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.

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.

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.

Prosigna® breast cancer assay: histopathologic correlation, development, and assessment of size, nodal status, Ki-67 (SiNK™) index for breast cancer prognosis.

The Prosigna® assay is a United States Food and Drug Administration (US-FDA) cleared molecular test for prognostic use in hormone receptor-positive stage I/II breast cancer in postmenopausal women. We analyzed histopathologic features of 79 cases with Prosigna® assay results and found a significant correlation between tumor size, grade, and Ki-67 labeling index with Prosigna® score (0-40, 41-60, and 61-100) and Prosigna® risk categories. Since the Prosigna® risk stratification is influenced by lymph node status, we designed an index that included lymph node status and the two most correlated variables (size and Ki-67 labeling index). This was termed the size, nodal, and Ki-67 (SiNK™) index and is calculated as follows: (size in mm) + (pN × 10) + (Ki-67 labeling index). The SiNK™ index was divided into ≤40 and >40 to test its prognostic significance in a well-characterized dataset of 106 ER+/HER2-negative stage I-II invasive breast cancers treated with standard multi-modality therapy with long term follow-up (average 101 months follow-up). Patients with SiNK™ ≤40 showed significantly improved distant recurrence-free survival (96% distant recurrence-free survival in SiNK™ ≤40 compared to 81% in SiNK™ >40; log-rank test p value: 0.0027). SiNK™ provides strong prognostic information in ERo+/HER2-negative breast cancers. SiNK™ index is simple to calculate using data from routine pathology reports. This should be further evaluated in larger datasets.

Magee Equations™ and response to neoadjuvant chemotherapy in ER+/HER2-negative breast cancer: a multi-institutional study.

Magee Equations™ (ME) are multivariable models that can estimate oncotype DX® recurrence score. One of the equations, Magee Equation 3 (ME3) which utilizes only semi-quantitative receptor results has been shown to provide chemopredictive value in the neoadjuvant setting in a single institutional study. This multi-institutional study (seven institutions contributed cases) was undertaken to examine the validity of ME3 in predicting response to neoadjuvant chemotherapy in estrogen receptor positive, HER2-negative breast cancers. Stage IV cases were excluded. The primary endpoint was the pathologic complete response (pCR) rate in different categories of ME3 scores calculated based on receptor results in the pre-therapy core biopsy. A total of 166 cases met the inclusion criteria. The patient age ranged from 24 to 83 years (median 53 years). The average pre-therapy tumor size was 3.9 cm, and axillary lymph nodes were confirmed positive by pre-therapy core biopsy in 85 of 166 cases (51%). The pCR rate according to ME3 scores was 0% (0 of 64) in ME3 < 18, 0% (0 of 46) in ME3 18-25, 14% (3 of 21) in ME3 > 25 to <31, and 40% (14 of 35) in ME3 score 31 or higher (p value: <0.0001). There were no distant recurrences and no deaths in the 17 patients with pCR. In the remaining 149 cases with residual disease, ME3 score of >25 was significantly associated with shorter distant recurrence-free survival and showed a trend for shorter breast cancer-specific survival. The results of this multi-institutional study are similar to previously published data from a single institution (PMID: 28548119) and confirm the chemo-predictive value of ME3 in the neoadjuvant setting. In addition, ME3 may provide prognostic information in patients with residual disease which should be further evaluated.

The effect of time spent in rehabilitation on activity limitation and impairment after stroke.

