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Objective.--Recent studies indicate that removal of the primary tumour may have a beneficial effect on mortality risk of patients with primary distant metastatic breast cancer (stage IV), although most of them did not rule out confounding by the presence of co-morbidity. In this retrospective study the impact of surgical resection of the primary tumour on the survival of patients with primary distant metastatic disease is investigated, taking into account the presence of co-morbidity and other potential confounders. Methods.--Between 1993 and 2004, 15769 patients with breast cancer were diagnosed in the south of the Netherlands. This study included the 728 patients with distant metastatic disease at initial presentation, which was 5% of all patients. Of them, 40% had surgery of the primary tumour. Follow-up was carried out until 1 July 2006. Results.--Median survival of the patients who had surgery of their primary tumour was significantly longer than for the patients who did not have surgery (31 vs. 14 months). The 5-year survival rates were 24.5% and 13.1%, respectively (p < 0.0001). In a multivariable Cox regression analysis, adjusting for age, period of diagnosis, T-classification, number of metastatic sites, co-morbidity, use of loco-regional radiotherapy and use of systemic therapy, surgery appeared to be an independent prognostic factor for overall survival (HR = 0.62; 95% CI 0.51-0.76). Conclusion.--Removal of the primary tumour in patients with primary distant metastatic disease was associated with a reduction of the mortality risk of around 40%. The association was independent of age, presence of co-morbidity and other potential confounders, but a randomized controlled trial will be needed to rule out residual confounding. [ABSTRACT FROM AUTHOR]

Abstract Background Brachytherapy as adjuvant treatment for early-stage breast cancer has become widely available and offers patients an expedited treatment schedule. Given this, many women are electing to undergo brachytherapy in lieu of standard fractionation radiotherapy. We compare outcomes between patients treated with accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy versus patients who were also eligible for and offered APBI but who chose whole breast radiation (WBI). Methods Patients treated from December 2002 through May 2007 were reviewed. Selection criteria included patients with pTis-T2N0 disease, ≤ 3 cm unifocal tumors, and negative margins who underwent breast conservation surgery. Local control (LC), cause-specific (CSS) and overall survival (OS) were analyzed. Results 202 patients were identified in the APBI cohort and 94 patients in the WBI cohort. Median follow-up for both groups exceeded 60 months. LC was 97.0% for the APBI cohort and 96.2% for the WBI cohort at 5 years (ns). Classification by 2010 ASTRO APBI consensus statement categories did not predict worse outcomes. Conclusion APBI via multicatheter interstitial brachytherapy provides similar local failure rates compared to WBI at 5 years for properly selected patients. Excellent results were seen despite the high fraction of younger patients (< 60 years old) and patients with DCIS.

Abstract Background Metastases to the breast occur rarely, but may be increasing in incidence as patients live longer with malignant diseases. The aim of this study is to characterize metastatic disease to the breast and to describe the management and prognosis of patients who present with this diagnosis. Methods A retrospective review of our institution's pathology and breast cancer databases was performed in order to identify patients with breast malignancies that were not of primary breast origin. Chart review provided additional information about the patients' primary malignancies and course of illness. Results Between 1991 and 2006, eighteen patients with metastatic disease to the breast of non-hematologic origin were identified and all had charts available for review. Among the 18 patients with disease metastatic to the breast, tissues of origin included 3 ovarian, 6 melanoma, 3 medullary thyroid, 3 pulmonary neuroendocrine, 1 pulmonary small cell, 1 oral squamous cell, and 1 renal cell. Overall mean survival after diagnosis of metastatic disease to the breast was 22.4 months. Treatment of metastases varied and included combinations of observation, surgery, radiation, and chemotherapy. Five patients (27.8%) required a change in management of their breast disease for local control. Conclusion Due to the variable course of patients with metastatic disease, a multi-disciplinary approach is necessary for each patient with disease metastatic to the breast to determine optimal treatment. Based on our review, many patients survive for long periods of time and local treatment of metastases to the breast may be beneficial in these patients to prevent local complications.

Breast cancer (BC) is defined by distinct molecular subtypes with different cells of origin. The transcriptional networks that characterize the subtype-specific tumor-normal lineages are not established. In this work, we applied bulk, single-cell and single-nucleus multi-omic techniques as well as spatial transcriptomics and multiplex imaging on 61 samples from 37 patients with BC to show characteristic links in gene expression and chromatin accessibility between BC subtypes and their putative cells of origin. Regulatory network analysis of transcription factors underscored the importance of BHLHE40 in luminal BC and luminal mature cells and KLF5 in basal-like tumors and luminal progenitor cells. Furthermore, we identify key genes defining the basal-like (SOX6 and KCNQ3) and luminal A/B (FAM155A and LRP1B) lineages. Exhausted CTLA4-expressing CD8 +  T cells were enriched in basal-like BC, suggesting an altered means of immune dysfunction. These findings demonstrate analysis of paired transcription and chromatin accessibility at the single-cell level is a powerful tool for investigating cancer lineage and highlight transcriptional networks that define basal and luminal BC lineages., (© 2024. The Author(s).)

