Progesterone Receptor Testing Research Articles

Proliferation Index in “HER2 Low” Metastatic Breast Cancer

Abstract Introduction/Objective There is considerable genetic heterogeneity between primary and metastatic breast cancer. The new classification of the "HER2-low" category includes tumors characterized by a low level of HER2 expression (immunohistochemistry (IHC) score 1+ or 2+ without in situ hybridization (ISH) amplification), in addition to the known HER2 negative (HER2-0) and HER2+ (amplified) cases. The Ki67 proliferation index (PI) can predict breast cancer prognosis. Proliferation changes in metastatic breast cancer and in different HER2 categories are not well delineated in clinical cohorts. In this study, we delineate proliferation characteristics of primary and metastatic breast cancer in association with HER2 status. Methods/Case Report We retrospectively reviewed the biological data from 98 metastatic breast cancer specimens for 90 patients from 2018-2021 (see Table 1). As part of the clinical workup, 72 metastatic cancer specimens had PI/Ki67, estrogen receptor (ER), and progesterone receptor (PR) testing by (IHC). HER2 was tested by IHC and reflexed ISH. We identified the overall frequency of breast cancer patients with different HER2 subtypes and compared the PI between primary and metastatic breast cancer within different HER2 categories. Results (if a Case Study enter NA) The median age at primary breast diagnosis was 51 (IQR; 42 – 58), and the median for metastatic cancer was 64 (IQR;57-70). Average PI/Ki67 was lower in metastatic cancers than in primary breast cancer samples, 38% and 46%, respectively (t-test, p < .001, two-tailed). Most metastatic and primary tumors were HR-positive, 24 (56%) and 16 (64%). The triple-negative subtype HR-HER2- has the highest PI/Ki67 in primary and metastatic tumors. Among the metastatic specimens, we found “HER2 low” expression in 45 (62.5%); 19 (26.4%) were HER2-positive, and 8 (6.3%) were HER2-0. 85% of traditionally HER2-negative samples were “HER2 low”. There were no statistically significant differences between the Ki67 proliferation index of “HER2 low”, HER2+, and HER2-0 patients (ANOVA, p= 0.488). Five patients (7%) showed different HER2 expressions between primary and metastatic cancer. Conclusion The average PI in our cohort is lower in metastatic breast cancers compared to primary breast cancers. This is an unexpected finding considering the pathophysiology of the metastatic cascade. Including "HER2 low" criteria increases the number of patients with metastatic breast cancer potentially eligible for HER2 targeted treatment from 26.4% (HER2+ / amplified) to over 60% (HER2 1+/2+ not amplified).

Abstract P2-03-16: Quantifying estrogen and progesterone receptor status in early-stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series

