Breast Cancer

Scanning the Horizon

Prof Fran Boyle

BCNA Summit Sydney 2013

Feature Interview: Dr Fran Boyle :: Sunday Nights - ABC www.abc.net.au/sundaynights/stories/s1544975.htm

Familial breast cancer • Inherited changes in BRCA 1 and 2 genes

• Impair DNA repair, allowing more mutations to accumulate

• Only 5% of women with breast cancer carry these genes

• Features of inherited breast cancer

– Breast cancer at a young age on either side of the family

– A woman with cancer in both breasts in the family

– May lack estrogen, progesterone and Her 2 receptors (Triple negative)

– Ovarian cancer in the family

– Male breast cancer in the family

– Ashkenazi Jewish heritage (Eastern Europe)

• Testing (blood) is available through family cancer clinics

– Assists treatment planning (eg surgery to other breast, ovaries)

– Testing for other family members (gene tests, early screening with MRI)

How to respond?

Tamoxifen halves risk of CBC in mutation carriers. K Phillips et al, JCO 2013

Surgery reduces BC risk to almost zero. A Jolie. 2013

Targeted MRI screening

• Useful in addition to

Mammogram and

ultrasound in young

women with

– Strong family history

– Known BRCA mutations

– Prior radiation to the chest

• Funded on medicare

through high risk clinics

• More false positives

MRI for treatment planning

Medicare rebate under consideration by MSAC

Variable growth rates

LUMINAL A: Hormonal and slow

LUMINAL B: Hormonal and fast

HER 2 amplified: Hormonal /not

Triple Negative: Non hormonal / fast Faster Growth

May appear between mammograms Better Chemo response

Slower Growth Better hormonal response Easier to pick on screening

With variable mutation patterns

How to classify?

Standard Pathology

• Grade

• Extent of hormone

receptors

– Estrogen

– Progesterone

• Her 2 amplification

• Ki67 index

• Other basal markers

New profiling approaches

• Oncotype Dx

– Only hormonal breast cancer

– Sent to USA

– Takes 2 weeks

– Approx $4000

– Medicare considering

coverage

• PAM 50 classifier

– Any breast cancer

Some Grey areas

Changing powers

• Secondary cancers may have additional

mutations

– Altered after initial treatment as ”survival of the

fittest”

• May be worthwhile to rebiopsy to check

ER/PR and Her2

• Profiling mutations in metastases may open

up other treatment options

– CARIS Target Now – around $7000, send to USA

– Foundation Medicine

– Australian research emerging

Refining surgery

• Increasing use of

sentinel node biopsy

• Axillary dissection may

sometimes be omitted if

chemo and RT given

• Increasing use of

immediate

reconstruction

• Preoperative chemo

may allow breast

preservation in some

Focusing Rays

• Increasing use of

partial breast

radiation for low risk

cancers

• New trials will test

whether some may

avoid RT after

lumpectomy if on

hormone blockers

– Selected by MRI

– Selected by Oncotype

Brain metastases

• Standard treatment has

been radiotherapy to whole

brain

– Hair loss

– Some cognitive problems

• New Guidelines suggest

consider

– Surgery if few or one large

metastasis causing symptoms

– Lapatinib plus capecitabine

first if Her 2 positive and small

– Localised RT if small and few

• Stereotactic or gamma knife

www.canceraustralia.gov

www.canceraustralia.gov

Combined Her 2 blocking therapies

• Lapatinib (Tykerb) +

herceptin + chemo

– In trial early BC (ALTTO)

• Herceptin + Pertuzumab

(Perjeta) + chemo

– First line secondary BC

– In trials early BC (Aphinity)

• T-DM1 (Kadcyla)

– Chemo linked to herceptin

second line secondary BC

– Fewer sider effects as

chemo only released in

cancer cells Cost issues – PBS delays likely

Improving hormone blocking therapies

• Longer Tamoxifen

– 10 years better than 5 in ATLAS trial

– Might be most useful in younger (premenopausal) women

• For post menopausal women using Letrozole after 5 years

of Tamoxifen possible

– Trials still underway for 10 years of Aromatase Inhibitors

• Overcoming resistance in secondary breast cancer by

adding other drugs

– Everolimus (Affinitor)

• TGA approved, PBS approval likely in early 2014

– Buparlisib (BKM120) and Palbociclib (PD033)

• In trials in Australia

– BH3 mimetics (ABT199)

• Mice at the WEHI doing really well and recently in the news….

Triple negative BC

• Modern Chemo with taxanes / cyclophosphamide /

anthracyclines

– better than historically bad results, which were in patients who did

not have chemo

• Adding Avastin did not provide additional benefit in early

breast cancer (Beatrice Trial)

• Parp inhibitors back in trial in women with BRCA mutations

– Olaparib reformulated and ready to go

– Others in development

• Platinum drugs and capecitabine useful in secondary BC

• Other Antiangiogenics in trial eg Ramacirumab

Scalp cooling for prevention of hair loss

• Widely used in UK,

Europe and Canada

• Effective in 50% of

women having 4 or 6

cycles of chemo

• Equipment costs $40-50K

for 2 women

• Additional time in the

chair may be a barrier to

use in busy units

• Some discomfort due to

cold

www.dignitana.com

Diet?

• Weight associated with BC risk and

outcome

• “sarcopenic obesity” where muscle is lost

and fat is deposited on the abdomen

• Weight gain common during treatment

– Menopause

– Inactivity

– Steroids

– Comfort food

• Beware of “food fairies” bearing carbohydrates

Weight management

• Calorie restriction on

2 days per week

– Low carbohydrate

– High protein

• Mediterranean diet on

the other days

• Increase exercise

• Moderate alcohol

• Vitamin D and

calcium

Exercise

• Aerobic 3 hours per week

– Walk the dog

– Swim or aquarobics

– Run or Bike or dance

• Resistance 2-3 hours per week

– Weights under supervision

– Pilates

– Yoga

• Dragon Boating does both

• Get input from an exercise physiologist

– Get referral from your GP with care plan

Ask for referral to a psychologist

Mental Health Plan from GP to access Medicare coverage

Critical role of Consumers in advocating for improvements in care.