T3b-T4 breast cancer: factors affecting results in combined modality treatments

Abstract

Two hundred and seventy-seven consecutive patients with T3b-T4 breast cancer referred to the Milan Cancer Institute between 1973 and 1980 were treated with a combined modality approach. Chemotherapy (CT) consisted of AV, i.e. adriamycin (60-75 mg/m2 day 1) and vincristine (1.2 mg/m2 days 1 and 8) and was given for three to four cycles prior to local regional modality. Local-regional treatment consisted of either radiotherapy (RT) in 198 patients or surgery (S) in 79 women. Additional chemotherapy was then administered to a total of 205 patients. In the absence of distant metastases, frequency of good local control was significantly inferior in patients given CT + RT (63.9 per cent) compared to those treated with CT + RT + CT (75.4 per cent) and CT + S + CT (82.3 per cent, P = 0.033). Also freedom from progression (FFP) and overall survival (SURV) were significantly superior in the groups receiving more prolonged chemotherapy treatment compared to patients treated with CT + RT (FFP: P less than 0.0001; SURV: P = 0.002). None of the variables examined was able to affect the response rate, while axillary nodal status and tumor size played a major role in the duration of FFP and SURV. Our findings indicate that a more aggressive treatment is needed to improve current results in this stage of disease. To overcome the problem of local-regional recurrence, treatment should probably begin with cytoreductive surgery followed by postoperative radiotherapy in all patients with the exception of those having inflammatory carcinoma. Systemic treatment should then be delivered to control distant micrometastases.

Efficacy of up-front 5-fluorouracil – epidoxorubicin – cyclophosphamide (FEC) chemotherapy with an increased dose of epidoxorubicin in high-risk breast cancer patients

“…A relationship between anthracyclin dose and response has been reported by several investigators (Valagussa et al, 1983;Habeshaw et al, 1991;Chevallier et al, 1993;Focan et al, 1993) and it appears reasonable to ascribe the high objective response rate obtained in the present study to the elevated dose of epidoxorubicin. Recently, however, similar high rates of clinical and pathological complete remissions were reported following the up-front administration of a standard dose of epidoxorubicin (50 mg m-2) in combination with cisplatin and continuous infusion of 5-fluorouracil (5FU) in large primary breast cancers (Smith et al, 1995).…”

Neoadjuvant Therapy in Breast Cancer

“…Further, NCT allows down staging of tumors by decreasing tumor size and extent of tumor mass, thereby facilitating breast conservation therapy (BCT). Neoadjuvant chemotherapy was first used in 1973 at the Milan Cancer Institute 2,3,4 . Their goal at the time of the study was to achieve prompt tumor response or shrinkage in locally advanced inoperable disease in order to facilitate the delivery of radiation therapy.…”

Combined sequential approach in locally advanced breast cancer

“…Bone marrow toxicity was mild. WBC count less than 2500/mm 3 and neutrophil count less than 1000/mm 3 were recorded in 3% and 7% of cycles respectively. No platelets decrease below 100,000/mm 3 was observed.…”

“…Local control is generally obtained by radical mastectomy and radiotherapy on chest wall, but in a selected subgroup of women, i.e., with tumor of limited size without diffuse edema or erythema, conservative surgery may be offered, even though this option can not yet be considered conventional [6][7][8]. The standard approach of sequential administration of systemic and loco-regional treatment has improved the long-term outcome of these patients, but the prognosis is still deadly in about two thirds of them at five years [2,3].…”

“…The most widely used therapeutic programs are generally comprehensive of anthracyclines and obtain high incidence of tumor regression, although the reported rate of complete remission is widely variable among different reports [2][3][4][5]. Local control is generally obtained by radical mastectomy and radiotherapy on chest wall, but in a selected subgroup of women, i.e., with tumor of limited size without diffuse edema or erythema, conservative surgery may be offered, even though this option can not yet be considered conventional [6][7][8].…”