Background: The purpose was to determine what factors help predict benefit from preoperative MRI., Methods: We conducted an IRB approved retrospective review of patients with breast cancer who underwent preoperative MRI (2018-2021). Patients were divided into a cohort of no new disease detected on MRI versus new disease detected., Results: Of 420 patients with a new diagnosis of breast cancer who underwent preoperative MRI, 17% had new multicentric, multifocal, or contralateral disease detected. There was no difference between the two cohorts for age (p = 0.23), race (p = 0.45), family history (p = 0.47), breast density (p = 0.14), or hormone status (p = 0.90). In multivariate analysis, age (p = 0.61, OR 0.99), race (p = 0.58, OR 1.26), family history (p = 0.54, OR 0.82), breast density (p = 0.83, OR 0.87), grade (p = 0.87, OR 1.09), tumor size (p = 0.37, OR 0.92), and use of neoadjuvant therapy (p = 0.41, OR 0.72) were not predictive of detection of additional new disease. Presence of positive nodes on ultrasound or mammogram was associated with new or multifocal disease on MRI (p = 0.0005, OR 3.48). Pre-MRI positive nodes increased the likelihood of detection of new disease (p = 0.0002, OR 3.04). Preoperative MRI resulted in more extensive surgery than indicated for 22.2% of the no new disease detected cohort and 6.9% of the new multicentric disease cohort (p < 0.001)., Conclusions: Patients with nodal disease detected in their evaluation are more likely to have new multifocal, multicentric, or contralateral disease detected on MRI. The use of preoperative MRI may be particularly helpful in patients with node-positive disease in identifying additional disease that would alter surgical management., (© 2023. Society of Surgical Oncology.)

Background: Shared decision making (SDM) in breast cancer care improves outcomes, but it is not routinely implemented. Results from the What Matters Most trial demonstrated that early-stage breast cancer surgery conversation aids, when used by surgeons after brief training, improved SDM and patient-reported outcomes. Trial surgeons and patients both encouraged using the conversation aids in routine care. We will develop and evaluate an online learning collaborative, called the SHared decision making Adoption Implementation Resource (SHAIR) Collaborative, to promote early-stage breast cancer surgery SDM by implementing the conversation aids into routine preoperative care. Learning collaboratives are known to be effective for quality improvement in clinical care, but no breast cancer learning collaborative currently exists. Our specific aims are to (1) provide the SHAIR Collaborative resources to clinical sites to use with eligible patients, (2) examine the relationship between the use of the SHAIR Collaborative resources and patient reach, and (3) promote the emergence of a sustained learning collaborative in this clinical field, building on a partnership with the American Society of Breast Surgeons (ASBrS)., Methods: We will conduct a two-phased implementation project: phase 1 pilot at five sites and phase 2 scale up at up to an additional 32 clinical sites across North America. The SHAIR Collaborative online platform will offer free access to conversation aids, training videos, electronic health record and patient portal integration guidance, a feedback dashboard, webinars, support center, and forum. We will use RE-AIM for data collection and evaluation. Our primary outcome is patient reach. Secondary data will include (1) patient-reported data from an optional, anonymous online survey, (2) number of active sites and interviews with site champions, (3) Normalization MeAsure Development questionnaire data from phase 1 sites, adaptations data utilizing the Framework for Reporting Adaptations and Modifications-Extended/-Implementation Strategies, and tracking implementation facilitating factors, and (4) progress on sustainability strategy and plans with ASBrS., Discussion: The SHAIR Collaborative will reach early-stage breast cancer patients across North America, evaluate patient-reported outcomes, engage up to 37 active sites, and potentially inform engagement factors affecting implementation success and may be sustained by ASBrS., (© 2023. The Author(s).)

Introduction: Breast reconstruction after a mastectomy is an important component of breast cancer care that improves the quality of life in breast cancer survivors. African American women are less likely to receive breast reconstruction than Caucasian women. The purpose of this study was to further investigate the reconstruction disparities we previously reported at a comprehensive cancer center by assessing breast reconstruction rates, patterns, and predictors by race., Methods: Data were obtained from women treated with definitive mastectomy between 2000 and 2012. Sociodemographic, tumor, and treatment characteristics were compared between African American and Caucasian women, and logistic regression was used to identify significant predictors of reconstruction by race., Results: African American women had significantly larger proportions of public insurance, aggressive tumors, unilateral mastectomies, and modified radical mastectomies. African American women had a significantly lower reconstruction rate (35% vs. 49%, p < 0.01) and received a larger proportion of autologous reconstruction (13% vs. 7%, p < 0.01) compared to Caucasian women. The receipt of adjuvant radiation therapy was a significant predictor of breast reconstruction in Caucasian but not African American women., Conclusions: We identified breast reconstruction disparities in rate and type of reconstruction. These disparities may be due to racial differences in sociodemographic, tumor, and treatment characteristics. The predictors of breast reconstruction varied by race, suggesting that the mechanisms underlying breast reconstruction may vary in African American women. Future research should take a target approach to examine the relative contributions of sociodemographic, tumor, and treatment determinants of the breast reconstruction disparities in African American women., (© 2021. W. Montague Cobb-NMA Health Institute.)

