Immunohistochemical Profile of Triple-Negative Breast Cancers: SOX10 and AR Dual Negative Tumors Have Worse Outcomes.

Triple-negative breast cancer (TNBC) refers to an estrogen receptor-negative, progesterone receptor-negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor subtype. Immunohistochemistry (IHC) has been used as a surrogate for basal and luminal subtypes within TNBC, but prognostication of TNBC using IHC is not routinely performed. We aimed to study immunophenotypic correlations in a well-annotated cohort of consecutive TNBCs, excluding postneoadjuvant chemotherapy cases. Tissue microarrays were constructed from a total of 245 TNBC cases. IHC stains were performed and consisted of luminal (AR and INPP4B), basal (SOX10, nestin, CK5, and EGFR), and diagnostic (GCDFP15, mammaglobin, GATA3, and TRPS1) markers. Survival analysis was performed to assess the significance of clinical-pathologic variables including age, histology, grade, lymphovascular invasion, Nottingham prognostic index category, American Joint Committee on Cancer (AJCC) stage, stromal tumor-infiltrating lymphocytes at 10% increment, CD8+ T-cell count, Ki-67 index, PD-L1 status, and chemotherapy along with the results of IHC markers. Apocrine tumors show prominent reactivity for luminal markers and GCDFP15, whereas no special-type carcinomas are often positive for basal markers. TRPS1 is a sensitive marker of breast carcinoma but shows low or no expression in apocrine tumors. High AJCC stage, lack of chemotherapy, and dual SOX10/AR negativity are associated with worse outcomes on both univariable and multivariable analyses. Lymphovascular invasion and higher Nottingham prognostic index category were associated with worse outcomes on univariable but not multivariable analysis. The staining for IHC markers varies based on tumor histology, which may be considered in determining breast origin. Notably, we report that SOX10/AR dual negative status in TNBC is associated with a worse prognosis along with AJCC stage and chemotherapy status.

Upgrade Rates of Variant Lobular Carcinoma In Situ Compared to Classic Lobular Carcinoma In Situ Diagnosed in Core Needle Biopsies: A 10-Year Single Institution Retrospective Study.

The primary aim of this study was to determine the upgrade rates of variant lobular carcinoma in situ (V-LCIS, ie, combined florid [F-LCIS] and pleomorphic [P-LCIS]) compared with classic LCIS (C-LCIS) when diagnosed on core needle biopsy (CNB). The secondary goal was to determine the rate of progression/development of invasive carcinoma on long-term follow-up after primary excision. After institutional review board approval, our institutional pathology database was searched for patients with "pure" LCIS diagnosed on CNB who underwent subsequent excision. Radiologic findings were reviewed, radiologic-pathologic (rad-path) correlation was performed, and follow-up patient outcome data were obtained. One hundred twenty cases of LCIS were identified on CNB (C-LCIS = 97, F-LCIS = 18, and P-LCIS = 5). Overall upgrade rates after excision for C-LCIS, F-LCIS, and P-LCIS were 14% (14/97), 44% (8/18), and 40% (2/5), respectively. Of the total cases, 79 (66%) were deemed rad-path concordant. Of these, the upgrade rate after excision for C-LCIS, F-LCIS, and P-LCIS was 7.5% (5 of 66), 40% (4 of 10), and 0% (0 of 3), respectively. The overall upgrade rate for V-LCIS was higher than for C-LCIS (P = .004), even for the cases deemed rad-path concordant (P value: .036). Most upgraded cases (23 of 24) showed pT1a disease or lower. With an average follow-up of 83 months, invasive carcinoma in the ipsilateral breast was identified in 8/120 (7%) cases. Six patients had died: 2 of (contralateral) breast cancer and 4 of other causes. Because of a high upgrade rate, V-LCIS diagnosed on CNB should always be excised. The upgrade rate for C-LCIS (even when rad-path concordant) is higher than reported in many other studies. Rad-path concordance read, surgical consultation, and individualized decision making are recommended for C-LCIS cases. The risk of developing invasive carcinoma after LCIS diagnosis is small (7% with ∼7-year follow-up), but active surveillance is required to diagnose early-stage disease.

