GLOSSARY

A

ACCRUAL TARGET: The targeted number of participants to be recruited to a clinical trial.

ADJUVANT THERAPY: Additional treatment used to improve the effects of surgical treatment. In cancer, adjuvant therapy may include chemotherapy, hormonal or radiation therapy after surgery, which is aimed at killing any remaining cancer cells.

ADVANCED BREAST CANCER: Cancer that has spread from the original site in the breast to other organs or tissues in the body. Also known as metastatic, secondary or stage 4 breast cancer.

ADVERSE EVENT (AE): Any untoward medical occurrence in a patient or clinical trial participant who has been treated as part of a clinical trial and which does not necessarily have to have a causal relationship with this treatment.

ANTI-OESTROGENS: Medications that work by stopping oestrogen from causing breast cancer cells to grow and reproduce. Examples include tamoxifen and fulvestrant.

AROMATASE INHIBITORS (AI): A class of drugs used in the treatment of breast cancer in postmenopausal women. Some cancers require oestrogen to grow. Aromatase is an enzyme that synthesises oestrogen. Aromatase inhibitors block the synthesis of oestrogen which lowers the oestrogen level and slows the growth of cancers. Examples include anastrozole, exemestane, letrozole.

AXILLA: The armpit.

AXILLARY DISSECTION: Surgery to remove all the lymph nodes from the armpit. The procedure can be performed either at the same time as breast surgery or as a separate operation.

AXILLARY LYMPH NODES: Lymph nodes in and near the armpit.

B

BIOMARKERS: Biological markers that can be measured to show the presence or absence of disease. These may be measured in the tumour, blood, normal body tissue or through scans. Biomarkers can help with the diagnosis, prognosis and treatment of diseases such as cancer.

BIOPSY: The removal of a small sample of tissue or cells, usually with a needle, from the body to help diagnose a disease.

BRCA1 AND BRCA2: Inherited gene mutations that are a higher than average risk of breast cancer in those who carry the faulty gene. Women who carry these mutations are also at increased risk of developing ovarian cancer.

BREAST CONSERVING SURGERY: Surgery to remove part of the breast. Also called a lumpectomy or a wide local excision.

BREAST DENSITY: A measure used to describe the relative amounts of fat and tissue in the breasts as seen on a mammogram.

C

CHEMOTHERAPY: The use of medications that are toxic to cancer cells. These drugs kill the cells, or prevent or slow their growth. A standardised combination of such drugs in the treatment of cancer is referred to as a ‘treatment regimen’ e.g. cyclophosphamide, doxorubicin, docetaxel and capecitabine.

CLINICAL TRIAL: Research conducted with participants’ consent, which usually involves an evaluation of a new treatment or diagnostic method. Clinical trials are conducted to gain a better understanding of whether these treatments are effective and safe, as well as about the underlying disease process. Depending on how advanced the investigational product is in its evaluation, a trial may be described as Phase I, II, or III.

CONTRALATERAL PROPHYLACTIC MASTECTOMY: Removal of the breast on the side that did not have cancer, to reduce the risk of cancer recurrence in that breast.

CYCLIN-DEPENDENT KINASE 4/6 INHIBITOR (CDK): A drug that blocks the CDK4 and CDK6 proteins, which stops certain processes that cause cancer cells to grow and multiply. Examples include palbociclib, ribociclib, abemaciclib.

D

DE-ESCALATION: While many clinical trials focus on developing new treatments for cancer or using existing treatments in new ways, some clinical trials have a different focus: to reduce the amount and intensity of treatment, whilst maintaining equally good outcomes. De-escalation helps researchers to better identify those patients at high or low risk of cancer coming back (recurrence) and can optimise treatment to best suit each patient.

DOUBLE-BLIND TRIAL: A clinical trial in which neither the participating individual nor the study staff knows which participants are receiving the experimental drug and which are receiving a placebo or another therapy.

DUCTAL CARCINOMA IN SITU (DCIS): Abnormal cells in the breast ducts, which over time could develop into invasive breast cancer.