Background: Conversation aids can facilitate shared decision-making and improve patient-centered outcomes. However, few examples exist of sustained use of conversation aids in routine care due to numerous barriers at clinical and organizational levels. We explored factors that will promote the sustained use of two early-stage breast cancer conversation aids. We examined differences in opinions between the two conversation aids and across socioeconomic strata., Methods: We nested this study within a randomized controlled trial that demonstrated the effectiveness of two early-stage breast cancer surgery conversation aids, one text-based and one picture-based. These conversation aids facilitated more shared decision-making and improved the decision process, among other outcomes, across four health systems with socioeconomically diverse patient populations. We conducted semi-structured interviews with a purposive sample of patient participants across conversation aid assignment and socioeconomic status (SES) and collected observations and field notes. We interviewed trial surgeons and other stakeholders. Two independent coders conducted framework analysis using the NOrmalization MeAsure Development through Normalization Process Theory. We also conducted an inductive analysis. We conducted additional sub-analyses based on conversation aid assignment and patient SES., Results: We conducted 73 semi-structured interviews with 43 patients, 16 surgeons, and 14 stakeholders like nurses, cancer center directors, and electronic health record (EHR) experts. Patients and surgeons felt the conversation aids should be used in breast cancer care in the future and were open to various methods of giving and receiving the conversation aid (EHR, email, patient portal, before consultation). Patients of higher SES were more likely to note the conversation aids influenced their treatment discussion, while patients of lower SES noted more influence on their decision-making. Intervention surgeons reported using the conversation aids did not lengthen their typical consultation time. Most intervention surgeons felt using the conversation aids enhanced their usual care after using it a few times, and most patients felt it appeared part of their normal routine., Conclusions: Key factors that will guide the future sustained implementation of the conversation aids include adapting to existing clinical workflows, flexibility of use, patient characteristics, and communication preferences., Trial Registration: ClinicalTrials.gov Identifier: NCT03136367 , registered on May 2, 2017.

Background: Little is known about the effect of health professionals' advice on promoting healthy lifestyle behaviors (diet and exercise) among breast cancer patients., Purpose: To identify predictors of receiving lifestyle advice from health professionals and its impact on healthy lifestyle behaviors., Methods: We used data from a randomized controlled trial of an interactive, cancer-communication video program using African American breast cancer survivor stories for newly diagnosed African American breast cancer patients (Stages 0-III). Participants completed five interviews over 2 years. This intervention did not significantly affect changes in quality-of-life outcomes. In secondary analysis, we examined differences in baseline variables between women with and without diabetes. Logistic regression models identified independent predictors of receiving advice from "a doctor or other health professional" to improve diet and exercise and of self-reported change in diet and exercise habits at 2 year follow-up., Results: Of 193 patients included (85% of 228 enrolled), 53 (28%) had diabetes. At 2 year follow-up, a greater proportion of women with (vs. without) diabetes reported receiving advice by a doctor/health professional to improve their diet (73% vs. 57%, p = .04,). Predictors of receiving dietary advice were obesity, diabetes, and breast-conserving surgery (each p < .05). Women receiving dietary advice were 2.75 times more likely to report improving their diet (95% confidence interval: 1.17, 6.46) at follow-up, but receiving physical activity advice was not significantly associated with patients reporting an increase in exercise., Conclusions: Although receiving dietary advice predicted dietary improvements, receiving exercise advice did not lead to an increase in physical activity., Clinical Trial Registration: Trial Number NCT00929084., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Women of lower socioeconomic status (SES) with early-stage breast cancer are more likely to report poorer physician-patient communication, lower satisfaction with surgery, lower involvement in decision making, and higher decision regret compared to women of higher SES. The objective of this study was to understand how to support women across socioeconomic strata in making breast cancer surgery choices., Methods: We conducted a 3-arm (Option Grid, Picture Option Grid, and usual care), multisite, randomized controlled superiority trial with surgeon-level randomization. The Option Grid (text only) and Picture Option Grid (pictures plus text) conversation aids were evidence-based summaries of available breast cancer surgery options on paper. Decision quality (primary outcome), treatment choice, treatment intention, shared decision making (SDM), anxiety, quality of life, decision regret, and coordination of care were measured from T0 (pre-consultation) to T5 (1-year after surgery., Results: Sixteen surgeons saw 571 of 622 consented patients. Patients in the Picture Option Grid arm (n = 248) had higher knowledge (immediately after the visit [T2] and 1 week after surgery or within 2 weeks of the first postoperative visit [T3]), an improved decision process (T2 and T3), lower decision regret (T3), and more SDM (observed and self-reported) compared to usual care (n = 257). Patients in the Option Grid arm (n = 66) had higher decision process scores (T2 and T3), better coordination of care (12 weeks after surgery or within 2 weeks of the second postoperative visit [T4]), and more observed SDM (during the surgical visit [T1]) compared to usual care arm. Subgroup analyses suggested that the Picture Option Grid had more impact among women of lower SES and health literacy. Neither intervention affected concordance, treatment choice, or anxiety., Conclusions: Paper-based conversation aids improved key outcomes over usual care. The Picture Option Grid had more impact among disadvantaged patients., Lay Summary: The objective of this study was to understand how to help women with lower incomes or less formal education to make breast cancer surgery choices. Compared with usual care, a conversation aid with pictures and text led to higher knowledge. It improved the decision process and shared decision making (SDM) and lowered decision regret. A text-only conversation aid led to an improved decision process, more coordinated care, and higher SDM compared to usual care. The conversation aid with pictures was more helpful for women with lower income or less formal education. Conversation aids with pictures and text helped women make better breast cancer surgery choices., (© 2020 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: Our purpose was to describe the risk of radiation-induced brachial plexopathy (RIBP) in patients with breast cancer who received comprehensive adjuvant radiation therapy (RT)., Methods and Materials: Records for 498 patients who received comprehensive adjuvant RT (treatment of any residual breast tissue, the underlying chest wall, and regional nodes) between 2004 and 2012 were retrospectively reviewed. All patients were treated with conventional 3 to 5 field technique (CRT) until 2008, after which intensity modulated RT (IMRT) was introduced. RIBP events were determined by reviewing follow-up documentation from oncologic care providers. Patients with RIBP were matched (1:2) with a control group of patients who received CRT and a group of patients who received IMRT. Dosimetric analyses were performed in these patients to determine whether there were differences in ipsilateral brachial plexus dose distribution between RIBP and control groups., Results: Median study follow-up was 88 months for the overall cohort and 92 months for the IMRT cohort. RIBP occurred in 4 CRT patients (1.6%) and 1 IMRT patient (0.4%) ( P = .20). All patients with RIBP in the CRT cohort received a posterior axillary boost. Maximum dose to the brachial plexus in RIBP, CRT control, and IMRT control patients had median values of 56.0 Gy (range, 49.7-65.1), 54.8 Gy (47.4-60.5), and 54.8 Gy (54.2-57.3), respectively., Conclusions: RIBP remains a rare complication of comprehensive adjuvant breast radiation and no clear dosimetric predictors for RIBP were identified in this study. The IMRT technique does not appear to adversely affect the development of this late toxicity., (© 2020 The Authors.)

