ORLANDOBreast cancer patients whose tumors respond to induction chemotherapy and who have no clinical axillary node disease following induction may be safely treated with axillary irradiation rather than axillary lymph node dissection, Jeffrey Lenert, MD, said at the Society of Surgical Oncologys Annual Cancer Symposium.
Dr. Lenert and his associates at M.D. Anderson Cancer Center compared pathologic node status in patients with T2-3, N0-1 invasive breast cancer who were treated with either axillary lymph node dissection or axillary irradiation following induction chemotherapy.
The role of axillary node dissection in the treatment of breast cancer is being reassessed because:
Screening mammography is detecting small tumors with lower risk of metastasis.
Adjuvant chemotherapy is often recommended even in node-negative patients.
Induction chemotherapy does not rely on staging information obtained from axillary node dissection.
Node dissection causes significant morbidity.
Dr. Lenert pointed out that induction chemotherapy also often downstages the N1 axilla to N0 status.
Dr. Lenerts study had two objectives: to determine if the primary tumors response to induction chemotherapy could predict the extent of axillary nodal disease and to compare the results of axillary lymph node dissection alone to those of axillary irradiation without dissection in patients with a negative axilla following induction chemotherapy.
The study population was drawn from 172 patients with biopsy-proven stage T2 or 3A invasive breast carcinoma. Patients were prospectively randomized to receive four cycles of either doxorubicin(Drug information on doxorubicin)-based or paclitaxel(Drug information on paclitaxel) (Taxol) induction chemotherapy.
Following induction chemotherapy, 67 patients were considered candidates for breast-conserving surgery, of whom 61 were evaluable for the purposes of the study. Of these, 30 had N1 disease by physical exam or axillary ultrasound and received axillary nodal dissection with segmental mastectomy.
Thirty-one patients had N0 disease by physical exam and ultrasound of the axilla. They were offered a second randomization to either axillary lymph node dissection or axillary irradiation. Eleven patients chose not to participate in the second randomization and went on to axillary nodal dissection.
Patients were stratified into responders (43 patients, 70%) and nonresponders (18 patients, 30%) to induction chemotherapy, depending on whether their primary tumors had decreased by at least 50%, compared with pretherapy size estimates. There were no significant differences between responders and nonre-sponders with regard to age, ER/PR status, or tumor size prior to therapy.
There was a difference with regard to clinical axillary node status, with significantly more patients in the nonresponder group having N1 disease prior to therapy, Dr. Lenert said, and this translated into a higher stage at diagnosis in nonresponders, specifically stage T2B breast cancer.
One-third of patients in the responding group and one-fourth of patients in the nonresponding group had downstag-ing of their status from N1 to N0 following induction chemotherapy. Axillary node dissection was done in 47 of the 61 patients after induction chemotherapy.
We found that 86% of patients in the responder group with N0 exams after induction chemotherapy had no histological evidence of tumor in their axillary specimens, Dr. Lenert said. Of patients who had N1 disease after induction chemotherapy, 65% had no histological evidence of tumor in their axilla. Nonre-sponders almost always had evidence of axillary metastasis in their specimens, even if they had N0 exams after induction chemotherapy.
There were no axillary recurrences among the patients who had undergone axillary irradiation alone. At a median follow-up of 21 months, the researchers have seen one local recurrence in the ipsilateral breast (at 20 months follow-up) and one patient with liver metastasis (at 33 months follow-up), Dr. Lenert said.
Four of 47 patients in the node dissection group had recurrences, three of whom were nonresponders. All four had distant metastases and two also had local-regional recurrences. All patients with recurrences had clinically positive axillae after induction chemotherapy.
We conclude that patients with a significant primary tumor response to induction chemotherapy have a high probability of having no histologically identifiable tumor in the axilla, Dr. Lenert said. Furthermore, patients with residual disease in the axilla have fewer involved nodes than patients whose tumors were not responsive to induction chemotherapy. Patients with nonresponsive tumors to induction have significant residual nodal disease, even if they have a clinically negative axilla.
The implications for therapy, he said, are that axillary irradiation may be an acceptable alternative to axillary node dissection in patients with a good response to induction chemotherapy who either were or became N0 after induction chemotherapy. Nonresponders have significant nodal disease and should continue to undergo node dissection, he said.