Translating evidence in a priority setting partnership: knowledge gaps between healthcare providers and oesophageal cancer patients.

INTRODUCTION: Despite the fact that health information is now more accessible than ever, knowledge gaps remain between patients and healthcare providers (HCPs). To date, the patients' need for information following a diagnosis of oesophageal cancer has not been adequately met. PURPOSE: The purpose of this study was to identify why knowledge gaps exist between oesophageal cancer patients and HCPs and how to address them. METHODS: Purposive sampling of a group of people living with and after oesophageal cancer who had participated in a priority-setting partnership where 45% of questions from patients had existing evidence-based answers. A 7-set question series was developed for use in a patient/HCP focus group in addition to 11 individual phone interviews with survivors of oesophageal cancer. Qualitative semistructured interviews were conducted to explore oesophageal cancer patients' access to information. The data was analysed thematically, which involved coding all patient transcripts before identifying and reviewing key themes. RESULTS: The three primary themes that emerged were as follows: opportunity (HCP team factors and relationship development), ability (patient factors) and priority (pacing of information delivery). CONCLUSION: Effective communication between patients and HCPs was identified as an integral component of the enhancement of patient knowledge. HCPs should continue to refine and improve methods of information delivery and encourage conversations regarding information preferences.

A qualitative study examining young peoples' perceptions and adherence to COVID-19 public health guidelines in Ireland.

BACKGROUND: Public health measures are the main intervention to stop the spread of COVID-19. They rely on the adherence to everyday health behaviors, and depend on those at high and low personal risk of serious disease to comply. Young people are crucial to stemming community transmission, and are often living in shared housing and at a stage of their lives with more economic uncertainty than older groups. Public health messaging has relied on the mantra that we are 'in it together,' despite very diverse experiences of the pandemic across different groups. The central aim of this research is to understand and optimize young peoples' engagement with public health guidelines with the view to improve future adherence with public health initiatives. METHOD: Twelve young people were interviewed as part of this research, ranging from 18 to 24 years. Interviewees were chosen to ensure that there was a diverse range of opinions within the participant pool. Interviews were semi-structured with open questions and the flexibility to explore the topics of interest that arose. All interviews were fully transcribed and analyzed using thematic analysis. RESULTS: This study found that participants deemed the consequences of lockdown a greater threat than infection with SARS-COV-2. Participants expressed concerns about the government's handling of the pandemic. Some felt young peoples' interests were not represented by authorities. There were concerns that messaging was inaccurate, difficult to understand, and filled with statistical and medical jargon. These perceptions underpinned a sense that the guidelines could be broken in good conscience as well as result in accidental breaches of the guidelines. Though wider community factors were often cited as having a positive influence on health behavior, differences and division were seen to inspire trust or adherence. CONCLUSION: These findings provide an insight into the psychological, financial and physical difficulties young people face as a consequence of pandemic public health measures and lockdowns in particular. They highlight the need for better communication with young people to support and embed trust in authorities and the scientific and political community.

The Effect of the 2009 USPSTF breast cancer screening recommendations on breast cancer in Michigan: A longitudinal study.

In 2009, the revised United States Preventive Services Task Force (USPSTF) guidelines recommended against routine screening mammography for women age 40-49 years and against teaching self-breast examinations (SBE). The aim of this study was to analyze whether breast cancer method of presentation changed following the 2009 USPSTF screening recommendations in a large Michigan cohort. Data were collected on women with newly diagnosed stage 0-III breast cancer participating in the Michigan Breast Oncology Quality Initiative (MiBOQI) registry at 25 statewide institutions from 2006 to 2015. Data included method of detection, cancer stage, treatment type, and patient demographics. In all, 30 008 women with breast cancer detected via mammogram or palpation with an average age of 60.1 years were included. 38% of invasive cancers were identified by palpation. Presentation with palpable findings decreased slightly over time, from 34.6% in 2006 to 28.9% in 2015 (P < .001). Over the 9-year period, there was no statistically significant change in rate of palpation-detected tumors for women age <50 years or ≥50 years (P = .27, .30, respectively). Younger women were more likely to present with palpable tumors compared to older women in a statewide registry. This rate did not increase following publication of the 2009 USPSTF breast cancer screening recommendations.

