factor of this PBI protocol that varied from standard WBI, local tumor control was the focus and sole end point of this trial. Only once PBI has been determined to confer the same local tumor control benefits as WBI can this technique be examined in phase II trials.
Discussion
Individualized treatment for patients with early-stage breast cancer consists of BCS and irradiation (WBI or PBI) or BCS only, based on the fact that two subgroups of patients co-exist: those who are presumed to have occult disease and those who are free of tumor residue. However, it is not currently possible to identify these two patient subgroups.
To date, all trials regarding the omission of irradiation therapy, even in highly selected low-risk early breast cancer patients treated with BCS, have been unsuccessful (7–9). In addition, it has been consistently demonstrated that the local recurrence rate is significantly lower when adjuvant radiotherapy is administered to the mammary gland (10,11). As a result, combined with the concept of the multicentric origin of breast cancer, WBI has become the standard procedure after BCS. However, many authors have questioned the necessity of WBI in early-stage breast cancer, since most of the local recurrences have been observed to occur near or close to the tumor bed, justifying the administration of PBI (12,13). If PBI proves to be efficacious, it will offer the potential advantage of reduced treatment-related toxicity and improvement in the quality of life of patients by confining treatment to a limited volume of breast tissue adjacent to the lumpectomy cavity and by decreasing the volume of lung and heart that is irradiated as compared to WBI (14).
A number of studies on PBI have been carried out in North America and Europe, and most clinical results are promising (15–17). Recently, a detailed systematic review analyzed almost all aspects of accelerated PBI (APBI), including the history of the patients and the rationale for the selection of the APBI, treatment techniques used, as well as the radiobiological aspects (18). In this review, the ipsilateral breast recurrence rates for most APBI cases were lower than 8% compared to patients receiving WBI. The most comprehensive study was from the William Beaumont Hospital, USA, where 199 patients were enrolled from 1993. The inclusion criteria included patients ≥40 years of age with ductal carcinoma only, T ≤3 cm, no EIC, pN0 (prior to 1997 also pN1) and negative surgical margins ≥2 mm. The 5-year actuarial local failure rate was only 1.2% after APBI with interstitial brachytherapy, as compared to WBI. We based our inclusion criteria for APBI on those of the William Beaumont Hospital (19), with certain adjustments: negative surgical margins were increased to ≥5 mm and only patients who placed extreme emphasis on the protection of normal tissues were included.
The only non-invasive technique for APBI is three-dimensional conformal radiotherapy (3D-CRT). The local failure rate for APBI by 3D-CRT is comparable to that of brachytherapy or other invasive techniques, such as mammosite or intraoperative radiation (20). 3D-CRT is more acceptable as it eliminates the need for an additional surgical procedure, has an improved dose homogeneity, and reduces the risk of fat necrosis. Furthermore, 3D-CRT has become common practice at most cancer centers, including those in developing countries, and does not require additional medical staff training, unlike brachytherapy. In the present study, 12 patients were treated with 3D-CRT; 95% of the isodose surface covered 100% of the PTV, the average area of the breast that received 115% of the prescribed dose was zero. The most common adverse reactions were grade 2 radioactive erythema in 2 (17%) cases and pigment deposition in 10 (83%). All patients had satisfactory cosmetic results.
In China, BCS is not a commonly opted for procedure compared to Western countries. In the West, younger women with a higher education level and a good socioeconomic status generally tend to undergo BCS. Some patients have no alternative besides BCS due to combined heart and/or lung morbidity. Almost all patients treated with BCS fulfill 5–6 weeks of conventional fractionated irradiation. In mainland China, patients who decide to undergo BCS are usually prepared for conventional fraction irradiation, but consider tumor control and improvement in the quality of life. Thus, our PBI trial design was focused on controlling the local tumor recurrence rate. In our opinion, the goal of any PBI trial is the comparability of the local tumor control of PBI to that of WBI. Although each of the APBI dose-fractionation schedules is determined by referring to the equivalent biological dose (BED) (21), in comparison with conventional fractionation, the BED is an indeterminate factor that may impact the results of an APBI trial. Therefore, a combination of conventional fractionation with 3D-CRT was used to ensure a logistically simpler and more practical method for PBI testing.
In our study, 12 patients complied with the conditions of the trial. The patients were followed up for more than 41 months, and no cases of recurrence or distant metastasis were noted. PBI and WBI appeared to demonstrate an equivalent local tumor control rate. In addition, the present study demonstrated the superior efficacy and cosmetic results of BPI, and the patients experienced few adverse reaction.
Due to the slow nature of local recurrences in breast cancer, a very long follow-up is required. This research is therefore still in its initial stages. Moreover, the number of cases was limited. Thus, further studies are necessary in order to reach an objective conclusion.