Pretreating May Help Improve Outcomes for Patients with Hard-to-treat Breast Cancers

Researchers are exploring the long-term impact of treating breast cancer before surgery

At this year’s San Antonio Breast Cancer Symposium, which takes place this week, researchers will discuss how the treatment of breast cancer prior to surgery—known as neoadjuvant therapy—may extend survival or help women live without their cancer longer, especially those with aggressive or difficult-to-treat subtypes.

“It’s a hot topic among breast cancer researchers,” said George Somlo, principal investigator at the City of Hope Comprehensive Cancer Center, who studies the topic. “What we’re trying to figure out now is exactly what neoadjuvant treatment means for patients in the long-term.”

Surgery remains the primary treatment option for breast cancer, but some women have tumors so large that breast preservation or even a mastectomy could not be performed with clear margins or an acceptable aesthetic outcome. Pretreating these patients with chemotherapy has been an effective way to shrink these tumors, making surgery a viable option. In other cases, shrinking the tumor may mean it can be excised without removing the entire breast.

What we’re trying to figure out now is exactly what neoadjuvant treatment means for patients in the long-term.

Occasionally, this pre-treatment can even shrink the tumor so well that the surgery no longer identifies any trace of cancer. Such success is known as a pathological complete response (pCR).

Several recent meta-analyses have shown that achieving pCR improves outcomes for some patients. In one study, researchers found that patients who achieved pCR had a 36 percent increase in overall survival. For patients with difficult-to-treat subtypes, including HER2 over-expressive (particularly hormone receptor negative) and triple-negative breast cancers, pre-treatment offered a 75 percent decrease in cancer recurrence.

Last year, the Food and Drug Administration (FDA) acknowledged the potential of pCR to measure the efficacy of possible new breast cancer therapies in an effort to accelerate new drug approvals. Using pCR as an endpoint allows researchers to examine a therapy’s effects on a shorter timescale, making clinical trials in early stage disease (for which patient survival times are long) more feasible. Typically, new therapies were only tested in late-stage disease, when survival times are shortest.

“The FDA’s allowance of the use of pCR as an endpoint has allowed patients’ access to novel and effective therapeutic agents before the disease metastasizes,” Somlo said. “This is a positive evolution in the thinking of how to develop drugs.”

Some physicians urge caution in using pCR to make clinical decisions until we know more about its correlation with long-term survival outcomes. Others note that trials examining treatment before surgery should be reserved for patient groups for whom a benefit is clearest, such as those with hormone receptor-negative cancer. Still others point to data suggesting that neoadjuvant therapy may cause the cancer to mutate, leading to new tumors.

Yet many like Somlo remain optimistic about the mounting evidence supporting the association between neoadjuvant treatment and improved survival. Perhaps one day, muses Somlo, the need for surgery may even be eliminated.

“That would be the ideal situation,” he said. “We’re not at that point today, but in the future, I wouldn’t be surprised if this was an acceptable approach.”