De-escalation of Post-mastectomy Irradiation in Hormone Receptor-Positive Breast Cancer with One to Three Positive Nodes.

BACKGROUND: The 21-gene recurrence score (RS) is used to predict benefit from chemotherapy in hormone receptor (HR)-positive breast cancer with one to three positive lymph nodes. Prospective-retrospective studies have shown that the RS is prognostic for both systemic and locoregional recurrence in tamoxifen-treated patients. We aimed to assess whether RS could be utilized to predict a survival benefit from postmastectomy radiation therapy (PMRT). PATIENTS AND METHODS: The National Cancer Database (NCDB) was used to identify women ≤ 75 years of age with HR+, HER2-negative, T1-3, N1, M0 breast cancer who underwent mastectomy and axillary staging with available RS during the years 2010-2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). Univariate and multivariate analyses were used to identify variables correlating with PMRT and OS. RESULTS: A total of 8907 patients were identified. Of the total, 3203 (36%) patients received adjuvant PMRT and 5704 (64%) did not. Across the entire cohort, 5-year OS was 97.5% for patients receiving PMRT and 96.8% for those who did not (P = 0.063). After adjusting for all covariates, in patients with RS ≤ 25, there was no statistically significant improvement in 5-year OS with the addition of adjuvant PMRT (97.5% versus 98.1% P = 0.093). Moreover, no survival benefit was seen with axillary node dissection (P = 0.58) or with the addition of chemotherapy (P = 0.312). CONCLUSIONS: In our cohort of patients with one to three positive nodes and a RS ≤ 25, omission of post-mastectomy radiation therapy had no impact on OS. Our results suggest that RS may be utilized in the individualized decision making on PMRT.

Role of 21-Gene Recurrence Score in Predicting Prognostic Benefit of Radiation Therapy After Breast-Conserving Surgery for T1N0 Breast Cancer.

PURPOSE: The 21-gene RT-PCR recurrence score (RS) is performed in patients with hormone receptor-positive (ER+, PR+), human epidermal growth factor receptor 2 (HER2)-negative, N0 breast cancer to determine which patients will likely benefit from chemotherapy after breast-conserving surgery (BCS). The purpose of this study was to evaluate whether the RS can predict for patients likely to benefit from radiation therapy (RT) after BCS. METHODS AND MATERIALS: The National Cancer Database was queried (2004-2017) for female patients with pT1N0 ER+ PR+ HER2-negative breast cancer treated with BCS who had an available RS. Patients were stratified based on their RS (low risk [LR], 1-10; intermediate risk [IR], 11-25; high risk [HR], 26-100). For each RS cohort, propensity score matching was conducted to create 1:1 matched cohorts of patients who received RT and patients who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable and multivariable (MVA) Cox proportional hazard analysis identified clinical and treatment factors prognostic for OS. RESULTS: A total of 79,040 patients met the selection criteria: 18,823 in the LR cohort, 52,341 in the IR cohort, and 7876 in the HR cohort. A total of 92% of patients received RT: 91% in the LR cohort, 93% in the IR cohort, and 92% in the HR cohort. After propensity score matching, the 5-year OS in the LR cohort was 95% for those who received RT and 93% for those who did not (P = .184). In the IR cohort, the 5-year OS was 95% for those who received RT and 93% for those who did not (P = .001). In the HR cohort, the 5-year OS was 95% for those who received RT and 84% for those who did not (P < .001). MVA demonstrated that RT was a positive prognostic factor for OS in both the IR cohort (P = .001) and HR cohort (P < .001). On MVA in the LR cohort, RT (P = .186) was not predictive of improved OS. CONCLUSIONS: An OS benefit was observed with the use of RT in patients with IR or HR RS but not in patients with LR RS. Future prospective evaluation is warranted.

Prognostic Impact of Radiation Therapy in Pure Mucinous Breast Carcinoma.