BACKGROUND: Stroke affects millions of people every year and is a leading cause of disability, resulting in significant financial cost and reduction in quality of life. Rehabilitation after stroke aims to reduce disability by facilitating recovery of impairment, activity, or participation. One aspect of stroke rehabilitation that may affect outcomes is the amount of time spent in rehabilitation, including minutes provided, frequency (i.e. days per week of rehabilitation), and duration (i.e. time period over which rehabilitation is provided). Effect of time spent in rehabilitation after stroke has been explored extensively in the literature, but findings are inconsistent. Previous systematic reviews with meta-analyses have included studies that differ not only in the amount provided, but also type of rehabilitation. OBJECTIVES: To assess the effect of 1. more time spent in the same type of rehabilitation on activity measures in people with stroke; 2. difference in total rehabilitation time (in minutes) on recovery of activity in people with stroke; and 3. rehabilitation schedule on activity in terms of: a. average time (minutes) per week undergoing rehabilitation, b. frequency (number of sessions per week) of rehabilitation, and c. total duration of rehabilitation. SEARCH METHODS: We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, eight other databases, and five trials registers to June 2021. We searched reference lists of identified studies, contacted key authors, and undertook reference searching using Web of Science Cited Reference Search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults with stroke that compared different amounts of time spent, greater than zero, in rehabilitation (any non-pharmacological, non-surgical intervention aimed to improve activity after stroke). Studies varied only in the amount of time in rehabilitation between experimental and control conditions. Primary outcome was activities of daily living (ADLs); secondary outcomes were activity measures of upper and lower limbs, motor impairment measures of upper and lower limbs, and serious adverse events (SAE)/death. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data, assessed methodological quality using the Cochrane RoB 2 tool, and assessed certainty of the evidence using GRADE. For continuous outcomes using different scales, we calculated pooled standardised mean difference (SMDs) and 95% confidence intervals (CIs). We expressed dichotomous outcomes as risk ratios (RR) with 95% CIs. MAIN RESULTS: The quantitative synthesis of this review comprised 21 parallel RCTs, involving analysed data from 1412 participants.  Time in rehabilitation varied between studies. Minutes provided per week were 90 to 1288. Days per week of rehabilitation were three to seven. Duration of rehabilitation was two weeks to six months. Thirteen studies provided upper limb rehabilitation, five general rehabilitation, two mobilisation training, and one lower limb training. Sixteen studies examined participants in the first six months following stroke; the remaining five included participants more than six months poststroke. Comparison of stroke severity or level of impairment was limited due to variations in measurement. The risk of bias assessment suggests there were issues with the methodological quality of the included studies. There were 76 outcome-level risk of bias assessments: 15 low risk, 37 some concerns, and 24 high risk. When comparing groups that spent more time versus less time in rehabilitation immediately after intervention, we found no difference in rehabilitation for ADL outcomes (SMD 0.13, 95% CI -0.02 to 0.28; P = 0.09; I2 = 7%; 14 studies, 864 participants; very low-certainty evidence), activity measures of the upper limb (SMD 0.09, 95% CI -0.11 to 0.29; P = 0.36; I2 = 0%; 12 studies, 426 participants; very low-certainty evidence), and activity measures of the lower limb (SMD 0.25, 95% CI -0.03 to 0.53; P = 0.08; I2 = 48%; 5 studies, 425 participants; very low-certainty evidence). We found an effect in favour of more time in rehabilitation for motor impairment measures of the upper limb (SMD 0.32, 95% CI 0.06 to 0.58; P = 0.01; I2 = 10%; 9 studies, 287 participants; low-certainty evidence) and of the lower limb (SMD 0.71, 95% CI 0.15 to 1.28; P = 0.01; 1 study, 51 participants; very low-certainty evidence). There were no intervention-related SAEs. More time in rehabilitation did not affect the risk of SAEs/death (RR 1.20, 95% CI 0.51 to 2.85; P = 0.68; I2 = 0%; 2 studies, 379 participants; low-certainty evidence), but few studies measured these outcomes. Predefined subgroup analyses comparing studies with a larger difference of total time spent in rehabilitation between intervention groups to studies with a smaller difference found greater improvements for studies with a larger difference. This was statistically significant for ADL outcomes (P = 0.02) and activity measures of the upper limb (P = 0.04), but not for activity measures of the lower limb (P = 0.41) or motor impairment measures of the upper limb (P = 0.06). AUTHORS' CONCLUSIONS: An increase in time spent in the same type of rehabilitation after stroke results in little to no difference in meaningful activities such as activities of daily living and activities of the upper and lower limb but a small benefit in measures of motor impairment (low- to very low-certainty evidence for all findings). If the increase in time spent in rehabilitation exceeds a threshold, this may lead to improved outcomes. There is currently insufficient evidence to recommend a minimum beneficial daily amount in clinical practice. The findings of this study are limited by a lack of studies with a significant contrast in amount of additional rehabilitation provided between control and intervention groups. Large, well-designed, high-quality RCTs that measure time spent in all rehabilitation activities (not just interventional) and provide a large contrast (minimum of 1000 minutes) in amount of rehabilitation between groups would provide further evidence for effect of time spent in rehabilitation.

