Part I: Not all DCIS is "Risky"

Ductal carcinoma in situ (DCIS) is considered the earliest form of breast cancer and noninvasive, meaning it hasn't spread out of the milk duct and has a low risk of becoming invasive. In part 1 of the DCIS webinar series, you will learn about different types and grades of DCIS and why that is important. The grade of a cancer describes how the cells look and how quickly they grow compared with normal cells. It also indicates how likely it is to develop into an invasive cancer. There is no one-size-fits-all treatment plan for DCIS.

Our speaker, Deborah Collyar, a DCIS survivor, author, and President of Patient Advocates In Research (PAIR) will discuss the specific factors needed as you consider treatment options vs active monitoring.

1. Deborah Collyar President, Patient Advocates in Research  Part 1: Not all DCIS is risky SHARE Educational Program January 9, 2024 Part 2 will be on February 6, 2024 “ DCIS Latest Research: De-escalating the Fear of Recurrence ”

2. What do people want to know about DCIS? Why so many opinions: Aren’t there standards for DCIS? Is DCIS cancer or not? Will it come back? If so, will I die? What type of treatment should I consider? Adapted from Liz Frank, Dana-Farber Cancer Institute, and 2021 SHARE DCIS Webinar What is risk about? Why am I being referred to cancer doctors? Are my family members at risk? Why is this so confusing?

3. Misunderstandings are common People often hear about DCIS through varied sources Media, prior DCIS patients, message boards, blogs, anecdotes, etc. Celebrity sources often mix up DCIS with invasive cancer Some healthcare providers lead with opinions unrelated to research Reliable sources (e.g., radiologists, surgeons, oncologists) Can set fearful mindsets We’re working on better communication DCIS may be a person’s first experience with the “cancer” world https://en.wikipedia.org/wiki/Misinformation https://www.padf.org/covid-19/covid-awareness/ COVID examples…

4. Ductal carcinoma in situ (DCIS) is… A breast condition that includes abnormal cells that stay inside the milk duct. Carcinoma/cancer: disease in which some of the body’s cells grow uncontrollably and can spread to other parts of the body By Cancer Research UK - Original email from CRUK, CC BY-SA 4.0, https:// commons.wikimedia.org /w/ index.php?curid =34333197 https://www.cancer.gov/about-cancer/understanding/what-is-cancer https://www.slideshare.net/doctorbobm/dcis-breast-cancer-30985400#10 DCIS has many names: Pre-invasive tumor/lesion Pre-cancerous tumor/lesion Non-cancerous tumor/lesion Non-invasive breast cancer Intraductal carcinoma “Non-obligate pre-cursor” to breast cancer Stage 0 breast cancer Breast disease or condition

5. Poll question #1 What sounds better to you? Non-cancerous lesion Stage 0 breast cancer Abnormal cells that look like cancer Pre-cancerous lesion A “non-obligate pre-cursor” to breast cancer Non-invasive breast cancer Breast disease

6. DCIS in perspective: Most live longer than general population DCIS Dilemmas eBook 2015 https://pubmed.ncbi.nlm.nih.gov/10761960/ DCIS: Ductal Carcinoma In Situ IBC: Invasive Breast Cancer “ Among women diagnosed with DCIS, risk of death from breast cancer was low, at least within the 10 years following diagnosis. This may reflect the effectiveness of treatment for DCIS, the "benign" nature of DCIS, or both. At 10 years… their risk of dying of all causes combined was lower than that in the general population.” - Virginia L. Ernster  

7. Ductal Carcinoma In Situ (DCIS) is still confusing! Screening At least 75 breast diseases/conditions https://bit.ly/3cYiigu Misunderstanding (internet, social media, etc.) Mixed messages

8.                       1980 1983 1985 1987 1989 1991 5 10 15 20 25 Thousands DCIS # of MMG Machines 1 in 1300 screening MMG diagnose DCIS DCIS = unintended consequence of increased screening DCIS increased with mammography machines (~80% is detected by mammogram) Courtesy of Shelley Hwang, MD, Duke University