PURPOSE: Pure Mucinous breast carcinoma (PMBC) is an invasive breast cancer with favorable prognosis. While pathology-specific guidelines exist for PMBC regarding adjuvant chemotherapy and endocrine therapy, no recommendations exist regarding locoregional treatment based on tumor histology. Prognostic impact of radiotherapy for patients with PMBC remains unclear. MATERIALS AND METHODS: The National Cancer Database was queried (2004-2017) for patients with pN0M0 PMBC who underwent lumpectomy. Chi-square testing compared categorical frequencies between patients who received radiotherapy versus those who did not. Propensity score matching created a 1:1 matched cohort of patients who received radiotherapy and patients who didn't. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS. RESULTS: 17,259 patients met selection criteria; 11,087 (74%) received radiotherapy while 3852 (26%) did not. After PSM, radiotherapy (HR 0.629; 95% CI 0.531-0.746), endocrine therapy (HR 0.676; 95% CI 0.567-0.805), black race (HR 0.703; 95% CI 0.498-0.991), and private insurance (HR 0.184; 95% CI 0.078-0.432) were favorable prognostic factors on multivariate Cox regression analysis while age ≥ 70 years (HR 2.668; 95% CI 1.903-3.740), tumor size > 20 mm (HR 1.964; 95% CI 1.613-2.391), and CDCC score > 0 (HR 1.770; 95% CI 1.474-2.126) were unfavorable prognostic factors. After PSM, 5-year OS was 86% for those who received radiotherapy and 81% for those who did not (P < .001). CONCLUSION: This is the largest study to date on PMBC and the prognostic impact of adjuvant radiotherapy. Radiotherapy is associated with a survival advantage, suggesting omission of radiotherapy is not warranted.

A combinatorial system to examine the enzymatic repair of multiply damaged DNA substrates.

DNA damage drives genetic mutations that underlie the development of cancer in humans. Multiple pathways have been described in mammalian cells which can repair this damage. However, most work to date has focused upon single lesions in DNA. We present here a combinatorial system which allows assembly of duplexes containing single or multiple types of damage by ligating together six oligonucleotides containing damaged or modified bases. The combinatorial system has dual fluorescent labels allowing examination of both strands simultaneously, in order to study interactions or competition between different DNA repair pathways. Using this system, we demonstrate how repair of oxidative damage in one DNA strand can convert a mispaired T:G deamination intermediate into a T:A mutation. We also demonstrate that slow repair of a T:G mispair, relative to a U:G mispair, by the human methyl-binding domain 4 DNA glycosylase provides a competitive advantage to competing repair pathways, and could explain why CpG dinucleotides are hotspots for C to T mutations in human tumors. Data is also presented that suggests repair of closely spaced lesions in opposing strands can be repaired by a combination of short and long-patch base excision repair and simultaneous repair of multiply damage sites can potentially lead to lethal double strand breaks.

21-Gene recurrence score predictive for prognostic benefit of radiotherapy in patients age ≥ 70 with T1N0 ER/PR + HER2- breast cancer treated with breast conserving surgery and endocrine therapy.

PURPOSE: Based on the results of the Cancer and Leukemia Group B (CALGB) 9343 trial, patients age ≥70 with T1N0 hormone receptor positive (ER/PR+), human epidermal growth factor receptor-2 negative (HER2-) breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). Because the CALGB 9343 trial did not stratify based on recurrence score (RS) test (Oncotype Dx), we conducted the present retrospective study to determine whether RS is predictive of who may benefit from RT following BCS in this cohort. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried (2004-2017) for patients age ≥ 70 with pT1N0 ER+/PR + HER2- breast cancer treated with BCS and ET. Patients were stratified based on their RS (low risk [LR] = 1-10, intermediate risk [IR] = 11-25, high risk [HR] = 26-99). Propensity score matching (PSM) created 1:1 matched cohorts of patients who received radiotherapy and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable (MVA) Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS. RESULTS: A total of 11,891 patients met the selection criteria: 3364 in the LR cohort, 7305 in the IR cohort, and 1222 in the HR cohort. A total of 79 % received RT: 77 % in the LR cohort, 79 % in the IR cohort, and 85 % in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, the 5-year OS in the LR cohort was 91 % for those who received RT and 89 % for those who did not (p = 0.605). In the IRHR cohort, the 5-year OS was 91 % for those who received RT and 87 % for those who did not (p = 0.003). On MVA in the LR cohort, RT (p = 0.727) was not predictive of improved OS. On MVA in the IRHR cohort, RT (p = 0.010) was a positive prognostic factor for OS. CONCLUSION: In this older cohort of patients, there is an OS benefit with the use of RT in patients with IRHR RS but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11.

Adjuvant chemotherapy in patients with invasive lobular carcinoma and use of the 21-gene recurrence score: A National Cancer Database analysis.

BACKGROUND: Invasive lobular carcinoma (ILC) is traditionally considered less responsive to chemotherapy. Although the Oncotype recurrence score (RS) has been validated to identify high-risk patients who benefit from chemotherapy, some studies have questioned its relevance in patients with ILC. The objective of this study was to better characterize potential use of the RS in these patients. METHODS: The National Cancer Database was used to identify women with stage I through III, T1 through T3, N0 or N1, hormone receptor-positive, HER2-negative ILC or invasive ductal carcinoma (IDC) who had an available RS between 2010 and 2016. Multivariable Cox regression was used to model the effect of variables on 5-year overall survival (OS). The Kaplan-Meier method was used to estimate OS according to the RS, nodal status, and chemotherapy. RESULTS: In total, 15,763 patients with ILC and 100,070 with IDC were identified. The mean age of patients with ILC and IDC was 59.2 ± 9.1 and 57.2 ± 9.8, respectively. A lower percentage of patients with ILC versus those with IDC had a high RS, defined as >25 (6.6% vs 16.0%; P < .0001). ILC patients with a high RS who had N0 or N1 disease received approximately 10% less chemotherapy compared with similar patients who had IDC. The results indicated that the RS had statistically significant prognostic value for patients with ILC. In addition, an absolute OS advantage was correlated with the receipt of chemotherapy by patients with ILC who had a high RS with N0 or N1 disease. CONCLUSIONS: Patients with ILC who have a high RS are treated less often with chemotherapy compared with similar patients who have IDC. Nevertheless, the RS has a prognostic as well as a predictive value in ILC, with an association between OS benefit and chemotherapy receipt in patients who have ILC with a high RS, especially if they have N1 disease. LAY SUMMARY: Invasive lobular carcinoma (ILC) is a subtype of breast cancer comprising about 15% of cases. The Oncotype recurrence score (RS) is a genetic test of breast tumors that helps predict which patients might benefit from chemotherapy. Some have doubted the relevance of the RS for patients with ILC. In this study, the authors show that the RS is relevant for patients who have ILC. The RS has the potential of predicting the risk of recurrence and identifying patients with ILC who might benefit from chemotherapy.

De-escalation of Endocrine Therapy in Early Hormone Receptor-positive Breast Cancer: When Is Local Treatment Enough?

OBJECTIVE: To identify subgroups of hormone receptor-positive (HR+) breast cancer patients that might not benefit from adding endocrine therapy (ET) to their local treatment. BACKGROUND: De-escalation in breast cancer treatment has included surgery, radiation, and chemotherapy and has often focused on older patient populations. Systemic ET has yet to be de-escalated, though it carries serious side-effects, decreasing quality of life over 5 to 10 years. We hypothesize the 21-gene recurrence score (RS) could identify subgroups of younger patients whose long-term survival is unaffected by adjuvant ET. METHODS: The National Cancer Database was used to identify women aged ≥50, with HR+, HER2-negative tumors, ≤3 cm in size, N0 status, and a RS≤25, who underwent breast-conserving surgery in 2010 to 2016. Kaplan-Meier and Cox proportional hazards models were used to identify association between treatment and overall survival (OS). RESULTS: Of the 45,217 patients identified, 80.6% were 50 to 69 years old. 42,632 (94.3%) patients received ET and 2585 (5.7%) did not. The 5-year OS was 96.4% for patients receiving ET and 93.1% for those who did not (P < 0.001). After adjusting for all covariates, patients aged 50 to 69 with RS < 11 showed no statistically significant improvement in OS when adding ET to surgery, with or without radiation (P = 0.40). With RS 11 to 25, there was a significant improvement of OS with ET plus radiation (P < 0.001). CONCLUSIONS: Local treatment only, with de-escalation of long-term ET, for patients aged 50 to 69 with RS < 11, seems not to impact OS and should have an anticipated quality of life improvement. Prospective studies investigating this approach are warranted.

The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast.

BACKGROUND: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER 2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004-2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. CONCLUSION: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding.

Prognosis and Chemotherapy Use in Breast Cancer Patients with Multiple Lymphatic Micrometastases: An NCDB Analysis.

