PROACT: Can we Prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?

Inclusion Criteria:

* Written informed consent.
* Adult patients with histopathologically\* confirmed breast carcinoma who have received surgery for their breast cancer; planned to receive 6 cycles of EC 90 (total planned dose 540mg/m2 epirubicin) or FEC 75 (total planned dose 450mg/m2 epirubicin) adjuvant chemotherapy regimen. Patients with HER2+ breast cancer are eligible for inclusion.

OR

* Adult patients with histopathologically confirmed non-Hodgkin lymphoma (NHL), planned to receive 6 cycles of R-CHOP or CHOP (total planned dose 300mg/m2 doxorubicin) chemotherapy\*\*

  * Patients with HER2+ breast cancer are eligible for inclusion. \*\* Patients who will receive an alternative anti-CD20 monoclonal antibody are eligible (for example O-CHOP), as long as the total planned doxorubicin dose is ≥300mg/m2 over 6 cycles

Exclusion Criteria:

* Positive baseline cardiac troponin T (≥14ng/L);
* known contraindication to ACE inhibitor e.g. renal artery stenosis, severe aortic stenosis;
* are taking, or have a previous intolerance to ACEI (e.g. angioedema);
* patient already taking other agents acting on the renin-angiotensin-aldosterone system e.g. Aliskiren, angiotensin receptor blockers (ARBs), Entresto (sacubitril/valsartan), spironolactone, eplerenone;
* LVEF \<50%\*;
* estimated GFR \< 30 mL/min/1.73m2 at baseline;
* hyperkalaemia defined as serum potassium ≥5.5mmol/L;
* symptomatic hypotension, or Systolic Blood Pressure \<100mmHg;
* poorly-controlled hypertension (Blood Pressure \>160/100mmHg\*\*, or ambulatory BP of 150/95mmHg);
* previous myocardial infarction;
* known metastatic breast cancer;
* previous exposure to anthracycline chemotherapy;
* are pregnant or breastfeeding;
* previous Herceptin treatment or planned Herceptin treatment within four weeks following anthracycline chemotherapy;
* for patients of childbearing potential: refusal to use adequate contraception throughout the trial;\*\*\*
* any other invasive cancer diagnosed and treated in the past 5 years;
* symptomatic or severe asymptomatic radiation-induced cardiac disease;
* judgement by the investigator that the patient has a prognosis of \< 1 year or are unlikely to complete 6 cycles of chemotherapy;
* judgement by the investigator that the patient is high risk for tumour lysis syndrome (applicable only to NHL patients);
* judgement by the Investigator that the patient should not participate in the study, for example, if the patient is unlikely to comply with study procedures, restrictions, and requirements.

  \*\<50% as defined by Simpson's biplane method; if absolute measurements are not possible, then a visually normal assessment of LVEF is acceptable for inclusion.

  \*\*White coat hypertension is more common, and should be ruled out by an ambulatory blood pressure monitor

  \*\*\*Female patients between the ages of 18 and 50 will receive a pregnancy test at baseline. Adequate methods of contraception are those that can achieve a failure rate of less than

  1% per year when used consistently and correctly, such methods include:
* combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation

  * oral
  * intravaginal
  * transdermal
* progestogen-only hormonal contraception associated with inhibition of ovulation

  * oral
  * injectable
  * implantable
* intrauterine device (IUD)
* intrauterine hormone-releasing system (IUS)
* bilateral tubal occlusion
* vasectomy/vasectomised partner
* true sexual abstinence