ABSTRACT
Thirty women with locally advanced breast cancer (LABC), but no evidence of distant metastases, were prospectively treated with four fixed cycles of neoadjuvant chemotherapy (CT). This regimen consisted of epidoxorubicin (Epi) alternated every 21 days with cyclophosphamide, methotrexate and 5-fluorouracil (CMF). After this induction CT, subsequent therapy was planned according to the response obtained as follows: (a) modified mastectomy with axillary dissection was performed in patients who had major objective response (complete or partial), followed by four doses of adjuvant CT and radiotherapy (RT); (b) debulking rescue surgery followed by RT and 2nd line CT with mitomycin C were given in patients with stable disease or minor response. The response rate to induction CT was 63% (19 of 30 patients) (95% confidence limits 46-80%). Overall, 43% of patients had no persistance of tumor at the end of the planned therapy. After a median follow-up time of 36 months, disease-free survival (DFS) and overall survival (OS) were 35% and 47%, respectively. The median duration of DFS was 16 + months (4-52+ months). A significantly better OS was observed in complete responders compared to the others (77% versus 23.5%; p=0.01). Compliance to treatment was high, gastrointestinal and hematological toxicities were the most common side-effects. Thus, this multimodal approach is effective in reducing primary tumor size with acceptable morbidity. Five of the 11 (45%) patients non responsive to induction CT obtained a transient local control of disease after debulking surgery, RT and mitomycin C. To assess the role of alternating non cross resistant regimens as induction therapy in LABC vs conventional schedules, phase III comparative studies are warrented.
ABSTRACT
From 1980 to 1987, 243 evaluable patients with pT1, pT2 (less than 3 centimeters in diameter), N0, M0, invasive breast cancer were treated with "quadrantectomy" with axillary dissection followed by electron beam radiation therapy (QUART) at the St. Bortolo Hospital, Vicenza. Stage II patients received adjuvant chemotherapy (CMF) if preperimenopausal or hormonotherapy (tamoxifen) if postmenopausal. The median follow-up was 54 months (26 to 116 months). The 4.5-year overall survival (OS) and disease-free survival (DFS) were respectively 91% and 85%; the 10-year actuarially estimated OS and DFS was 77%. Thirty-three patients relapsed, 11 of whom had local recurrence, and 23 developed distant metastases. A significantly longer OS and DFS were observed in stage I versus stage II (p = 0.0008) and in pT1 versus pT2 (p = 0.001) tumors. No difference was found regarding menopausal status and histotype. The local control of disease was very high (95.5%), with a significantly higher local recurrence rate in premenopausal women compared to postmenopausal (10/117 versus 1/126; p = 0.009). Tumor size did not influence the frequency of local recurrence. No major complications occurred but a significantly higher rate of reversible radiation-pneumonitis occurred in patients treated with higher energies of electrons (17 to 20 MeV) compared with lower (6 to 13 MeV) (33/177 versus 7/66; p less than 0.05). Cosmetic results were judged as excellent in 20%, satisfactory in 68%, unsatisfactory in 6% and not evaluable in 6% of cases. We conclude first, that small pT2 breast carcinomas may also be safely treated with QUART, second, that the electron beam is a radiotherapeutic technique able to produce a good cosmetic result and to assure a satisfactory local control and, finally, that the use of tamoxifen in postmenopausal stage II breast carcinomas is safe and easy to combine with radiotherapy in the conservative management of early breast cancer due to the lower toxic effects, compared to those observed in premenopausal women treated with chemotherapy.
