Prediction of breast cancer-related lymphedema by dermal backflow detected with near-infrared fluorescence lymphatic imaging.

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL. METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4-8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI. RESULTS: By 18 months after RT, 30 of 42 study subjects (71%) developed mild-moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by "dermal backflow" of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL. CONCLUSION: BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes.

Exclusion of Men from Randomized Phase III Breast Cancer Clinical Trials.

Male breast cancer treatment regimens are often extrapolated from female-based studies because of a paucity of literature analyzing male breast cancer. Using ClinicalTrials.gov, we analyzed breast cancer randomized clinical trials (RCTs) to determine which factors were associated with male-gender inclusion. Of 131 breast cancer RCTs identified, male patients represented 0.087% of the total study population, which is significantly less than the proportion of male patients with breast cancer in the U.S. (0.95%; p < .001). Twenty-seven trials included male patients (20.6%). Lower rates of male inclusion were seen in trials that randomized or mandated hormone therapy as part of the trial protocol compared with trials that did not randomize or mandate endocrine therapy (2.5% vs. 28.6% male inclusion; p < .001). It is imperative for breast cancer clinical trials to include men when allowable in order to improve generalizability and treatment decisions in male patients with breast cancer.

Randomized trial of Tibetan yoga in patients with breast cancer undergoing chemotherapy.

BACKGROUND: The current randomized trial examined the effects of a Tibetan yoga program (TYP) versus a stretching program (STP) and usual care (UC) on sleep and fatigue in women with breast cancer who were undergoing chemotherapy. METHODS: Women with stage (American Joint Committee on Cancer (AJCC) TNM) I to III breast cancer who were undergoing chemotherapy were randomized to TYP (74 women), STP (68 women), or UC (85 women). Participants in the TYP and STP groups participated in 4 sessions during chemotherapy, followed by 3 booster sessions over the subsequent 6 months, and were encouraged to practice at home. Self-report measures of sleep disturbances (Pittsburgh Sleep Quality Index), fatigue (Brief Fatigue Inventory), and actigraphy were collected at baseline; 1 week after treatment; and at 3, 6, and 12 months. RESULTS: There were no group differences noted in total sleep disturbances or fatigue levels over time. However, patients in the TYP group reported fewer daily disturbances 1 week after treatment compared with those in the STP (difference, -0.43; 95% confidence interval [95% CI], -0.82 to -0.04 [P = .03]) and UC (difference, -0.41; 95% CI, -0.77 to -0.05 [P = .02]) groups. Group differences at the other time points were maintained for TYP versus STP. Actigraphy data revealed greater minutes awake after sleep onset for patients in the STP group 1 week after treatment versus those in the TYP (difference, 15.36; 95% CI, 7.25-23.48 [P = .0003]) and UC (difference, 14.48; 95% CI, 7.09-21.87 [P = .0002]) groups. Patients in the TYP group who practiced at least 2 times a week during follow-up reported better Pittsburgh Sleep Quality Index and actigraphy outcomes at 3 months and 6 months after treatment compared with those who did not and better outcomes compared with those in the UC group. CONCLUSIONS: Participating in TYP during chemotherapy resulted in modest short-term benefits in sleep quality, with long-term benefits emerging over time for those who practiced TYP at least 2 times a week. Cancer 2018;124:36-45. © 2017 American Cancer Society.

A 10-Year Experience with Mastectomy and Tissue Expander Placement to Facilitate Subsequent Radiation and Reconstruction.