Exploring farmer and advisor lameness management behaviors using the COM-B model of behavior change.

Introduction: This paper applies the COM-B framework to farmer and farm advisor understandings and responses to lameness in sheep, beef, and dairy systems. It reflects on how farmers' and advisors' capability, opportunity, and motivation (COM-B) influence lameness management practices in these farming systems, and considers the interaction between these three factors, and stakeholders' behavior. Methods: Interviews with 29 farmers and 21 farm advisors in the north of England were conducted. Thematic analysis was undertaken with results categorized in relation to the COM-B framework focusing on barriers and enablers of lameness management. Use of the COM-B model provides a useful means of understanding the underlying behavioral mechanisms that contribute toward the persistence of lameness. This includes the complexities and interactions which hamper implementation of lameness management best practice. Results and discussion: The findings highlight three key areas to address with interventions to improve lameness management on farm: (1) removing physical and social barriers for lameness management; (2) improving psychological capability and motivation for lameness management; and (3) facilitating relationships and developing communication between farmers and advisors. In particular, the value of exploring both farmer and advisor perspectives on behavior in the animal health context is demonstrated. Future interventions should look to target these three areas to overcome barriers and focus on factors that enable positive lameness practices to occur.

Implementation of Digital Image Analysis in Assessment of Ki67 Index in Breast Cancer.

The clinical utility of the proliferation marker Ki67 in breast cancer treatment and prognosis is an active area of research. Studies have suggested that differences in pre-analytic and analytic factors contribute to low analytical validity of the assay, with scoring methods accounting for a large proportion of this variability. Use of standard scoring methods is limited, in part due to the time intensive nature of such reporting protocols. Therefore, use of digital image analysis tools may help to both standardize reporting and improve workflow. In this study, digital image analysis was utilized to quantify Ki67 indices in 280 breast biopsy and resection specimens during routine clinical practice. The supervised Ki67 indices were then assessed for agreement with a manual count of 500 tumor cells. Agreement was excellent, with an intraclass correlation coefficient of 0.96 for the pathologist-supervised analysis. This study illustrates an example of a rapid, accurate workflow for implementation of digital image analysis in Ki67 scoring in breast cancer.

Why do some people who had a stroke not receive the recommended 45 min of occupational therapy and physiotherapy? A Delphi study.

OBJECTIVES: To gain a consensus among therapists for reasons why a person who had a stroke may not receive the Royal College of Physicians' recommended minimum of 45 min of daily therapy. DESIGN: Three-round remote e-Delphi study. SETTING: National study, based in the UK. PARTICIPANTS: Occupational therapists and physiotherapists with experience of delivering therapy after stroke and awareness of the 45 min guideline. RESULTS: Forty-five therapists consented to participate in the study. Thirty-five (78%) completed round one, 29 of 35 (83%) completed round 2 and 26 of 29 (90%) completed round three. A consensus (75%) was reached for 32 statements. Reasons why a person may not receive 45 min were related to the suitability of the guideline for the individual (based on factors like therapy tolerance or medical status) or the capability of the service to provide the intervention. In addition to the statements for which there was a consensus, 32 concepts did not reach a consensus. Specifically, there was a lack of consensus concerning the suitability of the guideline for people receiving Early Supported Discharge (ESD) services and a lack of agreement about whether people who need more than 45 min of therapy actually receive it. CONCLUSION: Some people do not receive 45 min of therapy as they are considered unsuitable for it and some do not receive it due to services' inability to provide it. It is unclear which reasons for guideline non-achievement are most common. Future research should focus on why the guideline is not achieved in ESD, and why people who require more than 45 min may not receive it. This could contribute to practical guidance for therapists to optimise therapy delivery for people after stroke.

Why do some people with stroke not receive the recommended 45 min of occupational therapy and physiotherapy after stroke? A qualitative study using focus groups.

