scholarly journals RADI-13. Systemic Therapy Type and Timing Effects on Radiation Necrosis Risk in HER2+ Breast Cancer Brain Metastases Patients Treated with Stereotactic Radiosurgery

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii20-iii20
Author(s):  
Christine Park ◽  
Evan Buckley ◽  
Amanda Van Swearingen ◽  
Will Giles ◽  
James Herndon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Radiation Necrosis ◽  
Standard Of Care ◽  
Current Standard ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis ◽  
The Impact ◽  
Systemic Therapies

Abstract Background Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) include radiation therapy, brain permeable systemic therapies, and in select cases, neurosurgical resection. There is a concern that HER2-directed systemic therapies when administered concurrently with stereotactic radiosurgery (SRS) may increase the risk of radiation necrosis (RN). This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters, and timing (“during” defined as four weeks before/after SRS) and type of systemic therapy were evaluated. Results Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age (mean 53.3 vs 50.4 years, respectively), radiotherapy parameters (dose, fraction, CTV, GTV, CI, V12Gy, all p>0.05), and receipt of any type of systemic therapy during SRS (60.7% vs 55.6%, p = 0.97) did not differ between patients who did or did not develop RN. However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during a given SRS treatment compared to those did not develop RN (35.7% vs 5.6%, p<0.05). Conclusions Patients with HER2+ BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. Collectively, this data supports a practice of holding HER2-directed therapy during treatment with SRS if medically acceptable.

Effect of type and timing of systemic therapy on risk of radiation necrosis in patients with HER2+ breast cancer brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14002-e14002
Author(s):  
Christine Park ◽  
Evan Buckley ◽  
Amanda E.D. Van Swearingen ◽  
Will Giles ◽  
James Emmett Herndon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Radiation Necrosis ◽  
Treatment Modalities ◽  
Conformity Index ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis ◽  
The Impact ◽  
Systemic Therapies

e14002 Background: It is estimated that 30% of patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer will develop brain metastases. Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) includes radiation therapy (stereotactic radiosurgery [SRS] or whole brain radiation), brain permeable systemic therapies, and in select cases, neurosurgical resection. A multimodal approach combining these different treatment modalities has improved the overall survival and functional outcomes of patients with BCBrM. Some HER2-directed systemic therapies, however, may increase the risk of radiation necrosis (RN), a longer-term consequence of SRS. This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods: This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 at Duke University with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters (total dose, fractions, clinical target volume [CTV], gross tumor volume [GTV], conformity index [CI], volume receiving 12 gray [V12Gy]), and timing (during [within 4 weeks of SRS] vs. not during SRS) and type of systemic therapy (HER2-directed therapy, mitosis inhibitors, DNA synthesis inhibitors, others) were evaluated. Results: Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age at time of SRS did not differ between those who developed RN and those who did not (mean 53.3 vs 50.4 years, respectively). There was a higher percentage of African Americans in the RN group (28.6% vs 11.1%, p = 0.3). There were no significant differences between the measured radiotherapy parameters—including dose, fraction, CTV, GTV, CI, V12Gy—between the two groups (all p > 0.05). Receipt of any type of systemic therapy during SRS did not differ between patients who did or did not develop RN (60.7% vs 55.6%, p = 0.97). However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during SRS compared to those did not develop RN (35.7% vs 5.6%, p<0.05). Conclusions: Patients with HER2 BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. This data supports a practice of holding HER2-directed therapy during SRS if medically acceptable. Further investigation of next generation HER2-directed therapies in a larger cohort of patients should be investigated to help guide best practice to minimize RN.

scholarly journals Automated Tumour Recognition and Digital Pathology Scoring Unravels New Role for PD-L1 in Predicting Good Outcome in ER-/HER2+ Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Matthew P. Humphries ◽  
Sean Hynes ◽  
Victoria Bingham ◽  
Delphine Cougot ◽  
Jacqueline James ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Significance ◽  
Digital Pathology ◽  
Scoring Systems ◽  
Standard Of Care ◽  
Inflammatory Cells ◽  
Predictive Biomarker ◽  
Current Standard ◽  
Her2 Breast Cancer ◽  
Biomarker Quantitation