BACKGROUND: The number of involved lymph nodes negatively affects prognosis in breast cancer patients. Nevertheless, current staging and treatment recommendations do not distinguish between patients with single versus multiple lymphatic micrometastases. In this study, we aim to better characterize these patients. METHODS: The National Cancer Database was retrospectively queried to identify 486,800 women with stage I-III, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER+/PR+/HER2-) breast cancer and nodal status of N0, N1mi with 1 (Nmic1) or more (Nmic > 1) involved nodes, and N1 with 1 involved node (N1.1), from 2010 to 2016. Patients with different nodal statuses were compared regarding treatment characteristics, survival, and benefit from chemotherapy by their 21-gene recurrence score (RS). RESULTS: Of the 23,072 N1mi patients, 88.3% were Nmic1 and 11.7% were Nmic > 1. Nmic > 1 patients were younger, had larger and higher-grade tumors, with more lymphovascular invasion, and were more commonly treated by axillary dissection, radiation, and chemotherapy than Nmic1 patients. In that, they were comparable with N1.1 patients. Five-year survival of Nmic > 1 patients (88.1%) was worse than Nmic1 patients (90.1%; p = 0.02), but similar to N1.1 patients (87.9%). Nmic1, Nmic > 1, and N1.1 patients with RS 11-25 exhibited a < 2% absolute survival benefit associated with chemotherapy. With RS > 25, Nmic > 1 patients showed a 3.5% benefit, similar to Nmic1 (4.8%) and lower than N1.1 (10.9%) patients. CONCLUSIONS: Nmic > 1 breast cancer patients have worse prognoses than Nmic1 patients, similar to N1.1 patients. Our data suggest those patients with RS 11-25 have minimal benefit from chemotherapy. These findings should be taken into account when discussing prognosis and considering chemotherapy in patients with lymphatic micrometastases.

The 21-gene recurrence score in node-positive, hormone receptor-positive, HER2-negative breast cancer: a cautionary tale from an NCDB analysis.

PURPOSE: The 21-gene recurrence score assay (RS) has not been prospectively validated to predict adjuvant chemotherapy benefit in hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer patients. Nevertheless, de-escalation based on RS has been demonstrated and partially advocated by retrospective data. The purpose of this study was to identify subgroups of node-positive patients with low to intermediate RS who still benefit from adjuvant chemotherapy. METHODS: The National Cancer Database was used to identify 28,591 women with stage I-III, T1-T3, N1, HR+, HER2- breast cancer and a RS ≤ 25 between 2010 and 2016. Univariate and multivariate analyses were used to identify variables correlating with chemotherapy use and 5-year survival. Subgroup analysis was performed to discern patients in whom the use of adjuvant chemotherapy correlated with better survival. RESULTS: A 35% decline in chemotherapy use was observed from 2010 to 2016. Patients with younger age, higher RS, larger tumors and more positive lymph nodes, and those treated by mastectomy, axillary lymph node dissection and radiation, were more likely to receive chemotherapy. Chemotherapy use was associated with an improved 5-year survival (HR = 1.63, 95% CI 1.28-2.07). Upon subgroup analysis, this association was lost in patients > 70 years and those with a RS ≤ 11, while patients ≤ 70 with a RS of 12-25 treated with chemotherapy had an absolute 5-year survival advantage of 3.0% (HR = 1.91, 95% CI 1.42-2.57). CONCLUSION: Clinicians should be cautious when considering omission of adjuvant chemotherapy in patients ≤ 70 years, with HR+, HER2-, N1 tumors and a RS 12-25, at least until the results of the anticipated RxPONDER trial become available.

Eye plaque brachytherapy versus enucleation for ocular melanoma: an analysis from the National Cancer Database.