9. More breast cancer More DCIS No change in overall deaths This means Screening results? ‘Over-treatment’ for many (3 in 10 estimated)* * 2017 University of Oslo

10. Screening Screening: different than diagnostic mammograms https://www.cancer.gov/types/breast/patient/breast-screening-pdq https://www.rahwaynj.gov/ImageRepository/Document?documentID=892 https://www.acr.org/-/media/ACR/Files/Practice-Parameters/Screen-Diag-Mammo.pdf Before symptoms Used in populations Can find abnormal cells or very small cancer Calcifications can be benign, DCIS, or invasive breast cancer Can lead to diagnostic mammogram

11. Diagnostic A fter screening if signs or symptoms of breast condition More images & magnified Can also include: C omputed tomography ( CT ) Digital breast tomosynthesis ( DBT/3D ) M agnetic resonance ( MR/MRI ) P ositron emission tomography/ computed tomography ( PET/CT ) Ultrasound ( US ) Screening Screening: different than diagnostic mammograms Before symptoms Used in populations Can find abnormal cells or very small cancer Can lead to diagnostic mammogram https://www.cancer.gov/types/breast/patient/breast-screening-pdq https://www.rahwaynj.gov/ImageRepository/Document?documentID=892 https://www.acr.org/-/media/ACR/Files/Practice-Parameters/Screen-Diag-Mammo.pdf

12. DCIS is found with a biopsy Biopsy collects small sample of breast tissue Pathologist examines sample & writes a report with diagnosis Lesion/tumor can be benign or malignant Report includes: Type of condition (DCIS, LCIS, invasive, etc.) Grade (growth rate: slow, fast, etc.) Hormone receptor status (ER/PR) HER2 receptor status (HER2) There are some standards, but reports, diagnoses, and hospitals can vary greatly 2023 DCIS Patient Forum, Dana Farber Cancer Institute, https://www.youtube.com/watch?v=qEzgMl9sNdA https://simbiosys.com

13. What is DCIS? It depends… Low risk Not low risk Grade 2 Grade 1 Grade 3 Slower growth Cells look normal to abnormal Rapid growth Cells in different sizes & shapes Often has ‘ comedo necrosis’ (dead cancer cells) “…more what you'd call (pathology) guidelines than actual rules.” Barbossa , Pirates of the Caribbean https://www.iheartpathology.net/post/breast-dcis

14. More on DCIS grades Different grades & structures In general, Grade 1 (14.3%) Slow-growing, smaller, ER/PR+, HER2- Grade 2 (43.4%) Varies, in between grades 1 & 3 Grade 3 (42.3%) Larger, grows faster, more ER/PR-, HER2+, Comedo necrosis (dead cells, higher risk) “… a large proportion of DCIS… is mixed, which is difficult to categorize.” – D. Craig Allred, 2010 https://academic.oup.com/jncimono/article/2010/41/134/890446 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679771/ A s econd pathology opinion may help.

15. Note: DCIS is different with “microinvasion” DCIS w/microinvasion is often called Stage 1 invasive breast cancer (IBC) - or - DCIS with microinvasion Considered to be Stage 1 IBC If invasive breast cancer is found, surrounded by DCIS All are treated as Stage 1 IBC No further discussion in this webinar https://en.wikipedia.org/wiki/Ductal_carcinoma_in_situ College of American Pathologists: https://documents.cap.org/protocols/Breast.DCIS_4.4.0.0.REL_CAPCP.pdf Stage 1 invasive breast cancer (IBC) Image annotation by Mikael Häggström , MD, using source image from: Moatasim A, Mamoon N (2022).

