Breast cancer and diabetes

Transcription

1 Breast cancer and diabetes Dr Marina Parton, Consultant Medical Oncologist, The Royal Marsden NHS Foundation Trust Dr Narda Chaabouni, Clinical fellow in Breast Cancer, NHS Foundation Trust 1

2 2 Focusing on: Breast cancer and diabetes overlap- a common scenario in primary care Common treatments for breast cancer and diabetic related complications Case studies

3 61 Breast cancer is a common cancer Breast cancer is the most common malignant neoplasm in women affecting 1 in 8 women 55,000 patients are diagnosed with breast cancer in the UK one person every 10 minutes

4 4 Breast cancer and diabetes have a multifactorial relationship The relationship between diabetes and breast cancer is complex and not completely understood Diabetes is associated with multiple factors that can potentially influence breast cancer: Obesity Fitness Metabolic syndrome

5 63 Up to 16% of patients with breast cancer have diabetes studies suggest that Type 2 DM may be associated with 10%-20% excess relative risk of breast cancer 1 Up to 30% of breast cancer patients may have undiagnosed or delayed diagnosed diabetes Wolf et al: Diabetes mellitus and breast cancer. Lancet Oncology 2005;6(2): Erikson et al: Clinically defined type 2 diabetes mellitus and prognosis in early stage breast cancer. JCO 2011:29(1):54-60

6 64 Diabetes may affect Breast Cancer directly Activation of insulin signalling pathway Activation of insulin- like-growth factor pathway Alteration of endogenous sex-hormone regulation

7 7

8 66 Diabetes may affect breast cancer indirectly because end organ damage may: Influence screening and treatment choices Affect treatment toxicities Evidence that this may lead to worse outcome of breast cancer

9 9 Toxicity of chemotherapy Srokowski et al 3 analysed data on 11,826 women with early breast cancer who received adjuvant chemotherapy to assess toxicity Diabetes was associated with an increased risk of being hospitalised for: Chemotherapy toxicity Infection/ fever Neutropenia 3. Srokowski et al: Impact of Diabetes Mellitus on Complications and outcomes of Adjuvant chemotherapy in older patients with breast cancer. JCO 2009:27(13):

10 67 Effects of Chemotherapy on diabetic cancer patients Wound healing problems Peripheral neuropathy (platinum, taxanes, vinca alkaloids, TDM1, pertuzumab Other end organ damage (cardiac, renal) Steroid induced hyperglycaemia SIH

11 11 TRM experience of SIH during adjuvant chemotherapy for breast cancer Retrospective study to examine the incidence of SIH during chemotherapy for early breast cancer 249 women included from treated with FEC-T At least 1 random BG recorded at the time of T (Docetaxel)

12 12 Analysis of TRM patients 249 patients 3 groups -A Normal -B 14.4% had glucose >11 mmol/l after steroids (SIH) -C 5.2% had diabetes (DM) SIH and DM group older and higher BMI Group B+C had higher rates of any admission with any toxicity (19v 32%) and sepsis (17 v 26%) Schiavon et al EBBC 9 accessed at

13 13 Case Study 1 Patient: 50 year old mother of 4 Type II DM, hyperlipidaemia, raised BP Metformin, sitagliptin, atorvastin Non- smoker Feb 2015: self detected left breast cancer 6x8cm Grade 3 IDC Oestrogen receptor positive (ER+ve) HER2 positive Staging scans all clear Baseline MUGA LVEF 55%

14 Standard treatment plan: chemotherapy indicated Treatment schema Taxol Surg R T EC Herceptin 18# Completed 3#EC -transferred care OE SOBOE, resting tachycardia 120, no pyrexia/chest pain

15 15 Question: What is the underlying cause? 1. Progressive breast cancer 2. Chemotherapy related toxicity 3. Infection 4. PE 5. Cardiac cause

16 All of those answers! Good response in the breast Septic screen normal- CRP/WCC normal CTPA normal/no lung fibrosis/changes relook at patient

17 Re-Exam (!) JVP3-4cm, tachy 120bpm reg, mild SOA Invx Troponins sl raised ECHO LVEF 40% global hypokinesia ECG LAD, Q waves lead III and AVF, poor R wave progression in the anterior leads Anthracycline cardiomyopathy

18 18 ACE I B-blocker Ivabradine Gradual recovery. proceeded with taxane, added herceptin later Final surgery no breast cancer in the specimen. Good oncological outlook Complications of therapy on heart may be the main future problem.