Variation in the use of advanced imaging at the time of breast cancer diagnosis in a statewide registry.

BACKGROUND: Although national guidelines do not recommend extent of disease imaging for patients with newly diagnosed early stage breast cancer given that the harm outweighs the benefits, high rates of testing have been documented. The 2012 Choosing Wisely guidelines specifically addressed this issue. We examined the change over time in imaging use across a statewide collaborative, as well as the reasons for performing imaging and the impact on cost of care. METHODS: Clinicopathologic data and use of advanced imaging tests (positron emission tomography, computed tomography, and bone scan) were abstracted from the medical records of patients treated at 25 participating sites in the Michigan Breast Oncology Quality Initiative (MiBOQI). For patients diagnosed in 2014 and 2015, reasons for testing were abstracted from the medical record. RESULTS: Of the 34,078 patients diagnosed with stage 0-II breast cancer between 2008 and 2015 in MiBOQI, 6853 (20.1%) underwent testing with at least 1 imaging modality in the 90 days after diagnosis. There was considerable variability in rates of testing across the 25 sites for all stages of disease. Between 2008 and 2015, testing decreased over time for patients with stage 0-IIA disease (all P < .001) and remained stable for stage IIB disease (P = .10). This decrease in testing over time resulted in a cost savings, especially for patients with stage I disease. CONCLUSION: Use of advanced imaging at the time of diagnosis decreased over time in a large statewide collaborative. Additional interventions are warranted to further reduce rates of unnecessary imaging to improve quality of care for patients with breast cancer. Cancer 2017;123:2975-83. © 2017 American Cancer Society.

Associations between use of the 21-gene recurrence score assay and chemotherapy regimen selection in a statewide registry.

BACKGROUND: The 21-gene recurrence score (RS) assay predicts response to adjuvant chemotherapy in patients with early-stage, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer, but to the authors' knowledge, the role of the assay in guiding the selection of chemotherapy regimen has not been established. The current study was conducted to examine patterns of use of the RS assay for selecting chemotherapy regimens across a statewide registry from 2006 through 2013. METHODS: Demographic, pathologic, and treatment data were abstracted from medical records for 16,666 women with breast cancer who were treated at 25 hospital systems across Michigan that were participating in the Michigan Breast Oncology Quality Initiative. Treatment patterns were examined based on the RS assay test result. RESULTS: Approximately 25% of patients with lymph node-negative disease who underwent testing with the RS assay and who were treated with chemotherapy received an anthracycline-based regimen, compared with 49% of patients with lymph node-negative disease who were treated with chemotherapy and who had not undergone testing with the RS assay. Of those patients with lymph node-positive disease who underwent testing with the RS assay and who received chemotherapy, 31% received an anthracycline-based regimen. In comparison, 71% of patients with lymph node-positive, chemotherapy-treated disease who did not undergo testing received an anthracycline. From 2006 through 2013, there was a statistically significant decrease in the use of anthracycline-containing regimens in both patients with lymph node-negative and lymph node-positive disease. CONCLUSIONS: Use of anthracycline-containing chemotherapy regimens in eligible patients appears to vary with use of the RS assay, despite the lack of evidence supporting use of the assay to guide regimen selection. Results of ongoing prospective trials should help to define the role of the RS assay in this setting. Cancer 2017;123:948-56. © 2016 American Cancer Society.

University of Michigan Comprehensive Cancer Center opportunities for improvement project.

The University of Michigan Comprehensive Cancer Center (UMCCC) Opportunities for Improvement project involved a detailed patient-level medical record review, feedback to medical providers and clinical leadership, and discussion of potential predictors of discordant or delayed care. The medical record review revealed that reasons for discordant or delayed care were well documented by clinical providers, and medical comorbidity was the most common predisposing factor. Another common theme was the difficulty in obtaining treatment records for patients who received a portion of their care outside UMCCC. The project provided a valuable opportunity to examine established processes of care and data collection and consider how the newly implemented electronic health record might support future efforts aimed at improving efficiency and communication among providers.