BACKGROUND: An integrated approach to skin sparing mastectomy with tissue expander placement followed by radiotherapy and delayed reconstruction was initiated in our institution in 2002. The purpose of this study was to assess the surgical outcomes of this strategy. METHODS: Between September 2002 and August 2013, a total of 384 reconstructions had a tissue expander placed at the time of mastectomy and subsequently underwent radiotherapy. Rates and causes of tissue expander explantation before, during, and after radiotherapy, as well as tumor specific outcomes and reconstruction approaches, were collected. RESULTS: Median follow-up after diagnosis was 5.6 (range 1.3-13.4) years. In the study cohort, 364 patients (94.8%) had stage II-III breast cancer, and 7 patients (1.8%) had locally recurrent disease. The 5-year rates of actuarial locoregional control, disease-free survival, and overall survival were 99.2, 86.1, and 92.4%, respectively. The intended delayed-immediate reconstruction was subsequently completed in 325 of 384 mastectomies (84.6% of the study cohort). Of the remaining 59 tissue expanders, 1 was explanted before radiotherapy, 1 during radiotherapy, and 7 patients (1.8%) were lost to follow-up. Fifty patients (13.0%) required tissue expander explantation after radiation and before their planned final reconstruction, primarily due to cellulitis. Nonetheless, the cumulative rate of completed reconstructions was 89.6%. The median time from placement of the tissue expander until reconstruction was 12 (interquartile range 9-15) months. CONCLUSIONS: Tissue expander placement at skin-sparing mastectomy in patients who require radiotherapy appears to be a viable strategy for combining reconstruction and radiotherapy.

Depressive symptoms and positive affect in Chinese and United States breast cancer survivors: a cross-cultural comparison.

PURPOSE: Research in the area of cultural response pattern on questionnaires in the oncological setting and direct cross-cultural comparisons are lacking. This study examined response pattern in the reporting of depressive symptoms in Chinese and US women with breast cancer. We hypothesized that Chinese women are less likely to endorse positive affect items compared to their US counterparts. Additionally, we explored cultural differences in the association between positive affect and QOL. METHODS: Secondary analyses of baseline assessments of two mind-body intervention studies for women with breast cancer undergoing radiotherapy in the USA (N = 62) and China (N = 97) are presented. All participants completed measures of depressive symptoms (CES-D) and cancer-specific QOL (FACT-B). We examined cultural differences on positive and negative affect items on the CES-D. RESULTS: Controlling for demographic factors, ANCOVA revealed a significant cultural difference in positive (F = 7.99, p = 0.005) but not negative affect (p = 0.82) with Chinese women reporting lower positive affect compared to US women (Chinese = 6.97 vs. US = 8.31). There was also a significant cultural difference (F = 3.94, p = 0.03) in the association between positive affect and QOL so that lower positive affect was more strongly associated with worse emotional well-being in Chinese (beta = 0.57, p < 0.0001) than US women (beta = 0.35, p < 0.01). CONCLUSIONS: Chinese women reported lower positive affect compared to US women and lower levels of positive affect were more strongly associated with worse QOL. Special attention is needed when examining mental health in different cultures to ascertain effective delivery of clinical services to those in need.

Differences in quality of life between American and Chinese breast cancer survivors.

OBJECTIVE: It has been speculated that cancer survivors in Asia may have lower quality of life (QOL) compared with their Western counterparts. However, no studies have made international comparisons in QOL using a comprehensive measure. This study aimed to compare Chinese breast cancer survivors' QOL with US counterparts and examine if demographic and medical factors were associated with QOL across groups. METHOD: The sample consisted of 159 breast cancer patients (97 Chinese and 62 American) who completed the Functional Assessment for Cancer Therapy Breast Cancer (FACT-B) scale before the start of radiotherapy in Shanghai, China and Houston, USA. RESULTS: Higher income was associated with higher QOL total scores in both Chinese and American cancer patients, but QOL was not significantly associated with other factors including age, education, disease stage, mastectomy, and chemotherapy. Consistent with hypotheses, compared to their US counterparts, Chinese breast cancer survivors reported lower QOL and all four subdimensions including functional well-being (FWB), physical well-being (PWB), emotional well-being (EWB), and social well-being (SWB); they also reported more breast cancer-specific concerns (BCS). Differences were also clinically significant for Functional Assessment for Cancer Therapy General (FACT-G) scale total scores and the FWB subscale. After controlling for demographic and medical covariates, these differences remained except for the SWB and BCS. Furthermore, Chinese breast cancer survivors receiving chemotherapy reported significantly lower FACT-G scores than those who did not, but this difference did not emerge among US breast cancer survivors. DISCUSSION: Chinese breast cancer survivors reported poorer QOL on multiple domains compared to US women. Findings indicate that better strategies are needed to help improve the QOL of Chinese breast cancer survivors, especially those who underwent chemotherapy.

