MarginProbe 101 PDF - Dilan Medical Technologies

® MARGIN PROBE Proven to reduce re-excisions in breast cancer Margin Probe® Radiofrequency Spectroscopy System Identifies, in real-time, positive margins by detecting microscopic residual cancer and DCIS at the surface of excised breast tissu...

® MARGIN PROBE Proven to reduce re-excisions in breast cancer Margin Probe® Radiofrequency Spectroscopy System Identifies, in real-time, positive margins by detecting microscopic residual cancer and DCIS at the surface of excised breast tissue, enabling immediate action by the surgeon, thereby MARGIN PROBE reducing the need for re-excision surgery. Did I get it all? Current margin assessment methods cannot fully address need APPROVED Gross Assessment, Specimen X-Ray Cannot palpate/visualize microscopic invasive cancer nor DCIS Low sensitivity for ILC Frozen Section Difficult due to fatty nature of breast tissue May add significant time to procedure Full Cavity Shave Can compromise cosmetic outcomes due to volume of healthy tissue removed Thinner shaves to manage tissue volume can result in reduced success clearing final margins Re-excision impacts everyone t Increased ca V) !.... Disappointment of..'! Tremendous cost V) (1) telling patient to healthcare financial burden C ·- 1J V) Increased "I didn't get it all" system ·-(1) !.... Decreased patient complications Delays adjuvant > satisfaction >- (1) Average $16k/procedure 0 0 Compromises IORT 0 Not aligned with a... treatment a... a... !.... Poor cosmesis and oncoplastic shift from volume procedures to value 1 Metcalfe LN, Zysk AM, Yemul KS, et al. Beyond the Margins-Economic Costs and Complications Associated With Repeated Breast-Conserving Surgeries. JAMA Surg. 2017;152(11):1084-1086. How does MarginProbe® work? As tissue becomes malignant, its cellular morphology and electrical behavior change I o.~c--------+--l---,,L--------------+-+~ ~--+---4 0.4 r - - - - - - + - - - - - - + - + - - - - - J ~ - + - - - - - + - - ---------+ !e2. 2::- 0.4~ - - - - - - t - -------,,'--j - - - - -- - - - -<. - - -~ -------j ·;; 0·3 r - - - - - - + - - -N - orm - a c+--- 1 l-----+-----+-----+----------' g 0.3 ~ -----+, 500 u 0 2007 2008 2010 2014 2015 201 6 2017 2018 2019 2020 2021 * *Jan-Mar MarginProbe®. Do it once. Get it all. MARGIN PROBE Dilan Medical Technologies Inc, 12050 Jefferson Avenue, Newport News, VA 23606 877-GO-DILON - www.dilon.com MRK-00156 Rev 1  4/16/2024 1 2 1  4/16/2024 MarginProbe’s journey to Dilon Technologies Company founded Dune Medical Devices, Ltd. CPT III code founded in Israel to Dune awarded develop proprietary RF FDA PMA study standalone CPT III spectroscopy technology US launch code specific to ~600 patient US United States for tissue characterization pivotal study of MarginProbe commercialization MarginProbe begins begins 2006 2013 2016 2020 2002 2008 2014 2018 Acquisition Dune acquired by Dilon EU CE Mark FDA approval Technologies First commercial application, MarginProbe MarginProbe for approved for intraoperative margin intraoperative assessment in breast margin Horizon 2020 grant conserving surgery receives assessment in BCS Dune receives $3.4M grant funding CE Mark for breast cancer from EC to develop SmartBiopsy product prototype 3 Breast Cancer in the United States 1 in 8 develop breast cancer in her lifetime 60-70% choose lumpectomy1 1 in 5 hear… “I’m sorry. I didn’t get all of the cancer.” ~40,000 women per year undergo repeat operations due to positive margins 1Katipamula R, Degnim AC, Hoskin T, et al. Trends in mastectomy rates at the Mayo Clinic Rochester: effect of surgical year and preoperative magnetic resonance imaging. The Science Behind Your Peace of Mind J Clin Oncol 2009;27(5):4082-4088. 