19 19 Reflection Pre-disposition to cardiac complications anthracycline sparing schedules closer monitoring current pilot; troponins with every cycle For the future; Upfront cardio-protection with ACE I and B blocker

20 20 Case Study 2: Patient aged 46yrs 4cm self detected R breast lump Grade 3 IDC triple negative (ER-, PgR- and HER2-) Co morbidities: BP, lipid, Type II DM Metformin, sitagliptin, ezetimibe, amlodpine. Moderately obese

21 Standard of care Neoadjuvant chemotherapy 6 cycles FEC-T anthracycline- baseline echo+ monitor High dose steroids- change type of taxane Neuropathy-?monitor High risk of infection give GCSF Small scope for 4 cycles short course chemo if path more favourable. Surgery with reconstruction and post op RT Higher rates of infection and delayed would healing with implants esp if smoker/ obese

22 Modified management plan; Opted for upfront surgery, no reconstruction Post op infection, delays in start of Rx (sig?) Pathology high risk- still recommended 6 cycles of chemo (FEC-T) Switched to insulin during chemo due to routine glucose in high teens, hard to manage But still. mouth ulcers, folliculitis, vulval abscess Grade 2 peripheral neuropathy at end of treatment- last cycle of taxane not given (incomplete Rx) Recovery to grade 1 neuropathy after

23 23 18 months later, in FU Worsening pain in feet- difficulty during prolonged walking Nil OE Sock distribution- wakes her up at night sometimes

24 24 Question: What are the causes of the neuropathy? 1. Progressive diabetes complications as occurring long after breast cancer treatment 2. Breast therapy taxane neuropathy, as only in the feet 3. Neither- as feet only may be paraneoplastic syndrome or early spinal cord compression from relapsed breast cancer

25 25 Not so clear cut! Steroid use and neurotoxic agents appear to trigger progressive diabetic neuropathy Pattern and time scale can still be Taxane related Management similar- neuropathic agents. although unclear if better glycaemic control helps. Taxane neuropathy likely to be long term at this point. Incomplete therapy implications long term uncertain

26 26 Endocrine agents - Tamoxifen Weight gain NAFLD or due to weight gain or previous insult from steroids Endometrial cancer risk (+diabetes + obese) AIs Lipid profiles Weight gain Joint stiffness++

27 27 Early Breast cancer outcomes in diabetes Patients with breast cancer and pre-existing diabetes suffer allcause mortality twice as high if the HbA1C >_ 7.0% compared with women with HbA1Cless than 6.5% (HR 2.35 CI ) Median FU 10.3 yrs Erikson et al: Clinically defined type 2 diabetes mellitus and prognosis in early stage breast cancer. JCO 2011:29(1):54-60

28 28 Unadjusted all-cause mortality curve of patients with and without diabetes and breast cancer 3 Baronne et al JAM 2009, Baronne et al Diabetes Care 2010, Pears et al J Clin Oncol 2010, Be Bruijn et al Br J Surg 2013

29 29 Association between breast cancer specific mortality and diabetes is not clear (Fleming el al) Srokowski et al 4 observed increased breast cancer specific mortality only in patients with diabetes receiving chemotherapy 3. Fleming et al: A Comprehensive prognostic index to predict survival based on multiple comorbidities A focus on Breast cancer. Med Care 37: , Srokowski el al: Impact of Diabetes Mellitus on Complications and outcomes of Adjuvant chemotherapy in older patients with breast cancer. JCO 2009:27(13):

30 90 Unadjusted breast cancer-specific mortality curve of patients with and without diabetes and breast cancer: Who did receive chemotherapy: Who did not receive chemotherapy:

31 91 Metformin Overwhelming evidence supporting metformin as a preventative drug for breast cancer Prospective randomized clinical trials are on-going to test the efficacy of metformin on breast cancer MA.32: phase III randomized trial metformin versus placebo on recurrence and survival in early stage breast cancer (n=3,600). 1 st reports after 2017

32 92 Conclusion Diabetes increases breast cancer risk. Diabetic breast cancer patients treated with chemotherapy have an increased risk of toxicities/admissions. Good glycaemic control during treatment may reduce toxicities and improve long term outcomes If MA32 positive, Metformin could become a standard of care for all breast cancer patients regardless of glycaemic control

33 33 Evaluation Breast cancer and Diabetes Please rate this session for relevance to you as a GP: 1. Poor 2. Fair 3. Good 4. Very good 5. Excellent