NEW ORLEANSNeoadjuvant chemotherapy is being employed increasingly in breast cancer, both in the research and clinical setting. A surgeons perspective on this modality was offered at the American Society of Breast Disease annual meeting by Benjamin O. Anderson, MD, medical director of the BioClinical Breast Care Program, University of Washington, Seattle.
Categories of Use Changing
The lines between local and systemic therapy are becoming blurred. The categories for which we use neoadjuvant chemotherapy are changing, he said.
Neoadjuvant chemotherapy is being used in inflammatory breast cancer, where it is thought to prolong survival; in locally advanced noninflammatory breast cancer, where it makes marginally operable tumors more resectable; and in primary operable breast cancer, to potentially increase breast-conservation rates.
While studies to date have not found an increase in survival among patients with primary operable breast cancer treated with neoadjuvant therapy, marked tumor shrinkage can occur, which may correlate with outcome. Bonadonna and colleagues, in their clinical trial, suggested the question to answer is not whether to shift from adjuvant to neoadjuvant chemotherapy, but how to integrate these regimens to maximize tumor kill, Dr. Anderson said.
Several investigations have found that neoadjuvant chemotherapy can render nonoperative breast cancer operable, in many cases.
The recently reported NSABP B-18 trial of 1,523 women with primary operable breast cancer found similar disease-free, distant disease-free, and overall survival rates between neo-adjuvant and adjuvant groups. However, patients treated preoperatively were more likely to be eligible for lumpectomy and radiation therapy than those receiving adjuvant therapy (68% vs 60%).
In another study (Avril A et al: Chirurgie 123:247-256, 1998), about two-thirds of patients with operable breast cancers larger than 3 cm were rendered operable with breast-conserving surgery, initially considered impossible to achieve. While locoregional recurrences were more frequent than with mastectomy and adjuvant chemotherapy, more than 60% of these women were nevertheless alive at 5 years with their breast intact, Dr. Anderson commented.
It appears that a subset of women with locally advanced breast cancer can preserve their breast with acceptable cosmesis without compromising local control or survival, but local recurrence rates remain uncertain, he said.
Most primary breast tumors will respond to neoadjuvant chemotherapy, and clinical response is a significant predictor of long-term outcome. One study found the probability of survival at 5 years to be 74% in patients with a complete response, and 36% in those with a partial clinical response. Another study found a significantly increased 10-year survival for patients achieving a complete vs incomplete response (70% vs 50%).
A study of 300 women with stage IIIb breast cancer found that 83% achieved a complete or partial clinical response after neoadjuvant chemotherapy with the FAC regimen (fluorouracil, Adriamycin, cyclophosphamide(Drug information on cyclophosphamide)) [Glinski B et al: J Surg Oncol 66:179-185,1997], Dr. Anderson said.
But clinical response only partially correlates with pathologic response as assessed at surgery. The pathologic response to neoadjuvant chemotherapy is highly individualized and variable, Dr. Anderson said, and mammographic assessment of response to treatment is relatively unreliable.
The combination of physical examination with either mammography or sonography significantly improves the accuracy of noninvasive assessment of tumor dimensions, investigators have found.
The surgeon needs to look at the pretreatment imaging and the post-treatment imaging, using these tools together in a uniform management strategy, Dr. Anderson advised.
A significant percentage of patients with complete clinical response still have residual microscopic disease, especially ductal carcinoma in situ (DCIS). Therefore, while clinical response is predictive of a favorable outcome, it is not a guarantee, he said.
The Goal of Surgery
At our center, we do not try to convert patients who obviously need mastectomies to lumpectomy candidates. Generally, the goal is to resect the same area of tissue. Converting the patient to negative margins does not mean taking less tissue, he said. We are concerned that taking reduced amounts of breast tissue will leave residual disease that can precipitate high local recurrence rates.
The presence or absence of lymph node metastases remains a key prognostic factor in the neoadjuvant treatment of breast cancer. While a complete clinical response predicts for good disease-free survival, residual metastatic axillary lymph nodes after neoadjuvant treatment is a predictor of poor survival. Patients should be adequately treated with surgery, regardless of the tumors response to neoadjuvant chemotherapy, Dr. Anderson said.
He also advised surgeons not to use sentinel node mapping after neoadjuvant chemotherapy, since neoadjuvant treatment is associated with excessive false-positive rates, meaning that patients are more likely to be incorrectly classified as node negative.
In Dr. Andersons series, 9 of 12 neoadjuvant chemotherapy patients were node positive on axillary dissection, but 3 of the 9 had benign sentinel nodes. A false-negative rate of 33% would mean that an excessive number of patients would have been understaged and potentially undertreated, he said.