Early-stage Breast Cancer: Tailored External Beam Fractionation Approaches for Treatment of the Whole or Partial Breast.

Historically, radiotherapy fractionation for early-stage breast cancer primarily consisted of 1.8-2 Gy per fraction given once daily to a total dose of 45-66 Gy over 5-7 weeks for whole breast treatment. Partial breast treatment employed larger dose per fraction (3.4-3.85 Gy) in 10 fractions given twice daily over 1 week. Radiobiologically, breast cancer is increasingly appreciated as a low alpha-beta ratio malignancy that is best treated with larger dose per fraction. Over the past 10 years, there have been increasing data from multiple large randomized clinical trials that support the use of shorter treatment courses: first hypofractionated regimens consisting of 15-20 treatments, and more recently, ultra-hypofractionated regimens as short as 5 treatments. Simultaneously, data from modern partial breast irradiation (PBI) trials support once daily treatment regimens ranging from 1-5 treatments. Shorter treatment courses represent less treatment burden on patients, reduced financial impact, and potentially improved access to care for patients with transportation and/or socioeconomic barriers. Here we review the evolution of whole and partial breast treatment regimens for early-stage breast cancer.

Utilization of neoadjuvant chemotherapy in high-risk, node-negative early breast cancer.

BACKGROUND: Controversy exists regarding the optimal sequence of chemotherapy among women with operable node-negative breast cancers with high-risk tumor biology. We evaluated national patterns of neoadjuvant chemotherapy (NACT) use among women with early-stage HER2+, triple-negative (TNBC), and high-risk hormone receptor-positive (HR+) invasive breast cancers. METHODS: Women ≥18 years with cT1-2/cN0 HER2+, TNBC, or high recurrence risk score (≥31) HR+ invasive breast cancers who received chemotherapy were identified in the National Cancer Database (2010-2016). Cochran-Armitage and logistic regression examined temporal trends and likelihood of undergoing NACT versus adjuvant chemotherapy based on patient age and molecular subtype. RESULTS: Overall, 96,622 patients met study criteria; 25% received NACT and 75% underwent surgery first, with comparable 5-year estimates of overall survival (0.90, 95% CI 0.892-0.905 vs 0.91, 95% CI 0.907-0.913). During the study period, utilization of NACT increased from 14% to 36% and varied according to molecular subtype (year*molecular subtype p < 0.001, p-corrected < 0.001). Women with HER2+ (OR 4.17, 95% CI 3.70-4.60, p < 0.001, p-corrected < 0.001) and TNBC (OR 3.81, 95% CI 3.38-4.31, p < 0.001, p-corrected < 0.001) were more likely to receive NACT over time, without a change in use among those with HR+ disease (OR 1.58, 95% CI 0.88-2.87, p = 0.13, p-corrected = 0.17). CONCLUSION: Among women with early-stage triple-negative and HER2+ breast cancers, utilization of NACT increased over time, a trend that correlates with previously reported improved rates of pCR and options post-neoadjuvant treatment with residual disease. Future research is needed to better understand multidisciplinary decisions for NACT and implications for breast cancer patients.

Optimizing Adjuvant Treatment Recommendations for Older Women with Biologically Favorable Breast Cancer: Short-Course Radiation or Long-Course Endocrine Therapy?

Omission of radiotherapy among older women taking 5 years of adjuvant endocrine therapy following breast conserving surgery for early-stage, hormone sensitive breast cancers is well-studied. However, endocrine therapy toxicities are significant, and many women have difficulty tolerating endocrine therapy, particularly elderly patients with comorbidities. Omission of endocrine therapy among women receiving adjuvant radiation is less well-studied, but available randomized and non-randomized data suggest that this approach may confer equivalent local control and survival for select patients. Herein we review available randomized and non-randomized outcome data for women treated with radiation monotherapy and emphasize the need for future prospective, randomized studies of endocrine therapy omission.

Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.

Overall health at diagnosis predicts the risk of complications within the first year after breast cancer diagnosis.