4 2  4/16/2024 Re-excision negatively impacts everyone ~40,000 higher financial reoperations worsens clinical burden and each year outcomes emotional stress average reduces patient 2x risk infection $16,000 satisfaction Providers and 49% additional cost compromises Patients surgical per procedure IORT and Payers complications >$600 million oncoplastic delays adjuvant increased cost procedures therapy to healthcare system The Science Behind Your Peace of Mind 5 MarginProbe® Radiofrequency Spectroscopy (RFS) System Identifies, in real time, positive margins on the lumpectomy specimen by findingmicroscopic residual cancer and DCIS at the surface, enabling immediate action by the surgeon, thereby reducing the need for re-excisions The Science Behind Your Peace of Mind 6 3  4/16/2024 Reflection of electromagnetic MarginProbe® measures and waves depends upon tissue’s analyzes the bioelectric signature electrical of tissue to immediately identify it as properties malignant or benign As tissue becomes malignant, its cellular morphology and electrical behavior change Therefore, reflection of cancerous tissue is different than that of normal tissue The Science Behind Your Peace of Mind 7 8 4  4/16/2024 Future: RFS has applications in most oncology biopsy, surgery, and targeted treatments Annual Worldwide Incidence1 Study complete Paper published Esophageal Commercial use 455,800/yr Lung, bronchus, trachea Breast Cancer 1,824,700/yr 1,676,600/yr Prostate 2 Colorectal 1,111,700/yr 1,360,600/yr 1Global Cancer Statistics 2012, CA Cancer J Clin 2015;65:87-108 2Dotan, ZA et al. Detection of prostate cancer by radio-frequency near-field spectroscopy in radical prostatectomy ex vivo specimens. Prostate Cancer and Prostatic Disease. 2013 Mar;16(1):132 9 “One person can make a difference, and everyone should try.” ~John F Kennedy 10 5  4/16/2024 Breast Cancer 101 1 MarginProbe is a value-based sell requiring the ability to lead and manage in-depth clinical conversations. Objective This session provides a base of knowledge on breast anatomy and physiology, breast cancer disease-state, diagnosis, and treatment, facilitating the process of becoming a subject matter expert. The Science Behind Your Peace of Mind 2 1  4/16/2024 Breast Anatomy and Physiology 3 lobes 15-20 surrounding nipple Parenchyma lobules mammary clustered inside lobes glandular produce milk ducts transfer milk to nipple ligaments (fibrous) support and give shape to breast fascia Stroma envelopes and supports tissue supportive adipose (fat) connective fills space between glandular and connective tissue determines breast size nipple Skin openings allow milk to flow during lactation areola The Science Behind Your Peace of Mind 4 2  4/16/2024 lobes 15-20 surrounding nipple Parenchyma lobules mammary clustered inside lobes glandular produce milk ducts transfer milk to nipple ligaments (fibrous) support and give shape to breast fascia Stroma envelopes and supports tissue supportive adipose (fat) connective fills space between glandular and connective tissue determines breast size nipple Skin openings allow milk to flow during lactation areola The Science Behind Your Peace of Mind 5 lobes 15-20 surrounding nipple Parenchyma lobules mammary clustered inside lobes glandular produce milk ducts transfer milk to nipple ligaments (fibrous) support and give shape to breast fascia Stroma envelopes and supports tissue supportive adipose (fat) connective fills space between glandular and connective tissue determines breast size nipple Skin openings allow milk to flow during lactation areola The Science Behind Your Peace of Mind 6 3  4/16/2024 lobes 15-20 surrounding nipple Parenchyma lobules mammary clustered inside lobes glandular produce milk ducts transfer milk to nipple ligaments (fibrous) support and give shape to breast fascia Stroma envelopes and supports tissue supportive adipose (fat) connective fills space