Case presentationER+Her2-

Daniela Katz M.D

Assaf Harofeh Medical Center

Case presentation

A 55 year old women diagnosed with locally advanced IDC T=2 cm, LN + 1.

ER+2, PR-, HER2- KI67 40%

Patient initiated neoadjuvant chemotherapy with DD AC followed by 12 cycles of paclitaxel with a good clinical response.

She underwent L+SLNB

Pathology

• IDC T=1.2 + DCIS

• SLN 0/2

What type of adjuvant therapy will you recommend?

What type of adjuvant therapy will you recommend?

1. Hormonal therapy+ RTX

2. Chemotherapy followed by hormonal therapy+ RTX

Kaplan–Meier Estimates of Disease-free Survival and Overall Survival.

Masuda N et al. N Engl J Med 2017;376:2147-2159

Adjuvant hormonal therapy with letrozole was initiated + adjuvant RTXThe patient was on letrozole for 21 months, when she returned to the office complaining of difficulty walking. A PET CT demonstrated 3 new bone mets: rt. ramus pubis, D6, D8.After completing palliative radiation to the ramus pubis

What type of systemic therapy will you recommend?

What type of systemic therapy will you recommend?

1. Fulvestrant + Zolandronic acid

2. Fulvestrant + palbocilib/ribociclib + Zolandronic acid

3. Fulvestrant + abemaciclib + Zolandronic acid

4. Exemestane+ everolimus + Zolandronic acid

5. Letrozole+ palbociclib + Zolandronic acid

Slide 18

Presented By Nicholas Turner at 2017 ASCO Annual Meeting

PFS by duration of prior ET

Presented By Luca Malorni at 2017 ASCO Annual Meeting

Treatment with fulvestrant + palbociclib was recommended.

After 21 months, she returns to the office complaining of progressive lower back pain and difficulty walking.

Her tumor markers have increased and an updated PET CT demonstrated multiple new bone lesions and several new liver mets without elevated liver function tests.

What next treatment will you recommend?

What next treatment will you recommend?

1. Capecitabine

2. Paclitaxel

3. Afinitor+ Exemestane

4. Liver Bx for NGS

Patient initiated treatment with capcitabine.

Unfortunately, her disease continued to progress with an increase in size and number of the liver mets.

What next treatment will you recommend?

What next treatment will you recommend?

1. Paclitaxel

2. Liver Bx for NGS

3. Clinical trial

The rational for genomic profiling

• Identify driver mutations that promote cancer proliferation and individualize treatment with targeted drugs

• “Re-classify” missed HER2 + patients

• Identify patients with high mutational burden

Schumacher and Schreiber (2015) Science

Adapted from Ross et al, SABCS 2016

•ERBB2 mutation ~2% of non-

HER2 amplified breast

cancers

•May be enriched in lobular

and metastatic breast

cancers

•Cell lines resistant to

reversible HER2 TKI,

sensitive to irreversible HER2

TKI

Bose R et al Cancer Discovery 2013. 3(2):1-14.

Ross J et al CCR 2013. 19(10); 2668–76

ERBB2 Mutation as an Oncogenic Driver

in HER2 non amplified ER+ breast cancers

San Antonio Breast Cancer Symposium, December 6 -10, 2016

Adopted Philippe Bedard

22

AZD5363 (AKT inhibitor) monotherapy

in AKT1 E17K mutant, ER+ breast cancer

Hyman DM, Smyth L et a Jclin Oncol 2017 May

San Antonio Breast Cancer Symposium, December 6 -10, 2016

Adopted Philippe Bedard

J Clin Oncol. 2017 May

J Clin Oncol. 2017 May