The role of PD-L1 as a prognostic and predictive biomarker is an area of great interest. However, there is a lack of consensus on how to deliver PD-L1 as a clinical biomarker. At the heart of this conundrum is the subjective scoring of PD-L1 IHC in most studies to date. Current standard scoring systems involve separation of epithelial and inflammatory cells and find clinical significance in different percentages of expression, e.g., above or below 1%. Clearly, an objective, reproducible and accurate approach to PD-L1 scoring would bring a degree of necessary consistency to this landscape. Using a systematic comparison of technologies and the application of QuPath, a digital pathology platform, we show that high PD-L1 expression is associated with improved clinical outcome in Triple Negative breast cancer in the context of standard of care (SoC) chemotherapy, consistent with previous findings. In addition, we demonstrate for the first time that high PD-L1 expression is also associated with better outcome in ER- disease as a whole including HER2+ breast cancer. We demonstrate the influence of antibody choice on quantification and clinical impact with the Ventana antibody (SP142) providing the most robust assay in our hands. Through sampling different regions of the tumour, we show that tumour rich regions display the greatest range of PD-L1 expression and this has the most clinical significance compared to stroma and lymphoid rich areas. Furthermore, we observe that both inflammatory and epithelial PD-L1 expression are associated with improved survival in the context of chemotherapy. Moreover, as seen with PD-L1 inhibitor studies, a low threshold of PD-L1 expression stratifies patient outcome. This emphasises the importance of using digital pathology and precise biomarker quantitation to achieve accurate and reproducible scores that can discriminate low PD-L1 expression.

scholarly journals Deep learning trained on H&E tumor ROIs predicts HER2 status and Trastuzumab treatment response in HER2+ breast cancer

2021 ◽  
Author(s):  
saman farahmand ◽  
Aileen Fernandez ◽  
Fahad Shabbir Ahmed ◽  
David Rimm ◽  
Jeffrey H Chuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Cross Validation ◽  
Area Under The Curve ◽  
Standard Of Care ◽  
Her2 Status ◽  
Current Standard ◽  
Her2 Positive ◽  
Trastuzumab Therapy ◽  
Her2 Breast Cancer

The current standard of care for many patients with HER2-positive breast cancer is neoadjuvant chemotherapy in combination with anti-HER2 agents, based on HER2 amplification as detected by in situ hybridization (ISH) or protein immunohistochemistry (IHC). However, hematoxylin & eosin (H&E) tumor stains are more commonly available, and accurate prediction of HER2 status and anti-HER2 treatment response from H&E would reduce costs and increase the speed of treatment selection. Computational algorithms for H&E have been effective in predicting a variety of cancer features and clinical outcomes, including moderate success in predicting HER2 status. In this work, we present a novel convolutional neural network (CNN) approach able to predict HER2 status with increased accuracy over prior methods. We trained a CNN classifier on 188 H&E whole slide images (WSIs) manually annotated for tumor regions of interest (ROIs) by our pathology team. Our classifier achieved an area under the curve (AUC) of 0.90 in cross-validation of slide-level HER2 status and 0.81 on an independent TCGA test set. Within slides, we observed strong agreement between pathologist annotated ROIs and blinded computational predictions of tumor regions / HER2 status. Moreover, we trained our classifier on pre-treatment samples from 187 HER2+ patients that subsequently received trastuzumab therapy. Our classifier achieved an AUC of 0.80 in a five-fold cross validation. Our work provides an H&E-based algorithm that can predict HER2 status and trastuzumab response in breast cancer at an accuracy that is better than IHC and may benefit clinical evaluations.

scholarly journals 143P The impact of de-escalation of adjuvant systemic therapy on the outcome of women with early ER+/HER2+ breast cancer

2021 ◽  
Vol 32 ◽  
pp. S423
Author(s):  
V. Jerič Horvat ◽  
D. Manevski ◽  
M. Pohar Perme ◽  
B. Gazić ◽  
P. Drev ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Therapy ◽  
Adjuvant Systemic Therapy ◽  
Her2 Breast Cancer ◽  
The Impact

scholarly journals Integration of Systemic Therapy and Stereotactic Radiosurgery for Brain Metastases

