Dr. Colditz has reviewed the potential hazards of hormone replacement therapy in breast cancer survivors. Let us presume, for the sake of brevity, that his assumptions are correct. With so many risks, why would a breast cancer survivor consider taking hormone replacement, and why would an oncologist prescribe it?
For the breast cancer survivor, the issue is usually quality of life. Although nonhormonal medications (eg, clonidine(Drug information on clonidine)) sometimes relieve vasomotor symptoms, they usually fail.
Consider the following case:
Patient A, faced with abrupt chemical castration and clonidine-resistant vasomotor symptoms, experienced hot flashes every half hour. They disrupted her sleep. One evening she dressed for a formal gala. After drenching the first gown, she showered and donned a second. Soaking that one, she repeated the procedure. After the third attempt, she gave up and phoned her regrets. What should she and her oncologist do? Her quality of life is poor to intolerable.
Physicians who care for breast cancer survivors are concerned about quality of life and longevity. No one approach is right for all patients; treatments must be tailored to the individual.
Consider another case:
Patient B is a 45-year-old woman who had a 1-cm, node-negative breast cancer at age 40. She suffered chemotherapy-induced menopause. Because her menopause occurred a decade earlier than normal, her relative risk for heart attack increases 10-fold if hormone replacement cannot be used. She has a family history of heart disease and a high cholesterol level. She also has vasomotor symptoms, dyspareunia, and osteopenia.
First and foremost, this patient should be encouraged to pursue a healthy life style; ie, eat a proper diet, refrain from smoking, exercise, and use calcium and vitamin D supplements. She will also require a nonhormonal pharmacologic treatment regimen, which may be expensive. The patient could spend as much as $250 per month on cholesterol-lowering agents, bisphosphonates, clonidine, vaginal moisturizers, and antidepressants. Also, the side effects of taking multiple drugs can be substantial.
Patient Bs oncologist believes that she is probably cured of her breast cancer. Her tumor was estrogen receptor(ER)-negative, and thus dormant tumor cells most probably would not be activated by hormone replacement therapy. Estrogen causes proliferation of ER-positive but not ER-negative human breast cancer cells in vitro. Human breast cancer xenografts that exhibit an estrogen-responsive phenotype are all ER-positive, whereas xenografts that are ER-negative are uniformly estrogen-unresponsive.
Given this information, it seems that patient Bs only risk from hormone replacement therapy may be promotion of a new breast cancer. Since there has never been a large randomized clinical trial of hormone replacement therapy in breast cancer survivors, that risk is unknown. Hormone replacement therapy does not, however, appear to increase the rate of breast cancer in other high-risk groups (first-degree relatives of breast cancer survivors and women who have undergone breast biopsies that show atypical hyperplasia).
Limited Data for Making Decisions
What will this patient/physician team do? They will make the best decision, given the current state of knowledge, as limited as it is.
As yet, no full-scale clinical trials of hormone replacement therapy in breast cancer survivors have been completed, despite the desire of patients and doctors to participate in such trials. Although initially supportive of randomized studies after pilot trials were completed, the National Cancer Institutes Division of Cancer Prevention and Control recently stated, NCI is not sponsoring HRT [hormone replacement therapy] symptom relief or disease prevention studies in breast cancer survivors. Using computer modeling, they conclude that hormone replacement therapy can only harm breast cancer survivors.
Is computer modeling a valid substitute for clinical research, or is it a modern version of the Ouija board? What is clear is that the gold standard of trialsthe definitive prospective randomized trialwill not happen, at least not in this country. This is unfortunate for both patients and physicians.