OBJECTIVES: To generate qualitative data on the views of Occupational Therapists and Physiotherapists about why people do not receive the Royal College of Physicians' recommended minimum of 45 minutes (min) of daily therapy after stroke, in order to inform a Delphi study. DESIGN: Focus group study. SETTING: Stroke services in the South of England. PARTICIPANTS: A total of nine participants, in two groups, including therapists covering inpatient and Early Supported Discharge (ESD) services with awareness of the 45 min guideline. RESULTS: Thematic analysis of focus group data identified five factors that influence the amount of therapy a person receives: The Person (with stroke), Individual Therapist, Stroke Multidisciplinary Team, the Organisation and the Guideline. Study findings suggest that the reasons why a person does not receive the therapy recommendation in inpatient and ESD services relate to either the suitability of the guideline for the person with stroke, or the ability of the service to deliver the guideline. CONCLUSION: This study provides evidence for possible reasons why some people do not receive a minimum of 45 minutes of therapy, 5 days per week, related to (1) the suitability of the guideline for people with stroke and (2) services' ability to deliver this amount of intervention. These two factors are related; therapists decide who should receive therapy and how much in the context of (a) resource availability and (b) people's need and the benefit they will experience. The study findings, combined with the findings from other studies, will be used to initiate a Delphi study, which will establish consensus among therapists regarding the reasons why some people do not receive the guideline amount of therapy.

Improving personalised care, through the development of a service evaluation tool to assess, understand and monitor delivery.

Systematically implementing personalised care has far reaching benefits to individuals, communities and health and social care systems. If done well, personalised care can result in better health outcomes and experiences, more efficient use of health services and reduced health inequalities. Despite these known benefits, implementation of personalised care has been slow. Evaluation is an important step towards achieving the ambition of universally delivered personalised care. There are currently few comprehensive assessments or tools that are designed to understand the implementation of personalised care at a service or system level, or the cultural, practical and behavioural factors influencing this. The aim of this paper is to describe the development and testing of a system-wide evaluation tool. The tool offers a process through which healthcare systems can better understand the current delivery of personalised care and the factors influencing this. With a focus on implementation, the development of the tool was informed by the Consolidated Framework for Implementation Research, and its content is structured using behaviour change theory (COM-B Theory of Behaviour Change Model). The tool consists of four mirrored surveys, which were developed using an iterative exploratory design. This included a series of testing cycles, in which its structure and content were continually refined. To date, it has been used by 24 clinical services, involving 397 service users, 313 front-line practitioners, 73 service managers and 40 commissioners. These services have used the evaluation process to initiate quality improvement, targeted at one of the more aspects of personalised care. The use of the COM-B model increases the likelihood of those improvements being sustained, through identification of the core factors that enable or limit personalised care behaviours among healthcare staff. We have shown this process to be applicable in a wide range of settings, thus it potentially has broad applicability as a tool for cultural change and quality improvement. The next stage of this work will focus on implementation and evaluation, to fully understand if and how the tool can be used to drive improvements in personalised care delivery.

Clinicopathologic and genomic features of lobular like invasive mammary carcinoma: is it a distinct entity?

This study describes "lobular-like invasive mammary carcinomas" (LLIMCas), a group of low- to intermediate-grade invasive mammary carcinomas with discohesive, diffusely infiltrative cells showing retained circumferential membranous immunoreactivity for both E-cadherin and p120. We analyzed the clinical-pathologic features of 166 LLIMCas compared to 104 classical invasive lobular carcinomas (ILCs) and 100 grade 1 and 2 invasive ductal carcinomas (IDCs). Tumor size and pT stage of LLIMCas were intermediate between IDCs and ILCs, and yet often underestimated on imaging and showed frequent positive margins on the first resection. Despite histomorphologic similarities to classical ILC, the discohesion in LLIMCa was independent of E-cadherin/p120 immunophenotypic alteration. An exploratory, hypothesis-generating analysis of the genomic features of 14 randomly selected LLIMCas and classical ILCs (7 from each category) was performed utilizing an FDA-authorized targeted capture sequencing assay (MSK-IMPACT). None of the seven LLIMCas harbored CDH1 loss-of-function mutations, and none of the CDH1 alterations detected in two of the LLIMCas was pathogenic. In contrast, all seven ILCs harbored CDH1 loss-of-function mutations coupled with the loss of heterozygosity of the CDH1 wild-type allele. Four of the six evaluable LLIMCas were positive for CDH1 promoter methylation, which may partially explain the single-cell infiltrative morphology seen in LLIMCa. Further studies are warranted to better define the molecular basis of the discohesive cellular morphology in LLIMCa. Until more data becomes available, identifying LLIMCas and distinguishing them from typical IDCs and ILCs would be justified. In patients with LLIMCas, preoperative MRI should be entertained to guide surgical management.

