Component Of Breast-conserving Therapy Research Articles

Technique Matters: Pearls for Excellent Breast Brachytherapy by Various Techniques Learned over 2500 Cases

In the 1970s and 1980s, brachytherapy covering the original tumor site was a common boost technique after 5 weeks of external beam breast irradiation. In 1991, wide-volume brachytherapy was introduced as a sole method of breast irradiation as a component of breast conservation therapy. Over the subsequent 28 years, significant improvements in target volume coverage, dose homogeneity, image-guided catheter insertion techniques, and quality measures have enhanced the field of accelerated partial breast irradiation (APBI). Now, approximately 15% of early breast cancers in the U.S. are treated by APBI, and randomized trials from Europe and North America have demonstrated non-inferiority and insignificant differences in ipsilateral breast tumor recurrence rates (IBTR) in comparison to traditional whole breast irradiation (WBI). Breast cancer is unforgiving: an appropriate risk-adapted target volume must be reproducibly treated by a tumoricidal dose or IBTR will become unacceptable. IBTR without WBI ranges between 25 and 35%, while quality APBI reduces IBTR to approximately 5%. This presentation examines the details that define quality breast brachytherapy.

Radiation Treatment Strategies in Patients Undergoing Breast-Conserving Surgery

Breast-conserving therapy offers patients an oncologically sound opportunity to cure their cancer, preserve their breast, and maintain an excellent quality of life. Historically, radiation delivered as a component of breast-conserving therapy required up to 7 weeks of daily treatment after surgery, exacting a burden both on individual patients and the health-care system as a whole. In the past several years, new strategies have emerged which seek to retain the benefits of breast-conserving therapy but decrease the burden of protracted radiation courses. These strategies include omission of radiation in selected patients, hypofractionated whole-breast irradiation, and accelerated partial-breast irradiation, which can be delivered using multicatheter interstitial brachytherapy, single-entry catheter-based brachytherapy, external beam techniques, proton therapy, or intraoperative techniques. The promise and potential problems with these newer radiation strategies are discussed herein, with guidance provided as to the appropriate application of these techniques in clinical practice.

Hypofractionation in the era of modulated radiotherapy (RT)

The use of radiation therapy (RT) as a component of breast-conserving therapy (BCT) has been shown to reduce the risk of local-regional recurrence and improve overall survival. As has been the common practice in the United States and Continental Europe, the majority of studies that demonstrated these benefits utilized daily radiation doses ranging from 1.8 to 2.0 Gray (Gy) per day given for approximately 5 weeks. However, due to geographic limitations, patient preferences, and financial considerations, there have been continued attempts to evaluate the efficacy and safety of abbreviated or hypofractionated courses of whole-breast radiation. Two key factors in these attempts have been: 1) advances in radiobiology allowing for a more precise estimation of equivalent dosing, and 2) advances in the delivery of RT (‘modulation’) that have resulted in substantially improved dose homogeneity in the target volume. Hypofractionated schedules have been compared to conventional radiation courses in several randomized controlled trials, as well as many prospective and retrospective experiences. These studies, now with about 10 years of follow-up, have demonstrated equivalent rates of local-regional recurrence, disease-free survival, and overall survival. The rates of toxicity have generally not been increased with hypofractionated regimens; however, certain toxicities may take decades to manifest. The generalizability of these results is unclear, as the majority of patients in the trials were elderly with early-stage hormone-receptor positive disease. Nevertheless, there is now sufficient evidence to recommend hypofractionated whole breast RT for a substantial percentage of patients.

Is Partial Breast Irradiation a Safe and Effective Treatment Approach for Women with Early-Stage Breast Cancer?

Breast-conserving therapy (BCT) represents the standard care in the management of early-stage breast cancer, because long-term outcomes with breast conservation are comparable with those of mastectomy. Adjuvant radiation therapy remains an essential component of BCT with standard techniques requiring 5–6½ weeks. Accelerated partial breast irradiation (APBI) is a technique developed over the past two decades that enables completion of treatment in one week or less. Review of the expanding literature reveals increasing support for APBI using several techniques, including interstitial brachytherapy, balloon-based brachytherapy, and external beam therapy. Novel treatment strategies, including intraoperative radiation therapy, hypofractionated APBI, and proton therapy, require further results before definitive conclusions can be made. Although there is currently a lack of level I evidence, with the pending publication of multiple phase III trials comparing whole-breast irradiation and APBI, modern treatment incorporating APBI should soon be developed.

