The evolution of adjuvant radiation therapy for early‐stage and locally advanced breast cancer

Adjuvant radiation therapy is often delivered after breast cancer surgery, both in the post‐lumpectomy and post‐mastectomy settings. Standard fractionation whole breast irradiation (SF‐WBI), which is typically delivered over 5‐7 weeks, was previously considered the standard of care. More recent data has helped to establish hypofractionated whole breast irradiation (HF‐WBI), which consists of a 3‐4 week regimen, as a new standard of care. This article provides an overview of the major randomized trials that support the routine use of HF‐WBI for the majority of patients undergoing breast‐conserving surgery for early‐stage breast cancer. Newer data on the use of a hypofractionated approach in the post‐mastectomy setting, as well as ongoing randomized trials addressing this topic, are also discussed.     

Intraoperative radiation therapy for breast cancer: technical notes

Interest in intraoperative radiation therapy (IORT) for breast cancer is increasing as the possible benefits of this technique for the patient become apparent. The rationale for the use of this segmental radiation therapy in place of whole-breast irradiation is based on the finding that approximately 85% of breast relapses are confined to the same quadrant of the breast as the primary tumor. Phase I and II trials have demonstrated no increase in postsurgical complication rates following the use of single-dose IORT in localized breast cancers. Longer follow-up is needed to assess the cosmetic outcome. Clinical trials to evaluate the effectiveness of IORT in the treatment of breast cancer are currently under way at the European Institute of Oncology (EIO) at the University of Milan, Italy, and at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York. Here we report the two different techniques in use in these trials.     

Breast conservation for male breast cancer: Case report of intraoperative radiation

Male breast cancer (MBC) comprises <1% of all breast cancers in the United States. MBC is typically treated with total mastectomy while the majority of female breast cancer is treated with breast conservation therapy combined with various forms of radiation. One method that has developed over the last two decades is the use of intraoperative radiation therapy (IORT) as a type of accelerated partial breast irradiation to direct the treatment field to the tumor bed. Since overall prognosis and systemic therapy recommendations for MBC are similar to breast cancer in women, we describe the first case of MBC treated with BCS and IORT. Our patient is a 62‐year‐old male who was found to have a right breast 1.6 cm palpable mass at the 10:00 position 1 cm radially from the nipple. Core biopsy demonstrated invasive ductal carcinoma, moderately differentiated, estrogen and progesterone receptor positive, and Her 2 Negative. The patient had a strong desire for breast conservation, and needed to minimize daily radiation treatments due to his work schedule. After discussion among our multidisciplinary tumor board, we felt this patient to be suitable for BCS and IORT given his age, favorable tumor subtype, size, and clinically early stage breast cancer. A right axillary sentinel lymph node biopsy and central lumpectomy was performed. The INTRABEAM device (Carl Zeiss Meditec, Oberkochen, Germany) was utilized for radiation delivery. The patient had negative margins on his final pathology. The postoperative course was uneventful and at the 6 month follow‐up visit there were no issues and he had an excellent cosmetic outcome. BCS and IORT is an option in appropriately selected male patients with favorable subtype early stage breast cancer.     

Prospective trial of intraoperative radiation treatment for breast cancer

BACKGROUND: A new device, Intrabeam, is available for intraoperative radiotherapy. We have prospectively examined its feasibility and tolerability in delivering adjuvant breast cancer treatment. METHODS: Thirty-five patients undergoing breast-conserving surgery received targeted tumour bed irradiation consisting of 5 Gy (at 10 mm) in a single fraction. This single intraoperative treatment was used to replace the external beam radiotherapy "boost" that would usually be given in 10 daily treatments following 5 weeks of whole breast irradiation. Patients later completed external beam radiotherapy as usual. Potential toxicities were prospectively assessed fortnightly prior to external beam radiotherapy, weekly during it, and 3 monthly subsequently. RESULTS: The intraoperative radiotherapy was able to be delivered without difficulty, either at time of initial cancer surgery or as a second procedure. When performed as a separate procedure the median operating time was 56 min. The treatment was well tolerated, with only one patient experiencing any grade 3 or 4 toxicities--this was acute grade three itch. There was an overall early breast infection rate of 17%. No unexpected toxicities were seen. CONCLUSIONS: This simple and well-tolerated treatment delivers a useful radiation dose to the area of highest risk of tumour recurrence. The early infection rate is similar to that reported in the literature, for treatments without intraoperative radiotherapy. Whether such a treatment may adequately replace the entire adjuvant radiation therapy treatment for low-risk patients is now being studied in a randomized trial.     