Abstract Background: Recent guidelines regarding estrogen (ER) and progesterone (PR) receptor testing from the American Society of Clinical Oncology and College of American Pathologists defined a new reporting category of ER-low positive breast cancer for tumors with 1-10% ER expression by immunohistochemistry (IHC). The clinical implications of ER-low positivity are incompletely understood, especially in invasive lobular carcinoma (ILC), the second most common type of breast cancer. Given the rarity of low-ER positivity in ILC, we evaluated tumor features and outcomes associated with a spectrum of ER/PR positivity in a monoinstitutional ILC cohort. Methods: We analyzed cases of stage I-III ILC with available IHC reports. Based on prior published categories in ILC, we classified ER as low, medium, or high as defined by ER staining of 10–69%, 70–89%, and ≥90% respectively. PR negative, low, and high tumors were defined by 0%, < 20%, or ≥20% staining respectively. We used chi-squared tests, t-tests, and Cox proportional hazards models in Stata 16.1 to evaluate associations between ER/PR categories including clinicopathologic variables and event-free survival (EFS). Results: Of 744 cases, 24 (3.2%) were ER negative and 10 (1.3%) were ER-low positive as defined by 1-10% positive staining. 713 remaining cases had ER positivity ≥ 10% and comprised the cohort categories of ER low, medium, and high for this study (11.2%, 15.0%, and 73.8% respectively). In 751 cases with PR data, 122 (16.2%) were PR negative, 145 (19.4%) were PR low and 483 (64.3%) were PR high. ER high status was significantly associated with older age (mean 56.7, 56.7, and 60.6 years in ER low, medium, and high respectively, p=0.0005). ER low was associated with PR negative and low status (42.3% were PR neg/low and ER low, versus 37.4% with ER medium and 29.9% in ER high, p=0.045), and more likely to have overexpression of HER2 (9.7%, 9.0%, and 2.9% ER low, medium, high, respectively, p=0.002). ER low tumors were more likely to be grade 1 than ER medium or high (41.8%, 29.8% and 24.5% respectively, p=0.025), and have positive surgical margins (39.4%, 35.9% and 23.9% respectively, p=0.002). ER status was not associated with Ki67, stage, body mass index (BMI), lymphovascular invasion, lobular carcinoma in situ (LCIS), pleomorphic histology, local therapy, or chemotherapy use. In contrast, PR high was significantly associated with younger age (57.6 versus 63.5 years in PR low, p< 0.0001). PR low was associated with HER2 overexpression (8.6% versus 3.2% in PR high, p=0.002). PR low cases were more likely to present at higher stages (15.8% stage III versus 10.1% stage III in PR high, p=0.032), to be pleomorphic (16.8% versus 8.2%, p< 0.001), and to receive chemotherapy (30.8% versus 23.1%, p=0.022) but were less likely to have associated LCIS (64.0 versus 74.2%, p=0.004). PR status was not associated with Ki67, BMI, lymphovascular invasion, local therapy, or surgical margins. In a Cox proportional hazards model adjusting for age, stage, grade, pleomorphic histology, and chemotherapy use, ER category was not associated with EFS but both PR negative and PR low status each had significantly worse EFS compared to PR ≥20% (HR 3.5, 95% CI 1.8-6.7, p< 0.001 for PR negative, and HR 2.0, 95% CI 1.1-3.5, p=0.015 for PR low). The estimated cumulative 5-year EFS for patients with ER low, medium, and high tumors was 87.1%, 93.4%, and 90.1% respectively. The estimated cumulative 5-year EFS for patients with PR negative, low, and high tumors was 78.9%, 90.2%, and 92.7% respectively. Conclusions: Using ILC-specific categories for ER expression, we found associations between ER category and clinicopathologic variables but not with EFS. In contrast, PR negative and low status was associated with worse EFS. These findings highlight the importance of exploring the spectrum of ER/PR activity within ILC, a classically strongly hormone receptor-positive tumor type, using more quantitative methods. Citation Format: Elle Clelland, Harriet T. Rothschild, Anne Patterson, Julissa Molina-Vega, Mandeep Kaur, Mary Kathryn Abel, W. Fraser Symmans, Jo Chien, Christopher J. Schwartz, Rita Mukhtar. Quantifying estrogen and progesterone receptor status in early-stage invasive lobular carcinoma of the breast: associated factors and outcomes in an institutional series [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-16.

European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis

Worldwide, it is estimated that about 1.3 million new gynecological cancer cases are diagnosed each year. For 2018, the predicted annual totals were cervix uteri 569 847, corpus uteri 382...

European Menopause and Andropause Society (EMAS) and International Gynecologic Cancer Society (IGCS) position statement on managing the menopause after gynecological cancer: focus on menopausal symptoms and osteoporosis

IntroductionWorldwide, it is estimated that about 1.3 million new gynecological cancer cases are diagnosed each year. For 2018, the predicted annual totals were cervix uteri 569,847, corpus uteri 382,069, ovary 295,414, vulva 44,235 and va​gina 17,600. Treatments include hysterectomy with or without bilateral salpingo-oophorectomy, radiotherapy and chemotherapy. These can result in loss of ovarian function and, in women under the age of 45, early menopause. AimThe aim of this position statement is to set out an individualized approach to the management, with or without menopausal hormone therapy, of menopausal symptoms and the prevention and treatment of osteoporosis in women with gynecological cancer. Materials and methodsLiterature review and consensus of expert opinion. Summary recommendationsThe limited data suggest that women with low-grade, early-stage endometrial cancer may consider systemic or topical estrogens. However, menopausal hormone therapy may stimulate tumor growth in patients with more advanced disease, and non-hormonal approaches are recommended. Uterine sarcomas may be hormone dependent, and therefore estrogen and progesterone receptor testing should be undertaken to guide decisions as to whether menopausal hormone therapy or non-hormonal strategies should be used. The limited evidence available suggests that menopausal hormone therapy, either systemic or topical, does not appear to be associated with harm and does not decrease overall or disease-free survival in women with non-serous epithelial ovarian cancer and germ cell tumors. Caution is required with both systemic and topical menopausal hormone therapy in women with serous and granulosa cell tumors because of their hormone dependence, and non-hormonal options are recommended as initial therapy. There is no evidence to contraindicate the use of systemic or topical menopausal hormone therapy by women with cervical, vaginal or vulvar cancer, as these tumors are not considered to be hormone dependent.

Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update.

To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen (ER) and progesterone receptor (PgR) testing in breast cancer guideline. A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature. The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines.

Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update.

To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline. A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature. The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Estrogen and progesterone receptor testing in breast cancer: American society of clinical oncology/college of American pathologists guideline update

Estrogen and progesterone receptor testing in breast cancer: American society of clinical oncology/college of American pathologists guideline update

Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update

Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update

Disparities in HER2 testing in breast cancer.

e13084 Background: Although targeted therapies directed at human epidermal growth factor-2 (HER2) impact breast cancer outcomes, studies have found geographic variation in testing rates. We report population-based patterns of HER2 testing by patient, tumor and geographic characteristics. Methods: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) data included women diagnosed 2010-2015 with de novo breast cancer. Women were categorized by age, race, stage, year of diagnosis, and receipt of estrogen receptor (ER), progesterone receptor (PR), and HER2 testing. SEER classified lack of testing with “test ordered, results not in chart” and “test not done.” We report on cases with HER2 “test not done”. Records missing any variables were excluded. County-level measures of socioeconomic status were included for each woman. Univariate and multivariate logistic regressions identified factors associated with testing. Results: Of 281,214 new breast cancer diagnoses, 1.75% had HER2 “test not done”. ER and PR testing were “not done” in 0.57% and 0.74% of cases, respectively. HER2-testing rates improved over time: 2.54% not tested in 2010 and 1.30% in 2015 (p &lt; 0.01). The following characteristics were associated with higher rates of “test not done”: age &gt;70 vs &lt; 50 (OR = 1.33, p &lt; 0.01), blacks vs whites (OR = 1.23, p &lt; 0.01), Stage IV vs I (OR = 2.27, p &lt; 0.01). Regional variation was also seen, with registries reporting HER2 “test not done” ranging from 0.18%-2.89%. On multivariate analysis (Table), HER2 testing was less likely for women age ≥ 70, blacks, Stage IV disease, and those living in counties with high rates of less than high school education. Conclusions: Rates of HER2 testing have increased. However, disparities exist and are associated with age, race, stage, geography, and education. Understanding the cause of these disparities could ultimately enhance access to appropriate therapy and improve disease outcomes. Odds of not having HER2 testing (select results from multivariate analysis). [Table: see text]

Molecular Testing in Breast Cancer: A Guide to Current Practices.

-Molecular diagnostics play a role in the management of many cancers, including breast cancer. -To provide an update on molecular testing in current clinical practice, targeted at practicing pathologists who are not breast cancer specialists. -This study is a narrative literature review. -In addition to routine hormone (estrogen and progesterone) receptor testing, new and recurrent tumors are tested for HER2 amplification by in situ hybridization or overexpression by immunohistochemistry. Intrinsic subtyping of tumors represents a fundamental advance in our understanding of breast cancer biology, but currently it has an indirect role in patient management. Clinical next-generation sequencing (tumor profiling) is increasingly used to identify potentially actionable mutations in tumor tissue. Multianalyte assays with algorithmic analysis, including MammaPrint, Oncotype DX, and Prosigna, play a larger role in breast cancer than in many other malignancies. Given that a proportion of breast cancers are familial, testing of nontumor tissue for cancer predisposition mutations also plays a role in breast cancer care.

Erratum to: Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach

Erratum to: Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach

Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach.

Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve optimization of their immunohistochemical assays. Nine Dutch pathology departments provided tissue blocks containing invasive breast cancers which were all previously tested for estrogen receptor and/or progesterone receptor expression during routine practice. From these tissue blocks, tissue microarrays were constructed and tested for hormone receptor expression. When a discordant result was found between the local and TMA result, the original testing slide was revised and staining was repeated on a whole-tissue block. Sensitivity and specificity of individual laboratories for testing estrogen receptor expression were high, with an overall sensitivity of 99.7 and 95.4 %, respectively. Overall sensitivity and specificity of progesterone receptor testing were 94.8 and 92.6 %, respectively. Out of 96 discordant cases, 36 cases would have been concordant if the recommended cut-off value of 1 % instead of 10 % was followed. Overall sensitivity and specificity of estrogen and progesterone receptor testing were high among participating laboratories. Continued enrollment of laboratories into quality control schemes is essential for achieving and maintaining the highest standard of care for breast cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-015-3444-x) contains supplementary material, which is available to authorized users.

