1992, The British Journal of Radiology, 65, 248-251
Neoadjuvant intra-arterial chemotherapy in inflammatory carcinoma of the breast By J. I. Bilbao, MD, *J. Rebollo, MD, J. M. Longo, MD, F. Mansilla, MD, * L Mufioz-Galindo, MD and *J. M. Vieitez, MD Departments of Radiology and 'Oncology, Clinica Universitaria, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain (Received 4 February 1991 and in revised form 18 July 1991, accepted 3 October 1991) Keywords: Breast cancer, Neo-adjuvant chemotherapy, Intra-arterial chemotherapy
Abstract. From 1982 to 1989, 18 eligible patients (median age 50.5 years, range 30-72 years) with inflammatory breast carcinoma have been treated with neoadjuvant intra-arterial (IA) chemotherapy. The treatment regimen includes IA cisplatin, adriamycin, mytomycin C and thiotepa on Day 1 and intravenous 5-fluorouracil on Days 1 and 2. An objective clinical response rate of 100% (eight complete and 10 partial) has been observed. The median disease-free and overall survivals are 27 months (range 5-85 + months) and 33 months (range 8-85+ months), respectively. With a median follow-up of 21.5 months, six (33.3%) patients remain alive and free of disease and 12 patients have died because of distant metastases. No local recurrences have been observed. Intra-arterial chemotherapy is an attractive technique for the treatment of locally advanced breast carcinoma with mild toxicity and high local control rate.
Inflammatory carcinoma is the most aggresive type of breast cancer. With local methods of treatment (surgery and/or radiotherapy) high local tumour control rates can be achieved, ranging from 50% to 80% (Barker et al, 1976; Ellis & Teistelbaum, 1974; Sicher & Waterhouse, 1973). However, long-term survival is poor (5% 5-year survival rate), because most of the patients have micrometastases at the moment of diagnosis. In patients with locally advanced (Stage III) breast cancer, the use of neoadjuvant systemic chemotherapy has shown a 70-80% response rate and a 5-year survival rate of 30% (Hortobagyi & Buzdar, 1986). This longterm survival compares favourably with that achieved with the use of local therapies. Hence, neoadjuvant chemotherapy was included in the protocols designed for the treatment of locally advanced breast carcinoma. Intra-arterial (IA) chemotherapy is an attractive technique that allows one to achieve high drug concentrations at the tumour site using catheters placed in the regional vessels (internal mammary and distal axillary arteries) (Koyama et al, 1975). The most encouraging results with IA therapy have been observed in some localized tumours of the limbs, head and neck, and stomach (Stephens, 1983). Results with neoadjuvant IA chemotherapy in a series of patients with inflammatory breast carcinoma are presented. Materials and methods
Selection criteria were (1) inflammatory carcinoma and (2) absence of distant metastases at diagnosis. The *Address correspondence to: J. I. Bilbao, Department of Radiology, Clinica Universitaria de Navarra, Avda. Pio XII s/n, 31080 Pamplona, Spain. 248
presence of axillary lymph node metastases was not a criterion for exclusion. Previous staging work-up included physical examination, complete blood count, liver profile, serum creatinine, echogram or computed tomographic (CT) scan of the liver, bone scintigraphy, chest radiographs and biopsy of the tumour. Treatment protocol An angiographic catheter is placed intra-arterially, using the Seldinger technique, through the common femoral artery and occasionally through the left or right axillary arteries. Catheters used were: Judkins right coronary 7F (USCI), Judkins right coronary 5F (CORDIS) and selective mammary 7F (CORDIS). The tip of the catheter is placed in the internal mammary (internal thoracic) artery; approximately 40-60% of the chemotherapeutic dose is administered selectively in this artery and the other 40-60% in the subclavian artery with a distal compressive cuff in the arm to include the axilla and related areas or, in some cases, selectively in the lateral thoracic artery. The infusion time ranges from 5 to 15 min. Treatment regimen I A therapy. Before the procedure, adequate hydration with normal saline at 150ml/h infusion rate for 3-4 h, 125 mg of methylprednisolone and 10 mg of deschlorpheniramine are administered. IA treatment consists of adriamycin (ADR) 40mg/m2, cisplatin (CDDP) 60 mg/m2, thiotepa (TSPA) 5 mg/m2 and mytomycin C (MMC) 6 mg/m2 on Day 1 and intravenous 5-fluorouracil (5-FU) 500 mg/m2 as a continuous infusion on Days 1 and 2. Immediately after the IA procedure, 50 g mannitol is administered to prevent nephrotoxicity of cisplatin. The regimen is repeated every 4 weeks. The The British Journal of Radiology, March 1992
Neoadjuvant intra-arterial chemotherapy in inflammatory carcinoma of the breast Table I. Characteristics of the patients No. of patients
Table II. Arteries used (49 procedures in 18 patients, one or two infused arteries in each procedure) 18
Age (years) Median Range
50.5 30-72
Menopausal status Pre-menopausal Post-menopausal
10
Histology Ductal infiltrating Lobular infiltrating Undifferentiated
11 6 1
Nodal stage NO Nl N2 N3
3 1 11 3
Artery
n
Internal mammary Subclavian" Axillary" Lateral thoracic Miscellaneous
22 11 38 6 2
"With a distal compressive cuff.