Angiosarcoma of the breast following breast preservation therapy and local radiation therapy for breast cancer

Abstract: This is a case of angiosarcoma following breast preservation therapy and local radiation therapy over a 3-year period.     

Intraoperative radiation therapy for breast cancer—Immediate and 30‐month oncological outcomes

There is growing evidence that intraoperative radiation therapy (IORT) may be a viable option in selected patients with early breast cancer. This study reports our 4‐year experience with IORT. The perioperative outcome and imaging data of all patients who underwent IORT for early breast cancer at a tertiary medical center in 2014‐2018 were retrospectively retrieved. The cohort included 158 patients aged 52‐84 years (mean 68) with stage I (n = 137) or II (n = 21) breast cancer. Mean applicator size was 4.13 cm; IORT added a mean of 29 minutes to the operative time. Minor wound infections (n = 18, 11.4%) requiring antibiotics and drainage were the only postoperative complication. In 25 patients (15%), postoperative mammography demonstrated a seroma (n = 22) or fat necrosis (n = 3). The risk of wound infection or a new postoperative imaging finding was unrelated to patient age, operative time, tumor size, or comorbid diabetes or obesity. After a mean of 30 months' follow‐up, none of the patients who met the institutional criteria for IORT had local recurrence, regardless of age, histology, tumor grade, KI67 proliferation index, pathologic stage, Recurrence Score, or additional whole‐breast irradiation or adjuvant treatment. Patients for whom a Recurrence Score was determined (n = 55, 35%) had a significantly higher tumor grade, pathologic stage, and whole‐breast irradiation/adjuvant chemotherapy rate than the remaining patients. IORT may be a safe alternative to traditional external beam radiation in well‐selected patients with early breast cancer, with few minor complications and good 30‐month outcome.     

Most patients are eligible for an alternative to conventional whole breast irradiation for early‐stage breast cancer: A National Cancer Database Analysis

We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast‐conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I‐III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET‐alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET‐alone based on the CALGB 9343/PRIME‐II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC‐ESTRO trial/ASTRO guidelines/ABS guidelines/GEC‐ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET‐alone. This analysis shows that a large proportion of patients with node‐negative breast cancer are eligible for HFRT, APBI and/or ET‐alone after breast‐conserving surgery.     

Outcomes of exclusive radiation therapy for older women with breast cancer according to age and comorbidity status: An observational retrospective study

The management of older patients with breast cancer, a public health issue, remains a highly topical subject. Among this heterogeneous population, only few studies have focused on outcomes of older women treated with exclusive radiation therapy for localized BC. This retrospective study provides data concerning the efficacy and safety of exclusive RT, as well as the impact of comorbidities according to the Charlson Comorbidity Index on survival in this subset of women not suitable for surgery or who have refused it. This analysis demonstrates that this treatment is well‐tolerated; however, the prognosis is strongly impacted by age and comorbidities.     

Adjuvant bisphosphonate therapy in early‐stage breast cancer—Treating the soil to kill the seed

Bisphosphonates alter the tumor microenvironment, possibly preventing cancer cell growth in the bone. Analyses of data from numerous clinical trials and a large individual patient‐level data meta‐analysis have suggested an anti‐tumor effect for bisphosphonates in patients with early‐stage breast cancer who are postmenopausal. The absolute benefit from the use of bisphosphonates on breast cancer‐related mortality reduction mirrors that seen with the use of anthracycline‐based chemotherapy versus a first‐generation chemotherapy regimen (CMF). In this review, we discuss the evidence base for the use of adjuvant bisphosphonates in early‐stage breast cancer and provide recommendations for clinical use.     

Accelerated partial breast irradiation—Redefining the treatment target for women with early stage breast cancer

Following breast conserving surgery, the standard of care has been to deliver adjuvant radiation therapy directed to the whole breast (WBI) over a period of 3‐7 weeks. Over the past decade, increasing data have supported the concept that treatment to the whole breast may not be required in selected patients, allowing for the emergence of partial breast irradiation (PBI). Multiple randomized trials with 5‐10 years of follow‐up have been published documenting the safety and efficacy associated with PBI using multiple techniques. Questions that remain to be answered include (a) what is the optimal PBI technique for each clinical scenario, (b) are there additional patients that can be effectively managed with PBI approaches, and (c) are there different techniques/dose schedules that allow for further reduction in treatment duration and/or toxicities? Partial breast irradiation represents a standard approach for appropriately selected patients. PBI provides comparable clinical outcomes to WBI while allowing for a reduction in the duration treatment and the potential for reduced toxicities. Future studies may also help to better define which patients require no radiation, PBI, hypofractionated WBI or conventional WBI, based upon patient, clinical, pathologic features as well as potentially using tumor genetics.     