Lipofilling has regenerative properties used to improve deformities after breast conserving surgery. Our hypothesis is that there is inadequate data to ensure that lipofilling does not increase locoregional cancer recurrence after breast conserving surgery. A PRISMA comprehensive literature review was conducted of articles published prior to October 2019 investigating recurrence in patients who underwent lipofilling after breast conserving surgery. All forms of breast conserving surgery, fat grafting, and injection intervals were included. Patients undergoing mastectomy were excluded. Requirements to define lipofilling as "safe" included (I) a defined interval between resection and lipofilling; (II) a minimum follow-up period of 6 years from tumor resection; (III) a minimum follow-up period of 3 years from lipofilling; (IV) presence of a control group; (V) controls matched for ER/PR/Her-2; (VI) a sub-group analysis focusing on ER/PR/Her-2; (VII) adequate powering. Nineteen studies met inclusion criteria. The range in time from breast conserving surgery to fat injection was 0-76 months. The average time to follow-up after lipofilling was 23 days-60 months. Two studies had a sufficient follow-up time from both primary resection and from lipofilling. Seventeen of the nineteen studies specified the interval between resection and lipofilling, but there is currently no consensus regarding how soon lipofilling can be performed following BCS. Eight studies performed a subgroup analysis in cases of recurrence and found recurrence after lipofilling was associated with number of positive axillary nodes, intraepithelial neoplasia, high grade histology, Luminal A subtype, age <50, Ki-67 expression, and lipofilling within 3 months of primary resection. Of the eleven studies that included a comparison group, one matched patient for Her-2 and there was a statistically significant difference in Her-2 positive cancers in the study arms of two articles. Several studies deemed lipofilling "safe," two showed association of lipofilling and local recurrence, and most studies concluded that further research was needed. Insufficient and contradictory data exists to demonstrate the safety of lipofilling after breast conserving surgery. A multicentered, well designed study is needed to verify the safety of this practice., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Gland Surgery. All rights reserved.)

Background: There is limited compensation data for breast surgery benchmarking. In 2018, the American Society of Breast Surgeons conducted its second membership survey to obtain updated compensation data as well as information on practice type and setting., Methods: In October 2018, a survey was emailed to 2676 active members. Detailed information on compensation was collected, as well as data on gender, training, years in and type of practice, percent devoted to breast surgery, workload, and location. Descriptive statistics and multivariate analyses were performed to analyze the impact of various factors on compensation., Results: The response rate was 38.2% (n = 1022, of which 73% were female). Among the respondents, 61% practiced breast surgery exclusively and 54% were fellowship trained. The majority of fellowship-trained surgeons within 5 years of completion of training (n = 126) were female (91%). Overall, mean annual compensation was $370,555. On univariate analysis, gender, years of practice, practice type, academic position, ownership, percent breast practice, and clinical productivity were associated with compensation, whereas fellowship training, region, and practice setting were not. On multivariate analysis, higher compensation was significantly associated with male gender, years in practice, number of cancers treated per year, and wRVUs. Compensation was lower among surgeons who practiced 100% breast compared with those who did a combination of breast and other surgery., Conclusions: Differences in compensation among breast surgeons were identified by practice type, academic position, ownership, years of practice, percent breast practice, workload, and gender. Overall, mean annual compensation increased by $40,000 since 2014.

