1. COMPREHENSIVE BREAST CANCER CARE IN SWFL Chaundre Cross, M.D. 21 st Century Oncology Harvard Medical School Chaundre Cross, M.D. 21 st Century Oncology Harvard Medical School

2. COLLABORATIVE EFFORT 21 st Century Oncology Florida Cancer Specialists Radiologists Breast Cancer Surgeons Breast Cancer Pathologists 21 st Century Oncology Florida Cancer Specialists Radiologists Breast Cancer Surgeons Breast Cancer Pathologists

3. NCCN GUIDELINES “The NCCN Clinical Practice Guidelines in Oncology are recognized by clinicians around the world as the standard for oncology care” “Women who are living with breast cancer today not only have to contend with the reality of their diagnosis, but also have to live in an increasingly complex and changing world. We understand that breast cancer is not a single disease. You have to know the sub-type of the cancer, the stage of your disease and be able to evaluate the options available for you.” “The NCCN Clinical Practice Guidelines in Oncology are recognized by clinicians around the world as the standard for oncology care” “Women who are living with breast cancer today not only have to contend with the reality of their diagnosis, but also have to live in an increasingly complex and changing world. We understand that breast cancer is not a single disease. You have to know the sub-type of the cancer, the stage of your disease and be able to evaluate the options available for you.”

4. SCREENING DIGITAL MAMMOGRAMS/ ULTASOUNDS BSGI MRI DIGITAL MAMMOGRAMS/ ULTASOUNDS BSGI MRI

5. SURGICAL OPTIONS 1. Mastectomy- complete removal of breast tissue. Probably, no need for radiation therapy. 2. Lumpectomy with sentinel node biopsy- partial removal of breast tissue. A need for radiation therapy. 3. Axillary dissection increases risk for lymphedema dramatically. 1. Mastectomy- complete removal of breast tissue. Probably, no need for radiation therapy. 2. Lumpectomy with sentinel node biopsy- partial removal of breast tissue. A need for radiation therapy. 3. Axillary dissection increases risk for lymphedema dramatically.

6. SURGICAL OPT. CONT’D 4.Significance of sentinel lymph node biopsy versus axillary dissection, Z11 Study limiting usage of AXD 5.Lymphedema physical therapy referral 6. Reconstruction after mastectomy- timing and different techniques 7. Mammosite Brachytherapy and TARGIT 4.Significance of sentinel lymph node biopsy versus axillary dissection, Z11 Study limiting usage of AXD 5.Lymphedema physical therapy referral 6. Reconstruction after mastectomy- timing and different techniques 7. Mammosite Brachytherapy and TARGIT

7. MEDICAL ONCOLOGY 1.Options include no therapy, hormone therapy, or chemotherapy 2.Dependent on certain characteristics of the breast cancer, treatments are recommended 3. Oncotype DX - new advancement in genetic testing of the breast cancer. Recommended by both NCCN and ASCO. This is the only test validated to provide both prognostic and predictive data for treatment decisions. 1.Options include no therapy, hormone therapy, or chemotherapy 2.Dependent on certain characteristics of the breast cancer, treatments are recommended 3. Oncotype DX - new advancement in genetic testing of the breast cancer. Recommended by both NCCN and ASCO. This is the only test validated to provide both prognostic and predictive data for treatment decisions.

8. MED. ONC. CONT’D 4. Estrogen receptor status - positive status is a predictive factor for Tamoxifen, Arimidex, Femara, Aromasin and etc. as hormone therapy for 5-10 years. 5. Her2-Neu status - positive status is a predictive factor for Herceptin as therapy for one year. 6. Chemotherapy - different regimens based on pathology findings, 4-8 cycles. FCS protocols. Adjuvant Online risk for recurrence. 4. Estrogen receptor status - positive status is a predictive factor for Tamoxifen, Arimidex, Femara, Aromasin and etc. as hormone therapy for 5-10 years. 5. Her2-Neu status - positive status is a predictive factor for Herceptin as therapy for one year. 6. Chemotherapy - different regimens based on pathology findings, 4-8 cycles. FCS protocols. Adjuvant Online risk for recurrence.