早期乳腺癌的保乳综合治疗疗效分析

目的　评价早期乳腺癌保乳综合治疗的疗效。方法　保乳组 92例 ,行保留乳房的肿瘤切除加腋窝淋巴结清扫术 ;对照组 60例 ,行乳癌改良根治术。术后给予放疗、全身化疗和 /或内分泌治疗。结果　平均随访 5 7个月 ,保乳组中无局部复发病例 ,3年生存率为 97.2 % ,5年生存率为 89.3 % ,远隔脏器转移率为 6.5 % ;对照组局部复发 2例 ,3年生存率为 97.5 % ,5年生存率为90 .1% ,远隔脏器转移率为 5 .0 % ,两组各指标对比无明显差异 (P >0 .0 5 )。结论　早期乳腺癌采用保乳综合疗法 ,可以达到与根治术相似的治疗效果 ,可作为首选方法     

术中定向放疗推量照射在乳腺癌保乳术中临床应用研究

目的 研究乳腺癌保乳手术联合IntraBeam术中放疗系统进行术中靶向瘤床推量放射治疗的可行性、安全性、有效性及美容效果。方法 共69例早期乳腺癌保乳手术患者接受了治疗,其中18.8%（13/69）患者年龄少于45岁,52.2%（36/69）肿物大于2 cm,40.6%（28/69）组织细胞学分级3级,29.0%（20/69）病人有淋巴结转移。病人保乳术后采用IntraBeam术中放疗系统瘤床表面20 Gy剂量进行术中靶向瘤床推量放射治疗,待化疗完成（或伤口愈合后）2周后给予传统全乳外照射放射疗治疗（50 Gy,共25次,省略瘤床推量照射）,评估患者近期疗效及不良反应。结果 总共27.5%（19/69）患者出现急性并发症,2.9%（2/69）患者出现血肿,8.7%（6/69）出现血清肿,7.2%（5/69）出现切口感染,8.7%（6/69）切口愈合延迟,切口中位愈合时间3.8（1.0~11）个月,中位随访24.8个月（12~51）,2.9%（2/69）患者出现同侧乳房内复发,未出现远处转移及死亡病例,乳房美容效果评估优、良者术后1年占89.9%,术后2年占89.7%。结论 乳腺癌保乳手术联合IntraBeam术中放疗系统进行术中靶向瘤床推量放射治疗近期疗效满意、不良反应较少,由于病人数量较少,随访时间较短,长远疗效仍需要进一步的验证。     

Initial outcomes with image‐guided partial breast irradiation delivered with intensity‐modulated radiation therapy

Patients were treated at a single institution to a dose of 30 Gy in five fractions delivered every other day using image‐guided intensity modulated radiation therapy (IMRT) partial breast irradiation. A total of 34 patients were treated with a median follow‐up of 4.6 months. The rate of acute Grade 1 dermatitis was 23.5% (n = 8), and Grade 1 fatigue was 17.6% (n = 6), with no Grade 2 or higher acute toxicities. The rate of chronic Grade 1 dermatitis was 25.0% (n = 6), Grade 1 fat necrosis 4.2% (n=1), with no patients demonstrating other chronic toxicities. Image‐guided APBI delivered with IMRT is associated with low rates of acute and chronic toxicity though additional follow‐up is warranted.     

Recurrent radiation recall dermatitis 40 years after radiation therapy for breast cancer

Radiation recall dermatitis is an inflammatory reaction of the skin, which occurs at previously irradiated areas, usually following a subsequent exposure to an aggravating factor. Recall dermatitis can occur weeks to months after radiation, and the longest duration between radiation and dermatitis has been reported to be about 25 years. Here, we report a case of recurrent radiation recall dermatitis that developed spontaneously after 40 years following radiation for breast cancer. This case suggests that radiation recall dermatitis can occur much later than previously reported. In spite of this late presentation, topical anti-inflammatory agents managed the condition well.     

