breast cancer scanning the horizon
TRANSCRIPT
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
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.