Response in axillary lymph nodes to neoadjuvant chemotherapy for breast cancers: correlation with breast response, pathologic features, and accuracy of radioactive seed localization.

OBJECTIVES: This study examined the accuracy of radioactive seed localization (RSL) of lymph nodes (LNs) following neoadjuvant chemotherapy (NAC) for invasive breast carcinoma, recorded pathologic features of LNs following NAC, evaluated concordance of response between breast and LNs, and identified clinicopathologic factors associated with higher risk of residual lymph node involvement. METHODS: Clinical records, imaging, and pathology reports and slides were retrospectively reviewed for 174 breast cancer patients who received NAC. Chi-square and Fisher's exact tests were used to compare differences in risk of residual lymph node disease. RESULTS: Retrieval of biopsied pre-therapy positive LN was confirmed in 86/93 (88%) cases overall, and in 75/77 (97%) of cases utilizing RSL. Biopsy clip site was the best pathologic feature to confirm retrieval of a biopsied lymph node. Pre-therapy clinical N stage > 0, positive pre-therapy lymph node biopsy, estrogen and progesterone receptor positivity, Ki67 < 50%, HR + /HER2- tumors, and residual breast disease had higher likelihood of residual lymph node disease after NAC (p < 0.001). CONCLUSIONS: RSL-guided LN excision improves retrieval of previously biopsied LNs following NAC. The pathologist can use histologic features to confirm retrieval of targeted LNs, and tumor characteristics can be used to predict a higher risk of residual LN involvement.

Utility of TRPS1 immunohistochemistry in confirming breast carcinoma: Emphasis on staining in triple-negative breast cancers and gynecologic tumors.

OBJECTIVES: Our aim was to explore the performance of TRPS1 as an immunohistochemical diagnostic marker; find the optimal conditions for its use in breast carcinomas, especially triple-negative breast cancers (TNBCs); and compare its results in carcinomas of a select few organ sites, with an emphasis on gynecologic tumors. METHODS: Tissue microarrays from breast carcinomas (n = 197), endometrial adenocarcinomas (n = 69), ovarian tumors (n = 250), vulvar squamous cell carcinomas (n = 97), pancreatic ductal adenocarcinomas (n = 20), and gastric adenocarcinomas (n = 12) were stained with TRPS1 using 2 different conditions (protocol 1: high pH; protocol 2: low pH). Breast carcinomas consisted of hormone receptor (HR)-positive/ERBB2 (formerly HER2 or HER2/neu)-negative (n = 53) samples, HR-positive/ERBB2-positive (n = 6) samples, and TNBCs (n = 138). RESULTS: Comparing TRPS1 results in breast carcinomas vs tumors from other organ sites, the sensitivity of TRPS1 was 91% and 87%, respectively, while the specificity was 66% and 74% for protocol 1 and 2, respectively. For TNBCs vs gynecologic tumors, the sensitivity of TRPS1 was 89% and 85%, respectively, while the specificity was 65% and 73%, respectively. CONCLUSIONS: TRPS1 stains approximately 90% of breast carcinomas but also up to 71% of endometrial carcinomas, albeit with a weaker median expression. Our data show that although TRPS1 is a highly sensitive marker for TNBCs, it is not as highly specific as previously reported.

Changes over time in papanicolaou cytology test and HPV test in a large women's academic center laboratory.

