A case of localized breast cancer Antonella Brunello

A case of localized breast cancer Antonella Brunello Kwok-Leung Cheung

Disclosure No conflict of interests

Learning objectives To discuss the pros and cons of adjuvant chemotherapy for breast cancer in the elderly To discuss the initial diagnostic work-up for breast cancer To incorporate Comprehensive Geriatric Assessment in the multidisciplinary evaluation of the patient To discuss treatment options for localized breast cancer To learn about tools to help balancing expected benefits and risks from adjuvant chemotherapy Toxicity management

Past medical history • • • Diabetes since 2002 Hypercholesterolemia Hypertension Obesity Psoriasis Mild visual impairment due to exudative diabetic maculopathy

History of present illness • • 76 year-old lady In November 2012 found a nodule in the left breast. She was referred by her GP to a community hospital surgeon. At mammogram a 1. 5 cm nodule was confirmed, and there was a clinically suspicious axillary lymphnode Biopsy was performed on the left breast nodule which confirmed IDC grade 2, ER 100% Pg. R 50% Ki 67 15%, HER 2 1+. A FNAC of the axillary lymphnode was not diagnostic. Staging with chest x-ray and abdominal ultrasound was negative.

Q#1 Which is the life expectancy of this patient?

Q#2 What would you do at this point? Surgery Neoadjuvant chemotherapy Neoadjuvant endocrine therapy Radiation therapy

Comprehensive Geriatric Assessment ADL=6/6, IADL=8/8 Comprehensive Geriatric Assessment MMSE: 29/30 BMI=22. 7 (87 kg, 156 cm) GDS=3/15 7 drugs: - repaglinide - lercanidipine - metformin - nebivolol - lysine acetylsalicylate - valsartan/hydrochlorothiazide - esomeprazole - doxazosine - simvastatin

Q#3 Based on CGA, how would you classify this lady in the grandfather of Geriatric Oncology’s scale?

Comprehensive Geriatric Assessment Assuming she went for conservative surgery upfront Final pathologic report: “IDC grade 2 stage p. T 1 c (1. 5 cm) p. N 3 a (12 metastatic axillary lymphnode out of 24 examined), ER 100% Pg. R 45% Ki 67 14%, HER 2 2+, FISH negative”. Q#4 Further work-up / treatment?

History of present illness 10/2/2013: left upper outer quadrantectomy and lymphnode dissection (after positive sentinel node biopsy). • Patient was referred to our Institution for further management. • Staging was completed with bone scan, which revealed mild and disomogenous uptake in D 12. Plain x-ray did not show bone lesions

Adjuvant therapy? Discussion with patient and her family on adjuvant treatment options. Patient was very motivated to be treated with all available options, therefore a plan for adjuvant chemotherapy and subsequent endocrine therapy, plus radiation therapy was proposed.

Adjuvant chemotherapy After cardiology evaluation (good cardiac function, LVEF 64%), adjuvant chemotherapy was planned with sequential schedule Epirubicin/Cyclophosphamide (EC) 4 cycles followed by Paclitaxel weekly, given the N 3 stage. After second cycle of EC patient presented diarrhea with progressive dehydration, decompensated diabetes and subsequent acute renal failure and she was admitted to hospital for intensive care.

Would the choice of giving only endocrine therapy an option? HIGH-RISK LOW-RISK

Which is the expected benefit of chemotherapy in this patient ?

Adjuvant endocrine therapy • After recovering, the adjuvant chemotherapy was stopped and patient was started on Letrozole, and received radiation therapy. • In January 2014 patient developed back pain, and new x-ray and MRI revealed L 3 -L 4 vertebral fracture. A biopsy was taken which revealed no neoplastic cells, and patient underwent vertebroplasty. DEXA showed lumbar T-score -2. 6 and left femur T-score -3. 6. She was therefore started on Zoledronate 5 mg once a year. • At last follow-up on December 2017 patient status was NED. • March 2018: diagnosis of AML, started on Oncocarbide • Exitus September 2018

Recurrence Data: All Women

Bone recurrence by menopausal status Premenopausal‡ Postmenopausal Heterogeneity between menopausal groups χ21 = 5. 6 ; P=0. 02 ‡ includes women aged < 45 if unknown Coleman RE, Lancet 2015

Mortality: all women

Breast Cancer Mortality by Menopausal Status Premenopausal‡ ‡ includes women aged < 45 if unknown Postmenopausal Coleman RE, Lancet 2015

Conclusions • Metabolic syndrome must be taken into account for a very high risk of toxicity from chemotherapy, CGA-based tools may help in considering the toxicity risk. • Hormonal therapy alone may be a good treatment option in the older patients with high-risk ER+HER 2 - breast cancer. • Early start of bisphonate may be beneficial for comorbidity but also for oncological outcomes. • Multidisciplinary evaluation should be applied along with CGA in order to have a full picture and to allow the best treatment plan.