Estrogen receptor negative/progesterone receptor positive breast cancer is not a reproducible subtype

IntroductionEstrogen receptor (ER) and progesterone receptor (PR) testing are performed in the evaluation of breast cancer. While the clinical utility of ER as a predictive biomarker to identify patients likely to benefit from hormonal therapy is well-established, the added value of PR is less well-defined. The primary goals of our study were to assess the distribution, inter-assay reproducibility, and prognostic significance of breast cancer subtypes defined by patterns of ER and PR expression.MethodsWe integrated gene expression microarray (GEM) and clinico-pathologic data from 20 published studies to determine the frequency (n = 4,111) and inter-assay reproducibility (n = 1,752) of ER/PR subtypes (ER+/PR+, ER+/PR-, ER-/PR-, ER-/PR+). To extend our findings, we utilized a cohort of patients from the Nurses’ Health Study (NHS) with ER/PR data recorded in the medical record and assessed on tissue microarrays (n = 2,011). In both datasets, we assessed the association of ER and PR expression with survival.ResultsIn a genome-wide analysis, progesterone receptor was among the least variable genes in ER- breast cancer. The ER-/PR+ subtype was rare (approximately 1 to 4%) and showed no significant reproducibility (Kappa = 0.02 and 0.06, in the GEM and NHS datasets, respectively). The vast majority of patients classified as ER-/PR+ in the medical record (97% and 94%, in the GEM and NHS datasets) were re-classified by a second method. In the GEM dataset (n = 2,731), progesterone receptor mRNA expression was associated with prognosis in ER+ breast cancer (adjusted P <0.001), but not in ER- breast cancer (adjusted P = 0.21). PR protein expression did not contribute significant prognostic information to multivariate models considering ER and other standard clinico-pathologic features in the GEM or NHS datasets.ConclusionER-/PR+ breast cancer is not a reproducible subtype. PR expression is not associated with prognosis in ER- breast cancer, and PR does not contribute significant independent prognostic information to multivariate models considering ER and other standard clinico-pathologic factors. Given that PR provides no clinically actionable information in ER+ breast cancer, these findings question the utility of routine PR testing in breast cancer.

Identification of the activated form of the estrogen receptor (ER) in breast cancer (BC).

e11535 Background: : About 50% of ER positive (ERpos) BC are resistant to hormone treatment. In absence of ligand, ERs are evenly distributed in nuclei in normal tissue. Upon ligand binding, ERs dimerizes and form a discrete focal subnuclear distribution pattern (FDP), which are associated with transcriptional activation of ER. This ER FDP is observed in BC. We hypothesized that in BC that the presence/absence of ER in the FDP could predict antiestrogen activity. This study describes an immunohistochemistry (IHC) method, by which a biomarker could be developed to investigate this hypothesis. Methods: 37 paraffin embedded, formalin fixed archived BC samples were processed using 4 ER-alpha antibodies (Ab) under different IHC conditions to develop and refine this biomarker, the ER nuclear morphology was analyzed with standard microscopy at x1000. Interpretation of the IHC slides was done by an experienced pathologist. Standard ER, progesterone receptor (PR), and Ki67 testing were done. Tumor grade was obtained from the patients’ records. Analysis of the different Ab was with the kappa statistics. Comparison of the IHC technique to immunofluorescence (IHF) was done on 8 samples. Results: Consistent with prior research observations, tumors had two ER nuclear morphologies: 1. Diffuse pattern (D) where the ER was distributed evenly in a fine granular pattern, 2. Aggregate pattern (A) where the ER is distributed in distinct clumps or aggregates. This defined 3 tumor phenotypes: A cells only (A) 1% (4/37), D cells only (D) 65% (24/37), and a heterogenous mix of A + D cells (AD) 18% (7/37), ER Neg 14% (5/37). IHC and IHF analysis for ER nuclear morphology was concordant. The ER activation status (A/AD or D) was not correlated with staining ER intensity, ERpos %, PRpos%, but was correlated with % Ki67 staining (p=0.09) and tumor grade (0.035). Conclusions: ERpos early BC biopsies can be grouped in two categories based on ER nuclear morphology: A group with diffuse and homogenous nuclear staining, and a different group with heterogeneous area of cells having a nuclear pattern consistent with a functional or activated ER. These observations warrant clinical pathological studies to determine if this biomarker is potentially predictive of clinical outcomes.