terized in 11 procedures and the drugs were infused at the origin of the subclavian artery and distal to the vertebral artery with a brachial compressive cuff" (Table II).
Response and follow-up (Table III) Clinical response rate was 100% (81.4-100% at 95% number of cycles administered changes according to the confidence interval). Axillary nodes exhibited the same clinical tumour response and tolerance. grade of clinical response as the primary tumour except Surgery. One month after the last course of chemo- in five patients, who presented a clinical complete therapy, modified radical mastectomy is performed. response at the primary site and partial response in the Adjuvant therapy. A total dose of 50 Gy to the chest regional nodes. wall and axillary nodes, 30 Gy to the supraclavicular Histological study of the resected breast showed resiarea and a 10 Gy boost to the surgical scar is adminis- dual viable tumour cells at the primary site and regional tered. Adjuvant chemotherapy (six monthly cycles of nodes, with different grades of necrosis in all specimens cyclophosphamide, methotrexate and 5-fluorouracil) but one, which presented complete pathological and/or hormonotherapy are administered from the start response. of radiotherapy according to different criteria such as IA chemotherapy was followed by radiotherapy in all pathological nodal stage, menopausal status and the patients: surgery in 17 patients (one patient who had presence of hormone receptors. achieved clinical complete response rejected mastectomy), chemotherapy in 12 and hormonotherapy in Response and toxicity criteria seven. Response and toxicity were evaluated following All patients with recurrence were treated with conventional criteria (Hayward et al, 1977; World different protocols of chemotherapy that included Health Organization (WHO), 1979). several active agents. Chemotherapy was continued until progression or death. Statistical methods Confidence intervals for response rates were calculated using standard techniques (Fleiss, 1981). Survival Table III. Results and follow-up curves were estimated using the method of Kaplan and Meier (1958). Response Results
From 1982 to 1989, 18 consecutive patients with inflammatory breast carcinoma were treated with neoadjuvant IA chemotherapy (Table I). Median age was 50.5 years (range 30-72 years). Ten patients were post-menopausal. Histologically there were 11 ductal infiltrating, six lobular infiltrating and one undifferentiated tumours. Tumour and nodal stages were as follows: 18 inflammatory, three N3, 11 N2, one Nl and three NO. None had either distant metastases or received previous therapy. The total number of procedures was 49: one patient received four cycles, 12 patients three cycles, four patients two cycles and one patient one cycle. The internal mammary artery could not be selectively catheVol. 65, No. 771
Complete Partial
10
Further treatment Radiotherapy Surgery Chemotherapy Hormonotherapy
18 17 12 7
Follow-up NED DWD MDFS (months) MOS (months)
6 12 25 33
NED: no evidence of disease; DWD: dead with disease; MDFS: median disease-free survival; MOS: median overall survival.
249
J. I. Bilbao et al 100
Table IV. Toxicity Local Hyperpigmentation Reversible brachial nerve paralysis Mammary pruritus Cutaneous ulceration
12
24
36
48
60
72
84
96
Figure 1. Actuarial median disease-free and overall survival according to Kaplan and Meier (1958).
