Philippa Mercer

2018

BREAST CANCER

UPDATE

• Gender

Age•

What else?•

RISK FACTORS Genetic mutation • – BRCA 1 & 2 …

High mammographic breast density•

High risk family history•

Chest irradiation <• 30y

Affluent• country of residence

Past breast cancer•

Risk lesion on biopsy•

Moderate risk family history•

Hormonal history /HRT usage•

DES women and daughters•

Ethnicity / Lifestyle • – exercise, diet, weight...

‘Mammographic density and the risk and detection of breast cancer’ (Boyd et al NEJM 2007)

Odds ratios adjusted for age at menarche, age at first birth, nulliparity, family history, HRT etc

For density • >75% versus <10% (film screen):

⬆️– risk of overall cancer development OR 4.7

⬆️– risk of screen-detected cancer OR 3.5

⬆️– risk of interval cancer <12 months OR 17.8

>12 months OR 5.7

MAMMOGRAPHIC DENSITY RISKS

Modifiable factors • – HORMONES

⬇️– menopausal status, weight, number of live births, Tamoxifen, radiotherapy

⬆️– HRT, lactation

Non• -modifiable factors – GENETICS

Responsible for ~– 63% of density variation

Some common breast cancer susceptibility genetic variants are –

associated with higher mammographic density (Cancer Res 2010)

WHAT DETERMINES DENSITY?

• VISUAL ASSESSMENT

ACR BIRADS – pattern and % density

• A = predominantly fatty <25%

• B = scattered fibroglandular densities 25-50%

• C = heterogeneously dense 50-75%

• D = extremely dense >75%

• QUANTITATIVE METHODS

– % area – dense area / total area

– % volume – CT or tomosynthesis

– Other methods – US or MRI

HOW DO WE CLASSIFY DENSITY?

MethodSubjectivityReproducibilityTraining

Mammography•

Tomosynthesis•

Contrast enhanced mammo (or DBT)•

Ultrasound: •

• Hand held physician or sonographer

ABUS (automated whole breast)•

MRI:•

Traditional pre and post contrast•

Fast MR screen•

SCREENING DENSE BREASTS

ACRIN 6666: 2008

Diagnostic yield:•

Mammogram alone – 7.6 per 1,000

Mam + US – 11.8 per 1,000

Supplemental yield of US was • 4.2 per 1,000(95% CI = 1.1 – 7.2)

RESULTS

40 CANCERS- 8 mam + US- 12 mam only- 12 US only- 8 neither

ACRIN 6666: 2012

RESULTS

111 CANCERS26 - mam + US33 - mam only32 - US only9 - MRI11 - none

Supplemental detection:▪

Ultrasound – 3.7 per 1,000 (incidence)

MRI – 14.7 per 1,000 (after negative mam+US)

• US had better incremental BC detection than DBT

• Similar false positive rate

• DBT detected more than 50% of additional BC

• DBT could be considered as a primary screening modality

• Interim report

• If you use both US and DBT you get all of the false +ve

CONCLUSIONS

29%

30%

28%

13%

Density

A B C D

LOCAL DENSITY DATA

▪ June to Sept 2015

▪ 8,129 screening exams

A – 29%

B – 30%

C – 28%

D – 13%

C + D = 41% = 3252 US

finding 13 to 32 additional cancers (ASTOUND)

Should we be supplemental screening? Who?•

How do we inform women?•

With DBT and/or US?•

Sonographer training?•

How do we determine density? • Volpara?

Protocol • – follow up? Biopsy limits?

What about targeted US in dense breasts?•

DISCUSSION

FIG. 2. RANGE OF RISKS IN 10,500 WOMEN ON ENTRY TO

THE MANCHESTER FAMILY HISTORY CLINIC

• Validated risk prediction tool , UK

• Womans age

• Results BRCA 1/2 in family

• FHx, age of Dx

• Family structure, age/ number female rels

• NZ BC incidence data

GENETIC

ASSESSMENT/TESTING

CHRISTCHURCH 2018

BRCA 1/2 - BOADICEA

• >= 10% probability on affected person (BC or OvC)

• >= 20% probability in unaffected person

• Calculated using BOADICEA

• Routine panel – BRCA 1/2, +/- ATM, PALB2, TP53, CHEK2, ATM, . (If patient wants all tested)

GENETIC

ASSESSMENT/TESTING

CHRISTCHURCH 2018

BRCA 1/2 - BOADICEA

• High Risk – estimated risk of BC by 75 yrs - 29% or >er

• Mod Risk - estimated risk of BC by 75 yrs– 18-28%

• IF NO pathogenic mutation –significantly reduces risk for at risk relatives

GENETIC

ASSESSMENT/TESTING

CHRISTCHURCH 2018

BRCA 1/2 - BOADICEA

• BC – Triple neg and <= 50yrs, regardless of FHx

• BC – Triple neg any age if FHx BC, non mucinous epithelial Ov ca, fallopian tube or primary peritoneal Ca in close rel

• OVC – individual with higher grade non mucinous epithelial ovarian, fallopian, primary peritioneal <=70 yrs