Abbreviated course of radiotherapy (RT) for breast cancer

The use of RT as a component of breast-conserving therapy or after mastectomy has been proven to reduce the risk of local-regional recurrence (LRR) and to improve long-term breast cancer-specific and overall survival. As has been the common practice in the United States and Continental Europe, the majority of studies that demonstrated these benefits utilized daily radiation doses ranging from 1.8-2 Gray (Gy). However, due to geographic limitations, patient preferences and financial considerations, there have been continued attempts to evaluate the efficacy and toxicity of abbreviated courses of breast RT. Two key factors in these attempts have been: (1) advances in radiobiology allowing for a more precise estimation of equivalent dosing; and (2) advances in the delivery of RT that have resulted in substantially improved dose homogeneity in the target volume. As an alternative to approximately five weeks of daily treatment at 1.8-2 Gy, delivering radiobiologically-equivalent total doses in hypofractionated, abbreviated schedules has been evaluated in five randomized controlled trials, as well as many prospective and retrospective experiences. These studies have generally demonstrated equivalent rates of LRR, disease-free survival and overall survival with the use of hypofractionated regimens. Despite theoretical and historic concerns that hypofractionated regimens could increase damage to normal tissue, the rates of acute and long-term toxicities have generally not been increased in most recent series. Some toxicities, however, may take years to decades to manifest. Questions still remain regarding which patients are appropriate for abbreviated treatment. The majority of patients included in the studies supporting hypofractionated treatment were of older age with early-stage invasive ER+ disease of predominantly lower histological grade. This favorable subset of patients is also the most eligible for other alternative treatment approaches, such as partial-breast irradiation or hormonal therapy alone. Additionally, few to none of the patients included in most studies were treated with mastectomy, lymph node irradiation, a lumpectomy cavity radiation boost, or adjuvant chemotherapy. The existing evidence prompted the American Society for Radiation Oncology (ASTRO) to convene a task force to issue an evidence-based guideline in 2010 delineating the patients for whom an abbreviated radiation course is most supported by the current evidence [Smith et al. 2010, Int J Radiat Oncol Biol Phys]. Ongoing and future studies will further clarify the suitability of a hypofractionated treatment approach for the patient subgroups underrepresented in available trials. Additionally, alternative abbreviated treatment regimens, including those in which treatment is given once weekly and treatments that include an integrated lumpectomy cavity boost, are actively being investigated. Finally, innovative radiation techniques, such as the use of higher energies, prone treatment, and breathing-adapted therapy have further increased the homogeneity of breast irradiation and minimized dose delivered to nearby critical normal structures. Consequently, increasing experience with these techniques may expand the population of patients amenable to hypofractionated therapy.

Status of Accelerated Partial Breast Irradiation

Breast-conserving therapy is accepted as a standard of care option for patients with early-stage breast cancer. However, studies examining patterns of failure after treatment suggest that a lengthy course of adjuvant whole breast irradiation delivered as a component of breast-conserving therapy may not always be necessary; indeed, in appropriately selected patients, radiation therapy delivered only to the tumor bed may be acceptable. Several modalities of delivering accelerated partial breast irradiation (APBI) have been developed, the most prevalent being multi-catheter interstitial brachytherapy, the MammoSite breast brachytherapy catheter (Hologic Corporation, Bedford, MA) and three-dimensional conformal external-beam radiation therapy. The purpose of this article is to review the published experiences on the most common modalities of delivering APBI and to outline the current open national phase 3 trial. To date, phase 1/2 studies have demonstrated excellent local control and cosmetic outcomes in early-stage breast cancer patients treated with APBI. As increasing knowledge is accumulated regarding the efficacy and safety of APBI, a consensus will emerge regarding its potential replacement of whole breast irradiation in selected early-stage breast cancer patients.

Overview of accelerated partial breast irradiation

Breast conserving therapy (BCT) has become an accepted option in the management of patients with early-stage breast cancer. However, studies have suggested that a lengthy course of adjuvant whole breast irradiation, as a component of BCT, may not always be necessary and that radiation therapy delivered only to the region of the tumor bed may be acceptable in appropriately selected patients. Several modalities are currently being explored as a means to deliver accelerated partial breast irradiation (APBI), including multicatheter interstitial brachytherapy, the MammoSite breast brachytherapy catheter (Cytyc Corporation, Marlborough, MA), and three-dimensional conformal external-beam radiation therapy. To date, phase 1/2 published data have demonstrated excellent local control rates and cosmesis. As additional data addressing the effectiveness of this treatment approach accumulate, a new standard of care may emerge. This review discusses data accumulated to date exploring the experience with all APBI modalities and presents future studies exploring this concept.

