The Trials TeamSally Pearce Lisa Saville
We are involved in several of these in the Breast Care Centre as they are really the only way to improve the treatment and detection of breast cancer. Some are where we are part of a national or international study where large numbers of patients are needed to measure a possible effect, others are research taking place just in our centre. Our Trials co-ordinator is Dr Mike Shere and full time breast trials nurse is Catharine Dawe. Andrew Harvey is the North Bristol Trust cancer trials nurse, Sally Pearce is the IBIS I trials nurse, Lisa Saville is the North Bristol Trust cancer trials officer and Bern Thompson is the trials data manager.
Andrew
Catharine
Bernadette Mike
Harvey
Dawe
Thompson Shere
The Trials Team
Sally
Pearce
Lisa Saville
IBIS Study - Does Tamoxifen prevent Breast Cancer?
IBIS 2 Study - Does Anastrozole prevent Breast Cancer
TEAM Trial - Comparing a new drug Exemestane with Tamoxifen after Surgery for Breast Cancer
HRT Trial - Is it safe to give Hormone Replacement Therapy after having Breast Cancer
MARIBS Study - Is MRI scanning a good way to screen genetically high risk women?
SEALANT Trial - The use of a special adhesive to reduce fluid (seroma) in the armpit after surgery
ATAC Trial - Which is best, Tamoxifen, Arimidex or Both?
ATTOM Trial - Should we give Tamoxifen for more than 5 Years?
Breast Cyst Study - Does Wearing a bra cause more breast cysts?
Mammotome - Is this an effective way of biopsying lumps without an operation?
Buttress Suture Trial - Can we stop fluid (seroma) building up in the armpit after surgery?
Exemestane Study - Is Exemestane better than Tamoxifen after 2 to 3 years of Tamoxifen after surgery?
Prolactin Receptor Study - Is the Prolactin Receptor affected by tamoxifen treatment
POSH Study - Is Breast Cancer in under 40s different if there is a family history.
COMICE Study - Does doing a detailed MRI scan pre-operatively increase the accuracy of the operation and reduce re-operations
PRIME Trial - Is radiotherapy necessary for older patients with breast cancer
MATCH Study - What are the psychological effects of breast cancer in men
Adjuvant Trial in Post-Menopausal Breast Cancer
Arimidex, Tamoxifen Alone or in Combination
RESULTS ANNOUNCED!
The first results of this trial have just been announced (Dec 2001) and these show a benefit for Arimidex over Tamoxifen of 17% and actually less benefit for the combination of the two. If you are on the Trial and want to discuss these results please get in touch, but in general the advice is to carry on with the Trial drugs.
This is a trial designed to evaluate Arimidex (anastrozole) as adjuvant hormonal therapy in early breast cancer.
Oestrogen deprivation is an established method of treating breast cancer and until recently the only appropriate way of achieving this in the adjuvant setting was with tamoxifen. But tamoxifen has limitations: it is a partial oestrogen agonist and may be associated with endometrial changes, including cancer. Arimidex reduces oestrogen to below detectable levels and therefore may be superior to tamoxifen. Published data in advanced disease shows that Arimidex is as effective as megestrol acetate1, however a more recent analysis of the data shows that Arimidex offers survival benefit over megestrol acetate. Megestrol acetate has previously been shown to have a similar efficacy to tamoxifen. Tamoxifen may exert an effect via the modulation of growth factors, hence combining both therapies may offer more than either alone.
ATAC is an international collaboration of the leading groups in breast cancer research. It is a three way, randomised, double-blind study to compare the safety and efficacy of tamoxifen (Nolvadex) alone with a) Arimidex only and b) Arimidex and tamoxifen in combination.
Patients will receive either :
1) Arimidex (1mg) plus tamoxifen placebo
2) tamoxifen (20mg) plus Arimidex placebo
3) Arimidex (1mg) plus tamoxifen(20mg)
Hence all patients will be issued with two containers of tablets, one from each container to be taken every day. Trial therapy will be taken for 5 years and will be provided free of charge.
The trial is designed to fit with normal practice in terms of follow up and assessments. Patients must be post-menopausal thus an FSH measurement will be made to establish menopausal status in patients aged under 60 if they have had a hysterectomy, are taking HRT or have been rendered amenorrhoeic by chemotherapy. No constraints are imposed on the clinical management of the patient. Patients will be seen at 3 months and 6 months after the start of trial therapy, thereafter 6 monthly up to 5 years and annually up to 10 years.
Should the patient develop a recurrence or suffer intolerable side -effects, trial therapy will be stopped and may be unblinded so that future management may be determined. The clinical investigator is familiar with this procedure.