Introduction. Breast cancer is the second most common malignancy in women. The Decision Quality Instrument (DQI) measures the extent to which patients are informed and involved in breast surgery decisions and receive treatment that aligns with their preferences. There are limited data on the performance of the DQI in women of lower socioeconomic status (SES). Our aims were to 1) examine (and if necessary adapt) the readability, usability, and acceptability of the DQI and 2) explore whether it captures factors important to breast cancer surgery decisions among women of lower SES (relevance). Methods. We conducted semistructured cognitive interviews with women of lower SES (based on insurance status, income, and education) who had completed early-stage breast cancer treatments at three cancer centers. We used a two-step thematic analysis with dual independent coding. The study team (including Patient Partners and a Community Advisory Board) reviewed and refined suggested changes. The revised DQI was presented in two focus groups of breast cancer survivors. Results. We conducted 39 interviews. Participants found most parts of the DQI to be helpful and easy to understand. We made the following suggested changes: 1) added a glossary of key terms, 2) added two answer choices and an open text question in the goals and concerns subscale, 3) reworded the treatment intention question, and 4) revised the knowledge subscale instructions since several women disliked the wording and were unsure of what was expected. Discussion. The readability, usability, acceptability, and relevance of a measure that was primarily developed and validated in women of higher SES required adaptation for optimal use by women of lower SES. Further research will test these adaptations in lower SES populations., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GE and M-AD have developed the Option Grid patient decision aids, which are licensed to EBSCO Health. They receive consulting income from EBSCO Health and may receive royalties in the future. M-AD is a consultant for ACCESS Community Health Network. KS receives salary support as a member of the scientific advisory board for Healthwise, a not-for-profit foundation that develops and distributes patient education and decision support materials. MCP received a speaker fee from Merck & Co. and as a research contract from Merck, both unrelated to this study or manuscript. The other authors have no conflicts of interest to disclose.

Background: Breast cancer is the most commonly diagnosed malignancy in women. Mastectomy and breast-conserving surgery (BCS) have equivalent survival for early stage breast cancer. However, each surgery has different benefits and harms that women may value differently. Women of lower socioeconomic status (SES) diagnosed with early stage breast cancer are more likely to experience poorer doctor-patient communication, lower satisfaction with surgery and decision-making, and higher decision regret compared to women of higher SES. They often play a more passive role in decision-making and are less likely to undergo BCS. Our aim is to understand how best to support women of lower SES in making decisions about early stage breast cancer treatments and to reduce disparities in decision quality across socioeconomic strata., Methods: We will conduct a three-arm, multi-site randomized controlled superiority trial with stratification by SES and clinician-level randomization. At four large cancer centers in the United States, 1100 patients (half higher SES and half lower SES) will be randomized to: (1) Option Grid, (2) Picture Option Grid, or (3) usual care. Interviews, field-notes, and observations will be used to explore strategies that promote the interventions' sustained use and dissemination. Community-Based Participatory Research will be used throughout. We will include women aged at least 18 years of age with a confirmed diagnosis of early stage breast cancer (I to IIIA) from both higher and lower SES, provided they speak English, Spanish, or Mandarin Chinese. Our primary outcome measure is the 16-item validated Decision Quality Instrument. We will use a regression framework, mediation analyses, and multiple informants analysis. Heterogeneity of treatment effects analyses for SES, age, ethnicity, race, literacy, language, and study site will be performed., Discussion: Currently, women of lower SES are more likely to make treatment decisions based on incomplete or uninformed preferences, potentially leading to poorer decision quality, quality of life, and decision regret. This study hopes to identify solutions that effectively improve patient-centered care across socioeconomic strata and reduce disparities in decision and care quality., Trial Registration: NCT03136367 at ClinicalTrials.gov Protocol version: Manuscript based on study protocol version 2.2, 7 November 2017.

Image-guided surgery can enhance cancer treatment by decreasing, and ideally eliminating, positive tumor margins and iatrogenic damage to healthy tissue. Current state-of-the-art near-infrared fluorescence imaging systems are bulky and costly, lack sensitivity under surgical illumination, and lack co-registration accuracy between multimodal images. As a result, an overwhelming majority of physicians still rely on their unaided eyes and palpation as the primary sensing modalities for distinguishing cancerous from healthy tissue. Here we introduce an innovative design, comprising an artificial multispectral sensor inspired by the Morpho butterfly's compound eye, which can significantly improve image-guided surgery. By monolithically integrating spectral tapetal filters with photodetectors, we have realized a single-chip multispectral imager with 1000 × higher sensitivity and 7 × better spatial co-registration accuracy compared to clinical imaging systems in current use. Preclinical and clinical data demonstrate that this technology seamlessly integrates into the surgical workflow while providing surgeons with real-time information on the location of cancerous tissue and sentinel lymph nodes. Due to its low manufacturing cost, our bio-inspired sensor will provide resource-limited hospitals with much-needed technology to enable more accurate value-based health care., Competing Interests: The authors declare no competing financial interests.

Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor-positive (ER + ) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA -mutant ER + breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER + breast cancer. Experimental Design: Potential eligible patients with clinical stage II/III ER + /HER2 - breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing. Patients positive for PIK3CA mutation in the tumor were eligible to start MK-2206 (150 mg orally weekly, with prophylactic prednisone) on cycle 1 day 2 (C1D2) and to receive a maximum of four 28-day cycles of combination therapy before surgery. Serial biopsies were collected at preregistration, C1D1 and C1D17. Results: Fifty-one patients preregistered and 16 of 22 with PIK3CA -mutant tumors received study drug. Three patients went off study due to C1D17 Ki67 >10% ( n = 2) and toxicity ( n = 1). Thirteen patients completed neoadjuvant therapy followed by surgery. No pCRs were observed. Rash was common. MK-2206 did not further suppress cell proliferation and did not induce apoptosis on C1D17 biopsies. Although AKT phosphorylation was reduced, PRAS40 phosphorylation at C1D17 after MK-2206 persisted. One patient acquired an ESR1 mutation at surgery. Conclusions: MK-2206 is unlikely to add to the efficacy of anastrozole alone in PIK3CA -mutant ER + breast cancer and should not be studied further in the target patient population. Clin Cancer Res; 23(22); 6823-32. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Rationale: Social support plays an important role in quality of life and health outcomes after breast cancer diagnosis and treatment., Objective: To examine changes in perceived social support in African American women during the two years following a new breast cancer diagnosis., Methods: This secondary analysis uses data collected from 2009 to 2015 from 227 newly diagnosed, African American women with breast cancer (mean age 56 [SD = 10], 59% household income < $25,000; 28% married/partnered, 72% early stage) participating in a randomized controlled trial testing the effects of a video-communication intervention on quality-of-life and follow-up care. Participants, all of whom received treatment in one metropolitan area of the Midwestern United States, completed five telephone interviews over 2-year follow-up; demographic, psychosocial, quality of life, and clinical data were collected. Growth curve models were used to examine change in perceived social support (measured by the Medical Outcomes Study Social Support Survey) as well as correlates of baseline levels of social support and predictors of change in individuals' social support. Additional analyses examined whether change in social support over the first year affected depressive symptoms (Center for Epidemiologic Studies Depression Scale) and general health perceptions (RAND SF-36 subscale) at two years., Results: Being married, reporting greater spirituality, and reporting fewer depressive symptoms at baseline were significantly associated with higher initial levels of perceived social support. Women whose social support declined during the first year after diagnosis reported more severe depressive symptoms and worse general health perceptions at two years., Conclusion: Clinicians should periodically assess perceived social support among African American women with breast cancer to help find support resources for those who have low initial social support and for those whose support declines in the first year after diagnosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER + ) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design: Eligible patients with clinical stage II/III ER + /HER2 - breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 > 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%). Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P < 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression. Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055-65. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: The inability to visualize the patient and surgical site directly, limits the use of current near infrared fluorescence-guided surgery systems for real-time sentinel lymph node biopsy and tumor margin assessment., Methods: We evaluated an optical see-through goggle augmented imaging and navigation system (GAINS) for near-infrared, fluorescence-guided surgery. Tumor-bearing mice injected with a near infrared cancer-targeting agent underwent fluorescence-guided, tumor resection. Female Yorkshire pigs received hind leg intradermal indocyanine green injection and underwent fluorescence-guided, popliteal lymph node resection. Four breast cancer patients received 99m Tc-sulfur colloid and indocyanine green retroareolarly before undergoing sentinel lymph node biopsy using radioactive tracking and fluorescence imaging. Three other breast cancer patients received indocyanine green retroareolarly before undergoing standard-of-care partial mastectomy, followed by fluorescence imaging of resected tumor and tumor cavity for margin assessment., Results: Using near-infrared fluorescence from the dyes, the optical see-through GAINS accurately identified all mouse tumors, pig lymphatics, and four pig popliteal lymph nodes with high signal-to-background ratio. In 4 human breast cancer patients, 11 sentinel lymph nodes were identified with a detection sensitivity of 86.67 ± 0.27% for radioactive tracking and 100% for GAINS. Tumor margin status was accurately predicted by GAINS in all three patients, including clear margins in patients 1 and 2 and positive margins in patient 3 as confirmed by paraffin-embedded section histopathology., Conclusions: The optical see-through GAINS prototype enhances near infrared fluorescence-guided surgery for sentinel lymph node biopsy and tumor margin assessment in breast cancer patients without disrupting the surgical workflow in the operating room.