16. Poll question #2 What type of DCIS have you had? Low grade DCIS Intermediate grade DCIS High grade DCIS DCIS + invasive breast cancer I have not had DCIS I’m not sure

17. LCIS Atypical Ductal Hyperplasia (ADH) Sclerosing adenosis DCIS In the milk gland In the milk duct Benign growth In the milk duct Why is DCIS treated more like invasive breast cancer and these other conditions are not? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932853/ https://bit.ly/3f0UuLy https://www.melbournebreastcancersurgery.com.au/wp-content/themes/ypo-theme/images/ductal-carcinoma-in-situ-dcis-img-8.jpg Cancer cells inside Cancer cells inside Arbitrarily defined as ≤ 2 mm ADH: “some but not all the requisite features of DCIS”

18. m Grade 1 5 % risk @ 10 years Grade 3 19% risk @ 10 years Grade 2 DCIS biology: all DCIS is not the same! Sagara Y et al JAMA Surg 2015, https://pubmed.ncbi.nlm.nih.gov/26039049/ 10-year Survival Surgery: 98.8% No surgery: 98.6% All Grades

19. Low/Grade 1 Active Monitoring/Surveillance (being studied) Surgery (lumpectomy, sometimes mastectomy) Endocrine/hormonal therapy (optional) Radiation (optional) Diet/exercise (optional) Intermediate/Grade 2 High/Grade 3 Treatment options for DCIS (based on many studies) Surgery (lumpectomy or mastectomy) Endocrine/hormonal therapy (optional) Radiation (optional) Diet/exercise (optional)   Radiation can lower risk for local future DCIS or IBC, but not survival Hormonal therapy: tamoxifen (pre-menopausal) or aromatase inhibitor (post-menopausal) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414216/pdf/nihms-1001707.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382977/pdf/nihms-1554678.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797705/ Risk factors exist for all treatments Similar survival rates for lumpectomy and mastectomy Find IBC at surgery 17% of the time Active Monitoring/Surveillance (being studied) Surgery (lumpectomy, sometimes mastectomy) Endocrine/hormonal therapy (optional) Radiation (optional) Diet/exercise (optional)

20. DCIS is not an emergency There is no “right” answer Treatment is often more about personal preference: Active Monitoring Surgery Radiation Hormonal therapy Reconstruction You have time to decide!

21. Many patients have uncertainty, fear, concern over side effects, loss of control and anxiety Confused to see cancer doctors and hear cancer terms instead of breast Financial concerns, e.g., C o-pays, deductibles, missed work-time may add to emotional burden Patients worry if they are “true cancer survivors” Sometimes ridiculed by other patients What is the right treatment decision? Too much treatment vs. too little treatment DCIS is different for every body and medical communities need to better explain it! https://rlv.zcache.com/psychologically_scarred_postcard-ref6328ebb40441a6a6687bfb877b78b9_vgbaq_8byvr_630.jpg?view_padding=[285%2C0%2C285%2C0 ]

22. For “low risk” DCIS… “Generally, low and intermediate grades (Grades I and 2) are considered to be “ low risk ,” with the lowest chance of becoming an invasive cancer or of recurrence. There is increasing scientific evidence that low-risk DCIS grows slowly and if left untreated, most would not cause health problems during a woman’s lifetime.” Violet Merle McIntosh, MD,  Chief of breast surgery at Englewood Health, New Jersey https://www.englewoodhealth.org/comet-clinical-trial-an-option-for-patients-with-low-risk-dcis-available-at-englewood-health Other factors considered for “low risk” DCIS: ER/PR+ HER2- Postmenopausal ( + 50 years old)

23. LORIS COMET LORD LORETTA Country UK US Netherlands Japan Age > 48 > 40 > 45 > 40, < 75 Design/ standards of care RCT/ local care RCT/guideline concordant RCT/ local care Pt preference Single arm Endocrine therapy Possible Possible Not allowed Tamoxifen Primary outcome 10 years 2, 5, 7 years 10 years 5, 10 years Opened 2014/2016 2017 2017/ 2021 2017 Sites open 63/63 82 (+17) /100 36/? 43/43 Number of patients 188 997 73/ 800+ ongoing Target 932; closed 900+; closed 1240/2500 340 Low-risk DCIS “active monitoring” trials Waiting for future breast events before results might change clinical practice!