Outpatient parenteral antimicrobial therapy (OPAT) across the world: a comparative analysis-what lessons can we learn?

This paper presents a comparative analysis of Outpatient Parenteral Antimicrobial Therapy (OPAT) structures and delivery options across different countries. OPAT, a cost-effective alternative to inpatient care for patients requiring IV antimicrobial therapy, has demonstrated multiple benefits such as patient satisfaction, economic cost savings, and reduced hospital-acquired infections. Despite these advantages, there is considerable international variation in OPAT use and implementation. By examining the OPAT structures of multiple countries, we aim to identify areas of variation and explore opportunities for expansion and improvement of OPAT services.

Trends in advanced imaging use for women undergoing breast cancer surgery.

BACKGROUND: Evidence-based guidelines recommend limited perioperative diagnostic imaging for new breast cancer diagnoses. For patients aged >65 years, conventional imaging use (mammography, plain radiographs, and ultrasound) has remained stable, whereas advanced imaging (computed tomography [CT], nuclear medicine scans [positron emission tomography/bone scans], and magnetic resonance imaging [MRI]) use has increased. In this study, the authors evaluated traditional and advanced imaging use among younger patients (aged ≤ 65 years) undergoing breast cancer surgery. METHODS: The MarketScan Commercial Claims and Encounters Research Database from 2005 through 2008 was analyzed to evaluate the use of conventional and advanced diagnostic imaging associated with surgery for ductal carcinoma in situ (DCIS) or stage I through III invasive breast cancer. RESULTS: The study cohort included 52,202 women (13% with DCIS and 87% with stage I-III breast cancer). The proportion of patients undergoing conventional imaging remained stable, whereas the average number of conventional imaging tests per patient increased from 4.21 tests in 2005 to 4.79 tests per patient in 2008 (P < .0001). For advanced imaging, the proportion of women who underwent imaging increased from 48.8% in 2005 to 68.8% in 2008 (P < .0001), as did the number of tests per patient (from 1.53 tests in 2005 to 1.98 tests in 2008; P < .0001). MRI examinations accounted for nearly all of the increase in advanced imaging. Patients who underwent MRI examinations received significantly more traditional imaging tests compared with to those who did not, indicating that these tests are additive and are not replacing traditional imaging. CONCLUSIONS: The current results demonstrate that the use of perioperative breast MRI has increased among women aged <65 years. Further study is indicated to determine whether the benefits of this procedure justify increased use.

Is duct excision still necessary for all cases of suspicious nipple discharge?

Despite the low likelihood of malignancy, it is recommended that all women with pathologic nipple discharge undergo duct excision based on the inadequate sensitivity of diagnostic modalities. However, these data originates prior to recent improvements in breast imaging. We performed a retrospective review of patients evaluated in the setting of modern diagnostic breast imaging. Of 175 women referred to our breast clinic with a primary complaint of nipple discharge, 142 (81%) had suspicious discharge. Of the 23 patients who opted for observation over duct excision, with a mean follow-up of 3.3 years, none have been diagnosed with cancer. Among patients who proceeded with surgery, cancer was diagnosed in seven patients (5%). Six of the seven patients had either an abnormal mammogram or ultrasound. Among 46 patients with suspicious nipple discharge, a normal physical exam and normal diagnostic mammogram/ultrasound, only one malignancy (2%) was identified in a 79-year-old patient with a personal history of breast cancer. In selected patients with suspicious nipple discharge, but normal physical exam and diagnostic imaging, short-term observation with repeat evaluation seems reasonable for patients who do not desire duct excision.

Residual disease after re-excision lumpectomy for close margins.