between glandular and connective tissue determines breast size nipple Skin openings allow milk to flow during lactation areola The Science Behind Your Peace of Mind 7 lobes 15-20 surrounding nipple Parenchyma lobules mammary clustered inside lobes glandular produce milk ducts transfer milk to nipple ligaments (fibrous) support and give shape to breast fascia Stroma envelopes and supports tissue supportive adipose (fat) connective fills space between glandular and connective tissue determines breast size nipple Skin openings allow milk to flow during lactation areola The Science Behind Your Peace of Mind 8 4  4/16/2024 Breast lymph fluid is drained by lymphatic vessels leading to lymph nodes The Science Behind Your Peace of Mind 9 Hormones regulate breast function Menstrual Cycle After ovulation, progesterone Breast Development stimulates formation of milk Estrogen causes ductal growth glands Progesterone causes growth of blood vessels enlarge and fill lobes with blood, which can cause breast swelling and tenderness Pregnancy Estrogen causes ductal elongation and creation of side Menopause branches Decrease in estrogen and Progesterone increases number progesterone causes glandular and size of lobules to prepare tissue to shrink, which is for milk production replaced by fat Prolactin and oxytocin work together to produce and eject milk during lactation The Science Behind Your Peace of Mind 10 5  4/16/2024 Breast Cancer Incidence, Types and Progression 11 Breast is the most common cancer diagnosed in women1 Stage at Diagnosis2 1 in 8 women will be diagnosed in her lifetime 100% distant 6% 90% regional 80% 27% median age at diagnosis is 62 70% 60% 50% typically no symptoms, with detection as result of 40% local 64% screening 30% 20% most common physical sign is painless lump 10% 0% 1) non-melanoma skin cancers excluded 2) local: confined to breast; regional: includes surround tissue and/or nearby lymph nodes; distant: has spread to The Science Behind Your Peace of Mind distant organs and/or lymph nodes, including nodes above collar bone 12 6  4/16/2024 Type Carcinoma: originating in epithelial layer of tissue (most common) Sarcoma: originating in bones and connective tissue (rare) Origin Ducts Lobules Breast Cancer Other is classified Progression In-situ: remains contained within structure by 3 criteria Invasive: has spread into surrounding tissue Invasive Ductal Ductal Carcinoma In Situ Invasive Lobular Carcinoma – “IDC” “DCIS” Carcinoma – “ILC” The Science Behind Your Peace of Mind 13 breast cancer incidence 20211 invasive dcis 281,550 49,290 ~330,000 new breast cancers 0 50,000 100,000 150,000 200,000 250,000 300,000 350,000 diagnosed annually ILC in U.S.1 the majority are invasive IDC DCIS ductal carcinoma2 Other 1. American Cancer Society. Cancer Facts & Figures 2021. Atlanta: American Cancer Society; 2021. The Science Behind Your Peace of Mind 2. Siegel, RL, Miller, KD, Fuchs, H, Jemal, A. Cancer Statistics, 2021. CA Cancer J Clin. 2021: 71: 7- 33. 14 7  4/16/2024 Histologic subtypes of note In Situ Invasive Ductal Carcinoma In-Situ (DCIS) normal basement membrane Invasive Ductal Carcinoma (IDC) “intraductal carcinoma” basal cells “infiltrating ductal carcinoma” most common in-situ epithelial cells represents 80% of invasive breast subtype cancer treated as cancer Invasive Lobular Carcinoma (ILC) difficult to resect “infiltrating lobular carcinoma” because does not comprises 15% invasive cancers present as mass that can be seen, felt or visualized harder to detect on imaging, with palpation and with gross Lobular Carcinoma In-Situ (LCIS) in-situ assessment increases risk of invasive Inflammatory Carcinoma breast cancer invades lymphatic vessels of skin typically not treated but requires active rare, aggressive surveillance Paget’s Disease rare ductal