The Use of Radiation As a Component of Breast Conservation Therapy in National Comprehensive Cancer Network Centers

Benchmark data regarding quality measures of breast cancer management are needed. We investigated rates of radiation use after breast conservation therapy (BCT) for patients treated for ductal carcinoma-in-situ (DCIS) or invasive breast cancer at National Comprehensive Cancer Network (NCCN) centers. We studied 3,333 consecutive patients treated between 1997 and 2002 with BCT for DCIS (n = 587) or for stage I or II breast cancer (n = 2,746) in eight NCCN centers. The overall rate of radiation therapy use was 91%, with a lower frequency of radiation use in DCIS versus invasive breast cancers (82% v 94%; odds ratio [OR] = 0.31; P < .0001). In a multivariable analysis of the patients with DCIS, the only factor significantly associated with lower rates of radiation use was low/intermediate grade (OR = 0.19; P = .0003). For patients with invasive breast cancer, significant factors were presence of comorbidity (OR = 0.53; P = .0005), tubular histology (OR = 0.39; P = .02), type of health insurance (P = .0072), and the NCCN institution (P = .0005). The model also showed lower rates of radiation use in patients with stage II disease who did not receive systemic therapy (OR = 0.01; P = .0001), younger patients who did not receive systemic therapy (P = .003); and older patients with stage I disease (P < .0001). Radiation use as a component of BCT was high for patients seen at NCCN centers; however, there was variability in practice patterns noted across institutions. Radiation was most commonly omitted in patients with favorable disease characteristics, patients with comorbidities, and patients who also did not receive guideline-recommended systemic treatment.

Breast Reduction as an Alternative Treatment Option for Early Breast Cancer in Women With Macromastia

Macromastia has been considered a relative contraindication to breast conservation therapy because of difficulties with postoperative radiation therapy and cosmesis. This study evaluates the feasibility of the inferior pedicle reduction mammaplasty as a component of breast conservation therapy for patients with early breast cancer. A retrospective review identified 6 patients with macromastia receiving oncologic treatment of breast cancer and simultaneous breast reduction. Mean age was 43.5 +/- 8.7 (mean +/- SD) years, and all breast cancers were stage I or II, averaging 2.3 +/- 1.5 cm in size. All patients underwent a Wise-pattern inferior pedicle breast reduction after cancer extirpation and received postoperative radiation as part of their treatment. They were evaluated for postoperative complications, esthetic outcome of the breasts, and local recurrence. Patients in this series were followed for an average of 30.3 months, with no significant postoperative complications and recurrences. Breast reduction incisions healed primarily and adjuvant radiation was completed without a delay. All patients were pleased with the esthetic result and had improvement of their symptoms related to macromastia. Thus, we believe that breast reduction is a reasonable and safe option for early breast cancer patients with macromastia who desire breast conservation therapy. Our combined oncologic and reconstructive approach may improve the outcome of this group of patients with early breast cancers.

Late Effects and Cosmetic Results of Conventional Versus Hypofractionated Irradiation in Breast-Conserving Therapy

Breast irradiation after lumpectomy is an integral component of breast-conserving therapy (BCT). As the prognosis is general good following BCT, late morbidity and cosmesis are important. The present study compares two different radiation schedules with respect to these two endpoints. 129 breast cancer patients (pT1-2 pN0-1 cM0) were irradiated between 09/1992 and 08/1994 with either a 22-day fractionation schedule (2.5 Gy to 55 Gy, 4x/week, n = 65) or with a conventional fractionation schedule (28 days, 2.0 Gy to 55 Gy, 5x/week, n = 64), both without additional boost. The equivalent dose of 2-Gy fractions (EQD2) was 55 Gy and 62 Gy, respectively. Late toxicity, assessed according to the LENT-SOMA criteria, and cosmetic outcome, graded on a 5-point scale, were evaluated after a median of 86 months (range 72-94 months) in tumor-free breast cancer patients. LENT-SOMA grade 2/3 toxicity (2.5 Gy vs. 2.0 Gy): breast pain (18% vs. 11%; p = 0.3), fibrosis (57% vs. 16%; p < 0.001), telangiectasia (22% vs. 3%; p = 0.002), atrophy (31% vs. 3%; p < 0.001). Medication to breast pain was taken by 8% versus 9% of patients. Cosmesis was very good/good/acceptable in 75% versus 93% (2.5 Gy vs. 2.0 Gy; p = 0.006). Late morbidity was significantly frequent and cosmesis was significantly worse after hypofractionated radiotherapy (2.5 Gy to 55 Gy). However, morbidity was not associated with major implications on daily life.