18 1 2 1
Systemic Nausea/vomiting Alopecia Mucositis Aplasia Leukopenia Nephrotoxicity
18 18
1 1 2 0
Figure 1 shows the actuarial disease-free and overall inflammatory and non-inflammatory carcinoma have survival curves according to the Kaplan and Meier been 20% and 56%, respectively (Stephens, 1990). method. With a median follow-up of 21.5 months, six In the present series a 100% response rate has been (33.3%) patients remain alive and free of disease at 18, observed. However, a histologically complete response 19, 24, 28, 68 and 85 months, respectively. The median has been seldom observed (only one out of 18 patients). actuarial overall survival is 33 months (range 8-85 + The median actuarial disease-free and overall survivals months) and the median disease-free actuarial survival have been 25 and 33 months, respectively. This 25 months (5-85+ months). 12 patients have died from compares unfavourably with previous reports and probdistant metastases. No local recurrences have been ably represents the need for a more aggressive adjuvant observed. therapy; nevertheless, the local tumour control rate has been as high as 100%. The internal mammary artery has to be catheterized Toxicity (Table IV) Local. All patients presented with hyperpigmentation for IA therapy; this vessel has been used for the treatof the cutaneous area supplied by the internal mammary ment of other chest wall malignancies (Mattson et al, artery. One patient developed cutaneous ulceration so 1980), mesothelioma and lung carcinomas (Jonsson & treatment was shifted to an intravenous route. Two Karlsson, 1985). The technique of cannulation of this patients developed significant mammary pruritus during vessel is well known and does not represent additional the IA infusion time and one reversible brachial nerve morbidity. paralysis. There have been no surgical complications attributable to IA therapy. Systemic. All patients presented with some grade of References J. L., NELSON, A. J. & MONTAGUE, E. D., 1976. nausea and/or vomiting and alopecia. Three patients BARKER, Inflammatory carcinoma of the breast. Radiology, 121, presented with varying degrees of myelotoxicity (one 173-176. patient Grade III and two Grade II). CARTER, R. D., FADIS, D. M., KREMENTZ, E. T., SALWEN, W. A., PUYAU, F. A. & MUCHMORE, J. H., 1988. Treatment
of locally advanced breast cancer with regional intra-arterial chemotherapy. Regional Cancer Treatment, 1, 108-111.
Discussion
The principal aims in the treatment of locally advanced breast carcinoma with neoadjuvant chemotherapy are both to achieve the best response prior to local therapy (surgery and/or radiotherapy) and the systemic treatment of micrometastases that exist at diagnosis. The response rate with neoadjuvant intravenous chemotherapy ranges from 70% to 80% and the 3-year survival rate has improved to 50% (Rouesse et al, 1986; Segel et al, 1988). Results with neoadjuvant IA chemotherapy have been reported by a number of groups in several countries. In all the experiences, response rates have been about 90% (Carter et al, 1988; de Dicker etal, 1988; Koyama et al, 1975; Noguchi etal, 1988). Noguchi et al (1988) have reported a 94% response rate in 27 patients with locally advanced breast carcinoma. The 5-year disease-free survival rates for patients with 250
DE
DICKER,
R.
P., TIMMERMANN, J., SCHUMACHER, T. &
SCHLINDER, A. E., 1988. The influence of arterial regional chemotherapy on the local recurrence rate of advanced breast cancer. Regional Cancer Treatment, 1, 112-116. ELLIS, D. L. & TEISTELBAUM,
S. L.,
1974.
Inflammatory
carcinoma of the breast. A pathologic definition. Cancer, 33, 1045-1047. FLEISS, S. L., 1981. Statistical Methods for Rates and Proportions (Wiley, New York). HAYWARD, J. L., CARBONE, P. P., HEUSO, J. C , KUMAOKA, S., SEGALOFF, A. & RUBENS, R. D., 1977. Assessment of
response to therapy in advanced breast cancer. British Journal of Cancer, 13, 89-94. HORTOBAGYI, G. M. & BUZDAR, A. V., 1986. Progress in
inflammatory breast cancer: causes for a cautious optimism. Journal of Clinical Oncology, 12, 1727-1729 (Editorial). JONSSON, K. & KARLSSON, S.,
1985. Angiography
of the
internal mammary artery. Acta Radiologica, 26, 113-120. KAPLAN, E. L. & MEIER, P., 1958. Nonparametric estimation
The British Journal of Radiology, March 1992
Neoadjuvant intra-arterial chemotherapy in inflammatory carcinoma of the breast from incomplete observations. Journal of the American Statistical Association, 53, 457-481.
