Jacques R. Vilcoq

Prognostic factors of breast recurrence in the conservative management of early breast cancer: A 25-year follow-up☆

Between 1960 and 1980, 518 patients with T1, T2, N0, N1a, invasive breast cancer were treated by limited surgery at Institute Curie with (183 patients) or without (335 patients) axillary node dissection, followed by radiation therapy to breast and nodes. Median follow-up was 8.6 years (1.3 to 25 years). Fifty-six breast recurrences occurred, including 49 breast recurrences alone, 3 simultaneous breast and node recurrences, and 4 simultaneous breast recurrences and metastasis. Five-year, 10-year, and 15-year actuarial risks of breast recurrences were 7 +/- 1%, 11 +/- 1.5%, and 18 +/- 3%, respectively. Univariate analysis of 14 clinical and pathological prognostic factors revealed that local control in breast was significantly impaired by young age, premenopausal status, inadequate gross surgical excision, extensive ductal in situ component, and endolymphatic extension. On multivariate analysis with a Cox regression model, the most important contributors to local breast control in order of importance were age (p less than 10(-4), relative risk = 2.44), adequacy of surgery (p = 0.003, relative risk = 2.78), and endolymphatic extension (p = 0.03, relative risk = 2.98). The 5-year actuarial survival rate following breast recurrence was 73%, and was significantly worse when breast recurrence occurred in the first 3 years after treatment: 44% versus 87%, respectively (p less than 0.01). This study confirms the relationship between young age and low breast control rates, and demonstrates the importance of adequate initial surgical procedures. It emphasizes the adverse prognosis of early breast recurrences as compared to the relatively favorable outcome of late recurrences.

Age as prognostic factor in premenopausal breast carcinoma

Whether or not young age at diagnosis is an adverse prognostic factor in breast cancer has long been controversial, in part because much previous work has not taken due account of menopausal status and confounding factors. We have analysed the influence of age on prognosis in a consecutive series of 1703 patients with stage I-III breast cancer. All were premenopausal and all were treated in one centre (Institut Curie, Paris) between 1981 and 1985. Mean age was 44 years (range 23-55) and median follow-up was 82 months. Younger patients had significantly lower survival rates and higher local and distant relapse rates than older patients. The hazard rate of relapse decreased over time in the youngest age group (< or = 33) to reach that of older patients after 5 years. The relation between the hazard of recurrence and age was a continuous one, best fitted by a log-linear function and indicating a 4% decrease in recurrence for every year of age. Multivariate analysis of both survival and disease-free interval demonstrated that the worse prognosis of young age was independent of other factors such as clinical tumour size, clinical node status, histological grade, hormone receptor status, locoregional treatment procedure, and adjuvant systemic therapy. This difference in outlook has yet to be explained biologically but it does suggest the need for a closer look at the natural history of breast cancer in young women.

Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: Preliminary results of a randomised trial: S6

The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a persisting mass after irradiation, and aimed to be as conservative as possible. 390 patients were evaluable. With a median follow-up of 54 months, we observed a statistically significant difference (P = 0.039) in survival in favour of the neoadjuvant chemotherapy group. A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or local recurrence between these two groups could be observed. The mean total dose of chemotherapy administered was similar in both groups. On average, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the treated patients in group II. Haematological tolerance was reduced when chemotherapy succeeded to exclusive irradiation. Breast conservation was identical for both groups at the end of primary treatment (82 and 77% for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (> 50% regression) following four cycles of chemotherapy. The objective response rate to primary irradiation (55 Gy) was 85%. Improved survival figures in the neoadjuvant treatment arm could be the result of the early initiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically significant. The local control appeared similar in both subgroups.

Value of axillary dissection in addition to lumpectomy and radiotherapy in early breast cancer

Axillary dissection in early breast cancer remains controversial because of its substantial side-effects and because its value with respect to recurrence or survival has not been unequivocally proven. Between 1982 and 1987, 658 patients were included in a prospective randomised comparison of lumpectomy alone with lumpectomy plus axillary dissection. All patients had a unilateral breast tumour not exceeding 3 cm in diameter and lymph-node involvement or metastases. Radiation therapy was given to both groups. The two groups of patients were similar with respect to mean age, TNM stage, and presence of hormonal receptors. Median follow-up was 54 months. 5-year survival of the patients was 94.2% (95% Cl: 92.1-96.4). There was a significant advantage in survival in the axillary dissection group (p = 0.014). Recurrence of tumour in the breast was similar in the two groups but visceral metastases, supraclavicular metastases, and lymph-node recurrences were less frequent in the axillary dissection group. Survival was related to the age of the patients (p = 0.005), the presence of positive nodes (p = 0.006), the histological grading (p less than 0.0001), and the presence of hormonal receptors (progesterone p = 0.0008, oestrogen p less than 0.0001). Treatment-adjusted relative risk was 2.4 (95% Cl: 1.3-4.2). The findings show that axillary dissection is justified for treatment of small breast cancers, although whether the better survival is due to axillary clearance itself or to adjuvant treatment for lymph-node involvement is unclear.

Conservative management of operable breast cancer. Ten years experience at the Foundation Curie

514 patients were treated for a surgically operable (T1, T2, T3, N0, N1a, N1b) infiltrating breast carcinoma at the Foundation Curie, Paris, France, from 1960 to 1970 inclusive. Patients with tumors 3 cm or less and without axillary adenopathy had lumpectomy followed by radiotherapy. Patients with larger tumors and all patients with clinically significant lymph nodes (N1b) had exclusive radiotherapy (without lumpectomy). 120 had lumpectomy and 394 had exclusive radiotherapy. The five and ten years absolute survivals, free of disease (N.E.D.), for the lumpectomy group are 85% and 75%, respectively. 12% had secondary surgery for local recurrence. The cosmetic results were satisfactory in 98%, with no severe radiation sequelae. The five and ten years, N.E.D., of the exclusive radiotherapy group are 68% and 43%. 55% had secondary surgery for persistent or recurrent disease. The cosmetic results were satisfactory in 85%. There were only three patients with severe radiation sequelae. The overall survival for 514 patients at five and ten years are 72% and 51%. Two‐thirds of patients, alive at five years, had a preserved breast. Our conservative treatment resulted in survival at five and ten years comparable to those of radical surgery. Cancer 42:2045–2053, 1978.

