International experts issue plea for better research and education for advanced breast cancer

Breast cancer experts around the world have issued a plea to researchers, academics, drug companies, funders and advocates to carry out high quality research and clinical trials for advanced breast cancer, a disease which is almost always fatal and for which there are many unanswered questions.

In the latest international consensus guidelines for the management of advanced breast cancer, published simultaneously in the leading cancer journals The Breast and Annals of Oncology [1], the experts say that further research and clinical trials are “urgently needed” to find the best treatments for:

– patients with breast cancer that has spread to the liver, or the space around the lungs (pleural cavity) or the skin;
– patients with HER2 positive advanced breast cancer who relapse during or shortly after adjuvant treatment with trastuzumab;
– patients with stage IV disease (where the cancer has spread to other parts of the body), regarding whether or not surgery to remove the primary tumour improves survival and quality of life;
– men with advanced breast cancer who need to receive aromatase inhibitors (such as anastrozole, exemestane, letrozole);

In addition, there are a number of other areas in advanced breast cancer that require more and better research and international, multidisciplinary clinical trials. There also needs to be greater effort made to educate health professionals to apply existing knowledge in their treatment of breast cancer patients.

Advanced breast cancer is defined as cancer that has spread beyond the site of the first (primary) tumour to other sites either within the same breast such as the skin, chest wall and some lymph nodes (locally advanced) or other parts of the body (metastatic cancer). There are no reliable figures for the numbers of women (and men) living with advanced breast cancer. However, there are over 1.6 million new cases of breast cancer a year in the world and 0.5 million deaths. About 20% of cases are either locally advanced or have spread to other parts of the body (metastasised) at diagnosis, and these figures reach almost 60% in developing countries. A third of all early breast cancer cases will become metastatic even with the best care, and the average overall survival for these patients is around two to three years.

Professor Fatima Cardoso, lead author and co-chair of these latest international guidelines and Director of the Breast Unit of the Champalimaud Cancer Centre in Lisbon, Portugal, said: “Our plea is for strong commitment from everyone involved – academia, the pharmaceutical industry, funders and advocacy groups – to develop well-designed, high quality, multidisciplinary trials for advanced breast cancer. This is of critical importance as many questions are still unanswered relating to managements strategies, better drugs and drug use, and individualising treatments so that they are specific to a particular patient and their tumour.”

She said that, at present, there was a problem with the way new treatments were tested in the clinic. Initially, researchers would investigate a treatment in patients with metastatic disease but once there were enough data on efficacy and safety, attention shifted quickly to further testing in patients with early breast cancer, leaving little if any research continuing in advanced breast cancer patients.

“In one sense this is correct because we need to provide the highest number of patients as early as possible with the new drugs. But if we do that all the time, we will leave the metastatic patients without any good knowledge of how to treat them,” said Prof Cardoso. “For instance, it took us ten years to understand how to use trastuzumab in metastatic patients, and that we should continue to use it beyond disease progression in these patients. Even though we recommend that it should continue to be used, the level of evidence on which we base that recommendation is lower than usual because there were no good trials performed for that because everyone was moving to examining its use in early breast cancer. The same thing happened for paclitaxel, which we use all the time. It took us 15 years to understand the best dose and schedule in the metastatic setting, again because everyone moved to investigating it in the early setting without answering the important questions in the metastatic setting.

“So this is what we plead for: that yes, once you have enough data, move to the early setting, but remain and keep investing some effort in understanding how best to treat the advanced breast cancer patient. They are one third of all breast cancer patients and they deserve that.”

These latest international guidelines were formulated by a group of international experts meeting at the second International Consensus Guidelines Conference on Advanced Breast Cancer (ABC) in Lisbon (Portugal) in November last year. The conference was created by the European School of Oncology (ESO) to improve outcomes for patients with advanced breast cancer and was attended by 1100 participants from 71 countries. The ABC2 consensus guidelines contain several updates on the 2011 ABC1 guidelines and new areas of focus.

One new focus is on inoperable, locally advanced breast cancer (LABC). LABC may often have lymph node involvement, but no metastases in other parts of the body, and often the primary tumour may be too large to be removed surgically. LABC occurs in one-fifth of breast cancer patients worldwide (in 15% of breast cancer patients in developed countries, but in up to 50-60% in developing countries), has a bad prognosis but is potentially curable. “These patients are half way between early and metastatic disease, and so nobody really knows where they fit and the best way to treat them. So we decided to include them in advanced breast cancer and these are a set of new guidelines for inoperable LABC. There are very few clinical trials providing data for the best treatment of this disease,” said Prof Cardoso.

Guidelines that have been updated from ABC1 include new recommendations for triple negative breast cancer (breast cancer that has no receptors for the hormones oestrogen and progesterone and the HER2 protein), HER2 positive disease, and hormone receptor positive disease. The new guidelines reflect information that has emerged from clinical trials on two new drugs pertuzumab and trastuzumab emtansine (TDM1) for HER2 positive disease, and everolimus for hormone receptor positive disease.

Co-chair of ABC2, Dr Eric Winer, director of breast oncology at the Dana-Farber Cancer Institute (Boston, USA), said: “We have made several important general recommendations in the ABC2 guidelines. We emphasise the importance of outstanding nursing care and the critical nature of their involvement with the multidisciplinary team. Nurses involved in the longitudinal care of breast cancer patients should have oncology training. Among other roles, the nurse often helps navigate the medical system for the patient.

“We also address issues related to access to care, in particular, to palliative care. Such treatment should be available to all patients with advanced breast cancer from the very beginning of their illness. Patients need to have access to medication for good pain control and for all the symptoms relating to the disease and treatment. There are many patients with advanced breast cancer who are suffering needlessly.

“Finally, we emphasise that age alone should not determine the type and intensity of treatment. Treatment should not be withheld just because a patient is elderly; nor should young patients be over-treated.”

The experts highlight the fact that there are huge variations between and within countries on the treatment of advanced breast cancer. “We hope that carefully developed, high-quality guidelines, such as the ABC2 guidelines, will help to improve the care and long-term outcomes of advanced breast cancer patients worldwide,” said Prof Cardoso.



[1] “ESO-ESMO 2nd international consensus guidelines for advance breast cancer (ABC2)”, by F. Cardoso et al. The Breast, doi: 10.1016/j.breast.2014.08.009 and Annals of Oncology, doi:10.1093/annonc/mdu385
The Breast – paper is free access at:
Annals of Oncology – paper is free access at:

[2] The ABC2 international consensus guidelines have been developed in a joint effort by ESO and ESMO (European Society for Medical Oncology).