Conditions for shared decision making in the care of transgender youth in Canada.

Information is lacking on the role shared decision making plays in the care of transgender (trans) youth. This qualitative, descriptive study explored how trans youth, parents and health care providers engaged or did not engage in shared decision-making practices around hormone therapy initiation and what conditions supported shared decision-making approaches in clinical practice. Semi-structured interviews were conducted with 47 participants in British Columbia, Canada, and analyzed using a constructivist grounded theory approach. While formal shared decision-making models were not used in practice, many participants described elements of such approaches when asked about their health care decision-making processes. Others described health care interactions that were not conducive to a shared decision-making approach. The key finding that emerged through this analysis was a set of five conditions for supporting shared decision making when making decisions surrounding initiation of hormone therapy with trans youth. Both supportive relationships and open communication were necessary among participants to support shared decision making. All parties needed to agree regarding what decisions were to be made and what role each person would play in the process. Finally, adequate time was needed for decision-making processes to unfold. When stakeholders meet these five conditions, a gender-affirming and culturally safer shared decision-making approach may be used to support decision making about gender-affirming care. Implications for clinical practice and future research are discussed.

The healthcare value of the Magee Decision Algorithm™: use of Magee Equations™ and mitosis score to safely forgo molecular testing in breast cancer.

Magee Equations™ are multivariable models that can estimate oncotype DX® Recurrence Score, and Magee Equation 3 has been shown to have chemopredictive value in the neoadjuvant setting as a standalone test. The current study tests the accuracy of Magee Decision Algorithm™ using a large in-house database. According to the algorithm, if all Magee Equation scores are <18, or 18-25 with a mitosis score of 1, then oncotype testing is not required as the actual oncotype recurrence score is expected to be ≤25 (labeled "do not send"). If all Magee Equation scores are 31 or higher, then also oncotype testing is not required as the actual score is expected to be >25 (also "do not send"). All other cases could be considered for testing (labeled "send"). Of the 2196 ER+, HER2-negative cases sent for oncotype testing, 1538 (70%) were classified as "do not send" and 658 (30%) as "send". The classification accuracy in the "do not send" group was 95.1%. Of the 75 (4.9%) discordant cases (expected score ≤25 by decision algorithm but the actual oncotype score >25), 26 received endocrine therapy alone. None of these 26 patients experienced distant recurrence (average follow-up of 73 months). The Magee Decision Algorithm accurately identifies cases that will not benefit from oncotype testing. Such cases constitute ~70% of the routine clinical oncotype requests, an estimated saving of $300,000 per 100 test requests. The occasional discordant cases (expected ≤25, but actual oncotype score >25) appears to have an excellent outcome on endocrine therapy alone.

Hormone therapy decision-making processes: Transgender youth and parents.

INTRODUCTION: This study explored how transgender (trans) youth and parents of trans youth made decisions around hormone therapy initiation as well as trans youth experiences of barriers to care. METHODS: Participants included 21 trans youth (ages 14-18) and 15 parents of trans youth who resided in British Columbia, Canada. Data for this grounded theory research consisted of transcripts and lifeline drawings collected through semi-structured interviews conducted August 2016 through February 2017. RESULTS: The decision-making processes of youth and of parents are illustrated in three-phase temporal models, starting with discovery, leading to (inter)action while seeking care, and reflection after hormone therapy initiation. Youth who sought hormone therapy were clear about their decision to access this care. Throughout these processes, youth experienced numerous parent- and system-related barriers to care. Youth with the lowest levels of parent support experienced more system barriers, with non-binary/genderfluid youth experiencing greater barriers and less support for hormone therapy than youth with binary genders. A new barrier identified in this study was health care provider imposed requirements for parental involvement and/or approval, which rendered some youth unable access to hormone therapy. CONCLUSIONS: Health care providers should be aware of the deliberation and information-seeking in which youth engage prior to seeking care as well as the temporally misaligned decision-making processes of youth and parents. Understanding the challenges trans youth experience due to insufficient parental support and system barriers can provide important context for health care providers striving to provide accessible, gender-affirming care and decision-making support for trans youth.