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3682
Author(s):  
Raees Tonse ◽  
Martin C. Tom ◽  
Minesh P. Mehta ◽  
Manmeet S. Ahluwalia ◽  
Rupesh Kotecha
Keyword(s):  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Whole Brain Radiotherapy ◽  
Cancer Therapeutics ◽  
Optimal Timing ◽  
The Impact ◽  
Systemic Therapies

Brain metastasis (BM) represents a common complication of cancer, and in the modern era requires multi-modal management approaches and multi-disciplinary care. Traditionally, due to the limited efficacy of cytotoxic chemotherapy, treatment strategies are focused on local treatments alone, such as whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and resection. However, the increased availability of molecular-based therapies with central nervous system (CNS) penetration now permits the individualized selection of tailored systemic therapies to be used alongside local treatments. Moreover, the introduction of immune checkpoint inhibitors (ICIs), with demonstrated CNS activity has further revolutionized the management of BM patients. The rapid introduction of these cancer therapeutics into clinical practice, however, has led to a significant dearth in the published literature about the optimal timing, sequencing, and combination of these systemic therapies along with SRS. This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis.

Cytokeratin 7, GATA3, and SOX-10 is a Comprehensive Panel in Diagnosing Triple Negative Breast Cancer Brain Metastases

2021 ◽  
pp. 106689692199071
Author(s):  
Eric Statz ◽  
Julie M. Jorns
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Tumor ◽  
Cytokeratin 7 ◽  
Breast Cancer Metastases ◽  
Her2 Breast Cancer ◽  
Cancer Metastases ◽  
Breast Cancer Brain Metastasis ◽  
The Brain

Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.

scholarly journals Comparison of Estrogen and Progesterone Receptor Antibody Reagents Using Proficiency Testing Data

2017 ◽  
Vol 141 (10) ◽  
pp. 1402-1412 ◽  
Author(s):  
Megan L. Troxell ◽  
Thomas Long ◽  
Jason L. Hornick ◽  
Abiy B. Ambaye ◽  
Kristin C. Jensen
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Proficiency Testing ◽  
Immunohistochemical Analysis ◽  
Predictive Testing ◽  
Standard Of Care ◽  
Tissue Microarrays ◽  
Current Standard ◽  
Testing Data ◽  
Positive Results

Context.— Immunohistochemical analysis of estrogen receptor (ER) and progesterone receptor (PgR) expression in breast cancer is the current standard of care and directly determines therapy. In 2010 the American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) published guidelines for ER and PgR predictive testing, encompassing preanalytic, analytic, postanalytic factors; antibody validation; and proficiency testing. Objective.— To compare the performance of different antibody reagents for ER and PgR immunohistochemical analysis by using CAP proficiency testing data. Design.— The CAP PM2 survey uses tissue microarrays of ten 2-mm cores per slide. We analyzed survey data from 80 ER and 80 PgR cores by antibody clone from more than 1200 laboratories. Results.— Laboratories used the ER antibodies SP1 (72%), 6F11 (17%), 1D5 (3%), and the PgR antibodies 1E2 (61%), 16 (12%), PgR-636 (13%), PgR-1294 (8%) in 2015. While 63 of 80 ER cores (79%) were scored similarly using each of the 3 antibodies, there were significant differences for others, with SP1 yielding more positive interpretations. Four cores were scored as ER negative by more than half of the laboratories using 1D5 or 6F11, while SP1 produced positive results in more than 70% of laboratories using that antibody. Despite the greater variety of PgR antibody reagents and greater PgR tumor heterogeneity, 61 of 80 cores (76%) were scored similarly across the 4 PgR antibodies. Conclusions.— Accurate ER and PgR testing in breast cancer is crucial for appropriate treatment. The CAP proficiency testing data demonstrate differences in staining results by ER clone, with SP1 yielding more positive results.