INTRODUCTION: While a positive margin after an attempt at breast conservation therapy (BCT) is a reason for concern, there is more controversy regarding close margins. When re-excisions are performed, there is often no residual disease in the new specimen, calling into question the need for the procedure. We sought to examine the incidence of residual disease after re-excision for close margins and to identify predictive factors that may better select patients for re-excision. METHODS: Our IRB-approved prospective breast cancer database was queried for all breast cancer patients who underwent a re-excision lumpectomy for either close or positive margins after an attempt at BCT. Close margins are defined as < or =2 mm for invasive carcinoma and < or =3 mm for DCIS. Clinicopathologic features were correlated with the presence of residual disease in the re-excision specimen. RESULTS: Three hundred three patients (32%) underwent re-operation for either close (173) or positive (130) margins. Overall, 33% had residual disease identified, 42% of DCIS patients and 29% of patients with invasive disease, nearly identical to patients with positive margins. For patients with DCIS, only younger age was significantly related to residual disease. For patients with invasive cancer, only multifocality was significantly associated with residual disease (OR 3.64 [1.26-10.48]). However, patients without multifocality still had a substantial risk of residual disease. DISCUSSION: The presence of residual disease appears equal between re-excisions for close and positive margins. No subset of patients with either DCIS or invasive cancer could be identified with a substantially lower risk of residual disease.

Determinants of breast conservation rates: reasons for mastectomy at a comprehensive cancer center.

Bias in referral patterns and variations in multi-disciplinary management may impact breast conservation therapy (BCT) rates between hospitals. Retrospective studies of BCT rates are limited by their inability to differentiate indicated mastectomies versus those chosen by the patient. Our prospective breast cancer data base was queried for patients with invasive breast cancer who underwent surgical therapy at the University of Michigan over a 3-year period. Demographics, stage and histology were recorded along with the reason mastectomy was performed, categorized as "by need" (contraindication to BCT) or "by choice." Multivariate analysis was used to identify factors significantly associated with mastectomy by choice. BCT was associated with tumor size, histology and nodal status, but not older age, either by choice or by need. Of the 34% of patients initially felt to be poor candidates for BCT, it was absolutely contraindicated in 44%, while 56% were thought to have a tumor-to-breast size ratio too large for successful BCT. Of this latter group, 80% underwent neo-adjuvant chemotherapy in an attempt to downstage the primary tumor and perform BCT, which was successful in over half the patients. For the patients initially thought to be good candidates for BCT, only 15% chose to undergo mastectomy, while 5% eventually required mastectomy due to failed attempts to achieve negative margins. Overall, the BCT rate was 63%, however without the use of neo-adjuvant chemotherapy, the BCT rate would have been only 53%. At a tertiary referral center, BCT rates are driven more by contraindications than patient choice, and may be heavily skewed towards mastectomy due to referral patterns. In addition to tumor factors such as stage and histology, BCT rate can be dramatically impacted by neo-adjuvant chemotherapy or genetic counseling. Examining BCT rates alone as a measure of quality, therefore, is not an appropriate standard across institutions serving diverse populations.

Model based and empirical spectral analysis for the diagnosis of breast cancer.

We explored the use of both empirical (Partial Least Squares, PLS) and Monte Carlo model based approaches for the analysis of fluorescence and diffuse reflectance spectra measured ex vivo from freshly excised breast tissues and for the diagnosis of breast cancer. Features extracted using both approaches, i.e. principal components (PCs) obtained from empirical analysis or tissue properties obtained from model based analysis, displayed statistically significant difference between malignant and non-malignant tissues, and can be used to discriminate breast malignancy with comparable sensitivity and specificity of up to 90%. The PC scores of a subset of PCs also displayed significant correlation with the tissue properties extracted from the model based analysis, suggesting both approaches likely probe the same sources of contrast in the tissue spectra that discriminate between malignant and non-malignant breast tissues but in different ways.

Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach.