Case control study of women treated with chemotherapy for breast cancer during pregnancy as compared with nonpregnant patients with breast cancer.

BACKGROUND: The purpose of this analysis was to compare disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) between pregnant and nonpregnant patients with breast cancer. METHODS: From 1989 to 2009, 75 women were treated with chemotherapy during pregnancy. Each pregnant case was matched on age and cancer stage to two nonpregnant patients with breast cancer (controls). Fisher's exact test, the Kaplan-Meier method, and Cox proportional hazards regression models were used. RESULTS: Median follow-up time for patients who were alive at the end of follow-up (n = 159) was 4.20 years (range: 0.28-19.94 years). DFS at 5 years was 72% (95% confidence interval [CI]: 58.3%-82.1%) for pregnant patients and 57% (95% CI: 46.7%-65.8%) for controls (p = .0115). Five-year PFS was 70% (95% CI: 56.8%-80.3%) for pregnant patients and 59% (95% CI: 49.1%-67.5%) for controls (p = .0252). Five-year OS was 77% (95% CI: 63.9%-86.4%) for pregnant patients and 71% (95% CI: 61.1%-78.3%) for controls (p = .0461). Hazard ratio estimates favored improved survival for pregnant patients in univariate analyses and multivariate analyses, controlling for age, year of diagnosis, stage, and tumor grade. CONCLUSIONS: For patients who received chemotherapy during pregnancy, survival was comparable to-if not better than-that of nonpregnant women. Pregnant patients with breast cancer should receive appropriate local and systemic therapy for breast cancer.

Prospective, early longitudinal assessment of lymphedema-related quality of life among patients with locally advanced breast cancer: The foundation for building a patient-centered screening program.

BACKGROUND: We examined how breast cancer-related lymphedema (BCRL) affects health-related quality of life (HRQOL), productivity, and compliance with therapeutic interventions to guide structuring BCRL screening programs. METHODS: We prospectively followed consecutive breast cancer patients who underwent axillary lymph node dissection (ALND) with arm volume screening and measures assessing patient-reported health-related quality of life (HRQOL) and perceptions of BCRL care. Comparisons by BCRL status were made with Mann-Whitney U, Chi-square, Fisher's exact, or t tests. Trends over time from ALND were assessed with linear mixed-effects models. RESULTS: With a median follow-up of 8 months in 247 patients, 46% self-reported ever having BCRL, a proportion that increased over time. About 73% reported fear of BCRL, which was stable over time. Further in time from ALND, patients were more likely to report that BCRL screening reduced fear. Patient-reported BCRL was associated with higher soft tissue sensation intensity, biobehavioral, and resource concerns, absenteeism, and work/activity impairment. Objectively measured BCRL had fewer associations with outcomes. Most patients reported performing prevention exercises, but compliance decreased over time; patient-reported BCRL was not associated with exercise frequency. Fear of BCRL was positively associated with performing prevention exercises and using compressive garments. CONCLUSIONS: Both incidence and fear of BCRL were high after ALND for breast cancer. Fear was associated with improved therapeutic compliance, but compliance decreased over time. Patient-reported BCRL was more strongly associated with worse HRQOL and productivity than was objective BCRL. Screening programs must support patients' psychological needs and aim to sustain long-term compliance with recommended interventions.

Contemporary Outcomes After Multimodality Therapy in Patients With Breast Cancer Presenting With Ipsilateral Supraclavicular Node Involvement.