Safety will be closely monitored. The action of both tamoxifen and Arimidex may give rise to aggravated menopausal symptoms. Use of oestrogen replacement therapy will be discouraged since this will counteract the trial therapy, however, if the patient is suffering intolerable symptoms, the progestins may be prescribed, with notification to the trials centre. Other side effects that may be encountered are gastrointestinal disturbances and skin rash. Patients taking Arimidex have reported somnolence and weakness. Tamoxifen may interact with coumarin-type anticoagulants to increase the anticoagulant effect. It is also advised that patients should not be prescribed systemic ketoconazole due to its association with fatal hepatotoxicity.
Should you require more information please do not hesitate to contact the Clinical Trials Nurse at Frenchay Breast Care Centre, 0117 975 3752 or your consultant or the ATAC Trial Co-ordinator -
Dr Norman Williams
ATAC Trial Co-ordinator
CRC and UCL Trials Centre
Royal Free and University College Medical School
University College
Stephenson House
158-160 North Gower Street
LONDON NW1 2ND Tel 020 76798020 Fax 020 76798041
n.williams@ctc.ucl.ac.uk
1 Buzdar et al., J Clin Oncol 14:20000-2011, 1996
Patients currently being asked to join the ATAC trial are also being asked to join the above protocol as well, the main trial having closed for new entries other than those joining this sub protocol. The idea is to try and measure the effect of the two drugs on bone density i.e. whether they cause or protect against osteoporosis. This is done by doing doing a DEXA scan, which measures bone density and doing tests on blood and urine specimens at the beginning of the trial and repeating this again at the end of the trial, as well as taking the tablets as detailed above. A DEXA scan is a painless, non-invasive method of measuring the bone density, but you have to go to the Bristol Royal Infirmary for it as they have the latest machine, we will provide a taxi to take you there and back.
This is a national trial to try and find out the best length of time to give tamoxifen for in the treatment of breast cancer. We know that 5 years is better than 2 from several studies that have been done already, but we don't know if there is any benefit to giving it for longer than 5 years over the risk of possible long term side effects. The trial is therefore for women who have completed 5 years of tamoxifen and with their consent, after discussing it, they would randomly either carry on with tamoxifen or stop it. If you didn't want to take part in the trial you could decide for yourself whether you want to carry on with it or not. No other aspect of treatment or follow-up appointments is changed by being in this study.
There is a theory that breast cysts are caused by or made worse or more numerous by wearing a bra, because of making the tissue warmer and not allowing the skin to breath. We are therefore doing a study in our centre, funded by Channel 4! Taking women who have cysts already, we are counting and measuring them using an ultrasound machine and then getting them to not wear a bra for 3 months, measuring them again, and then wearing a bra for 3 months and measuring them again.
The research was presented on Channel 4 television and showed that whilst not wearing a bra did not reduce the number of cysts, in many women it it did reduce their breast pain, in some cases dramatically.
This a machine recently purchased from the USA, using funds raised by B.U.S.T., which uses a large needle and suction to remove most of a lump through just one insertion point. . It is done with local anaesthetic under ultrasound control in the clinic and therefore avoids an operation and large scar. It is hoped to buy a low dose digital x-ray table to use the mammotome under x-ray control as well in the near future.
If you are about to undergo surgery for breast cancer, part of this surgery involves removing lymph nodes (glands) from your armpit (axilla). The reasons for this will have been explained to you but the main reasons are to make sure that the disease hasn't spread to the lymph glands, because this helps us to decide on treatment after surgery and also to prevent problems in the armpit at a later stage if it had spread there.
One of the short term complications of this part of the operation is the formation of fluid (seroma) in the space left where the glands have been removed and occurs to some extent in up to a half of all people undergoing this type of surgery. This is because there is a cavity left with raw surfaces around it which exude fluid into the cavity which builds up over a few days, and doesn't tend to stop until the edges of the cavity have healed together inside. This rarely becomes a serious problem but can be a real nuisance for you as the swelling can be very uncomfortable and we usually have to drain the fluid using a needle and syringe to relieve the discomfort and allow the sides of the cavity to heal together. This usually needs to be done several times over a period of a week or two after the operation and you therefore need to come back to the breast clinic several times for this procedure until the fluid stops accumulating.
Several methods have been tried in the past to try and stop this fluid from accumulating. One of these is putting in a drain (tube) which is uncomfortable in itself, keeps you in hospital for a long time until the fluid stops draining (or a visit back to the clinic to remove it if you are sent home with the drain and bag) and may even prolong the fluid formation. Another is bandaging up the arm to the chest to close up the cavity but this leads to a stiff shoulder, sometimes permanently, after it is removed .