9. NCCN GUIDELINES

10. RADIATION ONCOLOGY 1. Conventional radiation therapy- 6.5 weeks 2. Hypofractionation radiotherapy- 3 weeks 3. Accelerated partial breast radiotherapy APBI - 1 week 1. Conventional radiation therapy- 6.5 weeks 2. Hypofractionation radiotherapy- 3 weeks 3. Accelerated partial breast radiotherapy APBI - 1 week

11. ACCELERATED PARTIAL BREAST IRRADIATION (APBI) Rationale; majority of recurrence occur within a short distance of the original tumor, 20% elsewhere Brachytherapy, balloon catheter (Mammosite), external beam radiotherapy

12. MAMMOSITE

14. 1.At the time of surgery, the device is implanted into the cavity created by removing the tumor. A few days after surgery, a radioactive source is placed through the catheter and into the balloon. 2.Treatment is given for 5 days 1.At the time of surgery, the device is implanted into the cavity created by removing the tumor. A few days after surgery, a radioactive source is placed through the catheter and into the balloon. 2.Treatment is given for 5 days

15. MAMMOSITE CLINICAL RESULTS Clinical Trial Data The MammoSite Radiation Therapy System received FDA clearance in 2002. The 5-year results of the initial MammoSite clinical trial involving 43 patients are now available, as is data from other studies. 5-Year Clinical Trial Results (N=43) No local recurrences. 83.3% of patients had good/excellent cosmetic results. 100% of patients would recommend MammoSite Therapy to a friend or family member. 100% of patients would use MammoSite Therapy if they had to do it over. The American Society of Breast Surgeons MammoSite Registry Trial 13. (N=1440) 44 month follow-up of the first 400 consecutive cases. Local recurrence rates between 0 -2.65%. Cancer-specific survival of 100.0%DCIS: Phase II Clinical Study (12 institutions) Fifteen-month mean results (n=100) 3.0% local recurrence rate (1 Elsewhere; 2 True Recurrence, Marginal Miss) 95% of patients had good/excellent cosmetic results. NSABP-39 Prospective randomized trial of whole breast radiation therapy compared to partial breast radiation therapy. Closed to low risk women as of December, 2006

16. TRUEBEAM

17. 1.25% LESS DOSE 2.50% FASTER DOSE DELIVERY 3.21 ST CENTURY ONCOLOGY IS THE EXCLUSIVE PROVIDER IN NAPLES, FL 4.21 ST CENTURY ONCOLOGY IS THE 2 ND PLACE IN THE U.S. TO ACQUIRE BEHIND MEMORAL SLOAN KETTERING CANCER CENTER 1.25% LESS DOSE 2.50% FASTER DOSE DELIVERY 3.21 ST CENTURY ONCOLOGY IS THE EXCLUSIVE PROVIDER IN NAPLES, FL 4.21 ST CENTURY ONCOLOGY IS THE 2 ND PLACE IN THE U.S. TO ACQUIRE BEHIND MEMORAL SLOAN KETTERING CANCER CENTER TRUEBEAM

18. APBI TRIALS Christie 1993 Exteranl beam radiotherapy, electrons N=708, 1982-1987, 5 yr f/u Electron 40 Gy/8 fractions APBI Exteranl beam 40 Gy/15 fractions Whole breast Whole breast radiotherapy superior

19. APBI EXTERNAL BEAM Ontario Rapid 2006-2010, N=2135, 3 yr f/u 38.5 Gy/10 fractions BID (3.85 Gy) 50 Gy/25 fractions (2 Gy) 3yr cosmesis, worse in APBI arm JCO 2013

20. APBI EXTERNAL BEAM NSABP B-39 2005-2013, N=4300, 3.5 yr f/u 38.5 Gy/10 fractions BID (3.85 Gy) 50 Gy/25 fractions (2 Gy) No toxicity difference ASTRO abstract 2011

21. TARGIT 1. Targeted Intraoperative radiotherapy (London 1998) 2.Radiotherapy given at the time of surgery in 1 day 3.Takes 30 minutes TARGIT

24. 1.2000-2012, Randomized trial comparing conventional vs TARGIT, 3451 patients, median f/u 3 yrs, Local Recurrence, 3.3% (Targit) vs 1.3%, p- value= significant 2.Disadvantage- partial breast and final margin status Oncology 2014 TARGIT

25. 1. Intra-operative radiotherapy versus Whole breast radiotherapy, 2000-2007, 5.8 yr f/u 21 Gy (651 pts) versus 60 Gy (654 pts) Local recurrence 4.4% versus 0.7%, p-value.0002 Whole breast better Lancet 2013 ELIOT TRIAL

26. APBI ASTRO Consensus Statement Age > 60, negative BRCA, < 2cm tumor size, negative nodes, ER+, not multifocal, DCIS not allowed, no chemotherapy

27. HYPOFRACTIONATION SHORTENED FRACTIONATION OF EXTERNAL BEAM RADIOTHERAPY TO THE WHOLE BREAST COMPARED TO CONVENTIONAL 6 WEEKS OF RADIOTHERAPY