• OVC individual with above + FHx BC or OVC in close rel –any age

• OVC – individual with above or high grade serous component and meets MBS criteria for BRCA 1/2 testing

GENETIC ASSESSMENT/TESTING CHRISTCHURCH 2018

BRCA 1/2 HISTOLOGY

• < 30 yrs at diagnosis– MDT consensus

• 30 - 59 yrs – Annual until 70 years, alt years to 74

• 60 – 70 yrs – Annual for 10 years, alt years 70-74

• 71 -79 yrs – Annual to 80 years

• 80 + years – 1 Baseline mammogram at 1 year

• NB - 5 years from diagnosis alternate mammograms with screening program 45 - 69 years

CDHB AT RISK PROGRAM – MAMMOGRAPHY (FUNDED)PERSONAL HISTORY OF BREAST CANCER

• Ist Degree Rel Bilat BC --- start 5 yrs younger until 74

• Ist Degree Rel < 40yr BC --- start 5 yrs younger until 74

• Ist Degree Rel < 60yr Male BC --- start 5 yrs younger until 74

• 2x 1st Degree Rel < 50 BC --- start 5 yrs younger until 74

• BRCA mutation --- annual until 74

• CH MDT agreed high risk

• At Risk Histology --- annual for 5 yrs

• Chest wall radiotherapy (young) --- 30 -74

CDHB AT RISK PROGRAM – MAMMOGRAPHY (FUNDED)

FAMILY HISTORY - HIGH RISK

CDHB AT RISK PROGRAM – MAMMOGRAPHY (FUNDED)

FAMILY HISTORY – MODERATE RISK

• 1 x 1st deg Rel < 50 BC --- start 5 yrs younger – annual until 60

• 2 x 1st or 2nd deg Rel – incl 1 x < 50 ---- start 5 years younger annual until 60

Large locally advanced/inoperable tumours•

Inflammatory breast cancer•

Down stage primary so BCS possible•

Down stage axilla • – less axillary clearance

Young patients • - better control of cancer

Smaller Ca with aggressive features•

Allows time for BRCA testing if required•

Allows ability to assess response•

WHY

NEOADJUVANT

CHEMOTHERAPY?

Risk delaying surgery•

Rare to get progression on NAC (– 3% vs >90% response)

Lack pathological data for prognosis•

Have to rely on clinical and –radiological staging

Lesser role in certain sub• -typesLow grade ER+ (?Eliminate trial)–

Lobular ca–

Multicentric– (>1 quadrant)

POTENTIAL

LIMITATIONS OF

NAC

Higher rates of Breast Conserving •

surgery

30– -40% Mast to BCS conversion rate

Need assessment of breast & axilla prior •

NAC

MRI useful for both (nodes negative –

predictive factor 94%)

Clip placement into tumour (+/• - node)

?Radio• -iodine seed placement into node

NAC – IMPLICATIONS FOR SURGICAL MANAGEMENT

cN• 0

SNB post– -NAC 14/17 studies in favour

Papa et al Prospective study SNB –

pre and post NAC

Id rate • 100% vs 87%

False • –ve rate 2-4% vs 15.8%

cN• 1-2

SNB post NAC – 11/15 studies in favour

30• -40% conversion of N+ to N-

TIMING SNB –

METANALYSIS

(2013)

NSABP• -B27 – Safe to do SNB post NAC

False – –ve 11% (8% if dual dye and tracer)

Id rate – 84.8%

No – signif diffce between node +veand node -ve

ACOSOG• -Z1071

Node +– ve, clip the node pre-NAC and excise with SNB post-NAC

False • –ve rate 13.4% -> 6.8%

TIMING SNB -

POST-NAC

72 • studies, 7,451 patients

SNB id rate • 87% (vs 95% in EBC)

False • –ve rate 16% (vs 6% in EBC)

Average node +• ve rate 50% therefore false –ve rate significant

Conclusion • – limited benefits of SNB in locally advanced BC

SNB POST NAC FOR LOCALLY ADVANCED BC -

METANALYSIS

72 • studies, 7,451 patients

SNB id rate • 87% (vs 95% in EBC)

False • –ve rate 16% (vs 6% in EBC)

Average node +• ve rate 50% therefore false –ve rate significant

Conclusion • – limited benefits of SNB in locally advanced BC

SNB POST NAC FOR LOCALLY ADVANCED BC -

METANALYSIS

ANC indicated•

Lymphoedema– rates 15-20%

Sentibras• protocol to reduce lymphoedema rates (27%)

Axillary reverse mapping (inject isotope in hand to identify axillary –

nodes that drain arm)

If Metastatic – ax nodes, Zone D nodes only make up 9%, therefore selective avoidance Zone D nodes

? Role RT to axilla post NAC•

SNB +VE POST NAC

NAC will become more common•

– ‘lesser’ surgery -> ‘lesser’ morbidity, improved cosmesis

Mx• Axilla post NAC

cN– 0 = SNB (if +ve ANC)

cN– 1 -> cN0 = SNB + clipped node (if +ve ANC)

cN– 1 -> cN1 = ANC

For locally advanced and inflammatory ca • –ANC

If ANC •

?consider selective preservation Zone D nodes–

CONCLUSIONS