Gustave-Roussy. 1765-1771.
Journal
of
Clinical
Oncology,
12,
KOYAMA, H, WADA, T., NISHIZAWA, I. & TERASAWA, T., 1975.
SEGEL, M. C , PAULUS, D. D. & HORTOBAGYI G. M., 1988.
Intra-arterial infusion chemotherapy as a preoperative treatment of locally advanced breast cancer. Cancer, 36, 1603-1612.
Advanced primary breast cancer: assessment with mammography of response to induction chemotherapy. Radiology, 169, 49-54.
MATTSON,
W.,
MELLEKANT,
C.
&
JONSSON,
K.,
1980.
Intraarterial chemotherapy, (Letter to editor). Lancet, 2, 925. NOGUCHI, S., MlYAUCHI, K., MlSHIZAWA, Y., KOYAMA, H. &
TERESA WA, T., 1988. Management of inflammatory carcinoma of the breast with combined modality therapy including intraarterial infusion chemotherapy as an induction therapy. Long-term follow-up results of 28 patients. Cancer, 61, 1483-1491. ROUESSE, J., FRIEDMAN, S., SARRAZIN, D., MOURIESSE, H., LE CHEVALIER, T., ARRIAGADA, R., SPIELMANN, M., PAPACHARALAMBOVS, A. & MAY-LEVIN, F., 1986. Primary
chemotherapy in the treatment of inflammatory breast carcinoma: a study of 230 cases from the Institut
Vol. 65, No. 771
SICHER, K. & WATERHOUSE, J. A., 1973. Evaluation of TNM
classification of carcinoma of the breast. British Journal of Cancer, 28, 580-588. STEPHENS, F. O. 1983. Clinical experience in the use of intraarterial infusion chemotherapy in the treatment of cancers in the head and neck, the extremities, the breast and the stomach. Recent Results in Cancer Research, 86, 122-127. STEPHENS, F. O., 1990. Intraarterial induction chemotherapy in locally advanced stage III breast cancer. Cancer, 66, 645-650. WHO, J979. WHO Handbook for Reporting Results of Cancer Treatment. (World Health Organization, Geneva, Switzerland).
251
Neoadjuvant intra-arterial chemotherapy in inflammatory carcinoma of the breast By J. I. Bilbao, MD, *J. Rebollo, MD, J. M. Longo, MD, F. Mansilla, MD, * L Mufioz-Galindo, MD and *J. M. Vieitez, MD Departments of Radiology and 'Oncology, Clinica Universitaria, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain (Received 4 February 1991 and in revised form 18 July 1991, accepted 3 October 1991) Keywords: Breast cancer, Neo-adjuvant chemotherapy, Intra-arterial chemotherapy
Abstract. From 1982 to 1989, 18 eligible patients (median age 50.5 years, range 30-72 years) with inflammatory breast carcinoma have been treated with neoadjuvant intra-arterial (IA) chemotherapy. The treatment regimen includes IA cisplatin, adriamycin, mytomycin C and thiotepa on Day 1 and intravenous 5-fluorouracil on Days 1 and 2. An objective clinical response rate of 100% (eight complete and 10 partial) has been observed. The median disease-free and overall survivals are 27 months (range 5-85 + months) and 33 months (range 8-85+ months), respectively. With a median follow-up of 21.5 months, six (33.3%) patients remain alive and free of disease and 12 patients have died because of distant metastases. No local recurrences have been observed. Intra-arterial chemotherapy is an attractive technique for the treatment of locally advanced breast carcinoma with mild toxicity and high local control rate.