RADT-03. OUTCOMES OF PATIENTS WITH HER2-POSITIVE BREAST CANCER METASTATIC TO BRAIN TREATED WITH HER2-TARGETED SYSTEMIC THERAPY AND STEREOTACTIC RADIOSURGERY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi41-vi41
Author(s):  
John Shumway ◽  
Marina Torras ◽  
Katherine Reeder-Hayes ◽  
Trevor Jolly ◽  
Elizabeth Dees ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Stereotactic Radiosurgery ◽  
Systemic Therapy ◽  
Survival Outcomes ◽  
Maximal Dimension ◽  
Her2 Positive ◽  
Intracranial Metastasis ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract OBJECTIVE For patients with HER2-positive breast cancer metastatic to brain, HER2-directed systemic therapies are increasingly used with stereotactic radiosurgery (SRS). These include monoclonal antibodies such as trastuzumab (H) and pertuzumab (P), antibody-drug conjugates such as ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib. Limited data exist regarding appropriate timing with SRS and outcomes of this treatment regimen. METHODS A single-institution retrospective review collected clinical data on patients with breast cancer metastatic to brain who were treated with SRS from 2009-2020. Statistical analyses were performed using the Kaplan-Meier method and chi-square statistic. RESULTS Of 82 patients with breast cancer metastatic to brain treated with SRS, 33 (40%) were HER2-positive, 18 of whom were hormone receptor-positive. At brain metastasis diagnosis, 15 patients (45%) had &gt;1 intracranial metastasis (range 2-7), and the median brain metastasis maximal dimension was 2.0 cm. Fifteen patients had uncontrolled extracranial disease. After brain metastasis diagnosis, 9 patients (27%) were treated with systemic therapy first (T-DM1+/-HP, lapatinib+HP, chemotherapy+/-HP) followed by SRS at a median of 18.6 months after starting systemic therapy. Seven patients (21%) were treated with SRS first, followed by systemic therapy in 6 of these patients (multi-agent regimens, 4 including T-DM1 or lapatinib). Seventeen (52%) received concurrent systemic therapy and SRS (T-DM1+/-chemotherapy, lapatinib, HP, hormone therapy, chemotherapy). Median follow-up time was 21.1 months. Median overall survival was 24.8 months and not statistically different between treatment groups. Four patients (12%) developed symptomatic radionecrosis; 3 were on T-DM1 concurrent with SRS. CONCLUSION In this small patient sample, we noted favorable survival outcomes for patients with HER2-positive breast cancer metastatic to brain when treated with HER2-targeted therapies together with SRS. The sequence of systemic therapy and SRS does not appear to impact survival outcomes. Concurrent treatment with T-DM1 and SRS may be associated with higher rates of radionecrosis.

scholarly journals Use of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in older patients with ER-positive HER2-negative breast cancer: Young International Society of Geriatric Oncology review paper

2018 ◽  
Vol 10 ◽  
pp. 175883591880961 ◽  
Author(s):  
Nicolò Matteo Luca Battisti ◽  
Nienke De Glas ◽  
Mina S. Sedrak ◽  
Kah Poh Loh ◽  
Gabor Liposits ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Adults ◽  
Older Patients ◽  
Geriatric Oncology ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Cyclin Dependent Kinase ◽  
Current Standard ◽  
Oncology Review ◽  
Er Positive

The current standard of care for the management of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer has been redefined by the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Although adults aged 65 years and older account for the majority of patients with breast cancer, limited data are available about the age-specific dosing, tolerability, and benefit of CDK4/6 inhibitors in this growing population. Older adults are under-represented in clinical trials and as a result, clinicians are forced to extrapolate from findings in younger and healthier patients when making treatment decisions for older patients. In this article, we review the limited age-specific evidence on the efficacy, toxicity, and quality of life (QoL) outcomes associated with the use of CDK4/6 inhibitors in older adults. We also describe ongoing trials evaluating CDK4/6 inhibitors in the older population and highlight that only a minority of adjuvant and metastatic trials of CDK4/6 inhibitors in the general breast cancer population includes geriatric assessments. Finally, we propose potential strategies to help guide decision making for fit and unfit older patients based on disease endocrine sensitivity, the need for rapid response and geriatric assessment.

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