The Effect of 96-Hour Formalin Fixation on the Immunohistochemical Evaluation of Estrogen Receptor, Progesterone Receptor, and HER2 Expression in Invasive Breast Carcinoma

We studied the impact of 96 hours of formalin fixation on estrogen receptor (ER), progesterone receptor (PR), and HER2 testing by comparing immunohistochemical results from core biopsy specimens fixed under current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines with results for corresponding resection samples fixed for 96 hours. Samples enriched with cases showing weak to moderate receptor expression on core biopsy were included in the study. Cases were scored using ASCO/CAP guidelines. Of the 47 cases, only 1 case (2%) showed a qualitative change in result. However, this change was a positive ER result (H score, 1) on the 96-hour fixed resected sample compared with a negative ER result (H score, 0) for the core biopsy. Minimal changes in semiquantitative H scoring were noted for ER and PR that were likely due to tumor heterogeneity and/or intraobserver variability as the variation occurred in both directions. ER, PR, and HER2 immunohistochemical results should be considered valid for cases fixed up to 96 hours.

Breast Cancer Pharmacogenomics: Where we are going

There is perhaps no field of therapeutics in which personalized medicine has been more successfully implemented than in breast cancer. The routine use of estrogen receptor, progesterone receptor and HER-2 testing supports the value of biomarker-driven therapeutics in cancer in general. In addition, the use of somatic and transcriptomic arrays to guide therapy has been pioneered in the treatment of breast cancer. These advances have resulted in quantifiable improvements in the lives of patients with breast cancer, such that life expectancy of a Caucasian woman diagnosed early with low-grade disease in her mid 50s is 15 years or more. It might reasonably be asked why we need even more progress, but the worldwide burden of this disease remains huge, such that many women diagnosed at a younger age or with more advanced disease, or who are of African or Asian ancestry have much worse prognoses with many dying within two years of presentation. Breast cancer worldwide remains the second most lethal cancer in women, responsible for more than 1 million premature deaths per year worldwide, and for healthcare costs that are astronomic by any measure, not least because the disease affects so many women in their prime. This is particularly true in Asia, where the incidence of breast cancer is rising rapidly, and the diagnosis of breast cancer is made approximately 10 years earlier than that in the western world, and where it is predominantly a disease of pre menopausal women [1]. It follows that optimization of existing therapies is critical, and the development of new and tolerable therapies remains a high priority. For this reason, efforts to identify biomarkers that further focus treatment remain crucial and for this reason, this issue of pharmacogenomics is focused on the ongoing effort around the world to do so.

Reliability of Her2/neu, estrogen receptor, and progesterone receptor testing by immunohistochemistry on cell block of FNA and serous effusions from patients with primary and metastatic breast carcinoma

The prognostic and predictive value of Her2/neu and the hormone receptors in patient with primary or metastatic breast cancer is essential for a favorable outcome of treatment. We have been experiencing increasing requests to test cytologic specimens for these markers in patients with metastatic breast carcinoma. A recent study threw some doubts on the validity of such testing using cell blocks. In this study we compared our immunohistochemical Her2/neu, ER and PR testing performed on 42 formalin-fixed, paraffin-embedded cell blocks from 27 fine needle aspirations (FNA) and 15 serous effusions of 42 patients with metastatic (n = 38) and primary (n = 4) breast carcinoma to the test results obtained on tissue sections. In seven cases the Her2/neu immunohistochemistry (IHC) results on cell blocks were also compared with Her2/neu fluorescence in situ hybridization (FISH) on tissue or cell block. The study revealed 100% correlation for positive and negative Her2/neu results. For ER testing the results showed 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 85.7% negative predictive value (NPV). For PR testing the results showed 80% sensitivity, 100% specificity, 100% PPV, and 88.8% NPV respectively. In conclusion, IHC for Her2/neu, ER and PR performed on formalin-fixed, paraffin-embedded cell blocks prepared from fresh FNA and serous fluid is reliable in predicting the expression of these markers when correlated with IHC and FISH performed on the corresponding tumor tissue.

Estrogen and progesterone receptor testing in breast carcinoma: concordance of results between local and reference laboratories in Brazil.