We explore the use of Monte-Carlo-model-based approaches for the analysis of fluorescence and diffuse reflectance spectra measured ex vivo from breast tissues. These models are used to extract the absorption, scattering, and fluorescence properties of malignant and nonmalignant tissues and to diagnose breast cancer based on these intrinsic tissue properties. Absorption and scattering properties, including beta-carotene concentration, total hemoglobin concentration, hemoglobin saturation, and the mean reduced scattering coefficient are derived from diffuse reflectance spectra using a previously developed Monte Carlo model of diffuse reflectance. A Monte Carlo model of fluorescence described in an earlier manuscript was employed to retrieve the intrinsic fluorescence spectra. The intrinsic fluorescence spectra were decomposed into several contributing components, which we attribute to endogenous fluorophores that may present in breast tissues including collagen, NADH, and retinol/vitamin A. The model-based approaches removes any dependency on the instrument and probe geometry. The relative fluorescence contributions of individual fluorescing components, as well as beta-carotene concentration, hemoglobin saturation, and the mean reduced scattering coefficient display statistically significant differences between malignant and adipose breast tissues. The hemoglobin saturation and the reduced scattering coefficient display statistically significant differences between malignant and fibrous/benign breast tissues. A linear support vector machine classification using (1) fluorescence properties alone, (2) absorption and scattering properties alone, and (3) the combination of all tissue properties achieves comparable classification accuracies of 81 to 84% in sensitivity and 75 to 89% in specificity for discriminating malignant from nonmalignant breast tissues, suggesting each set of tissue properties are diagnostically useful for the discrimination of breast malignancy.

Exploring the effect of the referring general surgeon's attitudes on breast reconstruction utilization.

BACKGROUND: Breast reconstruction rates remain low, at 5%-15% of mastectomy patients, despite the safety and high patient satisfaction of these procedures. Reasons for this are multifactorial, including the attitudes and biases of the referring breast surgeon, as well as patient factors. The purpose of this study was to explore attitudes of general surgeons towards breast reconstruction. METHODS: We surveyed 369 general surgeons in Wisconsin with questions about breast surgery. Responses from 135 (36%) surgeons were analyzed. RESULTS: Seventy-three percent of the respondents performed at least some breast surgery and were eligible for the study. For a little over 50% of the general surgeons surveyed, breast surgery made up less than 10% of their practice. Fifty-one percent never performed a skin-sparing mastectomy. A large number of breast surgeons (40%) did not refer all mastectomy patients for reconstruction. Reasons cited for not referring patients included the concerns over cancer recurrence and advanced patient age. Reasons for patients not undergoing reconstruction included patient's refusal, need for radiation therapy, delaying adjuvant oncologic treatment, patient factors, and having no plastic surgeon available locally. CONCLUSIONS: The decision by a patient to undergo breast reconstruction involves many complex factors. As a specialty, we should focus on improving the availability of breast reconstructive surgeons and educating referring surgeons and patients about reconstructive indications and options in order to positively affect the utilization of breast reconstruction.

A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries.

The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer.

We explore the effects of the illumination and collection geometry on optical spectroscopic diagnosis of breast cancer. Fluorescence and diffuse reflectance spectroscopy in the UV-visible spectral range are made with a multiseparation probe at three illumination-collection separations of 735, 980, and 1225 microm, respectively, from 13 malignant and 34 nonmalignant breast tissues. Statistical analysis is carried out on two types of data inputs: (1) the fluorescence and diffuse reflectance spectra recorded at each of the three illumination-collection separations and (2) the integrated fluorescence (at each excitation wavelength) or diffuse reflectance over the entire spectrum at all three illumination-collection separations. The results show that using the integrated fluorescence intensities recorded at a single excitation wavelength at all three illumination-collection separations can discriminate malignant from nonmalignant breast tissues with similar classification accuracy to that using spectral data measured at several excitation wavelengths with a single illumination-collection separation. These findings have significant implications with respect to the design of an optical system for breast cancer diagnosis. Examining the intensity attenuation at a single wavelength rather than spectral intensities at multiple wavelengths can significantly reduce the measurement and data processing time in a clinical setting as well as the cost and complexity of the optical system.