E

EARLY (Primary) BREAST CANCER: Breast cancer that has not spread beyond the breast or the axillary lymph nodes. This includes ductal carcinoma in situ and stage I, IIA, IIB, and IIIA breast cancers.

EARLY STAGE BREAST CANCER: Breast cancer that has not spread beyond the breast or the axillary lymph nodes. This includes stage I, IIA, IIB, and IIIA breast cancers.

ELIGIBILITY CRITERIA: Participant eligibility criteria define whether a trial is suitable for an individual to participate. Eligibility criteria for clinical trials varies depending on the specific purpose of the trial. Typical criteria include age, stage of cancer, cancer type, prior treatment regimens and tumour characteristics.

ENDOCRINE-RESPONSIVE: Another name for hormone-responsive, or hormone receptor-positive breast cancer. Refer also to “hormone (endocrine) treatment”.

ENDPOINT: Endpoints are used to measure the effect of a treatment being used in a clinical trial. Primary endpoints measure outcomes that will answer the primary (or most important) question being asked in a clinical trial, such as whether a new treatment is better at preventing disease-related death than the standard therapy. Secondary endpoints measure other relevant trial outcomes.

G

GENOMIC TESTS: These tests analyse a sample of breast tumour to provide information about the genes and their activity in breast cancer cells. The activity of these genes affects the behaviour of the cancer, including how likely it is to spread to other parts of the body and to come back after treatment (“recurrence”), and how it may respond to treatment. Examples include Prosigna (PAM50), Oncotype DX, EndoPredict, and Mammaprint.

GONADOTROPIN-RELEASING HORMONE (GnRH) ANALOGUE/AGONIST: A medication such as goserelin or triptorelin that temporarily stops the ovaries from producing oestrogen. This treatment (e.g. Zoladex) is used as treatment of early stage or metastatic hormone receptor positive breast cancer in premenopausal women. It may be used for pre-menopausal women with hormone receptor negative breast cancer in combination with chemotherapy, with the aim of protecting fertility.

GOOD CLINICAL PRACTICE (GCP): An international standard for the design, conduct, performance, recording and reporting of clinical trials; that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity and confidentiality of trial subjects are protected.

GRADE (TUMOUR GRADE): The degree of similarity of the cancer cells to normal cells. Grade is assessed by a pathologist. Grade 1 carcinoma is well differentiated and is associated with a better prognosis. Grade 2 carcinoma is moderately differentiated and is associated with an intermediate prognosis. Grade 3 carcinoma is poorly differentiated and is generally associated with a worse prognosis.

H

HER2-POSITIVE (HER2-amplified): HER2 stands for Human Epidermal Growth Factor Receptor 2. In HER2-positive breast cancer, the cancer cells have an abnormally high number of HER2 genes per cell. When this happens, too much HER2 protein appears on the surface of these cancer cells. This is called HER2 protein over expression or amplified. Too much HER2 protein is thought to cause cancer cells to grow and divide more quickly.

HER SIGNALLING PATHWAYS: One of the many complex processes associated with cell communication and action. The role of specific molecules in a cell which, via a cascade effect, inhibit or allow particular cell functions. Drugs being developed to inhibit these pathways might lead to new ways to block cancer cell growth and kill cancer cells.

HORMONE (ENDOCRINE) TREATMENT: Hormone (endocrine) treatment is used to treat breast cancers that are hormone receptor-positive, also known as hormone-responsive or endocrine-responsive. These cancers have receptors for the hormones oestrogen and/or progesterone; they are called ER and/or PR-positive cancers. There are several different types of hormone treatments. Some are taken as tablets (tamoxifen or aromatase inhibitors) and some are treatments to turn off or remove the ovaries (injections, surgery and sometimes radiotherapy).

HORMONE RECEPTORS: Proteins in a cell which bind to specific hormones. This stimulates the cell to act in a particular way.

HORMONE REPLACEMENT THERAPY (HRT): Drug therapy that supplies the body with hormones that it is no longer able to produce; usually to relieve menopausal symptoms.

HORMONE-RESPONSIVE: Also known as hormone receptor-positive or endocrine-responsive breast cancer.