PURPOSE: Breast cancer patients with overall poor health are at a greater risk of both complications during treatment and mortality from competing causes. We sought to determine the association of pre-existing comorbidities on treatment-related complications and overall survival. METHODS: We identified women ages 40-90 years old from our institutional registry with stage I-II invasive breast cancer from 2005 to 2014. Recursive partitioning was used to stratify women based on pre-existing comorbidities as low, moderate, or high risk of treatment-associated complications. Cox proportional hazards model was constructed to estimate the association of risk with overall survival. RESULTS: 2077 women were studied. Mean age was 60 (IQR 51-68). Over half (54%) had ≥ 1 comorbid condition, and 29% experienced at least one adverse medical event within 1 year of diagnosis. Risk categories included low (no comorbidities or hypertension), moderate (combinations of comorbidities excluding congestive heart failure), and high (congestive heart failure in isolation or in combination with other conditions). High-risk women had a lower 10-year OS compared to moderate- or low-risk women (89% vs 90% vs 96%, log-rank p < 0.001). After adjustment, being at moderate (HR 2.20, 95% CI 1.30-3.72, p = 0.003) or high risk (HR 5.07, 95% CI 1.66-15.52, p = 0.004) of adverse sequelae was associated with reduced OS compared to those at low risk of these adverse medical events. CONCLUSIONS: Following breast cancer diagnosis, overall poor health was associated with a greater risk of mortality and complications within the first year of treatment, which was driven by a pre-existing diagnosis of congestive heart failure.

Immediate Breast Reconstruction Allows for the Timely Initiation of Postmastectomy Radiation Therapy.

BACKGROUND: Complications from breast reconstruction may delay postmastectomy radiation therapy and impact breast cancer outcomes. The authors hypothesized that immediate breast reconstruction may be associated with delays in the initiation of radiation, but that this delay would not significantly impact overall patient survival. METHODS: Using the National Cancer Database, the authors identified women with breast cancer who underwent mastectomy and received postmastectomy radiation therapy. Delayed radiation was defined as treatment initiated 6 months or more after surgery in patients who received adjuvant chemotherapy or 12 weeks or more after surgery in patients who received neoadjuvant or no chemotherapy. RESULTS: Women undergoing breast reconstruction had an increased time to postmastectomy radiation therapy, 154 days versus 132 days (p < 0.001), and were more likely to experience a delay in initiating radiation (OR, 1.25; 95 percent CI, 1.188 to 1.314). Other factors associated with delayed radiation included increased Charlson/Deyo scores, neoadjuvant chemotherapy, nonprivate insurance, and black race. Cox proportional hazards models revealed no evidence of a reduced adjusted overall survival in the immediate breast reconstruction group (hazard ratio, 0.836; 95 percent CI, 0.802 to 0.871; p < 0.001). Restricted cubic spline analysis identified the threshold number of days at which the start of radiation began to impact survival at 169 days (95 percent CI, 160 to 190 days), 75 days (95 percent CI, 42 to 90 days), and 71 days (95 percent CI, 41 to 90 days) in patients undergoing adjuvant, neoadjuvant, and no chemotherapy, respectively. CONCLUSION: Immediate breast reconstruction is associated with a modest delay in initiating postmastectomy radiation therapy but does not impact overall survival. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Goal-Driven Beam Setting Optimization for Whole-Breast Radiation Therapy.

PURPOSE: To develop an automated optimization program to generate optimal beam settings for whole-breast radiation therapy driven by clinically oriented goals. MATERIALS AND METHODS: Forty patients were retrospectively included in this study. Each patient's planning images, contoured structures of planning target volumes, organs-at-risk, and breast wires were used to optimize for patient-specific-beam settings. Two beam geometries were available tangential beams only and tangential plus supraclavicular beams. Beam parameters included isocenter position, gantry, collimator, couch angles, and multileaf collimator shape. A geometry-based goal function was defined to determine such beam parameters to minimize out-of-field target volume and in-field ipsilateral lung volume. For each geometry, the weighting in the goal function was trained with 10 plans and tested on 10 additional plans. For each query patient, the optimal beam setting was searched for different gantry-isocenter pairs. Optimal fluence maps were generated by an in-house automatic fluence optimization program for target coverage and homogeneous dose distribution, and dose calculation was performed in Eclipse. Automatically generated plans were compared with manually generated plans for target coverage and lung and heart sparing. RESULTS: The program successfully produced a set of beam parameters for every patient. Beam optimization time ranged from 10 to 120 s. The automatic plans had overall comparable plan quality to manually generated plans. For all testing cases, the mean target V95% was 91.0% for the automatic plans and 88.5% for manually generated plans. The mean ipsilateral lung V20Gy was lower for the automatic plans (15.2% vs 17.9%). The heart mean dose, maximum dose of the body, and conformity index were all comparable. CONCLUSION: We developed an automated goal-driven beam setting optimization program for whole-breast radiation therapy. It provides clinically relevant solutions based on previous clinical practice as well as patient specific anatomy on a substantially faster time frame.