PURPOSE: There is no current randomized data comparing the efficacy of brachytherapy and enucleation for patients with larger sized tumors. The purpose of the present study was to use a large, contemporary database to determine current practice patterns and compare survival outcomes between different management options for patients with choroidal melanoma of various sizes. MATERIAL AND METHODS: The National Cancer Database was queried (2004-2014) for histologically-confirmed choroidal melanoma for patients treated with brachytherapy versus enucleation. Chi-square test was used to compare categorized demographic and clinical variables in both arms. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazards assessment determined variables associated with OS. Patients were divided into cohorts representing small, medium, and large tumors. Propensity scores matching (PSM) was utilized to compare more similar cohorts. RESULTS: A total of 7,096 patients met the selection criteria; 5,501 (78%) patients received brachytherapy and 1,595 (22%) patients were treated with enucleation. After PSM, 5-yr OS for small tumors was 87% vs. 64%, for medium tumors was 77% vs. 57%, and for large tumors was 68% vs. 46% for brachytherapy and enucleation, respectively (p < 0.001). Following PSM, multivariate Cox regression found older age (hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.51-2.06), more comorbidities (HR = 1.46, 95% CI = 1.25-1.70), extraocular extension (EOE) (HR = 1.25, 95% CI = 1.06-1.48), ciliary body invasion (CBI) (HR = 1.20, 95% CI = 1.02-1.40), and larger size (HR = 1.52, 95% CI = 1.40-1.66) were negative prognosticators of survival. Brachytherapy was a positive prognosticator of survival (HR = 0.45, 95% CI = 0.40-0.51). CONCLUSIONS: Patients selected for brachytherapy had improved survival compared to enucleation in all size cohorts. EOE and CBI are significantly higher in the enucleation cohort and are important negative prognosticators for survival selected against patients having brachytherapy. Brachytherapy is a reasonable treatment option for certain patients with large size tumors.

Long-Term Institutional Experience With Telemedicine Services for Radiation Oncology: A Potential Model for Long-Term Utilization.

PURPOSE: With the development of the coronavirus disease 2019 (COVID-19) pandemic, health care practices and radiation oncology departments have begun to incorporate telemedicine services to practice social distancing and minimize the chances of disease spread. Given the severity of this pandemic, it will likely fundamentally affect the use of these services for years to come. Our institution and radiation oncology department have used telemedicine services for many years; we would like to report on our departmental experience to guide other radiation oncology practices on its long-term use for clinical evaluation and patient care. METHODS AND MATERIALS: Our institution's telemedicine program provides clinical services for a number of remote locations and represents the largest telehealth network in the world, with over 300 sites and 60,000 patient encounters a year. RESULTS: Specifically for our radiation oncology department, over 200 patient encounters occur via telemedicine a year. Patients report great appreciation and satisfaction with these encounters, as they eliminate the time and energy needed for travel from long distances. It has resulted in improved efficiency and cost-effectiveness as well. CONCLUSIONS: Based on our institutional experience, our long-term vision for telemedicine (after COVID-19 pandemic has hopefully subsided) is as an excellent and cost-efficient tool to provide long-term follow-up for patients, especially for those who live far away in rural or underserved areas.

Prognosis of lymphotropic invasive micropapillary breast carcinoma analyzed by using data from the National Cancer Database.

BACKGROUND: Invasive micropapillary carcinoma (IMPC) is an uncommon subtype of breast cancer. Previous studies of this subtype demonstrated a higher propensity for lymph node metastases as compared with invasive ductal carcinoma (IDC). The purpose of the present study was to determine the clinical characteristics, outcomes, and propensity for lymph node metastasis of patients with IMPC of the breast recorded in the National Cancer Database (NCDB). METHODS: Records of patients with IMPC diagnosed between 2004 and 2014 were retrieved from the NCDB. Log-rank test was performed to evaluate associations of clinical characteristics with overall survival (OS). Cox proportional hazards model was used to determine variables associated with OS. RESULTS: Overall, 2660 patients with IMPC met the selection criteria; the 5-year OS rate was 87.5% and 24.9% of patients had nodal involvement at presentation. Patients with ≥ 4 positive lymph nodes had shorter OS than node-negative patients, whereas patients with 1-3 positive nodes had similar OS to node-negative patients. Age < 65 years, receipt of radiotherapy, and estrogen receptor positivity were also associated with prolonged OS. The benefit of radiotherapy was limited to IMPC patients undergoing lumpectomy; there was no benefit for the patients undergoing mastectomy (regardless of nodal positivity/negativity). CONCLUSIONS: Favorable prognostic factors of IMPC patients included age < 65 years, < 4 positive lymph nodes, receipt of radiotherapy, and estrogen receptor positivity. The results presented herein suggest a survival benefit associated with radiotherapy in IMPC treatment, though this may be limited to the patients treated with lumpectomy.