Purpose: We report the toxicity of patients treated with strut-adjusted volume implant (SAVI) for accelerated partial breast irradiation treated at our institution., Methods and Materials: Patients treated from January 2013 to July 2015 with SAVI planned for 10 b.i.d. fractions for a total dose of 34 Gy were included. Acute and late toxicities were prospectively collected on patients in followup and graded by the Common Terminology Criteria for Adverse Events, version 4.0., Results: A total of 132 patients were included, with 1 patient having synchronous breast cancer treated in each breast. Median followup was 20.0 months (range, 2.7-37.4 months). The median age at diagnosis was 61 years (range, 41-83 years). Forty-two lesions (32%) were in situ, 88 lesions (66%) were Stage 1, and 3 (2%) lesions were Stage 2. The median planning target volume was 58.2 cc (range, 24.2-109.9 cc), median V150 was 26.3 cc (range, 11.5-47.5 cc), and median V200 was 13.0 cc (range, 6.3-26.1 cc). On a pain scale of 0-10 (10 = worst pain), pain was worst on Day 2 of treatment, with an average score of 0.46. There was one acute skin infection; there were three late skin infections, two of which was Grade 3. Other late toxicities were Grade 1 or 2: hyperpigmentation (44%), telangiectasia (0.8%), seroma (9%), fat necrosis (5%), and fibrosis (12%). Crude local recurrence rate was 4%., Conclusion: SAVI is a safe treatment option for patients who are candidates for accelerated partial breast irradiation. Local control seems to be excellent, but longer followup is needed., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Breast reconstruction after mastectomy is an integral part of breast cancer treatment that positively impacts quality of life in breast cancer survivors. Although breast reconstruction rates have increased over time, African American women remain less likely to receive breast reconstruction compared to Caucasian women. National Cancer Institute-designated Comprehensive Cancer Centers, specialized institutions with more standardized models of cancer treatment, report higher breast reconstruction rates than primary healthcare facilities. Whether breast reconstruction disparities are reduced for women treated at comprehensive cancer centers is unclear. The purpose of this study was to further investigate breast reconstruction rates and determinants at a comprehensive cancer center in St. Louis, Missouri., Methods: Sociodemographic and clinical data were obtained for women who received mastectomy for definitive surgical treatment for breast cancer between 2000 and 2012. Logistic regression was used to identify factors associated with the receipt of breast reconstruction., Results: We found a breast reconstruction rate of 54 % for the study sample. Women who were aged 55 and older, had public insurance, received unilateral mastectomy, and received adjuvant radiation therapy were significantly less likely to receive breast reconstruction. African American women were 30 % less likely to receive breast reconstruction than Caucasian women., Conclusion: These findings suggest that racial disparities in breast reconstruction persist in comprehensive cancer centers. Future research should further delineate the determinants of breast reconstruction disparities across various types of healthcare institutions. Only then can we develop interventions to ensure all eligible women have access to breast reconstruction and the improved quality of life it affords breast cancer survivors.

The inability to identify microscopic tumors and assess surgical margins in real-time during oncologic surgery leads to incomplete tumor removal, increases the chances of tumor recurrence, and necessitates costly repeat surgery. To overcome these challenges, we have developed a wearable goggle augmented imaging and navigation system (GAINS) that can provide accurate intraoperative visualization of tumors and sentinel lymph nodes in real-time without disrupting normal surgical workflow. GAINS projects both near-infrared fluorescence from tumors and the natural color images of tissue onto a head-mounted display without latency. Aided by tumor-targeted contrast agents, the system detected tumors in subcutaneous and metastatic mouse models with high accuracy (sensitivity = 100%, specificity = 98% ± 5% standard deviation). Human pilot studies in breast cancer and melanoma patients using a near-infrared dye show that the GAINS detected sentinel lymph nodes with 100% sensitivity. Clinical use of the GAINS to guide tumor resection and sentinel lymph node mapping promises to improve surgical outcomes, reduce rates of repeat surgery, and improve the accuracy of cancer staging.

Background: For stage I-II breast cancer, routine radiologic staging in the absence of symptoms suggesting distant metastasis is not recommended. This study aims to determine the yield of these studies at a National Comprehensive Cancer Network member institution., Methods: Patients presenting with clinical stage I-II breast cancer between 1998 and 2012 were identified in a prospective database. Charts were reviewed to document staging studies (computed tomography, bone scan, and positron emission tomography) performed within 6 mo of diagnosis. Results and additional diagnostic procedures were recorded. Appropriate statistical tests were used for the analysis., Results: A total of 3291 patients were included (2044 stage I and 1247 stage II). Eight hundred eighty-two patients (27%) received computed tomography, bone scan, or positron emission tomography within 6 mo of diagnosis. Three hundred twelve patients were stage I (15% of the stage I cohort) and 570 patients were stage II (46% of the stage II cohort). Patients receiving staging studies were more often younger and had estrogen receptor/progesterone receptor-negative or HER2/neu-positive tumors. Of the 882 patients, 194 (22%) required additional imaging and/or biopsies to further evaluate abnormalities. Only 11 of those (5%) were confirmed to have metastasis (1.2% of the imaged patients, 0.3% of the total cohort). Of these, 1 was stage I at presentation and 10 were stage II., Conclusions: Identification of distant metastasis among stage I-II patients was rare. Even among patients judged appropriate for staging, only 1.2% were diagnosed with metastatic disease. These findings suggest that even at a National Comprehensive Cancer Network member institution staging studies are overused and lead to additional testing in over 20% of patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Atypical lesions and lobular carcinoma in situ (LCIS) are associated with an increased risk of breast malignancy. The utility of breast magnetic resonance imaging (MRI) screening in this cohort of women after excision of a high-risk lesion has not been previously established. The objective of this study was to investigate outcomes of breast MRI surveillance in this subgroup of high-risk patients., Materials and Methods: We performed a retrospective review of women who required excision of an atypical lesion or LCIS who underwent at least one screening breast MRI from April 2005-December 2011. We collected information on demographics, number of second-look imaging studies recommended, number of biopsies performed and pathologic outcomes., Results: A total of 179 patients met the inclusion criteria, including 131 (73%) with atypical lesions and 48 (27%) with LCIS. Second-look imaging was recommended for 31 of 131 (23.7%) patients with atypical lesions and 8 of 48 (16.7%) with LCIS. Ten biopsies were performed in the atypical cohort (7.6%) with two revealing a malignancy (Positive Predictive Value [PPV] of 20%). In the LCIS cohort, five biopsies were performed (10.4%) with one revealing a malignancy (PPV of 20%)., Conclusions: The benefit of breast MRI surveillance in patients after excision of atypical lesions or LCIS has not been clearly delineated previously. Our data demonstrate that the use of screening breast MRI in this cohort results in additional work-up in one-fifth of patients, but a PPV of only 20%. Large, prospective studies would be needed to determine whether breast cancer outcomes differ between patients undergoing conventional breast screening and those undergoing conventional breast screening plus breast MRI surveillance., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Breast cancer is a major health problem worldwide. The median survival duration for patients with metastatic breast cancer is two to three years. Approximately 1% of populations worldwide have schizophrenia. The manner in which schizophrenic patients fare when diagnosed with metastatic breast carcinoma (MBC) was evaluated. We queried the National Department of Veterans Affairs (DVA) datasets using computer codes for a pre-existing diagnosis of schizophrenia and a later diagnosis of breast carcinoma. Chart-based data concerning the identified subjects were then requested. Previously determined inclusion and exclusion criteria were applied to select evaluable patients from the medical records, prior to extracting demographic details and data concerning the treatment course in each subject. Ten patients had distant metastases at initial diagnosis, while seven developed MBC following prior curative-intent treatment. Two patients refused therapy. Ten did not comply with recommended management. Five harmed or threatened physicians, other caregivers or themselves. Schizophrenic patients with MBC often fail to understand the nature of their illnesses. Often they do not accept palliative treatment, while a number of them do not comply with therapy, once initiated. They often exhibit behaviors that are detrimental to themselves or others. Formal psychiatric consultation is therefore necessary in patients. Several detrimental behaviors may be predicted reliably by history alone.

