Clinical trials that evaluate hormone-dependent advanced breast cancer (ABC) should be more inclusive and allow pre-menopausal women to participate, according to an expert panel from the Advanced Breast Cancer Fourth International Consensus Conference (ABC 4) in Lisbon, Portugal.
The intention of the international consensus conference is to develop and update guidelines for the management of patients with ABC based on evidence-based medicine, as well as the experience of more than 1,300 healthcare professionals and patient advocates from more than 88 countries.
ABC is defined as cancer that has spread beyond the site of the primary tumor to other sites either within the same region, 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 number of women and men living with advanced breast cancer, but more than 1.6 million new cases of breast cancer are diagnosed worldwide each year, with about 500,000 patients dying from the disease. About 20% of cases are either locally advanced or have metastasized at diagnosis, with numbers reaching 60% to 80% in developing countries. One-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.
The panel believes that the majority of clinical trials for hormone-dependent ABC either explicitly exclude pre-menopausal women, or deter them with unnecessarily restrictive inclusion criteria. Updated guidelines for treating ABC request that trials be designed to enable enrollment of both pre- and post-menopausal women.
“At present, not only are younger women denied the opportunity to take part in clinical trials, but also clinicians lack the evidence on how best to treat these patients who have advanced breast cancer with limited therapies available,” stated Fatima Cardoso, MD, director of the Breast Unit of the Champalimaud Cancer Centre in Lisbon, Portugal, and Chair of ABC 4.
Dr. Cardoso adds that around one-third of advanced breast cancers are diagnosed in pre-menopausal women. Most are estrogen receptor (ER)-positive, in which tumor growth is fueled by estrogen. This subtype of ABC has recently seen a major advance with the introduction of drugs called cyclin-dependent kinase (CDK) inhibitors.
A key treatment for pre-menopausal women with ER-positive advanced breast cancer is to shut down their bodies’ production of estrogen—either permanently through removal of the ovaries or temporarily with medication.
Dr. Cardoso believes there is no reason to exclude young women from clinical trials as the treatment will ultimately make them menopausal. Furthermore, including young women may make trial recruitment easier and give valuable information regarding how best to treat women of all ages.
Bella Kaufman, MD, a breast cancer oncologist at the Sheba Medical Center, Tel Hashomer, Israel, is herself an advanced breast cancer patient.
“Although breast cancer is less common in pre-menopausal women, this is an important group of patients who have a complicated set of needs,” she said, “To understand and address these needs, it’s vital that pre-menopausal women take part in clinical trials. Younger patients, for example, may have additional concerns about their fertility, their ability to work, or their body image.”
Eric Winer, MD, director of Breast Oncology at the Dana-Farber Cancer Institute in Boston and co-chair of the conference, said, “This new set of guidelines offers clarity on the vast amount of research and information available to women with advanced breast cancer and the people who treat and care for them. What sets them apart is that they are produced by a partnership of patients and researchers.
“In the end, it is all about listening to our patients and communicating clearly,” he added. “Whether we are talking about standard therapies or complementary approaches, we need to ensure that all lines of communication are wide open.”
Other topics discussed at the conference included the impact of alternative and complementary therapies for women with breast cancer.
The panel stated that alternative therapies such as antioxidant supplements, Chinese herbal medicine, oxygen and ozone therapy, or high dose vitamins fail to show benefits and are not recommended at any stage of cancer treatment in place of evidence-based medicine.
However, the panel believes that some complementary therapies, such as exercise, mindfulness, and acupuncture, may reduce symptoms or treatment side effects and improve quality of life when used in conjunction with standard-of-care treatments.
The ABC guidelines are jointly developed by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO).