1-anderson-breast cancer.ppt

9/22/2017

©AllinaHealthSystems 1

Breast Cancer 2017 Updates

Casandra Anderson, MD, FACSSurgical Oncologist

Allina Health Surgical SpecialistVPCI ANW & West Health

Disclosures

• None

Agenda

• Review Screening Guideline • Treatment of High Risk Patient• Controversy of Treatment for DCIS• Overview of Treatment of Invasive Disease• Lymphedema Screening

BENEFIT OF SCREENING MAMMOGRAPHY

Invitation to screening mammography results in a reduction in breast cancer mortality of

approximately 20%

History of Screeing Mammograph Guidelines SCREENING RECOMMENDATIONS UNITED STATES PREVENTIVE SERVICES TASK FORCE (USPSTF) 2016

Screening mammography biennial: age 50 -74 (Grade B recommendation)

Against routine screening mammography for women 40-49 (Grade C recommendation)

Insufficient evidence to recommend for or against screening mammography for women > 74

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Meta-analysis of screening trials–mortality reduction by age

15% women 40-4914% women 50-5932% women 60-69

Analysis of screening data from Breast Cancer Surveillance Consortium (BCS

Need to invite to screening to save 1 life

–1904 women 40-49–1339 women 50-59–337 women 60-69

AMERICAN CANCER SOCIETY BREAST CANCER SCREENING GUIDELINES OCT 2015

• Women with average risk should undergo regular screening mammography starting at age 45 (Strong recommendation)

• Women aged 45 to 55 should be screened annually (Qualified recommendation)

• At age 55, begin to transition to biennial screening or have the opportunity to continue annual screening (Qualified recommendation)

AMERICAN CANCER SOCIETY BREAST CANCER SCREENING GUIDELINES OCT 2015

• Women should have the opportunity to begin annual screening at age 40 (Qualified recommendation)

• Continue screening as long as woman is in good health with a life expectancy of at least 10 years (Qualified recommendation)

• Does not recommend clinical breast exam for average risk women (Qualified recommendation)

OTHER ORGANIZATION GUIDELINES

• National Comprehensive Cancer Network• American College of Obstetrics and

Gynecology• American College of Radiology• Society of Breast Imaging

Annually beginning at age 40

• Mortality reduction 7% to 23%

• Cumulative risk of false positive 20% to 56% after 10 mammograms

Armstrong et al Ann Int Med 2007;146:516

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False Positives

• 10 year cumulative probability of recall 61.3%(annual) and 41.6%(biennial) after 10 years

• 10 year cumulative probability false positive leading to biopsy 7.0%(annual) and 4.8% (biennial)

Oeffingeret al JAMA 2015;314:1599

Mammography Rates Incidence by Age

High Risk Factors

• BRCA mutation : lifetime risk 56-85%

• Other Genetic Mutations:

– CDH1,ATM, PALB2, CHEK2

• Family History ( primarily first degree)

• Radiation Exposure

• LCIS, ADH, ALH

Gail ModelModel for annual risk of breast cancer

• Age/race

• Family history

• Age at first birth and menarche

• Number of breast bx

• Hx of atypia

Risk reduction strategies considered if >1.7 % 5-yr risk

Risk Reduction Interventions• Chemoprevention (reduction of 50-86%)

– Tamoxifen– Raloxifene– AI

• Increased Screeing (MRI/Mammo q 6 mons)• Bilateral Mastectomy• Lifestyle

– HRT– Alcohol consumption– Exercise– Diets– weight

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What are 3D mammograms and should we be using them in

screening?

Tomosynthesis Dose

• Current mammography units operate at 1-2mGy

• USFDA sets dose for screening at 3mGy/view

• 2D + 3D mammography image is Approximately 2.65mGy

TomosynthesisReimbursement

• Medicare covers 3D January 2015• Cigna (first national payer) covers tomosynthesis September

2016 (NCCN)• Minnesota

– BCBS of Minnesota– HealthPartners– Medicaid– Preferred One

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DCIS: THE PROBLEM

Treatment options for DCIS are many:– Observation without surgery– Wide excision– Wide excision with radiation– Wide excision with endocrine therapy– Wide excision with RT and endocrine therapy– Mastectomy– Bilateral mastectomy