INTRODUCTION: In the past 2 decades, cervical cancer screening guidelines in the United States have undergone numerous revisions with recent greater emphasis on primary high-risk human papillomavirus (hrHPV) testing. MATERIALS AND METHODS: We examine the trends of Papanicolaou test and hrHPV testing at our large academic center across 4 years (2006, 2011, 2016, and 2021) over a 15-year period. The number of ThinPrep Papanicolaou and hrHPV tests, as well as the triggers for HPV testing, were retrospectively analyzed. RESULTS: A total of 308,355 Papanicolaou tests and 117,477 hrHPV tests were reported across the 4 years. The number of Papanicolaou tests performed decreased nearly 3-fold over the study period, with only 43,230 Papanicolaou tests performed in 2021. The HPV test to Papanicolaou test ratio increased: 17% of Papanicolaou tests had an associated HPV test in 2006, whereas 72% of Papanicolaou tests ordered in 2021 had a companion hrHPV. The use of co-testing also increased. Overall, 73% were co-tests and 27% were reflexively ordered in the 4 one-year time periods. Co-tests constituted only 46% of HPV tests in 2006, but this increased to 93% in 2021. The percentage of positive hrHPV results decreased; in 2006, 18.3% of cases were positive, dropping to 8.6% in 2021 due to the marked increase in co-testing. Stratifying by diagnostic category, hrHPV results have remained relatively constant. CONCLUSION: With the numerous recent revisions of cervical screening guidelines, screening strategies at our institution reflected these changes in clinical practice. Papanicolaou and HPV co-testing became the most common screening method for women 30 to 65 years of age in our cohort.

Ovarian serous borderline tumor with mural nodules of anaplastic carcinoma and omental involvement: A case report.

Mural nodules are rarely identified in cystic ovarian neoplasms, and have been categorized into sarcoma-like, sarcomatous, and anaplastic carcinomatous types. Most reports of these mural nodules have been described in mucinous ovarian tumors. In this case report, we describe an ovarian serous borderline tumor with mural nodules composed of high-grade carcinoma with anaplastic features and necrosis, including the morphologic features, immunoprofile, and results of tumor DNA sequencing. Omental involvement was also identified. Recognition of this phenomenon in serous tumors is important, so that thickened areas of cyst wall in ovarian serous tumors will be thoroughly examined.

Changing interventions in farm animal health and welfare: A governmentality approach to the case of lameness.

Lameness is a significant health and welfare issue in farmed animals. This paper uses a governmentality approach, which focuses on how a problem is made governable, to examine an emerging 'ecology of devices' introduced to intervene in, and attempt to reduce, on-farm incidence of lameness. These devices are associated with advisers who work with farmers on-farm; they enact lameness as a governable entity, are tools to assess the existence of lameness against established norms, and prescribe actions to be taken in response to evidence of lameness. In doing this they subjectify farmers and advisers into seeing and responding to lameness in particular ways. Using concepts of governmentality alongside other perspectives on the power relations and the simplifications and complexities involved in interventions in animal health and farm practice, the paper draws on in-depth research with advisers including vets and other paraprofessionals who work with farmers, and their cows and sheep. It explores how this set of devices introduces particular techniques and practices in lameness management, and produces farmer and adviser subjectivities. It then explores some of the problematics of this mode of governing lameness, including analysis of the limitations and unintended consequences of attempts to simplify lameness management. The paper concludes by arguing that its approach is valuable in analysing ongoing intensification of interventions in farming practices and in understanding the limits of such interventions and the unanticipated divergences from expected conduct.

How can rural businesses thrive in the digital economy? A UK perspective.

Unlocking the digital potential of the UK's rural areas is important for the future of rural businesses, rural communities and the UK economy as a whole. The use of digital technologies is yielding new opportunities for businesses, including those located rurally, to enhance business growth and economic development, which significantly contributes to UK prosperity. However, businesses, especially small and medium-sized enterprises (SMEs), in rural areas are often digitally disconnected due to inferior digital connectivity and digital exclusion, including lack of internet access and lower levels of digital literacy. Therefore, this paper provides a better understanding of the rural digital economy, highlighting key digital challenges and opportunities for rural businesses in the UK. An extensive review of both academic and non-academic literature is conducted to identify key digital challenges, digital opportunities, and solutions to overcome the digital disadvantage for rural businesses in the UK in the digital age. Our review emphasises the effectiveness of public sector market interventions in developing broadband infrastructure and smarter digital training and skills development to help address digital deprivation in rural areas. A series of policy recommendations is then formulated to support rural business growth in the digital age and contributing to debates regarding smart rural development in rural areas. This paper has potential limitations due to a non-systematic literature review. Therefore, we recommend applying a systematic review as well as empirical and place-based research to explore the emerging themes of this study for future research.