We have therefore devised a simple method to try and stop this problem which having tried out and perfected, we think works quite well. This involves a surgical technique to put in a stitch (suture) to close the cavity and tied tightly on the skin so t hat it can be easily removed after a week. So that it doesn't cut into the skin we tie it over a small piece of sterile foam rubber. This is all covered over by a dressing which can usually all stay in place until we see you in the clinic a week after the operation to discuss the results of what we found at your operation and then cut the stitch to remove it, which is painless. You will not have a drain in the axilla but will usually have a drain under the skin if you are having a mastectomy.
The purpose of this trial, is to scientifically prove that it works, by randomly, before the operation, choosing whether to put in this new stitch or to not put it in. We would then see you in the clinic after the operation in the same way as we normally do, at one week after and 2 weeks after the operation to check the wound and to see if any fluid has accumulated. In the same way as usual we would drain the fluid if it was necessary and record how many times this needed to be done and how much fluid was drained. We would also ask you about how comfortable it was and assess how well you were able to move your arm. In this way we would be able to measure the difference between the people who had the new technique and those who didn't.
This wouldn't involve any extra visits to the clinic and indeed we would hope that if you have the new technique, you would have fewer visits. We are running the trial for 4 months and will then analyse the results.
May 2004
You may have heard in the press that the preliminary results of this trial have been published. These have shown that women taking Tamoxifen then switching to Exemestane had fewer recurrences of their breast cancer than women who were taking Tamoxifen for the whole five years. We will be talking to you all individually about this but as most women in the study have finished or nearly finished the five years of treatment they would probably carry on with what they are taking. However the choice is theirs.
RANDOMISED DOUBLE-BLIND TRIAL IN POSTMENOPAUSAL WOMEN
WITH PRIMARY BREAST CANCER WHO HAVE RECEIVED ADJUVANT
TAMOXIFEN FOR 2-3 YEARS, COMPARING SUBSEQUENT ADJUVANT
EXEMESTANE TREATMENT WITH FURTHER TAMOXIFEN
STUDY NO: 96 0EXE 031 - C/ 13/96
AN INTER CO-OPERATIVE GROUP STUDY
PATIENT INFORMATION SHEET
Background
Until now Tamoxifen has been the standard treatment for patients with your type of breast cancer. Tamoxifen reduces the chances of your breast cancer recurring and the benefit is maintained for many years to come. You will have received Tamoxifen for a minimum of 2 years and up to 3 years plus one month, and will be familiar with its tolerability.
Pharmacia & Upjohn has developed a drug called Exemestane which works (like Tamoxifen) by reducing the amount of oestrogen in the body and slowing the growth of any microscopic cancer cells that may be left in the body.
You are being asked to take part in a study to find out if it is better after approximately 2-3 years of Tamoxifen to switch to Exemestane or simply continue with Tamoxifen for a total of 5 years. The best way to answer this question is to follow patients over time and seeing what degree of protection the change of treatment gives
Please note that your participation in this study is entirely voluntary and you may refuse to participate or withdraw at any time, without giving a reason and without affecting your future treatment and care. If you take such a decision during the study, please consult your doctor for alternative treatment(s), if you so wish.
Exemestane
Exemestane is a drug presently used in clinical research which has been tested in over 800 women with breast cancer. The studies so far show that the drug is well tolerated. At the dose to be used in this study (25mg every day), the most frequent side-effects (experienced in more than 20% of women) were hot flushes, nausea, dizziness and fatigue. Rarely, (in less than 20% of women) increased sweating, headache, sleeplessness, skin rash or anorexia were experienced. Very rarely (2% of women) experienced side effects were mild hair loss, dyspepsia, vomiting or abdominal pain. In most cases these side effects were mild to moderate in intensity.
Study design and drug dosage
The study you have been asked to take part in will include more than 2000 women all over the world. When you enter the study a procedure called randomisation will select you to either continue Tamoxifen for a total of 5 years or switch to Exemestane 25mg daily for the remaining years to complete the total of 5 years treatment. You will be monitored by your doctor as before, except that before entering the study you may need to undergo some additional tests such as a bone scan and liver ultrasound if your doctor thinks it necessary. You will be required to visit the hospital every 3 months during the first year, every 6 months during the second and third year and once a year from then on. At each visit you will be asked to answer a questionnaire about side-effects. Once a year you will be asked to have blood tests.
It is important that you do not take any hormone therapy while you are taking study medication. Your General Practitioner (and Gynaecologist if appropriate) will be informed that you are taking part in the study.