HUMAN RESEARCH ETHICS COMMITTEE (HREC): The Human Research Ethics Committee’s function is to review proposed research in order to ensure that the subject’s rights are protected and that risk of harm is minimised.

HYPOTHESIS: In research it relates to testing a concept or theory, or it can be developed as a result of research conducted.

I

IMMUNOHISTOCHEMISTRY (or IHC): Used to identify tissue components (e.g. abnormal cells in a cancerous tumour, different parts of biological tissue) by using a marker such as a fluorescent dye or an enzyme. The marker is attached to a type of protein (antigen) that finds another type of protein (antibody) and reacts to colour the target cells.

IMMUNOTHERAPY: a type of cancer treatment designed to boost the body’s natural defences to fight the cancer.

INDEPENDENT DATA MONITORING COMMITTEE (IDMC): An independent group of experts or adequately qualified individuals who monitor participant safety and treatment effectiveness data while a clinical trial is ongoing.

INFORMED CONSENT: Informed consent is a process whereby a person gives consent based on a clear understanding of the facts, any implications and possible future consequences. In the case of a clinical trial, these facts, implications and consequences are conveyed in the Participant Information Sheet and any associated materials.

INVESTIGATOR: A clinician who recruits clinical trial participants to trials at his/her hospital or treatment centre. Investigators take responsibility for protocol adherence at site and often collaborates with peers in a multidisciplinary team to ensure that patients are receiving the most suitable treatment options.

iPREVENT: A breast cancer risk assessment and risk management decision support tool designed to facilitate prevention and screening discussions between women and their doctors.

IPSILATERAL: On or affecting the same side of the body.

L

LETROZOLE: An oral non-steroidal aromatase inhibitor for the treatment of hormonally responsive breast cancer.

LOBULAR CARCINOMA IN SITU (LCIS): An area (or areas) of abnormal cell growth that increases a person’s risk of developing invasive breast cancer later on in life. Lobular means that the abnormal cells start growing in the lobules, the milk-producing glands at the end of breast ducts.

LOCALLY ADVANCED BREAST CANCER: Cancer that has spread beyond the breast to the skin or chest wall, but not to distant organs such as the lungs or liver. It also refers to a tumour that is larger than 5 cms in size.

LUMPECTOMY: Also called “Breast Conserving Surgery”.

LYMPHOEDEMA: Swelling caused by a build-up of lymph fluid, as a result of lymph nodes being removed or not working properly.

M

MACROMETASTASES: Cancer cells that have spread (metastases) into the lymph nodes or distant organs beyond the primary tumour.

MADAROSIS: Loss of the eyelashes or of the hair of the eyebrows.

MAGNETIC RESONANCE IMAGING (MRI): A medical imaging device using a strong magnetic field and radio frequency to produce detailed images of internal body parts and structures. MRI is especially useful for imaging soft tissue like the brain, heart, muscles and tumours.

MAMMOGRAM: An x-ray of the breast.

MASTECTOMY: The surgical removal of the whole breast.

METASTATIC BREAST CANCER: Cancer that has spread from the original site in the breast to other organs or tissues in the body. Also known as secondary breast cancer or advanced breast cancer.

MICROMETASTASES: Small cancer cells that have spread (metastases) into the lymph nodes beyond the primary tumour and can only be detected by microscopic evaluation.

MONOCLONAL ANTIBODIES: A treatment designed to specifically target on the surface of a cell within the body, particularly cancer cells. Different cancer types can be targeted with different monoclonal antibodies, examples include trastuzumab and bevacizumab.

N

NEOADJUVANT THERAPY (Preoperative Therapy): Chemotherapy or hormone therapy used as a first treatment. Often used for large or locally-advanced cancers to shrink tumours before surgery.

NODAL STATUS: Whether a breast cancer has spread (node-positive) or has not spread (node-negative) to lymph nodes in the armpit (axillary nodes). The number and site of positive axillary nodes can help predict the risk of cancer recurrence.

O

OESTROGEN: The main female sex hormone produced mostly by the ovaries.

OESTROGEN RECEPTOR (ER): A protein that may be present on certain cells to which oestrogen molecules can attach. The term “ER-positive” refers to tumour cells that contain the oestrogen-receptor protein. These cells are generally sensitive to hormone therapy.