Diagnosis and Management of Metastatic Breast Cancer in a 33-year-old Pregnant Female: A Case Report.

Despite the rarity, breast cancer diagnosed during pregnancy implies multiple therapeutic dilemmas. The initial diagnostic process can be complicated by the physiological changes that occur in the breast during pregnancy, which can further lead to a delayed diagnosis. Moreover, treatment methods, as well as treatment onset and time of pregnancy termination, remain controversial. This case report highlights some of the inherent difficulties associated with breast cancer diagnosis and treatment in a pregnant patient. It also discusses how to optimize a multidisciplinary approach to improve health outcomes for both the mother and the infant.

The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)-positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow-up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2- disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR-HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African-American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.

Rare Mesenchymal Breast Entities that Mimic Malignancy: A Single-institution Experience of a Challenging Diagnosis.

Background Benign mesenchymal tumors of the breast are rare and may mimic invasive carcinoma on imaging and morphology, thus becoming clinically challenging for clinicians, radiologists, and pathologists. To improve the understanding of these lesions and to avoid erroneous diagnosis and inappropriate treatment, we report our institution's experience with seven cases of granular cell tumor (GCT) and myofibroblastoma (MFB) in the past 10 years. Materials and methods Seven cases of benign mesenchymal tumors of the breast were identified at the University of Texas Medical Branch from 2008 to 2018. Breast biopsies were collected from all patients after mammography and ultrasound imaging classified their results as suspicious or highly suggestive of malignancy by the Breast Imaging Reporting and Data System (BI-RADS ≥ 4A). All cases were reviewed to study the morphologic features and their immunoprofiles. The demographic characteristics, methods of treatment, postoperative pathological results, and follow-up results of the cases were then analyzed and compared to peer-reviewed literature. Results The study consisted of five females and two males with a mean age of 50 years in the GCT patients and 62 years in MFB patients. We identified four cases of GCT and three cases of MFB. The mean tumor size was 1.9 cm. Clinically, five patients presented with a palpable nontender mass, one with breast asymmetry, and one was asymptomatic. All patients underwent imaging studies prior to core needle biopsy. BI-RADS was ≥4B in patients with GCT and 4A-C in MFB. Definitive diagnosis was made by histopathology and confirmed by immunohistochemistry in accordance with the features described in the literature. Six patients underwent wide excision. The mean follow-up duration was 44.5 months. All patients remained well, without recurrence. Conclusions MFB and GCT can mimic malignant neoplasms and the clinical significance of these entities lies primarily in their recognition as distinctive benign neoplasms. The gold standard for the diagnosis of GCT and MFB is histopathology. All the cases in our series were clinically or radiologically mistaken for carcinoma, which has been largely reported in the literature. Pathologists should bear this in mind to avoid misdiagnosis and unnecessary treatment.

A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women.

BACKGROUND: Cancer cachexia negatively impacts cancer-related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was undertaken to assess the potential therapeutic role of adjunct testosterone to limit loss of body mass in patients with squamous cell carcinoma of the cervix or head and neck undergoing standard of care treatment including chemotherapy and chemoradiation. Patients were randomly assigned in blocks to receive weekly injections of either 100 mg testosterone enanthate or placebo for 7 weeks. The primary outcome was per cent change in lean body mass, and secondary outcomes included assessment of quality of life, tests of physical performance, muscle strength, daily activity levels, resting energy expenditure, nutritional intake, and overall survival. RESULTS: A total of 28 patients were enrolled, 22 patients were studied to completion, and 21 patients were included in the final analysis (12 placebo, nine testosterone). Adjunct testosterone increased lean body mass by 3.2% (95% confidence interval [CI], 0-7%) whereas those receiving placebo lost 3.3% (95% CI, -7% to 1%, P = 0.015). Although testosterone patients maintained more favourable body condition, sustained daily activity levels, and showed meaningful improvements in quality of life and physical performance, overall survival was similar in both treatment groups. CONCLUSIONS: In patients with advanced cancer undergoing the early phase of standard of care therapy, adjunct testosterone improved lean body mass and was also associated with increased quality of life, and physical activity compared with placebo.

Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data.

