Guideline-Concordant Surgical Care for Lobular Versus Ductal Inflammatory Breast Cancer.

INTRODUCTION: Quality of surgical care is understudied for lobular inflammatory breast cancer (IBC), which is less common, more chemotherapy-resistant, and more mammographically occult than ductal IBC. We compared guideline-concordant surgery (modified radical mastectomy [MRM] without immediate reconstruction following chemotherapy) for lobular versus ductal IBC. METHODS:  Female individuals with cT4dM0 lobular and ductal IBC were identified in the National Cancer Database (NCDB) from 2010-2019. Modified radical mastectomy receipt was identified via codes for "modified radical mastectomy" or "mastectomy" and "≥10 lymph nodes removed" (proxy for axillary lymph node dissection). Descriptive statistics, chi-square tests, and t-tests were used. RESULTS: A total of 1456 lobular and 10,445 ductal IBC patients were identified; 599 (41.1%) with lobular and 4859 (46.5%) with ductal IBC underwent MRMs (p = 0.001). Patients with lobular IBC included a higher proportion of individuals with cN0 disease (20.5% lobular vs. 13.7% ductal) and no lymph nodes examined at surgery (31.2% vs. 24.5%) but were less likely to be node-negative at surgery (12.7% vs. 17.1%, all p < 0.001). Among those who had lymph nodes removed at surgery, patients with lobular IBC also had fewer lymph nodes excised versus patients with ductal IBC (median [interquartile range], 7 (0-15) vs. 9 (0-17), p = 0.001). CONCLUSIONS: Lobular IBC patients were more likely to present with node-negative disease and less likely to be node-negative at surgery, despite having fewer, and more frequently no, lymph nodes examined versus ductal IBC patients. Future studies should investigate whether these treatment disparities are because of surgical approach, pathologic assessment, and/or data quality as captured in the NCDB.

Temporal Trends and Factors Associated with Receipt of Post-mastectomy Radiation After Neoadjuvant Chemotherapy in Women with cT3 Breast Cancer.

INTRODUCTION: Given the potential impact of increasingly effective neoadjuvant chemotherapy (NACT) on post-mastectomy radiotherapy (PMRT) recommendations, we examined temporal trends in post-NACT PMRT for cT3 breast cancer. METHODS: We identified women ≥ 18 years in the National Cancer Database (NCDB) diagnosed 2004-2019 with cT3N0-1M0 breast cancer treated with chemotherapy and mastectomy. Multivariable logistic regression and Cox proportional hazards models were used to estimate associations between pathologic NACT response [complete response (CR), partial response (PR), or no response (NR); or disease progression (DP)] and PMRT and between PMRT and overall survival (OS), respectively. RESULTS: We identified 39,901 women (Asian/Pacific Islander 1731, Black 5875, Hispanic 3265, White 27,303). Among cN0 patients with CR, PMRT rates declined from 67% in 2004 to 35% in 2019 but remained unchanged for patients with DP. Relative to NR, CR [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.29-0.46] and PR (OR 0.44, 95% CI 0.36-0.55) in cN0 patients were associated with lower odds of PMRT while DP (OR 1.33, 95% CI 1.05-1.69) was associated with higher odds. Among cN1 patients, PMRT rates decreased from 90% to 73% for CR between 2005 and 2019 and increased from 76% to 82% for DP between 2004 and 2019. Relative to NR, CR (OR 0.78, 95% CI 0.63-0.95) was associated with lower odds of PMRT while DP (OR 1.93, 95% CI 1.58-2.37) was associated with higher odds. PMRT was associated with improved OS among cN1 patients (hazard ratio (HR) 0.77, 95% CI 0.67-0.88). CONCLUSION: CR was associated with decreased PMRT receipt over time, while temporal trends following PR and DP differed by cN status, suggesting that nodal involvement guided PMRT receipt more than in-breast disease.

Immediate Breast Reconstruction for Inflammatory Breast Cancer: Trends in Use and Clinical Outcomes 2004-2016.