Breast cancer accounts for approximately one quarter of all cancers in females. Estrogen and progesterone receptor testing has become an essential part of the clinical evaluation of breast carcinoma patients, and accurate results are critical in identifying patients who may benefit from hormone therapy. The present study had the aim of investigating the concordance of the results from hormone receptor tests between a reference laboratory and local (or community) laboratories in Brazil. Retrospective study at a reference pathology laboratory. The concordance in the results from hormone receptor tests between a reference laboratory and 146 local laboratories in Brazil was compared in relation to 500 invasive breast carcinoma cases, using immunohistochemistry. There was concordance in 89.4% (447/500 cases) and 85.0% (425/500 cases) of the results from estrogen (κ = 0.744, P < 0.001) and progesterone (κ = 0.688, P < 0.001) receptor tests, respectively, between local and reference laboratories. This was similar to findings in other countries. The false negative rates from estrogen and progesterone receptor tests in local laboratories were 8.7% and 14.4%, respectively. The false positive rates from estrogen and progesterone receptor tests in local laboratories were 15.5% and 16.0%, respectively. Technical and result interpretation issues may explain most of the discordances in hormone receptor testing in local laboratories. Validation of estrogen and progesterone receptor tests at local laboratories, with rigorous quality control measures, is strongly recommended in order to avoid erroneous treatment of breast cancer patients.

Thyroid Transcription Factor-1 Expression in Breast Carcinomas

Immunostaining for thyroid transcription factor-1 (TTF-1) is frequently used to help assess the site of origin of metastatic carcinomas. TTF-1 expression is most frequently seen in carcinomas of thyroid and lung origin. Furthermore, it has been assumed that the expression of TTF-1 in a carcinoma excludes the possibility of a breast origin. We have recently encountered in our consultation practice 4 cases of invasive breast carcinoma (confirmed by clinical findings and other immunophenotypic features) that showed unequivocal tumor cell expression of TTF-1. However, the frequency with which TTF-1 expression is observed in breast carcinomas is unknown. To address this, we carried out immunostaining for TTF-1 on 546 primary breast carcinomas submitted for routine estrogen receptor, progesterone receptor, and/or HER2 testing. Cases were considered TTF-1 positive if they showed any nuclear staining for this marker. TTF-1 expression was identified in 13 cases (2.4%). Expression varied from focal and weak to diffuse and strong and was seen in both invasive and in situ components. We conclude that a small proportion of breast carcinomas show TTF-1 expression. Therefore, the presence of TTF-1 immunoreactivity in a carcinoma cannot by itself be used to exclude the possibility of a breast origin.

Enhancing Patient Safety through Undergraduate Inter-professional Health Education

The Context Patient safety is a timely and important topic in Newfoundland and Labrador. In 2007, the provincial government established the Commission of Inquiry on Hormone Receptor Testing – conducted by Justice Cameron – as a result of significant estrogen and progesterone receptor testing errors by the Eastern Health Regional Health Authority between 1997 and 2005. Among 60 recommendations outlined in her final report, Justice Cameron recommended the establishment of clear policies relating to adverse event disclosure, electronic occurrence reporting and senior leads for quality in all regional health authorities. Also in 2007, the provincial government established the Task Force on Adverse Health Events with a mandate to “examine and evaluate how the health system identifies, evaluates, responds, and communicates” adverse events (2009: ix). The task force recommended that all regional health authorities and the provincial Department of Health and Community Services commit to a culture of patient safety. One of the 41 recommendations of the task force was that Memorial University of Newfoundland (MUN) consider implementing an inter-professional curriculum focused on patient safety and that the Canadian Patient Safety Institute (CPSI 2008) Safety Competencies Framework be used for guidance in the curriculum’s development. This article describes the development, implementation and evaluation of an undergraduate inter-professional patient safety education module that resulted from this recommendation. Enhancing a culture of patient safety begins with educating students of health professional programs about concepts such as the importance of working well as an inter-professional team. The ability to work collaboratively can enhance a culture of safety in the workplace and the effective management of adverse health events when they do occur. There is growing evidence that when healthcare professionals communicate effectively and know how to work as a team, the quality of patient care increases (Health Council of Canada 2009). Inter-professional education (IPE) – when two or more professions learn from and about each other (Centre for the Advancement of Interprofessional Education 1997) – is one way to improve communication and collaboration among members of a healthcare team. In response to the provincial government task force’s final report, the dean of medicine at MUN asked the Centre for Collaborative Health Professional Education to develop a proposal for the delivery of IPE concerning patient safety. This centre has a mandate to provide IPE to undergraduate and postgraduate students at MUN and practising healthcare professionals within the healthcare system.