Combined modality approach for high-risk breast cancer. The Milan Cancer Institute experience.
After 20 years of successive clinical trials, the results achieved at the Milan Cancer Institute have helped to establish the effectiveness of adjuvant combination chemotherapy in high-risk women with resectable breast cancer. The most significant findings can be summarized as follows: (1) the clinical benefit in terms of relapse-free and total survival can be prolonged up to 20 years from surgery; (2) the use of anthracyclines (doxorubicin) can contribute to improved treatment outcome; (3) dose intensity and dose size are the leading prognostic variables; and (4) adjuvant treatments are not associated with important iatrogenic morbidity. New modalities that could profoundly change current treatment strategies will involve high-dose sequential chemotherapy and primary chemotherapy. In fact, the use of rhG-CSF-elicited hematopoietic progenitors will grant a substantial reduction in granulocytopenia and related toxicities; this, in turn, will permit the administration of regimens based on high dose size and dose intensity. As far as primary chemotherapy is concerned, the shift from mutilating to breast-conserving operations has led to important advantages in a society concerned for body integrity. In the few studies with sufficient follow-up, objective tumor response to primary chemotherapy has been translated into superior relapse-free survival compared with that of nonresponders. In particular, from the first Milan study the knowledge is clearly emerging that the response rate is inversely related to the initial tumor volume and that the degree of tumor regression (complete pathologic remission versus moderate versus minimal response) appears to represent a marker of outcome. Should this crucial observation be confirmed in other ongoing trials, then the amount of tumor shrinkage could rank among the most important prognostic variables because it is reproducible and inexpensive. As a consequence, the achievement of complete (or near complete) pathologic remission will become the major goal of properly intensified drug regimens to ensure a durable relapse-free survival rate. To make legitimate the wide adoption of the strategy involving primary chemotherapy, most breast cancer specialists correctly advocate that the initial promising results be validated through classic randomized trials. The question to answer appears simple: Will preoperative chemotherapy be superior to postoperative chemotherapy in terms of relapse-free and total survival? In our opinion, the simple attempt to shift from postoperative (adjuvant) to preoperative (primary) chemotherapy may not be enough, although formally correct, to maximize treatment outcome, and thus become the new strategy of choice.(ABSTRACT TRUNCATED AT 250 WORDS)
Bonadonna
G
G
Division of Medical Oncology, Instituto Nazionale Tumori, Milan, Italy.
Valagussa
P
P
D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015409:Mastectomy, Radical; D012307:Risk Factors