INTRODUCTION: National guidelines specify against immediate breast reconstruction (IBR) among inflammatory breast cancer (IBC) patients. However, limited data exist regarding this practice. We report practice patterns and oncologic outcomes among nonmetastatic IBC patients receiving trimodality therapy, with or without IBR. METHODS: Using the National Cancer Database, we identified nonmetastatic IBC patients treated with trimodality therapy from 2004 to 2016. Primary outcome was overall survival (OS), assessed on unadjusted analysis using Kaplan-Meier estimates and on adjusted analysis using multivariable Cox proportional hazards and inverse probability weighting (IPW) models. OS analysis was also conducted with propensity score matched (PSM) cohorts. Secondary outcomes included IBR utilization rates, time to postmastectomy radiotherapy (PMRT), and surgical outcomes. RESULTS: 6589 women were included, including 5954 (90.4%) non-reconstructed and 635 (9.6%) IBR. Among IBR recipients, 250 (39.4%) underwent autologous reconstruction, 171 (26.9%) underwent implant-based reconstruction, and 214 (33.7%) unspecified. IBR utilization increased from 6.3% to 10.1% from 2004 to 2016 at a 4% average annual growth rate (P < 0.001). Median follow-up was 43 and 45 months for IBR and non-reconstructed patients, respectively (P = 0.29). On Cox multivariable analysis, IBR was associated with improved OS (HR 0.63, 95% CI 0.44-0.90, P = 0.01), but this association was not significant on IPW analysis (P = 0.06). In PSM cohorts, this association remained significant (HR 0.60, 95% CI 0.40-0.92, P = 0.02). Margin status, time to PMRT, 30-day readmission, and 30-/90-day mortality did not differ between groups (all P > 0.05). CONCLUSION: Although not endorsed by national guidelines, IBR is increasing among IBC patients; however, more granular data are needed to determine oncologic safety.

Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome.

PURPOSE: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy. METHODS: A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses. RESULTS: We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the control cohort. CONCLUSIONS: We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients.

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.

Comparison of acute toxicities between contemporary forward-planned 3D conformal radiotherapy and inverse-planned intensity-modulated radiotherapy for whole breast radiation.

The use of inverse-planned intensity-modulated radiation therapy for whole breast radiation treatment has become more prevalent, but this may impose an increased cost on the health system. We hypothesized that when applied with the same treatment planning goals, tangential forward-planned field-in-field 3D conformal radiotherapy and tangential inverse-planned intensity-modulated radiotherapy would be associated with comparable toxicities. Women who underwent tangential whole breast irradiation at our institution from 2011 to 2015 planned using either forward-planned field-in-field 3D conformal radiotherapy or intensity-modulated radiotherapy were retrospectively analyzed. Grade 2+ Radiation dermatitis was the primary endpoint. A total of 201 and 212 women had undergone field-in-field 3D conformal radiotherapy and intensity-modulated radiotherapy, respectively. No differences were observed between the two modalities regarding acute radiation dermatitis, breast pain, or fatigue. In a multivariable logistic regression that incorporated the use of boost, hypofractionation, use of chemotherapy, patient positioning, use of a supraclavicular field, and breast planning target volume, intensity-modulated radiotherapy was not correlated with different rates of Grade 2+ radiation dermatitis. This study supports the routine first-line use of field-in-field 3D conformal radiotherapy for whole breast radiation instead of tangential intensity-modulated radiotherapy from the standpoint of equivalence in acute toxicity. Further investigation is needed to assess whether there are subgroups of women who may still benefit from intensity-modulated radiotherapy.

No impact of breast magnetic resonance imaging on 15-year outcomes in patients with ductal carcinoma in situ or early-stage invasive breast cancer managed with breast conservation therapy.

BACKGROUND: For women undergoing breast conservation therapy (BCT), the added value of breast magnetic resonance imaging (MRI) at the time of initial diagnosis remains controversial. The current study was performed to determine long-term outcomes after BCT for women with and without pretreatment breast MRI. METHODS: Between 1992 and 2001, a total of 755 women with ductal carcinoma in situ or early-stage invasive breast cancer underwent breast-conserving surgery (with axillary lymph node staging for invasive carcinoma) followed by definitive breast radiotherapy. Evaluation at the time of the initial diagnosis included conventional mammography in all subjects and breast MRI in 215 women (28%). Clinical, pathologic, and treatment characteristics were comparable for patients with and without breast MRI. Outcomes were determined using the Kaplan-Meier method and compared using the log-rank method. RESULTS: At a median follow-up of 13.8 years, there were 49 local failures (15 women with and 34 women without breast MRI, respectively). The 15-year local failure rates were 8% for women with and 8% for women without MRI (P = .59). There also were no differences noted between women with and without breast MRI with regard to 15-year rates of overall survival (77% vs 71%; P = .24), freedom from distant metastases (86% vs 90%; P = .08), and contralateral breast cancer (10% vs 8%; P = .10). Multivariate analysis demonstrated no significant impact of breast MRI on local failure (P = .96). CONCLUSIONS: Breast MRI during the initial evaluation for BCT appears to have no significant impact on 15-year rates for local control, overall survival, freedom from distant metastases, or contralateral breast cancer. The routine use of pretreatment breast MRI is not indicated for patients undergoing BCT. Cancer 2017;123:1324-1332. © 2016 American Cancer Society.