PURPOSE: Patients with breast cancer and ipsilateral supraclavicular (SCV) node involvement at the time of diagnosis (TNM cN3c) have historically had poor outcomes. Radiation therapy (RT) has an important role because SCV nodes are not routinely surgically dissected. However, optimal locoregional management, contemporary outcomes, and prognostic factors are not well defined. METHODS AND MATERIALS: We reviewed the data of patients with cN3c breast cancer treated at our institution between 2014 and 2019 with curative intent, including neoadjuvant chemotherapy, surgery, and adjuvant RT. All patients received comprehensive regional RT, including to the SCV nodes. Institutional guidelines recommend a 10-Gy or 16-Gy boost to resolved and unresolved N3 nodes, respectively. Overall survival (OS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and supraclavicular recurrence-free survival (SCRFS) were analyzed. RESULTS: Data from 173 consecutive patients were analyzed with a median follow-up time of 2.8 years. The median age was 54 years, 76 patients (44%) were estrogen receptor positive/human epidermal growth factor receptor 2 negative, 100 patients (58%) had T3/4 disease, and 10 patients (6%) underwent a neck dissection. In addition, 156 patients (90%) received a cumulative SCV dose of ≥60 Gy. The 5-year OS, SCRFS, LRRFS, and RFS rates were 73%, 95%, 86%, and 50%, respectively. The 5-year OS rate for a cumulative SCV dose of ≥60 Gy versus <60 Gy was 75% versus 39% (P = .04). In the multivariable analysis, a cumulative SCV dose of ≥60 Gy, extranodal extension, receptor status, and Eastern Cooperative Oncology Group performance status were associated with OS. The 5-year SCRFS rates with and without neck dissection were 100% versus 95% (P = .57). Among patients with a postchemotherapy SCV node size of ≥1 cm without neck dissection, the 5-year SCRFS rate was 83%. CONCLUSIONS: In one of the largest series of patients with cN3c breast cancer, multimodality therapy using adjuvant RT with a SCV boost resulted in a 5-year LRRFS rate of 86%. There is a limited role for neck dissection as the 5-year SCRFS rate was 95% overall and 83% for residual SCV disease ≥1 cm after chemotherapy with RT alone. A cumulative SCV dose of ≥60 Gy was associated with improved OS, but not SCRFS, LRRFS, or RFS. A SCV boost should be considered in these patients as treatment was well-tolerated. Despite advances in systemic therapy, nearly half of patients developed distant metastases, highlighting the need for close observation after treatment.

Adoption of Ultrahypofractionated Radiation Therapy in Patients With Breast Cancer.

Introduction: The first high-quality clinical trial to support ultrahypofractionated whole-breast irradiation (ultra-HF-WBI) for invasive early-stage breast cancer (ESBC) was published in April 2020, coinciding with the beginning of the COVID-19 pandemic. We analyzed adoption of ultra-HF-WBI for ductal carcinoma in situ (DCIS) and ESBC at our institution after primary trial publication. Methods and Materials: We evaluated radiation fractionation prescriptions for all patients with DCIS or ESBC treated with WBI from March 2020 to May 2021 at our main campus and regional campuses. Demographic and clinical characteristics were extracted from the electronic medical record. Treating physician characteristics were collected from licensure data. Hierarchical logistic regression models identified factors correlated with adoption of ultra-HF-WBI (26 Gy in 5 daily factions [UK-FAST-FORWARD] or 28.5 Gy in 5 weekly fractions [UK-FAST]). Results: Of 665 included patients, the median age was 61.5 years, and 478 patients (71.9%) had invasive, hormone-receptor-positive breast cancer. Twenty-one physicians treated the included patients. In total, 249 patients (37.4%) received ultra-HF-WBI, increasing from 4.3% (2 of 46) in March-April 2020 to a high of 45.5% (45 of 99) in July-August 2020 (P < .001). Patient factors associated with increased use of ultra-HF-WBI included older age (≥50 years old), low-grade WBI without inclusion of the low axilla, no radiation boost, and farther travel distance (P < .03). Physician variation accounted for 21.7% of variance in the outcome, with rate of use of ultra-HF-WBI by the treating physicians ranging from 0% to 75.6%. No measured physician characteristics were associated with use of ultra-HF-WBI. Conclusions: Adoption of ultra-HF-WBI at our institution increased substantially after the publication of randomized evidence supporting its use. Ultra-HF-WBI was preferentially used in patients with lower risk disease, suggesting careful selection for this new approach while long-term data are maturing. Substantial physician-level variation may reflect a lack of consensus on the evidentiary standards required to change practice.