Factors influencing consumption of traditional diets: stakeholder views regarding sago consumption among the indigenous peoples of West Papua.

Background: The indigenous people living in the province of West Papua may experience potential food insecurity, in part attributable to increased local adoption of, and reliance on, imported foods such as rice. At the same time, the consumption of sago, a traditional local food, is lower than other types of carbohydrate foods such as wheat and cassava. Various factors may act as influential drivers of local diets and related agricultural practices, such as local socio-economic and agronomic factors, as well as cultural practices which in turn may be influenced by the attitudes and opinions of stakeholders with interests in the supply chain. Methods: Qualitative methodology (semi-structured interviews) was applied to understand the various factors perceived by a selected number of stakeholders that influence sago consumption among the indigenous peoples of West Papua. These stakeholders included politicians, local and national civil servants, academics, sago farmers, and food activists (n = 18). Thematic analysis was used to analyse the data. Results: The results indicate that the stakeholders perceive that the majority of the West Papuan people regard sago as a traditional food that is critical to, and inseparable from, local culture and food production practices. The results suggest that the stakeholders interviewed support the consumption of sago to improve food security for the indigenous people in West Papua, with a need for future policy to be developed to support this. Conclusions: The evidence presented here suggests a diverse range of local stakeholders support the continuation of sago production and consumption, both from the perspective of improved food security, and in order to conserve cultural associations and activities within local communities. According to the stakeholders interviewed, this can be best achieved through improved engagement of local communities with sago production policies, innovation in current practices, and agronomic management. Local policies should be developed to ensure that sago remains an integral component of the Papuan people's culture, and develops into a significant commodity with economic value which simultaneously contributes to environmental targets. Supplementary Information: The online version contains supplementary material available at 10.1186/s40066-022-00390-5.

The Utility of SOX10 Immunohistochemical Staining in Breast Pathology.

OBJECTIVES: SOX10 expression helps identify melanocytic lesions. Over time, novel uses have been identified, such as expression in triple-negative breast cancer (TNBC). We evaluated the usefulness of SOX10 in breast pathology-specifically, identification and subtyping of TNBC and distinction from gynecologic carcinomas, use as a myoepithelial marker, and in the distinction of usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH). METHODS: Several breast and gynecologic carcinoma tissue microarrays containing a total of 492 cases were stained with SOX10. Whole sections of 34 ADH, 50 UDH, and 29 ductal carcinoma in situ (DCIS) samples were also stained with SOX10. RESULTS: SOX10 expression was identified in 67% of consecutive TNBC cases. Expression was mostly seen in nonapocrine, androgen receptor (AR)-negative TNBCs. All gynecologic carcinomas (n = 157) were negative. All UDH cases showed mosaic SOX10 expression, while all ADH cases lacked expression. All estrogen receptor (ER)-positive DCIS (n = 19) specimens were negative for SOX10, while 2 of 10 ER-negative DCIS specimens were positive for SOX10. The latter 2 cases showed SOX10-positive invasive carcinomas. CONCLUSIONS: SOX10 identifies nonluminal AR-type TNBC and is useful in distinguishing TNBC from gynecologic carcinomas. SOX10 can distinguish UDH from ADH. SOX10 is not useful in distinguishing ADH from DCIS.

Prognostic Significance of Three-Tiered World Health Organization Classification of Phyllodes Tumor and Correlation to Singapore General Hospital Nomogram.