Inflammatory carcinoma is the most aggresive type of breast cancer. With local methods of treatment (surgery and/or radiotherapy) high local tumour control rates can be achieved, ranging from 50% to 80% (Barker et al, 1976; Ellis & Teistelbaum, 1974; Sicher & Waterhouse, 1973). However, long-term survival is poor (5% 5-year survival rate), because most of the patients have micrometastases at the moment of diagnosis. In patients with locally advanced (Stage III) breast cancer, the use of neoadjuvant systemic chemotherapy has shown a 70-80% response rate and a 5-year survival rate of 30% (Hortobagyi & Buzdar, 1986). This longterm survival compares favourably with that achieved with the use of local therapies. Hence, neoadjuvant chemotherapy was included in the protocols designed for the treatment of locally advanced breast carcinoma. Intra-arterial (IA) chemotherapy is an attractive technique that allows one to achieve high drug concentrations at the tumour site using catheters placed in the regional vessels (internal mammary and distal axillary arteries) (Koyama et al, 1975). The most encouraging results with IA therapy have been observed in some localized tumours of the limbs, head and neck, and stomach (Stephens, 1983). Results with neoadjuvant IA chemotherapy in a series of patients with inflammatory breast carcinoma are presented. Materials and methods
Selection criteria were (1) inflammatory carcinoma and (2) absence of distant metastases at diagnosis. The *Address correspondence to: J. I. Bilbao, Department of Radiology, Clinica Universitaria de Navarra, Avda. Pio XII s/n, 31080 Pamplona, Spain. 248
presence of axillary lymph node metastases was not a criterion for exclusion. Previous staging work-up included physical examination, complete blood count, liver profile, serum creatinine, echogram or computed tomographic (CT) scan of the liver, bone scintigraphy, chest radiographs and biopsy of the tumour. Treatment protocol An angiographic catheter is placed intra-arterially, using the Seldinger technique, through the common femoral artery and occasionally through the left or right axillary arteries. Catheters used were: Judkins right coronary 7F (USCI), Judkins right coronary 5F (CORDIS) and selective mammary 7F (CORDIS). The tip of the catheter is placed in the internal mammary (internal thoracic) artery; approximately 40-60% of the chemotherapeutic dose is administered selectively in this artery and the other 40-60% in the subclavian artery with a distal compressive cuff in the arm to include the axilla and related areas or, in some cases, selectively in the lateral thoracic artery. The infusion time ranges from 5 to 15 min. Treatment regimen I A therapy. Before the procedure, adequate hydration with normal saline at 150ml/h infusion rate for 3-4 h, 125 mg of methylprednisolone and 10 mg of deschlorpheniramine are administered. IA treatment consists of adriamycin (ADR) 40mg/m2, cisplatin (CDDP) 60 mg/m2, thiotepa (TSPA) 5 mg/m2 and mytomycin C (MMC) 6 mg/m2 on Day 1 and intravenous 5-fluorouracil (5-FU) 500 mg/m2 as a continuous infusion on Days 1 and 2. Immediately after the IA procedure, 50 g mannitol is administered to prevent nephrotoxicity of cisplatin. The regimen is repeated every 4 weeks. The The British Journal of Radiology, March 1992
Neoadjuvant intra-arterial chemotherapy in inflammatory carcinoma of the breast Table I. Characteristics of the patients No. of patients
Table II. Arteries used (49 procedures in 18 patients, one or two infused arteries in each procedure) 18
Age (years) Median Range
50.5 30-72
Menopausal status Pre-menopausal Post-menopausal
10
Histology Ductal infiltrating Lobular infiltrating Undifferentiated
11 6 1
Nodal stage NO Nl N2 N3
3 1 11 3
Artery
n
Internal mammary Subclavian" Axillary" Lateral thoracic Miscellaneous
22 11 38 6 2
"With a distal compressive cuff.
terized in 11 procedures and the drugs were infused at the origin of the subclavian artery and distal to the vertebral artery with a brachial compressive cuff" (Table II).