You will be given a bottle of capsules. One capsule should be taken every day. Please bring your bottle of capsules every time you attend for an appointment whether the bottle is empty or not. Neither you not your doctor will know which of the two treatments you have been given. However, if the need arises, your doctor will able to find out very quickly.
Please note that if further scientific data indicates a potential benefit in longer treatment with both drugs, you may be asked if you are willing to continue in the study at the end of the 5 year period.
If the study is stopped prematurely for any reason, you will be informed and further treatment, if any, will be discussed and decided with your doctor.
Foreseeable risks and Expected Benefit from this research.
If you are allocated to receive Exemestane you may experience the side effects already described for Exemestane, (i.e. hot flushes, nausea, dizziness and fatigue and more rarely increased sweating, sleeplessness, skin rash, anorexia, abdominal pain, headache and mild hair loss). If you are allocated to continue with Tamoxifen, you may experience the side effects of Tamoxifen, (i.e. hot flushes, swelling, itchiness, stomach upset, dizziness and skin rash, and more rarely there have been reports of headache, depression, fatigue, confusion, leg cramps and dry skin).
It is not possible to exactly define the expected benefits of switching from Tamoxifen to Exemestane at this stage as most of the studies have been carried out in women with more advanced disease. Preliminary data show that the drug is active in women with advanced breast cancer, and therefore there is a reasonable chance to obtain positive results in this study, although you might not benefit directly from the treatment.
Confidentiality
Your clinical data relevant for the study will be collected on forms and sent to the co-ordinating centre and/or Pharmacia & Upjohn. Your personal data will be kept strictly confidential. However the following will have access to your records for verification of data and clinical study procedures, without violating the confidentiality of your data, and as permitted by the applicable laws and regulations.
· Auditor(s) of the study
· Institutional Review Board! Ethics Committee, or Regulatory Health Authorities,
Records identifying yourself will not be made publicly available, and in the event of any publications of the results, your identity will remain confidential.
By giving your consent to participating in the study by means of the enclosed consent form you authorise such access.
Indemnity
Pharmacia & Upjohn does not believe that you will suffer injury by participating in this trial. You should know, however that in the event that you do Pharmacia & Upjohn has entered into an agreement with [the authority] to abide by the Association of British Pharmaceutical Industry (ABPI) Guidelines. Broadly speaking the ABPI Guidelines recommend that Pharmacia & Upjohn, without legal commitment, should compensate you without you having to prove that it is negligent in cases where it is likely that such injury results from the administration of any new drug or any such procedure carried out in accordance with the protocol for the study. Pharmacia & Upjohn will not compensate you where such injury results from any procedure carried out not in accordance with the protocol for the study. Your right at law to claim compensation for injury where you can prove negligence is not affected.
This study conforms to the European Guidelines of Good Clinical Practice and has been considered and approved by the independent Multi Centre Research Ethics Committee and the independent Local Research Ethics Committee.
Information and further advice
You will be informed as soon as possible if information becomes available that might influence your decision to continue participating in the study.
If you wish to have further advice, you can ask your doctor before you enter the study or at any point during follow-up. It is extremely important that any concern is answered before you start the study. The names of your doctor and another person that might give you advice are as follows:
Doctor Mr S. Cawthorn
Nurse Mrs. J Barker or Ms. L. Jones
If you decide to take part in the study, you will receive, for your own record, a copy of this information sheet as well as a copy of the signed informed consent.
This a study being caried out by Ms. de Costello, our research registrar, to find out if the prolactin receptor in breast cancer cells is affected by a short period of treatment with Tamoxifen. It involves taking a tissue sample by needle biopsy at diagnosis and then again after a week of tamoxifen treatment. These are stored in liquid nitrogen and then analysed by her at the University of Bristol.
TEAM
A randomised comparison of 5 years adjuvant Exemestane versus 5 years adjuvant Tamoxifen treatment of postmenopausal women with early breast cancer : a research study.
___________________________________________________________________
This sheet provides some written information about a clinical research trial, and is intended to supplement your discussions about the trial with your doctor and nurses. Having read it you may well have further questions, and these should be discussed with your consultant or one of the doctors on the team.
___________________________________________________________________
You have recently had surgical treatment for your breast cancer and this has now been examined by the pathologist. The breast cancer has been removed and lymph glands under the arm have also been examined. The surgery has successfully removed all visible cancer. We know that despite apparently successful surgery there is a possibility of the breast cancer reoccurring in the future. We cannot tell if this will happen in your case but for many women we can reduce the risk of a recurrence using hormonal treatments. Your breast cancer shows features indicating that hormonal treatment should be recommended for you. This trial is trying to find out if a new form of hormonal drug treatment called exemestane is any better than the current standard hormone treatment with a drug called tamoxifen.