24. COMET Study Patient Leadership Team Words Matter! Need updated descriptions Need updated mindsets

25. Changing language & mindsets for low-risk DCIS https://cometstudy.org https://dcisoptions.org

26. Changing language & mindsets: PRECISION Patient Advocate Involvement Panel, https://www.dcisprecision.org

27. Finding DCIS by palpation (by feel) High grade DCIS (Grade 3) Unclear margins (>2mm for DCIS) DCIS size (studies vary) Being pre-menopausal (monthly periods) African-American ancestry High level of p16 marker Less access to medical system Genetic marker: BRCA, etc. What factors add to a 10-year risk of invasive breast cancer (IBC)? Treatment recommended for grade 3 Visser et al. Cancer Epidemiol Biomarkers Prev 2019, others Renée S J M Schmitz et al. BMJ 2023;383:bmj-2023-076022

28. Breast DCIS Score ( OncotypeDX ) Based on DCIS and invasive breast cancer; tumor only Predicts 10-year risk of recurrence Benefits v. risks of radiation therapy DCISionRT ( PreludeDx ) Based on DCIS only; tumor + stroma (communicators) Predicts an individual’s 10-year risk of recurrence Predicts an individual’s benefit of radiation therapy Can reclassify up to 50% v. grade and size Current tests for grade 3 (high grade) DCIS: https://preludedx.com/ https://preludedx.com/publications/ https://bit.ly/3c25SVM NOTE: There is a difference between relative risks and absolute risks! See Cancer Risks: What They Mean https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer/art-20044092

29. DCIS is becoming clearer with clinical trials & other study results Stay informed ( https://www.dcisprecision.org/ , http://cometstudy.org/ (coming soon), https://dcisoptions.org/ , dcis411 .com, etc.) Give us feedback If you have/get DCIS You have TIME It’s a trade-off between future risk v. treatment effects: use decision tools Patient/provider communication is important Ask about resources you can use Takeaway messages

30. DCIS Latest Research: De-escalating the Fear of Recurrence Please join us on February 6, 2024 Deborah Collyar Patient Advocates in Research Shelley Hwang, MD Duke University

31. Discussion time

32. Poll question #3 Do you feel less anxious after hearing this program? Yes No No change Unsure

33. Resources (a few examples) SHARE services & materials (e.g. Novela in English & Spanish) 2021 SHARE DCIS webinar: What we Know & Don’t YET Know about DCIS https://www.sharecancersupport.org https://www.sharecancersupport.org/wp-content/uploads/sites/1731/2016/04/Be_Brave_They_re_Your_Breasts_en-us.pdf Ideas for 2 nd opinions NCCN approved cancer centers: https://www.nccn.org/members/network.aspx ORIEN cancer centers: https://www.oriencancer.org/ Check your local hospitals DCIS resources https://www.macmillan.org.uk/cancer-information-and-support/breast-cancer/ductal-carcinoma-in-situ-dcis https://www.breastcancer.org/symptoms/types/dcis https://dcisoptions.org https://www.lbbc.org/news-opinion/understanding-dcis PRECISION research: https://www.dcisprecision.org/ COMET study: https://cometstudy.org Ebook : DCIS Dilemmas at https://amzn.to/3s799Zz For Active Monitoring: https://dcis411.com/resources/dcis-411-wellness-checklist/ Check your local hospitals for Social Workers and possible support groups

34. Deborah Collyar [email protected] https://collyar.wordpress.com/ www.facebook.com/DeborahCollyarAuthor @ deborahcollyar www.linkedin.com/in/deborahcollyar/ Thank you! Keep in touch Where research meets reality Patient Advocates In Research (PAIR)