Response and follow-up (Table III) Clinical response rate was 100% (81.4-100% at 95% number of cycles administered changes according to the confidence interval). Axillary nodes exhibited the same clinical tumour response and tolerance. grade of clinical response as the primary tumour except Surgery. One month after the last course of chemo- in five patients, who presented a clinical complete therapy, modified radical mastectomy is performed. response at the primary site and partial response in the Adjuvant therapy. A total dose of 50 Gy to the chest regional nodes. wall and axillary nodes, 30 Gy to the supraclavicular Histological study of the resected breast showed resiarea and a 10 Gy boost to the surgical scar is adminis- dual viable tumour cells at the primary site and regional tered. Adjuvant chemotherapy (six monthly cycles of nodes, with different grades of necrosis in all specimens cyclophosphamide, methotrexate and 5-fluorouracil) but one, which presented complete pathological and/or hormonotherapy are administered from the start response. of radiotherapy according to different criteria such as IA chemotherapy was followed by radiotherapy in all pathological nodal stage, menopausal status and the patients: surgery in 17 patients (one patient who had presence of hormone receptors. achieved clinical complete response rejected mastectomy), chemotherapy in 12 and hormonotherapy in Response and toxicity criteria seven. Response and toxicity were evaluated following All patients with recurrence were treated with conventional criteria (Hayward et al, 1977; World different protocols of chemotherapy that included Health Organization (WHO), 1979). several active agents. Chemotherapy was continued until progression or death. Statistical methods Confidence intervals for response rates were calculated using standard techniques (Fleiss, 1981). Survival Table III. Results and follow-up curves were estimated using the method of Kaplan and Meier (1958). Response Results
From 1982 to 1989, 18 consecutive patients with inflammatory breast carcinoma were treated with neoadjuvant IA chemotherapy (Table I). Median age was 50.5 years (range 30-72 years). Ten patients were post-menopausal. Histologically there were 11 ductal infiltrating, six lobular infiltrating and one undifferentiated tumours. Tumour and nodal stages were as follows: 18 inflammatory, three N3, 11 N2, one Nl and three NO. None had either distant metastases or received previous therapy. The total number of procedures was 49: one patient received four cycles, 12 patients three cycles, four patients two cycles and one patient one cycle. The internal mammary artery could not be selectively catheVol. 65, No. 771
Complete Partial
10
Further treatment Radiotherapy Surgery Chemotherapy Hormonotherapy
18 17 12 7
Follow-up NED DWD MDFS (months) MOS (months)
6 12 25 33
NED: no evidence of disease; DWD: dead with disease; MDFS: median disease-free survival; MOS: median overall survival.
249
J. I. Bilbao et al 100
Table IV. Toxicity Local Hyperpigmentation Reversible brachial nerve paralysis Mammary pruritus Cutaneous ulceration
12
24
36
48
60
72
84
96
Figure 1. Actuarial median disease-free and overall survival according to Kaplan and Meier (1958).
18 1 2 1
Systemic Nausea/vomiting Alopecia Mucositis Aplasia Leukopenia Nephrotoxicity
18 18
1 1 2 0
Figure 1 shows the actuarial disease-free and overall inflammatory and non-inflammatory carcinoma have survival curves according to the Kaplan and Meier been 20% and 56%, respectively (Stephens, 1990). method. With a median follow-up of 21.5 months, six In the present series a 100% response rate has been (33.3%) patients remain alive and free of disease at 18, observed. However, a histologically complete response 19, 24, 28, 68 and 85 months, respectively. The median has been seldom observed (only one out of 18 patients). actuarial overall survival is 33 months (range 8-85 + The median actuarial disease-free and overall survivals months) and the median disease-free actuarial survival have been 25 and 33 months, respectively. This 25 months (5-85+ months). 12 patients have died from compares unfavourably with previous reports and probdistant metastases. No local recurrences have been ably represents the need for a more aggressive adjuvant observed. therapy; nevertheless, the local tumour control rate has been as high as 100%. The internal mammary artery has to be catheterized Toxicity (Table IV) Local. All patients presented with hyperpigmentation for IA therapy; this vessel has been used for the treatof the cutaneous area supplied by the internal mammary ment of other chest wall malignancies (Mattson et al, artery. One patient developed cutaneous ulceration so 1980), mesothelioma and lung carcinomas (Jonsson & treatment was shifted to an intravenous route. Two Karlsson, 1985). The technique of cannulation of this patients developed significant mammary pruritus during vessel is well known and does not represent additional the IA infusion time and one reversible brachial nerve morbidity. paralysis. There have been no surgical complications attributable to IA therapy. Systemic. All patients presented with some grade of References J. L., NELSON, A. J. & MONTAGUE, E. D., 1976. nausea and/or vomiting and alopecia. Three patients BARKER, Inflammatory carcinoma of the breast. Radiology, 121, presented with varying degrees of myelotoxicity (one 173-176. patient Grade III and two Grade II). CARTER, R. D., FADIS, D. M., KREMENTZ, E. T., SALWEN, W. A., PUYAU, F. A. & MUCHMORE, J. H., 1988. Treatment
of locally advanced breast cancer with regional intra-arterial chemotherapy. Regional Cancer Treatment, 1, 108-111.
