Among the many difficult decisions women face after receiving a diagnosis of breast cancer is whether to undergo mastectomy, not only of the breast with cancer but, as a preventive measure, of the unaffected breast as well. Cancer detected in one breast has a tendency to spread to the other, healthy breast, and an increasing number of women are choosing to excise the unaffected breast, just to be safe. Numerous studies have documented the reduction in breast-cancer recurrence in women who elect to remove both breasts, but until now, no studies had confirmed that this decision actually increases a woman's overall chance of survival.
In a new study, researchers at MD Anderson Cancer Center in Houston provide the first evidence that preventive mastectomy prolongs life, but only for a subset of breast-cancer patients. For the majority of women diagnosed with the disease, the drastic and deforming surgery is more than they need, the study concludes.
The results may finally give clinicians a bit of solid ground for counseling their patients. "We have not had real data to guide us," says Dr. Isabelle Bedrosian, the study's lead author and an assistant professor in the department of surgical oncology at MD Anderson. "We can't sit down with a woman and say, 'If you do this, this is your expected benefit.' And when we don't have those data, then biases become the big drivers of decisionmaking."
Those biases, which err mostly on the side of "better safe than sorry," have fueled a trend toward excessive and, argues Bedrosian, unnecessary surgery to remove both breasts. From 1998 to 2003, the rate of such double mastectomies in the U.S. jumped 150%.
Part of the reason for the rise, say experts, has to do with improved genetic and imaging techniques that give women a lot of information about their tumors and the prognosis of their disease, which may sway them to take extreme measures to avoid recurrence.
In Bedrosian's study, however, which involved 107,000 women undergoing mastectomy for breast cancer, most women did not obtain a survival benefit from preventive surgery in the unaffected breast. Only a specific group of patients women under age 50 who had early-stage cancer (I or II) and tumors that were negative for the estrogen receptor saw an increase in their chances of surviving to five years. That increase was small, just 4.8%, compared with women who did not have preventive mastectomy. Further, less than 10% of the breast-cancer population fits these criteria.
"We hope this study helps women make a better decision," says Bedrosian. "For the majority of women in the study, we can't document a survival benefit for you. So our results provide some reassurance that perhaps a [preventive] mastectomy is not necessary, perhaps overly aggressive and perhaps a bit too much."/p>
But while the benefit may seem slight, Bedrosian notes that in cancer terms, any percentage boost in survival is meaningful, particularly to patients. And when women are facing the decision to lose a healthy breast, every piece of information counts.
The MD Anderson study highlights the combined effect of three major factors in improving breast-cancer survival: age, type of tumor and stage of cancer. Taken together, this suite of criteria makes sense, says Bedrosian. Women with estrogen-positive cancers can be treated with hormone-therapy drugs like tamoxifen or, if they are postmenopausal, the new aromatase inhibitors, which block the production of cancer-enhancing estrogen in the body. Women whose tumors lack the estrogen receptor, however, cannot take advantage of these drugs, since their cancers are not as dependent on estrogen for fuel. As a result, they have a lower survival rate to begin with. That's why women with these cancers showed a survival benefit from removing both breasts, says Bedrosian.
Whether the findings are sufficient to translate to the clinic, though, is another matter. Some experts are not convinced yet that the study results should be part of clinical decisionmaking, pointing out that many factors other than mastectomy may be driving the increase in survival. "Women who undergo a [preventive] mastectomy in the unaffected breast may be different from women who do not," says Dr. George Sledge, president-elect of the American Society of Clinical Oncology and a professor of medicine at Indiana University. "They may be overall healthier in that they see their physician more frequently, and their physicians may be more aggressive in treating their cancer in terms of what chemotherapy they use, and therefore these women may happen to have a greater benefit from having received more generally aggressive treatment."
Dr. Larry Norton, a breast-cancer expert at Memorial Sloan-Kettering Cancer Center in New York City, agrees and cautions against applying these findings immediately to the clinic. "This is an observational study, and hence it is impossible to control for confounding variables," he says, "and should not be used for individual clinical decisionmaking." But Norton acknowledges that the ideal study in which women would be randomly assigned to either have a double mastectomy or not could never be done, since it would not be ethical to prevent women from having a procedure known to reduce the risk of cancer recurrence.
Aware of these concerns, Bedrosian says her team was rigorous in its statistical analysis and feels confident enough in the numbers to begin using the information to help patients decide whether a preventive mastectomy is right for them. "We looked at this in multiple different ways, and we got the same answer every time. And the results make good clinical sense. That adds another level of reassurance," she says. "Our hope is that when women hear the numbers, they will take a second look and decide not to go forward with a preventive mastectomy [in their healthy breast] if it won't give them a survival benefit."
The findings clearly do not apply to every breast-cancer patient, she says, but at the very least, it's one more piece of information that women and their doctors can discuss when weighing their best treatment options.