Suppression of tumorigenesis and induction of p15(ink4b) by Smad4/DPC4 in human pancreatic cancer cells.

PURPOSE: The tumor suppressor gene Smad4/DPC4, a key transcription factorin transforming growth factor beta (TGF-beta) signaling cascades,is inactivated in 50% of pancreatic adenocarcinomas. We seek to determine the role of Smad4/DPC4 in the suppression of tumor cell growth and in the regulation of TGF-beta-mediated expression of cell-cycle regulatory genes p15(ink4b) and p21(waf1). EXPERIMENTAL DESIGN: Smad4/DPC4 is overexpressed by adenoviral infection in CFPac-1 pancreatic cancer cells, in which the Smad4/DPC4 is homozygously deleted, and in Capan-1 pancreatic cancer cells, in which Smad4/DPC4 is not expressed. Expression of the TGF-beta downstream target gene p21(waf1), regulation of the p15(ink4b) promoter, anchorage-independent growth, and tumorigenesis were examined. RESULTS: We demonstrate that expression of Smad4/DPC4 in Capan-1 cells reduced anchorage-independent growth by more than 50%, and inhibited xenograft tumor growth. However, overexpression of Smad4/DPC4 did not inhibit CFPac-1 cell growth. Interestingly, Smad4/DPC4 induced expression of p15(ink4b), p21(waf1), and TGF-beta-responsive reporter gene in Capan-1 but not in CFPac-1 cells. Furthermore, we found a previously unidentified Smad4 binding element (SBE) located in the region between -356 and -329 bp of the p15(ink4b) promoter. The p15(ink4b) promoter reporter gene assays revealed that Smad4-dependent transcriptional activation is mediated by this SBE, which indicates that p15(ink4b) is one of the downstream target genes regulated by Smad/DPC4. CONCLUSION: These results explain the role of Smad4/DPC4 in TGF-beta-mediated inhibition of cell proliferation in vitro and in vivo. Moreover, these results suggest that Smad4/DPC4-mediated tumor suppression and induction of TGF-beta-regulated cell-cycle-inhibitory genes may depend on additional factors that are absent in CFPac-1 cells.

Lymphatic drainage patterns on early versus delayed breast lymphoscintigraphy performed after injection of filtered Tc-99m sulfur colloid in breast cancer patients undergoing sentinel lymph node biopsy.

The axillary lymph node status is the most important predictor of prognosis and aids in breast cancer treatment planning. Patients with breast cancer now frequently undergo sentinel lymph node (SLN) biopsy rather than axillary lymph node dissection to determine the status of the regional lymph nodes. However, the optimal timing of radionuclide injection relative to the timing of SLN biopsy remains controversial. The objective of this study was to compare the lymphatic drainage patterns on lymphoscintigraphy performed at 15 minutes to 4 hours and at 18 to 24 hours after injection of filtered Tc-99m sulfur colloid, and to determine whether, over time, radiocolloid migrates to second-echelon nodes that are not the SLNs. Fifteen women with breast cancer (mean age, 55 years; range, 38-78 years) were scheduled to undergo SLN biopsy after each received an injection of 18.5 MBq (0.5 mCi) filtered Tc-99m sulfur colloid into the breast parenchyma surrounding the tumor or biopsy cavity. Both early (15 minutes to 4 hours after radionuclide injection) and delayed (18-24 hours after radionuclide injection) lymphoscintigraphy was performed in each patient. SLN biopsy was performed, followed by completion axillary lymph node dissection and planned breast surgery. In each patient the patterns of distribution of the radionuclide in the lymph nodes were the same on early and delayed lymphoscintigrams. These findings, that the distributions of radionuclide in lymph nodes are identical on early and delayed images obtained after injection of filtered Tc-99m sulfur colloid, suggest that performing SLN biopsy on the day after injection does not diminish the accuracy of the technique in predicting the potential site of metastasis in the regional lymph nodes in patients undergoing this procedure for breast cancer.

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

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