Discussion
The principal aims in the treatment of locally advanced breast carcinoma with neoadjuvant chemotherapy are both to achieve the best response prior to local therapy (surgery and/or radiotherapy) and the systemic treatment of micrometastases that exist at diagnosis. The response rate with neoadjuvant intravenous chemotherapy ranges from 70% to 80% and the 3-year survival rate has improved to 50% (Rouesse et al, 1986; Segel et al, 1988). Results with neoadjuvant IA chemotherapy have been reported by a number of groups in several countries. In all the experiences, response rates have been about 90% (Carter et al, 1988; de Dicker etal, 1988; Koyama et al, 1975; Noguchi etal, 1988). Noguchi et al (1988) have reported a 94% response rate in 27 patients with locally advanced breast carcinoma. The 5-year disease-free survival rates for patients with 250
DE
DICKER,
R.
P., TIMMERMANN, J., SCHUMACHER, T. &
SCHLINDER, A. E., 1988. The influence of arterial regional chemotherapy on the local recurrence rate of advanced breast cancer. Regional Cancer Treatment, 1, 112-116. ELLIS, D. L. & TEISTELBAUM,
S. L.,
1974.
Inflammatory
carcinoma of the breast. A pathologic definition. Cancer, 33, 1045-1047. FLEISS, S. L., 1981. Statistical Methods for Rates and Proportions (Wiley, New York). HAYWARD, J. L., CARBONE, P. P., HEUSO, J. C , KUMAOKA, S., SEGALOFF, A. & RUBENS, R. D., 1977. Assessment of
response to therapy in advanced breast cancer. British Journal of Cancer, 13, 89-94. HORTOBAGYI, G. M. & BUZDAR, A. V., 1986. Progress in
inflammatory breast cancer: causes for a cautious optimism. Journal of Clinical Oncology, 12, 1727-1729 (Editorial). JONSSON, K. & KARLSSON, S.,
1985. Angiography
of the
internal mammary artery. Acta Radiologica, 26, 113-120. KAPLAN, E. L. & MEIER, P., 1958. Nonparametric estimation
The British Journal of Radiology, March 1992
Neoadjuvant intra-arterial chemotherapy in inflammatory carcinoma of the breast from incomplete observations. Journal of the American Statistical Association, 53, 457-481.
Gustave-Roussy. 1765-1771.
Journal
of
Clinical
Oncology,
12,
KOYAMA, H, WADA, T., NISHIZAWA, I. & TERASAWA, T., 1975.
SEGEL, M. C , PAULUS, D. D. & HORTOBAGYI G. M., 1988.
Intra-arterial infusion chemotherapy as a preoperative treatment of locally advanced breast cancer. Cancer, 36, 1603-1612.
Advanced primary breast cancer: assessment with mammography of response to induction chemotherapy. Radiology, 169, 49-54.
MATTSON,
W.,
MELLEKANT,
C.
&
JONSSON,
K.,
1980.
Intraarterial chemotherapy, (Letter to editor). Lancet, 2, 925. NOGUCHI, S., MlYAUCHI, K., MlSHIZAWA, Y., KOYAMA, H. &
TERESA WA, T., 1988. Management of inflammatory carcinoma of the breast with combined modality therapy including intraarterial infusion chemotherapy as an induction therapy. Long-term follow-up results of 28 patients. Cancer, 61, 1483-1491. ROUESSE, J., FRIEDMAN, S., SARRAZIN, D., MOURIESSE, H., LE CHEVALIER, T., ARRIAGADA, R., SPIELMANN, M., PAPACHARALAMBOVS, A. & MAY-LEVIN, F., 1986. Primary
chemotherapy in the treatment of inflammatory breast carcinoma: a study of 230 cases from the Institut
Vol. 65, No. 771
SICHER, K. & WATERHOUSE, J. A., 1973. Evaluation of TNM
classification of carcinoma of the breast. British Journal of Cancer, 28, 580-588. STEPHENS, F. O. 1983. Clinical experience in the use of intraarterial infusion chemotherapy in the treatment of cancers in the head and neck, the extremities, the breast and the stomach. Recent Results in Cancer Research, 86, 122-127. STEPHENS, F. O., 1990. Intraarterial induction chemotherapy in locally advanced stage III breast cancer. Cancer, 66, 645-650. WHO, J979. WHO Handbook for Reporting Results of Cancer Treatment. (World Health Organization, Geneva, Switzerland).
251
