Trials & Triumphs

Trials & Triumphs

Strategies for treatment now involve many alternatives or complements to drug therapy

Words: Jenni Scarlet and Ian campbell

When we think of treatments for breast cancer it is easy to think “drugs”, but breast cancer trials include screening for the diagnosis of cancer, new radiotherapy or surgery techniques, supportive care programmes, complementary therapies or even exercise.  Clinical trials are important as they help establish whether treatment options are safe and effective. Common medications that we take for granted in our lives, such as paracetamol and antibiotics, have all been tested in clinical trials.
In this article we briefly outline a few interesting trial results, trials currently “open” and enrolling New Zealand women, and upcoming research.
Research Results
Herceptin reduces death rate by 39%
New Zealand women are taking part in international trials continuing to test the long term benefits and side effects of Herceptin after standard chemotherapy. Two large American trials (the NCCTG N9831 and NSABP B-31) have recently published four-year follow-up results. These show that there continues to be a highly significant improvement in disease free survival and a 39 percent reduction in the death rate with the addition of Herceptin to chemotherapy for women with HER 2 positive breast cancer.
We are awaiting further results, due 2012, from the HERA (HERceptin Adjuvant) trial, another large international trial that is testing one versus two years treatment with Herceptin. Next year we also anticipate first results from the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (or ALTTO) trial – another worldwide trial comparing Herceptin with the broader spectrum anti-HER2 oral tablet called Lapatinib (Tykerb). The ALTTO study is comparing these two drugs separately, sequentially, and in combination. The treatment was given over one year.
Exercise is medicine!
There are a number of worldwide studies showing that exercise may be a very important factor in reducing breast cancer recurrence after diagnosis. Once cancer survivors have completed treatment there is a risk of cancer return/recurrence, other chronic diseases occurring (e.g. heart disease, diabetes, stroke) and late effects of treatment (e.g. fatigue, depression, anxiety, weight gain, poor body image, sleeping difficulties, and joint aches). There are many studies that prove that healthy lifestyle behaviors help overcome late treatment concerns, improve quality of life and reduce chronic illness in cancer survivors.
One such clinical trial is an Australian based research which has evaluated a healthy lifestyle programme called the ENRICH (Exercise and Nutrition Routine Improving Cancer Health) programme. This was developed by the University of Newcastle and Hunter Institute of Medical Research, New South Wales. The ENRICH programme involved six face to face coaching sessions over eight weeks with an exercise physiologist and dietitian.  
The ENRICH programme showed that moderate activity (e.g. power walking for one hour three-four times per week) along with healthy eating over a sustained time can reduce side effects/health concerns related to a cancer diagnosis and treatment and improve quality of life.
Some clinical trials currently underway in New Zealand
Extending endocrine treatment beyond five years
The standard length of time that hormonal or endocrine treatment is taken (daily) is five years. However, after reaching the end of treatment there is still an ongoing risk for women of developing another breast cancer, or the original breast cancer returning in another part of the body. For these women, the chance of this happening can be 1 in 50 (2 percent) each year or more – this risk translates to 1 in 5 over 10 years.  Long term management of early breast cancer after completion of five years of endocrine treatment, has until recently, been confined to annual checks and mammography.  
Research has shown that extending hormone or endocrine treatment with an aromatase inhibitor, after five years of tamoxifen, improves breast cancer outcomes. It is not certain if this is the case after five years of treatment including an aromatase inhibitor (e.g. letrozole). 
the LATER or  “Later adjuvant Aromatase inhibitor Therapy for post-menopausal women with Endocrine Responsive breast cancer” study is finding out whether taking the drug letrozole a year or more after finishing five years treatment with endocrine therapy (e.g. tamoxifen) can prevent or delay breast cancer recurring in post-menopausal women. This study is coordinated by the ANZBCTG and is currently only available to women in the Waikato area. For further information please phone 0800 770 119.
the SOLE or “Study Of Letrozole Extension” trial is investigating five years continuous letrozole versus nine months with a three month break each year,  for post-menopausal women with lymph node positive early breast cancer. There is evidence to suggest that having a break from oestrogen deprivation may re-sensitise a breast cancer to this treatment.  This study is also coordinated by the ANZBCTG and is currently available to women in the Waikato and Canterbury areas. For further information please phone 0800 804 591. 
Research continues to answer questions about sentinel lymph node biopsy