carcinoma affecting invasive nipple/skin 97% have cancer elsewhere in The Science Behind Your Peace of Mind breast 15 solid DCIS: tumor cells completely fill duct subtypes of a cribiform subtype tumor cells do not completely fill duct, contains holes (often like swiss cheese) papillary finger-like projections into ducts micropapillary smaller finger-like projections into ducts comedo more aggressive, usually accompanied by necrosis higher risk of invasive cancer and recurrence The Science Behind Your Peace of Mind 16 8  4/16/2024 solid DCIS: tumor cells completely fill duct subtypes of a cribiform subtype tumor cells do not completely fill duct, contains holes (often like swiss cheese) papillary finger-like projections into ducts micropapillary smaller finger-like projections into ducts comedo more aggressive, usually accompanied by necrosis higher risk of invasive cancer and recurrence The Science Behind Your Peace of Mind 17 Biologic markers approximate molecular subtypes Hormone Receptor Status: Estrogen Receptor (ER): cancer has receptors enabling estrogen to fuel Estrogen Receptor growth ER+ ER enables estrogen to fuel Progesterone cancer cell Receptor (PR): enabling progesterone to fuel growth PR+ growth Hormone Receptor+ the cancer is ER+ and/or PR+ Luminal A Luminal B Her2 – growth promoting protein. If cancer cells have too many copies of Her2 gene, it is HR+ Her2+ HR+ Progesterone Receptor HER2- HER2+ and/or PR enables progesterone to fuel cancer high Ki67* cell growth Hormone Receptor Basal Like HER2 Enriched HR HR+ cancer is ER+ and/or PR+ (Triple Negative) HR- cancer is both ER- and PR- HR- HR- HER2+ HER2- Human Epidermal Growth Factor HER2 Receptor 2 higher than normal level is HER2+ The Science Behind Your Peace of Mind *protein associated with high cellular proliferation and growth 18 9  4/16/2024 Breast Cancer Progression – a story in six pictures normal ductal atypical ductal DCIS DCIS with invasive ductal hyperplasia hyperplasia microinvasion cancer (ADH) (IDC) The Science Behind Your Peace of Mind 19 Breast Cancer Progression – a story in 6 pictures ADH/DCIS is the line between benign and malignant. Keep this progression in mind as we learn about MarginProbe Technology and Pathology processing normal ductal atypical ductal DCIS DCIS with invasive ductal hyperplasia hyperplasia microinvasion cancer (ADH) (IDC) The Science Behind Your Peace of Mind 20 10  4/16/2024 Lymph Nodes Bones Regional and Distant Breast Brain Cancer Progression Lungs Liver The Science Behind Your Peace of Mind 21 Breast Cancer Diagnosis and Treatment 22 11  4/16/2024 Diagnosis - Imaging Tools Mammogram Ultrasound MRI Low Dose X-ray Soundwaves Radio waves and Analog/Digital/3D Helpful in dense strong magnets Tomosynthesis breasts For those diagnosed to Used for screening and Distinguishes fluid vs get detailed info on diagnosis solid suspicious areas size or other tumors Dense breasts can User dependent For high-risk screening mask tumor Many false positives The Science Behind Your Peace of Mind 23 Breast density can mask tumors Category A Category B Category C Category D Almost entirely Areas of Heterogeneously Extremely dense Easily identified fatty scattered dense Lowers sensitivity IDC in fatty breast 10% population fibroglandular May obscure of mammogram density small masses 10% population 40% population 40% population The Science Behind Your Peace of Mind 24 12  4/16/2024 Breast density can mask tumors Does the surgeon see a lot of dense breast? How does it present unique challenges along the spectrum of breast cancer screening, diagnosis and treatment? How does s/he feel about dense breast legislation? Category A Category B Category C Category D Almost entirely Areas of Heterogeneously Extremely dense Easily identified fatty scattered dense Lowers sensitivity IDC