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.

Background: C57BL/6 mice transfected with the L(d) gene coupled to the alpha-myosin heavy chain promoter result in transgenic mice with L(d) antigen expressed only on cardiac tissue. These transgenic animals allow the examination of immune reactivity against cardiac L(d) by "self" or by adoptively transferred L(d) specific 2C cells, and the response of nontransgenic C57BL/6 mice to the transplanted L(d+) heart., Methods: Naïve cardiac L(d+) transgenic mice were examined for evidence of L(d) "autoimmunity." Forty million fresh 2C cells or 2C cells sensitized in vitro for 7 days against Balb/c (L(d+)) + interleukin-2 were also given intravenously to L(d+) transgenic mice. At 5 and 12 days after injection, heart-infiltrating lymphocytes were analyzed by fluorescence-activated cell sorter. The L(d+) transgenic hearts were also transplanted to syngeneic L(d-) nontransgenic C57BL/6 to evaluate the heart's immunogenicity., Results: Naïve L(d+) transgenic mice did not exhibit any evidence of lymphocytic infiltration on histologic examination. Adoptive transfer of either fresh or in vitro sensitized 2C cells was also unable to reject the native L(d+) heart in transgenic mice (100% of the mice survived long term [more than 60 days]). Sensitization of the L(d+) transgenic mice with a Balb/c skin graft and interleukin-2 pump infusion (7 days) beginning 1 day before 2C cell injection also did not promote rejection of the native L(d+) heart. However, fluorescence-activated cell sorter analysis did reveal that a significantly greater number of in vitro sensitized 2C cells homed to the L(d+), but not L(d-), heart after both 5 and 12 days (P <.01, P <.001). In contrast, C57BL/6 mice rejected the L(d+) (C57BL/6 background) transgenic heart in a mean survival time of 17 +/- 9.7 days (P <.01), whereas a syngeneic C57BL/6 heart transplant was accepted indefinitely. Lymphocytic infiltration consistent with rejection was present in all animals receiving an Ld+ transgenic heart transplant, whereas no infiltrate was present in those receiving a syngeneic C57BL/6 heart transplant., Conclusions: Although the class I L(d) transgene is not recognized in its native host, its immunogenicity is shown by the homing of anti-L(d) 2C cells to the heart in situ and rejection of L(d+) heart grafts when transplanted into syngeneic C57BL/6 mice.

The intensity of post-treatment melanoma patient follow-up varies widely among physicians. We investigated whether physician age accounts for the observed variation in surveillance intensity among plastic surgeons. A custom-designed questionnaire was mailed to USA and non-USA surgeons, all of whom were members of the American Society of Plastic and Reconstructive Surgeons. Subjects were asked how they use 14 specific follow-up modalities during years 1-5 and 10 following primary treatment for patients with cutaneous melanoma. Repeated-measures analysis of variance was used to compare practice patterns by TNM stage, year post-surgery, and age. Of the 3,032 questionnaires mailed, 1,142 (38%) were returned. Of those returned, 395 (35%) were evaluable. Non-evaluability was usually due to lack of melanoma patient follow-up in surgeons' practices. Follow-up strategies for most of the 14 modalities were highly correlated across TNM stages and years post-surgery, as expected. The pattern of testing varied significantly by surgeon age for 3 modalities (complete blood count, liver function tests, and chest X-ray), but the variation was quite small. We concluded that the post-treatment surveillance practice patterns of ASPRS members caring for patients with cutaneous melanoma vary only marginally with physician age. Continuing medical education could account for this observation.