What is tamoxifen?
Tamoxifen is a drug taken once a day which prevents the natural hormone oestrogen from encouraging breast cancer cells to grow by blocking the effects of oestrogen in cells. When taken after surgery for breast cancer we know it reduces the risk of a breast cancer reoccurrence. Breast cancer reoccurrence can happen near the original cancer (local relapse) or at distant sites such as bones or liver (distant relapse). Tamoxifen reduces the risk of this happening. We know that tamoxifen should be taken for at least 5 years to gain maximum benefit. Tamoxifen is a very valuable treatment and is saving many lives when used after breast cancer surgery. Tamoxifen given after surgery is a standard treatment for women with oestrogen receptor positive breast cancer and is an effective way to reduce but not eliminate the risk of reoccurrence. Tamoxifen can cause a very long list of side effects but the commonest side effects are menopausal type hot flushes. Tamoxifen also helps maintain bone strength. Although some women experience vaginal discharge or even vaginal bleeding, this is uncommon and you should always tell your doctor if this happens. Tamoxifen increases the risk of developing cancer of the womb lining (endometrial cancer) Tamoxifen also increases the risk of blood clots in the legs (deep vein thrombosis) and blood clots on the lung (pulmonary embolus). These increased risks are very small and are greatly outweighed by the benefits of taking tamoxifen.
What is Exemestane?
Exemestane is a new drug that is currently used to treat breast cancer after tamoxifen has stopped working in patients with relapsed or advanced breast cancer. Exemestane is being compared to tamoxifen as treatment for advanced breast cancer and early indications show that exemestane works well in this situation. We do not have any information on how well exemestane works when given as an adjuvant therapy after breast cancer surgery. Exemestane works by preventing the formation of oestrogen. It only works in women who have gone through the change and are no longer having menstrual periods (postmenopausal women). Exemestane is taken orally once per day. Exemestane also has a long list of possible side effects including hot flushes, nausea and fatigue. For most people these side effects are mild. We do not know if exemestane is a better hormone treatment to use after surgery and the TEAM study is designed to find out if exemestane is better than tamoxifen or not.
Differences between tamoxifen and exemestane
|
Tamoxifen |
Exemestane |
|
|
Mechanism |
Blocks oestrogen action |
Blocks oestrogen production |
|
Effectiveness after surgery |
Reduces risk of relapse by about 40% if taken for 5 years |
Unknown |
|
Effectiveness after recurrence |
Can work well but eventually stops working. Limited information sugests that exemestane could be better (ongoing research) |
Also effective but also eventually stops working. Effective after tamoxifen failure. |
|
Main Side effect |
Hot flushes |
Hot flushes |
|
Other recognised side effects |
Sweating, Postmenopausal bleeding/discharge nausea dizziness |
Nausea, sweating fatigue dizziness |
|
Bone density |
Preserves bone density |
unknown |
|
Cholesterol |
reduced |
unchanged |
|
Blood clots |
Increased risk (small) |
unknown |
|
Endometrial (womb) cancer |
An increased risk of this rare cancer is far outweighed by benefit |
Unknown but not expected to increase risk |
What happens if I go in the study?
I you agree to take part in this study we will ask you to sign a consent form and we will then register your details with the trial centre and check that you are suitable for the trial. The trial centre will allocate your treatment which will either be exemestane or tamoxifen. Treatment is allocated at random so there is an equal chance of being allocated to tamoxifen or exemestane. We will ask you to take this medication once daily for 5 years. After 5 years we will review your treatment. We will see you in a follow up clinic on a regular basis and check on how you are getting on. We will record any adverse medical events and check you are still taking your medication. We do not usually need any extra tests for this study but we need to check that you have had a recent chest X-ray and blood test results are satisfactory (tests from around the time of surgery or chemotherapy are usually sufficient). In some cases we need a blood test to confirm that you are postmenopausal.
Quality of life study
As well as being interested in how effective these two treatments are we are also interested in how the treatment affects how you feel. We would like to ask you to complete a questionnaire about current symptoms and well being before you have your treatment allocated. We will also ask you to complete a similar questionaire 3 months after starting treatment and again after 12 months. These questionaires will be sent to you by post. You do not have to fill in these forms if you do not wish to and can still take part in the rest of the study.