Breast cancer global tumor biomarkers: a quality assurance study of intratumoral heterogeneity.

Biomarker analysis of invasive breast carcinoma is useful for prognosis, as surrogate for molecular subtypes of breast cancer, and prediction of response to adjuvant and neoadjuvant systemic therapies. Breast cancer intratumoral heterogeneity is incompletely studied. Comprehensive biomarker analysis of estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 labeling index was performed on each tissue block of 100 entirely submitted breast tumors in 99 patients. Invasive carcinoma and in situ carcinoma was scored using semiquantitative histologic score (H-score) for ER and PR, HER2 expression from 0 to 3+, and percentage positive cells for Ki67. Core biopsy results were compared with surgical excision results, invasive carcinoma was compared with in situ carcinoma, and interblock tumoral heterogeneity was assessed using measures of dispersion (coefficient of variation and quartile coefficient of dispersion). Overall concordance between core biopsy and surgical excision was 99% for ER and 95% for PR. Mean histologic score of ER was significantly lower in invasive carcinoma between core biopsy and surgical excision (p = 0.000796). Intratumoral heterogeneity was higher for PR than for ER (mean coefficient of variation for ER 0.08 stdv 0.13 vs. PR 0.26 stdv 0.41). Ki67 labeling index was significantly higher in invasive carcinoma as compared with associated ductal carcinoma in situ on surgical resection specimen (p ≤ 0.0001). Ki67 hotspots were identified in 47% of cases. Of 52 HER2 negative cases on core biopsy, 10 were scored as equivocal on surgical resection. None (0/10) were amplified by Her-2/neu fluorescence in situ hybridization. Overall, biomarkers on core biopsy showed concordance with the surgical excision specimen in the vast majority of cases. Biomarker expression of in situ closely approximates associated invasive carcinoma. Intratumoral heterogeneity of PR is greater than ER. Biomarker expression on diagnostic core biopsy or single tumor block is representative of breast carcinoma as a whole in most cases and is appropriate for clinical decision-making.

Metaplastic breast carcinoma: a clinical-pathologic study of 97 cases with subset analysis of response to neoadjuvant chemotherapy.

Metaplastic breast carcinoma is a rare heterogeneous category of breast cancer, often associated with a poor prognosis. Clinical-pathologic studies with respect to varied morphologic subtypes are lacking. There is also a dearth of studies assessing the response of metaplastic breast carcinoma to neoadjuvant chemotherapy. Cases of metaplastic breast carcinoma diagnosed between 2007 and 2017 were identified. Various clinical-pathologic variables were tested for association with survival. Patients who underwent neoadjuvant chemotherapy were assessed for pathologic response. Median age at diagnosis with metaplastic breast carcinoma was 64 years. With a median follow-up of 39 months, 26 patients (27%) recurred (24 distant and 2 loco-regional). The overall survival rate of the cohort was 66% (64/97). A number of variables were associated with survival in univariable analysis; however, in multivariable analysis, only lymph node status and tumor size (pT3 vs. pT1/2) were significantly associated with all survival endpoints: recurrence-free survival, distant recurrence-free survival, overall survival and breast cancer-specific survival. Twenty-nine of 97 (30%) patients with metaplastic breast carcinoma received neoadjuvant chemotherapy. Five (17%) patients achieved pathologic complete response. Matrix-producing morphology was associated with higher probability of achieving pathologic complete response (p = 0.027). Similar to other breast cancer subtypes, tumor size and lymph node status are prognostic in metaplastic carcinomas. The pathologic complete response rate of metaplastic breast carcinoma in our cohort was 17%, higher than previously reported. Although the matrix-producing subtype was associated with pathologic complete response, there was no survival difference with respect to tumor subtypes.