in fatty breast 10% population fibroglandular May obscure of mammogram density small masses 10% population 40% population 40% population The Science Behind Your Peace of Mind 25 Breast biopsy enables cancer diagnosis Fine Needle Aspiration (FNA) Thin needle inserted through the skin to collect sample of cells. Helpful in distinguishing fluid-filled cysts from solid masses. Core Needle Biopsy Removes a core of tissue, rather than collection of cells May be ultrasound, stereotactic, or MRI guided Vacuum-assisted breast biopsy needs only one needle insertion Surgical (Open) Biopsy May be incisional (involving the removal of part of the abnormality) or excisional (removing all of the abnormality) The Science Behind Your Peace of Mind 26 13  4/16/2024 Mastectomy Complete removal of the entire breast 60-70% of Often followed by breast women reconstruction diagnosed with breast cancer undergo breast Breast Conserving Surgery conserving (BCS) surgery1 Removal of the cancerous lesion and a small ‘margin’ of healthy tissue Generally followed by radiation therapy The Science Behind Your Peace of Mind 27 DCIS is challenging to surgically excise No visible mass; growth pattern follows milk ducts Generally presents as calcifications on mammogram Not visual nor palpable during surgery The Science Behind Your Peace of Mind 28 14  4/16/2024 DCIS is challenging to surgically excise Does the surgeon see a lot of No visible DCIS? Does mass; growth s/he perform more pattern follows milk re-excisions ducts in DCIS patients? (yes) Does s/he follow Consensus Margin Guideline for DCIS? Generally presents as calcifications on mammogram Not visual nor palpable during surgery The Science Behind Your Peace of Mind 29 ILC is also challenging to successfully excise Does not show up well on imaging Harder to grossly visualize and palpate during surgery Often much larger in final pathology than known before surgery The Science Behind Your Peace of Mind 30 15  4/16/2024 ILC is also challenging to successfully exercise Does not show up well on Does the surgeon perform more imaging re-excisions in ILC? (yes) Harder to grossly visualize and palpate during surgery Often much larger in final pathology than known before surgery The Science Behind Your Peace of Mind 31 American Joint Committee on Cancer (AJCC) TNM cancer staging 8th edition effective January, 20181 Genomic T: Extent (size) of HER2: Her2/neu Profiles tumor status i.e. Oncotype and Mammaprint N: Spread to ER: Estrogen Receptor / nearby lymph nodes PR: Progesterone Staging is no longer Receptor status based solely on “TNM” criteria G: Grade of M: Metastasis cancer The Science Behind Your Peace of Mind 1) https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx 32 16  4/16/2024 American Joint Committee on Cancer (AJCC) TNM cancer staging 8th edition effective January, 20181 Genomic T: Extent (size) of HER2: Her2/neu Profiles tumor status i.e. Oncotype and Mammaprint N: Spread to ER: Estrogen nearby Receptor / G: Grade of cancer PR: Progesterone lymph nodes Indicates status Receptor how closely malignant cells resemble normal cells Provides idea how quickly the cancer may grow and spread Tumors are graded between 1 and 3 M: Metastasis Grading for DCIS is different, defined as low, medium or high grade The Science Behind Your Peace of Mind 1) https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx 33 American Joint Committee on Cancer (AJCC) TNM cancer staging 8th edition effective January, 20181 Genomic T: Extent (size) of ER: Estrogen ReceptorProfiles HER2: Her2/neu / tumor PR: Progesterone Receptor status status and i.e. Oncotype Mammaprint Cancer cells grow in response to hormone ~80% of all breast cancers are “ER-positive” ~65% of all breast cancers are “PR-positive” ER/PR+ cancers more likely to respond to N: Spread to hormone