Surgical Resection of the Primary Tumor in Women With De Novo Stage IV Breast Cancer: Contemporary Practice Patterns and Survival Analysis.

OBJECTIVE: We evaluated patterns of surgical care and their association with overall survival among a contemporary cohort of women with stage IV breast cancer. BACKGROUND: Surgical resection of the primary tumor remains controversial among women with stage IV breast cancer. METHODS: Women diagnosed with clinical stage IV breast cancer from 2003 to 2012 were identified from the American College of Surgeons National Cancer Database. Those with intact primary tumors who were alive 12 months after diagnosis were categorized by treatment sequence: (1) surgery before systemic therapy, (2) systemic therapy before surgery, and (3) systemic therapy alone. Multivariate logistic regression was used to estimate the association of treatment sequence with surgery type. Overall survival was estimated using multivariate Cox proportional hazards models. RESULTS: Among 24,015 women, 56.2% (13,505) underwent systemic therapy alone and 43.8% (10,510) underwent surgical resection. Rates of surgery decreased slightly over time (43.1% in 2003 to 41.9% in 2011). Treatment with systemic therapy before surgery was associated with larger tumor size (median 4.5 vs 3.1 cm, P < 0.001) and receipt of mastectomy (81.4% vs 52.2%, P < 0.001) when compared to those who underwent surgery first. Receipt of surgery, whether before or after systemic therapy (Hazard Ratio, 0.68; 95% confidence interval, 0.62-0.73; Hazard Ratio, 0.56; 95% confidence interval, 0.52-0.61; P < 0.001), was independently associated with improved adjusted overall survival when compared to systemic therapy alone. CONCLUSIONS: Surgical resection of the primary tumor occurs in almost half of women with stage IV breast cancer alive 1 year after diagnosis, and is increasingly occurring after systemic therapy. Coordinated multidisciplinary care remains highly relevant in the setting of metastatic breast cancer, where surgical decisions should be made on an individual basis and may affect survival in select women.

The Association of Extent of Axillary Surgery and Survival in Women with N2-3 Invasive Breast Cancer.

BACKGROUND: Although surgical management of the axilla for breast cancer continues to evolve, axillary lymphadenectomy remains the standard of care for women with advanced nodal disease. We sought to evaluate national patterns of care in axillary surgery, and its association with overall survival (OS) among women with N2-3 invasive breast cancer. METHODS: Women (18-90 years) with clinical N2-3 invasive breast cancer who underwent axillary surgery were identified from the National Cancer Data Base (NCDB) from 2004 to 2013. Axillary surgery was categorized as sentinel lymph node biopsy (SLNB, 1-5 nodes) or axillary lymph node dissection (ALND, ≥ 10 nodes). Patient and treatment characteristics, trends over time, and overall survival (OS) were compared by surgical treatment. RESULTS: Overall, 22,156 patients were identified. At diagnosis, 68.5% had cN2 and 31.5% had cN3 disease. Treatment included: lumpectomy (27%), mastectomy (73%), adjuvant chemotherapy (53.4%), neoadjuvant chemotherapy (NAC) (39.7%), radiation (74%), and endocrine therapy (54.4%). In total, 9.9% (n = 2190) underwent SLNB and 90.1% (n = 19,966) underwent ALND. Receipt of SLNB was associated with private insurance, grade 3 disease, invasive ductal cancer, NAC, and lumpectomy (all p < 0.001). After adjustment for known covariates, including chemotherapy use, ALND was associated with improved survival [hazard ratio (HR) 0.68, p < 0.001] and this effect was similar for N2 and N3 patients (axillary surgery × cN-stage interaction p = 0.29). CONCLUSIONS: Axillary lymphadenectomy was associated with improved survival in patients presenting with clinical N2-3 invasive breast cancer. Further studies, particularly in the neoadjuvant setting, are needed to identify breast cancer patients with advanced nodal disease who may safely avoid a lesser extent of axillary surgery.

