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? Surgery reduces BC risk to almost zero. A Jolie. 2013 Tamoxifen halves risk of CBC in mutation carriers. K Phillips et al, JCO 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 Slower Growth Better hormonal response Easier to pick on screening 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
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 www.canceraustralia.gov www.canceraustralia.gov 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
Combined Her 2 blocking therapies Cost issues PBS delays likely 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
Longer Tamoxifen Improving hormone blocking therapies 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 www.dignitana.com 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
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.