therapy preventing recurrence nearby lymph nodes G: Grade of M: Metastasis cancer The Science Behind Your Peace of Mind 1) https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx 34 17  4/16/2024 American Joint Committee on Cancer (AJCC) TNM cancer staging 8th edition effective January, 20181 Genomic HER2: Her2/neu status T: Extent (size) of Profiles tumor Breast cancer with higher than i.e.normal levels Oncotype and of HER2, protein on outside of allMammaprint breast cells Tend to grow and spread faster than other breast cancer Very likely to benefit from therapy targeting ER: Estrogen HER2 protein N: Spread to Receptor / nearby PR: Progesterone lymph nodes Receptor status G: Grade of M: Metastasis cancer The Science Behind Your Peace of Mind 1) https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx 35 American Joint Committee on Cancer (AJCC) TNM cancer staging 8th edition effective January, 20181 T: Extent (size) of HER2: Her2/neu Genomic Profiles tumor status i.e. Oncotype and Mammaprint Used to inform risk of breast cancer recurrence as well as ER: Estrogen How likely to benefit from N: Spread to chemotherapy Receptor / nearby PR: Progesterone lymph nodes Receptor status G: Grade of M: Metastasis cancer The Science Behind Your Peace of Mind 1) https://cancerstaging.org/references-tools/deskreferences/Pages/Breast-Cancer-Staging.aspx 36 18  4/16/2024 Breast Cancer treatment most often includes adjuvant therapy to reduce recurrence risk Radiation Therapy (RT): may be delivered to whole breast or to limited area at highest risk for recurrence (partial breast) protocols vary, with standard RT delivered over 6 weeks Whole Breast Radiation Therapy in select patients, radiation may be delivered in one dose in the operating room (called IORT) Chemotherapy: may be delivered prior to surgery as a means to shrink tumor before excision (neoadjuvant) or may be delivered post- surgery to treat metastatic disease (adjuvant) Hormone (Endocrine) Therapy: often prescribed to hormone receptor positive patients after surgery to reduce risk of recurrence most cancers are hormone receptor positive or use female hormones to grow Biological (Targeted) Therapy: often prescribed to HER2 positive patients, it binds to receptor on cancer cells and prevents growth targets cell for destruction by immune system can be used in conjunction with chemotherapy The Science Behind Your Peace of Mind 37 Breast Cancer treatment most often includes adjuvant therapy to reduce recurrence risk Radiation Therapy (RT): may be delivered to whole breast or to limited area at highest Does the surgeon offer IORT? What risk for recurrence (partial breast) protocols vary, with standard RT delivered over 6 weeks happens if margin is positive at time Whole of surgery? WhatBreast Radiation percentage of Therapy in select patients, radiation may be delivered in one dose in the operating room (called IORT) patients receive IORT? Does surgeon use neoadjuvant Chemotherapy: chemo in HER2+ and Triple Negative may be delivered prior to surgery as a means to shrink tumor (ER/PR- HER2-) patients? What before excision (neoadjuvant) or may be delivered post- surgery to treat metastatic disease (adjuvant) percentage of patients is that? Hormone (Endocrine) Therapy: often prescribed to hormone receptor positive patients after surgery to reduce risk of recurrence most cancers are hormone receptor positive or use female hormones to grow Biological (Targeted) Therapy: often prescribed to HER2 positive patients, it binds to receptor on cancer cells and prevents growth targets cell for destruction by immune system can be used in conjunction with chemotherapy The Science Behind Your Peace of Mind 38 19  4/16/2024 Radiation Therapy Most common form of Accelerated Partial Breast Internal Radiation External Beam