The Effect of Hospital Volume on Breast Cancer Mortality.

OBJECTIVE: The aim of this study was to determine whether hospital volume was associated with mortality in breast cancer, and what thresholds of case volume impacted survival. BACKGROUND: Prior literature has demonstrated improved survival with treatment at high volume centers among less common cancers requiring technically complex surgery. METHODS: All adults (18 to 90 years) with stages 0-III unilateral breast cancer diagnosed from 2004 to 2012 were identified from the American College of Surgeons National Cancer Data Base (NCDB). A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital volume and overall survival, after adjusting for measured covariates. Intergroup comparisons of patient and treatment characteristics were conducted with X and analysis of variance (ANOVA). The log-rank test was used to test survival differences between groups. A multivariable Cox proportional hazards model was used to estimate hazard ratios (HRs) associated with each volume group. RESULTS: One million sixty-four thousand two hundred and fifty-one patients met inclusion criteria. The median age of the sample was 60 (interquartile range 50 to 70). Hospitals were categorized into 3 groups using restricted cubic spline analysis: low-volume (<148 cases/year), moderate-volume (148 to 298 cases/year), and high-volume (>298 cases/year). Treatment at high volume centers was associated with an 11% reduction in overall mortality for all patients (HR 0.89); those with stage 0-I, ER+/PR+ or ER+/PR- breast cancers derived the greatest benefit. CONCLUSIONS: Treatment at high volume centers is associated with improved survival for breast cancer patients regardless of stage. High case volume could serve as a proxy for the institutional infrastructure required to deliver complex multidisciplinary breast cancer treatment.

Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011.

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial established the safety of omitting axillary lymph node dissection (ALND) for early-stage breast cancer patients with limited nodal disease undergoing lumpectomy. We examined the extent of axillary surgery among women eligible for Z0011 based on patient age and tumor subtype. METHODS: Patients with cT1-2, cN0 breast cancers and one or two positive nodes diagnosed from 2009 to 2014 and treated with lumpectomy were identified in the National Cancer Data Base. Sentinel lymph node biopsy (SLNB) was defined as the removal of 1-5 nodes and ALND as the removal of 10 nodes or more. Tumor subtype was categorized as luminal, human epidermal growth factor 2-positive (HER2+), or triple-negative. Logistic regression was used to estimate the odds of receiving SLNB alone versus ALND. RESULTS: The inclusion criteria were met by 28,631 patients (21,029 SLNB-alone and 7602 ALND patients). Patients 70 years of age or older were more likely to undergo SLNB alone than ALND (27.0% vs 20.1%; p < 0.001). The radiation therapy use rate was 89.4% after SLNB alone and 89.7% after ALND. In the multivariate analysis, the uptake of Z0011 recommendations increased over time (2014 vs 2009: odds ratio [OR] 13.02; p < 0.001). Younger patients were less likely to undergo SLNB alone than older patients (age <40 vs ≥70: OR 0.59; p < 0.001). Patients with HER2+ (OR 0.89) or triple-negative disease (OR 0.79) (p < 0.001) were less likely to undergo SLNB alone than those with luminal subtypes. CONCLUSIONS: Among women potentially eligible for ACOSOG Z0011, the use of SLNB alone increased over time in all groups, but the extent of axillary surgery differed by patient age and tumor subtype.

Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer.