Extra research on your cancer tissue
If you are entered into the TEAM study we would like to do some further research on your breast cancer tissue. With your permission we would like to send a part of your breast cancer to a central laboratory where we can analyse the tissue for some special molecular features. One test we would like to do is the HER-2 test which might be important in predicting the effectiveness of hormone treatments. This information will be sent back to your hospital and may be helpful in future if you need further treatment and is already tested routinely in a few hospitals. We would also like to retain a tiny piece of your breast cancer tissue and use this in the future for research to help understand more about breast cancer and hormone treatments. After removing this sample we will return the rest of the cancer tissue to your hospital. The tissue would be stored in a way such that it would not be identifiable. We do not yet know precisely what molecular markers or genes we will be looking at but the tissue we collect could be analysed for the presence of up to three hundred different proteins and genes inside the breast cancer cells. We will be looking at proteins or genes that we think might help improve our ability to treat breast cancer and in particular to help predict if some cancers are best treated with different types of hormone therapy. Because the samples are not identifiable results of this research will have no influence on your treatment but doctors taking part in the study will be informed of the general findings of this research. If you do not want your tissue used in this way please tell us. You can still take part in the trial.
Tumour material collected during this study will not be sold to third parties or used for commercial gain. Intellectual property rights that may arise as a result of findings from this research could be exploited commercially. The rights to any intellectual property will reside with the investigators.
What we will do with information about you
With your agreement, your GP and any other doctors who may treat you will be informed that you are taking part in this trial. All information collected about you for this study is strictly confidential and will be covered under the Data Protection Act. With your permission, your doctor will give us your name when s/he telephones to register you on the study. However, all other information about you which leaves the hospital will refer to you only by a unique trial number allocated to you, or by your initials. All information will be securely stored at the trials office on paper and electronically in an encoded format. We may need to check clinical information from your medical records. This will be done by clinical staff or designated trials office personnel, and possibly by responsible individuals from the pharmaceutical companies mentioned above, or from government regulatory agencies. Under no circumstances will you be identified in any way in any report arising from the trial. The results of the research may be published in medical journals, but this will not include any reference to individual patients. Your medical records may be reviewed by the trial monitor or authorised persons from regulatory bodies, in which case your confidentiality will be maintained at all times.
If during the course of this trial we become aware of any new information which may have a bearing on your treatment or continued participation in this study we will inform you and invite you to discuss the implications of this information.
What about other treatments?
Depending on your individual circumstances you may be recommended for other treatment such as radiotherapy or chemotherapy. These treatments will form part of your normal treatment and will not be effected by taking part in the trial. Many doctors like to start hormone treatment after chemotherapy treatment is completed so if you are having chemotherapy your hormone treatment will not start until your chemotherapy has been completed.
What if I do not want to go into the study?
If you do not want to take part in the study we will still recommend hormone therapy and recommend you are treated with tamoxifen as exemestane is not currently available for this indication outside the study.
Participation in this study is entirely voluntary. If you decide not to participate, this will not affect your routine treatment in any way. Also if you decide to participate, then change your mind at a later date, you may withdraw from the study. This will not affect your routine treatment or your relationship with your doctor.
Compensation
The TEAM study is a clinician-initiated and clinician-led study. The study is being run by the Cancer Research Campaign Trials Office in Birmingham and by other research groups in Holland France and The USA. Financial support is being provided by Pharmacia Corporation the pharmaceutical company that makes exemestane. Neither the CRC Trials Unit nor the supporting pharmaceutical company hold insurance against claims for compensation for injury caused by participation in this trial and they cannot offer any indemnity. However, NHS Trust and Non-Trust Hospitals have a duty of care to patients treated, whether or not the patient is taking part in a clinical trial. Compensation is only available in the event of clinical negligence being proven. There are no specific arrangements for compensation made in respect of any serious adverse events occurring through your participation in this study, whether side effects listed above, or others as yet unforeseen.
______________________________________________________________________
Thank you for reading this information leaflet If you have problems or questions now or during your treatment, please do not hesitate to get in touch. Please use one of the following contact numbers.
Dr Mr. S.J. Cawthorn_______________________________Tel____0117 9753752
Research Nurse Julie Davidson_______________________________Tel____0117 9753752
A Regional research ethics committee and your local
research ethics committee have approved this study
Title of study: A prospective study of breast cancer treatment outcomes.
INFORMATION SHEET FOR PATIENTS
Introduction
You are being invited to take part in a research study. Before you decide it is important for you to understand why the research is being done and what it will involve. Please take time to read the following information carefully and discuss it with friends, relatives and your GP if you wish. Ask your breast care nurse or the national study co-ordinator if there is anything you do not understand or if you would like more information. Take time to decide whether or not you wish to take part. Thank you for taking the time to read this information.
What is the purpose of the study?
Most breast cancer occurs by chance and usually with increasing age. Breast cancer is less common at young ages and this is why you have been asked to join this study. A small percentage of breast cancers arise because of a genetic predisposition (hereditary) These hereditary breast cancers are uncommon but may behave in a different way to cancers arising by chance (sporadic cancers). We are trying to learn more about any differences in the effect of treatment for hereditary compared to sporadic breast cancer.