OBJECTIVES: Phyllodes tumors (PTs) are categorized by the World Health Organization (WHO) as benign, borderline, and malignant. Singapore General Hospital (SGH) nomogram is a recurrence risk assessment tool for PT, which uses cytologic atypia, mitosis, stromal overgrowth, and the surgical margin status. We studied the prognostic significance of WHO classification and its correlation to the SGH nomogram. METHODS: We identified 270 consecutive cases of PT (195 benign, 49 borderline, 26 malignant). Follow-up was available on 246 cases (mean follow-up of 51 months). RESULTS: The recurrence rates were 2% (4 of 176) for benign, 4% (2 of 46) for borderline, and 25% (6 of 24) for malignant (log-rank test P < .0001 for recurrence-free survival). Only five patients with malignant PT experienced distant recurrence. Stromal overgrowth was an independent predictor of recurrence-free survival on multivariable analysis. The mean nomogram scores for benign, borderline, and malignant PT were 20, 20.3, and 32, respectively. The higher than expected score for benign PT was due to positive margins in 39% of cases. CONCLUSIONS: The WHO three-tiered classification of PT is prognostic. Despite positive margin status, most benign PTs do not recur. Other features of the nomogram help in determining recurrence but are also used for WHO classification.

Assessing the Sampleability of Bennu's Surface for the OSIRIS-REx Asteroid Sample Return Mission.

NASA's first asteroid sample return mission, OSIRIS-REx, collected a sample from the surface of near-Earth asteroid Bennu in October 2020 and will deliver it to Earth in September 2023. Selecting a sample collection site on Bennu's surface was challenging due to the surprising lack of large ponded deposits of regolith particles exclusively fine enough ( ≤ 2 cm diameter) to be ingested by the spacecraft's Touch-and-Go Sample Acquisition Mechanism (TAGSAM). Here we describe the Sampleability Map of Bennu, which was constructed to aid in the selection of candidate sampling sites and to estimate the probability of collecting sufficient sample. "Sampleability" is a numeric score that expresses the compatibility of a given area's surface properties with the sampling mechanism. The algorithm that determines sampleability is a best fit functional form to an extensive suite of laboratory testing outcomes tracking the TAGSAM performance as a function of four observable properties of the target asteroid. The algorithm and testing were designed to measure and subsequently predict TAGSAM collection amounts as a function of the minimum particle size, maximum particle size, particle size frequency distribution, and the tilt of the TAGSAM head off the surface. The sampleability algorithm operated at two general scales, consistent with the resolution and coverage of data collected during the mission. The first scale was global and evaluated nearly the full surface. Due to Bennu's unexpected boulder coverage and lack of ponded regolith deposits, the global sampleability efforts relied heavily on additional strategies to find and characterize regions of interest based on quantifying and avoiding areas heavily covered by material too large to be collected. The second scale was site-specific and used higher-resolution data to predict collected mass at a given contact location. The rigorous sampleability assessments gave the mission confidence to select the best possible sample collection site and directly enabled successful collection of hundreds of grams of material.

Clinical-pathologic characteristics and response to neoadjuvant chemotherapy in triple-negative low Ki-67 proliferation (TNLP) breast cancers.

Triple-negative breast cancers (TNBCs) often have a high Ki-67 proliferation index and respond favorably to neoadjuvant chemotherapy (NACT) with pathologic complete response (pCR) resulting in ~40% of cases. Nevertheless, morbidity/mortality remain high, mostly due to recurrence in patients with residual disease. In contrast, the incidence and clinical features of TNBC with low proliferation (TNLP), defined as TNBC with a Ki-67 index of ≤30% remains unknown. We report 70 cases of TNLP identified at our center from 2008 to 2018, including 18 treated with NACT. TNLP tumors represent <1% of all breast cancers, and ~5-10% of TNBCs. Ninety percent of carcinomas were grade I/II and 70% were either pure apocrine or showed apocrine differentiation. Fifty cases had available immunohistochemistry results; 80%, 84%, 22%, and 20% were positive for AR, INPP4B, nestin, and SOX10, respectively. With a median follow-up of 72 months, 14% experienced recurrence, and 11% died of breast cancer. The tumor stage was prognostic. Among 39 stage-I patients, 18 (46%) received chemotherapy, but this did not impact survival. There was a trend for improved recurrence-free survival with chemotherapy in stage-II patients. Of the 18 patients treated with NACT, 2 (11%) showed pCR; these were notable for either high stromal TILs or a high mitotic count despite a low Ki-67 index. TNLPs are enriched in low to intermediate-grade carcinomas with apocrine features. Due to overall good prognosis of stage-I TNLP and the lack of clear benefit of chemotherapy, de-escalation of chemotherapy may be considered in select patients with stage-I TNLP.