Eating Disorder Diagnoses and Symptom Presentation in Transgender Youth: a Scoping Review.

PURPOSE OF REVIEW: This scoping review includes recent literature on eating disorder diagnoses and evaluation of eating disorder symptom presentation among transgender youth (ages 8-25). RECENT FINDINGS: A total of 20 publications from the previous 5 years were identified, including case reports, retrospective chart reviews, and surveys. Significantly higher rates of eating disorder symptoms were documented in transgender youth compared to cisgender youth. Similarly, some studies reported transgender youth were more likely to be diagnosed with an eating disorder than cisgender youth, though the proportion of youth with eating disorder diagnoses varied across studies. A consistent theme across case studies was engagement in food restriction and/or compensatory eating behaviors to prevent puberty onset or progression, suggesting that for some transgender youth, these behaviors may be understood as a means of coping with gender-related distress. Clinical care could be enhanced through establishment of best practices for screening in settings offering eating disorder treatment and gender-affirming care, as well as greater collaboration among these programs. Research is needed to validate eating disorder measures for use with transgender youth and evaluate the effects of eating disorder treatment and gender-affirming medical interventions on the well-being of transgender youth.

Pathologist's health-care value in the triage of Oncotype DX® testing: a value-based pathology study of tumour biology with outcomes.

AIMS: Pathologists provide expert tissue assessment of breast cancer, yet their value to guide the appropriate use of breast cancer gene expression profile tests (GEPT) is underutilised. The specific aims of this study are to report morpho-immunohistological characteristics of breast tumours with Oncotype DX® (ODx) recurrence scores (RS) of 10 or fewer (ultra-low risk) and 25 or fewer (low risk) in order to determine if pathologists can identify prospectively patient tumours that do not require ODx testing. METHODS AND RESULTS: Oncotype DX® cases with RS < 10 from 2005 to 2010 comprised 441 of 2594 (17%) of clinical cases; this cohort had 5 years' follow-up and was treated with endocrine therapy alone. Tumours were analysed for tumour type, Nottingham grade, mitosis score (MS) semi-quantitative (H-score) hormone receptor content and Magee equation 3. Knowledge derived from this data set was used to develop algorithms in order to identify prospectively tumours with RS of 10 or fewer or 25 or fewer. Thirty-four per cent of tumours were low-grade special types, while the remainder were enriched with high hormone receptor content with MS of 1. These algorithmic selection criteria identified correctly all patient cases below the chemotherapy cut-point, i.e. RS < 25, indicating that these oncotype test orders were an unnecessary cost. CONCLUSIONS: This unique study demonstrates that (i) pathologists add great value to triage breast cancer for GEPT; and (ii) can identify prospectively low-grade tumour biology with high sensitivity and high specificity for those cases which do not require chemotherapy (RS < 25) using MS and hormone receptor content.

Primary care access and foregone care: a survey of transgender adolescents and young adults.

Objective: To examine the issues of primary care access and foregone health care among transgender adolescents and young adults. Methods: This cross-sectional analysis of data from the Canadian Trans Youth Health Survey was conducted online during 2013-2014. Participants included 923 youth aged 14-25 (323 adolescents aged 14-18 and 600 young adults aged 19-25). Main outcome measures were self-reported general and mental health status, comfort discussing transgender identity and health care needs with general practitioners, and types of and reasons for self-identified foregone health care. Results: Most youth reported poor/fair general and mental health status. Comfort with a family doctor was positively correlated with both general health (r(528) = 21, P < 0.001) and mental health (r(450) = 26, P < 0.001) status, as was having a doctor who was aware of one's transgender status. 47.2% (n = 219) of young adults reported foregoing needed health care. Among adolescents, levels of comfort with family doctor were negatively correlated with foregone mental health care in the previous 12 months (F3,166 = 3.829, P = 0.011), but not correlated with foregone physical health care (F3,165 = 0.506, P = 0.679). Reasons for missing needed care spanned the dimensions of health care access, ranging from cost barriers to previous negative experiences with health care providers, and concerns that a doctor would be uneducated about transgender people. Conclusion: General practitioners can play a key role in improving the health of transgender youth by demonstrating understanding of the health care needs of transgender youth and competence in gender-affirming care, and by ensuring that their practices are accessible to all transgender youth in need of care.