Why have I been chosen?
All women in participating centers across the UK who have been diagnosed with breast cancer at 40 years of age or younger are being invited to take part in the study.
Do I have to take part?
It is up to you to decide whether or not to take part in the research study. You can take up to a year to decide. If you decide to take part you should keep this information sheet in a safe place and you will be asked to sign a consent form. You may withdraw from the study at any time without giving a reason and this will not affect your routine medical care in any way.
What would I have to do?
We would like you to fill in a questionnaire about your family history and a few other simple questions.
We will also ask your hospital doctors to answer some questions about your treatment and request an update on your progress from time to time from the hospital or your GP.
If you agree, you will be asked to provide a blood sample for future genetic analysis.
If you agree we will ask your doctor for small samples of the tissue removed at your operation to help us to understand why cancers sometimes behave in different ways.
Confidentiality
The information you supply and details about your treatment from your hospital records will be stored at the co-ordinating centre in Southampton, England. The data will be completely confidential and will not be disclosed to anyone, not even other members of your family or your doctor. We will inform your doctor that you have been enrolled in the study.
Are there any results from the blood tests?
No, there will be no individual results. Although genetic analysis will eventually be carried out towards the end of the study period this will be done in the research laboratory. We cannot give results from research tests as these tests are not carried out under the same rigorous quality assurance that applies in diagnostic genetics services. If you and your doctor feel a genetic test might be helpful because of a strong family history of cancer you can be referred to your nearest genetic centre. The national study co-ordinator would be happy to advise informally about whether this might be a helpful course of action and you could discuss this with your GP or your hospital specialist. If at any time you want to pursue formal genetic analysis we will be able to provide information regarding what testing has been completed to your local genetics service so that formal testing in the diagnostic laboratory may be easier.
What if new information becomes available?
The study plans to follow 2,000 women over 20 years. No individual results will be available directly to study participants at any time to protect confidentiality. The results of analyses on all participants together carried out at various times during the study will be made available to all participating hospital specialists and if at any time the results indicate that alternative or additional treatment would be appropriate your hospital specialist will be able to discuss this with you.
If I have any questions, whom can I ask?
Your local study co-ordinator is:-
Dr Peter Simmonds
Consultant in Medical Oncology
Cancer Care
Royal South Hants Hospital
Telephone: 023 8079 2975
The Regional study co-ordinator is:-
Dr Diana M Eccles
Consultant in Cancer Genetics
Wessex Clinical Genetics Service
Princess Ann Hospital
Southampton SO16 5YA
Telephone: 023 8079 8537
One of the problems with removing the lymph nodes (glands) from the axilla (armpit), as part of the surgery for breast cancer, is that fluid can build up in the cavity left where the surgery was performed (seroma). This can be quite a nuisance and uncomfortable involving extra visits back to the clinic to have it drained with a needle and syringe.
This study, run by the manufacturer (Baxter), is to use a special substance which aims to seal the ends of the tiny cut vessels where the fluid is thought to come from, and also stick together the sides of the cavity. Patients will be randomised either to have the treatment or not and it will be sprayed into the cavity at the time of the operation. Careful measurements will then be made of the amount of fluid afterwards to see if it makes any difference.
This trial is to randomly do a Magnetic Resonance Scan before breast cancer surgery or not. The aim is to try and reduce the re-operation rate. The reason why further operations sometimes have to be done is that the cancer is sometimes more extensive than physical examination, mammography or ultrasound suggests and when the specimen is examined by the pathologist after the operation, it is found that the cancer goes right up to the edge of the specimen and further surgery, sometimes a mastectomy is required to make sure that all the cancer is removed. Magnetic Resonance imaging (MRI) is a very sensitive method of detecting cancer and it is hoped that it will show the true extent of the cancer.
Radiotherapy is used after an operation for breast cancer in most patients and has a major effect in stopping the breast cancer coming back in the area where the operation was done. However it is not without its side effects, such as damage to the skin, heart and lungs. For this reason, many people think that the benefit may be outweighed by this damage in older patients. This trial is to take women over the age of 65 and randomly give radiotherapy or not and see if it makes any difference in the long run.
Patient Information Sheet
You have recently been diagnosed with early breast cancer which has been completely removed by surgery. An anti-cancer drug, often Tamoxifen, will also be given as part of your treatment for five years and reduces the risk of the cancer returning. Another therapy which is currently routinely offered is radiotherapy to the breast. The radiotherapy is given to the affected breast and it is thought that it reduces the chances of the cancer coming back within the breast.
