COMPREHENSIVE BREAST CANCER CARE IN SWFL

Chaundre Cross, M.D. 21st Century OncologyHarvard Medical School

COLLABORATIVE EFFORT

• 21st Century Oncology

• Florida Cancer Specialists

• Radiologists

• Breast Cancer Surgeons

• Breast Cancer Pathologists

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.”

SCREENING

• DIGITAL MAMMOGRAMS/ ULTASOUNDS

• BSGI

• MRI

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.

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

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.

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.

NCCN GUIDELINES

RADIATION ONCOLOGY

1. Conventional radiation therapy- 6.5 weeks

2. Hypofractionation radiotherapy- 3 weeks

3. Accelerated partial breast radiotherapy APBI- 1 week

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

MAMMOSITE

MAMMOSITE

MAMMOSITE

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

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

TRUEBEAM

1. 25% LESS DOSE

2. 50% FASTER DOSE DELIVERY

3. 21ST CENTURY ONCOLOGY IS THE EXCLUSIVE PROVIDER IN NAPLES, FL

4. 21ST CENTURY ONCOLOGY IS THE 2ND PLACE IN THE U.S. TO ACQUIRE BEHIND MEMORAL SLOAN KETTERING CANCER CENTER

TRUEBEAM

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

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

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

TARGIT

1. Targeted Intraoperative radiotherapy (London 1998)

2. Radiotherapy given at the time of surgery in 1 day

3. Takes 30 minutes

TARGIT

TARGIT

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

• 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 betterLancet 2013

ELIOT TRIAL

APBI

• ASTRO Consensus Statement

• Age > 60, negative BRCA, < 2cm tumor size, negative nodes, ER+, not multifocal, DCIS not allowed, no chemotherapy

HYPOFRACTIONATION

• SHORTENED FRACTIONATION OF EXTERNAL BEAM

• RADIOTHERAPY TO THE WHOLE BREAST

• COMPARED TO CONVENTIONAL 6 WEEKS OF RADIOTHERAPY

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

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, NS10 yr: less toxicity 39 Gy vs 50 Gy, equivalent 42 GyLancet Oncol 2013

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, NS10 yr toxicity significant less breast shrinkage, telangiectasia and edema in 40 Gy vs 50 Gy

Lancet Oncol 2013

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, NSCosmesis equivalent

NEJM, 2010

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

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

RISK OF HEART DISEASESURVIVORSHIP

• 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.

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 2004N=769, No RT vs RT in age > 50, tamoxifenAt 8 yrs local recurrence 17.6% vs 3.5%, significant

CALGB, NEJM 2004, JCO 2013N=636, No RT vs RT in age > 70, tamoxifenAt 10 yrs local recurrence 10% vs 2%, significantRadiotherapy may be omitted in women > 70, case by case

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

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.

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

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MEN’S BREAST CANCERAWARENESS 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.

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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

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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

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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

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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

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SURVIVAL

• STAGE 0- 100%

• STAGE I- 96%

• STAGE II- 84%

• STAGE III-52%

• STAGE IV-24%

• 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!!!