Outcomes After Breast Radiation Therapy in a Diverse Patient Cohort With a Germline BRCA1/2 Mutation.

PURPOSE: BRCA1/2 pathogenic variant (PV) mutations confer radiation sensitivity preclinically, but there are limited data regarding breast cancer outcomes after radiation therapy (RT) among patients with documented BRCA1/2 PV mutations versus no PV mutations. METHODS AND MATERIALS: This retrospective cohort study included women with clinical stage I-III breast cancer who received definitive surgery and RT and underwent BRCA1/2 genetic evaluation at the The University of Texas MD Anderson Cancer Center. Rates of locoregional recurrence (LRR), disease-specific death (DSD), toxicities, and second cancers were compared by BRCA1/2 PV status. RESULTS: Of the 2213 women who underwent BRCA1/2 testing, 63% self-reported their race as White, 13.6% as Black/African American, 17.6% as Hispanic, and 5.8% as Asian/American Indian/Alaska Native; 124 had BRCA1 and 100 had BRCA2 mutations; and 1394 (63%) received regional nodal RT. The median follow-up time for all patients was 7.4 years (95% confidence interval [CI], 7.1-7.7 years). No differences were found between the groups with and without BRCA1/2 PV mutations in 10-year cumulative incidences of LRR (with mutations: 11.6% [95% CI, 7.0%-17.6%]; without mutations: 6.6% [95% CI, 5.3%-8.0%]; P = .466) and DSD (with mutations: 12.3% [95% CI, 8.0%-17.7%]; without mutations: 13.8% [95% CI, 12.0%-15.8%]; P = .716). On multivariable analysis, BRCA1/2 status was not associated with LRR or DSD, but Black/African American patients (P = .036) and Asians/American Indians/Alaska Native patients (P = .002) were at higher risk of LRR compared with White patients, and Black/African American patients were at higher risk of DSD versus White patients (P = .004). No in-field, nonbreast second cancers were observed in the BRCA1/2 PV group. Rates of acute and late grade ≥3 radiation-related toxicity in the BCRA1/2 PV group were 5.4% (n = 12) and 0.4% (n = 1), respectively. CONCLUSIONS: Oncologic outcomes in a diverse cohort of patients with breast cancer who had a germline BRCA1/2 PV mutation and were treated with RT were similar to those of patients with no mutation, supporting the use of RT according to standard indications in patients with a germline BRCA1/2 PV mutation.

Breast Radiation Therapy-Related Treatment Outcomes in Patients With or Without Germline Mutations on Multigene Panel Testing.