ONCOLOGIST: A doctor who specialises in treating cancer (oncology).

OOPHORECTOMY: The surgical removal of an ovary or ovaries.

OPEN-LABEL TRIAL: A clinical trial in which doctors and participants know which drug or treatment is being administered. Treatment trials may be open label, or alternatively can be placebo controlled (see definition of placebo and blinded trial).

OSTEOPOROSIS: A disease characterised by low bone mass and deterioration of bone architecture, which increases the susceptibility to fractures.

OVERALL SURVIVAL (OS): The time from trial randomisation until death from any cause. Overall survival is regarded as the gold standard measure of benefit in clinical trials and requires a large number of patients and long term follow-up.

P

PAM50: The Prosigna Breast Cancer Prognostic Gene Signature Assay is a genomic test that analyses the activity of certain genes is early-stage, HR-positive breast cancer. The Assay may be used to make treatment decisions based on the risk of recurrence for postmenopausal women within 10 years of diagnosis after 5 years of hormonal treatment.

PARP (poly (ADP-ribose) polymerase) Inhibitors: A class of targeted therapy drugs (e.g. olaparib) that block an enzyme involved in DNA repair.

PARTICIPANT INFORMATION SHEET: A document that provides clinical trial participants with important information relating to a specific trial. The purpose is to the assist the participant in the decision-making process regarding their potential participation in the trial.

PARTICIPATING INSTITUTION: Any public or private hospital or facility where clinical trials are conducted.

PHASE II CLINICAL TRIAL: The second stage of the evaluation of a new drug in humans; these trials evaluate drug safety and preliminary effectiveness in a large number of participants.

PHASE III CLINICAL TRIAL: Study the effectiveness of an intervention (e.g. study drug) in large groups of trial participants by comparing the intervention to other standard or experimental interventions (or to non-interventional standard care). Phase III studies are also used to monitor adverse effects and to collect information that will allow the intervention to be used safely.

PI3K (Phosphatidylinositol 3’-kinase): A protein produced by the body that can change the cell-to-cell communications which affect cell growth and survival.

PLACEBO: An inert tablet (such as a sugar pill), liquid or powder that has no active ingredient. In clinical trials, experimental treatments are often compared with a placebo, in combination with standard treatment, to assess the new treatment’s effectiveness.

PREDICTIVE FACTOR: A finding which assists a clinician to assess whether an individual’s cancer will respond either positively or negatively to a particular treatment. For example, the presence of oestrogen receptors predicts for response to hormone treatment. This term is often confused with “prognostic factor”.

PREVENTION TRIAL: Aims to find better ways to prevent breast cancer in healthy women.

PRINCIPAL INVESTIGATOR (PI): The person responsible for overseeing all aspects of a specific clinical trial at a BCT participating institution. Duties include recruiting participants, obtaining informed consent from participants, ensuring the trial protocol is adhered to, maintaining oversight of GCP at the site.

PROGESTERONE RECEPTOR (PR): A protein that may be present on certain cells to which progesterone molecules can attach. The term “PR-positive” refers to tumour cells that contain the progesterone- receptor protein. These cells are generally sensitive to hormone therapy.

PROGNOSTIC FACTORS: The combination of a number of aspects of a person’s general condition and disease diagnosis. General factors can include, but are not limited to, age, gender, lifestyle and medical history. Specific disease related factors can include disease diagnosis, stage, tumour size and location and treatment options. The combination of these factors can result in either a favourable or poor prognosis.

PROGRESSION-FREE SURVIVAL (PFS): The time from trial randomisation until cancer progression or death from any cause. PFS is considered a surrogate of overall survival, with the advantage that it can be measured in smaller clinical trials with shorter follow-up. Therefore it can be used to bring new therapies into clinical practice in a shorter timeframe.

PROPHYLACTIC MASTECTOMY: Surgery to remove one or both breasts to reduce the risk of developing breast cancer.

PROTOCOL: A written, detailed action plan for a clinical trial. The protocol provides the background, specifies the objectives, and describes the design and organisation of the trial.