The Timing of Breast Irradiation in Two-Stage Expander/Implant Breast Reconstruction.

Certain patients who initiate expander/implant (E/I) reconstruction following mastectomy may require radiation therapy (XRT). XRT may be delivered during the tissue expander (TE) expansion process or after exchange for a permanent implant (PI). We studied a series of women treated with E/I reconstruction and XRT to determine whether there is a difference in complication rates between those who had XRT to the TE versus PI. All two-stage E/I reconstructions at our institution from April 2005 to January 2013 were reviewed to identify patients who underwent XRT after TE placement. Our database was queried for reconstructive details, oncologic treatment, and complications. Statistical analyses were performed to establish significance of complication rate differences. Fifty-two patients underwent XRT after TE placement, 42 of which had XRT to the TE and 11 of which had XRT to the PI. The major complication rates (complications requiring emergent reoperation/readmission) were 27% versus 0% (p = 0.05) for XRT to the TE versus XRT to the PI, but there were no significant differences in minor complication rates (outpatient complications). Specifically, the rates of Grade 3/4 capsular contracture were similar between the two groups, 27% for the XRT to the TE group and 36% for the XRT to the PI group. Radiation of the PI versus radiation of the TE did not result in significant differences in overall surgical complication rates but had fewer major complications and no implant failures. Other factors must also be considered, such as patient preference, risk of cancer reoccurrence, and cosmesis. It is essential for a patient to have a team of a plastic surgeon and radiation, surgical, and medical oncologists working together to achieve each patient's goals.

ACR Appropriateness Criteria® Ductal Carcinoma in Situ.

Ductal carcinoma in situ (DCIS) is a breast neoplasm with potential for progression to invasive cancer. Management commonly involves excision, radiotherapy, and hormonal therapy. Surgical assessment of regional lymph nodes is rarely indicated except in cases of microinvasion or mastectomy. Radiotherapy is employed for local control in breast conservation, although it may be omitted for select low-risk situations. Several radiotherapy techniques exist beyond standard whole-breast irradiation (ie, partial-breast irradiation [PBI], hypofractionated whole-breast radiation); evidence for these is evolving. We present an update of the American College of Radiology (ACR) Appropriateness Criteria® for the management of DCIS. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions, which are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Margin index: a useful tool for the breast surgeon?

BACKGROUND: In breast conservation surgery (BCS) for breast cancer, the appropriate surgical margin is controversial. Margin index, a mathematical relationship between tumor size and closest margin, has been shown to be predictive of the probability of residual cancer after BCS for early stage breast cancer. We applied this tool to the same population of patients at our institution to evaluate its ability to predict residual disease after BCS. METHODS: We retrospectively reviewed a prospectively maintained database of women undergoing BCS between 1980 and 2010 at the University of Pennsylvania. A total of 246 women underwent re-excision because of close margins. Average margin index between groups with and without residual disease in the re-excision specimen was compared using the Student t-test. A receiver operating curve was created using logistic regression to assess the overall diagnostic ability of the margin index on the presence or absence of residual disease. RESULTS: Of patients who underwent re-excision, 29% of patients had residual disease. We analyzed several cutoff values for margin index, but none proved to be significant predictors of residual disease. Average margin index was significantly higher for patients without residual disease compared with patients with residual invasive cancer but not for patients with residual ductal carcinoma in situ. CONCLUSIONS: In women undergoing BCS for early stage breast cancer at our institution, margin index was not predictive of the presence of residual cancer on re-excision. We hypothesize that the predictive ability of a margin index is likely limited by several factors including the presence of ductal carcinoma in situ and the location and extent of the close margin.

ACR Appropriateness Criteria local-regional recurrence (LRR) and salvage surgery-breast cancer.

Although both breast-conserving surgery and mastectomy generally provide excellent local-regional control of breast cancer, local-regional recurrence (LRR) does occur. Predictors for LRR include patient, tumor, and treatment-related factors. Salvage after LRR includes coordination of available modalities, including surgery, radiation, chemotherapy, and hormonal therapy, depending on the clinical scenario. Management recommendations for breast cancer LRR, including patient scenarios, are reviewed, and represent evidence-based data and expert opinion of the American College of Radiology Appropriateness Criteria Expert Panel on LRR.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel.The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Shortened radiation therapy schedules for early-stage breast cancer: a review of hypofractionated whole-breast irradiation and accelerated partial breast irradiation.