PURPOSE: Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing. METHODS AND MATERIALS: We retrospectively reviewed the records of 286 women with clinical stage I-III breast cancer diagnosed from 1995 to 2017 who underwent surgery, breast or chest wall RT with or without regional nodal irradiation, multigene panel testing, and evaluation at a large cancer center's genetic screening program. We evaluated rates of overall survival, locoregional recurrence, disease-specific death, and radiation-related toxicities in 3 groups: BRCA1/2 PV carriers, non-BRCA1/2 PV carriers, and patients without PV mutations. RESULTS: PVs were detected in 25.2% of the cohort (12.6% BRCA1/2 and 12.6% non-BRCA1/2). The most commonly detected non-BRCA1/2 mutated genes were ATM, CHEK2, PALB2, CDH1, TP53, and PTEN. The median follow-up time for the entire cohort was 4.4 years (95% confidence interval, 3.8-4.9 years). No differences were found in overall survival, locoregional recurrence, or disease-specific death between groups (P > .1 for all). Acute and late toxicities were comparable across groups. CONCLUSION: Oncologic and toxicity outcomes after RT in women with PV germline mutations detected by multigene pane testing are similar to those in patients without detectable mutations, supporting the use of adjuvant RT as a standard of care when indicated.

Prospective randomized trial of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus paclitaxel and FAC (TFAC) in patients with operable breast cancer: impact of taxane chemotherapy on locoregional control.

A previous randomized trial (CALGB 9344/Intergroup 0148) compared four cycles of adjuvant doxorubicin/cyclophosphamide (AC) to four cycles of AC plus four cycles of paclitaxel (AC + T) and demonstrated that the addition of paclitaxel improved locoregional control (LRC) in patients with node-positive breast cancer. However, it could not be determined whether it was the paclitaxel or the increased duration of chemotherapy that led to this improvement. The present study aimed to analyze whether the addition of paclitaxel to a doxorubicin-based regimen improves LRC in a cohort of patients who all received eight total cycles of chemotherapy. Five hundred eleven women with operable breast cancer were randomized on a single-institution prospective trial to receive 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) × 8 cycles (n = 252) or FAC × 4 cycles plus paclitaxel × 4 cycles (TFAC) (n = 259). Rates of LRC and overall survival (OS) were analyzed. Median follow-up was 124 months (range 5-167 months). The 10-year LRC rate was 92.6 versus 93.1% in the FAC versus TFAC arms, respectively (P = 0.26). The LRC between treatment arms did not differ when analyzed by locoregional treatment group: breast conservation therapy (BCT), mastectomy alone (M), and mastectomy + radiation (M + RT). The 10-year LRC rates were 95.1% (FAC) versus 91.2% (TFAC) after BCT (P = 0.98), 89.5% (FAC) versus 93.4% (TFAC) after M (P = 0.24), and 94.7% (FAC) versus 96.5% (TFAC) after M + RT (P = 0.59). Additionally, there was no difference in OS between the treatment arms, with 10-year OS rates of 78.4% (FAC) versus 81.7% (TFAC) (P = 0.93). The addition of paclitaxel to a doxorubicin-based regimen had no impact on LRC, regardless of the type of local therapy received. Historically inferior LRC with AC chemotherapy alone versus AC + T may have been due to an inadequate duration of systemic therapy and not due to the absence of paclitaxel.

Proton Accelerated Partial Breast Irradiation: Clinical Outcomes at a Planned Interim Analysis of a Prospective Phase 2 Trial.

PURPOSE: To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience. RESULTS: Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients' mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy). CONCLUSIONS: Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.

Risk of subclinical micrometastatic disease in the supraclavicular nodal bed according to the anatomic distribution in patients with advanced breast cancer.

PURPOSE: To determine the anatomic distribution of gross supraclavicular nodes within the supraclavicular fossa using 2-deoxy-2-[F-18] fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans, and to evaluate likely coverage of specific regions of the supraclavicular fossa using standard radiation fields. METHODS AND MATERIALS: We identified 33 patients with advanced or metastatic breast cancer who had a PET/CT scan demonstrating hypermetabolic supraclavicular lymph nodes in 2005. The locations of the involved lymph nodes were mapped onto a single CT set of images of the supraclavicular fossa. These lymph nodes were also mapped onto the treatment-planning CT dataset of 4 patients treated in our institution (2 patients with biopsy-proven supraclavicular nodes and 2 patients with clinically negative supraclavicular nodes). RESULTS: We were able to determine the distribution of 52 supraclavicular lymph nodes in 32 patients. Of 32 patients, 28 (87%) had a history of metastatic disease, and 2 patients had isolated nodal recurrences. Five patients had supraclavicular nodes posterior to the vertebral body transverse process, and several lymph nodes were in close proximity to the medial field border, raising the possibility of geographic miss in these areas. CONCLUSIONS: In patients with locally advanced disease, increased coverage of the supraclavicular fossa medially and posteriorly may be warranted.