28. HYPOFRACTIONATION Royal Marsden N=1410, T1-3, N0-1 50 Gy/25 fractions (2 Gy) 39 Gy/13 fractions (3 Gy) 43 Gy/13 fractions (3.3 Gy) 10 yr IBTR- 12.1%, 14.8% and 9.6%, respectively, NS Lancet Oncol 2006

29. HYPOFRACTIONATION UK START A N=2236, T1-3, N0-1, 60% boost, 35% chemo 50 Gy/25 fractions (2 Gy) 39 Gy/13 fractions (3 Gy) 42 Gy/13 fractions (3.2 Gy) 10 yr IBTR 7.4%, 8.8% and 6.3%, respectively, NS 10 yr: less toxicity 39 Gy vs 50 Gy, equivalent 42 Gy Lancet Oncol 2013

30. HYPOFRACTIONATION UK START B N=2215, T1-3, N0-1, 43% boost 50 Gy/25 fractions (2 Gy) 40 Gy/15 fractions (2.67) 10 yr IBTR 5.5% and 4.3%, respectively, NS 10 yr toxicity significant less breast shrinkage, telangiectasia and edema in 40 Gy vs 50 Gy Lancet Oncol 2013

31. HYPOFRACTIONATION Canadian Trial N=1234, T1/2N0, no boost 50 Gy/25 fractions (2 Gy) 42.5 Gy/15 fractions (2.66 Gy) 10 yr IBTR 7.5% and 7.4%, respectively, NS Cosmesis equivalent NEJM, 2010

32. HYPOFRACTIONATION ASTRO Consensus Statement Hypofractionation appropriate for: 50 years or older BCS for pathological stage T1-2 N0 No chemotherapy Within the breast certain dose homogeneity guidelines IJROBP 2010

33. CONCLUSIONS ON HYPOFRACTIONATION AND APBI Hypofractionation should be considered if patient meets the criteria however long term effects on the heart should also be considered APBI is still supported by only a limited data, and patients should be considered for inclusion on a trial

34. RISK OF HEART DISEASE SURVIVORSHIP NEJM 2013 Population based case control study of major coronary events (MI, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy from 1958-2001 in Sweden and Denmark Rates of major events increased linearly with the mean dose to the heart by 7.4% per Gy with no apparent threshold. Started 5 yrs after XRT.

35. OMISSION OF RADIOTHERAPY AFTER BCS, NODE NEGATIVE NSABP B-21, JCO 2002 N=1,009, Tam vs RT vs Tam/RT Recurrence with XRT 12% lower Princess Margaret, NEJM 2004 N=769, No RT vs RT in age > 50, tamoxifen At 8 yrs local recurrence 17.6% vs 3.5%, significant CALGB, NEJM 2004, JCO 2013 N=636, No RT vs RT in age > 70, tamoxifen At 10 yrs local recurrence 10% vs 2%, significant Radiotherapy may be omitted in women > 70, case by case

36. PROGNOSTIC AND PREDICTIVE FACTORS Multigene signatures or classifiers are assays of a panel of genes from a tumor specimen, intended to provide a quantitative assessment of the likelihood of response to chemotherapy and to evaluate prognosis or distant recurrence. Oncotype DX and MammaPrint (also called MammoPrint) are two commercially available genomic tests. Oncotype predictive, MammaPrint only prognostic

37. BRCA SHOULD BE INCLUDED IN STAGING BRCA testing will become much more affordable with the Supreme Court’s invalidation of the Myriad patent which opens the door to market forces that will reduce the cost of testing to under $100. Downstream effects of this will be more imaging, more prophylactic surgery and a modest reduction in systemic treatment because of interventions that occur before med onc is needed.

38. CASE PRESENTATION 61 year old female Left breast grade 2 invasive ductal carcinoma Estrogen receptor positive and Her 2 FISH neg. 1/1 lymph node positive, 0.4cm deposit Oncotype DX low risk distant recurrence No chemotherapy and no AXD CASE PRESENTATION

