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Role Reversal: Chemo Before Surgery for Breast Cancer

When it comes to breast cancer treatment, there is usually a standard sequence of events. First a woman has surgery to remove the tumor, then, if necessary, she has chemotherapy to kill any remaining cancer cells in the body. But the results of a number of studies suggest reversing the order of treatment, giving chemotherapy before surgery in order to offer certain women with early-stage breast cancer an added benefit; this approach is called neoadjuvant therapy.

"Neoadjuvant chemotherapy refers to giving chemotherapy upfront before we do surgery." says Harry Bear, MD, PhD, a professor with the division of surgical oncology at Virginia Commonwealth University in Richmond. "It can be used for the express purpose of shrinking a tumor that might be too big for lumpectomy. For selected patients, if we’re able to shrink the tumor, we’re able to do a lumpectomy instead of having to remove the whole breast."

At one time, it was hoped that giving chemotherapy before surgery might give all women better treatment options. The idea was that neoadjuvant chemotherapy would offer better survival rates than post-operative chemotherapy because cancer cells would be killed earlier in the disease process. But such a survival advantage has not been demonstrated in studies. A review of nine clinical trials of neoadjuvant chemotherapy involving almost 4,000 women was published in February 2005 in the Journal of the National Cancer Institute (JNCI). The study researchers, from the University of Ioannina School of Medicine in Greece, found that women who received chemotherapy before surgery had similar rates of survival, disease progression and cancer spread as women who were treated with post-operative chemotherapy, which is known as adjuvant chemotherapy.

The researchers did find that the women who had neoadjuvant chemotherapy had higher rates of local recurrences, or recurrences in the breast and nearby lymph nodes. Local recurrences don’t hurt a woman’s chances of survival, but any return of the cancer in nearby tissue after the initial surgery means that a woman would most likely have to undergo a mastectomy after all. The researchers found that these recurrences were most likely to occur in women who did not have any surgery because their tumors had disappeared completely after the neoadjuvant chemotherapy.

And for women who do have surgery to remove the remains of their tumor after chemotherapy the procedure is often is often trickier. The goal of any surgery is to remove the cancer with a wide margin of tissue around it to ensure that you are getting all of the cancer cells out of the body. This wide margin is called a "negative" margin.

"If you’re doing surgery right away, you know where the cancer is, and we have a large body of knowledge that shows that if you take the cancer out with a large margin [around the tumor], there will be a low rate of recurrence." says Monica Morrow, MD, the chair of the department of surgery at the Fox Chase Cancer Center in Philadelphia. "But when some cancers die after chemotherapy, they die in a patchy fashion, so if you do surgery after chemotherapy, a negative margin might not mean the same thing." She adds that the greater possibility that part of the tumor will be left in the breast requires "a greater need for close communication between the surgeon, the pathologist and the radiation oncologist."

For now, neoadjuvant chemotherapy is only offered to women with a large tumor in a small breast who want a lumptectomy. But this approach to treatment may play a greater role in the future. Some researchers hope that neoadjuvant chemotherapy can one day be used to test the impact of a given chemotherapy drug on a particular tumor, allowing women to quickly switch to a more effective chemotherapy combination. But first scientists have to identify cancer markers that will indicate whether a chemotherapy drug is working.

"One of the other theoretical advantages to neoadjuvant chemotherapy—and this is really why it’s a very exciting focus for a lot of our research protocols—is that it allows us to look at features of the tumor that are associated with either a good response to a particular drug or no response to a particular drug." Dr. Bear says. "We are hoping that, eventually, we’ll get to a point where we can look at patient’s tumor with very sophisticated tests and be able to determine whether a particular tumor should be treated with drug A or drug B or whether neither one of those drugs is good."

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