Local control and survival of breast cancer treated by limited surgery followed by irradiation

Between 1960 and 1978, 324 patients with early breast cancer were treated by lumpectomy with or without axillary dissection followed by radiation therapy. All were followed for a minimum of 5 years. All patients were, retrospectively, classified T1, T2, N0, N1a, in the TNM (U.I.C.C.) Classification. The retrospective analysis of the local-regional patterns of failure revealed that young age (less than or equal to 32 years) and premenopausal status were associated with an increased rate of local failure, whereas tumor size and location showed no influence. No pathological features were associated with an increased risk of local recurrence, whether pathological subtypes, Scarff Bloom and Richardson grading, intraductal associated component, or vascular involvement. The absolute 5 year disease-free survival rate was 87% in patients who recurred and 93% in those who did not. The absolute 10 year disease-free survival rates were 75 and 82%, respectively. Therefore, these results confirm that loco-regional failure does not significantly influence the disease-free survival.

Ten‐year results of breast‐conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ) of the breast

An analysis of 259 women with 261 treated breasts from nine institutions in Europe and the United States was performed to determine the 10‐year results of the treatment of intraductal carcinoma of the breast with definitive irradiation. All patients had undergone complete gross excision of the primary intraductal carcinoma, and definitive breast irradiation was delivered in all cases. The median follow‐up time was 78 months (range, 11 to 197 months). The 10‐year actuarial overall survival rate was 94%, and the 10‐year actuarial cause‐specific survival rate (including deaths only from carcinoma of the breast) was 97%. The 10‐year actuarial rate of freedom from distant metastases was 96%. There were 28 failures in the breast, and the 10‐year actuarial rate of local failure was 16%. The pathologic type of local recurrences showed invasive ductal carcinoma in 14 of 28 recurrences (50%) and noninvasive ductal carcinoma in 14 of 28 recurrences (50%). The median time to local failure was 50 months (range, 17 to 129 months). Twenty‐four of 28 patients with local failure were salvaged with additional treatment, generally mastectomy, and 4 of 28 patients with local failure subsequently had distant metastases. Median follow‐up time after salvage treatment of breast recurrence was 29 months (range, 3 to 90 months). Two patients without local failure subsequently had distant metastases, one of which occurred after a node‐positive, contralateral breast carcinoma. These results demonstrate high rates of overall survival, cause‐specific survival, and freedom from distant metastases for the treatment of patients with intraductal carcinoma of the breast. The local recurrences within the treated breast were generally salvaged with additional treatment, although with limited follow‐up. Because of the long natural history of intraductal carcinoma of the breast, prolonged and careful follow‐up of patients after breast‐conservation and definitive irradiation is required. Cancer 68:2337–2344, 1991.

Conservative management of intraductal breast carcinoma with tumorectomy and radiation therapy

Between 1967 and 198354 patients with strictly noninvasive intraductal breast carcinoma were treated with tumorectomy and radiation therapy. Median follow‐up was 55 months. Three patients had a recurrence in the treated breast; two were noninvasiveand one was invasive. One patient died of disease. Actuarial 5‐year disease‐free survival rate was 95.2%. No axillary node recurrences occurred in patients treated with irradiation to the breast and regional nodes (34 patients)or in patients treated with breast irradiation alone (20 patients). These preliminary results suggest that combined tumorectomy and radiation therapy could be a valuable conservative alternative to mastectomy in the treatment of noninvasive intraductal breast carcinoma.

Time course and prognosis of local recurrence following primary radiation therapy for early breast cancer.

The frequency, time course, and prognosis of local recurrence following primary radiation therapy in 152 patients with early breast cancer treated before 1967 were examined. Local recurrence occurred at a constant rate over the first 14 years after treatment. The crude 15-year local recurrence rate was 22%. Of the 30 patients who developed an isolated local recurrence and underwent definitive secondary surgery, the 10-year freedom from distant relapse rate was 50%. These results indicate that breast cancer patients treated by primary radiation therapy require long-term follow-up to detect curable local recurrences.

The outcome of treatment by tumorectory and radiotherapy of patients with operable breast cancer

Abstract We performed a retrospective study on 314 patients treated for a localized breast cancer by tumorectomy and radiotherapy to determine the overall survival, incidence of loco-regional failure and outcome of salvage surgery. All patients were followed for at least three years. Two hundred and fourteen patients had tumors ≤ 3 cm and 74 had tumors ≤ 6 cm. The three and five years absolute survival, free of disease (NED), is 88% ( 276 314 ) and 84% ( 190 225 ). The incidence of loco-regional failures was not dependent on tumor size and did not exceed 10% for the entire group. Recurrences were common (35%) in young patients (≤ 30). No patient older than 50 had recurrences. Eighty-one percent of failures appeared within three years. Salvage surgery was performed on 78% ( 14 18 ) of patients with recurrences; 57% ( 8 14 ) were free of disease (NED). Local failure in this group was not necessarily associated with disseminated cancer. Tumorectomy followed by radiotherapy is an acceptable alternative to mastectomy, particularly since salvage surgery can usually be successfully performed for recurrences.