The status of the axillary or armpit lymph nodes remains the single most important indicator of outcome for women with breast cancer and helps predict the need for further treatment (e.g. chemo or radiotherapy). Traditionally, axillary node status has been determined by the removal of most of the nodes (axillary clearance). This operation may lead to arm swelling (lymphoedema), pain, some abnormal skin sensation or shoulder stiffness. 
Previous research has established that for women with small single (unifocal) breast cancers, the surgical removal of the “sentinel” nodes (i.e. the first lymph node/s draining from the region of the breast cancer) provides accurate information as to whether axillary nodes are involved with cancer or not, and reduces risk of side effects from surgery. Sentinel node based management in this setting is also proven to have cancer outcomes as good as axillary clearance.
Controversial results were published in 2010 from an American sentinel node biopsy study (the American College of Surgeons Oncology Group Trial Z0011) that claimed to obviate the need for completion axillary clearance for women with one or two positive sentinel nodes. There were a large number of limitations to this study that highlight the importance of completing the Society of Breast Surgeons ANZ sentinel node biopsy trial (SNAC 2) for women with larger or multi-focal tumours and cancers of more aggressive biological type. This is a very important trial because very few women with larger tumours, and none with multi-focal tumours, have been included in other international trials of sentinel node based management. We need to very carefully evaluate the safe limits of this reduced surgery to the axilla. North Shore, Waikato, New Plymouth, Christchurch and Tauranga Hospitals are centres for this research.
Looking into the future – research in the pipeline
Post-operative radiotherapy omission in selected patients
For women who undergo breast conservation surgery for early breast cancer, radiotherapy treatment is usually given to the affected breast after surgery, to reduce the risk of breast cancer returning in that breast.
Radiotherapy treatment requires daily treatment over four or five weeks, and receiving radiotherapy treatment can lead to some side effects such as fatigue, skin redness and discomfort (in the short term), and discomfort in the breast, thickening of breast tissue and very occasionally bone, lung and heart problems. Because treatment machines are only available at six major centres in New Zealand, many women have to travel significant distances away from home, family, friends and normal supports to have this treatment.
To determine whether radiotherapy treatment can be safely avoided in women whose risk of local recurrence is very low, researchers from the ANZ Breast Cancer Trials Group have developed a new pilot clinical trial called PROSPECT. This trial will use magnetic resonance imaging (MRI) scanning to help select women for whom radiotherapy may be avoided because their risk of cancer recurring in the breast is low.
If it is found that radiotherapy can be omitted without compromising local recurrence, this would result in a major saving in terms of both human and financial cost.
Can we use the arm that has undergone lymph node surgery for chemotherapy?
Health professionals involved in breast cancer care mostly advise women to avoid having venopuncture (e.g. insertion of IV lines or blood samples) into the arm that has had armpit lymph nodes removed.  This has been thought to reduce the risk of lymphoedema or arm swelling (one of the most feared complications of surgery) with intravenous chemotherapy.
Many women may run out of veins in the non-operated arm and choose to use a central venous access device (CVAD) inserted. The use of a CVAD (e.g. a portacath) isn’t without risk and potential complications include infection, thrombosis (blood clots), catheter blockage, catheter migration (travelling) and chest scarring.
However, several small studies show no increased risk of lymphoedema with venopuncture, or blood pressure, taken on the operated arm. A New Zealand-led protocol is being developed to test the safety of using venous access (for chemotherapy) in the arm that has undergone lymph node surgery.
Glucosamine for joint aches
Joint aches, or arthralgia, is one of the most common side effects related to taking aromatase inhibitor drugs, e.g. letrozole. Around one third of women develop some degree of arthralgia on an aromatase inhibitor and may stop the drug due to this side effect. International research is being planned to test the use of glucosamine sulphate for women taking letrozole for their breast cancer. Glucosamine is a natural compound found in cartilage and promoted to treat other joint problems such as osteoarthritis.
PARP inhibitors
Exciting new drugs for women who carry the breast cancer (BRCA) genes are now being tested in a number of trials around the world. PARP is an important molecule involved in DNA repair.
In conclusion
These are just some of the current and upcoming clinical trials available in New Zealand. For women undergoing breast cancer treatment discussions, a cancer specialist may raise the option of a clinical trial that includes a new treatment suitable for an individual woman’s situation. Alternatively, women can ask their doctors whether they know of any relevant trials available. A number of studies show that women in well conducted trials tend to do better. Part of this may be because doctors involved in trials tend to be most up-to-date with the latest developments in breast cancer care and treatments.
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