We know that breast cancer represents a spectrum of diseases, with variation in prognosis, and that RT can range from highly complex treatments to the breast and regional lymph nodes, to complete avoidance of radiation.
Accelerated partial breast irradiation (APBI) should not be used routinely in the treatment of breast cancer. Whole-breast irradiation (WBI) has an established local control benefit, which has been shown to confer a survival benefit not only in invasive cancer, but also in a subset of patients with ductal carcinoma in situ. Breast cancer recurrence increases linearly with time, and both radiotherapy (RT) and systemic therapy continue to reduce local failure beyond 5 years after diagnosis. Therefore, robust follow-up data are needed before the routine use of any therapy that may compromise local control and subsequently survival.
APBI is not expected to provide better local control than WBI, so its use should be considered only if it might offer some other tangible benefit to women. Proponents of APBI cite the increased convenience of this technique, the promise of lower toxicity, and the hope that this technique will allow more women to receive radiation. Currently, breast-conserving surgery (BCS) rates nationally are only 46% in seemingly eligible women, and APBI has been proposed as a modality that may increase the use of BCS. To address this issue thoroughly, we will explore the validity of the claims of efficacy, convenience, toxicity, and access surrounding APBI.
Early practice of APBI had unacceptably high local recurrence rates.[6,7] These trials included patients with node-positive disease and larger tumors, no uniform clinical target volume margin, variable radiation techniques, and suboptimal methods of tumor bed localization that undoubtedly contributed to the observed high rates of failure. More recently, APBI has demonstrated much more favorable results. Despite promising prospective studies of highly selected patients,[8,9] randomized trials with adequate follow-up are lacking. The populations included in the current randomized trials have tumors that are predominantly estrogen receptor (ER)-positive and luminal A subtype. The natural history of these tumors is indolent, and they remain under the effect of endocrine therapy, which makes the present follow-up inadequate to determine long-term efficacy.
Routine use of APBI would require that it could be applied to a broad population. Not only is the long-term efficacy of APBI uncertain, but there are also concerning data that suggest that local failure rates are high in women with ER-negative disease and other biologically adverse subtypes when a partial breast approach is used.[13,14] Therefore, a partial breast approach is not reasonable for routine use, but only for highly selected postmenopausal women with small tumors and no adverse pathologic features.
APBI is convenient. However, hypofractionated (HF) WBI is also a convenient option. With a treatment course of 15 fractions rather than 10, the UK Standardisation of Breast Radiotherapy (START) and Canadian phase III randomized trials have shown equivalent local control and reduced adverse effects with HF-WBI when compared with conventional fractionation (CF) WBI with long-term follow-up.[16,17] A randomized trial of HF- vs CF-WBI demonstrated significantly lower rates of acute grade 2 or higher toxicity and improved physical well-being and fatigue in the HF arm. Rates of pneumonitis remain extremely low; cardiac doses are modest, with minimal impact on outcomes[20-22]; and cosmesis is excellent with modern techniques.
In an effort to further expedite treatment, the UK FAST-Forward trial, which is testing two 5-fraction regimens over 1 week vs HF-WBI, was launched at the end of 2011. If the 1-week regimen is found to be noninferior to HF-WBI, it may eliminate the convenience advantage of APBI.
Although the convenience of APBI may be enticing, there are troubling toxicity reports in the APBI literature. Cosmetic results of the external beam technique have been reported to be inferior,[25-27] although this has not been uniformly found.[28,29] While the multicatheter-based interstitial brachytherapy literature has not echoed these findings, there are equipment and skill needs that prevent routine use of this technique. Balloon-based brachytherapy is also associated with significant toxicity to the chest wall, as well as softtissue necrosis.[31,32] Although the exact reasons for mastectomy in this setting are not clear, women who receive APBI with balloon-based brachytherapy have double the rate of mastectomy, as well as a higher risk of breast pain, fat necrosis, rib fracture, and postoperative complications, compared with women who receive WBI. Based on these data, the allegation that APBI always results in less toxicity than WBI is inaccurate.
No data support the notion that partial breast irradiation will allow more eligible women to undergo BCS. In fact, the available data conflict with this hypothesis. The rate of mastectomy rose by 36% from 2005 to 2013, despite an increase in the use of APBI from 8% in 2005 to 17% in 2008. Although access is a cited reason for promoting APBI, rural living areas were independently associated with less utilization of APBI. The reasons behind women’s selection of mastectomy are complex, and various factors influence their decision, including the use of MRI, physician advice, and fear of future recurrence. Other initiatives have found that clinician education can increase rates of BCS; however, to date APBI has not been shown to increase utilization of BCS or radiation following BCS.
We know that breast cancer represents a spectrum of diseases, with variation in prognosis, and that RT can range from highly complex treatments to the breast and regional lymph nodes, to complete avoidance of radiation. The challenge will be to select the most appropriate treatment for the individual patient and to personalize RT based on tumor biology.
The standard treatment for breast cancer patients at low risk for recurrence is conservative surgery followed by WBI. The APBI concept, developed more than 20 years ago, may be an option in carefully selected patients. However, the ideal patient profile for APBI is still not clearly identified, as evidenced by the heterogeneity of the inclusion criteria of the continuing APBI trials. The ongoing French SHARE trial will randomize 2,800 patients to three arms: APBI using three-dimensional conformal RT (1 week), CF-WBI (6.5 weeks), and HF-WBI (3 weeks). Results of this trial should give us more insight into the optimal therapy for women with early-stage breast cancer.
Until long-term follow-up data are available, APBI should be used with caution in selected patients at low risk for ipsilateral breast tumor recurrence only, after careful informed consent is obtained. HF-WBI is a clinically proven alternative to APBI and CF-WBI for women who desire a shorter course of RT without potentially compromising local control and survival.
Financial Disclosure:The authors have no significant interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article. For the sake of transparency, it should be noted that Dr. Evans’s institution receives funding from 21st Century Oncology for research in which she is involved.
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