BACKGROUND: Overtreatment is a common concern for patients with ductal carcinoma in situ (DCIS), but this entity is difficult to distinguish from invasive breast cancers in administrative claims data sets because DCIS often is coded as invasive breast cancer. Therefore, the authors developed and validated algorithms to select DCIS cases from administrative claims data to enable outcomes research in this type of data. METHODS: This retrospective cohort using invasive breast cancer and DCIS cases included women aged 66 to 70 years in the 2004 through 2011 Texas Cancer Registry (TCR) data linked to Medicare administrative claims data. TCR records were used as "gold" standards to evaluate the sensitivity, specificity, and positive predictive value (PPV) of 2 algorithms. Women with a biopsy enrolled in Medicare parts A and B at 12 months before and 6 months after their first biopsy without a second incident diagnosis of DCIS or invasive breast cancer within 12 months in the TCR were included. Women in 2010 Medicare data were selected to test the algorithms in a general sample. RESULTS: In the TCR data set, a total of 6907 cases met inclusion criteria, with 1244 DCIS cases. The first algorithm had a sensitivity of 79%, a specificity of 89%, and a PPV of 62%. The second algorithm had a sensitivity of 50%, a specificity of 97%. and a PPV of 77%. Among women in the general sample, the specificity was high and the sensitivity was similar for both algorithms. However, the PPV was approximately 6% to 7% lower. CONCLUSIONS: DCIS frequently is miscoded as invasive breast cancer, and thus the proposed algorithms are useful to examine DCIS outcomes using data sets not linked to cancer registries. Cancer 2018;124:2815-2823. © 2018 American Cancer Society.

Treatment Outcomes and Prognostic Factors in Male Patients With Stage IV Breast Cancer: A Population-based Study.

PURPOSE: Male breast cancer (MBC) represents < 1% of breast cancer patients, and limited data exists regarding metastatic MBC. To better characterize this patient subset, we performed a population-based study examining prognostic factors among patients with stage IV MBC. METHODS: Patients with stage IV MBC diagnosed between 1988 and 2012 were selected from the Surveillance, Epidemiology, and End Results database. Prognostic factors for overall survival (OS) and cause-specific survival (CSS) were evaluated. RESULTS: Overall, 394 patients had metastatic disease meeting inclusion criteria. The median follow-up was 21 months. The 5-year OS and CSS rates were 21.1% and 38.3%, respectively. Of those with known progesterone receptor (PR) status, 52% were PR-positive, which was associated with better OS (P < .001) and CSS (P = .003). Overall, 197 patients (50%) received surgery for the primary tumor, and 197 (50%) did not. Patients undergoing surgery had longer median CSS than those who did not (36 vs. 21 months; P < .001). Additional factors that correlated with prolonged OS and CSS were smaller tumor size (≤ 2 cm; P < .05) and younger age (≤ 65 years; P < .05). In multivariate analysis, smaller tumor size, PR-positivity, younger age, and resection of the primary tumor were associated with longer OS and CSS (P < .05). CONCLUSIONS: Although stage IV MBC has poor OS and CSS, patients with PR-positive disease, younger age (≤ 65 years), tumor size ≤ 2 cm, or who undergo surgery of the primary tumor have better OS and CSS. This is the largest study of stage IV MBC to date, and these findings address some of the questions regarding this rare presentation of breast cancer.

Accelerated partial breast irradiation: Past, present, and future.

Accelerated partial breast irradiation (APBI) focuses higher doses of radiation during a shorter interval to the lumpectomy cavity, in the setting of breast conserving therapy for early stage breast cancer. The utilization of APBI has increased in the past decade because of the shorter treatment schedule and a growing body of outcome data showing positive cosmetic outcomes and high local control rates in selected patients undergoing breast conserving therapy. Technological advances in various APBI modalities, including intracavitary and interstitial brachytherapy, intraoperative radiation therapy, and external beam radiation therapy, have made APBI more accessible in the community. Results of early APBI trials served as the basis for the current consensus guidelines, and multiple prospective randomized clinical trials are currently ongoing. The pending long term results of these trials will help us identify optimal candidates that can benefit from ABPI. Here we provide an overview of the clinical and cosmetic outcomes of various APBI techniques and review the current guidelines for selecting suitable breast cancer patients. We also discuss the impact of APBI on the economics of cancer care and patient reported quality of life.