•Local recurrence varies dramatically

Problem with Omission of Surgery for DCIS

• Needle biopsy may fail to reveal invasion

• Grade is difficult to determine

• Progression to invasive cancer occurs

• Morbidity of excision is low

Mortality is not the only important end point

1 Doebar SC, et al. The Breast 27: 15-21, 2016; 2 Caswell-Smith P, et al. J Med Imaging Radiat Oncol, 2016; 3 Pilewskie M, et al. Ann Surg Oncol, 2016; 4 Soumian S, et al. EJSO 39: 1337-1340, 2013;5 Yen TWF, et al. J Am Coll Surg, 2005;6 Hoorntje LE, et al. Ann Surg Oncol 10:748-753, 2003

DCIS Upgrade Rates to Invasive Cancer

Study (Year) DCIS Cases

(n)

Upgrade rate to invasive(%)

Doebar (2016)1 155 22

Caswell-Smith (2016)2

317 21

Pilewskie (2016)3 296 20

Soumian (2013)4 225 18

Yen (2005)5 398 20

Hoorntje (2003)6 255 16

Upgrade Rates

Soumian S et al. EJSO 39:1337-1340, 2013.

No SurgeryNo XRT (%)

LumpectomyNo XRT (%)

Lumpectomy+ XRT (%)

Unilateral Mtx (%)

Alive 81.0 85.7 93.7 88.1

Dead B.C. 3.8 1.1 0.7 1.1

Dead other causes

15.2 13.2 5.7 10.8

Mean age (years)

61.6 61.8 58.1 58.4

DCIS Treatment in USA

Median F/U: 71 monthsWorni M, HWANG ES, et al. JNCI 107(12):djv263, 2015.

SEER Data

Endpoints:• 2, 5, 7-year invasive cancer dx• 2, 5, 7-year OS, DSS• PRO endpoints (QOL, fear of cancer

recurrence, body image)

COMET (Comparison of Operative to MedicalEndocrine Therapy) Trial for low risk DCIS

Trial Schema

Eligiblity criteria:• Age ≥ 40• Grade I/II DCIS without invasive cancer• Diagnosed confirmed by core or surgical biopsy• ER(+) and/or PR(+), HER2(-) if tested• No mass on PE or imaging

Registered and randomized

(n=900)

GROUP 1: Usual Treatment

(n=450)

Surgery, Radiation or both

choice for endocrine therapy

Mammogram every 12 months for 5 years

GROUP 2: Close Monitoring

(n=450)

choice for endocrine therapy

Mammogram every 6 months for 5 years

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DCIS: THE PROBLEM

• Need to optimally integrate all of these factors to arrive at a LR risk estimate for an individual patient

• Known factors that influence recurrence:– Age– Family history– Clinical presentation– Margin status/width– Size– Nuclear grade– Necrosis– Radiation– Endocrine therapy

DCIS Nomogram Predicts 5 & 10yr RR• Age of Diagnosis• 1st relative with breast cancer• Presentation• Adjuvant Xrt• Adjuvant endocrine• Grade• Necrosis• Surgical margins• # of excisions• Yr of surgery

No tumor is the same“Precision Medicine”

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Approach to Breast Cancer Therapy

Local

Breast

Regional

Nodes

Systemic

ChemotherapyEndocrine Therapy

Local Therapy

Lumpectomy Mastectomy

Lumpectomy

• Removal of tumor with negative margins

• Post-op RadTx to decrease local recurrence– >70 with favorable

biology may omit therapy– Short-course for low stage

tumors

- margin

+ margin

Localization techniques

4.5 mm x .8mm titanium seed.1mCI of 125 iodine

Seed Wire

Contraindications for Lumpectomy

Absolute• Pregnancy before 18wks

• Prior Radiation

• Diffuse areas of suspicious calcs

• Inflammatory Breast Cancer

• Persistant + margins

Mastectomy

• Removal of entire breast

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Mastectomy

Skin Sparing Nipple Sparing Radiation Therapy After Mastectomy

• Large Tumors

• Multiple Lymph Nodes +

• Chest Wall Involvement

• Inflammatory

Lumpectomy vs Mastectomy

Institution Years #of pts

Overall Survival

Milan 73-80 348 (M)

352 (Q+RT

41%

41% 20 yrs

NSABP B-06 76-84 590 (M)

629(L+RT)

47%

46% 20yrs

NCI 80-86 116(M)

88 (L+RT)

75%

77% 10 yrs

Insitut

Gustave-Roussy

72-79 91(M)

88(L+RT)

65%

73% 15 yrs Survival in the three groups was 93%, 94% and 93%, respectively (P=.93).