There is some evidence that in older women radiotherapy may not always be needed and, like many treatments, it also has both short and long term side effects. Apart from the evidence that radiotherapy might not be needed in older women, it may not be required in women such as yourself who are at low risk of their cancer returning because your cancer: (1) has been removed with a generous margin of normal breast tissue; (2) did not have any bad features when examined by the pathologist under the microscope; and (3) has not spread to the lymph glands under your arm.
On this basis we would like to ask you to take part in our trial to help us decide whether radiotherapy is necessary for women with your particular type of cancer. Your specialist has indicated that he thinks that you are suitable to take part in the PRIME trial.
The trial will involve 240 women who will each be followed up for 5 years. If you agree to take part you will be reviewed by a nurse either at home or in the clinic whichever is most convenient to you and you will be asked to complete a questionnaire. To determine whether or not you will receive radiotherapy, your specialist will telephone a central office which runs the PRIME trial, to enter you in the trial. The trial office will check some details about you, your disease and the treatment you have been prescribed and will use a computer to allocate your treatment. You will have the same chance of receiving radiotherapy as you will of not receiving it. Your specialist will be told whether you have been allocated a course of radiotherapy.
The nurse will arrange three visits over 15 months and on each visit you will again be asked to complete a questionnaire which will monitor how you are coping with your condition and how you are feeling and managing at home. In addition, a short version of the questionnaire will be sent to you by post for self-completion at 3 and 5 years after surgery. You will also be seen three times during the first 15 months in hospital clinics for a routine examination by your specialist. This is to check that the cancer remains under control. It is also hoped to arrange a photograph of your breasts at two of your clinic visits. This will allow us to look at changes in the breast which have occurred as a result of your treatment. At the end of the trial you will continue to be reviewed by your specialist on a regular basis. A mammogram will be done at one year after your surgery. During the trial you will be asked to keep a record of all health and social services that you received.
If you decide not to take part in the trial you will receive the usual high standard treatment that is currently employed for patients with early breast cancer. You will be offered radiotherapy and be followed up at the surgical outpatient clinics in the usual way.
Radiotherapy to the breast is usually carried out over five to six weeks, usually as an outpatient. For the first attendance a series of breast measurements are taken to plan your further treatment. The radiotherapy is normally given to the breast in a small dose each day. Treatments are given for 10 to 15 minutes per day on weekdays. No treatment is given over the weekends. Four to five additional daily treatments may also be given to the site where the original cancer was excised. This extra treatment is normally given in the week following the initial course of radiotherapy to the whole breast.
Like all treatments there may be side effects with radiotherapy. Radiotherapy may cause skin reactions leading to breast tenderness and itching. These develop in the latter part of the course of radiotherapy and usually settle within one month of the treatment finishing. Breast pain, which is usually mild and intermittent, commonly occurs up to two years post-radiotherapy, but is less troublesome thereafter. Rarely radiotherapy may cause inflammation of the lung causing shortness of breath or it may cause ribs to fracture.
The possible risk of not being given radiotherapy is that there may be a slightly higher chance of the breast cancer coming back compared to women who have received radiotherapy. However, in women aged 65 or more, we know that the chance of the breast cancer returning is lower than in younger women. Also, from our knowledge of the results of your surgery and the type of your particular tumour we believe that the risk of your cancer coming back in the treated breast is much lower than average. If your cancer did recur in your breast further surgery would be considered.
Whether or not you take part in the trial you will receive the highest standards of care. The information that we get from the trial will help us gain knowledge about the best way of treating breast cancer. It will help us to measure the advantages and disadvantages of radiotherapy for women aged 65 or more who are diagnosed with early breast cancer, using assessments that are relevant to them.
No, taking part is voluntary. If you would prefer not to take part you do not have to give a reason. Your doctor would not be upset and your treatment would not be affected. If you take part but later change your mind you can withdraw from the trial without hindrance or detriment to your future treatment. We will give you a copy of your consent form to keep.
We would want to inform your GP that you are taking part with your permission and will send him/her a copy of your consent form.
All the trial data will be confidential to the research team. You will not be identified in any published results.
The research sister for the trial will contact you in a day or so. She can answer any questions and you can let her know if you are interested in taking part.
Thank you very much for considering taking part in our research. Please discuss this information with your family, friends or GP if you wish.
Local investigator: Mr S J Cawthorn/Mr A J Sahu
Breast Cancer Trials Lead Clinician: Dr. Mike Shere
Research Nurse: Catharine Dawe
If you would like to obtain independent advice about this research you may contact:
CancerBACUP Tel freephone 0808 800 1234