radiation Irradiation (APBI) Whole Breast “WBRT” Brachytherapy (Mammosite, Contura, SAVI) 5-7 weeks M-F Hypofractionated – 3 weeks M-F 5 days M-F 2x/day 3D Conformal IORT – Intraoperative Radiation Therapy One dose in operating room at time of lumpectomy The Science Behind Your Peace of Mind 39 Chemotherapy Drugs interfere with cell division or metabolic processes Adjuvant Chemotherapy Most harmful to rapidly dividing Given after surgery Neoadjuvant Chemotherapy cancer cells Reduces chance Given before Often used in Triple Often used in HER2 of micromets surgery Negative patients positive patients spreading to other tissues The Science Behind Your Peace of Mind 40 20  4/16/2024 Hormone (Endocrine) Therapy Patients who are ER (Estrogen Receptor) and/or PR (Progesterone Receptor) positive Breast cancer cells with proteins (receptors) that can attach to estrogen (ER+) and/or progesterone (PR+) supporting growth of the cancer Can be treated with hormone therapy drugs that lower estrogen levels or block estrogen receptors. i.e. tamoxifen breast cancers with neither estrogen nor progesterone receptors (ER-/PR-) hormonal therapy unlikely to work Tamoxifen Selective estrogen receptor modulator Binds to estrogen receptors in breast tissue, making them unavailable to effects of estrogen Other hormonal medications Aromatase inhibitors – (ie. Arimidex) stop estrogen production LHRH-inhibiting compounds – (ie. Lupron) suppresses pituitary hormones that cause ovaries to produce estrogen The Science Behind Your Peace of Mind 41 Biological (Targeted) Therapy Patients who are HER2+ HER2 + is an over-expression of a protein on the surface of breast cancer cells HER2 protein is an important pathway for cell growth & results in faster growth and spread of cancer About 10-20% of newly diagnosed cancers are HER2+1,2 HER2 status is not routinely checked in DCIS Herceptin (trastuzumab) Trastuzumab is an antibody that attaches to the HER2 protein to slow or stop the growth of cancer cells Dual agent targeted therapy Perjeta (pertuzumab) with Herceptin (trastuzumab) in neoadjuvant setting Pertuzumab is an antibody that targets HER2+ cells but in a different way than trastuzumab 1. Rakha EA, Pinder SE, Bartlett JM, et al. for the National Coordinating Committee for Breast Pathology. Updated UK recommendations for HER2 assessment in breast cancer. J Clin Pathol. 68(2):93-9, 2015. 2. Esserman LJ and Joe BN. Clinical features, diagnosis, and staging of newly diagnosed breast cancer. In: UpToDate. Hayes DF, Burstein H, Vora SR (eds.). The Science Behind Your Peace of Mind Waltham, MA: UpToDate, 2018. 42 21  4/16/2024 Triple-Negative Breast Cancer Tumor: Estrogen receptor negative (ER-) Progesterone receptor negative (PR-) HER2/neu negative (HER2-) Insensitive to many of the most effective therapies Not fueled by hormones & HER2 protein, so it does not typically respond to endocrine and biological drugs Is considered to be more aggressive and have a poorer prognosis than other cancers Occurs in 10-20% of breast cancer diagnoses About 70% of women with a BRCA mutation are triple-negative Neoadjuvant chemo works very well in Triple-Negative patients The Science Behind Your Peace of Mind 43 Tumor Grade describes how quickly a breast tumor is likely to grow and spread A score of 1-3 based on each set of factors: How much of the tumor has normal breast ducts Final Score 3-9 "tubule formation" Size and shape of the nuclei in tumor cells "nuclear pleomorphism" Total score 3-5: Total score 6-7: Total score 8-9: How many diving Grade 1 (low grade or Grade 2 (intermediate Grade 3 (high grade or cells are present “well differentiated”) grade or moderately poorly differentiated) "mitotic count" differentiated) The Science Behind Your Peace of Mind 44 22  4/16/2024 Biomarkers (ER, PR, Her2) affect treatment