Regional Therapy

Evaluation of axillary lymph nodes

Sentinel Lymph Node Biopsy

Nodes with the first and most direct connection to the place where the tracer was injected. If the sentinel node is removed and shows no signs of cancer, then the other lymph nodes rarely have any cancer.

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Axillary Dissection

Reasons for AxDx in 2016 1) Bulky Positive disease after chemotherapy2) + nodes in mastectomy patients wanting to avoid Radtx3) Multiple + nodes in patients undergoing lumpectomy

Complications

Webbing

Seroma

Lymphedema

Nerve injury“Winging”

SLN Ax Dx

2yr Complications

Seroma 4.5% 13.9%

Infection 2.7% 8.7%

10yrComplications

Paresthesia 10% 33%

Lymphedema 5.4% 18%

Wernicke et al, Am J Clin Oncol 2011

Standard of Care for Lumpectomy• Clinically Stage I or II

– Small tumors <5cm and clinically negative nodes

SLN Bx

Biopsy NegativeOr <2 positve

No further surgery

3 + nodesAxDx

ALND SLND

Breast Recurrence 3.6% 1.8%

Axilla/supraclavicular .5% .9%

Total locoregional 4.1%

P=0.11

2.8%

Median F/U 10 yrs

Results for Z11 Trial

Giuliano et al.Annals of Surgery 2010, Vol 252: 426

Standard of Care for Mastectomy• Clinically Stage I or II

– Small tumors <5cm and clinically negative nodes

SLN Bx

Biopsy Negativeor ITC/micromet

No further surgery

+macrometsAxDx or RadTx

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ALND RadTx

Axillary Recurrence .5% 1 %Lymphedema 23% 11%

Median F/U 6.1 yrs

AMAROS TRIALLocally Advanced Tumors

Large tumors OR Positive axillary nodes

Neoadjuvant Chemotherapy

Allow for lumpectomy Decrease Axillary Surgery

Pre-Chemo

Post Chemo

Why Chemo First? Down size tumors

Prognostic

• Triple –• H2N +

ypN is predictive of survival

Neoadjuvant Surgical Trials

NSABP B-51

• Is radiation needed if pCR

Alliance A011202

• Is axillary dissection needed in addition to Radiation for + nodal disease after chemotherapy

Systemic Therapy• Tumor Biology

• Receptor Characterization

– Triple Negative

– H2N +

– ER +

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Chemotherapy

Triple -

+ Her 2N

Bulky Nodal Disease

High Oncotype Scores

Oncotype DX™ 21-Gene Recurrence Score (RS) Assay

PROLIFERATIONKi-67

STK15Survivin

Cyclin B1MYBL2

ESTROGENERPRBcl2

SCUBE2

INVASIONStromelysin 3Cathepsin L2

HER2GRB7HER2

BAG1GSTM1

REFERENCEBeta-actinGAPDHRPLPO

GUSTFRC

CD68

Category RS (0-100)Low risk RS <18

Int risk RS ≥18 and <31

High risk RS ≥31

Estrogen + Tumors

RS predicts risk of systemic recurrences.

Predicts Chemotherapy Effect For ER+ Tumors

Lymphedema

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Incidence of lymphedema

F/U time 25.4 months•At 24 months 6.8%•At 60 months 13.7%

Median time to development of lymphedema 24 mons

XRT field SLNB ALND

None 0% 18%

Breast 2.8% 7.3%

Supraclavicular 7.4% 24%

Supraclavicular and Axillary

4.7% 24%

Incidence of lymphedema at 24 months Stratified by Radiation and Axillary Surgery

Risk Factors for lymphedema• Axillary Dissection• Regional nodal radiation• BMI >30• Arm volume increases >5 -<10 > 3 mons post-op

BIS protocol at VPCI Breast Center

• High risk patient: (ALND or Ax Xrt)• Pre-op BIS measurement• Post-op measurements• Early Sleeve usage

Questions

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