Radiation use and long-term survival in breast cancer patients with T1, T2 primary tumors and one to three positive axillary lymph nodes.

BACKGROUND: For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit. METHODS AND MATERIALS: We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT). RESULTS: Patients treated with BCT + XRT were younger, were more likely to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p < 0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p < 0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p < 0.001) and for overall death of 1.25 (p < 0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features. CONCLUSIONS: Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.

Locoregional treatment outcomes after multimodality management of inflammatory breast cancer.

PURPOSE: The aims of this study were to determine outcomes for patients with inflammatory breast cancer (IBC) treated with multimodality therapy, to identify factors associated with locoregional recurrence, and to determine which patients may benefit from radiation dose escalation. METHODS AND MATERIALS: We retrospectively reviewed 256 consecutive patients with nonmetastatic IBC treated at our institution between 1977 and 2004. RESULTS: The 192 patients who were able to complete the planned course of chemotherapy, mastectomy, and postmastectomy radiation had significantly better outcomes than the 64 patients who did not. The respective 5-year outcome rates were: locoregional control (84% vs. 51%), distant metastasis-free survival (47% vs. 20%), and overall survival (51% vs. 24%) (p < 0.0001 for all comparisons). Univariate factors significantly associated with locoregional control in the patients who completed plan treatment were response to neoadjuvant chemotherapy, surgical margin status, number of involved lymph nodes, and use of taxanes. Increasing the total chest-wall dose of postmastectomy radiation from 60 Gy to 66 Gy significantly improved locoregional control for patients who experienced less than a partial response to chemotherapy, patients with positive, close, or unknown margins, and patients <45 years of age. CONCLUSIONS: Patients with IBC who are able to complete treatment with chemotherapy, mastectomy, and postmastectomy radiation have a high probability of locoregional control. Escalation of postmastectomy radiation dose to 66 Gy appears to benefit patients with disease that responds poorly to chemotherapy, those with positive, close, or unknown margin status, and those <45 years of age.

Primary breast cancer in men: clinical, imaging, and pathologic findings in 57 patients.

OBJECTIVE: The purpose of our study was to describe the imaging findings in primary breast cancer in men. MATERIALS AND METHODS: Male patients from a single pathology database with the histologic diagnosis of breast cancer who had undergone preoperative mammography or sonography were included in this study. The mammograms and sonograms were retrospectively reviewed according to the American College of Radiology BI-RADS lexicon. Patients who did not have films available but had imaging reports available for review were also included. Sonograms of the regional nodal basins, including axillary, infraclavicular, internal mammary, and supraclavicular regions, were noted. Histopathology subtype of breast cancer and axillary nodal status were documented. RESULTS: A total of 57 patients with imaging and 187 patients without imaging were included. The median age was 62 years (range, 19-80 years). Forty-nine patients had undergone both mammography and sonography; six, mammography alone; and two, sonography alone. Ninety-five percent (54/57) of patients presented with a palpable mass and 4% (2/57) with nipple inversion. At mammography, 69% (38/55) of cancers showed a mass; 29% (16/55), mass with microcalcifications; and 2% (1/55), microcalcifications. Gynecomastia was noted in 22 (40%) of 55 patients. Mammographic features included an irregular mass with spiculated or indistinct margins. Calcifications were typically pleomorphic and segmental. Sonographic features were typically an irregular mass with microlobulated margins. Axillary nodal involvement was present in 47% of patients. Most cancers were ductal carcinoma, either invasive or in situ. CONCLUSION: Breast cancer in men characteristically presents as an irregular subareolar mass with spiculated or indistinct margins on mammography and can be associated with calcifications and gynecomastia. Sonography has a role in regional staging of lymph nodes.