Breast-conserving therapy consisting of segmental mastectomy followed by whole-breast irradiation (WBI) has become widely accepted as an alternative to mastectomy as a treatment for women with early-stage breast cancer. WBI is typically delivered over the course of 5-6 weeks to the whole breast. Hypofractionated whole-breast irradiation and accelerated partial breast irradiation have developed as alternative radiation techniques for select patients with favorable early-stage breast cancer. These radiation regimens allow for greater patient convenience and the potential for decreased health care costs. We review here the scientific rationale behind delivering a shorter course of radiation therapy using these distinct treatment regimens in this setting as well as an overview of the published data and pending trials comparing these alternative treatment regimens to WBI.

Risk of positive nonsentinel nodes in women with 1-2 positive sentinel nodes related to age and molecular subtype approximated by receptor status.

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1-2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1-2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1-10) and 14 (range 6-37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.

Five-Year Outcomes of a Phase 1/2 Trial of Accelerated Partial Breast Irradiation Using Proton Therapy for Women With Stage 0-IIA Breast Cancer.

Purpose: We report the results of a phase 1/2 trial of external beam partial breast radiation using proton therapy. Methods and Materials: Eligible patients included stage 0-IIA breast cancer pTis-T2, N0, and size ≤3 cm. Proton beam radiation was used to deliver 3.85 Gy twice daily to 38.5 Gy. The phase 1 portion determined feasibility based on criteria of successful plan creation, treatment delivery, and acute toxicity grade ≥3 in ≤20% of patients. The phase 2 portion had efficacy goals of acute toxicity grade ≥3 in ≤20% of patients and observing physician-rated cosmesis of excellent or good >85% of patients at 2 years. Results: From April 2013 to March 2015, there were 12 patients enrolled onto the phase 1 portion, and the preplanned analysis of feasibility was met in all 4 required criteria. From July 2015 through December 2019 there were 28 patients with 29 treated breasts (1 bilateral) enrolled onto the phase 2 portion of the trial out of 45 originally planned. The trial was closed to accrual because of the coronavirus pandemic and not reopened. Thirty-eight breasts were treated with double-scattering and 3 pencil-beam scanning protons. The median follow-up of the 40 patients is 5.4 years (range, 2.3-8.6 years). There was 1 local recurrence. There was no grade ≥3 acute or late toxicity. At baseline all patients had physician-rated cosmesis good or excellent but at 2 years was excellent in 56%, good in 19%, and fair in 25%. Conclusions: Proton-accelerated partial breast irradiation delivered with a twice-daily fractionation was feasible and associated with very low acute and long-term toxicity. However, the trial did not meet goals for cosmesis outcomes and was closed prematurely. Future study is needed to determine whether pencil-beam scanning protons or different fractionation could improve these outcomes.

Breast Reconstruction Complications After Postmastectomy Proton Radiation Therapy for Breast Cancer.

Purpose: Our purpose was to report complications requiring surgical intervention among patients treated with postmastectomy proton radiation therapy (PMPRT) for breast cancer in the setting of breast reconstruction (BR). Methods and Materials: Patients enrolled on a prospective proton registry who underwent BR with immediate autologous flap, tissue expander (TE), or implant in place during PMPRT (50/50.4 Gy +/- chest wall boost) were eligible. Major reconstruction complication (MRC) was defined as a complication requiring surgical intervention. Absolute reconstruction failure was an MRC requiring surgical removal of BR. A routine revision (RR) was a plastic surgery refining cosmesis of the BR. Kaplan-Meier method was used to assess disease outcomes and MRC. Cox regression was used to assess predictors of MRC. Results: Seventy-three courses of PMPRT were delivered to 68 women with BR between 2013 and 2021. Median follow-up was 42.1 months. Median age was 47 years. Fifty-six (76.7%) courses used pencil beam scanning PMPRT. Of 73 BR, 29 were flaps (39.7%), 30 implants (41.1%), and 14 TE (19.2%) at time of irradiation. There were 20 (27.4%) RR. There were 9 (12.3%) MRC among 5 implants, 2 flaps, and 2 TE, occurring a median of 29 months from PMPRT start. Three-year freedom from MRC was 86.9%. Three (4.1%) of the MRC were absolute reconstruction failure. Complications leading to MRC included capsular contracture in 5, fat necrosis in 2, and infection in 2. On univariable analysis, BR type, boost, proton technique, age, and smoking status were not associated with MRC, whereas higher body mass index trended toward significance (hazard ratio, 1.07; 95% CI, 0.99-1.16; P = .10). Conclusions: Patients undergoing PMPRT to BR had a 12.3% incidence of major complications leading to surgical intervention, and total loss of BR was rare. MRC rates were similar among reconstruction types. Minor surgery for RR is common in our practice.

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.