Q

QUALITY OF LIFE: An individual’s overall appraisal of their situation and subjective sense of well-being.

R

RADIOTHERAPY: The use of radiation, usually x-rays or gamma rays, to kill cancer cells or damage them so they cannot grow and multiply.

RANDOMISATION: A method of preventing bias in research by ‘randomly’ assigning clinical trial participants to treatment groups. Randomisation ensures each treatment group has a similar range and number of participants, such that any differences between treatment groups at the end of the trial can be attributed to the trial treatments.

RANDOMISED CLINICAL TRIAL: A study in which participants are randomly assigned to one of two or more treatment arms of a clinical trial.

RECURRENCE: The return of breast cancer after a period of remission. During a recurrence, breast cancer cells which have evaded treatment may reappear at the original site or in another part of the body.

RECURRENCE-FREE SURVIVAL: A measure of the time between an individual starting on a trial treatment until cancer recurrence or death. This is often used as an endpoint in adjuvant, or early-stage clinical trials.

RECURRENCE SCORE: Obtained by the Oncotype DX® Assay, is a numerical value between 0–100 representing the likelihood of recurrence to distant parts of the body at 10 years post diagnosis.

S

SENTINEL NODE: The hypothetical first lymph node or group of nodes reached by metastasising cancer cells from a primary tumour.

SENTINEL NODE BIOPSY: Sampling of the first axillary lymph node(s) into which the primary tumour drains to understand the prognosis of the tumour, and whether further axillary treatment is required.

SEROUS ADVERSE EVENT (SAE): A serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalisation; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or requires intervention to prevent permanent impairment or damage.

SIDE EFFECTS: Unwanted effects of a drug or treatment (e.g. nausea, headache, hair loss side effects) may be short or long term, ranging from minor inconveniences to serious adverse events.

STANDARD TREATMENT (THERAPY): The current best treatment known for a particular disease or condition.

STUDY CHAIR: An appropriately qualified clinician assigned by BCT to provide clinical advice and guidance for the development and ongoing conduct of a clinical trial.

STUDY (or Trial) COORDINATOR: A member of the research team at a BCT participating institution who works with site Investigators to ensure compliance with a clinical trial protocol. The role may include clinical and non-clinical tasks, such as data management.

SUPRA-CLAVICULAR FOSSA: An indentation immediately above the clavicle, or collar bone, where breast cancer can sometimes be found in lymph nodes.

SYSTEMIC (ADJUVANT) THERAPY: Treatment given in addition to surgery and radiation to treat early stage breast cancer that may have spread at a microscopic level to other parts of the body. It is given with curative intent. It may include chemotherapy, targeted therapy and/or hormone therapy.

T

TAMOXIFEN: Used for the treatment of early and advanced breast cancers that are hormone-receptor positive. These breast cancers need estrogen to grow. Tamoxifen stops or slows the growth of these tumours by blocking estrogen from attaching to hormone receptors in the cancer cells. It is also used to prevent breast cancer in women with high risk of developing the disease. It is the most common hormone treatment for male breast cancer.

TARGETED THERAPY: Agents designed to attack specific molecular agents or pathways involved in the development of cancer. Trastuzumab (Herceptin) is an example of a targeted therapy used to treat breast cancer.

TISSUE BANKING: Collection, preparation and storage of tissue samples (e.g. blood, tumour) for long-term use in scientific research. Tissue samples can be collected as part of standard biopsies, blood tests, or surgery, or may require extra procedures to be done.

TOXICITY: Side effects from a treatment being tested.

TREATMENT TRIALS: Treatment trials are designed to test the safety and effectiveness of new drugs, biological agents, techniques, or other interventions in people who have been diagnosed with cancer. These trials compare the new treatment to standard treatment, if applicable.

TRIPLE-NEGATIVE METASTATIC BREAST CANCER (TNBC): ‘Triple-negative’ is the term given to tumours which do not possess Oestrogen Receptor (ER) and Progesterone Receptor (PgR) proteins, and which do not over express the HER2 protein.

TYROSINE KINASE INHIBITOR: A drug that interferes with cell communication and growth and which may prevent tumour growth (e.g. lapatinib).