choices Hormone Receptor Status (ER/PR) Hormone Receptor Positive (ER+ and/or PR+) Breast cancer cells with proteins (receptors) that can attach to estrogen (ER+) and/or progesterone (PR+) supporting growth of the cancer Can be treated with hormone therapy drugs that lower estrogen levels or block estrogen receptors. i.e. tamoxifen Hormone Receptor Negative (ER-/PR-) breast cancers with neither estrogen nor progesterone receptors (ER-/PR-) hormonal therapy unlikely to work Human Epidermal Growth Factor Type 2 (HER2) HER2+ higher than normal levels of HER2 HER2 is a growth-promoting protein on the outside of all breast cells, but in different amounts HER2+ cancers are more aggressive than HER2- but respond well to targeted (endocrine) therapy i.e. Herceptin HER2 status is not routinely tested in DCIS Triple Negative ER-/PR-/HER2- Does not respond to hormone or targeted therapy, more aggressive, poorer prognosis The Science Behind Your Peace of Mind 45 Genomic Profiling predicts rate of recurrence for better treatment planning The Science Behind Your Peace of Mind 46 23  4/16/2024 Staging - T Category Description TX: Primary tumor cannot be assessed T0: No evidence of primary tumor Carcinoma in situ, or Paget's disease of the nipple, without detectable tumor Tis: mass T1: Tumor ≤ 2cm T2: Tumor > 2cm but ≤ 5cm T3: Tumor > 5cm Tumor of any size, with direct spread to chest wall or skin (includes T4: inflammatory carcinoma and ulceration of the breast skin) The Science Behind Your Peace of Mind 47 Staging – N, M Category Description NX: Nearby lymph nodes cannot be assessed N0: Cancer has not spread to nearby lymph nodes Cancer has spread to 1-3 axillary lymph nodes &/or tiny amounts of cancer N1: found in internal mammary lymph nodes on sentinel lymph node biopsy Cancer has spread to 4-9 axillary lymph nodes or cancer has enlarged internal N2: mammary lymph nodes Cancer has spread to 10 or more axillary lymph nodes -or- under collarbone (infraclavicular nodes) mets -or- 1 axillary + enlarged internal mammary nodes -or- 4 axillary + micromets at internal mammary on SLNB N3: -or- nodes above collarbone (supraclavicular nodes) mets Category Description MX: Presence of distant metastasis cannot be assessed M0: No distant metastases are found on imaging tests of by physical exam M1: Distant metastases are present The Science Behind Your Peace of Mind 48 24  4/16/2024 New staging classification has changed prognosis Addition of ER, PR, Her2 status and Grade makes new stage grouping complex More will classify as Stage 1 Example 1: T2,N0,M0, Grade 3, ER+, PR+, Her2-, Old = IIA Stage 5 Year Survival New = IB Example 2: T3,N2,M0, Grade 2, ER+, PR+, Her2+ 0-I Close to 100% Old = IIIA II 93% New = IB III 72% Example 3: T3,N2,M0, Grade 2, ER-, PR-, Her2- Old = IIIA IV 22% New IIIB Survival rates from NCI SEER database 2007-2013 The Science Behind Your Peace of Mind 49 1 in 8 The Science Behind Your Peace of Mind 50 25  4/16/2024 Lumpectomy 101 1 Breast Conserving Surgery (BCS) Wide Local Partial Excision Mastectomy One surgery, many names Wedge Segmental Resection Mastectomy Lumpectomy 2 1  4/16/2024 Successful Breast Conserving Surgery (BCS) is predicated on achieving negative margins1 A margin is a rim of healthy tissue surrounding tumor Negative margins ensure no cancerous tumor left behind Positive margins double the risk of local recurrence2 3 What is a negative margin? 4 2  4/16/2024 Negative margin = "No Tumor On Ink" Meta-analysis >28,000 patents Low rates of IBTR Has potential to reduce re-excision, improve cosmetic outcomes and decrease healthcare costs 5 Negative margin = 2mm >2mm negative margins do not significantly decrease IBTR Clinical judgment should be used for 2mm negative margins do not significantly decrease IBTR Clinical judgment should be used for