A component of lobular carcinoma in clinically lymph node-negative patients predicts for an increased likelihood of upstaging to pathologic stage III breast cancer.

PURPOSE: Physical examination and diagnostic imaging are often less precise in determining the extent of disease in invasive lobular carcinoma (ILC) relative to nonlobular histologies. Anecdotally, surgical axillary evaluation frequently reveals positive lymph nodes in clinically N0 patients with ILC; however, few studies quantify the likelihood of finding unsuspected disease at the time of surgery. In this study, we evaluate whether the presence of lobular histology increases the incidence of surgical upstaging to pathologic stage IIIA or greater in patients with a clinically node-negative axilla and positive sentinel lymph node (SLN) biopsy. METHODS AND MATERIALS: We examined patients from our institution between 1997 and 2009 treated specifically with mastectomy, SLN biopsy, and completion axillary lymph node dissection due to a positive SLN. For analysis, patients were grouped according to the presence of any lobular component on surgical pathology. The number of total positive lymph nodes, cancer stage, age, final tumor size, and ER/PR/HER2 status were assessed based on tumor histology. RESULTS: We evaluated 345 previously untreated women with clinical T0-T2 and N0 disease at the time of surgery. A total of 110 patients (32%) had a component of ILC on surgical pathology. In addition, 295 patients (85.5%) had ER + breast carcinoma, 243 (70.4%) had PR + disease, 56 (16.2%) were HER2 + , and 28 (8.1%) were triple negative. At the time of surgery, women with lobular disease were observed to have a greater number of positive lymph nodes (2.79 vs 2.26; P = .009) and were more frequently upstaged to at least pathologic stage IIIA compared with nonlobular patients (30.9% vs 17.4%; P = .007). CONCLUSIONS: In this cohort, patients with a component of lobular carcinoma were more often surgically upstaged to pathologic stage IIIA or higher, which is a classical indication for postmastectomy radiation therapy. Our findings suggest that ILC is often more extensive than it appears clinically and has significant implications for management of patients with lobular carcinoma after the discovery of a positive SLN.

Disease-control rates following intensity-modulated radiation therapy for small primary oropharyngeal carcinoma.

BACKGROUND: The purpose of this study was to assess the ability of intensity-modulated radiation therapy (IMRT) to achieve favorable disease-control rates while minimizing parotid gland doses in patients treated for small primary tumors of the oropharynx. METHODS AND MATERIALS: We retrospectively identified all patients who received IMRT as treatment for a small (<4 cm) primary tumor of the oropharynx between October 2000 and June 2002. Tumor characteristics, IMRT parameters, and patient outcomes were assessed. RESULTS: Fifty-one patients met the criteria for our study. All patients had treatment to gross disease with margin (CTV1), and all but 1 had treatment to the bilateral necks. The most common treatment schedule (39 patients) was a once-daily fractionation of prescribed doses of 63-66 Gy to the CTV1 and 54 Gy to subclinical sites, delivered in 30 fractions. Twenty-one patients (40%) had gastrostomy tubes placed during therapy; in 4 patients, the tube remained in place for more than 6 months after completion of IMRT. The median follow-up was 45 months. The 2-year actuarial locoregional control, recurrence-free, and overall survival rates were 94%, 88%, and 94%, respectively. CONCLUSIONS: These preliminary data suggest that treatment with IMRT results in favorable locoregional control of small primary oropharynx tumors. IMRT did not appear to have a more favorable acute toxicity profile in this group with respect to the use of a feeding tube; however, the mean dose of radiation delivered to the parotid gland by IMRT was decreased, because 95% of patients had a mean dose of <30 Gy to at least one gland.