Acute toxicities after proton beam therapy following breast‐conserving surgery for breast cancer: Multi‐institutional prospective PCG registry analysis

We investigated adverse events (AEs) and clinical outcomes for proton beam therapy (PBT) after breast‐conserving surgery (BCS) for breast cancer. From 2012 to 2016, 82 patients received PBT in the prospective multi‐institutional Proton Collaborative Group registry. AEs were recorded prospectively at each institution. Median follow‐up was 8.1 months. Median dose was 50.4 Gy in 28 fractions. Most patients received a lumpectomy bed boost (90%) and regional nodal irradiation (RNI)(83%). Six patients (7.3%) experienced grade 3 AEs (5 with dermatitis, 5 with breast pain). Body mass index (BMI) was associated with grade 3 dermatitis (P = .015). Fifty‐eight patients (70.7%) experienced grade ≥2 dermatitis. PBT including RNI after BCS is well‐tolerated. Elevated BMI is associated with grade 3 dermatitis.     

Effect of intraoperative radiotherapy for early breast cancer on 10‐year recurrence rates and overall survival

The aim of this study was to evaluate 10‐year local control and overall survival of IORT for early breast cancer treatment. We analyzed 68 patients submitted to breast conservative surgery and IORT, in the accelerator room of the Radiotherapy Service in South Brazil. In the long‐term follow‐up, we had 17.6% of patients with ipsilateral breast cancer recurrence, 2.9% with regional recurrence, 2.9% with contralateral breast recurrence, and 5.9% with distant metastasis. The 10‐year overall survival was 82.8%. Our data show high local recurrence rates, however, good overall survival in early breast cancer patients treated with breast‐conserving surgery and intraoperative radiotherapy with electron beams in the long‐term follow‐up.     

Proton beam therapy reirradiation for breast cancer: Multi‐institutional prospective PCG registry analysis

To investigate adverse events (AEs, CTCAE v4.0) and clinical outcomes for proton beam therapy (PBT) reirradiation (reRT) for breast cancer. From 2011 to 2016, 50 patients received PBT reRT for breast cancer in the prospective Proton Collaborative Group (PCG) registry. Acute AEs occurred within 180 days from start of reRT. Late AEs began or persisted beyond 180 days. Fisher's exact and Mann‐Whitney rank‐sum tests were utilized. Kaplan‐Meier methods were used to estimate overall survival (OS) and local recurrence‐free survival (LFRS). Median follow‐up was 12.7 months (0‐41.8). Median prior RT dose was 60 Gy (10‐96.7). Median reRT dose was 55.1 Gy (45.1‐76.3). Median cumulative dose was 110.6 Gy (70.6‐156.8). Median interval between RT courses was 103.8 months (5.5‐430.8). ReRT included regional nodes in 84% (66% internal mammary node [IMN]). Surgery included the following: 44% mastectomy, 22% wide local excision, 6% lumpectomy, 2% reduction mammoplasty, and 26% no surgery. Grade 3 AEs were experienced by 16% of patients (10% acute, 8% late) and were associated with body mass index (BMI) > 30 kg/m² (P = 0.04), bilateral recurrence (P = 0.02), and bilateral reRT (P = 0.004). All grade 3 AEs occurred in patients receiving IMN reRT (P = 0.08). At 1 year, LRFS was 93%, and OS was 97%. Patients with gross disease at time of PBT trended toward worse 1‐year LRFS (100% without vs. 84% with, P = 0.06). PBT reRT is well tolerated with favorable local control. BMI > 30, bilateral disease, and IMN reRT were associated with grade 3 AEs. Toxicity was acceptable despite median cumulative dose > 110 Gy.     

The efficacy and safety of hypofractionated radiotherapy with concurrent anti‐HER‐2 therapy following breast‐conserving therapy for breast cancer

The purpose of this study was to report rates and severities of radiation‐related toxicities and analyze disease‐control outcomes in patients who have received hypofractionated whole breast radiation (HF) with concurrent trastuzumab with or without pertuzumab. We conducted a retrospective cohort study including women with stage I‐III HER2‐positive breast cancer who received HF at the University of Pennsylvania between 1/2005 and 5/2018 with concurrent trastuzumab with or without pertuzumab. Fractionation was 266 cGy daily to a total dose of 4256 cGy with or without a sequential tumor bed boost. Eighty patients were included in the cohort with a median follow‐up time of 21.44 months. There was one grade 3 acute toxicity (fatigue) and no grade 3 late toxicities. 91% and 25% of patients experienced grade 1‐2 acute and late skin reactions, respectively. An excellent‐good cosmetic outcome was reported by 74% and 95% of patients and physicians, respectively. No patients experienced tumor recurrences, and the only death was due to a secondary cause. These results suggest that hypofractionated whole breast radiation administered concurrently with anti‐HER‐2 therapies is efficacious and has acceptable toxicity in early‐stage breast cancer patients treated with lumpectomy. Continued follow‐up is warranted to evaluate long‐term outcomes.