39. MEN’S BREAST CANCER AWARENESS INCREASING 1.Until puberty (usually around 13 or 14), young boys and girls have a small amount of breast tissue consisting of a few ducts located under the nipple and areola (area around the nipple). At puberty, a girl's ovaries make female hormones, causing breast ducts to grow, lobules to form at the ends of ducts, and the amount of stroma to increase. In boys, hormones made by the testicles keep breast tissue from growing much. Men's breast tissue has ducts, but only a few if any lobules. 2.Like all cells of the body, a man's breast duct cells can undergo cancerous changes. But breast cancer is less common in men because their breast duct cells are less developed than those of women and because their breast cells are not constantly exposed to the growth-promoting effects of female hormones. 1.Until puberty (usually around 13 or 14), young boys and girls have a small amount of breast tissue consisting of a few ducts located under the nipple and areola (area around the nipple). At puberty, a girl's ovaries make female hormones, causing breast ducts to grow, lobules to form at the ends of ducts, and the amount of stroma to increase. In boys, hormones made by the testicles keep breast tissue from growing much. Men's breast tissue has ducts, but only a few if any lobules. 2.Like all cells of the body, a man's breast duct cells can undergo cancerous changes. But breast cancer is less common in men because their breast duct cells are less developed than those of women and because their breast cells are not constantly exposed to the growth-promoting effects of female hormones. 39

40. 1.2,140 NEW MEN’S BREAST CANCER PER YEAR 2.450 MEN DIE OF BREAST CANCER PER YEAR 3.1 OUT OF 1,000 MEN GET BREAST CANCER 4.STAGE FOR STAGE OUTCOMES ARE THE SAME FOR MEN AND WOMEN 1.2,140 NEW MEN’S BREAST CANCER PER YEAR 2.450 MEN DIE OF BREAST CANCER PER YEAR 3.1 OUT OF 1,000 MEN GET BREAST CANCER 4.STAGE FOR STAGE OUTCOMES ARE THE SAME FOR MEN AND WOMEN 40

41. RISK FACTORS FOR MEN 1.AGING 2.FAMILY HISTORY OF BREAST CANCER, 1 OUT 5 MEN WITH BREAST CANCER 3.BRCA-2 GENE, 1 OUT OF 10 MEN WITH BREAST CANCER 4.KLINEFELTER SYNDROME- XXY, LOW LEVEL ANDROGEN AND HIGHER LEVEL OF ESTROGEN, SMALL TESTICLES AND GYNECOMASTIA 1.AGING 2.FAMILY HISTORY OF BREAST CANCER, 1 OUT 5 MEN WITH BREAST CANCER 3.BRCA-2 GENE, 1 OUT OF 10 MEN WITH BREAST CANCER 4.KLINEFELTER SYNDROME- XXY, LOW LEVEL ANDROGEN AND HIGHER LEVEL OF ESTROGEN, SMALL TESTICLES AND GYNECOMASTIA 41

42. RISK FACTORS FOR MEN 5.RADIATION EXPOSURE 6.LIVER DISEASE AND HEAVY ALCOHOL USAGE 7.MALFUNCTIONING TESTICLES, UNDESCENDED TESTICLES 8.OBESITY, FAT CELL CONVERT ANDROGENS INTO ESTROGEN 9.HORMONE THERAPY FOR PROSTATE CANCER MAY SLIGHTLY INCREASE RISK 5.RADIATION EXPOSURE 6.LIVER DISEASE AND HEAVY ALCOHOL USAGE 7.MALFUNCTIONING TESTICLES, UNDESCENDED TESTICLES 8.OBESITY, FAT CELL CONVERT ANDROGENS INTO ESTROGEN 9.HORMONE THERAPY FOR PROSTATE CANCER MAY SLIGHTLY INCREASE RISK 42

43. EARLY DETECTION FOR MEN 1.PHYSICAL EXAM AND AWARENESS OF RISK FACTORS 2.MAMMOGRAPHY AS DONE IN WOMEN 3.GENETIC TESTING FOR FAMILY HISTORY, BRCA-2 HAS A 5-10% LIFETIME RISK FOR DEVELOPING BREAST CANCER 1.PHYSICAL EXAM AND AWARENESS OF RISK FACTORS 2.MAMMOGRAPHY AS DONE IN WOMEN 3.GENETIC TESTING FOR FAMILY HISTORY, BRCA-2 HAS A 5-10% LIFETIME RISK FOR DEVELOPING BREAST CANCER 43

44. SURVIVAL STAGE 0- 100% STAGE I- 96% STAGE II- 84% STAGE III-52% STAGE IV-24% STAGE 0- 100% STAGE I- 96% STAGE II- 84% STAGE III-52% STAGE IV-24% 44

45. The goal is to provide excellence in breast cancer care with leading advancements and technology. Breast cancer experts in SWFL working together towards a common goal… CURE!!! The goal is to provide excellence in breast cancer care with leading advancements and technology. Breast cancer experts in SWFL working together towards a common goal… CURE!!!