Magee Equation 3 predicts pathologic response to neoadjuvant systemic chemotherapy in estrogen receptor positive, HER2 negative/equivocal breast tumors.

Magee Equations were derived as an inexpensive, rapid alternative to Oncotype DX. The Magee Equation 3 utilizes immunohistochemical and FISH data for estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 for its calculation (24.30812+ERIHC × (-0.02177)+PRIHC × (-0.02884)+(0 for HER2 negative, 1.46495 for equivocal, 12.75525 for HER2 positive)+Ki-67 × 0.18649). We hypothesize that Magee Equation 3 scores from pre-therapy core biopsy can predict response to neoadjuvant systemic chemotherapy. A prospectively-maintained database of patients who received neoadjuvant systemic therapy from 2010 to 2014 at a single institution was retrospectively reviewed. Pathologic complete response was defined as absence of invasive tumor in the breast and regional lymph nodes. Of the 614 cases, tumors with missing immunohistochemical results and those that were ER negative or HER2 positive were excluded. This resulted in 237 ER positive, HER2 negative/equivocal tumors that formed the basis of this study. Magee Equation 3 scores were divided into 3 categories similar to Oncotype DX, ie, 0 to <18 (low), 18 to <31 (intermediate), and 31 or higher (high) scores. The pathologic complete response rate for low, intermediate and high Magee Equation 3 scores was 0%, 4%, and 36%, respectively. Patients with high Magee Equation 3 scores were 13 times more likely to achieve pathologic complete response compared to those with Magee Equation 3 scores less than 31 (95% CI 5.09-32.87, P<0.0001). For patients that did not achieve pathologic complete response, high Magee Equation 3 correlated with higher recurrence rate, with the majority occurring in patients with positive lymph nodes in the resection specimen. Magee Equation 3 score ≥31 predicts pathologic complete response in the neoadjuvant setting and for tumor recurrence, when pathologic complete response is not achieved. These results show the utility of Magee Equation 3 in predicting patients who will benefit from chemotherapy but warrant prospective multi-institutional validation.

"I would have preferred more options": accounting for non-binary youth in health research.

As a research team focused on vulnerable youth, we increasingly need to find ways to acknowledge non-binary genders in health research. Youth have become more vocal about expanding notions of gender beyond traditional categories of boy/man and girl/woman. Integrating non-binary identities into established research processes is a complex undertaking in a culture that often assumes gender is a binary variable. In this article, we present the challenges at every stage of the research process and questions we have asked ourselves to consider non-binary genders in our work. As researchers, how do we interrogate the assumptions that have made non-binary lives invisible? What challenges arise when attempting to transform research practices to incorporate non-binary genders? Why is it crucial that researchers consider these questions at each step of the research process? We draw on our own research experiences to highlight points of tensions and possibilities for change. Improving access to inclusive health-care for non-binary people, and non-binary youth in particular, is part of creating a more equitable healthcare system. We argue that increased and improved access to inclusive health-care can be supported by research that acknowledges and includes people of all genders.

Molecular drivers of lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC). Many LCIS lesions do not progress to ILC, and the molecular changes that are necessary for progression from LCIS to ILC are poorly understood. Disruption in the E-cadherin complex is the hallmark of lobular lesions, but other signaling molecules, such as PIK3CA and c-src, are consistently altered in LCIS. This review focuses on the molecular drivers of lobular carcinoma, a more complete understanding of which may give perspective on which LCIS lesions progress, and which will not, thus having immense clinical implications.