INTRODUCTION: Breast cancer treatment costs are rising, and identification of high-value oncology treatment strategies is increasingly needed. We sought to determine the potential cost savings associated with an evidence-based radiation treatment (RT) approach among women with early-stage breast cancer treated in the United States. PATIENTS AND METHODS: Using the National Cancer Database, we identified women with T1-T2 N0 invasive breast cancers treated with lumpectomy during 2011. Adjuvant RT regimens were categorized as conventionally fractionated whole-breast irradiation, hypofractionated whole-breast irradiation, and omission of RT. National RT patterns were determined, and RT costs were estimated using the Medicare Physician Fee Schedule. RESULTS: Within the 43,247 patient cohort, 64% (n = 27,697) received conventional RT, 13.3% (n = 5,724) received hypofractionated RT, 1.1% (n = 477) received accelerated partial-breast irradiation, and 21.6% (n = 9,349) received no RT. Among patients who were eligible for shorter RT or omission of RT, 57% underwent treatment with longer, more costly regimens. Estimated RT expenditures of the national cohort approximated $420.2 million during 2011, compared with $256.2 million had women been treated with the least expensive regimens for which they were safely eligible. This demonstrated a potential annual savings of $164.0 million, a 39% reduction in associated treatment costs. CONCLUSION: Among women with early-stage breast cancer after lumpectomy, use of an evidence-based approach illustrates an example of high-value care within oncology. Identification of high-value cancer treatment strategies is critically important to maintaining excellence in cancer care while reducing health care expenditures.

Biological Subtype Predicts Risk of Locoregional Recurrence After Mastectomy and Impact of Postmastectomy Radiation in a Large National Database.

PURPOSE: To evaluate locoregional recurrence (LRR) after mastectomy and impact of postmastectomy radiation (PMRT) by breast cancer subtype. METHODS AND MATERIALS: Between 2000 and 2009, 5673 patients with stage I to III breast carcinoma underwent mastectomy and nodal evaluation; 30% received PMRT. Isolated LRR (iLRR) and LRR were compared across groups defined by biological subtype and receipt of trastuzumab: luminal A (estrogen [ER]/progesterone [PR]+, HER2-, low/intermediate grade), luminal B (ER/PR+, HER2-, high grade), HER2 with trastuzumab, HER2 without trastuzumab, and triple negative (TN; ER-, PR-, HER2-). LRR hazard ratios (HR) were estimated with multivariable Fine and Gray models. The effect of PMRT on LRR was evaluated with Fine and Gray models stratified by propensity for PMRT. RESULTS: With a median follow-up time of 50.1 months, there were 19 iLRR and 109 LRR events. HER2 patients with trastuzumab had no iLRR and only a single LRR. Compared with luminal A patients, TN patients had significantly greater adjusted risk of iLRR (HR 14.10; 95% CI 2.97%-66.90%), with a similar trend among luminal B (HR 4.94; 95% CI 0.94%-25.82%) and HER2 patients without trastuzumab (HR 4.41; 95% CI 0.61%-32.11%). Although PMRT reduced LRR, the effect of PMRT varied by subgroup, with the greatest and smallest effects seen among luminal A (HR 0.17; 95% CI 0.05%-0.62%) and TN patients (HR 0.59; 95% CI 0.25%-1.35%), respectively. CONCLUSIONS: TN patients had the highest risk of LRR and the least benefit from PMRT; these patients may benefit from alternative treatment strategies. In contrast, in the era of HER2-directed therapy, the role of local therapy may need to be reassessed among HER2 patients.

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers.

PURPOSE: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. METHODS AND MATERIALS: Women aged ≥55 years with clinically node-negative, estrogen receptor-positive, and/or progesterone receptor-positive HER2-, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. RESULTS: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. CONCLUSIONS: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.

A phase 1 trial of preoperative partial breast radiation therapy: Patient selection, target delineation, and dose delivery.

PURPOSE: Diffusion of accelerated partial breast irradiation into clinical practice is limited by the need for specialized equipment and training. The accessible external beam technique yields unacceptable complication rates, likely from large postoperative target volumes. We designed a phase 1 trial evaluating preoperative radiation therapy to the intact tumor using widely available technology. METHODS AND MATERIALS: Patients received 15, 18, or 21 Gy in a single fraction to the breast tumor plus margin. Magnetic resonance imaging (MRI) was used in conjunction with standard computed tomography (CT)-based planning to identify contrast enhancing tumor. Skin markers and an intratumor biopsy marker were used for verification during treatment. RESULTS: MRI imaging was critical for target delineation because not all breast tumors were reliably identified on CT scan. Breast shape differences were consistently seen between CT and MRI but did not impede image registration or tumor identification. Target volumes were markedly smaller than historical postoperative volumes, and normal tissue constraints were easily met. A biopsy marker within the breast proved sufficient for setup localization. CONCLUSIONS: This single fraction linear accelerator-based partial breast irradiation approach can be easily incorporated at most treatment centers. In vivo targeting may improve accuracy and can reduce the dose to normal tissues.

Exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy.

PURPOSE: Radiation therapy is associated with acute treatment-related complications that can lead to decreased quality of life (QOL). Exercise has been shown in other cancer treatment settings to improve negative outcomes. We conducted a prospective pilot study to explore the association between exercise, patient-reported outcomes, and acute radiation therapy toxicities. METHODS AND MATERIALS: Women receiving curative breast radiation therapy were enrolled. Each patient completed an exercise behavior/QOL survey before or during the first week of treatment and again during the last week of treatment. Exercise behavior was quantified with the Godin Leisure Time Exercise Questionnaire (metabolic equivalent [MET] hours per week). Measurements to evaluate upper extremity lymphedema and shoulder range of motion were completed. Skin toxicity was assessed weekly. Patient-reported outcomes were measured using standardized questionnaires. RESULTS: Forty-five patients were enrolled. Mean patient age was 54 (range, 28-73) years. Mean METs in the exercise cohort (≥9 METs/wk) was 21 per week (range, 11-38, n = 14); 3 per week (range, 0-8, n = 25) in the nonexercise cohort (<9 METs/wk). Women in the exercise cohort showed improvements in treatment-induced quality of life and fatigue (not significant) despite more extensive surgical, medical, and radiation treatment. No differences in treatment-related toxicities, pain, or sleep scores were noted. Lymphedema was mild (<3 cm) in the entire patient cohort. CONCLUSIONS: The vast majority of current exercise oncology literature implicates physical activity as an independent predictor of QOL in cancer patients. Our study noted similar trends, but they were not statistically significant. This may be due to our finding that patient-reported outcomes with radiation therapy are relatively high compared with other treatment modalities and remain stable throughout treatment. Thus, it may be that radiation therapy has a limited impact on QOL in breast cancer patients. Exercise may be best used as a targeted therapy in patients at high risk for poor QOL or radiation-related toxicities at baseline.

The use of adjuvant radiotherapy in elderly patients with early-stage breast cancer: changes in practice patterns after publication of Cancer and Leukemia Group B 9343.

BACKGROUND: The Cancer and Leukemia Group B (CALGB) 9343 randomized phase 3 trial established lumpectomy and adjuvant therapy with tamoxifen alone, rather than both radiotherapy and tamoxifen, as a reasonable treatment course for women aged >70 years with clinical stage I (AJCC 7th edition), estrogen receptor-positive breast cancer. An analysis of the Surveillance, Epidemiology, and End Results (SEER) registry was undertaken to assess practice patterns before and after the publication of this landmark study. METHODS: The SEER database from 2000 to 2009 was used to identify 40,583 women aged ≥70 years who were treated with breast-conserving surgery for clinical stage I, estrogen receptor-positive and/or progesterone receptor-positive breast cancer. The percentage of patients receiving radiotherapy and the type of radiotherapy delivered was assessed over time. Administration of radiotherapy was further assessed across age groups; SEER cohort; and tumor size, grade, and laterality. RESULTS: Approximately 68.6% of patients treated between 2000 and 2004 compared with 61.7% of patients who were treated between 2005 and 2009 received some form of adjuvant radiotherapy (P < .001). Coinciding with a decline in the use of external beam radiotherapy, there was an increase in the use of implant radiotherapy from 1.4% between 2000 and 2004 to 6.2% between 2005 to 2009 (P < .001). There were significant reductions in the frequency of radiotherapy delivery over time across age groups, tumor size, and tumor grade and regardless of laterality (P < .001 for all). CONCLUSIONS: Randomized phase 3 data support the omission of adjuvant radiotherapy in elderly women with early-stage breast cancer. Analysis of practice patterns before and after the publication of these data indicates a significant decline in radiotherapy use; however, nearly two-thirds of women continue to receive adjuvant radiotherapy.