MammoSite®

MammoSite® is a novel brachytherapy applicator for breast irradiation as a component of breast conservation therapy in the management of early stage breast carcinoma. Early stage breast cancer accounts for over two-thirds of newly diagnosed cases. Breast conservation therapy is an option for most women for local therapy. The standard treatment of partial mastectomy and whole-breast irradiation is being challenged. Physicians and patients are searching for alternatives to a 6- to 7-week course of external beam radiation therapy. The direct application of radioactive materials (brachytherapy) in this setting has been employed for over 10 years. MammoSite has been developed as an easier, more quality assured applicator to allow broader acceptance and wider availability of partial breast irradiation techniques. The background leading to the device will be examined, current clinical results will be reviewed and alternative technologies will be discussed.

Role of template guided interstitial implants in breast conservation therapy

Breast conservation therapy is currently considered as a viable alternative to mastectomy in early breast cancer. Radiotherapy by virtue of its ability to reduce local recurrences is an integral component of breast conservation therapy. Apart from irradiating the whole breast, the tumor bed is usually delivered a boost dose in breast conservation therapy to increase the local control rate. One of the methods which has been adopted to selectively boost the tumor bed to high doses is the use of per-operative high dose rate interstitial implants. This particular paper deals with our department's experience with breast conservation therapy using per-operative template guided, High Dose Rate (HDR) interstitial implants in early breast cancer. Local control rates, disease free survival and cosmetic benefit with this technique will be discussed along with literature review.

Patterns of Radiation Use as a Component of Breast Conservation Therapy for Noninvasive and Invasive Breast Cancers in United States National Comprehensive Cancer Network (NCCN) Centers

Patterns of Radiation Use as a Component of Breast Conservation Therapy for Noninvasive and Invasive Breast Cancers in United States National Comprehensive Cancer Network (NCCN) Centers

Reduction mammoplasty improves breast conservation therapy in patients with macromastia

Background: Macromastia has been considered a contraindication to breast conservation therapy because of difficulties with radiation therapy. This study evaluates the feasibility of bilateral reduction mammoplasty as a component of breast conservation therapy for breast cancer patients with pendulous breasts. Methods: Of 153 patients undergoing reduction mammoplasty at the University of Texas M. D. Anderson Cancer Center, 28 were identified as breast cancer patients with macromastia receiving breast conservation therapy. Median follow-up was 23.8 months. Results: Median patient age was 55 years. Nearly all patients were described as obese. Median weight of the reduction mammoplasty specimen on the cancerous side was 766 g. One patient (4%) required completion mastectomy for inadequate margin control. Major postoperative complications occurred in 2 patients (7%). There were no major postradiation complications. Patient survey revealed a satisfaction rate of 86%. Conclusion: Bilateral reduction mammoplasty is a reasonable and safe option for breast cancer patients with macromastia who desire breast conservation therapy.

Conservation Therapy of the Breast: Optimizing Long-term Results.

BACKGROUND: Radiation therapy is a key component of breast conservation therapy for breast cancer. There is great interest in safety and long-term outcome issues for this still underutilized approach. METHODS: The author reviews a series of factors that may affect the end results of conservation therapy and highlights those that are likely to be of clinical significance. RESULTS: Daily dose fractions are usually less than 2 Gy and a homogeneous whole-breast dose is used. Care is needed with patients with collagen vascular diseases, large breasts, breast trauma, and prior infections, but these factors are not absolute contraindications to breast conservation therapy. Acute skin reactions are not predictive of long-term complications. CONCLUSIONS: With adherence to proper surgical and radiation techniques, most patients presenting with localized breast cancer can be managed safely and effectively with breast conservation.