In Breast Cancer, Moving Toward More Personalized Hormone Therapies
After treatment for early-stage breast cancer, many postmenopausal women with estrogen-receptor positive tumors decide to take drugs, such as an aromatase inhibitor or tamoxifen, to prevent or delay a recurrence of their disease. Selecting which treatment strategy may be best for the individual patient is difficult, in part because there is conflicting scientific evidence.
Guidelines, such as those from the American Society of Clinical Oncology, suggest that all post-menopausal women should receive an aromatase inhibitor either alone or before or after tamoxifen, but they do not suggest an optimal approach.
—Dr. Shannon Puhalla
Clear recommendations may eventually come from ongoing clinical trials. In the meantime, a new study suggests doctors should consider the potential side effects of the drugs as well as a patient's health history when making a selection.
The study, published in the September 7 Journal of the National Cancer Institute (JNCI), largely confirmed what is known about these drugs. Compared with tamoxifen, the longer use of aromatase inhibitors was associated with higher rates of heart disease and bone fractures but with lower rates of blood clots and endometrial cancer.
Aromatase inhibitors and tamoxifen, often referred to as adjuvant hormonal therapies, are designed to interfere with the body's production of estrogen and the promotion of breast tumor growth by estrogen, respectively. Estrogen is a naturally occurring hormone that can contribute to the growth of breast cancer.
The new findings highlight the need for physicians to select a therapy based on more than its ability to prevent a recurrence of breast cancer, the study authors said.
"Because the risks of these adjuvant therapies are relatively low, physicians don't spend a lot of time thinking about side effects," said lead investigator Dr. Eitan Amir of the Princess Margaret Hospital in Toronto. But there are clearly serious side effects associated with both approaches, he continued, noting that doctors should be able to identify patients at risk for some of these toxicities before selecting therapies.
"Don't Ditch the Switch"
Based on an analysis of seven clinical trials using these antihormonal therapies, the researchers concluded that switching from one type of therapy to another could offset the potential cumulative side effects of individual drugs and allow many women to experience the maximum benefits with lower side effects.
"We know that the one-size-fits-all approach does not work for every woman," said Dr. Shannon Puhalla of the University of Pittsburgh Cancer Institute, who co-authored an accompanying editorial entitled "Adjuvant Endocrine Therapy for Breast Cancer: Don't Ditch the Switch."
"As oncologists, we always focus on preventing cancer from recurring, but it is important to look at other causes of morbidity and mortality in our patients," Dr. Puhalla continued. As she and her co-authors wrote in the editorial, the field needs a risk model that can help clinicians select the most appropriate treatment for an individual.
—Dr. Tito Fojo
The current study, she added, "is a first step in trying to personalize hormonal therapies."
Serious side effects from adjuvant hormonal therapies are rare but may occur more frequently in patients with certain health conditions, such as a history of heart problems, the researchers said.
"This study provides further validation that both of these options are very good for patients," said Dr. Tito Fojo of NCI's Center for Cancer Research, who was not involved in the research. "So it becomes incumbent on the doctor to think about toxicities and about which drug is best for an individual patient."
An Aromatase Inhibitor Puzzle
Clinical trials have shown that, compared with tamoxifen, aromatase inhibitors are better at delaying the time until disease recurs (disease-free survival or recurrence-free survival). But none of the trials has demonstrated improved overall survival for aromatase inhibitors.
The researchers hypothesized that the cumulative toxicity of aromatase inhibitors may lead to deaths from causes other than breast cancer. They tested their hypothesis by assessing the risks of six adverse events associated with therapies used by more than 30,000 women to interfere with cancer growth-promoting hormones.
The analysis suggested that the cumulative toxicity of aromatase inhibitors, when used as a first-line treatment, may explain the lack of an overall survival benefit despite improvements in disease-free survival.
Dr. Amir stressed that the findings should be considered preliminary and need to be validated. In the meantime, information about the potential risk of side effects should be clearly communicated to patients, he said.
"The key is to provide a more holistic assessment of the patient not just for preventing breast cancer, but also as it relates to the side effect profiles of drugs," Dr. Amir added.